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Sample records for genetic background pdf

  1. Genetical background of intelligence.

    PubMed

    Junkiert-Czarnecka, Anna; Haus, Olga

    2016-01-01

    Intelligence as an ability to reason, think abstractly and adapt effectively to the environment is a subject of research in the field of psychology, neurobiology, and in the last twenty years genetics as well. Genetical testing of twins carried out from XX century indicated heritebility of intelligence, therefore confirmed an influence of genetic factor on cognitive processes. Studies on genetic background of intelligence focus on dopaminergic (DRD2, DRD4, COMT, SLC6A3, DAT1, CCKAR) and adrenergic system (ADRB2, CHRM2) genes as well as, neutrofins (BDNF) and oxidative stress genes (LTF, PRNP). Positive effect of investigated gene polymorphism was indicated by variation c.957C>T DRD2 gene (if in polymorphic site is thymine), polymorphism c.472G>A COMT gene (presence of adenine) and also gene ADRB2 c.46A->G (guanine), CHRM2 (thymine in place c.1890A>T) and BDNF (guanine in place c.472G>A) Obtained results indicate that intelligence is a feature dependent not only on genetic but also an environmental factor. PMID:27333929

  2. Genetic background of supernumerary teeth

    PubMed Central

    Subasioglu, Asli; Savas, Selcuk; Kucukyilmaz, Ebru; Kesim, Servet; Yagci, Ahmet; Dundar, Munis

    2015-01-01

    Supernumerary teeth (ST) are odontostomatologic anomaly characterized by as the existence excessive number of teeth in relation to the normal dental formula. This condition is commonly seen with several congenital genetic disorders such as Gardner's syndrome, cleidocranial dysostosis and cleft lip and palate. Less common syndromes that are associated with ST are; Fabry Disease, Ellis-van Creveld syndrome, Nance-Horan syndrome, Rubinstein-Taybi Syndrome and Trico–Rhino–Phalangeal syndrome. ST can be an important component of a distinctive disorder and an important clue for early diagnosis. Certainly early detecting the abnormalities gives us to make correct management of the patient and also it is important for making well-informed decisions about long-term medical care and treatment. In this review, the genetic syndromes that are related with ST were discussed. PMID:25713500

  3. Role of genetic background in induced instability

    NASA Technical Reports Server (NTRS)

    Kadhim, Munira A.; Nelson, G. A. (Principal Investigator)

    2003-01-01

    Genomic instability is effectively induced by ionizing radiation. Recently, evidence has accumulated supporting a relationship between genetic background and the radiation-induced genomic instability phenotype. This is possibly due to alterations in proteins responsible for maintenance of genomic integrity or altered oxidative metabolism. Studies in human cell lines, human primary cells, and mouse models have been performed predominantly using high linear energy transfer (LET) radiation, or high doses of low LET radiation. The interplay between genetics, radiation response, and genomic instability has not been fully determined at low doses of low LET radiation. However, recent studies using low doses of low LET radiation suggest that the relationship between genetic background and radiation-induced genomic instability may be more complicated than these same relationships at high LET or high doses of low LET radiation. The complexity of this relationship at low doses of low LET radiation suggests that more of the population may be at risk than previously recognized and may have implications for radiation risk assessment.

  4. [The pathology and genetic background of myeloma].

    PubMed

    Timár, Botond

    2016-06-01

    Plasma cell myeloma is a heterogeneous hematologic malignancy of plasma cells, occurring dominantly in the elderly population. It is now accepted that all myeloma cases are preceded by a clinically silent expansion of clonal plasma cells, known as monoclonal gammopathy of undetermined significance. Our knowledge on the genetics of myeloma is still limited and lags behind other well-characterized hematological malignancies. One of the reasons of this fact is the difficulty to induce metaphases within the malignant plasma cell population. With the development of new molecular techniques (microarrays and next generation sequencing), our understanding of the pathogenesis and progression of myeloma has been highly improved in the past years. This review offers an insight into this newly gained knowledge. PMID:27275641

  5. [The genetic background for the eye malformations anophthalmia and microphthalmia].

    PubMed

    Roos, Laura Sønderberg; Grønskov, Karen; Jensen, Hanne; Tümer, Zeynep

    2012-03-12

    Anophthalmia and microphthalmia (AO/MO) are rare congenital eye malformations, in which the eyeball is apparently absent or smaller than normal, which causes various degrees of visual impairment. Over 200 different AO/MO-related syndromes have been described, but the genetic background is unknown in many cases. The aim of this article is to give an overview of AO/MO, focusing on the genetic background. It is illustrated that the future identification of new AO/MO related genes will benefit in the genetic counseling of AO/MO patients, and in the understanding of eye development and congenital eye malformations.

  6. Genetic background affects susceptibility to tumoral stem cell reprogramming

    PubMed Central

    García-Ramírez, Idoia; Ruiz-Roca, Lucía; Martín-Lorenzo, Alberto; Blanco, Óscar; García-Cenador, María Begoña; García-Criado, Francisco Javier; Vicente-Dueñas, Carolina; Sánchez-García, Isidro

    2013-01-01

    The latest studies of the interactions between oncogenes and its target cell have shown that certain oncogenes may act as passengers to reprogram tissue-specific stem/progenitor cell into a malignant cancer stem cell state. In this study, we show that the genetic background influences this tumoral stem cell reprogramming capacity of the oncogenes using as a model the Sca1-BCRABLp210 mice, where the type of tumor they develop, chronic myeloid leukemia (CML), is a function of tumoral stem cell reprogramming. Sca1-BCRABLp210 mice containing FVB genetic components were significantly more resistant to CML. However, pure Sca1-BCRABLp210 FVB mice developed thymomas that were not seen in the Sca1-BCRABLp210 mice into the B6 background. Collectively, our results demonstrate for the first time that tumoral stem cell reprogramming fate is subject to polymorphic genetic control. PMID:23839033

  7. Genetic background in nonalcoholic fatty liver disease: A comprehensive review

    PubMed Central

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-01-01

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease. PMID:26494964

  8. Genetic background in nonalcoholic fatty liver disease: A comprehensive review.

    PubMed

    Macaluso, Fabio Salvatore; Maida, Marcello; Petta, Salvatore

    2015-10-21

    In the Western world, nonalcoholic fatty liver disease (NAFLD) is considered as one of the most significant liver diseases of the twenty-first century. Its development is certainly driven by environmental factors, but it is also regulated by genetic background. The role of heritability has been widely demonstrated by several epidemiological, familial, and twin studies and case series, and likely reflects the wide inter-individual and inter-ethnic genetic variability in systemic metabolism and wound healing response processes. Consistent with this idea, genome-wide association studies have clearly identified Patatin-like phosholipase domain-containing 3 gene variant I148M as a major player in the development and progression of NAFLD. More recently, the transmembrane 6 superfamily member 2 E167K variant emerged as a relevant contributor in both NAFLD pathogenesis and cardiovascular outcomes. Furthermore, numerous case-control studies have been performed to elucidate the potential role of candidate genes in the pathogenesis and progression of fatty liver, although findings are sometimes contradictory. Accordingly, we performed a comprehensive literature search and review on the role of genetics in NAFLD. We emphasize the strengths and weaknesses of the available literature and outline the putative role of each genetic variant in influencing susceptibility and/or progression of the disease.

  9. Genetic polymorphism as a background of animal behavior.

    PubMed

    Inoue-Murayama, Miho

    2009-04-01

    Various studies have shown the associations between differences in human behavioral traits and genetic polymorphism of neurotransmitter-related proteins such as receptors, transporters and monoamine oxidase. To clarify the genetic background of animal behavior, corresponding regions in animals have been analyzed. The study has been especially focused on primates, as the evolutionally closest animal to humans, and on dogs, as the socially closest animal to humans. In primates, polymorphisms were discovered between or within species, and the functional effects on neural transmission were found to be different by alleles. Even in apes, the closest species to humans, function was different from that in humans. In dogs, allele distributions of several genes were different among breeds showing different behavioral traits, and genes associated with individual differences in aggressiveness and aptitude of working dogs were surveyed. The survey of behavior-related genes has also been carried out in other mammals such as horses and cetaceans. Genes controlling various behaviors in birds have also been reported. The marker genes for behavior will provide useful information for human evolution, welfare of zoo animals and effective selection of working dogs and industry animals. PMID:20163580

  10. Empathy Is Moderated by Genetic Background in Mice

    PubMed Central

    Lahvis, Garet P.

    2009-01-01

    Empathy, as originally defined, refers to an emotional experience that is shared among individuals. When discomfort or alarm is detected in another, a variety of behavioral responses can follow, including greater levels of nurturing, consolation or increased vigilance towards a threat. Moreover, changes in systemic physiology often accompany the recognition of distressed states in others. Employing a mouse model of cue-conditioned fear, we asked whether exposure to conspecific distress influences how a mouse subsequently responds to environmental cues that predict this distress. We found that mice are responsive to environmental cues that predict social distress, that their heart rate changes when distress vocalizations are emitted from conspecifics, and that genetic background substantially influences the magnitude of these responses. Specifically, during a series of pre-exposure sessions, repeated experiences of object mice that were exposed to a tone-shock (CS-UCS) contingency resulted in heart rate deceleration in subjects from the gregarious C57BL/6J (B6) strain, but not in subjects from the less social BALB/cJ (BALB) strain. Following the pre-exposure sessions, subjects were individually presented with the CS-only for 5 consecutive trials followed by 5 consecutive pairings of the CS with the UCS. Pre-exposure to object distress increased the freezing responses of B6 mice, but not BALB mice, on both the CS-only and the CS-UCS trials. These physiological and behavioral responses of B6 mice to social distress parallel features of human empathy. Our paradigm thus has construct and face validity with contemporary views of empathy, and provides unequivocal evidence for a genetic contribution to the expression of empathic behavior. PMID:19209221

  11. Influence of Genetic Background on Fluoride Metabolism in Mice

    PubMed Central

    Carvalho, J.G.; Leite, A.L.; Yan, D.; Everett, E.T.; Whitford, G.M.; Buzalaf, M.A.R.

    2009-01-01

    A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis, due to their genetic backgrounds. This study tested whether these differences are due to variations in water intake and/or F metabolism. A/J (susceptible to dental fluorosis) and 129P3/J mice (resistant) received drinking water containing 0, 10, or 50 ppm F. Weekly F intake, excretion and retention, and terminal plasma and femur F levels were determined. Dental fluorosis was evaluated clinically and by quantitative fluorescence (QF). Data were tested by two-way ANOVA. Although F intakes by the strains were similar, excretion by A/J mice was significantly higher due to greater urinary F excretion, which resulted in lower plasma and femur F levels. Compared with 129P3/J mice given 50 ppm F, significantly higher QF scores were recorded for A/J mice. In conclusion, these strains differ with respect to several features of F metabolism, and amelogenesis in the 129P3/J strain seems to be unaffected by high F exposure. PMID:19828896

  12. Influence of genetic background on fluoride metabolism in mice.

    PubMed

    Carvalho, J G; Leite, A L; Yan, D; Everett, E T; Whitford, G M; Buzalaf, M A R

    2009-11-01

    A/J and 129P3/J mouse strains have different susceptibilities to dental fluorosis, due to their genetic backgrounds. This study tested whether these differences are due to variations in water intake and/or F metabolism. A/J (susceptible to dental fluorosis) and 129P3/J mice (resistant) received drinking water containing 0, 10, or 50 ppm F. Weekly F intake, excretion and retention, and terminal plasma and femur F levels were determined. Dental fluorosis was evaluated clinically and by quantitative fluorescence (QF). Data were tested by two-way ANOVA. Although F intakes by the strains were similar, excretion by A/J mice was significantly higher due to greater urinary F excretion, which resulted in lower plasma and femur F levels. Compared with 129P3/J mice given 50 ppm F, significantly higher QF scores were recorded for A/J mice. In conclusion, these strains differ with respect to several features of F metabolism, and amelogenesis in the 129P3/J strain seems to be unaffected by high F exposure.

  13. Does your gene need a background check? How genetic background impacts the analysis of mutations, genes, and evolution.

    PubMed

    Chandler, Christopher H; Chari, Sudarshan; Dworkin, Ian

    2013-06-01

    The premise of genetic analysis is that a causal link exists between phenotypic and allelic variation. However, it has long been documented that mutant phenotypes are not a simple result of a single DNA lesion, but are instead due to interactions of the focal allele with other genes and the environment. Although an experimentally rigorous approach focused on individual mutations and isogenic control strains has facilitated amazing progress within genetics and related fields, a glimpse back suggests that a vast complexity has been omitted from our current understanding of allelic effects. Armed with traditional genetic analyses and the foundational knowledge they have provided, we argue that the time and tools are ripe to return to the underexplored aspects of gene function and embrace the context-dependent nature of genetic effects. We assert that a broad understanding of genetic effects and the evolutionary dynamics of alleles requires identifying how mutational outcomes depend upon the 'wild type' genetic background. Furthermore, we discuss how best to exploit genetic background effects to broaden genetic research programs.

  14. Does your gene need a background check? How genetic background impacts the analysis of mutations, genes, and evolution

    PubMed Central

    Chandler, Christopher H.; Chari, Sudarshan; Dworkin, Ian

    2013-01-01

    The premise of genetic analysis is that a causal link exists between phenotypic and allelic variation. Yet it has long been documented that mutant phenotypes are not a simple result of a single DNA lesion, but rather are due to interactions of the focal allele with other genes and the environment. Although an experimentally rigorous approach focused on individual mutations and isogenic control strains has facilitated amazing progress within genetics and related fields, a glimpse back suggests that a vast complexity has been omitted from our current understanding of allelic effects. Armed with traditional genetic analyses and the foundational knowledge they have provided, we argue that the time and tools are ripe to return to the under-explored aspects of gene function and embrace the context-dependent nature of genetic effects. We assert that a broad understanding of genetic effects and the evolutionary dynamics of alleles requires identifying how mutational outcomes depend upon the “wild-type” genetic background. Furthermore, we discuss how best to exploit genetic background effects to broaden genetic research programs. PMID:23453263

  15. On the relative roles of background selection and genetic hitchhiking in shaping human cytomegalovirus genetic diversity.

    PubMed

    Renzette, Nicholas; Kowalik, Timothy F; Jensen, Jeffrey D

    2016-01-01

    A central focus of population genetics has been examining the contribution of selective and neutral processes in shaping patterns of intraspecies diversity. In terms of selection specifically, surveys of higher organisms have shown considerable variation in the relative contributions of background selection and genetic hitchhiking in shaping the distribution of polymorphisms, although these analyses have rarely been extended to bacteria and viruses. Here, we study the evolution of a ubiquitous, viral pathogen, human cytomegalovirus (HCMV), by analysing the relationship among intraspecies diversity, interspecies divergence and rates of recombination. We show that there is a strong correlation between diversity and divergence, consistent with expectations of neutral evolution. However, after correcting for divergence, there remains a significant correlation between intraspecies diversity and recombination rates, with additional analyses suggesting that this correlation is largely due to the effects of background selection. In addition, a small number of loci, centred on long noncoding RNAs, also show evidence of selective sweeps. These data suggest that HCMV evolution is dominated by neutral mechanisms as well as background selection, expanding our understanding of linked selection to a novel class of organisms. PMID:26211679

  16. Novel genetic mutation in the background of Carney complex.

    PubMed

    Halászlaki, Csaba; Takács, István; Butz, Henriett; Patócs, Attila; Lakatos, Péter

    2012-04-01

    Carney complex is a rare disease inherited in an autosomal dominant manner. It is mostly caused by inactivating mutations of the subunit of protein kinase A. Carney complex is associated with atrial myxoma, nevi or myxomas of the skin, breast tumor and endocrine overactivity. Primary pigmented nodular adrenocortical disease is the specific endocrine manifestation. The authors present the history of a 53-year-old female patient who had undergone surgery for atrial myxomas, thyroid tumor and breast cancer. She was also operated for an adrenal adenoma causing Cushing’s syndrome. Genetic study revealed a novel mutation in the regulatory subunit of protein kinase A (ivs2-1G>A splice mutation in intron 2). Her heterozygous twins were also genetically screened and one of them carried the same mutation. The authors emphasize that despite the absence of specific treatment for patients with Carney complex, confirmation of the diagnosis by genetic studies is important for the close follow-up of the patient and early identification of novel manifestations. PMID:22297707

  17. [Genetic and molecular background in autoimmune diabetes mellitus].

    PubMed

    Kantárová, D; Prídavková, D; Ságová, I; Vrlík, M; Mikler, J; Buc, M

    2015-09-01

    Type 1 diabetes mellitus (T1 DM) is caused by autoimmune-mediated and idiopathic beta-cell destruction of the pancreatic islets of Langerhans resulting in absolute insulin deficiency. Susceptibility to T1 DM is influenced by both genetic and environmental factors. It is generally believed that in genetically susceptible individuals, the disease is triggered by environmental agents, such as viral infections, dietary factors in early infancy, or climatic influences. Many candidate genes for diabetes have been reported; those within the Major Histocompatibility Complex being among the most important. The most common autoantigens are insulin, glutamic acid decarboxylase 65, insuloma-associated antigen 2, and zinc transporter ZnT8. The destruction of beta-cells is mediated mainly by cellular mechanisms; antibodies only seem to reflect the ongoing autoimmune processes and are not directly involved in the tissue damage. They, however, appear prior to the onset of insulin deficiency which makes them suitable for use in the prevention of the disease. PMID:26448299

  18. Sarcoidosis and Autoimmunity: From Genetic Background to Environmental Factors.

    PubMed

    Bindoli, Sara; Dagan, Amir; Torres-Ruiz, José J; Perricone, Carlo; Bizjak, Mojca; Doria, Andrea; Shoenfeld, Yehuda

    2016-01-01

    Sarcoidosis is a chronic multisystem disease with variable course resulting from the interaction between environmental factors and the immune system of individuals genetically predisposed. The evidence linking sarcoidosis with environmental triggers such as metals is increasing. We describe the case of a 44 year old female with a history. of smoking since age 30 and previous mercury dental filling who presented at physical examination with numerous subcutaneous nodules. Laboratory data showed accelerated erythrocyte sedimentation rate and high titer of anti-U1 ribonucleoprotein antibodies (U1 RNP). Skin biopsy and chest X-ray suggested the diagnosis of sarcoidosis. In this report we illustrate the different causes involved in the onset of sarcoidosis. PMID:27228643

  19. Genetic background influences loss of heterozygosity patterns in radiation-induced mouse thymic lymphoma

    PubMed Central

    Hang, Michael; Huang, Yurong; Snijders, Antoine M.; Mao, Jian-Hua

    2015-01-01

    Previous studies have revealed that p53 heterozygous (p53+/−) mice are extremely susceptible to radiation-induced tumorigenesis. To investigate whether genetic background influences radiation induced tumor susceptibility, we crossed p53+/− 129/Sv mice with genetically diverse strains to generate p53+/− F1 hybrids. The results showed that genetic background had a profound impact on tumor latency after exposure to gamma radiation, while the tumor spectrum did not change. We further characterized the thymic lymphomas that arose in the p53+/− mice by genome-wide loss of heterozygosity (LOH) analyses and found that genetic background strongly influenced the frequency of LOH and the loss of which parental allele on different chromosomes. Further research is needed to identify which genetic variations control the LOH patterns in radiation-induced thymic lymphomas and to evaluate its relevance to human cancers. PMID:25932465

  20. Genetic background impacts soluble and cell wall-bound aromatics in brown midrib mutants of sorghum

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To evaluate the effects that genetic background has on two sorghum brown midrib (bmr) mutants, plant phenolics, lignin biosynthetic enzymes and stem anatomy were evaluated in wild-type (WT), bmr-6, bmr-12 and double-mutants (bmr-6 and bmr-12) in near isogenic , RTx430 and Wheatland backgrounds. The...

  1. Genetic background modulates phenotypes of serotonin transporter Ala56 knock-in mice

    PubMed Central

    2013-01-01

    Background Previously, we identified multiple, rare serotonin (5-HT) transporter (SERT) variants in children with autism spectrum disorder (ASD). Although in our study the SERT Ala56 variant was over-transmitted to ASD probands, it was also seen in some unaffected individuals, suggesting that associated ASD risk is influenced by the epistatic effects of other genetic variation. Subsequently, we established that mice expressing the SERT Ala56 variant on a 129S6/S4 genetic background display multiple biochemical, physiological and behavioral changes, including hyperserotonemia, altered 5-HT receptor sensitivity, and altered social, communication, and repetitive behavior. Here we explore the effects of genetic background on SERT Ala56 knock-in phenotypes. Methods To explore the effects of genetic background, we backcrossed SERT Ala56 mice on the 129 background into a C57BL/6 (B6) background to achieve congenic B6 SERT Ala56 mice, and assessed autism-relevant behavior, including sociability, ultrasonic vocalizations, and repetitive behavior in the home cage, as well as serotonergic phenotypes, including whole blood serotonin levels and serotonin receptor sensitivity. Results One consistent phenotype between the two strains was performance in the tube test for dominance, where mutant mice displayed a greater tendency to withdraw from a social encounter in a narrow tube as compared to wildtype littermate controls. On the B6 background, mutant pup ultrasonic vocalizations were significantly increased, in contrast to decreased vocalizations seen previously on the 129 background. Several phenotypes seen on the 129 background were reduced or absent when the mutation was placed on the B6 background, including hyperserotonemia, 5-HT receptor hypersensivity, and repetitive behavior. Conclusions Our findings provide a cogent example of how epistatic interactions can modulate the impact of functional genetic variation and suggest that some aspects of social behavior may be

  2. [Novel methods and their applicability in the evaluation of the genetic background of endocrine system tumours].

    PubMed

    Patócs, Attila; Likó, István; Butz, Henriett; Baghy, Kornélia; Rácz, Károly

    2015-12-20

    The technical developments leading to revolution in clinical genetic testing offer new approaches for patients with cancer. From one mutation or one gene approach the scale of genetic testing moved to whole exome or whole genome scale. It is well known that many tumours are genetically determined and they are part of familial tumour syndromes. In addition, some mutations indicate specific molecular targeted therapies. Although sampling and sample preparation are different for testing germline and somatic mutations, the technical background of the analysis is the same. The aim of clinical genetic testing is to identify patients who are carriers of disease-causing mutations or to test tumour tissue for the presence of genetic alterations which may be targets for therapeutic approaches. In this review the authors summarize novel possibilities offered by next-generation sequencing in clinical genetic testing of patients with endocrine tumours. In addition, the authors review recent guidelines on technical and ethical issues related to these novel methods.

  3. Modifying Behavioral Phenotypes in Fmr1 KO Mice: Genetic Background Differences Reveal Autistic-Like Responses

    PubMed Central

    Spencer, Corinne M.; Alekseyenko, Olga; Hamilton, Shannon M.; Thomas, Alexia M.; Serysheva, Ekaterina; Yuva-Paylor, Lisa A.; Paylor, Richard

    2010-01-01

    Scientific Abstract Fragile X syndrome (FXS) is the most common inherited form of intellectual disability in humans. In addition to cognitive impairment, patients may exhibit hyperactivity, attention deficits, social difficulties and anxiety, and autistic-like behaviors. The degree to which patients display these behaviors varies considerably and is influenced by family history, suggesting that genetic modifiers play a role in the expression of behaviors in FXS. Several studies have examined behavior in a mouse model of FXS in which the Fmr1 gene has been ablated. Most of those studies were done in Fmr1 knockout mice on a pure C57BL/6 or FVB strain background. To gain a better understanding of the effects of genetic background on behaviors resulting from the loss of Fmr1 gene expression, we generated F1 hybrid lines from female Fmr1 heterozygous mice on a pure C57BL/6J background bred with male Fmr1 wild-type mice of various background strains (A/J, DBA/2J, FVB/NJ, 129S1/SvImJ and CD-1). Male Fmr1 knockout and wild-type littermates from each line were examined in an extensive behavioral test battery. Results clearly indicate that multiple behavioral responses are dependent on genetic background, including autistic-like traits that are present on limited genetic backgrounds. This approach has allowed us to identify improved models for different behavioral symptoms present in FXS including autistic-like traits. PMID:21268289

  4. Identification of genetic variants associated with maize flowering time using an extremely large multi-genetic background population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Flowering time is one of the major adaptive traits in domestication of maize and an important selection criterion in breeding. To detect more maize flowering time variants we evaluated flowering time traits using an extremely large multi- genetic background population that contained more than 8000 l...

  5. Unravelling the complex genetic background of atopic dermatitis: from genetic association results towards novel therapeutic strategies.

    PubMed

    Hoffjan, Sabine; Stemmler, Susanne

    2015-10-01

    Atopic dermatitis (AD) is a chronic inflammatory skin disease arising from complex interaction between genetic and environmental factors. As the starting point of the so-called "atopic march", e.g. the progression towards allergic asthma in some but not all affected children, AD has come into focus for potential disease-modifying strategies. To elucidate the genetic factors influencing AD development, linkage, association as well as genome-wide association studies have been performed over the last two decades. The results suggest that besides variation in immune-mediated pathways, an intact skin barrier function plays a key role in AD development. Mutations in the gene encoding filaggrin, a major structural protein in the epidermis, have been consistently associated with AD, especially the early-onset persistent form of disease, and are regarded as the most significant known risk factor for AD development to date. Additionally, variation in some other genes involved in skin integrity and barrier function have shown association with AD. However, the known genetic risk factors can only explain a small part of the heritability at the moment. Whole-exome or whole-genome sequencing studies have not been reported yet, but will probably soon evaluate the influence of rare variations for AD development. Additionally, large multi-centre studies comprehensively incorporating gene-gene and gene-environment interactions as well as epigenetic mechanisms might further elucidate the genetic factors underlying AD pathogenesis and, thus, open the way for a more individualized treatment in the future.

  6. Farther, slower, stronger: how the plant genetic background protects a major resistance gene from breakdown.

    PubMed

    Quenouille, Julie; Montarry, Josselin; Palloix, Alain; Moury, Benoit

    2013-02-01

    Genetic resistance provides efficient control of crop diseases, but is limited by pathogen evolution capacities which often result in resistance breakdown. It has been demonstrated recently, in three different pathosystems, that polygenic resistances combining a major-effect gene and quantitative resistance controlled by the genetic background are more durable than monogenic resistances (with the same major gene in a susceptible genetic background), but the underlying mechanisms are unknown. Using the pepper-Potato virus Y system, we examined three mechanisms that could account for the greater durability of the polygenic resistances: (i) the additional quantitative resistance conferred by the genetic background; (ii) the increase in the number of mutations required for resistance breakdown; and (iii) the slower selection of adapted resistance-breaking mutants within the viral population. The three mechanisms were experimentally validated. The first explained a large part of the variation in resistance breakdown frequency and is therefore expected to be a major determinant of resistance durability. Quantitative resistance factors also had an influence on the second mechanism by modifying the virus mutational pathways towards resistance breakdown and could also have an influence on the third mechanism by increasing genetic drift effects on the viral population. The relevance of these results for other plant-pathogen systems and their importance in plant breeding are discussed.

  7. GENETIC BACKGROUND BUT NOT METALLOTHIONEIN PHENOTYPE DICTATES SENSITIVITY TO CADMIUM-INDUCED TESTICULAR INJURY IN MICE

    EPA Science Inventory

    Genetic Background but not Metallothionein Phenotype Dictates Sensitivity to
    Cadmium-Induced Testicular Injury in Mice

    Jie Liu1,2, Chris Corton3, David J. Dix4, Yaping Liu1, Michael P. Waalkes2
    and Curtis D. Klaassen1

    ABSTRACT

    Parenteral administrati...

  8. The Requirement of WHIRLY1 for Embryogenesis Is Dependent on Genetic Background in Maize

    PubMed Central

    Zhang, Ya-Feng; Hou, Ming-Ming; Tan, Bao-Cai

    2013-01-01

    Plastid gene expression is essential to embryogenesis in higher plants, but the underlying mechanism is obscure. Through molecular characterization of an embryo defective 16 (emb16) locus, here we report that the requirement of plastid translation for embryogenesis is dependent on the genetic background in maize (Zea mays). The emb16 mutation arrests embryogenesis at transition stage and allows the endosperm to develop largely normally. Molecular cloning reveals that Emb16 encodes WHIRLY1 (WHY1), a DNA/RNA binding protein that is required for genome stability and ribosome formation in plastids. Interestingly, the previous why1 mutant alleles (why1-1 and why1-2) do not affect embryogenesis, only conditions albino seedlings. The emb16 allele of why1 mutation is in the W22 genetic background. Crosses between emb16 and why1-1 heterozygotes resulted in both defective embryos and albino seedlings in the F1 progeny. Introgression of the emb16 allele from W22 into A188, B73, Mo17, Oh51a and the why1-1 genetic backgrounds yielded both defective embryos and albino seedlings. Similar results were obtained with two other emb mutants (emb12 and emb14) that are impaired in plastid protein translation process. These results indicate that the requirement of plastid translation for embryogenesis is dependent on genetic backgrounds, implying a mechanism of embryo lethality suppression in maize. PMID:23840682

  9. [Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)].

    PubMed

    Teramoto, Shinji

    2016-05-01

    A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD.

  10. [Recent progress in genetic background of chronic obstructive pulmonary disease (COPD)].

    PubMed

    Teramoto, Shinji

    2016-05-01

    A genetic contribution to develop chronic obstructive pulmonary disease(COPD) is estimated. However, candidate gene studies on COPD and related phenotypes have not been well replicated. Research on the genetic pathologic background of COPD using genome-wide association studies (GWASs) has progressed in recent years. The novel candidate genes including CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), and FAM13A (family with sequence similarity 13, member A) are identified in multiple populations. However, their pathological roles remain poorly understood. The nicotine dependency, pulmonary development, and pulmonary/systemic inflammatory diathesis may be involved in genetic background of COPD. PMID:27254938

  11. Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females.

    PubMed

    Hunter, Chad M; Robinson, Matthew C; Aylor, David L; Singh, Nadia D

    2016-01-01

    Meiotic recombination is a genetic process that is critical for proper chromosome segregation in many organisms. Despite being fundamental for organismal fitness, rates of crossing over vary greatly between taxa. Both genetic and environmental factors contribute to phenotypic variation in crossover frequency, as do genotype-environment interactions. Here, we test the hypothesis that maternal age influences rates of crossing over in a genotypic-specific manner. Using classical genetic techniques, we estimated rates of crossing over for individual Drosophila melanogaster females from five strains over their lifetime from a single mating event. We find that both age and genetic background significantly contribute to observed variation in recombination frequency, as do genotype-age interactions. We further find differences in the effect of age on recombination frequency in the two genomic regions surveyed. Our results highlight the complexity of recombination rate variation and reveal a new role of genotype by maternal age interactions in mediating recombination rate.

  12. Genetic Background, Maternal Age, and Interaction Effects Mediate Rates of Crossing Over in Drosophila melanogaster Females

    PubMed Central

    Hunter, Chad M.; Robinson, Matthew C.; Aylor, David L.; Singh, Nadia D.

    2016-01-01

    Meiotic recombination is a genetic process that is critical for proper chromosome segregation in many organisms. Despite being fundamental for organismal fitness, rates of crossing over vary greatly between taxa. Both genetic and environmental factors contribute to phenotypic variation in crossover frequency, as do genotype–environment interactions. Here, we test the hypothesis that maternal age influences rates of crossing over in a genotypic-specific manner. Using classical genetic techniques, we estimated rates of crossing over for individual Drosophila melanogaster females from five strains over their lifetime from a single mating event. We find that both age and genetic background significantly contribute to observed variation in recombination frequency, as do genotype–age interactions. We further find differences in the effect of age on recombination frequency in the two genomic regions surveyed. Our results highlight the complexity of recombination rate variation and reveal a new role of genotype by maternal age interactions in mediating recombination rate. PMID:26994290

  13. Enhanced biofilm formation and multi-host transmission evolve from divergent genetic backgrounds in Campylobacter jejuni.

    PubMed

    Pascoe, Ben; Méric, Guillaume; Murray, Susan; Yahara, Koji; Mageiros, Leonardos; Bowen, Ryan; Jones, Nathan H; Jeeves, Rose E; Lappin-Scott, Hilary M; Asakura, Hiroshi; Sheppard, Samuel K

    2015-11-01

    Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as Campylobacter, biofilms play a key role in transmission to humans as the bacteria are exposed to atmospheric oxygen concentrations when leaving the reservoir host gut. Genetic determinants of biofilm formation differ between species, but little is known about how strains of the same species achieve the biofilm phenotype with different genetic backgrounds. Our approach combines genome-wide association studies with traditional microbiology techniques to investigate the genetic basis of biofilm formation in 102 Campylobacter jejuni isolates. We quantified biofilm formation among the isolates and identified hotspots of genetic variation in homologous sequences that correspond to variation in biofilm phenotypes. Thirteen genes demonstrated a statistically robust association including those involved in adhesion, motility, glycosylation, capsule production and oxidative stress. The genes associated with biofilm formation were different in the host generalist ST-21 and ST-45 clonal complexes, which are frequently isolated from multiple host species and clinical samples. This suggests the evolution of enhanced biofilm from different genetic backgrounds and a possible role in colonization of multiple hosts and transmission to humans.

  14. New application of intelligent agents in sporadic amyotrophic lateral sclerosis identifies unexpected specific genetic background

    PubMed Central

    Penco, Silvana; Buscema, Massimo; Patrosso, Maria Cristina; Marocchi, Alessandro; Grossi, Enzo

    2008-01-01

    Background Few genetic factors predisposing to the sporadic form of amyotrophic lateral sclerosis (ALS) have been identified, but the pathology itself seems to be a true multifactorial disease in which complex interactions between environmental and genetic susceptibility factors take place. The purpose of this study was to approach genetic data with an innovative statistical method such as artificial neural networks to identify a possible genetic background predisposing to the disease. A DNA multiarray panel was applied to genotype more than 60 polymorphisms within 35 genes selected from pathways of lipid and homocysteine metabolism, regulation of blood pressure, coagulation, inflammation, cellular adhesion and matrix integrity, in 54 sporadic ALS patients and 208 controls. Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis Results Advanced intelligent systems based on novel coupling of artificial neural networks and evolutionary algorithms have been applied. The results obtained have been compared with those derived from the use of standard neural networks and classical statistical analysis. An unexpected discovery of a strong genetic background in sporadic ALS using a DNA multiarray panel and analytical processing of the data with advanced artificial neural networks was found. The predictive accuracy obtained with Linear Discriminant Analysis and Standard Artificial Neural Networks ranged from 70% to 79% (average 75.31%) and from 69.1 to 86.2% (average 76.6%) respectively. The corresponding value obtained with Advanced Intelligent Systems reached an average of 96.0% (range 94.4 to 97.6%). This latter approach allowed the identification of seven genetic variants essential to differentiate cases from controls: apolipoprotein E arg158cys; hepatic lipase

  15. Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

    PubMed

    Gidalevitz, Tali; Krupinski, Thomas; Garcia, Susana; Morimoto, Richard I

    2009-03-01

    Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation behavior and genetic interactions of mutant forms of SOD1. Expression of three structurally distinct SOD1 mutants in C. elegans muscle cells resulted in the appearance of heterogeneous populations of aggregates and was associated with only mild cellular dysfunction. However, introduction of destabilizing temperature-sensitive mutations into the genetic background strongly enhanced the toxicity of SOD1 mutants, resulting in exposure of several deleterious phenotypes at permissive conditions in a manner dependent on the specific SOD1 mutation. The nature of the observed phenotype was dependent on the temperature-sensitive mutation present, while its penetrance reflected the specific combination of temperature-sensitive and SOD1 mutations. Thus, the specific toxic phenotypes of conformational disease may not be simply due to misfolding/aggregation toxicity of the causative mutant proteins, but may be defined by their genetic interactions with cellular pathways harboring mildly destabilizing missense alleles. PMID:19266020

  16. The joint effects of background selection and genetic recombination on local gene genealogies.

    PubMed

    Zeng, Kai; Charlesworth, Brian

    2011-09-01

    Background selection, the effects of the continual removal of deleterious mutations by natural selection on variability at linked sites, is potentially a major determinant of DNA sequence variability. However, the joint effects of background selection and genetic recombination on the shape of the neutral gene genealogy have proved hard to study analytically. The only existing formula concerns the mean coalescent time for a pair of alleles, making it difficult to assess the importance of background selection from genome-wide data on sequence polymorphism. Here we develop a structured coalescent model of background selection with recombination and implement it in a computer program that efficiently generates neutral gene genealogies for an arbitrary sample size. We check the validity of the structured coalescent model against forward-in-time simulations and show that it accurately captures the effects of background selection. The model produces more accurate predictions of the mean coalescent time than the existing formula and supports the conclusion that the effect of background selection is greater in the interior of a deleterious region than at its boundaries. The level of linkage disequilibrium between sites is elevated by background selection, to an extent that is well summarized by a change in effective population size. The structured coalescent model is readily extendable to more realistic situations and should prove useful for analyzing genome-wide polymorphism data.

  17. Influence of Genetic Background on Apathy-Like Behavior in Triple Transgenic AD Mice.

    PubMed

    Pardossi-Piquard, R; Lauritzen, I; Bauer, C; Sacco, G; Robert, P; Checler, F

    2016-01-01

    Apathy is an early and common neuropsychiatric syndrome in Alzheimer's disease (AD) patients. In clinical trials, apathy is associated with decreased motor activity that can be monitored by actigraphy. The triple transgenic mouse AD model (3xTgAD) has been shown to recapitulate the biochemical lesions as well as many of the synaptic and cognitive alterations associated with AD. In the present work we found that these mice also develop an early and consistent apathy-like behavior as evidenced by a drastic decrease in spontaneous activity measured by actimetry. We recently established that these mice also display an intraneuronal accumulation of the β-secretase-derived βAPP fragment (C99) appearing early, in absence of Aβ. Interestingly, we found that the apathy-like behavior observed in 3xTgAD mice was temporally associated with C99 accumulation and synaptic alterations. Since it is well known that the genetic background can strongly influence behavior and can induce transcriptional variability in animal models, we decided to determine the influence of genetic background on the above-described alterations. We backcrossed 3xTgAD mice to C57BL/6 and found that the genetic background had no influence on either C99 accumulation or synaptic plasticity alterations, but strongly affected the apathy-like behavior. PMID:27040141

  18. Genetic backgrounds and redox conditions influence morphological characteristics and cell differentiation of osteoclasts in mice.

    PubMed

    Narahara, Shun; Matsushima, Haruna; Sakai, Eiko; Fukuma, Yutaka; Nishishita, Kazuhisa; Okamoto, Kuniaki; Tsukuba, Takayuki

    2012-04-01

    Osteoclasts (OCLs) are multinucleated giant cells and are formed by the fusion of mononuclear progenitors of monocyte/macrophage lineage. It is known that macrophages derived from different genetic backgrounds exhibit quite distinct characteristics of immune responses. However, it is unknown whether OCLs from different genetic backgrounds show distinct characteristics. In this study, we showed that bone-marrow macrophages (BMMs) derived from C57BL/6, BALB/c and ddY mice exhibited considerably distinct morphological characteristics and cell differentiation into OCLs. The differentiation of BMMs into OCLs was comparatively quicker in the C57BL/6 and ddY mice, while that of BALB/c mice was rather slow. Morphologically, ddY OCLs showed a giant cell with a round shape, C57BL/6 OCLs were of a moderate size with many protrusions and BALB/c OCLs had the smallest size with fewer nuclei. The intracellular signaling of differentiation and expression levels of marker proteins of OCLs were different in the respective strains. Treatment of BMMs from the three different strains with the reducing agent N-acetylcysteine (NAC) or with the oxidation agent hydrogen peroxide (H(2)O(2)) induced changes in the shape and sizes of the cells and caused distinct patterns of cell differentiation and survival. Thus, genetic backgrounds and redox conditions regulate the morphological characteristics and cell differentiation of OCLs.

  19. Host Genetic Background Strongly Influences the Response to Influenza A Virus Infections

    PubMed Central

    Srivastava, Barkha; Błażejewska, Paulina; Heßmann, Manuela; Bruder, Dunja; Geffers, Robert; Mauel, Susanne; Gruber, Achim D.; Schughart, Klaus

    2009-01-01

    The genetic make-up of the host has a major influence on its response to combat pathogens. For influenza A virus, several single gene mutations have been described which contribute to survival, the immune response and clearance of the pathogen by the host organism. Here, we have studied the influence of the genetic background to influenza A H1N1 (PR8) and H7N7 (SC35M) viruses. The seven inbred laboratory strains of mice analyzed exhibited different weight loss kinetics and survival rates after infection with PR8. Two strains in particular, DBA/2J and A/J, showed very high susceptibility to viral infections compared to all other strains. The LD50 to the influenza virus PR8 in DBA/2J mice was more than 1000-fold lower than in C57BL/6J mice. High susceptibility in DBA/2J mice was also observed after infection with influenza strain SC35M. In addition, infected DBA/2J mice showed a higher viral load in their lungs, elevated expression of cytokines and chemokines, and a more severe and extended lung pathology compared to infected C57BL/6J mice. These findings indicate a major contribution of the genetic background of the host to influenza A virus infections. The overall response in highly susceptible DBA/2J mice resembled the pathology described for infections with the highly virulent influenza H1N1-1918 and newly emerged H5N1 viruses. PMID:19293935

  20. Mutualism effectiveness and vertical transmission of symbiotic fungal endophytes in response to host genetic background

    PubMed Central

    Gundel, Pedro E; Martínez-Ghersa, María A; Omacini, Marina; Cuyeu, Romina; Pagano, Elba; Ríos, Raúl; Ghersa, Claudio M

    2012-01-01

    Certain species of the Pooideae subfamily develop stress tolerance and herbivory resistance through symbiosis with vertically transmitted, asexual fungi. This symbiosis is specific, and genetic factors modulate the compatibility between partners. Although gene flow is clearly a fitness trait in allogamous grasses, because it injects hybrid vigor and raw material for evolution, it could reduce compatibility and thus mutualism effectiveness. To explore the importance of host genetic background in modulating the performance of symbiosis, Lolium multiflorum plants, infected and noninfected with Neotyphodium occultans, were crossed with genetically distant plants of isolines (susceptible and resistant to diclofop-methyl herbicide) bred from two cultivars and exposed to stress. The endophyte improved seedling survival in genotypes susceptible to herbicide, while it had a negative effect on one of the genetically resistant crosses. Mutualism provided resistance to herbivory independently of the host genotype, but this effect vanished under stress. While no endophyte effect was observed on host reproductive success, it was increased by interpopulation plant crosses. Neither gene flow nor herbicide had an important impact on endophyte transmission. Host fitness improvements attributable to gene flow do not appear to result in direct conflict with mutualism while this seems to be an important mechanism for the ecological and contemporary evolution of the symbiotum. PMID:23346228

  1. Genetic Background Modulates Gene Expression Profile Induced by Skin Irradiation in Ptch1 Mice

    SciTech Connect

    Galvan, Antonella; Noci, Sara; Mancuso, Mariateresa; Pazzaglia, Simonetta; Saran, Anna; Dragani, Tommaso A.

    2008-12-01

    Purpose: Ptch1 germ-line mutations in mice predispose to radiation-induced basal cell carcinoma of the skin, with tumor incidence modulated by the genetic background. Here, we examined the possible mechanisms underlying skin response to radiation in F1 progeny of Ptch1{sup neo67/+} mice crossed with either skin tumor-susceptible (Car-S) or -resistant (Car-R) mice and X-irradiated (3 Gy) at 2 days of age or left untreated. Methods and Materials: We conducted a gene expression profile analysis in mRNA samples extracted from the skin of irradiated or control mice, using Affymetrix whole mouse genome expression array. Confirmation of the results was done using real-time reverse-transcriptase polymerase chain reaction. Results: Analysis of the gene expression profile of normal skin of F1 mice at 4 weeks of age revealed a similar basal profile in the nonirradiated mice, but alterations in levels of 71 transcripts in irradiated Ptch1{sup neo67/+} mice of the Car-R cross and modulation of only eight genes in irradiated Ptch1{sup neo67/+} mice of the Car-S cross. Conclusions: These results indicate that neonatal irradiation causes a persistent change in the gene expression profile of the skin. The tendency of mice genetically resistant to skin tumorigenesis to show a more complex pattern of transcriptional response to radiation than do genetically susceptible mice suggests a role for this response in genetic resistance to basal cell tumorigenesis.

  2. Genetic background of resistance to cadmium-induced testicular toxicity in inbred Wistar-Imamichi rats.

    PubMed

    Shimada, Hideaki; Hata, Iori; Hashiguchi, Takashi; Imamura, Yorishige

    2011-10-01

    We have previously reported that inbred Wistar-Imamichi (WI) rats are highly resistant to cadmium (Cd)-induced testicular toxicity compared with inbred Fischer 344 (F344) rats. The present study was to elucidate the genetic background of resistance to Cd-induced testicular toxicity in WI rats. The genetic analysis of susceptibility to Cd-induced testicular toxicity was conducted by using Cd-resistant WI and Cd-sensitive F344 strains as the parental rats and by using the testicular hemoglobin level as the indicator. In the frequency distribution of testicular hemoglobin levels in parental, first filial (F(1)) and second filial (F(2)) rats treated with Cd at a dose of 2.0 mg/kg, F(1) rats had testicular hemoglobin levels intermediate to WI and F344 rats, and F(2) rats segregated into three groups of low, intermediate, and high phenotypes at the expected ratio. Furthermore, the backcross progeny between WI and F(1) or between F344 and F(1) segregated into two groups with the expected ratio. Based on a simple Mendelian genetic analysis, these segregation patterns lead us to conclude that two codominant alleles at a gene locus are responsible for the susceptibility to Cd-induced testicular toxicity in rats. This is the first report for the genetic analysis of susceptibility to Cd-induced testicular toxicity in inbred rat strains. PMID:21318357

  3. Chromosome Fragments in DICTYOSTELIUM DISCOIDEUM Obtained from Parasexual Crosses between Strains of Different Genetic Background

    PubMed Central

    Williams, Keith L.; Robson, Gillian E.; Welker, Dennis L.

    1980-01-01

    The first aneuploid strains of Dictyostelium discoideum have been unambiguously characterized, using cytological and genetic analysis. Three independently isolated, but genetically similar, fragment chromosomes have been observed in segregants from diploids formed between haploid strains derived from the NC4 and V12 isolates of D. discoideum. Once generated, the fragment chromosomes, all of which have V12-derived centromeres, can be maintained in a NC4 genetic background. Genetic evidence is consistent with the view that all three fragment chromosomes studied encompass the region from the centromere to the whiA locus of linkage group II and terminate in the interval between whiA and acrA. From cytological studies, one of the fragment chromosomes consists of approximately half of linkage group II.—We observed no deleterious effect on viability or asexual fruiting-body formation in either haploid or diploid strains carrying an additional incomplete chromosome and hence are disomic or trisomic, respectively, for part of linkage group II. The incomplete chromosome is lost at a frequency of 2 to 3% from disomic and trisomic strains, but surprisingly this loss is not increased in the presence of the haploidizing agent, benlate. A new locus (clyA), whose phenotype is altered colony morphology, is assigned to the region of linkage group II encompassed by the fragment chromosome. PMID:17249037

  4. Genetic background of resistance to cadmium-induced testicular toxicity in inbred Wistar-Imamichi rats.

    PubMed

    Shimada, Hideaki; Hata, Iori; Hashiguchi, Takashi; Imamura, Yorishige

    2011-10-01

    We have previously reported that inbred Wistar-Imamichi (WI) rats are highly resistant to cadmium (Cd)-induced testicular toxicity compared with inbred Fischer 344 (F344) rats. The present study was to elucidate the genetic background of resistance to Cd-induced testicular toxicity in WI rats. The genetic analysis of susceptibility to Cd-induced testicular toxicity was conducted by using Cd-resistant WI and Cd-sensitive F344 strains as the parental rats and by using the testicular hemoglobin level as the indicator. In the frequency distribution of testicular hemoglobin levels in parental, first filial (F(1)) and second filial (F(2)) rats treated with Cd at a dose of 2.0 mg/kg, F(1) rats had testicular hemoglobin levels intermediate to WI and F344 rats, and F(2) rats segregated into three groups of low, intermediate, and high phenotypes at the expected ratio. Furthermore, the backcross progeny between WI and F(1) or between F344 and F(1) segregated into two groups with the expected ratio. Based on a simple Mendelian genetic analysis, these segregation patterns lead us to conclude that two codominant alleles at a gene locus are responsible for the susceptibility to Cd-induced testicular toxicity in rats. This is the first report for the genetic analysis of susceptibility to Cd-induced testicular toxicity in inbred rat strains.

  5. Genetic background matters: a plant-virus gene-for-gene interaction is strongly influenced by genetic contexts.

    PubMed

    Montarry, Josselin; Doumayrou, Juliette; Simon, Vincent; Moury, Benoìt

    2011-12-01

    Evolutionary processes responsible for parasite adaptation to their hosts determine our capacity to manage sustainably resistant plant crops. Most plant-parasite interactions studied so far correspond to gene-for-gene models in which the nature of the alleles present at a plant resistance locus and at a pathogen pathogenicity locus determine entirely the outcome of their confrontation. The interaction between the pepper pvr2 resistance locus and Potato virus Y (PVY) genome-linked protein VPg locus obeys this kind of model. Using synthetic chimeras between two parental PVY cDNA clones, we showed that the viral genetic background surrounding the VPg pathogenicity locus had a strong impact on the resistance breakdown capacity of the virus. Indeed, recombination of the cylindrical inclusion (CI) coding region between two PVY cDNA clones multiplied by six the virus capacity to break down the pvr2(3) -mediated resistance. High-throughput sequencing allowed the exploration of the diversity of PVY populations in response to the selection pressure of the pvr2(3) resistance. The CI chimera, which possessed an increased resistance breakdown capacity, did not show an increased mutation accumulation rate. Instead, selection of the most frequent resistance-breaking mutation seemed to be more efficient for the CI chimera than for the parental virus clone. These results echoed previous observations, which showed that the plant genetic background in which the pvr2(3) resistance gene was introduced modified strongly the efficiency of selection of resistance-breaking mutations by PVY. In a broader context, the PVY CI coding region is one of the first identified genetic factors to determine the evolvability of a plant virus. PMID:21726391

  6. Evolutionary concepts in ecotoxicology: tracing the genetic background of differential cadmium sensitivities in invertebrate lineages.

    PubMed

    Dallinger, Reinhard; Höckner, Martina

    2013-07-01

    In many toxicological and ecotoxicological studies and experimental setups, the investigator is mainly interested in traditional parameters such as toxicity data and effects of toxicants on molecular, cellular or physiological functions of individuals, species or statistical populations. It is clear, however, that such approaches focus on the phenotype level of animal species, whilst the genetic and evolutionary background of reactions to environmental toxicants may remain untold. In ecotoxicological risk assessment, moreover, species sensitivities towards pollutants are often regarded as random variables in a statistical approach. Beyond statistics, however, toxicant sensitivity of every species assumes a biological significance, especially if we consider that sensitivity traits have developed in lineages of species with common evolutionary roots. In this article, the genetic and evolutionary background of differential Cd sensitivities among invertebrate populations and species and their potential of adaptation to environmental Cd exposure will be highlighted. Important evolutionary and population genetic concepts such as genome structure and their importance for evolutionary adaptation, population structure of affected individuals, as well as micro and macroevolutionary mechanisms of Cd resistance in invertebrate lineages will be stressed by discussing examples of work from our own laboratory along with a review of relevant literature data and a brief discussion of open questions along with some perspectives for further research. Both, differences and similarities in Cd sensitivity traits of related invertebrate species can only be understood if we consider the underlying evolutionary processes and genetic (or epigenetic) mechanisms. Keeping in mind this perception can help us to better understand and interpret more precisely why the sensitivity of some species or species groups towards a certain toxicant (or metal) may be ranked in the lower or higher range of

  7. Effect of the genetic background on the reproduction of leptin-deficient obese mice.

    PubMed

    Ewart-Toland, A; Mounzih, K; Qiu, J; Chehab, F F

    1999-02-01

    Obesity is often associated with an impairment of the hypothalamic-pituitary-gonadal axis. The leptin-deficient ob/ob mouse model is characterized by a morbid obesity with a sterility in males and females that is corrected by continuous leptin treatment. Since ob/ob mice are maintained on the C57BL/6J inbred genetic background, we sought to determine whether their infertility can be corrected without leptin treatment but via the effect of modifier genes brought into the obese-sterile phenotype by a different genetic background. Thus, we generated via an F2 intercross ob/ob mice on a mixed C57BL/6J-BALB/cJ genetic background and assayed them for fertility by mating with wild-type C57BL/6J mice. Whereas genetically heterogeneous F2 obese females remained sterile like male and female C57BL/6J ob/ob mice, 41% of F2 C57BL/6J-BALB/cJ obese males were capable of reproducing despite a morbidly obese state. Therefore, the sterility of the original C57BL/6J ob/ob mouse model was genetically corrected independently of its obese state via the effects of modifier genes. Unlike testosterone levels, triglyceride levels, and testes weight-to-body weight ratios, which were all higher in fertile vs. sterile mice, glucose levels were similar in both groups, indicating that the underlying hyperglycemia of ob/ob mice was not an impediment to the onset of fertility. A genome-wide scan in F2 ob/ob males resulted in the localization of four modifier loci on chromosomes 1, 3, 5, and 14 with respective quantitative traits consisting of number of pregnancies, testes weights normalized to body weights, body weight at 8 weeks of age, and circulating testosterone. We conclude that the inheritance of modifier genes at the identified loci acts to promote fertility of otherwise sterile leptin-deficient obese male mice.

  8. The effect of genetic background on behavioral manifestation of Grid2(Lc) mutation.

    PubMed

    Cendelin, Jan; Tuma, Jan; Korelusova, Ivana; Vozeh, Frantisek

    2014-09-01

    Mutant mice are commonly used models of hereditary diseases. Nevertheless, these mice have phenotypic traits of the original strain, which could interfere with the manifestation of the mutation of interest. Lurcher mice represent a model of olivocerebellar degeneration, which is caused by the Grid2(Lc) mutation. Lurchers show ataxia and various cognitive and behavioral abnormalities. The most commonly used strains of Lurcher mice are B6CBA and C3H, but there is no information about the role of genetic background on the Grid2(Lc) manifestation. The aim of this work was to compare spatial navigation in the Morris water maze, spontaneous activity in the open field and motor skills on the horizontal wire, slanted ladder and rotarod in B6CBA and C3H Lurcher mutant and wild type mice. The study showed impaired motor skills and water maze performance in both strains of Lurcher mice. Both C3H Lurcher and C3H wild type mice had poorer performances in the water maze task than their B6CBA counterparts. In the open field test, C3H mice showed higher activity and lower thigmotaxis. The study showed that genetic backgrounds can modify manifestations of the Lurcher mutation. In this case, B6CBA Lurcher mice models probably have more validity when studying the behavioral aspects of cerebellar degeneration than C3H Lurcher mice, since they do not combine abnormalities related to the Grid2(Lc) mutation with strain-specific problems.

  9. Genetic background drives transcriptional variation in human induced pluripotent stem cells.

    PubMed

    Rouhani, Foad; Kumasaka, Natsuhiko; de Brito, Miguel Cardoso; Bradley, Allan; Vallier, Ludovic; Gaffney, Daniel

    2014-06-01

    Human iPS cells have been generated using a diverse range of tissues from a variety of donors using different reprogramming vectors. However, these cell lines are heterogeneous, which presents a limitation for their use in disease modeling and personalized medicine. To explore the basis of this heterogeneity we generated 25 iPS cell lines under normalised conditions from the same set of somatic tissues across a number of donors. RNA-seq data sets from each cell line were compared to identify the majority contributors to transcriptional heterogeneity. We found that genetic differences between individual donors were the major cause of transcriptional variation between lines. In contrast, residual signatures from the somatic cell of origin, so called epigenetic memory, contributed relatively little to transcriptional variation. Thus, underlying genetic background variation is responsible for most heterogeneity between human iPS cell lines. We conclude that epigenetic effects in hIPSCs are minimal, and that hIPSCs are a stable, robust and powerful platform for large-scale studies of the function of genetic differences between individuals. Our data also suggest that future studies using hIPSCs as a model system should focus most effort on collection of large numbers of donors, rather than generating large numbers of lines from the same donor.

  10. The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background

    PubMed Central

    Marsh, Sharon; Hu, Junbo; Feng, Wenke

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression. PMID:27247565

  11. The Pathogenesis of Nonalcoholic Fatty Liver Disease: Interplay between Diet, Gut Microbiota, and Genetic Background.

    PubMed

    Yu, Jinsheng; Marsh, Sharon; Hu, Junbo; Feng, Wenke; Wu, Chaodong

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world, and it comprises a spectrum of hepatic abnormalities from simple hepatic steatosis to steatohepatitis, fibrosis, cirrhosis, and liver cancer. While the pathogenesis of NAFLD remains incompletely understood, a multihit model has been proposed that accommodates causal factors from a variety of sources, including intestinal and adipose proinflammatory stimuli acting on the liver simultaneously. Prior cellular and molecular studies of patient and animal models have characterized several common pathogenic mechanisms of NAFLD, including proinflammation cytokines, lipotoxicity, oxidative stress, and endoplasmic reticulum stress. In recent years, gut microbiota has gained much attention, and dysbiosis is recognized as a crucial factor in NAFLD. Moreover, several genetic variants have been identified through genome-wide association studies, particularly rs738409 (Ile748Met) in PNPLA3 and rs58542926 (Glu167Lys) in TM6SF2, which are critical risk alleles of the disease. Although a high-fat diet and inactive lifestyles are typical risk factors for NAFLD, the interplay between diet, gut microbiota, and genetic background is believed to be more important in the development and progression of NAFLD. This review summarizes the common pathogenic mechanisms, the gut microbiota relevant mechanisms, and the major genetic variants leading to NAFLD and its progression. PMID:27247565

  12. [Genetic mapping of resistant gene to southern corn rust and the tagging analysis on different genetic background].

    PubMed

    Chen, Cui-Xia; Xing, Quan-Hua; Liang, Chun-Yang; Yu, Yuan-Jie; Liang, Feng-Shan; Wang, Hong-Gang; Wang, Zhen-Lin; Wang, Bin

    2003-04-01

    Southern corn rust (SCR) is a destructive disease in maize. The inbred line Qi319 is highly resistant to southern corn rust. SSR technique was employed to preliminary mapping of the resistance gene. Bulked segregant analysis revealed that two primers, phi 118 and phi 041, amplified polymorphic bands. SSR analysis on populations indicated the two primers were linked to the rust resistance gene, which was mapped on the short arm of chromosome 10. In addition, comparative analysis of the amplification bands among different populations revealed that the amplification products with the same primer in different populations were dissimilar. This result indicates that the genetic background may affect results of gene mapping and tagging. So, it is important to select suitable population to performing molecular marker analysis and gene mapping.

  13. Genetic background influences murine prostate gene expression: implications for cancer phenotypes

    PubMed Central

    Bianchi-Frias, Daniella; Pritchard, Colin; Mecham, Brigham H; Coleman, Ilsa M; Nelson, Peter S

    2007-01-01

    Background Cancer of the prostate is influenced by both genetic predisposition and environmental factors. The identification of genes capable of modulating cancer development has the potential to unravel disease heterogeneity and aid diagnostic and prevention strategies. To this end, mouse models have been developed to isolate the influences of individual genetic lesions in the context of consistent genotypes and environmental exposures. However, the normal prostatic phenotypic variability dictated by a genetic background that is potentially capable of influencing the process of carcinogenesis has not been established. Results In this study we used microarray analysis to quantify transcript levels in the prostates of five commonly studied inbred mouse strains. We applied a multiclass response t-test and determined that approximately 13% (932 genes) exhibited differential expression (range 1.3-190-fold) in any one strain relative to other strains (false discovery rate ≤10%). Expression differences were confirmed by quantitative RT-PCR, or immunohistochemistry for several genes previously shown to influence cancer progression, such as Psca, Mmp7, and Clusterin. Analyses of human prostate transcripts orthologous to variable murine prostate genes identified differences in gene expression in benign epithelium that correlated with the differentiation state of adjacent tumors. For example, the gene encoding apolipoprotein D, which is known to enhance resistance to cell stress, was expressed at significantly greater levels in benign epithelium associated with high-grade versus low-grade cancers. Conclusion These studies support the concept that the cellular, tissue, and organismal context contribute to oncogenesis and suggest that a predisposition to a sequence of events leading to pathology may exist prior to cancer initiation. PMID:17577413

  14. Genetic background of uric acid metabolism in a patient with severe chronic tophaceous gout.

    PubMed

    Petru, Lenka; Pavelcova, Katerina; Sebesta, Ivan; Stiburkova, Blanka

    2016-09-01

    Hyperuricemia depends on the balance of endogenous production and renal excretion of uric acid. Transporters for urate are located in the proximal tubule where uric acid is secreted and extensively reabsorbed: secretion is principally ensured by the highly variable ABCG2 gene. Enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) plays a central role in purine metabolism and its deficiency is an X-linked inherited metabolic disorder associated with clinical manifestations of purine overproduction. Here we report the case of a middle-aged man with severe chronic tophaceous gout with a poor response to allopurinol and requiring repeated surgical intervention. We identified the causal mutations in the HPRT1 gene, variant c.481G>T (p.A161S), and in the crucial urate transporter ABCG2, a heterozygous variant c.421C>A (p.Q141K). This case shows the value of an analysis of the genetic background of serum uric acid. PMID:27288985

  15. Genetic background modulates outcome of therapeutic amyloid peptides in treatment of neuroinflammation.

    PubMed

    Kraus, Allison; Race, Brent; Phillips, Katie; Winkler, Clayton; Saturday, Greg; Kurnellas, Michael; Rothbard, Jonathan B; Groveman, Bradley R; Steinman, Lawrence; Caughey, Byron

    2016-09-15

    Amyloid hexapeptide molecules are effective in the treatment of the murine model of neuroinflammation, known as experimental autoimmune encephalomyelitis (EAE). Efficacy however differs between two inbred mouse strains, C57BL/6J (B6) and C57BL/10SnJ (B10). Amyloid hexapeptide treatments improved the clinical outcomes of B6, but not B10 mice, indicating that genetic background influences therapeutic efficacy. Moreover, although previous studies indicated that prion protein deficiency results in more severe EAE in B6 mice, we observed no such effect in B10 mice. In addition, we found that amyloid hexapeptide treatments of B10 and B6 mice elicited differential IL4 responses. Thus, the modulatory potential of prion protein and related treatments with other amyloid hexapeptides in EAE depends on mouse strain. PMID:27609274

  16. SAP modulates B cell functions in a genetic background-dependent manner.

    PubMed

    Detre, Cynthia; Yigit, Burcu; Keszei, Marton; Castro, Wilson; Magelky, Erica M; Terhorst, Cox

    2013-06-01

    Mutations affecting the SLAM-associated protein (SAP) are responsible for the X-linked lympho-proliferative syndrome (XLP), a severe primary immunodeficiency syndrome with disease manifestations that include fatal mononucleosis, B cell lymphoma and dysgammaglobulinemia. It is well accepted that insufficient help by SAP-/- CD4+ T cells, in particular during the germinal center reaction, is a component of dysgammaglobulinemia in XLP patients and SAP-/- animals. It is however not well understood whether in XLP patients and SAP-/- mice B cell functions are affected, even though B cells themselves do not express SAP. Here we report that B cell intrinsic responses to haptenated protein antigens are impaired in SAP-/- mice and in Rag-/- mice into which B cells derived from SAP-/- mice together with wt CD4+ T cells had been transferred. This impaired B cells functions are in part depending on the genetic background of the SAP-/- mouse, which affects B cell homeostasis. Surprisingly, stimulation with an agonistic anti-CD40 causes strong in vivo and in vitro B cell responses in SAP-/- mice. Taken together, the data demonstrate that genetic factors play an important role in the SAP-related B cell functions. The finding that anti-CD40 can in part restore impaired B cell responses in SAP-/- mice, suggests potentially novel therapeutic interventions in subsets of XLP patients.

  17. A Wolbachia-associated fitness benefit depends on genetic background in Drosophila simulans

    PubMed Central

    Dean, Matthew D

    2006-01-01

    The α-proteobacteria Wolbachia infect a number of insect species and influence host reproduction to favour the spread of infected females through a population. The fitness effect of this infection is important in understanding the spread and maintenance of Wolbachia within and among host populations. However, a full elucidation of fitness effect requires careful control of host genetic background. Here, I transferred a single clone of Wolbachia (the wHa strain) into three genetically distinct isofemale lines of the fly Drosophila simulans using microinjection methodology. These lines carried one of the three described mitochondrial haplogroups (siI, siII or siIII) and differ in nuclear genome as well. Population cage assays showed that wHa-infected siIII flies enjoyed a dramatic fitness benefit compared to uninfected siIII. In contrast, wHa did not affect the fitness of siI or siII flies. This study points to the importance of host-by-symbiont interaction terms that may play an important role in organismal-fitness. PMID:16777731

  18. Chronic kidney disease induced in mice by reversible unilateral ureteral obstruction is dependent on genetic background.

    PubMed

    Puri, Tipu S; Shakaib, Mohammed I; Chang, Anthony; Mathew, Liby; Olayinka, Oladunni; Minto, Andrew W M; Sarav, Menaka; Hack, Bradley K; Quigg, Richard J

    2010-04-01

    Chronic kidney disease (CKD) begins with renal injury; the progression thereafter depends upon a number of factors, including genetic background. Unilateral ureteral obstruction (UUO) is a well-described model of renal fibrosis and as such is considered a model of CKD. We used an improved reversible unilateral ureteral obstruction (rUUO) model in mice to study the strain dependence of development of CKD after obstruction-mediated injury. C57BL/6 mice developed CKD after reversal of three or more days of ureteral obstruction as assessed by blood urea nitrogen (BUN) measurements (>40 mg/dl). In contrast, BALB/c mice were resistant to CKD with up to 10 days ureteral obstruction. During rUUO, C57BL/6 mice exhibited pronounced inflammatory and intrinsic proliferative cellular responses, disruption of renal architecture, and ultimately fibrosis. By comparison, BALB/c mice had more controlled and measured extrinsic and intrinsic responses to injury with a return to normal within several weeks after release of ureteral obstruction. Our findings provide a model that allows investigation of the genetic basis of events during recovery from injury that contribute to the development of CKD.

  19. Quantitative trait loci for life span in Drosophila melanogaster: interactions with genetic background and larval density.

    PubMed Central

    Leips, J; Mackay, T F

    2000-01-01

    The genetic architecture of variation in adult life span was examined for a population of recombinant inbred lines, each of which had been crossed to both inbred parental strains from which the lines were derived, after emergence from both high and low larval density. QTL affecting life span were mapped within each sex and larval density treatment by linkage to highly polymorphic roo-transposable element markers, using a composite interval mapping method. We detected a total of six QTL affecting life span; the additive effects and degrees of dominance for all were highly sex- and larval environment-specific. There were significant epistatic interactions between five of the life span QTL, the effects of which also differed according to genetic background, sex, and larval density. Five additional QTL were identified that contributed to differences among lines in their sensitivity to variation in larval density. Further fine-scale mapping is necessary to determine whether candidate genes within the regions to which the QTL map are actually responsible for the observed variation in life span. PMID:10924473

  20. MeCP2 Related Studies Benefit from the Use of CD1 as Genetic Background

    PubMed Central

    Cobolli Gigli, Clementina; Scaramuzza, Linda; Gandaglia, Anna; Bellini, Elisa; Gabaglio, Marina; Parolaro, Daniela; Kilstrup-Nielsen, Charlotte; Bedogni, Francesco

    2016-01-01

    MECP2 mutations cause a number of neurological disorders of which Rett syndrome (RTT) represents the most thoroughly analysed condition. Many Mecp2 mouse models have been generated through the years; their validity is demonstrated by the presence of a broad spectrum of phenotypes largely mimicking those manifested by RTT patients. These mouse models, between which the C57BL/6 Mecp2tm1.1Bird strain probably represents the most used, enabled to disclose much of the roles of Mecp2. However, small litters with little viability and poor maternal care hamper the maintenance of the colony, thus limiting research on such animals. For this reason, past studies often used Mecp2 mouse models on mixed genetic backgrounds, thus opening questions on whether modifier genes could be responsible for at least part of the described effects. To verify this possibility, and facilitate the maintenance of the Mecp2 colony, we transferred the Mecp2tm1.1Bird allele on the stronger CD1 background. The CD1 strain is easier to maintain and largely recapitulates the phenotypes already described in Mecp2-null mice. We believe that this mouse model will foster the research on RTT. PMID:27097329

  1. MeCP2 Related Studies Benefit from the Use of CD1 as Genetic Background.

    PubMed

    Cobolli Gigli, Clementina; Scaramuzza, Linda; Gandaglia, Anna; Bellini, Elisa; Gabaglio, Marina; Parolaro, Daniela; Kilstrup-Nielsen, Charlotte; Landsberger, Nicoletta; Bedogni, Francesco

    2016-01-01

    MECP2 mutations cause a number of neurological disorders of which Rett syndrome (RTT) represents the most thoroughly analysed condition. Many Mecp2 mouse models have been generated through the years; their validity is demonstrated by the presence of a broad spectrum of phenotypes largely mimicking those manifested by RTT patients. These mouse models, between which the C57BL/6 Mecp2tm1.1Bird strain probably represents the most used, enabled to disclose much of the roles of Mecp2. However, small litters with little viability and poor maternal care hamper the maintenance of the colony, thus limiting research on such animals. For this reason, past studies often used Mecp2 mouse models on mixed genetic backgrounds, thus opening questions on whether modifier genes could be responsible for at least part of the described effects. To verify this possibility, and facilitate the maintenance of the Mecp2 colony, we transferred the Mecp2tm1.1Bird allele on the stronger CD1 background. The CD1 strain is easier to maintain and largely recapitulates the phenotypes already described in Mecp2-null mice. We believe that this mouse model will foster the research on RTT.

  2. Unifying genetic canalization, genetic constraint, and genotype-by-environment interaction: QTL by genomic background by environment interaction of flowering time in Boechera stricta.

    PubMed

    Lee, Cheng-Ruei; Anderson, Jill T; Mitchell-Olds, Thomas

    2014-10-01

    Natural populations exhibit substantial variation in quantitative traits. A quantitative trait is typically defined by its mean and variance, and to date most genetic mapping studies focus on loci altering trait means but not (co)variances. For single traits, the control of trait variance across genetic backgrounds is referred to as genetic canalization. With multiple traits, the genetic covariance among different traits in the same environment indicates the magnitude of potential genetic constraint, while genotype-by-environment interaction (GxE) concerns the same trait across different environments. While some have suggested that these three attributes of quantitative traits are different views of similar concepts, it is not yet clear, however, whether they have the same underlying genetic mechanism. Here, we detect quantitative trait loci (QTL) influencing the (co)variance of phenological traits in six distinct environments in Boechera stricta, a close relative of Arabidopsis. We identified nFT as the QTL altering the magnitude of phenological trait canalization, genetic constraint, and GxE. Both the magnitude and direction of nFT's canalization effects depend on the environment, and to our knowledge, this reversibility of canalization across environments has not been reported previously. nFT's effects on trait covariance structure (genetic constraint and GxE) likely result from the variable and reversible canalization effects across different traits and environments, which can be explained by the interaction among nFT, genomic backgrounds, and environmental stimuli. This view is supported by experiments demonstrating significant nFT by genomic background epistatic interactions affecting phenological traits and expression of the candidate gene, FT. In contrast to the well-known canalization gene Hsp90, the case of nFT may exemplify an alternative mechanism: Our results suggest that (at least in traits with major signal integrators such as flowering time) genetic

  3. Identification of genetic variants associated with maize flowering time using an extremely large multi-genetic background population.

    PubMed

    Li, Yong-Xiang; Li, Chunhui; Bradbury, Peter J; Liu, Xiaolei; Lu, Fei; Romay, Cinta M; Glaubitz, Jeffrey C; Wu, Xun; Peng, Bo; Shi, Yunsu; Song, Yanchun; Zhang, Dengfeng; Buckler, Edward S; Zhang, Zhiwu; Li, Yu; Wang, Tianyu

    2016-06-01

    Flowering time is one of the major adaptive traits in domestication of maize and an important selection criterion in breeding. To detect more maize flowering time variants we evaluated flowering time traits using an extremely large multi- genetic background population that contained more than 8000 lines under multiple Sino-United States environments. The population included two nested association mapping (NAM) panels and a natural association panel. Nearly 1 million single-nucleotide polymorphisms (SNPs) were used in the analyses. Through the parallel linkage analysis of the two NAM panels, both common and unique flowering time regions were detected. Genome wide, a total of 90 flowering time regions were identified. One-third of these regions were connected to traits associated with the environmental sensitivity of maize flowering time. The genome-wide association study of the three panels identified nearly 1000 flowering time-associated SNPs, mainly distributed around 220 candidate genes (within a distance of 1 Mb). Interestingly, two types of regions were significantly enriched for these associated SNPs - one was the candidate gene regions and the other was the approximately 5 kb regions away from the candidate genes. Moreover, the associated SNPs exhibited high accuracy for predicting flowering time. PMID:27012534

  4. Sensitivity of the distribution of mutational fitness effects to environment, genetic background, and adaptedness: a case study with Drosophila.

    PubMed

    Wang, Alethea D; Sharp, Nathaniel P; Agrawal, Aneil F

    2014-03-01

    Heterogeneity in the fitness effects of individual mutations has been found across different environmental and genetic contexts. Going beyond effects on individual mutations, how is the distribution of selective effects, f(s), altered by changes in genetic and environmental context? In this study, we examined changes in the major features of f(s) by estimating viability selection on 36 individual mutations in Drosophila melanogaster across two different environments in two different genetic backgrounds that were either adapted or nonadapted to the two test environments. Both environment and genetic background affected selection on individual mutations. However, the overall distribution f(s) appeared robust to changes in genetic background but both the mean, E(s), and the variance, V(s) were dependent on the environment. Between these two properties, V(s) was more sensitive to environmental change. Contrary to predictions of fitness landscape theory, the match between genetic background and assay environment (i.e., adaptedness) had little effect on f(s).

  5. Genetic background but not metallothionein phenotype dictates sensitivity to cadmium-induced testicular injury in mice.

    PubMed

    Liu, J; Corton, C; Dix, D J; Liu, Y; Waalkes, M P; Klaassen, C D

    2001-10-01

    Sensitivity to cadmium (Cd)-induced testicular injury varies greatly among mouse strains. For instance, 129/SvJ (129) mice are highly sensitive while C57BL/6J (C57) mice are refractory to Cd-induced testicular injury. Metallothionein (MT), a Cd-binding protein, is thought to be responsible for the strain susceptibility to Cd toxicity. In this study, MT-I/II knockout (MT-null) and wild-type 129 mice were used to determine the role of MT in Cd-induced testicular injury. Two additional strains of mice (C57 and the C57 x 129 F1cross) were also used to help define the role of genetic background in Cd toxicity. Mice were given 5-20 micromol/kg ip CdCl(2) and testicular injury was examined 24 h later by histopathology and testicular hemoglobin concentration. Cd produced dose-dependent testicular injury in all strains of mice, except for C57 mice, in which testicular injury could not be produced. MT-null mice were more sensitive than C57 x 129 mice but were equally sensitive as 129 mice to Cd-induced testicular injury. Fourteen days after 15 micromol/kg ip Cd administration, testicular atrophy was evident in MT-null, 129, and C57 x 129 mice but was absent in C57 mice. The resistance of C57 mice to Cd-induced testicular injury could not be attributed solely to a decreased uptake of (109)Cd nor to a greater amount of testicular MT. Microarray analysis revealed a higher expression of glutathione peroxidase in the testes of C57 mice, as well as genes encoding antioxidant components and DNA damage/repair, but their significance to Cd-induced injury is not immediately clear. Thus, this study demonstrates that it is genetic strain, not MT genotype, that is mechanistically important in determining susceptibility to Cd-induced testicular injury. PMID:11578143

  6. Antibiotic Resistance, Virulence, and Genetic Background of Community-Acquired Uropathogenic Escherichia coli from Algeria.

    PubMed

    Yahiaoui, Merzouk; Robin, Frédéric; Bakour, Rabah; Hamidi, Moufida; Bonnet, Richard; Messai, Yamina

    2015-10-01

    The aim of the study was to investigate antibiotic resistance mechanisms, virulence traits, and genetic background of 150 nonrepetitive community-acquired uropathogenic Escherichia coli (CA-UPEC) from Algeria. A rate of 46.7% of isolates was multidrug resistant. bla genes detected were blaTEM (96.8% of amoxicillin-resistant isolates), blaCTX-M-15 (4%), overexpressed blaAmpC (4%), blaSHV-2a, blaTEM-4, blaTEM-31, and blaTEM-35 (0.7%). All tetracycline-resistant isolates (51.3%) had tetA and/or tetB genes. Sulfonamides and trimethoprim resistance genes were sul2 (60.8%), sul1 (45.9%), sul3 (6.7%), dfrA14 (25.4%), dfrA1 (18.2%), dfrA12 (16.3%), and dfrA25 (5.4%). High-level fluoroquinolone resistance (22.7%) was mediated by mutations in gyrA (S83L-D87N) and parC (S80I-E84G/V or S80I) genes. qnrB5, qnrS1, and aac(6')-Ib-cr were rare (5.3%). Class 1 and/or class 2 integrons were detected (40.7%). Isolates belonged to phylogroups B2+D (50%), A+B1 (36%), and F+C+Clade I (13%). Most of D (72.2%) and 38.6% of B2 isolates were multidrug resistant; they belong to 14 different sequence types, including international successful ST131, ST73, and ST69, reported for the first time in the community in Algeria and new ST4494 and ST4529 described in this study. Besides multidrug resistance, B2 and D isolates possessed virulence factors of colonization, invasion, and long-term persistence. The study highlighted multidrug-resistant CA-UPEC with high virulence traits and an epidemic genetic background.

  7. Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

    PubMed

    Schöpke, K; Gomez, A; Dunbar, K A; Swalve, H H; Döpfer, D

    2015-11-01

    Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0

  8. Malignant transformation in a defined genetic background: proteome changes displayed by 2D-PAGE

    PubMed Central

    2010-01-01

    Background Cancer arises from normal cells through the stepwise accumulation of genetic alterations. Cancer development can be studied by direct genetic manipulation within experimental models of tumorigenesis. Thereby, confusion by the genetic heterogeneity of patients can be circumvented. Moreover, identification of the critical changes that convert a pre-malignant cell into a metastatic, therapy resistant tumor cell, however, is one necessary step to develop effective and selective anti-cancer drugs. Thus, for the current study a cell culture model for malignant transformation was used: Primary human fibroblasts of the BJ strain were sequentially transduced with retroviral vectors encoding the genes for hTERT (cell line BJ-T), simian virus 40 early region (SV40 ER, cell line BJ-TE) and H-Ras V12 (cell line BJ-TER). Results The stepwise malignant transformation of human fibroblasts was analyzed on the protein level by differential proteome analysis. We observed 39 regulated protein spots and therein identified 67 different proteins. The strongest change of spot patterns was detected due to integration of SV40 ER. Among the proteins being significantly regulated during the malignant transformation process well known proliferating cell nuclear antigen (PCNA) as well as the chaperones mitochondrial heat shock protein 75 kDa (TRAP-1) and heat shock protein HSP90 were identified. Moreover, we find out, that TRAP-1 is already up-regulated by means of SV40 ER expression instead of H-Ras V12. Furthermore Peroxiredoxin-6 (PRDX6), Annexin A2 (p36), Plasminogen activator inhibitor 2 (PAI-2) and Keratin type II cytoskeletal 7 (CK-7) were identified to be regulated. For some protein candidates we confirmed our 2D-PAGE results by Western Blot. Conclusion These findings give further hints for intriguing interactions between the p16-RB pathway, the mitochondrial chaperone network and the cytoskeleton. In summary, using a cell culture model for malignant transformation analyzed

  9. The genetic tumor background is an important determinant for heterogeneous MYCN‐amplified neuroblastoma

    PubMed Central

    Bogen, Dominik; Brunner, Clemens; Walder, Diana; Ziegler, Andrea; Abbasi, Reza; Ladenstein, Ruth L.; Noguera, Rosa; Martinsson, Tommy; Amann, Gabriele; Schilling, Freimut H.; Ussowicz, Marek; Benesch, Martin

    2016-01-01

    Amplification of MYCN is the signature genetic aberration of 20–25% of neuroblastoma and a stratifying marker associated with aggressive tumor behavior. The detection of heterogeneous MYCN amplification (hetMNA) poses a diagnostic dilemma due to the uncertainty of its relevance to tumor behavior. Here, we aimed to shed light on the genomic background which permits hetMNA in neuroblastoma and tied the occurrence to other stratifying markers and disease outcome. We performed SNP analysis using Affymetrix Cytoscan HD arrays on 63 samples including constitutional DNA, tumor, bone marrow and relapse samples of 26 patients with confirmed hetMNA by MYCN‐FISH. Tumors of patients ≤18m were mostly aneuploid with numeric chromosomal aberrations (NCAs), presented a prominent MNA subclone and carried none or a few segmental chromosomal aberrations (SCAs). In older patients, tumors were mostly di‐ or tetraploid, contained a lower number of MNA cells and displayed a multitude of SCAs including concomitant 11q deletions. These patients often suffered disease progression, tumor dissemination and relapse. Restricted to aneuploid tumors, we detected chromosomes with uniparental di‐ or trisomy (UPD/UPT) in almost every sample. UPD11 was exclusive to tumors of younger patients whereas older patients featured UPD14. In this study, the MNA subclone appears to be constraint by the tumor environment and thus less relevant for tumor behavior in aggressive tumors with a high genomic instability and many segmental aberrations. A more benign tumor background and lower tumor stage may favor an outgrowth of the MNA clone but tumors generally responded better to treatment. PMID:26910568

  10. Influence of genetic background on tumor karyotypes: evidence for breed-associated cytogenetic aberrations in canine appendicular osteosarcoma

    PubMed Central

    Thomas, Rachael; Wang, Huixia J.; Tsai, Pei-Chien; Langford, Cordelia F.; Fosmire, Susan P.; Jubala, Cristan M.; Getzy, David M.; Cutter, Gary R.

    2013-01-01

    Recurrent chromosomal aberrations in solid tumors can reveal the genetic pathways involved in the evolution of a malignancy and in some cases predict biological behavior. However, the role of individual genetic backgrounds in shaping karyotypes of sporadic tumors is unknown. The genetic structure of purebred dog breeds coupled with their susceptibility to spontaneous cancers provides a robust model with which to address this question. We tested the hypothesis that there is an association between breed and the distribution of genomic copy number imbalances in naturally-occurring canine tumors through assessment of a cohort of Golden Retrievers and Rottweilers diagnosed with spontaneous appendicular osteosarcoma. Our findings reveal significant correlations between breed and tumor karyotypes that are independent from gender, age at diagnosis and histological classification. These data indicate for the first time that individual genetic backgrounds, as defined by breed in dogs, influence tumor karyotypes in a cancer with extensive genomic instability. PMID:19337847

  11. The impact of the genetic background in the Noonan syndrome phenotype induced by K-RasV14I

    PubMed Central

    Hernández-Porras, Isabel; Jiménez-Catalán, Beatriz; Schuhmacher, Alberto J; Guerra, Carmen

    2015-01-01

    Noonan syndrome (NS) is an autosomal dominant genetic disorder characterized by short stature, craniofacial dysmorphism, and congenital heart defects. A significant fraction of NS-patients also develop myeloproliferative disorders. The penetrance of these defects varies considerably among patients. In this study, we have examined the effect of 2 genetic backgrounds (C57BL/6J.OlaHsd and 129S2/SvPasCrl) on the phenotypes displayed by a mouse model of NS induced by germline expression of the mutated K-RasV14I allele, one of the most frequent NS-KRAS mutations. Our results suggest the presence of genetic modifiers associated to the genetic background that are essential for heart development and function at early stages of postnatal life as well as in the severity of the haematopoietic alterations. PMID:26458870

  12. Mitochondrial genetic background plays a role in increasing risk to asthma.

    PubMed

    Zifa, Emily; Daniil, Zoe; Skoumi, Eleutheria; Stavrou, Maria; Papadimitriou, Kostantinos; Terzenidou, Marini; Kostikas, Konstantinos; Bagiatis, Vasileios; Gourgoulianis, Konstantinos I; Mamuris, Zissis

    2012-04-01

    A number of studies suggest that mitochondrial dysfunction plays a role in the pathogenesis of asthma. To shed light for the first time on the role of the mitochondrial genome in the etiology of asthma we analyzed the mitochondrial tRNA genes and part of their flanking regions in patients with asthma compared with a set of healthy controls. We found a total of 10 mutations in 56 out of 76 asthmatic patients. Four of these mutations were not found in the control group, five were observed at a significantly lower frequency in controls, but none of the combinations of mutations detected in asthma patients was observed in the controls. Furthermore, we observed that 27.6% of the asthma patients (vs. 4% of the controls) belonged to the haplogroup U (Fisher test P = 0.00) and a positive significant correlation was found between the occurrence of the haplogroup U and the severity of the disease (Fisher test P = 0.02). Whereas further studies in larger cohorts are needed to confirm these observations we suggest that the mitochondrial genetic background plays a key role in asthma development.

  13. Genetic Background is a Key Determinant of Glomerular Extracellular Matrix Composition and Organization.

    PubMed

    Randles, Michael J; Woolf, Adrian S; Huang, Jennifer L; Byron, Adam; Humphries, Jonathan D; Price, Karen L; Kolatsi-Joannou, Maria; Collinson, Sophie; Denny, Thomas; Knight, David; Mironov, Aleksandr; Starborg, Toby; Korstanje, Ron; Humphries, Martin J; Long, David A; Lennon, Rachel

    2015-12-01

    Glomerular disease often features altered histologic patterns of extracellular matrix (ECM). Despite this, the potential complexities of the glomerular ECM in both health and disease are poorly understood. To explore whether genetic background and sex determine glomerular ECM composition, we investigated two mouse strains, FVB and B6, using RNA microarrays of isolated glomeruli combined with proteomic glomerular ECM analyses. These studies, undertaken in healthy young adult animals, revealed unique strain- and sex-dependent glomerular ECM signatures, which correlated with variations in levels of albuminuria and known predisposition to progressive nephropathy. Among the variation, we observed changes in netrin 4, fibroblast growth factor 2, tenascin C, collagen 1, meprin 1-α, and meprin 1-β. Differences in protein abundance were validated by quantitative immunohistochemistry and Western blot analysis, and the collective differences were not explained by mutations in known ECM or glomerular disease genes. Within the distinct signatures, we discovered a core set of structural ECM proteins that form multiple protein-protein interactions and are conserved from mouse to man. Furthermore, we found striking ultrastructural changes in glomerular basement membranes in FVB mice. Pathway analysis of merged transcriptomic and proteomic datasets identified potential ECM regulatory pathways involving inhibition of matrix metalloproteases, liver X receptor/retinoid X receptor, nuclear factor erythroid 2-related factor 2, notch, and cyclin-dependent kinase 5. These pathways may therefore alter ECM and confer susceptibility to disease.

  14. Genetic Background Modulates lncRNA-Coordinated Tissue Response to Low Dose Ionizing Radiation

    DOE PAGES

    Tang, Jonathan; Huang, Yurong; Nguyen, David H.; Costes, Sylvain V.; Snijders, Antoine M.; Mao, Jian-Hua

    2015-01-01

    Long noncoding RNAs (lncRNAs) are emerging as key regulators of diverse cell functions and processes. However, the relevance of lncRNAs in the cell and tissue response to ionizing radiation has not yet been characterized. Here we used microarray profiling to determine lncRNA and mRNA expression in mammary glands of BALB/c and SPRET/EiJ mice after low-dose ionizing radiation (LDIR) exposure. We found that unirradiated mammary tissues of these strains differed significantly in baseline expressions of 290 lncRNAs. LDIR exposure (10 cGy) induced a significant change in the expression of many lncRNAs. The vast majority of lncRNAs identified to be differentially expressed aftermore » LDIR in either BALB/c or SPRET/EiJ had a significantly correlated expression pattern with at least one LDIR responsive mRNA. Functional analysis revealed that the response to LDIR in BALB/c mice is highly dynamic with enrichment for genes involved in tissue injury, inflammatory responses, and mammary gland development at 2, 4, and 8 weeks after LDIR, respectively. Our study demonstrates that genetic background strongly influences the expression of lncRNAs and their response to radiation and that lncRNAs may coordinate the tissue response to LDIR exposure via regulation of coding mRNAs.« less

  15. Telomere length homeostasis and telomere position effect on a linear human artificial chromosome are dictated by the genetic background

    PubMed Central

    Weuts, An; Voet, Thierry; Verbeeck, Jelle; Lambrechts, Nathalie; Wirix, Evelyne; Schoonjans, Luc; Danloy, Sophie; Marynen, Peter; Froyen, Guy

    2012-01-01

    Telomere position effect (TPE) is the influence of telomeres on subtelomeric epigenetic marks and gene expression. Previous studies suggested that TPE depends on genetic background. As these analyses were performed on different chromosomes, cell types and species, it remains unclear whether TPE represents a chromosome—rather than genetic background-specific regulation. We describe the development of a Linear Human Artificial Chromosome (L-HAC) as a new tool for telomere studies. The L-HAC was generated through the Cre-loxP-mediated addition of telomere ends to an existing circular HAC (C-HAC). As it can be transferred to genetically distinct cell lines and animal models the L-HAC enables the study of TPE in an unprecedented manner. The HAC was relocated to four telomerase-positive cell lines via microcell-mediated chromosome transfer and subsequently to mice via blastocyst injection of L-HAC+-ES-cells. We could show consistent genetic background-dependent adaptation of telomere length and telomere-associated de novo subtelomeric DNA methylation in mouse ES-R1 cells as well as in mice. Expression of the subtelomeric neomycin gene was inversely correlated with telomere length and subtelomeric methylation. We thus provide a new tool for functional telomere studies and provide strong evidence that telomere length, subtelomeric chromatin marks and expression of subtelomeric genes are genetic background dependent. PMID:23066103

  16. Telomere length homeostasis and telomere position effect on a linear human artificial chromosome are dictated by the genetic background.

    PubMed

    Weuts, An; Voet, Thierry; Verbeeck, Jelle; Lambrechts, Nathalie; Wirix, Evelyne; Schoonjans, Luc; Danloy, Sophie; Marynen, Peter; Froyen, Guy

    2012-12-01

    Telomere position effect (TPE) is the influence of telomeres on subtelomeric epigenetic marks and gene expression. Previous studies suggested that TPE depends on genetic background. As these analyses were performed on different chromosomes, cell types and species, it remains unclear whether TPE represents a chromosome-rather than genetic background-specific regulation. We describe the development of a Linear Human Artificial Chromosome (L-HAC) as a new tool for telomere studies. The L-HAC was generated through the Cre-loxP-mediated addition of telomere ends to an existing circular HAC (C-HAC). As it can be transferred to genetically distinct cell lines and animal models the L-HAC enables the study of TPE in an unprecedented manner. The HAC was relocated to four telomerase-positive cell lines via microcell-mediated chromosome transfer and subsequently to mice via blastocyst injection of L-HAC(+)-ES-cells. We could show consistent genetic background-dependent adaptation of telomere length and telomere-associated de novo subtelomeric DNA methylation in mouse ES-R1 cells as well as in mice. Expression of the subtelomeric neomycin gene was inversely correlated with telomere length and subtelomeric methylation. We thus provide a new tool for functional telomere studies and provide strong evidence that telomere length, subtelomeric chromatin marks and expression of subtelomeric genes are genetic background dependent.

  17. Genetic Background, Adipocytokines, and Metabolic Disorders in Postmenopausal Overweight and Obese Women.

    PubMed

    Grygiel-Górniak, Bogna; Kaczmarek, Elżbieta; Mosor, Maria; Przysławski, Juliusz; Bogacz, Anna

    2016-10-01

    The relationship between the genetic background, adipocytokines, and metabolic state in postmenopausal women has not yet been fully described. The aim of this study was to determine the relationship between PPAR gamma-2 (Pro12Ala, C1431T) and ADRB3 (Trp64Arg) polymorphisms and serum adipocytokines (adiponectin, visfatin, and resistin) and metabolic disorders in 176 postmenopausal women with increased body mass (BMI ≥ 25 kg m(-2)). The distributions of selected alleles and genotype frequencies were determined with the PCR-RFLP method. The bioimpedance method was used to determine nutritional status, and enzyme-linked immunosorbent assays were applied to determine serum concentrations of adipocytokines. Viscerally obese postmenopausal women had higher body mass, body fat content, serum glucose, insulin, total cholesterol, LDL, triglycerides, uric acid, and HOMA-IR and a higher prevalence of the Ala12 allele. In models based on cytokine concentration, higher body mass and glucose concentration (visfatin model, p = 0.008) and higher insulin and triglyceride levels (resistin model, p = 0.002) were observed in visceral fat deposition and this was potentiated by the presence of the T1431 allele. In resistin models, co-existence of Ala12/X polymorphisms with the T1431 allele was associated with higher resistin and triglyceride concentrations (p = 0.045). In postmenopausal women, metabolic parameters are mainly determined by the distribution of body fat, but Ala12/X polymorphism may increase the metabolic disorders and this effect can be enhanced by the T1431 allele. PMID:27246401

  18. Study of the common genetic background for rheumatoid arthritis and systemic lupus erythematosus

    PubMed Central

    Orozco, Gisela; Eyre, Steve; Hinks, Anne; Bowes, John; Morgan, Ann W; Wilson, Anthony G; Wordsworth, Paul; Steer, Sophia; Hocking, Lynne; Thomson, Wendy; Worthington, Jane; Barton, Anne

    2011-01-01

    Background Evidence is beginning to emerge that there may be susceptibility loci for rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) that are common to both diseases. Objective To investigate single nucleotide polymorphisms that have been reported to be associated with SLE in a UK cohort of patients with RA and controls. Methods 3962 patients with RA and 9275 controls were included in the study. Eleven SNPs mapping to confirmed SLE loci were investigated. These mapped to the TNFSF4, BANK1, TNIP1, PTTG1, UHRF1BP1, ATG5, JAZF1, BLK, KIAA1542, ITGAM and UBE2L3 loci. Genotype frequencies were compared between patients with RA and controls using the trend test. Results The SNPs mapping to the BLK and UBE2L3 loci showed significant evidence for association with RA. Two other SNPs, mapping to ATG5 and KIAA1542, showed nominal evidence for association with RA (p=0.02 and p=0.02, respectively) but these were not significant after applying a Bonferroni correction. Additionally, a significant global enrichment in carriage of SLE alleles in patients with RA compared with controls (p=9.1×10−7) was found. Meta-analysis of this and previous studies confirmed the association of the BLK and UBE2L3 gene with RA at genome-wide significance levels (p<5×10−8). Together, the authors estimate that the SLE and RA overlapping loci, excluding HLA-DRB1 alleles, identified so far explain ∼5.8% of the genetic susceptibility to RA as a whole. Conclusion The findings confirm the association of the BLK and UBE2L3 loci with RA, thus adding to the list of loci showing overlap between RA and SLE. PMID:21068098

  19. Association of recurrent furunculosis with Panton-Valentine leukocidin and the genetic background of Staphylococcus aureus.

    PubMed

    Masiuk, Helena; Kopron, Katarzyna; Grumann, Dorothee; Goerke, Christiane; Kolata, Julia; Jursa-Kulesza, Joanna; Giedrys-Kalemba, Stefania; Bröker, Barbara M; Holtfreter, Silva

    2010-05-01

    Staphylococcus aureus is a major cause of skin and soft tissue infections, such as furuncles, carbuncles, and abscesses, but it also frequently colonizes the human skin and mucosa without causing clinical symptoms. Panton-Valentine leukocidin (PVL) is a pore-forming toxin that has been associated with soft tissue infections and necrotizing pneumonia. We have compared the genotypes, virulence gene repertoires, and phage patterns of 74 furunculosis isolates with those of 108 control strains from healthy nasal carriers. The large majority of furunculosis strains were methicillin sensitive. Clonal cluster (CC) 121 (CC121) and CC22 accounted for 70% of the furunculosis strains but for only 8% of the nasal isolates. The PVL-encoding genes luk-PV were detected in 85% of furunculosis strains, while their prevalence among colonizing S. aureus strains was below 1%. luk-PV genes were distributed over several lineages (CCs 5, 8, 22, 30, and 121 and sequence type 59). Even within the same lineages, luk-PV-positive phages characterized furunculosis strains, while their luk-PV-negative variants were frequent among nasal strains. The very tight epidemiological linkage between luk-PV and furunculosis, which could be separated from the genetic background of the S. aureus strain as well as from the gene makeup of the luk-PV-transducing phage, lends support to the notion of an important role for PVL in human furunculosis. These results make a case for the determination of luk-PV in recurrent soft tissue infections with methicillin-sensitive as well as methicillin-resistant S. aureus. PMID:20200289

  20. A potential role of the NOD genetic background in mouse peritoneal macrophages for the development of primary effusion lymphoma.

    PubMed

    Goto, Hiroki; Kariya, Ryusho; Matsuda, Kouki; Kudo, Eriko; Katano, Harutaka; Okada, Seiji

    2016-03-01

    Severe immunodeficient mice have become invaluable tools in human stem cell and tumor research. In this study, we compared the phagocytic activity of peritoneal macrophages against primary effusion lymphoma (PEL) among Rag-2/Jak3 double-deficient (Rag-2(-/-)Jak3(-/-)) mice with NOD and non-NOD (Balb/c and C57/BL6). We also evaluated lymphomatous effusion and infiltration in a PEL xenograft mouse model using these severe immunodeficient mice. In the phagocytic assay, peritoneal macrophages in the NOD background phagocytosed CFSE-labeled BCBL-1, a PEL cell line, less efficiently than those in the non-NOD background. BCBL-1 cells were successfully engrafted into both the NOD background and non-NOD background; however, the volume of ascites of the NOD background was significantly higher than that of the non-NOD background. Moreover, the organ invasion of PEL cells was suppressed in non-NOD background mice. Thus, the NOD genetic background is considered to contribute to more lymphomatous effusion and the infiltration of PEL cells than a non-NOD background. Our results showed that the NOD background allowed more lymphomatous effusion and infiltration than other backgrounds and peritoneal macrophages played a critical role in preventing the growth and infiltration of PEL cells. PMID:26859781

  1. Nineteenth century French rose (Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background.

    PubMed

    Liorzou, Mathilde; Pernet, Alix; Li, Shubin; Chastellier, Annie; Thouroude, Tatiana; Michel, Gilles; Malécot, Valéry; Gaillard, Sylvain; Briée, Céline; Foucher, Fabrice; Oghina-Pavie, Cristiana; Clotault, Jérémy; Grapin, Agnès

    2016-08-01

    Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies.

  2. Nineteenth century French rose (Rosa sp.) germplasm shows a shift over time from a European to an Asian genetic background

    PubMed Central

    Liorzou, Mathilde; Pernet, Alix; Li, Shubin; Chastellier, Annie; Thouroude, Tatiana; Michel, Gilles; Malécot, Valéry; Gaillard, Sylvain; Briée, Céline; Foucher, Fabrice; Oghina-Pavie, Cristiana; Clotault, Jérémy; Grapin, Agnès

    2016-01-01

    Hybridization with introduced genetic resources is commonly practiced in ornamental plant breeding to introgress desired traits. The 19th century was a golden age for rose breeding in France. The objective here was to study the evolution of rose genetic diversity over this period, which included the introduction of Asian genotypes into Europe. A large sample of 1228 garden roses encompassing the conserved diversity cultivated during the 18th and 19th centuries was genotyped with 32 microsatellite primer pairs. Its genetic diversity and structure were clarified. Wide diversity structured in 16 genetic groups was observed. Genetic differentiation was detected between ancient European and Asian accessions, and a temporal shift from a European to an Asian genetic background was observed in cultivated European hybrids during the 19th century. Frequent crosses with Asian roses throughout the 19th century and/or selection for Asiatic traits may have induced this shift. In addition, the consistency of the results with respect to a horticultural classification is discussed. Some horticultural groups, defined according to phenotype and/or knowledge of their pedigree, seem to be genetically more consistent than others, highlighting the difficulty of classifying cultivated plants. Therefore, the horticultural classification is probably more appropriate for commercial purposes rather than genetic relatedness, especially to define preservation and breeding strategies. PMID:27406785

  3. Elucidation of Genetic Backgrounds Necessary for Chlorophyll a Biosynthesis Toward Artificial Creation of Oxygenic Photosynthesis.

    PubMed

    Tsukatani, Yusuke; Masuda, Shinji

    2015-09-01

    We succeeded to create the genetically modified purple photosynthetic bacterium capable of synthesizing chlorophyll a. The results indicate that not only chlorophyll synthase, but also an enzyme for galactolipid synthesis and reaction center proteins are required for accumulating chlorophyll a.

  4. A trans-acting Variant within the Transcription Factor RIM101 Interacts with Genetic Background to Determine its Regulatory Capacity.

    PubMed

    Read, Timothy; Richmond, Phillip A; Dowell, Robin D

    2016-01-01

    Most genetic variants associated with disease occur within regulatory regions of the genome, underscoring the importance of defining the mechanisms underlying differences in regulation of gene expression between individuals. We discovered a pair of co-regulated, divergently oriented transcripts, AQY2 and ncFRE6, that are expressed in one strain of Saccharomyces cerevisiae, ∑1278b, but not in another, S288c. By combining classical genetics techniques with high-throughput sequencing, we identified a trans-acting single nucleotide polymorphism within the transcription factor RIM101 that causes the background-dependent expression of both transcripts. Subsequent RNA-seq experiments revealed that RIM101 regulates many more targets in S288c than in ∑1278b and that deletion of RIM101 in both backgrounds abrogates the majority of differential expression between the strains. Strikingly, only three transcripts undergo a significant change in expression after swapping RIM101 alleles between backgrounds, implying that the differences in the RIM101 allele lead to a remarkably focused transcriptional response. However, hundreds of RIM101-dependent targets undergo a subtle but consistent shift in expression in the S288c RIM101-swapped strain, but not its ∑1278b counterpart. We conclude that ∑1278b may harbor a variant(s) that buffers against widespread transcriptional dysregulation upon introduction of a non-native RIM101 allele, emphasizing the importance of accounting for genetic background when assessing the impact of a regulatory variant.

  5. Genetic Background Strongly Modifies the Severity of Symptoms of Hirschsprung Disease, but Not Hearing Loss in Rats Carrying Ednrbsl Mutations

    PubMed Central

    Dang, Ruihua; Torigoe, Daisuke; Suzuki, Sari; Kikkawa, Yoshiaki; Moritoh, Kanako; Sasaki, Nobuya; Agui, Takashi

    2011-01-01

    Hirschsprung disease (HSCR) is thought to result as a consequence of multiple gene interactions that modulate the ability of enteric neural crest cells to populate the developing gut. However, it remains unknown whether the single complete deletion of important HSCR-associated genes is sufficient to result in HSCR disease. In this study, we found that the null mutation of the Ednrb gene, thought indispensable for enteric neuron development, is insufficient to result in HSCR disease when bred onto a different genetic background in rats carrying Ednrbsl mutations. Moreover, we found that this mutation results in serious congenital sensorineural deafness, and these strains may be used as ideal models of Waardenburg Syndrome Type 4 (WS4). Furthermore, we evaluated how the same changed genetic background modifies three features of WS4 syndrome, aganglionosis, hearing loss, and pigment disorder in these congenic strains. We found that the same genetic background markedly changed the aganglionosis, but resulted in only slight changes to hearing loss and pigment disorder. This provided the important evidence, in support of previous studies, that different lineages of neural crest-derived cells migrating along with various pathways are regulated by different signal molecules. This study will help us to better understand complicated diseases such as HSCR and WS4 syndrome. PMID:21915282

  6. Expression of Drosophila mushroom body mutations in alternative genetic backgrounds: a case study of the mushroom body miniature gene (mbm).

    PubMed Central

    de Belle, J S; Heisenberg, M

    1996-01-01

    Mutations in 12 genes regulating Drosophila melanogaster mushroom body (MB) development were each studied in two genetic backgrounds. In all cases, brain structure was qualitatively or quantitatively different after replacement of the "original" genetic background with that of the Canton Special wild-type strain. The mushroom body miniature gene (mbm) was investigated in detail. mbm supports the maintenance of MB Kenyon cell fibers in third instar larvae and their regrowth during metamorphosis. Adult mbm1 mutant females are lacking many or most Kenyon cell fibers and are impaired in MB-mediated associative odor learning. We show here that structural defects in mbm1 are apparent only in combination with an X-linked, dosage-dependent modifier (or modifiers). In the Canton Special genetic background, the mbm1 anatomical phenotype is suppressed, and MBs develop to a normal size. However, the olfactory learning phenotype is not fully restored, suggesting that submicroscopic defects persist in the MBs. Mutant mbm1 flies with full-sized MBs have normal retention but show a specific acquisition deficit that cannot be attributed to reductions in odor avoidance, shock reactivity, or locomotor behavior. We propose that polymorphic gene interactions (in addition to ontogenetic factors) determine MB size and, concomitantly, the ability to recognize and learn odors. Images Fig. 1 Fig. 2 Fig. 3 PMID:8790424

  7. Inheritance of grain polyphenol oxidase (PPO) activity in multiple wheat (Triticum aestivum L.) genetic backgrounds

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Grain polyphenol oxidase (PPO) activity can cause discoloration of wheat (Triticum aestivum L.) food products. Five crosses (PI 117635/Antelope; Fielder/NW03681; Fielder/Antelope; NW07OR1070/Antelope; NW07OR1066/OR2050272H) were selected to study the genetic inheritance of PPO activity. STS marker...

  8. Influence of genetic background on anthocyanin and copigment composition and behavior during thermoalkaline processing of maize

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Visual color is a primary factor for foods purchase; identifying factors that influence in-situ color quality of pigmented maize during processing is important. We used 24 genetically distinct pigmented maize hybrids (red/blue, blue, red, and purple) to investigate the effect of pigment and copigme...

  9. The Historical/Philosophical Background of Education in Human Genetics in the United States

    ERIC Educational Resources Information Center

    Hurd, Paul DeHart

    1978-01-01

    The purpose of this paper is to isolate the historical and philosophical treatment of genetics in school and college curricula. To do this, a qualitative analysis was made of 128 biology textbooks or textbook series published between the years 1907 and 1977. The results of this study are reported. (Author/MA)

  10. Genetic Background Specific Hypoxia Resistance in Rat is Correlated with Balanced Activation of a Cross-Chromosomal Genetic Network Centering on Physiological Homeostasis

    PubMed Central

    Mao, Lei

    2012-01-01

    Genetic background of an individual can drastically influence an organism’s response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN), Dahl salt-sensitive (SS) rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome substitution methodology, this genome-based physiological predisposition could not be traced back to distinct quantitative trait loci. Upon the completion and public data availability of PhysGen SS-BN consomic (CS) rat platform, I employed systems biology approach attempting to further our understanding of the molecular basis of genetic background effect in light of hypoxia response. I analyzed the physiological screening data of 22 CS rat strains under normoxia and 2-weeks of hypoxia, and cross-compared them to the parental strains. The analyses showed that SS-9BN and SS-18BN represent the most hypoxia-resistant CS strains with phenotype similar to BN, whereas SS-6BN and SS-YBN segregated to the direction of SS. A meta-analysis on the transcriptomic profiles of these CS rat strains under hypoxia treatment showed that although polymorphisms on the substituted BN chromosomes could be directly involved in hypoxia resistance, this seems to be embedded in a more complex trans-chromosomal genetic regulatory network. Via information theory based modeling approach, this hypoxia relevant core genetic network was reverse engineered. Network analyses showed that the protective effects of BN chromosome 9 and 18 were reflected by a balanced activation of this core network centering on physiological homeostasis. Presumably, it is the system robustness constituted on such differential network activation that acts as hypoxia response modifier. Understanding of the intrinsic link between the individual genetic background and the network robustness will set a basis in the current scientific efforts toward personalized medicine. PMID

  11. Genetic Background Specific Hypoxia Resistance in Rat is Correlated with Balanced Activation of a Cross-Chromosomal Genetic Network Centering on Physiological Homeostasis.

    PubMed

    Mao, Lei

    2012-01-01

    Genetic background of an individual can drastically influence an organism's response upon environmental stress and pathological stimulus. Previous studies in inbred rats showed that compared to Brown Norway (BN), Dahl salt-sensitive (SS) rat exerts strong hypoxia susceptibility. However, despite extensive narrow-down approaches via the chromosome substitution methodology, this genome-based physiological predisposition could not be traced back to distinct quantitative trait loci. Upon the completion and public data availability of PhysGen SS-BN consomic (CS) rat platform, I employed systems biology approach attempting to further our understanding of the molecular basis of genetic background effect in light of hypoxia response. I analyzed the physiological screening data of 22 CS rat strains under normoxia and 2-weeks of hypoxia, and cross-compared them to the parental strains. The analyses showed that SS-9(BN) and SS-18(BN) represent the most hypoxia-resistant CS strains with phenotype similar to BN, whereas SS-6(BN) and SS-Y(BN) segregated to the direction of SS. A meta-analysis on the transcriptomic profiles of these CS rat strains under hypoxia treatment showed that although polymorphisms on the substituted BN chromosomes could be directly involved in hypoxia resistance, this seems to be embedded in a more complex trans-chromosomal genetic regulatory network. Via information theory based modeling approach, this hypoxia relevant core genetic network was reverse engineered. Network analyses showed that the protective effects of BN chromosome 9 and 18 were reflected by a balanced activation of this core network centering on physiological homeostasis. Presumably, it is the system robustness constituted on such differential network activation that acts as hypoxia response modifier. Understanding of the intrinsic link between the individual genetic background and the network robustness will set a basis in the current scientific efforts toward personalized medicine.

  12. Genomic selection for recovery of original genetic background from hybrids of endangered and common breeds

    PubMed Central

    Amador, Carmen; Hayes, Ben J; Daetwyler, Hans D

    2014-01-01

    Critically endangered breeds and populations are often crossed with more common breeds or subspecies. This results in genetic admixture that can be undesirable when it challenges the genetic integrity of wild and domestic populations, causing a loss in special characteristics or unique genetic material and ultimately extinction. Here, we present two genomic selection strategies, using genome-wide DNA markers, to recover the genomic content of the original endangered population from admixtures. Each strategy relies on the estimation of the proportion of nonintrogressed genome in individuals based on a different method: either genomic prediction or identification of breed-specific haplotypes. Then, breeding programs that remove introgressed genomic information can be designed. To test these strategies, we used empirical 50K SNP array data from two pure sheep breeds, Merino (used as target breed), Poll Dorset and an existing admixed population of both breeds. Sheep populations with varying degrees of introgression and admixture were simulated starting from these real genotypes. Both strategies were capable of identifying segment origin, and both removed up to the 100% of the Poll Dorset segments. While the selection process led to substantial inbreeding, we controlled it by imposing a minimum number of individuals contributing to the next generation. PMID:24567744

  13. Sardinians Genetic Background Explained by Runs of Homozygosity and Genomic Regions under Positive Selection

    PubMed Central

    Di Gaetano, Cornelia; Fiorito, Giovanni; Ortu, Maria Francesca; Rosa, Fabio; Guarrera, Simonetta; Pardini, Barbara; Cusi, Daniele; Frau, Francesca; Barlassina, Cristina; Troffa, Chiara; Argiolas, Giuseppe; Zaninello, Roberta; Fresu, Giovanni; Glorioso, Nicola; Piazza, Alberto; Matullo, Giuseppe

    2014-01-01

    The peculiar position of Sardinia in the Mediterranean sea has rendered its population an interesting biogeographical isolate. The aim of this study was to investigate the genetic population structure, as well as to estimate Runs of Homozygosity and regions under positive selection, using about 1.2 million single nucleotide polymorphisms genotyped in 1077 Sardinian individuals. Using four different methods - fixation index, inflation factor, principal component analysis and ancestry estimation - we were able to highlight, as expected for a genetic isolate, the high internal homogeneity of the island. Sardinians showed a higher percentage of genome covered by RoHs>0.5 Mb (FRoH%0.5) when compared to peninsular Italians, with the only exception of the area surrounding Alghero. We furthermore identified 9 genomic regions showing signs of positive selection and, we re-captured many previously inferred signals. Other regions harbor novel candidate genes for positive selection, like TMEM252, or regions containing long non coding RNA. With the present study we confirmed the high genetic homogeneity of Sardinia that may be explained by the shared ancestry combined with the action of evolutionary forces. PMID:24651212

  14. Ectopic differentiation of melanocyte stem cells is influenced by genetic background.

    PubMed

    Harris, Melissa L; Levy, Denise J; Watkins-Chow, Dawn E; Pavan, William J

    2015-03-01

    Hair graying in mouse is attributed to the loss of melanocyte stem cell function and the progressive depletion of the follicular melanocyte population. Single-gene, hair graying mouse models have pointed to a number of critical pathways involved in melanocyte stem cell biology; however, the broad range of phenotypic variation observed in human hair graying suggests that additional genetic variants involved in this process may yet be discovered. Using a sensitized approach, we ask here whether natural genetic variation influences a predominant cellular mechanism of hair graying in mouse, melanocyte stem cell differentiation. We developed an innovative method to quantify melanocyte stem cell differentiation by measuring ectopically pigmented melanocyte stem cells in response to the melanocyte-specific transgene Tg(Dct-Sox10). We make the novel observation that the production of ectopically pigmented melanocyte stem cells varies considerably across strains. The success of sensitizing for melanocyte stem cell differentiation by Tg(Dct-Sox10) sets the stage for future investigations into the genetic basis of strain-specific contributions to melanocyte stem cell biology.

  15. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep☆

    PubMed Central

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J.; Foster, Russell G.; Peirson, Stuart N.; Nolan, Patrick M.

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

  16. Genetic background influences age-related decline in visual and nonvisual retinal responses, circadian rhythms, and sleep.

    PubMed

    Banks, Gareth; Heise, Ines; Starbuck, Becky; Osborne, Tamzin; Wisby, Laura; Potter, Paul; Jackson, Ian J; Foster, Russell G; Peirson, Stuart N; Nolan, Patrick M

    2015-01-01

    The circadian system is entrained to the environmental light/dark cycle via retinal photoreceptors and regulates numerous aspects of physiology and behavior, including sleep. These processes are all key factors in healthy aging showing a gradual decline with age. Despite their importance, the exact mechanisms underlying this decline are yet to be fully understood. One of the most effective tools we have to understand the genetic factors underlying these processes are genetically inbred mouse strains. The most commonly used reference mouse strain is C57BL/6J, but recently, resources such as the International Knockout Mouse Consortium have started producing large numbers of mouse mutant lines on a pure genetic background, C57BL/6N. Considering the substantial genetic diversity between mouse strains we expect there to be phenotypic differences, including differential effects of aging, in these and other strains. Such differences need to be characterized not only to establish how different mouse strains may model the aging process but also to understand how genetic background might modify age-related phenotypes. To ascertain the effects of aging on sleep/wake behavior, circadian rhythms, and light input and whether these effects are mouse strain-dependent, we have screened C57BL/6J, C57BL/6N, C3H-HeH, and C3H-Pde6b+ mouse strains at 5 ages throughout their life span. Our data show that sleep, circadian, and light input parameters are all disrupted by the aging process. Moreover, we have cataloged a number of strain-specific aging effects, including the rate of cataract development, decline in the pupillary light response, and changes in sleep fragmentation and the proportion of time spent asleep. PMID:25179226

  17. Influence of genetic background on albuminuria and kidney injury in Ins2+/C96Y (Akita) mice

    PubMed Central

    Mach, Carrie L.; Stegbauer, Johannes; Yang, Jihong; Snow, Kamie P.; Hu, Ann; Meyer, Timothy W.; Coffman, Thomas M.

    2010-01-01

    Previous studies have shown that Akita mice bearing the Ins2+/C96Y mutation have significant advantages as a type I diabetes platform for developing models of diabetic nephropathy (DN; Gurley SB, Clare SE, Snow KP, Hu A, Meyer TW, Coffman TM. Am J Physiol Renal Physiol 290: F214–F222, 2006). In view of the critical role for genetic factors in determining susceptibility to DN in humans, we investigated the role of genetic background on kidney injury in Akita mice. To generate a series of inbred Akita mouse lines, we back-crossed the Ins2C96Y mutation more than six generations onto the 129/SvEv and DBA/2 backgrounds and compared the extent of hyperglycemia and renal disease with the standard C57BL/6-Ins2+/C96Y line. Male mice from all three Akita strains developed marked and equivalent hyperglycemia. However, there were significant differences in the level of albuminuria among the lines with a hierarchy of DBA/2 > 129/SvEv > C57BL/6. Renal and glomerular hypertrophy was seen in all of the lines, but significant increases in mesangial matrix compared with baseline nondiabetic controls were observed only in the 129 and C57BL/6 backgrounds. In F1(DBA/2 x C57BL/6)-Ins2+/C96Y mice, the extent of albuminuria was similar to the parental DBA/2-Ins2+/C96Y line; they also developed marked hyperfiltration. These studies identify strong effects of genetic background to modify the renal phenotype associated with the Ins2C96Y mutation. Identification of these naturally occurring strain differences should prove useful for nephropathy modeling and may be exploited to allow identification of novel susceptibility alleles for albuminuria in diabetes. PMID:20042456

  18. Genetic background influences embryonic lethality and the occurrence of neural tube defects in Men1 null mice: relevance to genetic modifiers.

    PubMed

    Lemos, Manuel C; Harding, Brian; Reed, Anita A C; Jeyabalan, Jeshmi; Walls, Gerard V; Bowl, Michael R; Sharpe, James; Wedden, Sarah; Moss, Julie E; Ross, Allyson; Davidson, Duncan; Thakker, Rajesh V

    2009-10-01

    Germline mutations of the multiple endocrine neoplasia type 1 (MEN1) gene cause parathyroid, pancreatic and pituitary tumours in man. MEN1 mutations also cause familial isolated primary hyperparathyroidism (FIHP) and the same MEN1 mutations, in different families, can cause either FIHP or MEN1. This suggests a role for genetic background and modifier genes in altering the expression of a mutation. We investigated the effects of genetic background on the phenotype of embryonic lethality that occurs in a mouse model for MEN1. Men1(+/-) mice were backcrossed to generate C57BL/6 and 129S6/SvEv incipient congenic strains, and used to obtain homozygous Men1(-/-) mice. No viable Men1(-/-) mice were obtained. The analysis of 411 live embryos obtained at 9.5-16.5 days post-coitum (dpc) revealed that significant deviations from the expected Mendelian 1:2:1 genotype ratio were first observed at 12.5 and 14.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively (P<0.05). Moreover, live Men1(-/-) embryos were absent by 13.5 and 15.5 dpc in the 129S6/SvEv and C57BL/6 strains respectively thereby indicating an earlier lethality by 2 days in the 129S6/SvEv strain (P<0.01). Men1(-/-) embryos had macroscopic haemorrhages, and histology and optical projection tomography revealed them to have internal haemorrhages, myocardial hypotrophy, pericardial effusion, hepatic abnormalities and neural tube defects. The neural tube defects occurred exclusively in 129S6/SvEv embryos (21 vs 0%, P<0.01). Thus, our findings demonstrate the importance of genetic background in influencing the phenotypes of embryonic lethality and neural tube defects in Men1(-/-) mice, and implicate a role for genetic modifiers.

  19. Large variations in ocular dimensions in a multiethnic population with similar genetic background

    PubMed Central

    Niu, Zhiqiang; Li, Jun; Zhong, Hua; Yuan, Zhonghua; Zhou, Hua; Zhang, Yang; Yuan, Yuansheng; Chen, Qin; Pan, Chen-Wei

    2016-01-01

    We aimed to describe the ethnic variations in ocular dimensions among three ethnic groups with similar genetic ancestry from mainland of China. We included 2119 ethnic Bai, 2202 ethnic Yi and 2183 ethnic Han adults aged 50 years or older in the study. Ocular dimensions including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD) and lens thickness (LT) were measured using A-scan ultrasonography. Bai Chinese had longer ALs (P < 0.001), deeper ACDs (P < 0.001) but shallower VCDs (P < 0.001) compared with the other two ethnic groups. There were no ethnic variations in LTs. Diabetes was associated with shallower ACDs and this association was stronger in Bai Chinese compared with Yi or Han Chinese (P for interaction = 0.02). Thicker lenses were associated with younger age (P = 0.04), male gender (P < 0.001), smoking history (P = 0.01), alcohol intake (P = 0.03), the presence of cataract (P < 0.001), and the presence of diabetes (P < 0.001). There were significant differences in ocular dimensions among different ethnic groups with small differences in genetics but large variations in cultures and lifestyles. PMID:26947903

  20. Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus.

    PubMed

    Gharahkhani, Puya; Tung, Joyce; Hinds, David; Mishra, Aniket; Vaughan, Thomas L; Whiteman, David C; MacGregor, Stuart

    2016-02-15

    Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3-11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA.

  1. Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus.

    PubMed

    Gharahkhani, Puya; Tung, Joyce; Hinds, David; Mishra, Aniket; Vaughan, Thomas L; Whiteman, David C; MacGregor, Stuart

    2016-02-15

    Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3-11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA. PMID:26704365

  2. Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus

    PubMed Central

    Gharahkhani, Puya; Tung, Joyce; Hinds, David; Mishra, Aniket; Vaughan, Thomas L.; Whiteman, David C.; MacGregor, Stuart

    2016-01-01

    Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3–11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA. PMID:26704365

  3. The Moral Reasoning of Genetic Dilemmas Amongst Jewish Israeli Undergraduate Students with Different Religious Affiliations and Scientific Backgrounds.

    PubMed

    Siani, Merav; Ben-Zvi Assaraf, Orit

    2016-06-01

    The main objective of this study was to shed light on the moral reasoning of undergraduate Israeli students towards genetic dilemmas, and on how these are affected by their religious affiliation, by the field they study and by their gender. An open ended questionnaire was distributed among 449 undergraduate students in institutions of higher education in Israel, and their answers were analyzed according to the framework described by Sadler and Zeidler (Science Education, 88(1), 4-27, 2004). They were divided into two major categories: those whose reasoning was based on the consideration of moral consequences (MC), and those who supported their opinion by citing non-consequentialist moral principles (MP). Students' elaborations to questions dealing with values towards genetic testing showed a correlation between the students' religious affiliation and their reasoning, with religious students' elaborations tending to be more principle based than those of secular ones. Overall, the students' elaborations indicate that their main concern is the possibility that their personal genetic information will be exposed, and that their body's personal rights will be violated. We conclude the paper by offering several practical recommendations based on our findings for genetic counseling that is specifically tailored to fit different patients according to their background. PMID:26642964

  4. Steatohepatitic variant of hepatocellular carcinoma in the absence of metabolic syndrome or background steatosis: a clinical, pathological, and genetic study.

    PubMed

    Yeh, Matthew M; Liu, Yajuan; Torbenson, Michael

    2015-11-01

    Association between the steatohepatitic hepatocellular carcinoma (SH-HCC) and metabolic syndrome has been suggested. Most SH-HCC morphology appears to result from a typical HCC that retains the ability to respond to the metabolic syndrome and develops features of steatohepatitis. We aim to ask if this is true for all SH-HCC cases, or does the SH-HCC morphology in some cases reflect genetic changes inherent to the HCC itself, as opposed to wide tissue response in liver to the metabolic syndrome. Twelve SH-HCC cases occurring in individuals without metabolic syndrome were identified and examined pathologically. Genomic microarray analysis was performed in a subset. The SH-HCC in all cases showed diffuse moderate to marked fatty change, abundant balloon cells often containing Mallory-Denk bodies, and pericellular fibrosis. The background livers showed no significant fatty change in any cases. The background livers showed cirrhosis in seven cases and had no fibrosis in five cases. The underlying liver diseases were hepatitis C (n = 4) and no known (n = 8). The clinical and pathological characteristics of these cases did not differ significantly from the cases with the classical HCC morphology. Loss of 9q12-q31.1 was observed in a subset of cases, a finding that has not been previously reported in HCC. Our results indicate HCC can also develop steatohepatitic morphology outside the setting of fatty liver disease or metabolic syndrome. This SH-HCC is more likely to result from genetic changes to shared genes or metabolic pathways within the tumor and is an ideal subtype for future genetic studies. In this regard, potential genetic alterations include loss of 9q12-q31.1.

  5. Interactions between the Bumblebee Bombus pascuorum and Red Clover (Trifolium pratense) Are Mediated by Plant Genetic Background.

    PubMed

    Sands, Richard J; Rowntree, Jennifer K

    2016-01-01

    Wildflower mixes are often planted around field margins to provide forage for pollinators. Although seed for these mixtures is often wild-sourced, for species where agricultural cultivars are available, for example red clover (Trifolium pratense), cultivars can also be included. Previous evidence suggests that plant genetic background can have a strong influence on plant-arthropod interactions and therefore the provenance and genetic background of the plants included in wildflower mixes could impact plant-pollinator interactions. We tested the performance of five individual T. pratense cultivars against two commercially available wild-sourced T. pratense populations in terms of their ability to attract potential pollinator species (focusing on bumblebees) and their floral traits using greenhouse and garden experiments. The main bumblebee observed interacting with T. pratense was Bombus pascuorum and we found no difference in the absolute number of B. pascuorum visiting the cultivars or wild populations. However, we found variation among cultivars and between wild populations in their ability to attract bumblebees, which seems to be related to their relative investment in different floral traits. There was a positive relationship between biomass and number of inflorescences produced by the wild populations of T. pratense, which was not apparent for the cultivars. This suggests that artificial selection on the cultivars has changed the G-matrix of correlated traits. We show that agricultural cultivars of T. pratense can be as effective as wild populations at attracting pollinators such as bumblebees, but that the genetic background of both cultivars and wild populations can have a significant impact on the attractiveness of the plant to pollinators. We also show divergence in the correlated traits of T. pratense cultivars and wild populations that could lead to outbreeding depression if the plants interbreed. PMID:27552193

  6. Interactions between the Bumblebee Bombus pascuorum and Red Clover (Trifolium pratense) Are Mediated by Plant Genetic Background

    PubMed Central

    Sands, Richard J.; Rowntree, Jennifer K.

    2016-01-01

    Wildflower mixes are often planted around field margins to provide forage for pollinators. Although seed for these mixtures is often wild-sourced, for species where agricultural cultivars are available, for example red clover (Trifolium pratense), cultivars can also be included. Previous evidence suggests that plant genetic background can have a strong influence on plant-arthropod interactions and therefore the provenance and genetic background of the plants included in wildflower mixes could impact plant-pollinator interactions. We tested the performance of five individual T. pratense cultivars against two commercially available wild-sourced T. pratense populations in terms of their ability to attract potential pollinator species (focusing on bumblebees) and their floral traits using greenhouse and garden experiments. The main bumblebee observed interacting with T. pratense was Bombus pascuorum and we found no difference in the absolute number of B. pascuorum visiting the cultivars or wild populations. However, we found variation among cultivars and between wild populations in their ability to attract bumblebees, which seems to be related to their relative investment in different floral traits. There was a positive relationship between biomass and number of inflorescences produced by the wild populations of T. pratense, which was not apparent for the cultivars. This suggests that artificial selection on the cultivars has changed the G-matrix of correlated traits. We show that agricultural cultivars of T. pratense can be as effective as wild populations at attracting pollinators such as bumblebees, but that the genetic background of both cultivars and wild populations can have a significant impact on the attractiveness of the plant to pollinators. We also show divergence in the correlated traits of T. pratense cultivars and wild populations that could lead to outbreeding depression if the plants interbreed. PMID:27552193

  7. Interactions between the Bumblebee Bombus pascuorum and Red Clover (Trifolium pratense) Are Mediated by Plant Genetic Background.

    PubMed

    Sands, Richard J; Rowntree, Jennifer K

    2016-01-01

    Wildflower mixes are often planted around field margins to provide forage for pollinators. Although seed for these mixtures is often wild-sourced, for species where agricultural cultivars are available, for example red clover (Trifolium pratense), cultivars can also be included. Previous evidence suggests that plant genetic background can have a strong influence on plant-arthropod interactions and therefore the provenance and genetic background of the plants included in wildflower mixes could impact plant-pollinator interactions. We tested the performance of five individual T. pratense cultivars against two commercially available wild-sourced T. pratense populations in terms of their ability to attract potential pollinator species (focusing on bumblebees) and their floral traits using greenhouse and garden experiments. The main bumblebee observed interacting with T. pratense was Bombus pascuorum and we found no difference in the absolute number of B. pascuorum visiting the cultivars or wild populations. However, we found variation among cultivars and between wild populations in their ability to attract bumblebees, which seems to be related to their relative investment in different floral traits. There was a positive relationship between biomass and number of inflorescences produced by the wild populations of T. pratense, which was not apparent for the cultivars. This suggests that artificial selection on the cultivars has changed the G-matrix of correlated traits. We show that agricultural cultivars of T. pratense can be as effective as wild populations at attracting pollinators such as bumblebees, but that the genetic background of both cultivars and wild populations can have a significant impact on the attractiveness of the plant to pollinators. We also show divergence in the correlated traits of T. pratense cultivars and wild populations that could lead to outbreeding depression if the plants interbreed.

  8. Genetic background influences adaptation to cardiac hypertrophy and Ca(2+) handling gene expression.

    PubMed

    Waters, Steve B; Diak, Douglass M; Zuckermann, Matthew; Goldspink, Paul H; Leoni, Lara; Roman, Brian B

    2013-01-01

    Genetic variability has a profound effect on the development of cardiac hypertrophy in response to stress. Consequently, using a variety of inbred mouse strains with known genetic profiles may be powerful models for studying the response to cardiovascular stress. To explore this approach we looked at male C57BL/6J and 129/SvJ mice. Hemodynamic analyses of left ventricular pressures (LVPs) indicated significant differences in 129/SvJ and C57BL/6J mice that implied altered Ca(2+) handling. Specifically, 129/SvJ mice demonstrated reduced rates of relaxation and insensitivity to dobutamine (Db). We hypothesized that altered expression of genes controlling the influx and efflux of Ca(2+) from the sarcoplasmic reticulum (SR) was responsible and investigated the expression of several genes involved in maintaining the intracellular and sarcoluminal Ca(2+) concentration using quantitative real-time PCR analyses (qRT-PCR). We observed significant differences in baseline gene expression as well as different responses in expression to isoproterenol (ISO) challenge. In untreated control animals, 129/SvJ mice expressed 1.68× more ryanodine receptor 2(Ryr2) mRNA than C57BL/6J mice but only 0.37× as much calsequestrin 2 (Casq2). After treatment with ISO, sarco(endo)plasmic reticulum Ca(2+)-ATPase(Serca2) expression was reduced nearly two-fold in 129/SvJ while expression in C57BL/6J was stable. Interestingly, β (1) adrenergic receptor(Adrb1) expression was lower in 129/SvJ compared to C57BL/6J at baseline and lower in both strains after treatment. Metabolically, the brain isoform of creatine kinase (Ckb) was up-regulated in response to ISO in C57BL/6J but not in 129/SvJ. These data suggest that the two strains of mice regulate Ca(2+) homeostasis via different mechanisms and may be useful in developing personalized therapies in human patients.

  9. Sensitivity to hepatotoxicity due to epigallocatechin gallate is affected by genetic background in diversity outbred mice

    PubMed Central

    Church, Rachel J.; Gatti, Daniel M.; Urban, Thomas J.; Long, Nanye; Yang, Xi; Shi, Qiang; Eaddy, J. Scott; Mosedale, Merrie; Ballard, Shawn; Churchill, Gary A.; Navarro, Victor; Watkins, Paul B.; Threadgill, David W.; Harrill, Alison H.

    2014-01-01

    Consumer use of herbal and dietary supplements has recently grown in the United States and, with increased use, reports of rare adverse reactions have emerged. One such supplement is green tea extract, containing the polyphenol epigallocatechin gallate (EGCG), which has been shown to be hepatotoxic at high doses in animal models. The Drug-Induced Liver Injury Network has identified multiple patients who have experienced liver injury ascribed to green tea extract consumption and the relationship to dose has not been straightforward, indicating that differences in sensitivity may contribute to the adverse response in susceptible people. The Diversity Outbred (DO), a genetically heterogeneous mouse population, provides a potential platform for study of interindividual toxicity responses to green tea extract. Within the DO population, an equal exposure to EGCG (50 mg/kg; daily for three days) was found to be tolerated in the majority of mice; however, a small fraction of the animals (16%; 43/272) exhibited severe hepatotoxicity (10–86.8% liver necrosis) that is analogous to the clinical cases. The data indicate that the DO mice may provide a platform for informing risk of rare, adverse reactions that may occur in consumer populations upon ingestion of concentrated herbal products. PMID:25446466

  10. The conserved genetic background for pluteus arm development in brittle stars and sea urchin.

    PubMed

    Morino, Yoshiaki; Koga, Hiroyuki; Wada, Hiroshi

    2016-01-01

    Echinoderm pluteus larvae are considered a classical example of convergent evolution that occurred in sea urchins and brittle stars. Several genes are known to be involved in the development of pluteus arms in sea urchins, including fgfA, pax2/5/8, pea3, otp, wnt5, and tet. To determine whether the convergent evolution of larval arms also involves these genes in brittle stars, their expression patterns were determined in brittle star. We found that all genes showed similar expression in the arms of ophiopluteus to that seen in echinopluteus, suggesting that convergent evolution of pluteus arms occurred by recruitment of a similar set of genes. This may be explained by our observation that some of these genes are also expressed in the spine rudiment of direct-type development sea urchins. We propose an evolutionary scenario wherein the pluteus arms of both echinopluteus and ophiopluteus were acquired by independent co-options of the genetic module responsible for the projection of the adult skeleton.

  11. Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy

    PubMed Central

    Feldmeyer, Laurence; Heidemeyer, Kristine; Yawalkar, Nikhil

    2016-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base and spontaneous resolution usually within two weeks. Systemic involvement occurs in about 20% of cases. The course is mostly benign, and only in rare cases complications lead to life-threatening situations. Recent studies highlight the importance of genetic variations in interleukin-36 receptor antagonist gene (IL-36RN) in the pathogenesis of this disease. The physiopathology of AGEP remains unclear, but an involvement of innate and acquired immune cells together with resident cells (keratinocytes), which recruit and activate neutrophils via production of cytokines/chemokines such as IL-17, IL-36, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα) and chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, has been postulated. Treatment is based on the removal of the causative drug, supportive care, infection prevention and use of potent topical or systemic steroids. PMID:27472323

  12. Acute Generalized Exanthematous Pustulosis: Pathogenesis, Genetic Background, Clinical Variants and Therapy.

    PubMed

    Feldmeyer, Laurence; Heidemeyer, Kristine; Yawalkar, Nikhil

    2016-01-01

    Acute generalized exanthematous pustulosis (AGEP) is a severe, usually drug-related reaction, characterized by an acute onset of mainly small non-follicular pustules on an erythematous base and spontaneous resolution usually within two weeks. Systemic involvement occurs in about 20% of cases. The course is mostly benign, and only in rare cases complications lead to life-threatening situations. Recent studies highlight the importance of genetic variations in interleukin-36 receptor antagonist gene (IL-36RN) in the pathogenesis of this disease. The physiopathology of AGEP remains unclear, but an involvement of innate and acquired immune cells together with resident cells (keratinocytes), which recruit and activate neutrophils via production of cytokines/chemokines such as IL-17, IL-36, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor alpha (TNFα) and chemokine (C-X-C motif) ligand 8 (CXCL8)/IL-8, has been postulated. Treatment is based on the removal of the causative drug, supportive care, infection prevention and use of potent topical or systemic steroids. PMID:27472323

  13. Epistasis between antibiotic resistance mutations and genetic background shape the fitness effect of resistance across species of Pseudomonas

    PubMed Central

    Kojadinovic, M.; MacLean, R. C.

    2016-01-01

    Antibiotic resistance often evolves by mutations at conserved sites in essential genes, resulting in parallel molecular evolution between divergent bacterial strains and species. Whether these resistance mutations are having parallel effects on fitness across bacterial taxa, however, is unclear. This is an important point to address, because the fitness effects of resistance mutations play a key role in the spread and maintenance of resistance in pathogen populations. We address this idea by measuring the fitness effect of a collection of rifampicin resistance mutations in the β subunit of RNA polymerase (rpoB) across eight strains that span the diversity of the genus Pseudomonas. We find that almost 50% of rpoB mutations have background-dependent fitness costs, demonstrating that epistatic interactions between rpoB and the rest of the genome are common. Moreover, epistasis is typically strong, and it is the dominant genetic determinant of the cost of resistance mutations. To investigate the functional basis of epistasis, and because rpoB plays a central role in transcription, we measured the effects of common rpoB mutations on transcriptional efficiency across three strains of Pseudomonas. Transcriptional efficiency correlates strongly to fitness across strains, and epistasis arises because individual rpoB mutations have differential effects on transcriptional efficiency in different genetic backgrounds. PMID:27170722

  14. BRCA1/2 genetic background-based therapeutic tailoring of human ovarian cancer: hope or reality?

    PubMed Central

    Tagliaferri, Pierosandro; Ventura, Monica; Baudi, Francesco; Cucinotto, Iole; Arbitrio, Mariamena; Di Martino, Maria Teresa; Tassone, Pierfrancesco

    2009-01-01

    Ovarian epithelial tumors are an hallmark of hereditary cancer syndromes which are related to the germ-line inheritance of cancer predisposing mutations in BRCA1 and BRCA2 genes. Although these genes have been associated with multiple different physiologic functions, they share an important role in DNA repair mechanisms and therefore in the whole genomic integrity control. These findings have risen a variety of issues in terms of treatment and prevention of breast and ovarian tumors arising in this context. Enhanced sensitivity to platinum-based anticancer drugs has been related to BRCA1/2 functional loss. Retrospective studies disclosed differential chemosensitivity profiles of BRCA1/2-related as compared to "sporadic" ovarian cancer and led to the identification of a "BRCA-ness" phenotype of ovarian cancer, which includes inherited BRCA1/2 germ-line mutations, a serous high grade histology highly sensitive to platinum derivatives. Molecularly-based tailored treatments of human tumors are an emerging issue in the "era" of molecular targeted drugs and molecular profiling technologies. We will critically discuss if the genetic background of ovarian cancer can indeed represent a determinant issue for decision making in the treatment selection and how the provocative preclinical findings might be translated in the therapeutic scenario. The presently available preclinical and clinical evidence clearly indicates that genetic background has an emerging role in treatment individualization for ovarian cancer patients. PMID:19825178

  15. Exome sequencing of lymphomas from three dog breeds reveals somatic mutation patterns reflecting genetic background

    PubMed Central

    Elvers, Ingegerd; Turner-Maier, Jason; Swofford, Ross; Koltookian, Michele; Johnson, Jeremy; Stewart, Chip; Zhang, Cheng-Zhong; Schumacher, Steven E.; Beroukhim, Rameen; Rosenberg, Mara; Thomas, Rachael; Mauceli, Evan; Getz, Gad; Palma, Federica Di; Modiano, Jaime F.; Breen, Matthew; Lindblad-Toh, Kerstin; Alföldi, Jessica

    2015-01-01

    Lymphoma is the most common hematological malignancy in developed countries. Outcome is strongly determined by molecular subtype, reflecting a need for new and improved treatment options. Dogs spontaneously develop lymphoma, and the predisposition of certain breeds indicates genetic risk factors. Using the dog breed structure, we selected three lymphoma predisposed breeds developing primarily T-cell (boxer), primarily B-cell (cocker spaniel), and with equal distribution of B- and T-cell lymphoma (golden retriever), respectively. We investigated the somatic mutations in B- and T-cell lymphomas from these breeds by exome sequencing of tumor and normal pairs. Strong similarities were evident between B-cell lymphomas from golden retrievers and cocker spaniels, with recurrent mutations in TRAF3-MAP3K14 (28% of all cases), FBXW7 (25%), and POT1 (17%). The FBXW7 mutations recurrently occur in a specific codon; the corresponding codon is recurrently mutated in human cancer. In contrast, T-cell lymphomas from the predisposed breeds, boxers and golden retrievers, show little overlap in their mutation pattern, sharing only one of their 15 most recurrently mutated genes. Boxers, which develop aggressive T-cell lymphomas, are typically mutated in the PTEN-mTOR pathway. T-cell lymphomas in golden retrievers are often less aggressive, and their tumors typically showed mutations in genes involved in cellular metabolism. We identify genes with known involvement in human lymphoma and leukemia, genes implicated in other human cancers, as well as novel genes that could allow new therapeutic options. PMID:26377837

  16. Bovine spastic paresis: A review of the genetic background and perspectives for the future.

    PubMed

    Goeckmann, Victoria; Rothammer, Sophie; Medugorac, Ivica

    2016-10-01

    Bovine spastic paresis (BSP) is a sporadic, progressive neuromuscular disease that is thought to affect all breeds of cattle. The disease manifests as a unilateral or bilateral hyperextension of the hind limb due to increased muscle tone or permanent spasm of mainly the gastrocnemius and/or the quadriceps muscle. Clinical signs only appear in rising, standing and moving animals, which is an important diagnostic feature. Although several medical treatments have been described, surgical procedures such as neurectomy or tenectomy are generally indicated. Even though complete recovery can be achieved, BSP-affected animals should not be used for breeding, since BSP is commonly considered a hereditary disease. The condition therefore negatively affects animal welfare, economics and breeding. When first described in 1922, BSP was already assumed to be heritable, and this assumption has been perpetuated by subsequent authors who have only discussed its possible modes of inheritance, which included monogenetic and polygenetic modes and gene-environment interactions. Besides some clinical aspects and the consideration of the tarsal joint angle as a BSP-correlated trait, this review mainly focuses on the assumed genetic aspects of BSP. Evaluation of the published literature demonstrates that to date, irrevocable proof for the assumed heritability of BSP is still missing. The assumption of heredity is further contradicted by known allele frequencies and incidences of proven hereditary diseases in cattle, such as arachnomelia or bovine spinal muscular atrophy. Consequently, future research is needed to determine the cause of spastic paresis. Procedures that will help test the null-hypothesis ('BSP is not hereditary') and possible modes of inheritance are discussed in this review. PMID:27687928

  17. The Effects of Background and Interference Selection on Patterns of Genetic Variation in Subdivided Populations.

    PubMed

    Zeng, Kai; Corcoran, Pádraic

    2015-12-01

    It is well known that most new mutations that affect fitness exert deleterious effects and that natural populations are often composed of subpopulations (demes) connected by gene flow. To gain a better understanding of the joint effects of purifying selection and population structure, we focus on a scenario where an ancestral population splits into multiple demes and study neutral diversity patterns in regions linked to selected sites. In the background selection regime of strong selection, we first derive analytic equations for pairwise coalescent times and FST as a function of time after the ancestral population splits into two demes and then construct a flexible coalescent simulator that can generate samples under complex models such as those involving multiple demes or nonconservative migration. We have carried out extensive forward simulations to show that the new methods can accurately predict diversity patterns both in the nonequilibrium phase following the split of the ancestral population and in the equilibrium between mutation, migration, drift, and selection. In the interference selection regime of many tightly linked selected sites, forward simulations provide evidence that neutral diversity patterns obtained from both the nonequilibrium and equilibrium phases may be virtually indistinguishable for models that have identical variance in fitness, but are nonetheless different with respect to the number of selected sites and the strength of purifying selection. This equivalence in neutral diversity patterns suggests that data collected from subdivided populations may have limited power for differentiating among the selective pressures to which closely linked selected sites are subject.

  18. Parent-of-origin genetic background affects the transcriptional levels of circadian and neuronal plasticity genes following sleep loss

    PubMed Central

    Tinarelli, Federico; Garcia-Garcia, Celina; Nicassio, Francesco; Tucci, Valter

    2014-01-01

    Sleep homoeostasis refers to a process in which the propensity to sleep increases as wakefulness progresses and decreases as sleep progresses. Sleep is tightly organized around the circadian clock and is regulated by genetic and epigenetic mechanisms. The homoeostatic response of sleep, which is classically triggered by sleep deprivation, is generally measured as a rebound effect of electrophysiological measures, for example delta sleep. However, more recently, gene expression changes following sleep loss have been investigated as biomarkers of sleep homoeostasis. The genetic background of an individual may affect this sleep-dependent gene expression phenotype. In this study, we investigated whether parental genetic background differentially modulates the expression of genes following sleep loss. We tested the progeny of reciprocal crosses of AKR/J and DBA/2J mouse strains and we show a parent-of-origin effect on the expression of circadian, sleep and neuronal plasticity genes following sleep deprivation. Thus, we further explored, by in silico, specific functions or upstream mechanisms of regulation and we observed that several upstream mechanisms involving signalling pathways (i.e. DICER1, PKA), growth factors (CSF3 and BDNF) and transcriptional regulators (EGR2 and ELK4) may be differentially modulated by parental effects. This is the first report showing that a behavioural manipulation (e.g. sleep deprivation) in adult animals triggers specific gene expression responses according to parent-of-origin genomic mechanisms. Our study suggests that the same mechanism may be extended to other behavioural domains and that the investigation of gene expression following experimental manipulations should take seriously into account parent-of-origin effects. PMID:24446504

  19. Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background.

    PubMed

    Rashtak, S; Marietta, E; Cheng, S; Camilleri, M; Pittelkow, M; David, C; Grande, J; Murray, J

    2010-06-01

    To investigate the role of HLA-DQ2 in the pathogenesis of associated immune disorders, we generated transgenic mice that expressed HLA-DQ2 in the absence of endogenous murine class II molecules (AE(0)DQ2). These AE(0)DQ2 mice with a mixed genetic background spontaneously developed skin lesions on their ears, whereas control AE(0)DQ6 genotype control mice (also with a mixed genetic background) did not. The skin lesions were characterized by deep subepidermal blistering with hydropic degeneration and lymphoid infiltration in the subepidermal area as determined by histopathology. Immunofluorescence analysis revealed thick band-like granular deposition of IgG, IgM, and a thin band of IgA deposition along the basement membrane. AE(0)DQ2 mice also developed significant and progressive hematuria and proteinuria as compared with the AE(0)DQ6 mice (p < 0.05). Histopathology showed immune complex deposits in the glomeruli of AE(0)DQ2 mice. Immunofluorescence analysis showed progressive mesangial and capillary wall deposition of IgA, IgM, IgG and C1q in the kidney. With electron microscopy, the deposits showed a 'fingerprint' substructure; and tubuloreticular structures were identified within endothelial cells. Conversely, these changes were not observed in AE(0)DQ6 mice. Serum anti-double stranded (ds)DNA IgM and IgG levels were also significantly elevated among AE(0)DQ2 mice compared with AE(0)DQ6 mice (p < 0.001). In conclusion, AE(0)DQ2 mice spontaneously develop an autoimmune lupus-like syndrome and are useful model for this disease. It remains to be determined whether genetic admixture played a role in the development of this systemic lupus erythematosus-like syndrome in HLA-DQ2 transgenic mice. Lupus (2010) 19, 815-829.

  20. The C57BL/6 genetic background confers cardioprotection in iron-overloaded mice

    PubMed Central

    Musumeci, Marco; Maccari, Sonia; Sestili, Paola; Massimi, Alessia; Corritore, Elisa; Marano, Giuseppe; Catalano, Liviana

    2013-01-01

    Background Chronic transfusion therapy causes a progressive iron overload that damages many organs including the heart. Recent evidence suggests that L-type calcium channels play an important role in iron uptake by cardiomyocytes under conditions of iron overload. Given that beta-adrenergic stimulation significantly enhances L-type calcium current, we hypothesised that beta-adrenergic blocking drugs could reduce the deleterious effects of iron overload on the heart. Methods Iron overload was generated by intraperitoneal injections of iron dextran (1g/kg) administered once a week for 8 weeks in male C57bl/6 mice, while propranolol was administered in drinking water at the dose of 40 mg/kg/day. Cardiac function and ventricular remodelling were evaluated by echocardiography and histological methods. Results As compared to placebo, iron injection caused cardiac iron deposition. Surprisingly, despite iron overload, myocardial function and ventricular geometry in the iron-treated mice resulted unchanged as compared to those in the placebo-treated mice. Administration of propranolol increased cardiac performance in iron-overloaded mice. Specifically, as compared to the values in the iron-overloaded group, in iron-overloaded animals treated with propranolol left ventricular fractional shortening increased (from 31.6% to 44.2%, P =0.01) whereas left ventricular end-diastolic diameter decreased (from 4.1±0.1 mm to 3.5±0.1 mm, P =0.03). Propranolol did not alter cardiac systolic function or left ventricular sizes in the placebo group. Conclusions These results demonstrate that C57bl/6 mice are resistant to iron overload-induced myocardial injury and that treatment with propranolol is able to increase cardiac performance in iron-overloaded mice. However, since C57bl/6 mice were resistant to iron-induced injury, it remains to be evaluated further whether propranolol could prevent iron-overload cardiomyopathy. PMID:22790263

  1. Functional analysis of the heterologous NSP1 genes in the genetic background of simian rotavirus SA11.

    PubMed

    Okada, J; Kobayashi, N; Taniguchi, K; Shiomi, H

    1999-01-01

    Function of rotavirus NSP1 was analyzed by using single-NSP1 gene-substitution reassortants, SKF, SDF, and SNF which have the NSP1 gene derived from human rotaviruses KU, DS-1, and canine rotavirus K9, respectively, in the genetic background of simian rotavirus SA11. The NSP1 genes from KU, DS-1, K9, and SA11 exhibited 58-76% nucleotide sequence identity to one another. No substantial difference in viral growth was observed among the reassortants and SA11. However, production of NSP1 was not detected in SNF when viral proteins were labelled with 35S-methionine during replication in MA104 cells, in contrast to SA11, SKF and SDF which exhibited evident expression of NSP1. Difference in reassortant formation was examined among the reassortant clones generated between human rotavirus strain 69M and either of SA11, SKF or SNF. Although reassortant formation rate was significantly lower in the cross 69M x SNF than the other crosses, selection rates of RNA segments from parent strain 69M in the resultant reassortants was similar among the crosses. Selectivity of homologous and heterologous NSP1 genes in SA11 background was also analyzed by mixed infection and multiple passages among the single-NSP1 gene-reassortants and/or SA11, KU NSP1 gene was selected most frequently, whereas homologous (SA11) NSP1 gene was least efficiently segregated. These results indicated that viral growth and genome segment reassortment with other viruses may not be influenced by the presence of heterologous NSP1 and its expression level, while genomic diversity of NSP1 genes might have been associated with the relative adaptability to the genetic background of SA11. PMID:10481750

  2. Generation of mouse induced pluripotent stem cells from different genetic backgrounds using Sleeping beauty transposon mediated gene transfer.

    PubMed

    Muenthaisong, Suchitra; Ujhelly, Olga; Polgar, Zsuzsanna; Varga, Eszter; Ivics, Zoltan; Pirity, Melinda K; Dinnyes, Andras

    2012-11-15

    Induced pluripotent stem (iPS) cell technology involves reprogramming somatic cells to a pluripotent state. The original technology used to produce these cells requires viral gene transduction and results in the permanent integration of exogenous genes into the genome. This can lead to the development of abnormalities in the derived iPS cells. Here, we report that non-viral transfection of a Sleeping Beauty (SB) transposon containing the coding sequences Oct3/4 (Pouf1), Sox-2, Klf-4 and c-Myc (OSKM) linked with 2A peptides, can reprogram mouse fibroblasts. We have established reprogrammed mouse cell lines from three different genetic backgrounds: (1) ICR-outbred, (2) C57BL/6-inbred and (3) F1-hybrid (C57BL/6 x DBA/2J), with parallel robust expression of all exogenous (Oct3/4, Sox-2, Klf-4, and c-Myc) and endogenous (e.g. Oct3/4 and Nanog) pluripotency genes. The iPS cell lines exhibited characteristics typical for undifferentiated embryonic stem (ES) cell lines: ES cell-like morphology, alkaline phosphatase (ALP) positivity and gene expression pattern (shown by reverse transcription PCR, and immunofluorescence of ES cell markers-e.g. Oct3/4, SSEA1, Nanog). Furthermore, cells were able to form embryoid bodies (EBs), to beat rhythmically, and express cardiac (assayed by immunofluorescence, e.g. cardiac Troponin T, desmin) and neuronal (assayed by immunofluorescence e.g. nestin, Tuj1) markers. The in vitro differentiation potential was found to be the highest in the ICR-derived iPS lines (ICR-iPS). Interestingly, the ICR-iPS lines had even higher differentiation potential than the ICR-ES cell lines: the rate of EBs forming rhythmically beating cardiomyocytes was 4% in ICR-ES and 79% in ICR-iPS cells, respectively. In vivo, the ICR and F1 hybrid iPS cells formed chimeras and one of the iPS cells from the F1 hybrid background transmitted to the germline. Our results suggest that iPS technology may be useful for generating pluripotent stem cells from genetic backgrounds

  3. Frequency and genetic background of the position 122 (Val----Ile) variant transthyretin gene in the black population.

    PubMed Central

    Jacobson, D R; Reveille, J D; Buxbaum, J N

    1991-01-01

    Transthyretin (TTR) (122 Val----Ile), caused by a point mutation which destroys a MaeIII restriction site, is associated with cardiac amyloidosis in black individuals. To estimate the frequency of the MaeIII(-) gene in the black population without overt cardiac disease, DNA from 177 black individuals without amyloidosis was amplified by the PCR around TTR codon 122 and was digested with MaeIII. The MaeIII(-) gene frequency was 4/354 (1.1%; 95% confidence interval 0.32%2.7%), suggesting that the variant is relatively common in blacks. HLA genotype testing did not suggest that the TTR (122 Val----Ile) heterozygotes were of a closely related genetic background. Images Figure 2 PMID:2063870

  4. Virulence Differences among Melissococcus plutonius Strains with Different Genetic Backgrounds in Apis mellifera Larvae under an Improved Experimental Condition.

    PubMed

    Nakamura, Keiko; Yamazaki, Yuko; Shiraishi, Akiyo; Kobayashi, Sota; Harada, Mariko; Yoshiyama, Mikio; Osaki, Makoto; Okura, Masatoshi; Takamatsu, Daisuke

    2016-01-01

    European foulbrood (EFB) caused by Melissococcus plutonius is an important bacterial disease of honeybee larvae. M. plutonius strains can be grouped into three genetically distinct groups (CC3, CC12 and CC13). Because EFB could not be reproduced in artificially reared honeybee larvae by fastidious strains of CC3 and CC13 previously, we investigated a method to improve experimental conditions using a CC3 strain and found that infection with a potassium-rich diet enhanced proliferation of the fastidious strain in larvae at the early stage of infection, leading to the appearance of clear clinical symptoms. Further comparison of M. plutonius virulence under the conditions revealed that the representative strain of CC12 was extremely virulent and killed all tested bees before pupation, whereas the CC3 strain was less virulent than the CC12 strain, and a part of the infected larvae pupated. In contrast, the tested CC13 strain was avirulent, and as with the non-infected control group, most of the infected brood became adult bees, suggesting differences in the insect-level virulence among M. plutonius strains with different genetic backgrounds. These strains and the improved experimental infection method to evaluate their virulence will be useful tools for further elucidation of the pathogenic mechanisms of EFB. PMID:27625313

  5. [Genetic background in common forms of obesity - from studies on identical twins to candidate genes of obesity].

    PubMed

    Bendlová, Běla; Lukášová, Petra; Vaňková, Markéta; Vejražková, Daniela; Bradnová, Olga; Včelák, Josef; Stanická, Soňa; Zamrazilová, Hana; Aldhoon-Hainerová, Irena; Dušátková, Lenka; Kunešová, Marie; Hainer, Vojtěch

    2014-01-01

    Common obesity is a result of interaction between genes and environmental/lifestyle factors, with heritability estimates 40-70%. Not only the susceptibility to obesity but also the success of weight management depends on the genetic background of each individual. This paper summarizes the up-to-date knowledge on genetic causes of common obesities. Introduction of genome-wide association studies (GWAS) led to an identification of a total of 32 variants associated with obesity/BMI and 14 with body fat distribution. Further, a great progress in revealing the mechanisms regulating the energy balance was also noted. However, the proportion of explained variance for BMI is still low, suggesting other mechanisms such as gene-gene and gene-environment interactions, rare gene variants, copy number variants polymorphisms, or epigenetic modifications and microRNAs regulating gene transcription. In summary, we present results of our studies on obesity risk variants in Czech adults, children and adolescents including those evaluating the influence of selected gene variants on the outcomes of weight management. PMID:25199545

  6. [Genetic background in common forms of obesity - from studies on identical twins to candidate genes of obesity].

    PubMed

    Bendlová, Běla; Lukášová, Petra; Vaňková, Markéta; Vejražková, Daniela; Bradnová, Olga; Včelák, Josef; Stanická, Soňa; Zamrazilová, Hana; Aldhoon-Hainerová, Irena; Dušátková, Lenka; Kunešová, Marie; Hainer, Vojtěch

    2014-01-01

    Common obesity is a result of interaction between genes and environmental/lifestyle factors, with heritability estimates 40-70%. Not only the susceptibility to obesity but also the success of weight management depends on the genetic background of each individual. This paper summarizes the up-to-date knowledge on genetic causes of common obesities. Introduction of genome-wide association studies (GWAS) led to an identification of a total of 32 variants associated with obesity/BMI and 14 with body fat distribution. Further, a great progress in revealing the mechanisms regulating the energy balance was also noted. However, the proportion of explained variance for BMI is still low, suggesting other mechanisms such as gene-gene and gene-environment interactions, rare gene variants, copy number variants polymorphisms, or epigenetic modifications and microRNAs regulating gene transcription. In summary, we present results of our studies on obesity risk variants in Czech adults, children and adolescents including those evaluating the influence of selected gene variants on the outcomes of weight management.

  7. Ultrasonic and sensory characterization of dry-cured ham fat from Iberian pigs with different genetics and feeding backgrounds.

    PubMed

    Niñoles, L; Sanjuan, N; Ventanas, S; Benedito, J

    2008-11-01

    The textural and ultrasonic properties of the subcutaneous fat from five batches of dry-cured hams from animals with different genetics (Iberian, Iberian×Duroc) and type of feeding ("montanera", concentrate feeds with different oleic acid content) were studied and related to the sensory traits (oiliness and brightness) of their biceps femoris muscle. The different genetics and feeding backgrounds found in the batches brought about differences in their ultrasonic velocities (average velocity from 4 to 20°C ranged from 1608 to 1650m/s) and textural parameters (maximum force at 8°C ranged from 11 to 21N). On average, batches with lower textural parameters had lower velocities and higher sensory scores. Ultrasonic measurements were used to carry out a discriminant analysis which allowed 78.3% of the samples to be correctly classified in the batches considered. Therefore, ultrasonic and sensory techniques could be useful in the characterization and differentiation of dry-cured hams from Iberian pigs.

  8. Virulence Differences among Melissococcus plutonius Strains with Different Genetic Backgrounds in Apis mellifera Larvae under an Improved Experimental Condition

    PubMed Central

    Nakamura, Keiko; Yamazaki, Yuko; Shiraishi, Akiyo; Kobayashi, Sota; Harada, Mariko; Yoshiyama, Mikio; Osaki, Makoto; Okura, Masatoshi; Takamatsu, Daisuke

    2016-01-01

    European foulbrood (EFB) caused by Melissococcus plutonius is an important bacterial disease of honeybee larvae. M. plutonius strains can be grouped into three genetically distinct groups (CC3, CC12 and CC13). Because EFB could not be reproduced in artificially reared honeybee larvae by fastidious strains of CC3 and CC13 previously, we investigated a method to improve experimental conditions using a CC3 strain and found that infection with a potassium-rich diet enhanced proliferation of the fastidious strain in larvae at the early stage of infection, leading to the appearance of clear clinical symptoms. Further comparison of M. plutonius virulence under the conditions revealed that the representative strain of CC12 was extremely virulent and killed all tested bees before pupation, whereas the CC3 strain was less virulent than the CC12 strain, and a part of the infected larvae pupated. In contrast, the tested CC13 strain was avirulent, and as with the non-infected control group, most of the infected brood became adult bees, suggesting differences in the insect-level virulence among M. plutonius strains with different genetic backgrounds. These strains and the improved experimental infection method to evaluate their virulence will be useful tools for further elucidation of the pathogenic mechanisms of EFB. PMID:27625313

  9. Genes and personality characteristics: Possible association of the genetic background with intelligence and decision making in 830 Caucasian Greek subjects.

    PubMed

    Marinos, Georgios; Naziris, Nikolaos; Limnaios, Stefanos A; Drakoulis, Nikolaos

    2014-12-01

    It is well known that intelligence consists of a variety of interactional and cognitive skills and abilities (e.g. tradecraft; critical and divergent thinking; perception of foreign information). Decision making is defined as the conscious choice between given options, relating to a problem. Both genetic background and environment comprise key elements for personality characteristics of the human being. The aim of this study is to determine the frequency distribution of rs324420, rs1800497, rs363050, rs6265, rs1328674 polymorphisms known to be involved in individual personality characteristics, in 830 Greek Subjects. The study is independent from direct clinical measurements (e.g. IQ measurements; physiological tests). The population of the volunteers is described, based on genotype, sex, with the respective gene frequencies, including the Minor Allele Frequency (MAF). A potential influence of the volunteer gender with the above characteristics (based on genotypes and alleles) is examined and finally, volunteers are classified as follows: A volunteer receives + 1, for each genotype/allele, which enhances his intelligence or his decision-making. In contrast, he receives - 1, for each genotype/allele, which relegates the individual characteristic. No statistically significant gender-characteristics correlation is observed. According to their genetic profile, a rate of 92.5%, of the volunteers may be characterized by prudence and temperance of thought, with only a small proportion of them (7.5%) may be classified as genetically spontaneous and adventurous. Regarding intelligence, the study population may lay around average and a little above it, at a rate of 96.3%, while the edges of the scale suggest only a 0.5% of the volunteers, who, although the "smartest", somehow seem to lack prudence. In conclusion, individuals with low cognitive ability may be more prudent than others and vice versa, while the "smartest" ones tend to be more risky, in decision

  10. Comparison of the genetic background of different Colombian populations using the SNPforID 52plex identification panel.

    PubMed

    Ibarra, Adriana; Freire-Aradas, Ana; Martínez, Martha; Fondevila, Manuel; Burgos, German; Camacho, Mauricio; Ostos, Henry; Suarez, Zuleyma; Carracedo, Angel; Santos, Sidney; Gusmão, Leonor

    2014-01-01

    Various strategies for analysing SNP markers and genotyping have been published with the goal of obtaining informative profiles from biological samples that contain only small amounts of template and/or degraded DNA. In this study, a multiplex assay of 52 autosomal single-nucleotide polymorphisms (SNPs) was used to analyse 438 individuals from urban populations from different regions of Colombia, as well as a sample of 50 Native American individuals of the Pastos ethnic group from Nariño. To determine if significant differences in these 52 SNPs exist between the distinct regions of Colombia, genetic distance and admixture analyses were performed based on the available data for 17 different Colombian population groups and for population groups from Africa, Europe and America. The results demonstrate significant differences between the populations from the Southwest Andean, Central-West Andean, Central-East Andean, Orinoquian and northern Colombian Pacific Coast regions. Most of the regions exhibited a European and Native American admixture. One exception is the population from the region of Chocó (on the northern Pacific Coast), which exhibits a high proportion of African admixture (54 %). From the observed genetic backgrounds, it is possible to conclude that a single reference database for the entire country would not be suitable for forensic purposes. The allele frequencies and the forensically relevant parameters were calculated for all of the markers in each Colombian region with significant values for the combined matching probability (power of discrimination ≥0.99999999999999990) and the combined probability of exclusion (≥0.9990) in trios that were obtained from all of the population groups. PMID:23665814

  11. Insulin-like signaling (IIS) responses to temperature, genetic background, and growth variation in garter snakes with divergent life histories.

    PubMed

    Reding, Dawn M; Addis, Elizabeth A; Palacios, Maria G; Schwartz, Tonia S; Bronikowski, Anne M

    2016-07-01

    The insulin/insulin-like signaling pathway (IIS) has been shown to mediate life history trade-offs in mammalian model organisms, but the function of this pathway in wild and non-mammalian organisms is understudied. Populations of western terrestrial garter snakes (Thamnophis elegans) around Eagle Lake, California, have evolved variation in growth and maturation rates, mortality senescence rates, and annual reproductive output that partition into two ecotypes: "fast-living" and "slow-living". Thus, genes associated with the IIS network are good candidates for investigating the mechanisms underlying ecological divergence in this system. We reared neonates from each ecotype for 1.5years under two thermal treatments. We then used qPCR to compare mRNA expression levels in three tissue types (brain, liver, skeletal muscle) for four genes (igf1, igf2, igf1r, igf2r), and we used radioimmunoassay to measure plasma IGF-1 and IGF-2 protein levels. Our results show that, in contrast to most mammalian model systems, igf2 mRNA and protein levels exceed those of igf1 and suggest an important role for igf2 in postnatal growth in reptiles. Thermal rearing treatment and recent growth had greater impacts on IGF levels than genetic background (i.e., ecotype), and the two ecotypes responded similarly. This suggests that observed ecotypic differences in field measures of IGFs may more strongly reflect plastic responses in different environments than evolutionary divergence. Future analyses of additional components of the IIS pathway and sequence divergence between the ecotypes will further illuminate how environmental and genetic factors influence the endocrine system and its role in mediating life history trade-offs. PMID:27181752

  12. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    NASA Astrophysics Data System (ADS)

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  13. Neurobehavioral abnormalities in the dysbindin-1 mutant, sandy, on a C57BL/6J genetic background

    PubMed Central

    Cox, M.M.; Tucker, A.M.; Tang, J.; Talbot, K.; Richer, D.C.; Yeh, L.; Arnold, S.E.

    2009-01-01

    Sandy mice have a deletion mutation in the gene encoding dysbindin-1, Dtnbp1, with consequent reduction of the protein in heterozygotes and its loss in homozygotes. The sandy mouse thus serves as an animal model of dysbindin-1 function. Since this protein is concentrated in synaptic tissue and affects transmitter release, it may affect neuronal processes that mediate behavior. To investigate the neurobehavioral effects of the Dtnbp1 mutation, we studied littermate sandy and wild-type controls on a C57BL/6J genetic background. The three animal groups were indistinguishable in their external physical characteristics, sensorimotor skills, and indices of anxiety-like behaviors. In the open field, however, homozygous animals were hyperactive and appeared to show less habituation to the initially novel environment. In the Morris water maze, homozygous animals displayed clear deficits in spatial learning and memory with marginal deficits in visual association learning. Apart from the last mention deficits, these abnormalities are consistent with hippocampal dysfunction and in some cases with elevated dopaminergic transmission via D2 dopamine receptors. Since similar deficits in spatial learning and memory have been found in schizophrenia, where decreased dysbindin-1 has been found in the hippocampus, the sandy mouse may also model certain aspects of cognition and behavior relevant to schizophrenia. PMID:19220483

  14. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds.

    PubMed

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-11-27

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO.

  15. A specific superoxide dismutase mutation is on the same genetic background in sporadic and familial cases of amyotrophic lateral sclerosis

    SciTech Connect

    Hayward, C.; Brock, D.J.H.; Swingler, R.J.

    1996-11-01

    Amyotrophic lateral sclerosis (ALS) is a degenerative disease of motor neurons, causing progressive muscular atrophy, weakness, and death from respiratory failure, often within 2-3 years. Although most cases are sporadic, some 5%-10% are inherited as autosomal dominants with age-dependent penetrance. An ALS locus has been mapped to chromosome 21q, and causative mutations identified in the Cu/Zn superoxide dismutase (SOD1) gene. A majority of SOD1 mutations have been found in cases with a clear family history of ALS. However, we and others have also described SOD1 mutations in patients where the disease appears to be sporadic. This is especially true for the missense mutation in codon 113 of the SOD1 gene, which substitutes threonine for isoleucine (I113T). One explanation for this finding is that this codon is a mutational hot spot with sporadic cases representing new mutations. Another is that the inherited nature of the cases is disguised by the reduced penetrance of this specific mutation. We have now shown that each of six unrelated cases of I113T mutation that we have collected in the Scottish population occurs on the same genetic background. Association analysis of multiple flanking loci on chromosome 21q supports the conclusion of a founder effect, with the original mutational event occurring {ge}10 generations ago. 12 refs., 1 fig., 1 tab.

  16. Lactic Acid Bacteria Protects Caenorhabditis elegans from Toxicity of Graphene Oxide by Maintaining Normal Intestinal Permeability under different Genetic Backgrounds

    PubMed Central

    Zhao, Yunli; Yu, Xiaoming; Jia, Ruhan; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2015-01-01

    Lactic acid bacteria (LAB) is safe and useful for food and feed fermentation. We employed Caenorhabditis elegans to investigate the possible beneficial effect of LAB (Lactobacillus bulgaricus) pretreatment against toxicity of graphene oxide (GO) and the underlying mechanisms. LAB prevented GO toxicity on the functions of both primary and secondary targeted organs in wild-type nematodes. LAB blocked translocation of GO into secondary targeted organs through intestinal barrier by maintaining normal intestinal permeability in wild-type nematodes. Moreover, LAB prevented GO damage on the functions of both primary and secondary targeted organs in exposed nematodes with mutations of susceptible genes (sod-2, sod-3, gas-1, and aak-2) to GO toxicity by sustaining normal intestinal permeability. LAB also sustained the normal defecation behavior in both wild-type nematodes and nematodes with mutations of susceptible genes. Therefore, the beneficial role of LAB against GO toxicity under different genetic backgrounds may be due to the combinational effects on intestinal permeability and defecation behavior. Moreover, the beneficial effects of LAB against GO toxicity was dependent on the function of ACS-22, homologous to mammalian FATP4 to mammalian FATP4. Our study provides highlight on establishment of pharmacological strategy to protect intestinal barrier from toxicity of GO. PMID:26611622

  17. Effect of parent genetic background on latency and antigenicity of UV-induced tumors originating in F1 hybrids.

    PubMed

    Kitajima, T; Iwashiro, M; Kuribayashi, K; Imamura, S

    1995-02-01

    Wide variations in susceptibility to skin tumor development by chronic ultraviolet light (UV) exposure and antigenicity of induced tumors which is estimated by tumor rejection in syngeneic recipients have been recognized among various murine strains. To examine the effect of parent genetic background on latency and antigenicity of UV-induced tumors originating in F1 hybrids, we induced skin tumors in three mouse strains: BALB/c, C57BL/6, (B6), and C3H/HeMs (C3H/He), and their F1 hybrids: (BALB/c x C3H/He)F1 (CC3F1), (BALB/c x B6)F1 (CB6F1) and (C3H/HexB6)F1 (C3B6F1) by exposing mice to UV radiation (0.44 mW/cm2 for 1 h) three times a week, and analyzed whether the UV-induced tumors originating in F1 hybrids possess the similar property in latency or antigenicity as seen in the UV-induced tumors derived from the parent strains. The latency of tumor induction by chronic UV exposure in C3H/He, BALB/c and their F1 hybrid CC3F1 was relatively short whereas that of B6 was relatively long, and that of F1 hybrids with B6 (CB6F1 and C3B6F1) was intermediate. On the other hand, the low antigenicity as progressive growth behavior of UV-induced tumors in syngeneic recipients was observed not only in tumors derived from C3H/He but also in those from F1 hybrids with C3H/He (C3B6F1 and CC3F1) whereas most tumors derived from B6, BALB/c and their F1 hybrid CB6F1 were highly antigenic as to be rejected in syngeneic recipients. These findings suggest that the parent genetic quality regulating the susceptibility to tumor induction by chronic UV exposure is co-dominantly inherited into F1 hybrids.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7757331

  18. Incomplete transfer of accessory loci influencing SbMATE expression underlies genetic background effects for aluminum tolerance in sorghum.

    PubMed

    Melo, Janaina O; Lana, Ubiraci G P; Piñeros, Miguel A; Alves, Vera M C; Guimarães, Claudia T; Liu, Jiping; Zheng, Yi; Zhong, Silin; Fei, Zhangjun; Maron, Lyza G; Schaffert, Robert E; Kochian, Leon V; Magalhaes, Jurandir V

    2013-01-01

    Impaired root development caused by aluminum (Al) toxicity is a major cause of grain yield reduction in crops cultivated on acid soils, which are widespread worldwide. In sorghum, the major Al-tolerance locus, AltSB , is due to the function of SbMATE, which is an Al-activated root citrate transporter. Here we performed a molecular and physiological characterization of various AltSB donors and near-isogenic lines harboring various AltSB alleles. We observed a partial transfer of Al tolerance from the parents to the near-isogenic lines that was consistent across donor alleles, emphasizing the occurrence of strong genetic background effects related to AltSB . This reduction in tolerance was variable, with a 20% reduction being observed when highly Al-tolerant lines were the AltSB donors, and a reduction as great as 70% when other AltSB alleles were introgressed. This reduction in Al tolerance was closely correlated with a reduction in SbMATE expression in near-isogenic lines, suggesting incomplete transfer of loci acting in trans on SbMATE. Nevertheless, AltSB alleles from the highly Al-tolerant sources SC283 and SC566 were found to retain high SbMATE expression, presumably via elements present within or near the AltSB locus, resulting in significant transfer of the Al-tolerance phenotype to the derived near-isogenic lines. Allelic effects could not be explained by coding region polymorphisms, although occasional mutations may affect Al tolerance. Finally, we report on the extensive occurrence of alternative splicing for SbMATE, which may be an important component regulating SbMATE expression in sorghum by means of the nonsense-mediated RNA decay pathway. PMID:22989115

  19. Mupirocin-induced mutations in ileS in various genetic backgrounds of methicillin-resistant Staphylococcus aureus.

    PubMed

    Lee, Andie S; Gizard, Yann; Empel, Joanna; Bonetti, Eve-Julie; Harbarth, Stephan; François, Patrice

    2014-10-01

    Topical mupirocin is widely used for the decolonization of methicillin-resistant Staphylococcus aureus (MRSA) carriers. We evaluated the capacity of various MRSA clonotypes to develop mutations in the ileS gene associated with low-level mupirocin resistance. Twenty-four mupirocin-sensitive MRSA isolates from a variety of genotypes (determined by a multilocus variable-number tandem-repeat assay) were selected. Mupirocin MICs were determined by Etest. The isolates were then incubated in subinhibitory concentrations of mupirocin for 7 to 14 days. Repeat MIC determinations and sequencing of the ileS gene were then performed. Doubling times of isolates exposed to mupirocin and of unexposed isolates were compared. We found that exposure to mupirocin led to rapid induction of low-level resistance (MICs of 8 to 24 μg/ml) in 11 of 24 (46%) MRSA isolates. This phenomenon was observed in strains with diverse genetic backgrounds. Various mutations were detected in 18 of 24 (75%) MRSA isolates. Acquisition of mutations appeared to be a stepwise process during prolonged incubation with the drug. Among the five isolates exhibiting low-level resistance and the highest MICs, four tested sensitive after incubation in the absence of mupirocin but there was no reversion to the susceptible wild-type primary sequence. Resistance was not associated with significant fitness cost, suggesting that MRSA strains with low-level mupirocin resistance may have a selective advantage in facilities where mupirocin is commonly used. Our findings emphasize the importance of the judicious use of this topical agent and the need to closely monitor for the emergence of resistance.

  20. Monitoring Perinatal Gut Microbiota in Mouse Models by Mass Spectrometry Approaches: Parental Genetic Background and Breastfeeding Effects

    PubMed Central

    Levi Mortera, Stefano; Del Chierico, Federica; Vernocchi, Pamela; Rosado, Maria M.; Cavola, Agnese; Chierici, Marco; Pieroni, Luisa; Urbani, Andrea; Carsetti, Rita; Lante, Isabella; Dallapiccola, Bruno; Putignani, Lorenza

    2016-01-01

    At birth, contact with external stimuli, such as nutrients derived from food, is necessary to modulate the symbiotic balance between commensal and pathogenic bacteria, protect against bacterial dysbiosis, and initiate the development of the mucosal immune response. Among a variety of different feeding patterns, breastfeeding represents the best modality. In fact, the capacity of breast milk to modulate the composition of infants’ gut microbiota leads to beneficial effects on their health. In this study, we used newborn mice as a model to evaluate the effect of parental genetic background (i.e., IgA-producing mice and IgA-deficient mice) and feeding modulation (i.e., maternal feeding and cross-feeding) on the onset and shaping of gut microbiota after birth. To investigate these topics, we used either a culturomic approach that employed Matrix Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MS), or bottom–up Liquid Chromatography, with subsequent MSMS shotgun metaproteomic analysis that compared and assembled results of the two techniques. We found that the microbial community was enriched by lactic acid bacteria when pups were breastfed by wild-type (WT) mothers, while IgA-deficient milk led to an increase in the opportunistic bacterial pathogen (OBP) population. Cross-feeding results suggested that IgA supplementation promoted the exclusion of some OBPs and the temporary appearance of beneficial species in pups fed by WT foster mothers. Our results show that both techniques yield a picture of microbiota from different angles and with varying depths. In particular, our metaproteomic pipeline was found to be a reliable tool in the description of microbiota. Data from these studies are available via ProteomeXchange, with identifier PXD004033. PMID:27725814

  1. Diversity of genetic backgrounds modulating the durability of a major resistance gene. Analysis of a core collection of pepper landraces resistant to Potato virus Y.

    PubMed

    Quenouille, Julie; Saint-Felix, Ludovic; Moury, Benoit; Palloix, Alain

    2016-02-01

    The evolution of resistance-breaking capacity in pathogen populations has been shown to depend on the plant genetic background surrounding the resistance genes. We evaluated a core collection of pepper (Capsicum annuum) landraces, representing the worldwide genetic diversity, for its ability to modulate the breakdown frequency by Potato virus Y of major resistance alleles at the pvr2 locus encoding the eukaryotic initiation factor 4E (eIF4E). Depending on the pepper landrace, the breakdown frequency of a given resistance allele varied from 0% to 52.5%, attesting to their diversity and the availability of genetic backgrounds favourable to resistance durability in the plant germplasm. The mutations in the virus genome involved in resistance breakdown also differed between plant genotypes, indicating differential selection effects exerted on the virus population by the different genetic backgrounds. The breakdown frequency was positively correlated with the level of virus accumulation, confirming the impact of quantitative resistance loci on resistance durability. Among these loci, pvr6, encoding an isoform of eIF4E, was associated with a major effect on virus accumulation and on the breakdown frequency of the pvr2-mediated resistance. This exploration of plant genetic diversity delivered new resources for the control of pathogen evolution and the increase in resistance durability.

  2. The anxiety-like phenotype of 5-HT receptor null mice is associated with genetic background-specific perturbations in the prefrontal cortex GABA-glutamate system.

    PubMed

    Bruening, S; Oh, E; Hetzenauer, A; Escobar-Alvarez, S; Westphalen, R I; Hemmings, H C; Singewald, N; Shippenberg, T; Toth, M

    2006-11-01

    A deficit in the serotonin 5-HT(1A) receptor has been found in panic and post-traumatic stress disorders, and genetic inactivation of the receptor results in an anxiety-like phenotype in mice on both the C57Bl6 and Swiss-Webster genetic backgrounds. Anxiety is associated with increased neuronal activity in the prefrontal cortex and here we describe changes in glutamate and GABA uptake of C57Bl6 receptor null mice. Although these alterations were not present in Swiss-Webster null mice, we have previously reported reductions in GABA(A) receptor expression in these but not in C57Bl6 null mice. This demonstrates that inactivation of the 5-HT(1A) receptor elicits different and genetic background-dependent perturbations in the prefrontal cortex GABA/glutamate system. These perturbations can result in a change in the balance between excitation and inhibition, and indeed both C57Bl6 and Swiss-Webster null mice show signs of increased neuronal excitability. Because neuronal activity in the prefrontal cortex controls the extent of response to anxiogenic stimuli, the genetic background-specific perturbations in glutamate and GABA neurotransmission in C57Bl6 and Swiss-Webster 5-HT(1A) receptor null mice may contribute to their shared anxiety phenotype. Our study shows that multiple strains of genetically altered mice could help us to understand the common and individual features of anxiety.

  3. Diversity of genetic backgrounds modulating the durability of a major resistance gene. Analysis of a core collection of pepper landraces resistant to Potato virus Y.

    PubMed

    Quenouille, Julie; Saint-Felix, Ludovic; Moury, Benoit; Palloix, Alain

    2016-02-01

    The evolution of resistance-breaking capacity in pathogen populations has been shown to depend on the plant genetic background surrounding the resistance genes. We evaluated a core collection of pepper (Capsicum annuum) landraces, representing the worldwide genetic diversity, for its ability to modulate the breakdown frequency by Potato virus Y of major resistance alleles at the pvr2 locus encoding the eukaryotic initiation factor 4E (eIF4E). Depending on the pepper landrace, the breakdown frequency of a given resistance allele varied from 0% to 52.5%, attesting to their diversity and the availability of genetic backgrounds favourable to resistance durability in the plant germplasm. The mutations in the virus genome involved in resistance breakdown also differed between plant genotypes, indicating differential selection effects exerted on the virus population by the different genetic backgrounds. The breakdown frequency was positively correlated with the level of virus accumulation, confirming the impact of quantitative resistance loci on resistance durability. Among these loci, pvr6, encoding an isoform of eIF4E, was associated with a major effect on virus accumulation and on the breakdown frequency of the pvr2-mediated resistance. This exploration of plant genetic diversity delivered new resources for the control of pathogen evolution and the increase in resistance durability. PMID:25967744

  4. The effects of pre- and post-natal nicotine exposure and genetic background on the striatum and behavioral phenotypes in the mouse.

    PubMed

    Balsevich, Georgia; Poon, Anna; Goldowitz, Dan; Wilking, Jennifer A

    2014-06-01

    Maternal tobacco use increases the risk of complications in pregnancy and also the risk of adverse fetal outcomes. Studies have established nicotine as the principal component of tobacco smoke that leads to the majority of negative reproductive outcomes associated with maternal tobacco use. It appears the neuroteratogenicity of nicotine is mediated by complex gene-environment interactions. Genetic background contributes to individual differences in nicotine-related phenotypes. The aim of the current study was to investigate the interaction between pre- and post-natal nicotine exposure and genetic background on the histology of the striatum and behavioral measures using DBA/2J (D2) and C57BL/6J (B6) inbred mice. Alterations in neuronal cell populations, striatal brain volume, and behavior - open field (OF) activity, novel object recognition (NOR), elevated plus maze (EPM), and passive avoidance (PA) - were evaluated on post-natal day (PN) 24 and PN75. Histological data showed that pre- and post-natal nicotine exposure resulted in decreased striatal volume among preadolescent B6 and reduced neuronal number within the striatum of preadolescent B6 mice. Behavioral data showed that pre- and post-natal nicotine exposure promoted hyperactivity in D2 female mice and disrupted NOR and PA memory. Specifically, NOR deficits were significant amongst adult male mice whereas PA deficits were seen across genetic background and sex. These data suggest that nicotine treatment, genetic background, developmental stage, and sex effect striatal morphology can lead to neurobehavioral alterations.

  5. ALTERED SENSITIVITY OF THE MOUSE FETUS TO IMPAIRED PROSTATIC BUD FORMATION BY DIOXIN: INFLUENCE OF GENETIC BACKGROUND AND NULL EXPRESSION OF TGF-ALFA AND EGF

    EPA Science Inventory

    Altered sensitivity of the mouse fetus to impaired prostatic bud formation by dioxin: Influence of genetic background and null expression of TGF and EGF.
    Rasmussen, N.T., Lin T-M., Fenton, S.E., Abbott, B.D. and R.E. Peterson.
    2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)...

  6. Recovery of Native Genetic Background in Admixed Populations Using Haplotypes, Phenotypes, and Pedigree Information – Using Cika Cattle as a Case Breed

    PubMed Central

    Simčič, Mojca; Smetko, Anamarija; Sölkner, Johann; Seichter, Doris; Gorjanc, Gregor; Kompan, Dragomir; Medugorac, Ivica

    2015-01-01

    The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP) Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which potentially have had

  7. Recovery of native genetic background in admixed populations using haplotypes, phenotypes, and pedigree information--using Cika cattle as a case breed.

    PubMed

    Simčič, Mojca; Smetko, Anamarija; Sölkner, Johann; Seichter, Doris; Gorjanc, Gregor; Kompan, Dragomir; Medugorac, Ivica

    2015-01-01

    The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP) Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which potentially have had

  8. Recovery of native genetic background in admixed populations using haplotypes, phenotypes, and pedigree information--using Cika cattle as a case breed.

    PubMed

    Simčič, Mojca; Smetko, Anamarija; Sölkner, Johann; Seichter, Doris; Gorjanc, Gregor; Kompan, Dragomir; Medugorac, Ivica

    2015-01-01

    The aim of this study was to obtain unbiased estimates of the diversity parameters, the population history, and the degree of admixture in Cika cattle which represents the local admixed breeds at risk of extinction undergoing challenging conservation programs. Genetic analyses were performed on the genome-wide Single Nucleotide Polymorphism (SNP) Illumina Bovine SNP50 array data of 76 Cika animals and 531 animals from 14 reference populations. To obtain unbiased estimates we used short haplotypes spanning four markers instead of single SNPs to avoid an ascertainment bias of the BovineSNP50 array. Genome-wide haplotypes combined with partial pedigree and type trait classification show the potential to improve identification of purebred animals with a low degree of admixture. Phylogenetic analyses demonstrated unique genetic identity of Cika animals. Genetic distance matrix presented by rooted Neighbour-Net suggested long and broad phylogenetic connection between Cika and Pinzgauer. Unsupervised clustering performed by the admixture analysis and two-dimensional presentation of the genetic distances between individuals also suggest Cika is a distinct breed despite being similar in appearance to Pinzgauer. Animals identified as the most purebred could be used as a nucleus for a recovery of the native genetic background in the current admixed population. The results show that local well-adapted strains, which have never been intensively managed and differentiated into specific breeds, exhibit large haplotype diversity. They suggest a conservation and recovery approach that does not rely exclusively on the search for the original native genetic background but rather on the identification and removal of common introgressed haplotypes would be more powerful. Successful implementation of such an approach should be based on combining phenotype, pedigree, and genome-wide haplotype data of the breed of interest and a spectrum of reference breeds which potentially have had

  9. Finding the most appropriate mouse model of juvenile CLN3 (Batten) disease for therapeutic studies: the importance of genetic background and gender.

    PubMed

    Kovács, Attila D; Pearce, David A

    2015-04-01

    Mutations in the CLN3 gene cause a fatal neurodegenerative disorder: juvenile CLN3 disease, also known as juvenile Batten disease. The two most commonly utilized mouse models of juvenile CLN3 disease are Cln3-knockout (Cln3(-/-)) and Cln3(Δex7/8)-knock-in mice, the latter mimicking the most frequent disease-causing human mutation. To determine which mouse model has the most pronounced neurological phenotypes that can be used as outcome measures for therapeutic studies, we compared the exploratory activity, motor function and depressive-like behavior of 1-, 3- and 6-month-old Cln3(-/-) and Cln3(Δex7/8)-knock-in mice on two different genetic backgrounds (129S6/SvEv and C57BL/6J). Although, in many cases, the behavior of Cln3(-/-) and Cln3(Δex7/8) mice was similar, we found genetic-background-, gender- and age-dependent differences between the two mouse models. We also observed large differences in the behavior of the 129S6/SvEv and C57BL/6J wild-type strains, which highlights the strong influence that genetic background can have on phenotype. Based on our results, Cln3(-/-) male mice on the 129S6/SvEv genetic background are the most appropriate candidates for therapeutic studies. They exhibit motor deficits at 1 and 6 months of age in the vertical pole test, and they were the only mice to show impaired motor coordination in the rotarod test at both 3 and 6 months. Cln3(-/-) males on the C57BL/6J background and Cln3(Δex7/8) males on the 129S6/SvEv background also provide good outcome measures for therapeutic interventions. Cln3(-/-) (C57BL/6J) males had serious difficulties in climbing down (at 1 and 6 months) and turning downward on (at 1, 3 and 6 months) the vertical pole, whereas Cln3(Δex7/8) (129S6/SvEv) males climbed down the vertical pole drastically slower than wild-type males at 3 and 6 months of age. Our study demonstrates the importance of testing mouse models on different genetic backgrounds and comparing males and females in order to find the most

  10. Finding the most appropriate mouse model of juvenile CLN3 (Batten) disease for therapeutic studies: the importance of genetic background and gender

    PubMed Central

    Kovács, Attila D.; Pearce, David A.

    2015-01-01

    Mutations in the CLN3 gene cause a fatal neurodegenerative disorder: juvenile CLN3 disease, also known as juvenile Batten disease. The two most commonly utilized mouse models of juvenile CLN3 disease are Cln3-knockout (Cln3−/−) and Cln3Δex7/8-knock-in mice, the latter mimicking the most frequent disease-causing human mutation. To determine which mouse model has the most pronounced neurological phenotypes that can be used as outcome measures for therapeutic studies, we compared the exploratory activity, motor function and depressive-like behavior of 1-, 3- and 6-month-old Cln3−/− and Cln3Δex7/8-knock-in mice on two different genetic backgrounds (129S6/SvEv and C57BL/6J). Although, in many cases, the behavior of Cln3−/− and Cln3Δex7/8 mice was similar, we found genetic-background-, gender- and age-dependent differences between the two mouse models. We also observed large differences in the behavior of the 129S6/SvEv and C57BL/6J wild-type strains, which highlights the strong influence that genetic background can have on phenotype. Based on our results, Cln3−/− male mice on the 129S6/SvEv genetic background are the most appropriate candidates for therapeutic studies. They exhibit motor deficits at 1 and 6 months of age in the vertical pole test, and they were the only mice to show impaired motor coordination in the rotarod test at both 3 and 6 months. Cln3−/− males on the C57BL/6J background and Cln3Δex7/8 males on the 129S6/SvEv background also provide good outcome measures for therapeutic interventions. Cln3−/− (C57BL/6J) males had serious difficulties in climbing down (at 1 and 6 months) and turning downward on (at 1, 3 and 6 months) the vertical pole, whereas Cln3Δex7/8 (129S6/SvEv) males climbed down the vertical pole drastically slower than wild-type males at 3 and 6 months of age. Our study demonstrates the importance of testing mouse models on different genetic backgrounds and comparing males and females in order to find the most

  11. Creating an Interactive PDF

    ERIC Educational Resources Information Center

    Branzburg, Jeffrey

    2008-01-01

    There are many ways to begin a PDF document using Adobe Acrobat. The easiest and most popular way is to create the document in another application (such as Microsoft Word) and then use the Adobe Acrobat software to convert it to a PDF. In this article, the author describes how he used Acrobat's many tools in his project--an interactive…

  12. Genetic background impacts developmental potential of enteric neural crest-derived progenitors in the Sox10Dom model of Hirschsprung disease.

    PubMed

    Walters, Lauren C; Cantrell, V Ashley; Weller, Kevin P; Mosher, Jack T; Southard-Smith, E Michelle

    2010-11-15

    Abnormalities in the development of enteric neural crest-derived progenitors (ENPs) that generate the enteric nervous system (ENS) can lead to aganglionosis in a variable portion of the distal gastrointestinal tract. Cumulative evidence suggests that variation of aganglionosis is due to gene interactions that modulate the ability of ENPs to populate the intestine; however, the developmental processes underlying this effect are unknown. We hypothesized that differences in enteric ganglion deficits could be attributable to the effects of genetic background on early developmental processes, including migration, proliferation, or lineage divergence. Developmental processes were investigated in congenic Sox10(Dom) mice, an established Hirschsprung disease (HSCR) model, on distinct inbred backgrounds, C57BL/6J (B6) and C3HeB/FeJ (C3Fe). Immuno-staining on whole-mount fetal gut tissue and dissociated cell suspensions was used to assess migration and proliferation. Flow cytometry utilizing the cell surface markers p75 and HNK-1 was used to isolate live ENPs for analysis of developmental potential. Frequency of ENPs was reduced in Sox10(Dom) embryos relative to wild-type embryos, but was unaffected by genetic background. Both migration and developmental potential of ENPs in Sox10(Dom) embryos were altered by inbred strain background with the most highly significant differences seen for developmental potential between strains and genotypes. In vivo imaging of fetal ENPs and postnatal ganglia demonstrates that altered lineage divergence impacts ganglia in the proximal intestine. Our analysis demonstrates that genetic background alters early ENS development and suggests that abnormalities in lineage diversification can shift the proportions of ENP populations and thus may contribute to ENS deficiencies in vivo.

  13. Genetic knockout of the α7 nicotinic acetylcholine receptor gene alters hippocampal long-term potentiation in a background strain-dependent manner.

    PubMed

    Freund, Ronald K; Graw, Sharon; Choo, Kevin S; Stevens, Karen E; Leonard, Sherry; Dell'Acqua, Mark L

    2016-08-01

    Reduced α7 nicotinic acetylcholine receptor (nAChR) function is linked to impaired hippocampal-dependent sensory processing and learning and memory in schizophrenia. While knockout of the Chrna7 gene encoding the α7nAChR on a C57/Bl6 background results in changes in cognitive measures, prior studies found little impact on hippocampal synaptic plasticity in these mice. However, schizophrenia is a multi-genic disorder where complex interactions between specific genetic mutations and overall genetic background may play a prominent role in determining phenotypic penetrance. Thus, we compared the consequences of knocking out the α7nAChR on synaptic plasticity in C57/Bl6 and C3H mice, which differ in their basal α7nAChR expression levels. Homozygous α7 deletion in C3H mice, which normally express higher α7nAChR levels, resulted in impaired long-term potentiation (LTP) at hippocampal CA1 synapses, while C3H α7 heterozygous mice maintained robust LTP. In contrast, homozygous α7 deletion in C57 mice, which normally express lower α7nAChR levels, did not alter LTP, as had been previously reported for this strain. Thus, the threshold of Chrna7 expression required for LTP may be different in the two strains. Measurements of auditory gating, a hippocampal-dependent behavioral paradigm used to identify schizophrenia-associated sensory processing deficits, was abnormal in C3H α7 knockout mice confirming that auditory gating also requires α7nAChR expression. Our studies highlight the importance of genetic background on the regulation of synaptic plasticity and could be relevant for understanding genetic and cognitive heterogeneity in human studies of α7nAChR dysfunction in mental disorders.

  14. Evidence That Transition from Health to Psychotic Disorder Can Be Traced to Semi-Ubiquitous Environmental Effects Operating against Background Genetic Risk

    PubMed Central

    Bruggeman, Richard; Cahn, Wiepke; de Haan, Lieuwe; Kahn, René S.; Meijer, Carin J.; Myin-Germeys, Inez; van Os, Jim; Wiersma, Durk

    2013-01-01

    Background In order to assess the importance of environmental and genetic risk on transition from health to psychotic disorder, a prospective study of individuals at average (n = 462) and high genetic risk (n = 810) was conducted. Method A three-year cohort study examined the rate of transition to psychotic disorder. Binary measures indexing environmental exposure (combining urban birth, cannabis use, ethnicity and childhood trauma) and proxy genetic risk (high-risk sibling status) were used to model transition. Results The majority of high-risk siblings (68%) and healthy comparison subjects (60%) had been exposed to one or more environmental risks. The risk of transition in siblings (n = 9, 1.1%) was higher than the risk in healthy comparison subjects (n = 2, 0.4%; ORadj  = 2.2,95%CI:5–10.3). All transitions (100%) were associated with environmental exposure, compared to 65% of non-transitions (p = 0.014), with the greatest effects for childhood trauma (ORadj  = 34.4,95%CI:4.4–267.4), cannabis use (OR = 4.1,95%CI:1.1, 15.4), minority ethnic group (OR = 3.8,95%CI:1.2,12.8) and urban birth (OR = 3.7,95%CI:0.9,15.4). The proportion of transitions in the population attributable to environmental and genetic risk ranged from 28% for minority ethnic group, 45% for urban birth, 57% for cannabis use, 86% for childhood trauma, and 50% for high-risk sibling status. Nine out of 11 transitions (82%) were exposed to both genetic and environmental risk, compared to only 43% of non-transitions (p = 0.03). Conclusion Environmental risk associated with transition to psychotic disorder is semi-ubiquitous regardless of genetic high risk status. Careful prospective documentation suggests most transitions can be attributed to powerful environmental effects that become detectable when analysed against elevated background genetic risk, indicating gene-environment interaction. PMID:24223116

  15. The gamma-ray-flux PDF from galactic halo substructure

    SciTech Connect

    Lee, Samuel K.; Ando, Shin'ichiro; Kamionkowski, Marc E-mail: ando@tapir.caltech.edu

    2009-07-01

    One of the targets of the recently launched Fermi Gamma-ray Space Telescope is a diffuse gamma-ray background from dark-matter annihilation or decay in the Galactic halo. N-body simulations and theoretical arguments suggest that the dark matter in the Galactic halo may be clumped into substructure, rather than smoothly distributed. Here we propose the gamma-ray-flux probability distribution function (PDF) as a probe of substructure in the Galactic halo. We calculate this PDF for a phenomenological model of halo substructure and determine the regions of the substructure parameter space in which the PDF may be distinguished from the PDF for a smooth distribution of dark matter. In principle, the PDF allows a statistical detection of substructure, even if individual halos cannot be detected. It may also allow detection of substructure on the smallest microhalo mass scales, ∼ M{sub ⊕}, for weakly-interacting massive particles (WIMPs). Furthermore, it may also provide a method to measure the substructure mass function. However, an analysis that assumes a typical halo substructure model and a conservative estimate of the diffuse background suggests that the substructure PDF may not be detectable in the lifespan of Fermi in the specific case that the WIMP is a neutralino. Nevertheless, for a large range of substructure, WIMP annihilation, and diffuse background models, PDF analysis may provide a clear signature of substructure.

  16. The role of CD1d-restricted NKT cells in the clearance of Pseudomonas aeruginosa from the lung is dependent on the host genetic background.

    PubMed

    Benoit, Patrick; Sigounas, Vaia Yioula; Thompson, Jenna L; van Rooijen, Nico; Poynter, Matthew E; Wargo, Matthew J; Boyson, Jonathan E

    2015-06-01

    Pseudomonas aeruginosa is an important human opportunistic pathogen, accounting for a significant fraction of hospital-acquired lung infections. CD1d-restricted NKT cells comprise an unusual innate-like T cell subset that plays important roles in both bacterial and viral infections. Previous reports have differed in their conclusions regarding the role of NKT cells in clearance of P. aeruginosa from the lung. Since there is significant strain-dependent variation in NKT cell number and function among different inbred strains of mice, we investigated whether the role of NKT cells was dependent on the host genetic background. We found that NKT cells did indeed play a critical role in the clearance of P. aeruginosa from the lungs of BALB/c mice but that they played no discernible role in clearance from the lungs of C57BL/6 mice. We found that the strain-dependent role of NKT cells was associated with significant strain-dependent differences in cytokine production by lung NKT cells and that impaired clearance of P. aeruginosa in BALB/c CD1d(-/-) mice was associated with an increase in neutrophil influx to the lung and increased levels of proinflammatory cytokines and chemokines after infection. Finally, we found that the role of alveolar macrophages was also dependent on the genetic background. These data provide further support for a model in which the unusually high level of variability in NKT cell number and function among different genetic backgrounds may be an important contributor to infectious-disease susceptibility and pathology. PMID:25870224

  17. Comments on PDF methods

    NASA Technical Reports Server (NTRS)

    Chen, J.-Y.

    1992-01-01

    Viewgraphs are presented on the following topics: the grand challenge of combustion engineering; research of probability density function (PDF) methods at Sandia; experiments of turbulent jet flames (Masri and Dibble, 1988); departures from chemical equilibrium; modeling turbulent reacting flows; superequilibrium OH radical; pdf modeling of turbulent jet flames; scatter plot for CH4 (methane) and O2 (oxygen); methanol turbulent jet flames; comparisons between predictions and experimental data; and turbulent C2H4 jet flames.

  18. Heterogeneous Genetic Background of the Association of Pheochromocytoma/Paraganglioma and Pituitary Adenoma: Results From a Large Patient Cohort

    PubMed Central

    Dénes, Judit; Swords, Francesca; Rattenberry, Eleanor; Stals, Karen; Owens, Martina; Cranston, Treena; Xekouki, Paraskevi; Moran, Linda; Kumar, Ajith; Wassif, Christopher; Fersht, Naomi; Baldeweg, Stephanie E.; Morris, Damian; Lightman, Stafford; Agha, Amar; Rees, Aled; Grieve, Joan; Powell, Michael; Boguszewski, Cesar Luiz; Dutta, Pinaki; Thakker, Rajesh V.; Srirangalingam, Umasuthan; Thompson, Chris J.; Druce, Maralyn; Higham, Claire; Davis, Julian; Eeles, Rosalind; Stevenson, Mark; O'Sullivan, Brendan; Taniere, Phillipe; Skordilis, Kassiani; Gabrovska, Plamena; Barlier, Anne; Webb, Susan M.; Aulinas, Anna; Drake, William M.; Bevan, John S.; Preda, Cristina; Dalantaeva, Nadezhda; Ribeiro-Oliveira, Antônio; Garcia, Isabel Tena; Yordanova, Galina; Iotova, Violeta; Evanson, Jane; Grossman, Ashley B.; Trouillas, Jacqueline; Ellard, Sian; Stratakis, Constantine A.; Maher, Eamonn R.; Roncaroli, Federico

    2015-01-01

    Context: Pituitary adenomas and pheochromocytomas/paragangliomas (pheo/PGL) can occur in the same patient or in the same family. Coexistence of the two diseases could be due to either a common pathogenic mechanism or a coincidence. Objective: The objective of the investigation was to study the possible coexistence of pituitary adenoma and pheo/PGL. Design: Thirty-nine cases of sporadic or familial pheo/PGL and pituitary adenomas were investigated. Known pheo/PGL genes (SDHA-D, SDHAF2, RET, VHL, TMEM127, MAX, FH) and pituitary adenoma genes (MEN1, AIP, CDKN1B) were sequenced using next generation or Sanger sequencing. Loss of heterozygosity study and pathological studies were performed on the available tumor samples. Setting: The study was conducted at university hospitals. Patients: Thirty-nine patients with sporadic of familial pituitary adenoma and pheo/PGL participated in the study. Outcome: Outcomes included genetic screening and clinical characteristics. Results: Eleven germline mutations (five SDHB, one SDHC, one SDHD, two VHL, and two MEN1) and four variants of unknown significance (two SDHA, one SDHB, and one SDHAF2) were identified in the studied genes in our patient cohort. Tumor tissue analysis identified LOH at the SDHB locus in three pituitary adenomas and loss of heterozygosity at the MEN1 locus in two pheochromocytomas. All the pituitary adenomas of patients affected by SDHX alterations have a unique histological feature not previously described in this context. Conclusions: Mutations in the genes known to cause pheo/PGL can rarely be associated with pituitary adenomas, whereas mutation in a gene predisposing to pituitary adenomas (MEN1) can be associated with pheo/PGL. Our findings suggest that genetic testing should be considered in all patients or families with the constellation of pheo/PGL and a pituitary adenoma. PMID:25494863

  19. Dual PDF signaling pathways reset clocks via TIMELESS and acutely excite target neurons to control circadian behavior.

    PubMed

    Seluzicki, Adam; Flourakis, Matthieu; Kula-Eversole, Elzbieta; Zhang, Luoying; Kilman, Valerie; Allada, Ravi

    2014-03-01

    Molecular circadian clocks are interconnected via neural networks. In Drosophila, PIGMENT-DISPERSING FACTOR (PDF) acts as a master network regulator with dual functions in synchronizing molecular oscillations between disparate PDF(+) and PDF(-) circadian pacemaker neurons and controlling pacemaker neuron output. Yet the mechanisms by which PDF functions are not clear. We demonstrate that genetic inhibition of protein kinase A (PKA) in PDF(-) clock neurons can phenocopy PDF mutants while activated PKA can partially rescue PDF receptor mutants. PKA subunit transcripts are also under clock control in non-PDF DN1p neurons. To address the core clock target of PDF, we rescued per in PDF neurons of arrhythmic per⁰¹ mutants. PDF neuron rescue induced high amplitude rhythms in the clock component TIMELESS (TIM) in per-less DN1p neurons. Complete loss of PDF or PKA inhibition also results in reduced TIM levels in non-PDF neurons of per⁰¹ flies. To address how PDF impacts pacemaker neuron output, we focally applied PDF to DN1p neurons and found that it acutely depolarizes and increases firing rates of DN1p neurons. Surprisingly, these effects are reduced in the presence of an adenylate cyclase inhibitor, yet persist in the presence of PKA inhibition. We have provided evidence for a signaling mechanism (PKA) and a molecular target (TIM) by which PDF resets and synchronizes clocks and demonstrates an acute direct excitatory effect of PDF on target neurons to control neuronal output. The identification of TIM as a target of PDF signaling suggests it is a multimodal integrator of cell autonomous clock, environmental light, and neural network signaling. Moreover, these data reveal a bifurcation of PKA-dependent clock effects and PKA-independent output effects. Taken together, our results provide a molecular and cellular basis for the dual functions of PDF in clock resetting and pacemaker output. PMID:24643294

  20. The genetics of multiple sclerosis: principles, background and updated results of the United Kingdom systematic genome screen.

    PubMed

    Chataway, J; Feakes, R; Coraddu, F; Gray, J; Deans, J; Fraser, M; Robertson, N; Broadley, S; Jones, H; Clayton, D; Goodfellow, P; Sawcer, S; Compston, A

    1998-10-01

    Genetic susceptibility to multiple sclerosis is implicated on the basis of classical family studies and phenotype analyses. The only reproducible legacy from the candidate gene approach has been the discovery of population associations with alleles of the major histocompatibility complex. Systematic genome scanning has since been applied using a panel of anonymous markers to identify areas of linkage in co-affected siblings. Here, we describe the principles of genome screening and update the UK survey of multiple sclerosis. This identified 20 regions of potential interest, but in none was there unequivocal linkage. In theory, attempting to replicate these findings in a second set of sibling pair families is the most appropriate way to distinguish true from false positives, but unfortunately the number of families required to do this reliably is prohibitively large. We used three approaches to increase the definition achieved by the screen: (i) the number of sibling pairs typed in an identified region of potential linkage was extended; (ii) the information extraction was increased in an identified region; and (iii) a search was made for missed regions of potential linkage. Each of these approaches has considerable limitations. A chromosome-by-chromosome account is given to direct future searches. Although an additional marker placed distal to the 'hit' on chromosome 14q increased linkage in this area, and typing extra sibling pairs increased linkage on chromosomes 6p and 17q, evidence for linkage was more commonly reduced and no additional regions of interest were found. A further refinement of the genome screen was undertaken by conditioning for the presence of HLA-DR15. This produced a surprising degree of segregation among the regions of interest, which divided into two distinct groups depending on DR15 sharing: the DR15-sharing cohort comprised loci on chromosomal areas 1p, 17q and X; and the DR15-non-sharing cohort was made up of loci on 1cen, 3p, 7p, 14q and

  1. Morphological variation of mutant sunflowers (Helianthus annuus) induced by space flight and their genetic background detection by SSR primers.

    PubMed

    Yang, J; Shen, S; Zhang, T; Chen, G D; Liu, H; Ma, X B; Chen, W Y; Peng, Z S

    2012-09-25

    After sunflower seeds were exposed to space conditions, various mutant plants were screened from the descendent plants. The morphological characters of plants changed in flower color from golden to yellow, light yellow, or even to yellowish green. The ligulate petals of the unisexual floret broadened, or became thin, while the short tubular petals of bisexual floret elongated to some extent, or even turned into semi-ligulate petals or ligulate petals, making the phenotype of the whole inflorescence like a chrysanthemum. The shape and thickness of leaves varied in some of these plants. Absolute sterile plants in mutant plants were found to possess neither normal bisexual florets nor unisexual florets, but the "pseudo-floret" only consisted of pieces of shield-like bracts on protuberant floral disc. Thirty-five pairs of simple sequence of repeat primers were used to detect the genetic variation of the plants, and the results showed that only a variation was tested in the mutant plants from 4 primers. The different PCR products obtained were extracted for sequencing and alignment analysis, and the aligned results showed that the DNA sequence changed by deletion, insertion and replacement that occurred at some sites. The results proved the high mutagenic efficacy of space flight, and ways of DNA transformation due to space conditions.

  2. Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background

    PubMed Central

    Capilla, Laia; Medarde, Nuria; Alemany-Schmidt, Alexandra; Oliver-Bonet, Maria; Ventura, Jacint; Ruiz-Herrera, Aurora

    2014-01-01

    Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation. PMID:24850922

  3. Muscle protein turnover in cattle of differing genetic backgrounds as measured by urinary N tau-methylhistidine excretion

    SciTech Connect

    McCarthy, F.D.; Bergen, W.G.; Hawkins, D.R.

    1983-12-01

    N tau-methylhistidine (N tau MH) was used as an index for muscle protein degradation and this index was utilized to evaluate degradation rates in young growing cattle. Initially, two Charolais crossbred heifers, 12 months of age, were used to measure the recovery of radioactivity in the urine for a 120-hour period after intravenous injection of (/sup 14/C)N tau MH. Of the radioactivity injected into the animals, 89.7% was recovered after 120 hours. With rate and amount of clearance as the criteria, the excretion of N tau MH in urine appears to be a valid index of muscle protein degradation in cattle. Eight steers of two genetic types were used to evaluate the effect of frame size on turnover rates of muscle proteins with N tau MH as an index. Large frame cattle (LG) excreted more N tau MH per day throughout the trial. Total daily creatinine excretion was less for small frame (SM) cattle showing an increase with time in LG and SM cattle. N tau MH-to-creatinine ratios showed a decline with time. Fractional breakdown rates (FBR) and fractional synthesis rates (FSR) appeared to parallel each other with rates tending to decrease with age. No differences were observed between LG and SM cattle for FBR, FSR or fractional growth rate (FGR).

  4. Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background.

    PubMed

    Capilla, Laia; Medarde, Nuria; Alemany-Schmidt, Alexandra; Oliver-Bonet, Maria; Ventura, Jacint; Ruiz-Herrera, Aurora

    2014-07-01

    Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation.

  5. Genetics

    MedlinePlus

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

  6. Genome survey sequencing and genetic background characterization of Gracilariopsis lemaneiformis (Rhodophyta) based on next-generation sequencing.

    PubMed

    Zhou, Wei; Hu, Yiyi; Sui, Zhenghong; Fu, Feng; Wang, Jinguo; Chang, Lianpeng; Guo, Weihua; Li, Binbin

    2013-01-01

    Gracilariopsis lemaneiformis has a high economic value and is one of the most important aquaculture species in China. Despite it is economic importance, it has remained largely unstudied at the genomic level. In this study, we conducted a genome survey of Gp. lemaneiformis using next-generation sequencing (NGS) technologies. In total, 18.70 Gb of high-quality sequence data with an estimated genome size of 97 Mb were obtained by HiSeq 2000 sequencing for Gp. lemaneiformis. These reads were assembled into 160,390 contigs with a N50 length of 3.64 kb, which were further assembled into 125,685 scaffolds with a total length of 81.17 Mb. Genome analysis predicted 3490 genes and a GC% content of 48%. The identified genes have an average transcript length of 1,429 bp, an average coding sequence size of 1,369 bp, 1.36 exons per gene, exon length of 1,008 bp, and intron length of 191 bp. From the initial assembled scaffold, transposable elements constituted 54.64% (44.35 Mb) of the genome, and 7737 simple sequence repeats (SSRs) were identified. Among these SSRs, the trinucleotide repeat type was the most abundant (up to 73.20% of total SSRs), followed by the di- (17.41%), tetra- (5.49%), hexa- (2.90%), and penta- (1.00%) nucleotide repeat type. These characteristics suggest that Gp. lemaneiformis is a model organism for genetic study. This is the first report of genome-wide characterization within this taxon.

  7. Genome Survey Sequencing and Genetic Background Characterization of Gracilariopsis lemaneiformis (Rhodophyta) Based on Next-Generation Sequencing

    PubMed Central

    Sui, Zhenghong; Fu, Feng; Wang, Jinguo; Chang, Lianpeng; Guo, Weihua; Li, Binbin

    2013-01-01

    Gracilariopsis lemaneiformis has a high economic value and is one of the most important aquaculture species in China. Despite it is economic importance, it has remained largely unstudied at the genomic level. In this study, we conducted a genome survey of Gp. lemaneiformis using next-generation sequencing (NGS) technologies. In total, 18.70 Gb of high-quality sequence data with an estimated genome size of 97 Mb were obtained by HiSeq 2000 sequencing for Gp. lemaneiformis. These reads were assembled into 160,390 contigs with a N50 length of 3.64 kb, which were further assembled into 125,685 scaffolds with a total length of 81.17 Mb. Genome analysis predicted 3490 genes and a GC% content of 48%. The identified genes have an average transcript length of 1,429 bp, an average coding sequence size of 1,369 bp, 1.36 exons per gene, exon length of 1,008 bp, and intron length of 191 bp. From the initial assembled scaffold, transposable elements constituted 54.64% (44.35 Mb) of the genome, and 7737 simple sequence repeats (SSRs) were identified. Among these SSRs, the trinucleotide repeat type was the most abundant (up to 73.20% of total SSRs), followed by the di- (17.41%), tetra- (5.49%), hexa- (2.90%), and penta- (1.00%) nucleotide repeat type. These characteristics suggest that Gp. lemaneiformis is a model organism for genetic study. This is the first report of genome-wide characterization within this taxon. PMID:23875008

  8. Oppositional defiant- and conduct disorder-like problems: neurodevelopmental predictors and genetic background in boys and girls, in a nationwide twin study.

    PubMed

    Kerekes, Nóra; Lundström, Sebastian; Chang, Zheng; Tajnia, Armin; Jern, Patrick; Lichtenstein, Paul; Nilsson, Thomas; Anckarsäter, Henrik

    2014-01-01

    Background. Previous research has supported gender-specific aetiological factors in oppositional defiant disorder (ODD) and conduct disorder (CD). The aims of this study were to identify gender-specific associations between the behavioural problems-ODD/CD-like problems-and the neurodevelopmental disorders-attention deficit hyperactivity disorder (ADHD), autism spectrum disorder (ASD)-and to investigate underlying genetic effects. Methods. 17,220 twins aged 9 or 12 were screened using the Autism-Tics, AD/HD and other Comorbidities inventory. The main covariates of ODD- and CD-like problems were investigated, and the relative importance of unique versus shared hereditary and environmental effects was estimated using twin model fitting. Results. Social interaction problems (one of the ASD subdomains) was the strongest neurodevelopmental covariate of the behavioural problems in both genders, while ADHD-related hyperactivity/impulsiveness in boys and inattention in girls stood out as important covariates of CD-like problems. Genetic effects accounted for 50%-62% of the variance in behavioural problems, except in CD-like problems in girls (26%). Genetic and environmental effects linked to ADHD and ASD also influenced ODD-like problems in both genders and, to a lesser extent, CD-like problems in boys, but not in girls. Conclusions. The gender-specific patterns should be considered in the assessment and treatment, especially of CD.

  9. Genetics Home Reference: Northern epilepsy

    MedlinePlus

    ... Understand Genetics Home Health Conditions Northern epilepsy Northern epilepsy Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Northern epilepsy is a genetic condition that causes recurrent seizures ( ...

  10. Genetics Home Reference: Silver syndrome

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions Silver syndrome Silver syndrome Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Silver syndrome belongs to a group of genetic disorders ...

  11. Expression of a mutant human fibrillin allele upon a normal human or murine genetic background recapitulates a Marfan cellular phenotype.

    PubMed Central

    Eldadah, Z A; Brenn, T; Furthmayr, H; Dietz, H C

    1995-01-01

    The Marfan syndrome (MFS) is a connective tissue disorder inherited as an autosomal dominant trait and caused by mutations in the gene encoding fibrillin, a 350-kD glycoprotein that multimerizes to form extracellular microfibrils. It has been unclear whether disease results from a relative deficiency of wild-type fibrillin; from a dominant-negative effect, in which mutant fibrillin monomers disrupt the function of the wild-type protein encoded by the normal allele; or from a dynamic and variable interplay between these two pathogenetic mechanisms. We have now addressed this issue in a cell culture system. A mutant fibrillin allele from a patient with severe MFS was expressed in normal human and murine fibroblasts by stable transfection. Immunohistochemical analysis of the resultant cell lines revealed markedly diminished fibrillin deposition and disorganized microfibrillar architecture. Pulse-chase studies demonstrated normal levels of fibrillin synthesis but substantially reduced deposition into the extracellular matrix. These data illustrate that expression of a mutant fibrillin allele, on a background of two normal alleles, is sufficient to disrupt normal microfibrillar assembly and reproduce the MFS cellular phenotype. This underscores the importance of the fibrillin amino-terminus in normal microfibrillar assembly and suggests that expression of the human extreme 5' fibrillin coding sequence may be sufficient, in isolation, to produce an animal model of MFS. Lastly, this substantiation of a dominant-negative effect offers mutant allele knockout as a potential strategy for gene therapy. Images PMID:7860770

  12. Quantitative trait locus mapping with background control in genetic populations of clonal F1 and double cross

    PubMed Central

    Zhang, Luyan; Li, Huihui; Ding, Junqiang; Wu, Jianyu

    2015-01-01

    Abstract In this study, we considered five categories of molecular markers in clonal F1 and double cross populations, based on the number of distinguishable alleles and the number of distinguishable genotypes at the marker locus. Using the completed linkage maps, incomplete and missing markers were imputed as fully informative markers in order to simplify the linkage mapping approaches of quantitative trait genes. Under the condition of fully informative markers, we demonstrated that dominance effect between the female and male parents in clonal F1 and double cross populations can cause the interactions between markers. We then developed an inclusive linear model that includes marker variables and marker interactions so as to completely control additive effects of the female and male parents, as well as the dominance effect between the female and male parents. The linear model was finally used for background control in inclusive composite interval mapping (ICIM) of quantitative trait locus (QTL). The efficiency of ICIM was demonstrated by extensive simulations and by comparisons with simple interval mapping, multiple‐QTL models and composite interval mapping. Finally, ICIM was applied in one actual double cross population to identify QTL on days to silking in maize. PMID:25881980

  13. Quantitative trait locus mapping with background control in genetic populations of clonal F1 and double cross.

    PubMed

    Zhang, Luyan; Li, Huihui; Ding, Junqiang; Wu, Jianyu; Wang, Jiankang

    2015-12-01

    In this study, we considered five categories of molecular markers in clonal F1 and double cross populations, based on the number of distinguishable alleles and the number of distinguishable genotypes at the marker locus. Using the completed linkage maps, incomplete and missing markers were imputed as fully informative markers in order to simplify the linkage mapping approaches of quantitative trait genes. Under the condition of fully informative markers, we demonstrated that dominance effect between the female and male parents in clonal F1 and double cross populations can cause the interactions between markers. We then developed an inclusive linear model that includes marker variables and marker interactions so as to completely control additive effects of the female and male parents, as well as the dominance effect between the female and male parents. The linear model was finally used for background control in inclusive composite interval mapping (ICIM) of quantitative trait locus (QTL). The efficiency of ICIM was demonstrated by extensive simulations and by comparisons with simple interval mapping, multiple-QTL models and composite interval mapping. Finally, ICIM was applied in one actual double cross population to identify QTL on days to silking in maize.

  14. An investigation into the genetic background of coat colour dilution in a Charolais x German Holstein F2 resource population.

    PubMed

    Kühn, Ch; Weikard, R

    2007-04-01

    The molecular background of many loci affecting coat colour inheritance in cattle is still incompletely characterized, although it is known that coat colour results from the joint effects of several loci, e.g. agouti, extension and dilution. Dilution alleles are responsible for a dilution effect on the original coat colour of an individual, which is determined by the agouti and extension loci. Different loci affecting dilution of pigment are suggested in Charolais (Dc) and Simmental (Ds). To enable chromosomal mapping of the Dc mutation, 133 animals from an F2 full-sib resource population generated from a cross of Charolais and German Holstein were scored for the coat colour dilution phenotype. Linkage analysis covering all autosomes revealed a significant linkage of the dilution phenotype with microsatellite markers on bovine chromosome 5. No recombination was observed between marker ETH10 and the Dc locus. Positional and functional information identified the bovine silver homolog (SILV) gene as a candidate for the Dc mutation. Results from comparative sequencing of the SILV gene in individuals with different dilution coat colour phenotypes confirmed the presence of a c.64G>A non-synonymous mutation, which had previously been identified in the Charolais breed. The alleles at this locus were associated with coat colour dilution in this study. However, further investigation of colour inheritance within the F2 resource population indicated that a single diallelic mutation in the SILV gene cannot explain the total observed variation of coat colour dilution.

  15. Prevalence and diversity of enterotoxin genes with genetic background of Staphylococcus aureus isolates from different origins in China.

    PubMed

    Chao, Guoxiang; Bao, Guangyu; Cao, Yongzhong; Yan, Wenguang; Wang, Yan; Zhang, Xiaorong; Zhou, Liping; Wu, Yantao

    2015-10-15

    illustrate the genetic clonal diversity and the identity of S. aureus isolates from different sources with respect to SE genes and highlight a correlation between SE genes or gene clusters and CCs, spa, and MRSA clones. The foodborne and human origin isolates were the main potential causes of classic staphylococcal foodborne poisonings, whereas isolates harboring novel genes were new potential hazards to food safety.

  16. Genetic and epigenetic background and protein expression profiles in relation to telomerase activation in medullary thyroid carcinoma

    PubMed Central

    Wang, Na; Kjellin, Hanna; Sofiadis, Anastasios; Fotouhi, Omid; Juhlin, C. Christofer; Bäckdahl, Martin; Zedenius, Jan; Xu, Dawei; Lehtiö, Janne; Larsson, Catharina

    2016-01-01

    Medullary thyroid carcinomas (MTCs) exhibit telomerase activation in strong association with shorter patient survival. To understand the background of telomerase activation we quantified TERT copy numbers and TERT promoter methylation in 42 MTCs and normal thyroid references. Gain of TERT was demonstrated by quantitative PCR in 5/39 sporadic MTC. Increased methylation index (MetI) for CpG methylation at the TERT promoter was found in sporadic MTCs (P < 0.0001) and in MEN 2 associated MTCs (P = 0.011) vs. normal thyroid tissues. MetI correlated positively with TERT gene expression (r = 0.432, P = 0.006) and negatively with telomere length (r = −0.343, P = 0.032). MTC cases with MetI above the median of 52% had shorter survival as compared to cases with lower MetI (P = 0.005 for overall survival and P = 0.007 for disease-related survival). Protein expression profiles obtained by mass spectrometry were then studied in relation to telomerase activation in MTCs. Comparing protein levels between tumors defined by telomerase activity status, 240 proteins were associated with telomerase activity. Among telomerase activation positive cases a set of proteins was found to discriminate between MTCs with high and low TERT gene expression with enrichment for proteins involved in telomerase regulation. XRCC5 mRNA expression was found increased in MTCs vs. normal thyroid (P = 0.007). In conclusion the findings suggest a role for TERT copy number gain, TERT promoter methylation and XRCC5 expression in telomerase activation and telomere maintenance of MTC. PMID:26870890

  17. Mitochondrial Genetic Background Modifies the Relationship between Traffic-Related Air Pollution Exposure and Systemic Biomarkers of Inflammation

    PubMed Central

    Wittkopp, Sharine; Staimer, Norbert; Tjoa, Thomas; Gillen, Daniel; Daher, Nancy; Shafer, Martin; Schauer, James J.; Sioutas, Constantinos; Delfino, Ralph J.

    2013-01-01

    Background Mitochondria are the main source of reactive oxygen species (ROS). Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD). We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin. Objective We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production) in this panel (38 subjects and 417 observations). Methods Inflammation biomarkers were measured weekly in each subject (≤12 weeks), including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx), carbon monoxide (CO), organic carbon, elemental and black carbon (EC, BC); and particulate matter mass, three size fractions (<0.25 µm, 0.25–2.5 µm, and 2.5–10 µm in aerodynamic diameter). Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH), and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models. Results IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH), and with mass and oxidative potential of quasi-ultrafine particles <0.25 µm. These associations were stronger for haplogroup H than haplogroup U. Conclusions Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects. PMID:23717615

  18. Genetic background can result in a marked or minimal effect of gene knockout (GPR55 and CB2 receptor) in experimental autoimmune encephalomyelitis models of multiple sclerosis.

    PubMed

    Sisay, Sofia; Pryce, Gareth; Jackson, Samuel J; Tanner, Carolyn; Ross, Ruth A; Michael, Gregory J; Selwood, David L; Giovannoni, Gavin; Baker, David

    2013-01-01

    Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) receptor and the orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6 (Cnr2 (tm1Zim)) CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2 (Dgen)) receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2 (tm1Zim) mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational value of some

  19. Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

    PubMed Central

    Jackson, Samuel J.; Tanner, Carolyn; Ross, Ruth A.; Michael, Gregory J.; Selwood, David L.; Giovannoni, Gavin; Baker, David

    2013-01-01

    Endocannabinoids and some phytocannabinoids bind to CB1 and CB2 cannabinoid receptors, transient receptor potential vanilloid one (TRPV1) receptor and the orphan G protein receptor fifty-five (GPR55). Studies using C57BL/10 and C57BL/6 (Cnr2tm1Zim) CB2 cannabinoid receptor knockout mice have demonstrated an immune-augmenting effect in experimental autoimmune encephalomyelitis (EAE) models of multiple sclerosis. However, other EAE studies in Biozzi ABH mice often failed to show any treatment effect of either CB2 receptor agonism or antagonism on inhibition of T cell autoimmunity. The influence of genetic background on the induction of EAE in endocannabinoid system-related gene knockout mice was examined. It was found that C57BL/6.GPR55 knockout mice developed less severe disease, notably in female mice, following active induction with myelin oligodendrocyte glycoprotein 35-55 peptide. In contrast C57BL/6.CB2 (Cnr2Dgen) receptor knockout mice developed augmented severity of disease consistent with the genetically and pharmacologically-distinct, Cnr2tm1Zim mice. However, when the knockout gene was bred into the ABH mouse background and EAE induced with spinal cord autoantigens the immune-enhancing effect of CB2 receptor deletion was lost. Likewise CB1 receptor and transient receptor potential vanilloid one knockout mice on the ABH background demonstrated no alteration in immune-susceptibility, in terms of disease incidence and severity of EAE, in contrast to that reported in some C57BL/6 mouse studies. Furthermore the immune-modulating influence of GPR55 was marginal on the ABH mouse background. Whilst sedative doses of tetrahydrocannabinol could induce immunosuppression, this was associated with a CB1 receptor rather than a CB2 receptor-mediated effect. These data support the fact that non-psychoactive doses of medicinal cannabis have a marginal influence on the immune response in MS. Importantly, it adds a note of caution for the translational value of some

  20. Genetics Home Reference: neuroblastoma

    MedlinePlus

    ... Help Me Understand Genetics Home Health Conditions neuroblastoma neuroblastoma Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Neuroblastoma is a type of cancer that most often ...

  1. Genetics Home Reference: anencephaly

    MedlinePlus

    ... Help Me Understand Genetics Home Health Conditions anencephaly anencephaly Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Anencephaly is a condition that prevents the normal development ...

  2. Protection from Severe Influenza Virus Infections in Mice Carrying the Mx1 Influenza Virus Resistance Gene Strongly Depends on Genetic Background

    PubMed Central

    Shin, Dai-Lun; Hatesuer, Bastian; Bergmann, Silke; Nedelko, Tatiana

    2015-01-01

    ABSTRACT Influenza virus infections represent a serious threat to human health. Both extrinsic and intrinsic factors determine the severity of influenza. The MX dynamin-like GTPase 1 (Mx1) gene has been shown to confer strong resistance to influenza A virus infections in mice. Most laboratory mouse strains, including C57BL/6J, carry nonsense or deletion mutations in Mx1 and thus a nonfunctional allele, whereas wild-derived mouse strains carry a wild-type Mx1 allele. Congenic C57BL/6J (B6-Mx1r/r) mice expressing a wild-type allele from the A2G mouse strain are highly resistant to influenza A virus infections, to both mono- and polybasic subtypes. Furthermore, in genetic mapping studies, Mx1 was identified as the major locus of resistance to influenza virus infections. Here, we investigated whether the Mx1 protective function is influenced by the genetic background. For this, we generated a congenic mouse strain carrying the A2G wild-type Mx1 resistance allele on a DBA/2J background (D2-Mx1r/r). Most remarkably, congenic D2-Mx1r/r mice expressing a functional Mx1 wild-type allele are still highly susceptible to H1N1 virus. However, pretreatment of D2-Mx1r/r mice with alpha interferon protected them from lethal infections. Our results showed, for the first time, that the presence of an Mx1 wild-type allele from A2G as such does not fully protect mice from lethal influenza A virus infections. These observations are also highly relevant for susceptibility to influenza virus infections in humans. IMPORTANCE Influenza A virus represents a major health threat to humans. Seasonal influenza epidemics cause high economic loss, morbidity, and deaths each year. Genetic factors of the host strongly influence susceptibility and resistance to virus infections. The Mx1 (MX dynamin-like GTPase 1) gene has been described as a major resistance gene in mice and humans. Most inbred laboratory mouse strains are deficient in Mx1, but congenic B6-Mx1r/r mice that carry the wild-type Mx1

  3. Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits.

    PubMed

    Fujita, Hayato; Hara, Kazuo; Shojima, Nobuhiro; Horikoshi, Momoko; Iwata, Minoru; Hirota, Yushi; Tobe, Kazuyuki; Seino, Susumu; Kadowaki, Takashi

    2012-12-01

    The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. We enrolled 2632 Japanese subjects with T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349 (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1), rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and rs174550 (FADS1) were significantly associated with T2D (P=0.0078, OR: 1.12; and P=0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to nine SNPs had an increased risk of T2D (P=0.0017), as well as a higher fasting plasma glucose level (P=0.018), higher HbA(1c) level (P=0.013) and lower HOMA-β (P=0.033) compared with subjects who had fewer risk alleles. We identified a significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a Japanese population. The present findings suggest that inclusion of SNPs with a tendency to increase the disease risk captured more of the genetic background of T2D than that revealed by only assessing significant SNPs.

  4. Diverse Genetic Background of Multidrug-Resistant Pseudomonas aeruginosa from Mainland China, and Emergence of an Extensively Drug-Resistant ST292 Clone in Kunming.

    PubMed

    Fan, Xin; Wu, Yue; Xiao, Meng; Xu, Zhi-Peng; Kudinha, Timothy; Bazaj, Alda; Kong, Fanrong; Xu, Ying-Chun

    2016-01-01

    For a better understanding of the multidrug resistant Pseudomonas aeruginosa (MDR-PA) epidemiology in mainland China, a nationwide surveillance network of 27 tertiary hospitals was established. Non-duplicate MDR-PA isolates from 254 cases of nosocomial infections, were collected during the period August 2011 to July 2012. Minimum inhibitory concentrations (MICs) of nine antimicrobial agents were determined by broth micro-dilution method according to the CLSI guidelines [M7-A10]. Genotyping analysis was performed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The presence of acquired carbapenemases was also determined by molecular approaches for 233 carbapenem-resistant isolates. Carbapenemase genes were detected in 19 (8.2%) isolates, with 13 of these isolates encoding IMP-type enzymes, five with VIM-2, and one with KPC-2. MLST analysis revealed significant genetic diversity among the MDR-PA isolates studied, and 91 STs (including 17 novel STs) were identified. However, a long-term outbreak of an emerging extensively drug-resistant (XDR) ST292/PFGE genotype A clone was detected in a hospital from Southwest China. This study has demonstrated that MDR-PA in mainland China have evolved from diverse genetic backgrounds. Evidence of clonal dissemination of the organism and nosocomial outbreaks in some regions, suggest a need to strengthen existing infection control measures. PMID:27198004

  5. Diverse Genetic Background of Multidrug-Resistant Pseudomonas aeruginosa from Mainland China, and Emergence of an Extensively Drug-Resistant ST292 Clone in Kunming

    PubMed Central

    Fan, Xin; Wu, Yue; Xiao, Meng; Xu, Zhi-Peng; Kudinha, Timothy; Bazaj, Alda; Kong, Fanrong; Xu, Ying-Chun

    2016-01-01

    For a better understanding of the multidrug resistant Pseudomonas aeruginosa (MDR-PA) epidemiology in mainland China, a nationwide surveillance network of 27 tertiary hospitals was established. Non-duplicate MDR-PA isolates from 254 cases of nosocomial infections, were collected during the period August 2011 to July 2012. Minimum inhibitory concentrations (MICs) of nine antimicrobial agents were determined by broth micro-dilution method according to the CLSI guidelines [M7-A10]. Genotyping analysis was performed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). The presence of acquired carbapenemases was also determined by molecular approaches for 233 carbapenem-resistant isolates. Carbapenemase genes were detected in 19 (8.2%) isolates, with 13 of these isolates encoding IMP-type enzymes, five with VIM-2, and one with KPC-2. MLST analysis revealed significant genetic diversity among the MDR-PA isolates studied, and 91 STs (including 17 novel STs) were identified. However, a long-term outbreak of an emerging extensively drug-resistant (XDR) ST292/PFGE genotype A clone was detected in a hospital from Southwest China. This study has demonstrated that MDR-PA in mainland China have evolved from diverse genetic backgrounds. Evidence of clonal dissemination of the organism and nosocomial outbreaks in some regions, suggest a need to strengthen existing infection control measures. PMID:27198004

  6. Plant Genetic Background Increasing the Efficiency and Durability of Major Resistance Genes to Root-knot Nematodes Can Be Resolved into a Few Resistance QTLs

    PubMed Central

    Barbary, Arnaud; Djian-Caporalino, Caroline; Marteu, Nathalie; Fazari, Ariane; Caromel, Bernard; Castagnone-Sereno, Philippe; Palloix, Alain

    2016-01-01

    With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs) in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes). However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a quantitative trait loci (QTL) analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, Meloidogyne incognita, M. arenaria, and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS–LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes. PMID:27242835

  7. Plant Genetic Background Increasing the Efficiency and Durability of Major Resistance Genes to Root-knot Nematodes Can Be Resolved into a Few Resistance QTLs.

    PubMed

    Barbary, Arnaud; Djian-Caporalino, Caroline; Marteu, Nathalie; Fazari, Ariane; Caromel, Bernard; Castagnone-Sereno, Philippe; Palloix, Alain

    2016-01-01

    With the banning of most chemical nematicides, the control of root-knot nematodes (RKNs) in vegetable crops is now based essentially on the deployment of single, major resistance genes (R-genes). However, these genes are rare and their efficacy is threatened by the capacity of RKNs to adapt. In pepper, several dominant R-genes are effective against RKNs, and their efficacy and durability have been shown to be greater in a partially resistant genetic background. However, the genetic determinants of this partial resistance were unknown. Here, a quantitative trait loci (QTL) analysis was performed on the F2:3 population from the cross between Yolo Wonder, an accession considered partially resistant or resistant, depending on the RKN species, and Doux Long des Landes, a susceptible cultivar. A genetic linkage map was constructed from 130 F2 individuals, and the 130 F3 families were tested for resistance to the three main RKN species, Meloidogyne incognita, M. arenaria, and M. javanica. For the first time in the pepper-RKN pathosystem, four major QTLs were identified and mapped to two clusters. The cluster on chromosome P1 includes three tightly linked QTLs with specific effects against individual RKN species. The fourth QTL, providing specific resistance to M. javanica, mapped to pepper chromosome P9, which is known to carry multiple NBS-LRR repeats, together with major R-genes for resistance to nematodes and other pathogens. The newly discovered cluster on chromosome P1 has a broad spectrum of action with major additive effects on resistance. These data highlight the role of host QTLs involved in plant-RKN interactions and provide innovative potential for the breeding of new pepper cultivars or rootstocks combining quantitative resistance and major R-genes, to increase both the efficacy and durability of RKN control by resistance genes. PMID:27242835

  8. Lack of CC chemokine ligand 2 differentially affects inflammation and fibrosis according to the genetic background in a murine model of steatohepatitis.

    PubMed

    Galastri, Sara; Zamara, Elena; Milani, Stefano; Novo, Erica; Provenzano, Angela; Delogu, Wanda; Vizzutti, Francesco; Sutti, Salvatore; Locatelli, Irene; Navari, Nadia; Vivoli, Elisa; Caligiuri, Alessandra; Pinzani, Massimo; Albano, Emanuele; Parola, Maurizio; Marra, Fabio

    2012-10-01

    Expression of CCL2 (CC chemokine ligand 2) (or monocyte chemoattractant protein-1) regulates inflammatory cell infiltration in the liver and adipose tissue, favouring steatosis. However, its role in the pathogenesis of steatohepatitis is still uncertain. In the present study, we investigated the development of non-alcoholic steatohepatitis induced by an MCD diet (methionine/choline-deficient diet) in mice lacking the CCL2 gene on two different genetic backgrounds, namely Balb/C and C57/Bl6J. WT (wild-type) and CCL2-KO (knockout) mice were fed on a lipid-enriched MCD diet or a control diet for 8 weeks. In Balb/C mice fed on the MCD diet, a lack of CCL2 was associated with lower ALT (alanine transaminase) levels and reduced infiltration of inflammatory cells, together with a lower generation of oxidative-stress-related products. Sirius Red staining demonstrated pericellular fibrosis in zone 3, and image analysis showed a significantly lower matrix accumulation in CCL2-KO mice. This was associated with reduced hepatic expression of TGF-β (transforming growth factor-β), type I procollagen, TIMP-1 (tissue inhibitor of metalloproteinases-1) and α-smooth muscle actin. In contrast, in mice on a C57Bl/6 background, neither ALT levels nor inflammation or fibrosis were significantly different comparing WT and CCL2-KO animals fed on an MCD diet. In agreement, genes related to fibrogenesis were expressed to comparable levels in the two groups of animals. Comparison of the expression of several genes involved in inflammation and repair demonstrated that IL (interleukin)-4 and the M2 marker MGL-1 (macrophage galactose-type C-type lectin 1) were differentially expressed in Balb/C and C57Bl/6 mice. No significant differences in the degree of steatosis were observed in all groups of mice fed on the MCD diet. We conclude that, in experimental murine steatohepatitis, the effects of CCL2 deficiency are markedly dependent on the genetic background.

  9. Conservational PDF Equations of Turbulence

    NASA Technical Reports Server (NTRS)

    Shih, Tsan-Hsing; Liu, Nan-Suey

    2010-01-01

    Recently we have revisited the traditional probability density function (PDF) equations for the velocity and species in turbulent incompressible flows. They are all unclosed due to the appearance of various conditional means which are modeled empirically. However, we have observed that it is possible to establish a closed velocity PDF equation and a closed joint velocity and species PDF equation through conditions derived from the integral form of the Navier-Stokes equations. Although, in theory, the resulted PDF equations are neither general nor unique, they nevertheless lead to the exact transport equations for the first moment as well as all higher order moments. We refer these PDF equations as the conservational PDF equations. This observation is worth further exploration for its validity and CFD application

  10. Differential Proinflammatory and Oxidative Stress Response and Vulnerability to Metabolic Syndrome in Habitual High-Fat Young Male Consumers Putatively Predisposed by Their Genetic Background

    PubMed Central

    González-Muniesa, Pedro; Marrades, María Pilar; Martínez, José Alfredo; Moreno-Aliaga, María Jesús

    2013-01-01

    The current nutritional habits and lifestyles of modern societies favor energy overloads and a diminished physical activity, which may produce serious clinical disturbances and excessive weight gain. In order to investigate the mechanisms by which the environmental factors interact with molecular mechanisms in obesity, a pathway analysis was performed to identify genes differentially expressed in subcutaneous abdominal adipose tissue (SCAAT) from obese compared to lean male (21–35 year-old) subjects living in similar obesogenic conditions: habitual high fat dietary intake and moderate physical activity. Genes involved in inflammation (ALCAM, CTSB, C1S, YKL-40, MIF, SAA2), extracellular matrix remodeling (MMP9, PALLD), angiogenesis (EGFL6, leptin) and oxidative stress (AKR1C3, UCHL1, HSPB7 and NQO1) were upregulated; whereas apoptosis, signal transcription (CITED 2 and NR3C1), cell control and cell cycle-related genes were downregulated. Interestingly, the expression of some of these genes (C1S, SAA2, ALCAM, CTSB, YKL-40 and tenomodulin) was found to be associated with some relevant metabolic syndrome features. The obese group showed a general upregulation in the expression of inflammatory, oxidative stress, extracellular remodeling and angiogenic genes compared to lean subjects, suggesting that a given genetic background in an obesogenic environment could underlie the resistance to gaining weight and obesity-associated manifestations. PMID:23975165

  11. Proanthocyanidins in Sea Buckthorn (Hippophaë rhamnoides L.) Berries of Different Origins with Special Reference to the Influence of Genetic Background and Growth Location.

    PubMed

    Yang, Wei; Laaksonen, Oskar; Kallio, Heikki; Yang, Baoru

    2016-02-17

    Wild sea buckthorn berries from Finland (Hippophaë rhamnoides ssp. rhamnoides) and China (ssp. sinensis) as well as berries of two varieties of ssp. rhamnoides cultivated in Finland and five of ssp. mongolica cultivated in Canada were compared on the basis of the content and composition of proanthocyanidins (PAs). Among all of the samples, only B-type PAs were found. The contents of dimeric, trimeric, tetrameric, and total PAs were in the range of 1.4-8.9, 1.3-9.5, 1.0-7.1, and 390-1940 mg/100 g of dry weight, respectively. The three subspecies were separated by three validated factors (R(2), 0.724; Q(2), 0.677) in the partial least squares discriminant analysis model. Significant differences in total PAs were found between the ssp. rhamnoides and mongolica samples (p < 0.05). In ssp. rhamnoides, samples grown in northern Finland were characterized by a high amount of total PAs, typically 2-3 times higher than that in the level found in southern Finland. In ssp. sinensis, altitude did not have a systematic effect on the PA composition, suggesting the significance of the interaction between genetic background and growth location. PMID:26798947

  12. Proanthocyanidins in Sea Buckthorn (Hippophaë rhamnoides L.) Berries of Different Origins with Special Reference to the Influence of Genetic Background and Growth Location.

    PubMed

    Yang, Wei; Laaksonen, Oskar; Kallio, Heikki; Yang, Baoru

    2016-02-17

    Wild sea buckthorn berries from Finland (Hippophaë rhamnoides ssp. rhamnoides) and China (ssp. sinensis) as well as berries of two varieties of ssp. rhamnoides cultivated in Finland and five of ssp. mongolica cultivated in Canada were compared on the basis of the content and composition of proanthocyanidins (PAs). Among all of the samples, only B-type PAs were found. The contents of dimeric, trimeric, tetrameric, and total PAs were in the range of 1.4-8.9, 1.3-9.5, 1.0-7.1, and 390-1940 mg/100 g of dry weight, respectively. The three subspecies were separated by three validated factors (R(2), 0.724; Q(2), 0.677) in the partial least squares discriminant analysis model. Significant differences in total PAs were found between the ssp. rhamnoides and mongolica samples (p < 0.05). In ssp. rhamnoides, samples grown in northern Finland were characterized by a high amount of total PAs, typically 2-3 times higher than that in the level found in southern Finland. In ssp. sinensis, altitude did not have a systematic effect on the PA composition, suggesting the significance of the interaction between genetic background and growth location.

  13. The genetic background affects composition, oxidative stability and quality traits of Iberian dry-cured hams: purebred Iberian versus reciprocal Iberian × Duroc crossbred pigs.

    PubMed

    Fuentes, Verónica; Ventanas, Sonia; Ventanas, Jesús; Estévez, Mario

    2014-02-01

    This study examined the physico-chemical characteristics, oxidative stability and sensory properties of Iberian cry-cured hams as affected by the genetic background of the pigs: purebred Iberian (PBI) pigs vs reciprocal cross-bred Iberian × Duroc pigs (IB × D pigs: Iberian dams × Duroc sires; D × IB pigs: Duroc dams × Iberian sires). Samples from PBI pigs contained significantly higher amounts of IMF, monounsaturated fatty acids, heme pigments and iron than those from crossbred pigs. The extent of lipid and protein oxidation was significantly larger in dry-cured hams of crossbred pigs than in those from PBI pigs. Dry-cured hams from PBI pigs were defined by positive sensory properties (i.e. redness, brightness and juiciness) while hams from crossbred pigs were ascribed to negative ones (i.e. hardness, bitterness and sourness). Hams from PBI pigs displayed a superior quality than those from crossbred pigs. The position of the dam or the sire in reciprocal Iberian × Duroc crosses had no effect on the quality of Iberian hams.

  14. The first bromodomain of the testis-specific double bromodomain protein Brdt is required for chromocenter organization that is modulated by genetic background

    PubMed Central

    Berkovits, Binyamin D.; Wolgemuth, Debra J.

    2011-01-01

    Mice homozygous for a mutation (BrdtΔBD1/ΔBD1) lacking the first bromodomain of Brdt, a testis-specific member of the BET family of double-bromodomain containing proteins, are sterile and exhibit profound defects in chromatin remodeling during spermiogenesis. We have now observed that a prominent feature of the aberrant spermatid nuclei is a fragmented chromocenter, a structure comprised of peri-centromeric heterochromatin. There was a concomitant increase in the levels of heterochromatin protein 1 alpha (Hp1α), suggesting that the presence of multiple chromocenters was correlated with a spread of heterochromatin beyond the normal centromeric region. Brdt protein was normally present throughout the nucleus but was excluded from the chromocenter. A more densely staining region of Brdt protein appeared to separate sirtuin 1 (Sirt1) protein from contact with the chromocenter. Although still nuclear, this unique localization of Brdt protein was lost in BrdtΔBD1/ΔBD1 mutant spermatids and Brdt and Sirt1 overlapped around the chromocenters. There was also ectopic localization of the H1 histone family, member N, testis-specific (H1fnt) protein in BrdtΔBD1/ΔBD1 round spermatids, which may be linked to the previously reported loss of polarized localization of peri-nuclear heterochromatin foci. The extent of chromocenter fragmentation was more severe and penetrant in mutant testes on a pure 129Sv/Ev as compared to a pure C57Bl/6 background. Indeed, all aspects of the mutant phenotype were more severe on the 129Sv/Ev background. Contrary to previous studies in genetic models where fragmented chromocenters were observed in spermatids, the BrdtΔBD1/ΔBD1 mutant spermatids do not undergo apoptosis (on either background). These observations suggest that the first bromodomain of Brdt is critical in the formation and/or maintenance of an intact chromocenter and implicate this structure in proper remodeling of the chromatin architecture of the sperm head. PMID:22020252

  15. What to Expect When Meeting with a Genetic Counselor

    MedlinePlus

    ... PDF What to Expect When Meeting With a Genetic Counselor Approved by the Cancer.Net Editorial Board , ... prevention, and treatment options and provide support. A genetic counselor’s training and certification A genetic counselor is ...

  16. Protection by low-dose kanamycin against noise-induced hearing loss in mice: dependence on dosing regimen and genetic background.

    PubMed

    Ohlemiller, Kevin K; Rybak Rice, Mary E; Rosen, Allyson D; Montgomery, Scott C; Gagnon, Patricia M

    2011-10-01

    . While we cannot presently judge the generality of protection across genetic backgrounds, it appears not to be universal, since B6 showed no benefit. Classical genetic approaches based on CBA/J × B6 crosses may reveal loci critical to protective cascades engaged by kanamycin and perhaps other preconditioners. Their human analogs may partly determine who is at elevated risk of acquired hearing loss.

  17. Characterization of the Contribution of Genetic Background and Gender to Disease Progression in the SOD1 G93A Mouse Model of Amyotrophic Lateral Sclerosis: A Meta-Analysis

    PubMed Central

    Pfohl, Stephen R.; Halicek, Martin T.; Mitchell, Cassie S.

    2015-01-01

    Background The SOD1 G93A mouse model of amyotrophic lateral sclerosis (ALS) is the most frequently used model to examine ALS pathophysiology. There is a lack of homogeneity in usage of the SOD1 G93A mouse, including differences in genetic background and gender, which could confound the field’s results. Objective In an analysis of 97 studies, we characterized the ALS progression for the high transgene copy control SOD1 G93A mouse on the basis of disease onset, overall lifespan, and disease duration for male and female mice on the B6SJL and C57BL/6J genetic backgrounds and quantified magnitudes of differences between groups. Methods Mean age at onset, onset assessment measure, disease duration, and overall lifespan data from each study were extracted and statistically modeled as the response of linear regression with the sex and genetic background factored as predictors. Additional examination was performed on differing experimental onset and endpoint assessment measures. Results C57BL/6 background mice show delayed onset of symptoms, increased lifespan, and an extended disease duration compared to their sex-matched B6SJL counterparts. Female B6SJL generally experience extended lifespan and delayed onset compared to their male counterparts, while female mice on the C57BL/6 background show delayed onset but no difference in survival compared to their male counterparts. Finally, different experimental protocols (tremor, rotarod, etc.) for onset determination result in notably different onset means. Conclusions Overall, the observed effect of sex on disease endpoints was smaller than that which can be attributed to the genetic background. The often-reported increase in lifespan for female mice was observed only for mice on the B6SJL background, implicating a strain-dependent effect of sex on disease progression that manifests despite identical mutant SOD1 expression. PMID:26594635

  18. Photosensitivity of murine skin greatly depends on the genetic background: clinically relevant dose as a new measure to replace minimal erythema dose in mouse studies.

    PubMed

    Gyöngyösi, Nóra; Lőrincz, Kende; Keszeg, András; Haluszka, Dóra; Bánvölgyi, András; Tátrai, Erika; Kárpáti, Sarolta; Wikonkál, Norbert M

    2016-07-01

    Artificial UV irradiation of murine skin is a frequently used method for testing photosensitivity, study carcinogenesis and photoprotective effects of different compounds. However, doses of UV radiation and mouse strains used in experiments vary greatly. The genetic background of mice may influence the photosensitivity as melanin content, pigmentation and hair cycle parameters are dissimilar. Doses of UV are often expressed in relation to the minimal erythema dose (MED) that was not necessarily determined for the given strain. We set out to standardize the method of measuring photosensitivity in three commonly used mouse strains, C57BL/6N, Balb/c and SKH-1. We found that MED may not be determined for some strains as erythema development in mice with diverse genotypes differs greatly. We measured the oedema response in vivo and ex vivo by using OCT. Given the strain-specific variability of erythema, we introduced Clinically Relevant Dose (CRD) as a new term to replace MED in experiments, to describe the lowest dose that triggers a perceptible skin reaction in mice. Not only the CRD but the proportion of erythema and oedema were different in strains examined. C57BL/6N mice display skin reactions at the lowest UVB dose, while SKH-1 hairless mice show changes, mostly oedema, after higher doses of UVB. The cellular composition and skin thickness were examined by histopathology. IL-1beta and IL-6 levels in skin correlated with the increasing doses of UVB. Despite the variations in the degree of erythema and oedema, no major differences in cytokine expressions were seen among various strains of mice. PMID:26910301

  19. Effects of feeding deoxynivalenol (DON)-contaminated wheat to laying hens and roosters of different genetic background on the reproductive performance and health of the newly hatched chicks.

    PubMed

    Ebrahem, Mohammad; Kersten, Susanne; Valenta, Hana; Breves, Gerhard; Beineke, Andreas; Hermeyer, Kathrin; Dänicke, Sven

    2014-08-01

    A total of 216 23-week-old laying hens from two different genetic backgrounds (half of the birds were Lohmann brown [LB] and [LSL] hens, respectively) and 24 adult roosters were assigned to a feeding trial to study the effect of increasing concentrations of deoxynivalenol (DON) in the diet (0, 5, 10 mg/kg) on the reproductive performance of hens and roosters, and the health of the newly hatched chicks. Hatchability was adversely affected by the presence of DON in LB hens' diet, while the hatchability of the LSL chicks was significantly higher than LB chicks. An interaction effect between DON in the hens' diet and the breed was noticed on fertility, as the fertility was decreased in the eggs of LB hens receiving 10 mg/kg DON in their diet and increased in the eggs of LSL hens fed 10 mg/kg DON. Moreover, spleen relative weight was significantly decreased in the chicks hatched from eggs of hens fed contaminated diets, while gizzard relative weight was significantly decreased in LB chicks with 10 mg/kg DON in their diet compared with the control group. On the other hand, the chicks' haematology and organ histopathology were not affected by the dietary treatment. Additionally, the presence of DON in the roosters' diet had no effect on fertility (the percentage of fertile eggs of all laid eggs). Consequently, the current results indicate a negative impact of DON in LB hens' diet on fertility and hatchability, indicating that the breed of the hens seems to be an additional factor influencing the effect of DON on reproductive performance of the laying hens.

  20. Residues of deoxynivalenol (DON) and its metabolite de-epoxy-DON in eggs, plasma and bile of laying hens of different genetic backgrounds.

    PubMed

    Ebrahem, Mohammad; Kersten, Susanne; Valenta, Hana; Breves, Gerhard; Dänicke, Sven

    2014-01-01

    In the present study, the potential for carry-over of deoxynivalenol (DON) into eggs and DON residues in plasma and bile of laying hens of different genetic backgrounds after long-term feeding trial was investigated. A total of 80, 23-week-old laying hens were assigned to a feeding trial with two diets, a control diet and a Fusarium toxin-contaminated diet (FUS) (0.4 and 9.9 mg DON kg(-1), respectively). In the 60th week of hen's life, 10 eggs from each group were collected. In the 70th week of hen's life, all hens were slaughtered and samples of blood and bile were collected. The samples were analysed by liquid chromatography tandem mass spectrometry (LC-MS/MS) for DON and de-epoxy-DON. DON was only detected in samples of hens which fed the FUS diet while none of the samples analysed had detectable levels of de-epoxy-DON. In plasma and bile samples, DON levels ranged from 0.2 to 0.6 ng ml(-1) and from 1.8 to 4.1 ng ml(-1), respectively. DON levels in egg yolk and albumen ranged between 0.0-0.46 ng g(-1) and 0.0-0.35 ng g(-1), respectively, corresponding to carry-over rates of DON into eggs from 0.0 to 0.000016. Moreover, no differences in DON levels or carry-over rates were noticed between the two tested breeds. These results show that very low levels of DON were transferred into eggs and indicate that although eggs could contribute to human exposure to DON, the levels are very low and insignificant.

  1. Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies.

    PubMed

    Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Zhang, Dongwei; Joly, Erik; Madiraju, S R Murthy; Prentki, Marc

    2016-01-01

    Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions.

  2. Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies.

    PubMed

    Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Zhang, Dongwei; Joly, Erik; Madiraju, S R Murthy; Prentki, Marc

    2016-01-01

    Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions. PMID:27403868

  3. Differential Insulin Secretion of High-Fat Diet-Fed C57BL/6NN and C57BL/6NJ Mice: Implications of Mixed Genetic Background in Metabolic Studies

    PubMed Central

    Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Zhang, Dongwei; Joly, Erik; Madiraju, S. R. Murthy; Prentki, Marc

    2016-01-01

    Many metabolic studies employ tissue-specific gene knockout mice, which requires breeding of floxed gene mice, available mostly on C57BL/6N (NN) genetic background, with cre or Flp recombinase-expressing mice, available on C57BL/6J (JJ) background, resulting in the generation of mixed C57BL/6NJ (NJ) genetic background mice. Recent awareness of many genetic differences between NN and JJ strains including the deletion of nicotinamide nucleotide transhydrogenase (nnt), necessitates examination of the consequence of mixed NJ background on glucose tolerance, beta cell function and other metabolic parameters. Male mice with NN and NJ genetic background were fed with normal or high fat diets (HFD) for 12 weeks and glucose and insulin homeostasis were studied. Genotype had no effect on body weight and food intake in mice fed normal or high fat diets. Insulinemia in the fed and fasted states and after a glucose challenge was lower in HFD-fed NJ mice, even though their glycemia and insulin sensitivity were similar to NN mice. NJ mice showed mild glucose intolerance. Moreover, glucose- but not KCl-stimulated insulin secretion in isolated islets was decreased in HFD-fed NJ vs NN mice without changes in insulin content and beta cell mass. Under normal diet, besides reduced fed insulinemia, NN and NJ mice presented similar metabolic parameters. However, HFD-fed NJ mice displayed lower fed and fasted insulinemia and glucose-induced insulin secretion in vivo and ex vivo, as compared to NN mice. These results strongly caution against using unmatched mixed genetic background C57BL/6 mice for comparisons, particularly under HFD conditions. PMID:27403868

  4. Genetics Home Reference: retroperitoneal fibrosis

    MedlinePlus

    ... Understand Genetics Home Health Conditions retroperitoneal fibrosis retroperitoneal fibrosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Retroperitoneal fibrosis is a disorder in which inflammation and extensive ...

  5. Genetics Home Reference: breast cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions breast cancer breast cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Breast cancer is a disease in which certain cells in ...

  6. Genetics Home Reference: retinitis pigmentosa

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions retinitis pigmentosa retinitis pigmentosa Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Retinitis pigmentosa is a group of related eye disorders that ...

  7. Genetics Home Reference: cyclic neutropenia

    MedlinePlus

    ... Understand Genetics Home Health Conditions cyclic neutropenia cyclic neutropenia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Cyclic neutropenia is a disorder that causes frequent infections and ...

  8. Genetics Home Reference: congenital hypothyroidism

    MedlinePlus

    ... Understand Genetics Home Health Conditions congenital hypothyroidism congenital hypothyroidism Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Congenital hypothyroidism is a partial or complete loss of function ...

  9. Genetics Home Reference: Danon disease

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions Danon disease Danon disease Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Danon disease is a condition characterized by weakening of the ...

  10. Genetics Home Reference: warfarin sensitivity

    MedlinePlus

    ... Understand Genetics Home Health Conditions warfarin sensitivity warfarin sensitivity Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Warfarin sensitivity is a condition in which individuals have a ...

  11. Genetics Home Reference: lung cancer

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions lung cancer lung cancer Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Lung cancer is a disease in which certain cells ...

  12. Genetics Home Reference: surfactant dysfunction

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions surfactant dysfunction surfactant dysfunction Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Surfactant dysfunction is a lung disorder that causes breathing ...

  13. Genetics Home Reference: allergic asthma

    MedlinePlus

    ... Understand Genetics Home Health Conditions allergic asthma allergic asthma Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Asthma is a breathing disorder characterized by inflammation of ...

  14. Genetics Home Reference: Arts syndrome

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions Arts syndrome Arts syndrome Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Arts syndrome is a disorder that causes serious neurological ...

  15. Genetics Home Reference: multiple sclerosis

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions multiple sclerosis multiple sclerosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Multiple sclerosis is a condition characterized by areas of damage ( ...

  16. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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 ...

  17. Genetics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Maintaining genetic variation in wild populations of Arctic organisms is fundamental to the long-term persistence of high latitude biodiversity. Variability is important because it provides options for species to respond to changing environmental conditions and novel challenges such as emerging path...

  18. Vaccination against Taenia solium cysticercosis in underfed rustic pigs of México: roles of age, genetic background and antibody response.

    PubMed

    Huerta, M; Sciutto, E; García, G; Villalobos, N; Hernández, M; Fragoso, G; Díaz, J; Díaz, A; Ramírez, R; Luna, S; García, J; Aguilar, E; Espinoza, S; Castilla, G; Bobadilla, J R; Avila, R; José, M V; Larralde, C; de Aluja, A S

    2000-06-27

    Vaccination of pigs of mixed genetic make-up, raised as rustically as done in rural Mexico, resulted in effective protection to experimental challenge against Taenia solium cysticercosis. Maximum protection was achieved if pigs were immunized at 70 days of age. There was large variation of viable parasite load within vaccinated pigs and controls, which is suggestive of significant genetic factors influencing susceptibility, besides immunization. Our results strengthen the advisability of pig vaccination for control of T. solium cysticercosis, since it lowers the number of viable cysticerci capable of transforming into tapeworms.

  19. [Organic Law 10/2007, of October 8, regulating the police database on identifiers obtained from DNA: historic background and genetic view].

    PubMed

    García, Oscar

    2007-01-01

    Recently, Basic Law 10/2007 of 8 October has entered into effect, which regulates the police database on identifiers that are obtained from DNA. In the following lines, the author reveals the process of approval of this law as well as approaching certain of its aspects from a genetic perspective.

  20. Genetic Effects and Heterosis of Yield and Yield Component Traits Based on Gossypium Barbadense Chromosome Segment Substitution Lines in Two Gossypium Hirsutum Backgrounds

    PubMed Central

    Gong, Juwu; Li, Junwen; Liu, Aiying; Shang, Haihong; Gong, Wankui; Chen, Tingting; Ge, Qun; Jia, Chaoyang; Lei, Yake; Hu, Yushu; Yuan, Youlu

    2016-01-01

    We hybridized 10 chromosome segment substitution lines (CSSLs) each from two CSSL populations and produced 50 F1 hybrids according to North Carolina Design II. We analyzed the genetic effects and heterosis of yield and yield components in the F1 hybrids and parents in four environments via the additive-dominance genetic model. Yield and yield components of the CSSLs were controlled by combined additive and dominance effects, and lint percentage was mainly controlled by additive effects, but boll weight, boll number, seedcotton yield and lint yield were mainly controlled by dominance effects. We detected significant interaction effects between genetics and the environment for all yields traits. Similar interactions were detected between two CSSL populations (Pop CCRI 36 and Pop CCRI 45). Significant positive mid-parent heterosis was detected for all yield traits in both populations, and significant positive better-parent heterosis was also detected for all yield traits except lint percentage. The differences among parents were relatively small, but significant heterosis was detected for yield and yield components. Therefore, the relationship between heterosis and genetic distance for yield traits is complicated and requires further study. These CSSLs represent useful tools for improving yield and yield components in cotton. PMID:27348815

  1. Nonsyndromic cleft lip with or without cleft palate and cancer: Evaluation of a possible common genetic background through the analysis of GWAS data.

    PubMed

    Dunkhase, Eva; Ludwig, Kerstin U; Knapp, Michael; Skibola, Christine F; Figueiredo, Jane C; Hosking, Fay Julie; Ellinghaus, Eva; Landi, Maria Teresa; Ma, Hongxia; Nakagawa, Hidewaki; Kim, Jong-Won; Han, Jiali; Yang, Ping; Böhmer, Anne C; Mattheisen, Manuel; Nöthen, Markus M; Mangold, Elisabeth

    2016-12-01

    Previous research suggests a genetic overlap between nonsyndromic cleft lip with or without cleft palate (NSCL/P) and cancer. The aim of the present study was to identify common genetic risk loci for NSCL/P and cancer entities that have been reported to co-occur with orofacial clefting. This was achieved through the investigation of large genome-wide association study datasets. Investigations of 12 NSCL/P single nucleotide polymorphisms (SNPs) in 32 cancer datasets, and 204 cancer SNPs in two NSCL/P datasets, were performed. The SNPs rs13041247 (20q12) and rs6457327 (6p21.33) showed suggestive evidence for an association with both NSCL/P and a specific cancer entity. These loci harbor genes of biological relevance to oncogenesis (MAFB and OCT4, respectively). This study is the first to characterize possible pleiotropic risk loci for NSCL/P and cancer in a systematic manner. The data represent a starting point for future research by identifying a genetic link between NSCL/P and cancer. PMID:27630819

  2. Arthroscopic removal of palmar/plantar osteochondral fragments (POF) in the metacarpo- and metatarso-phalangeal joints of standardbred trotters--outcome and possible genetic background to POF.

    PubMed

    Roneus, B; Arnason, T; Collinder, E; Rasmussen, M

    1998-01-01

    A clinical material of 133 Standardbred horses with palmar/plantar osteochondral fragments (POF) in the metacarpo- and metatarsophalangeal joints were studied. All horses had their fragments removed with arthroscopic surgery. 102 of the horses were 3 years old or younger when surgery was performed. Anatomical localisations of the fragments were in agreement with earlier reports. There was no statistical significant difference in month of birth in the POF--group compared to the total population. Eighty % of the horses that had raced before surgery came back to racing. The racing performance relative to their contemporaries remained the same after the POF operation. 65% of the horses that had not raced before surgery raced after the operation. The breeding index BLUP (Best Linear Unbiased Prediction) was used to evaluate if the POF-horses differed genetically in racing ability from the total population. The average BLUP value of the POF group was 103.4 (+/- 0.65), while the mean BLUP value of the total population was 98.9. This difference was highly significant and indicated that these POF horses belonged to a selected group. A homogeneity test of allele frequencies in blood type systems was performed to evaluate if any genetic difference was persistent between POF horses compared to the total population. The statistical analysis of gene frequencies for alleles in blood type systems indicated a genetic discrimination in blood type systems D and Tf.

  3. Somatic Point Mutations in mtDNA Control Region Are Influenced by Genetic Background and Associated with Healthy Aging: A GEHA Study

    PubMed Central

    Rose, Giuseppina; Romeo, Giuseppe; Dato, Serena; Crocco, Paolina; Bruni, Amalia C.; Hervonen, Antti; Majamaa, Kari; Sevini, Federica; Franceschi, Claudio; Passarino, Giuseppe

    2010-01-01

    Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions. PMID:20976236

  4. Multilocus sequence typing scheme for Enterococcus faecalis reveals hospital-adapted genetic complexes in a background of high rates of recombination.

    PubMed

    Ruiz-Garbajosa, Patricia; Bonten, Marc J M; Robinson, D Ashley; Top, Janetta; Nallapareddy, Sreedhar R; Torres, Carmen; Coque, Teresa M; Cantón, Rafael; Baquero, Fernando; Murray, Barbara E; del Campo, Rosa; Willems, Rob J L

    2006-06-01

    A multilocus sequence typing (MLST) scheme based on seven housekeeping genes was used to investigate the epidemiology and population structure of Enterococcus faecalis. MLST of 110 isolates from different sources and geographic locations revealed 55 different sequence types that grouped into four major clonal complexes (CC2, CC9, CC10, and CC21) by use of eBURST. Two of these clonal complexes, CC2 and CC9, are particularly fit in the hospital environment, as CC2 includes the previously described BVE clonal complex identified by an alternative MLST scheme and CC9 includes exclusively isolates from hospitalized patients. Identical alleles were found in genetically diverse isolates with no linkage disequilibrium, while the different MLST loci gave incongruent phylogenetic trees. This demonstrates that recombination is an important mechanism driving genetic variation in E. faecalis and suggests an epidemic population structure for E. faecalis. Our novel MLST scheme provides an excellent tool for investigating local and short-term epidemiology as well as global epidemiology, population structure, and genetic evolution of E. faecalis.

  5. Quantitative trait loci from the host genetic background modulate the durability of a resistance gene: a rational basis for sustainable resistance breeding in plants

    PubMed Central

    Quenouille, J; Paulhiac, E; Moury, B; Palloix, A

    2014-01-01

    The combination of major resistance genes with quantitative resistance factors is hypothesized as a promising breeding strategy to preserve the durability of resistant cultivar, as recently observed in different pathosystems. Using the pepper (Capsicum annuum)/Potato virus Y (PVY, genus Potyvirus) pathosystem, we aimed at identifying plant genetic factors directly affecting the frequency of virus adaptation to the major resistance gene pvr23 and at comparing them with genetic factors affecting quantitative resistance. The resistance breakdown frequency was a highly heritable trait (h2=0.87). Four loci including additive quantitative trait loci (QTLs) and epistatic interactions explained together 70% of the variance of pvr23 breakdown frequency. Three of the four QTLs controlling pvr23 breakdown frequency were also involved in quantitative resistance, strongly suggesting that QTLs controlling quantitative resistance have a pleiotropic effect on the durability of the major resistance gene. With the first mapping of QTLs directly affecting resistance durability, this study provides a rationale for sustainable resistance breeding. Surprisingly, a genetic trade-off was observed between the durability of PVY resistance controlled by pvr23 and the spectrum of the resistance against different potyviruses. This trade-off seemed to have been resolved by the combination of minor-effect durability QTLs under long-term farmer selection. PMID:24569635

  6. Generation of PDF with vector symbols from scanned document

    NASA Astrophysics Data System (ADS)

    Kurilin, Ilya V.; Safonov, Ilia V.; Rychagov, Michael N.; Lee, Hokeun; Kim, Sang Ho; Choi, Donchul

    2013-01-01

    The paper is devoted to the algorithm for generation of PDF with vector symbols from scanned documents. The complex multi-stage technique includes segmentation of the document to text/drawing areas and background, conversion of symbols to lines and Bezier curves, storing compressed background and foreground. In the paper we concentrate on symbol conversion that comprises segmentation of symbol bodies with resolution enhancement, contour tracing and approximation. Presented method outperforms competitive solutions and secures the best compression rate/quality ratio. Scaling of initial document to other sizes as well as several printing/scanning-to-PDF iterations expose advantages of proposed way for handling with document images. Numerical vectorization quality metric was elaborated. The outcomes of OCR software and user opinion survey confirm high quality of proposed method.

  7. Genetics Home Reference: alpha-mannosidosis

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions alpha-mannosidosis alpha-mannosidosis Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Alpha-mannosidosis is a rare inherited disorder that causes ...

  8. Genetics Home Reference: systemic lupus erythematosus

    MedlinePlus

    ... Genetics Home Health Conditions systemic lupus erythematosus systemic lupus erythematosus Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Systemic lupus erythematosus (SLE) is a chronic disease that causes ...

  9. Genetics Home Reference: white sponge nevus

    MedlinePlus

    ... Genetics Home Health Conditions white sponge nevus white sponge nevus Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description White sponge nevus is a condition characterized by the formation ...

  10. Genetics Home Reference: glucose phosphate isomerase deficiency

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions GPI deficiency glucose phosphate isomerase deficiency Enable Javascript to view the ... boxes. Download PDF Open All Close All Description Glucose phosphate isomerase (GPI) deficiency is an inherited disorder ...

  11. Genetics Home Reference: ataxia neuropathy spectrum

    MedlinePlus

    ... Genetics Home Health Conditions ataxia neuropathy spectrum ataxia neuropathy spectrum Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Ataxia neuropathy spectrum is part of a group of conditions ...

  12. Genetics Home Reference: congenital dyserythropoietic anemia

    MedlinePlus

    ... Understand Genetics Home Health Conditions CDA congenital dyserythropoietic anemia Enable Javascript to view the expand/collapse boxes. ... PDF Open All Close All Description Congenital dyserythropoietic anemia ( CDA ) is an inherited blood disorder that affects ...

  13. Genetics Home Reference: 3-M syndrome

    MedlinePlus

    ... Understand Genetics Home Health Conditions 3-M syndrome 3-M syndrome Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description 3-M syndrome is a disorder that causes short ...

  14. Genetics Home Reference: rippling muscle disease

    MedlinePlus

    ... Genetics Home Health Conditions rippling muscle disease rippling muscle disease Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Rippling muscle disease is a condition in which the muscles ...

  15. Genetics Home Reference: protein C deficiency

    MedlinePlus

    ... Understand Genetics Home Health Conditions protein C deficiency protein C deficiency Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Protein C deficiency is a disorder that increases the ...

  16. Genetics Home Reference: protein S deficiency

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions protein S deficiency protein S deficiency Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Protein S deficiency is a disorder of blood clotting. People ...

  17. Genetics Home Reference: Wolf-Hirschhorn syndrome

    MedlinePlus

    ... Understand Genetics Home Health Conditions Wolf-Hirschhorn syndrome Wolf-Hirschhorn syndrome Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Wolf-Hirschhorn syndrome is a condition that affects many ...

  18. Genetics Home Reference: fish-eye disease

    MedlinePlus

    ... Understand Genetics Home Health Conditions fish-eye disease fish-eye disease Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Fish-eye disease , also called partial LCAT deficiency, is ...

  19. Genetics Home Reference: Russell-Silver syndrome

    MedlinePlus

    ... Genetics Home Health Conditions Russell-Silver syndrome Russell-Silver syndrome Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Russell-Silver syndrome is a growth disorder characterized by slow ...

  20. Genetics Home Reference: adolescent idiopathic scoliosis

    MedlinePlus

    ... Understand Genetics Home Health Conditions adolescent idiopathic scoliosis adolescent idiopathic scoliosis Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Adolescent idiopathic scoliosis is an abnormal curvature of the ...

  1. Genetics Home Reference: Smith-Magenis syndrome

    MedlinePlus

    ... Understand Genetics Home Health Conditions Smith-Magenis syndrome Smith-Magenis syndrome Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description Smith-Magenis syndrome is a developmental disorder that affects ...

  2. Genetics Home Reference: Dubin-Johnson syndrome

    MedlinePlus

    ... Genetics Home Health Conditions Dubin-Johnson syndrome Dubin-Johnson syndrome Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Dubin-Johnson syndrome is a condition characterized by jaundice, which ...

  3. ATML1 and PDF2 Play a Redundant and Essential Role in Arabidopsis Embryo Development.

    PubMed

    Ogawa, Eriko; Yamada, Yusuke; Sezaki, Noriko; Kosaka, Sho; Kondo, Hitoshi; Kamata, Naoko; Abe, Mitsutomo; Komeda, Yoshibumi; Takahashi, Taku

    2015-06-01

    The epidermis of shoot organs in plants develops from the outermost layer (L1) of the shoot apical meristem. In Arabidopsis, a pair of homeobox genes, ARABIDOPSIS THALIANA MERISTEM LAYER1 (ATML1) and PROTODERMAL FACTOR2 (PDF2), play a role in regulating the expression of L1-specific genes. atml1-1 pdf2-1 double mutants show striking defects in the differentiation of shoot epidermal cells. However, because atml1-1 and pdf2-1 have a T-DNA inserted downstream of the respective homeobox sequences, these alleles may not represent null mutations. Here we characterized additional mutant alleles that have a T-DNA insertion at different positions of each gene. Double mutants of a strong atml1-3 allele with each pdf2 allele were found to cause embryonic arrest at the globular stage. Although with low frequency, all double mutant combinations of a weak atml1-1 allele with each pdf2 allele germinated and showed phenotypes defective in shoot epidermal cell differentiation. We further confirmed that transgenic induction of PDF2 fused to the Drosophila Engrailed repressor domain temporarily interferes with epidermal cell differentiation in the wild-type background. These results indicate that ATML1 and PDF2 act redundantly as a positive regulator of shoot epidermal cell differentiation and at least one copy of these genes is essential for embryo development. PMID:25766904

  4. Either the dorsal hippocampus or the dorsolateral striatum is selectively involved in consolidation of forced swim-induced immobility depending on genetic background.

    PubMed

    Colelli, V; Campus, P; Conversi, D; Orsini, C; Cabib, S

    2014-05-01

    Healthy subjects differ in the memory system they engage to learn dual-solution tasks. Both genotype and stress experience could contribute to this phenotypic variability. The present experiments tested whether the hippocampus and the dorsal striatum, the core nodes of two different memory systems, are differently involved in 24 h retention of a stress-associated memory in two genetically unrelated inbred strains of mice. Mice from both the C57BL/6J and the DBA/2J inbred strains showed progressive increase of immobility during 10 min exposure to forced swim (FS) and retrieved the acquired levels of immobility when tested 24h later. The pattern of c-fos immunostaining promoted by FS revealed activation of a large number of brain areas in both strains, including CA1 and CA3 fields of the hippocampus. However, only DBA/2J mice showed activation of the dorsolateral striatum (DLS). In addition, FS induced a positive correlation between c-fos expression in the amygdala and CA1 and CA3 in C57BL/6J mice whereas it induced a positive correlation between c-fos expression in the amygdala and DLS in DBA/2J mice. Finally, temporary post-training inactivation of the dorsal hippocampus, by local infusion of lidocaine, prevented 24h retention of immobility in C57BL/6J mice only, whereas inactivation of the DLS prevented retention in DBA/2J mice only. These findings support the view that genetic factors can determine whether the dorsal hippocampus or the DLS are selectively engaged to consolidate stress-related memory.

  5. Historical background.

    PubMed Central

    Epstein, M A

    2001-01-01

    close genetic relatedness to EBV and its comparable biological behaviour. The discovery of Kaposi's sarcoma-associated herpesvirus six years ago was made using unconventional new methods, but, unlike with EBV 30 years before, this did not hinder its acceptance. This contrast is discussed in the context of the great progress in human tumour virology which has been made in recent years. PMID:11313002

  6. PDF approach for compressible turbulent reacting flows

    NASA Technical Reports Server (NTRS)

    Hsu, A. T.; Tsai, Y.-L. P.; Raju, M. S.

    1993-01-01

    The objective of the present work is to develop a probability density function (pdf) turbulence model for compressible reacting flows for use with a CFD flow solver. The probability density function of the species mass fraction and enthalpy are obtained by solving a pdf evolution equation using a Monte Carlo scheme. The pdf solution procedure is coupled with a compressible CFD flow solver which provides the velocity and pressure fields. A modeled pdf equation for compressible flows, capable of capturing shock waves and suitable to the present coupling scheme, is proposed and tested. Convergence of the combined finite-volume Monte Carlo solution procedure is discussed, and an averaging procedure is developed to provide smooth Monte-Carlo solutions to ensure convergence. Two supersonic diffusion flames are studied using the proposed pdf model and the results are compared with experimental data; marked improvements over CFD solutions without pdf are observed. Preliminary applications of pdf to 3D flows are also reported.

  7. Preferential selection of heterologous G3-VP7 gene in the genetic background of simian rotavirus SA11 detected by using a homotypic single-VP7 gene-substitution reassortant.

    PubMed

    Okada, J; Kobayashi, N; Taniguchi, K; Urasawa, S

    1998-04-01

    Introduction of segmented genomes into virion is an important process in viral replication of rotavirus. We previously studied the assortment of the VP7 gene segment (encoding outer capsid protein VP7) in the genetic background of simian rotavirus SA11 (G serotype 3, G3) and found the preferential selection of homologous G3 VP7 gene over VP7 gene of heterologous G serotype (G1, G2 or G4). In the present study, in order to clarify whether or not VP7 gene derived from different G3 rotavirus (heterologous G3-VP7 gene) is also preferentially selected in the SA11 background, a single-VP7 gene-substitution reassortant was prepared from SA11 through multiple steps of coinfection with rotaviruses in vitro. The isolated reassortant, SNR1, possessed VP7 gene derived from canine G3 rotavirus K9 and all other gene segments of SA11 origin, and showed an identical growth characteristic to that of SA11. Amino acid sequence of K9 VP7 gene showed a high degree of identity (93.6%) to SA11 VP7 gene. In analysis by mixed infection and multiple passages of SNR1 and a single VP7 gene (with G1, G2 or G4 specificity) reassortant in the SA11 background, the G3-VP7 gene became predominant at early passage numbers. However, in mixed infection with SA11 and SNR1, homologous G3-VP7 gene (SA11-VP7 gene) was preferentially selected into progenies over heterologous one (K9-VP7 gene). These results together with our previous findings suggested that G3-VP7 gene, irrespective of origin of species, was functionally adapted to the genetic background of SA11, although the homologous gene had a better fit with other SA11 genes than did heterologous one, providing suggestions for efficaciousness of multivalent reassortant rotavirus vaccine. PMID:9614000

  8. A systematic analysis of TCA Escherichia coli mutants reveals suitable genetic backgrounds for enhanced hydrogen and ethanol production using glycerol as main carbon source.

    PubMed

    Valle, Antonio; Cabrera, Gema; Muhamadali, Howbeer; Trivedi, Drupad K; Ratray, Nicholas J W; Goodacre, Royston; Cantero, Domingo; Bolivar, Jorge

    2015-09-01

    Biodiesel has emerged as an environmentally friendly alternative to fossil fuels; however, the low price of glycerol feed-stocks generated from the biodiesel industry has become a burden to this industry. A feasible alternative is the microbial biotransformation of waste glycerol to hydrogen and ethanol. Escherichia coli, a microorganism commonly used for metabolic engineering, is able to biotransform glycerol into these products. Nevertheless, the wild type strain yields can be improved by rewiring the carbon flux to the desired products by genetic engineering. Due to the importance of the central carbon metabolism in hydrogen and ethanol synthesis, E. coli single null mutant strains for enzymes of the TCA cycle and other related reactions were studied in this work. These strains were grown anaerobically in a glycerol-based medium and the concentrations of ethanol, glycerol, succinate and hydrogen were analysed by HPLC and GC. It was found that the reductive branch is the more relevant pathway for the aim of this work, with malate playing a central role. It was also found that the putative C4-transporter dcuD mutant improved the target product yields. These results will contribute to reveal novel metabolic engineering strategies for improving hydrogen and ethanol production by E. coli.

  9. Enhancement of Experimental Cutaneous Leishmaniasis by Leishmania Molecules Is Dependent on Interleukin-4, Serine Protease/Esterase Activity, and Parasite and Host Genetic Backgrounds

    PubMed Central

    Silva, Virgínia M. G.; Larangeira, Daniela F.; Oliveira, Pablo R. S.; Sampaio, Romina B.; Suzart, Paula; Nihei, Jorge S.; Teixeira, Márcia C. A.; Mengel, José O.; dos-Santos, Washington L. C.; Pontes-de-Carvalho, Lain

    2011-01-01

    Most inbred strains of mice, like the BALB/c strain, are susceptible to Leishmania amazonensis infections and resistant to Leishmania braziliensis infections. This parasite-related difference could result from the activity of an L. amazonensis-specific virulence factor. In agreement with this hypothesis, it is shown here that the intravenous injection of BALB/c mice with L. amazonensis amastigote extract (LaE) but not the L. braziliensis extract confers susceptibility to L. braziliensis infection. This effect was associated with high circulating levels of IgG1 anti-L. amazonensis antibodies and with an increase in interleukin-4 (IL-4) production and a decrease in gamma interferon production by draining lymph node cells. Moreover, the effect was absent in IL-4-knockout mice. The biological activity in the LaE was not mediated by amphiphilic molecules and was inhibited by pretreatment of the extract with irreversible serine protease inhibitors. These findings indicate that the LaE contains a virulence-related factor that (i) enhances the Leishmania infection by promoting Th2-type immune responses, (ii) is not one of the immunomodulatory Leishmania molecules described so far, and (iii) is either a serine protease or has an effect that depends on that protease activity. In addition to being Leishmania species specific, the infection-enhancing activity was also shown to depend on the host genetic makeup, as LaE injections did not affect the susceptibility of C57BL/6 mice to L. braziliensis infection. The identification of Leishmania molecules with infection-enhancing activity could be important for the development of a vaccine, since the up- or downmodulation of the immune response against a virulence factor could well contribute to controlling the infection. PMID:21173308

  10. Identification and mapping stripe rust resistance gene YrLM168a using extreme individuals and recessive phenotype class in a complicate genetic background.

    PubMed

    Feng, Junyan; Chen, Guoyue; Wei, Yuming; Liu, Yaxi; Jiang, Qiantao; Li, Wei; Pu, Zhien; Lan, Xiujin; Dai, Shoufen; Zhang, Min; Zheng, Youliang

    2015-12-01

    The identification and characterization of resistance genes effective against stripe rust of wheat is beneficial for modern wheat breeding programs. Molecular markers to such genes facilitate their deployment. The variety Milan has resistance that is effective against the predominant stripe rust races in the Sichuan region. Two resistant and two susceptible F8 lines from a cross between Milan and the susceptible variety Chuannong 16 were used to investigate inheritance of the Milan resistance. Three F2 populations were developed from crosses between the resistant lines and their susceptible sibling lines (LM168a × LM168c, LM168c × LM168a, LM168b × LM168d) and used for genetic analysis and molecular mapping of the genes for resistance. The stripe rust resistance in LM168a and LM168b was conferred by a single dominant gene, temporarily designated as YrLM168a. Forty-five extreme susceptible plants from the F2 families of LM168d × LM168b were genotyped with 836 simple sequence repeat (SSR) markers to map YrLM168a. YrLM168a was mapped in chromosome 6BL. The nearest flanking markers Xwmc756 and Xbarc146 were 4.6 and 4.6 cM away from the gene at both sides, respectively. The amplification results of twenty extreme resistant (IT 0) and susceptible (IT 4) F2 plants of LM168c × LM168a and LM168a × LM168c with marker Xwmc756 further validated the mapping results. The study suggested that extreme individuals and recessive phenotype class can be successfully used for mapping genes, which should be efficient and reliable. In addition, the flanking markers near YrLM168a should be helpful in marker-assisted breeding.

  11. Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model.

    PubMed

    Flagel, Shelly B; Chaudhury, Sraboni; Waselus, Maria; Kelly, Rebeca; Sewani, Salima; Clinton, Sarah M; Thompson, Robert C; Watson, Stanley J; Akil, Huda

    2016-05-17

    This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with "temperament," including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor. PMID:27114539

  12. Genetic background and epigenetic modifications in the core of the nucleus accumbens predict addiction-like behavior in a rat model

    PubMed Central

    Flagel, Shelly B.; Chaudhury, Sraboni; Waselus, Maria; Kelly, Rebeca; Sewani, Salima; Clinton, Sarah M.; Thompson, Robert C.; Watson, Stanley J.; Akil, Huda

    2016-01-01

    This study provides a demonstration in the rat of a clear genetic difference in the propensity for addiction-related behaviors following prolonged cocaine self-administration. It relies on the use of selectively bred high-responder (bHR) and low-responder (bLR) rat lines that differ in several characteristics associated with “temperament,” including novelty-induced locomotion and impulsivity. We show that bHR rats exhibit behaviors reminiscent of human addiction, including persistent cocaine-seeking and increased reinstatement of cocaine seeking. To uncover potential underlying mechanisms of this differential vulnerability, we focused on the core of the nucleus accumbens and examined expression and epigenetic regulation of two transcripts previously implicated in bHR/bLR differences: fibroblast growth factor (FGF2) and the dopamine D2 receptor (D2). Relative to bHRs, bLRs had lower FGF2 mRNA levels and increased association of a repressive mark on histones (H3K9me3) at the FGF2 promoter. These differences were apparent under basal conditions and persisted even following prolonged cocaine self-administration. In contrast, bHRs had lower D2 mRNA under basal conditions, with greater association of H3K9me3 at the D2 promoter and these differences were no longer apparent following prolonged cocaine self-administration. Correlational analyses indicate that the association of H3K9me3 at D2 may be a critical substrate underlying the propensity to relapse. These findings suggest that low D2 mRNA levels in the nucleus accumbens core, likely mediated via epigenetic modifications, may render individuals more susceptible to cocaine addiction. In contrast, low FGF2 levels, which appear immutable even following prolonged cocaine exposure, may serve as a protective factor. PMID:27114539

  13. Vulnerability to depression: A moderated mediation model of the roles of child maltreatment, peer victimization, and 5-HTTLPR genetic variation among children from low-SES backgrounds

    PubMed Central

    Banny, Adrienne M.; Cicchetti, Dante; Rogosch, Fred A.; Oshri, Assaf; Crick, Nicki R.

    2014-01-01

    Child maltreatment, peer victimization, and a polymorphism of the serotonin transporter gene (5-HTTLPR) were examined as predictors of depressive symptomatology. Children (M age = 11.26, SD = 1.65), including 156 maltreated and 145 nonmaltreated children from comparable low socioeconomic backgrounds, provided DNA samples and self-reports of relational peer victimization, overt peer victimization, and depressive symptoms. Path analysis showed that relational and overt victimization mediated the association between child maltreatment and depressive symptoms. Bootstrapping procedures were used to test moderated mediation and demonstrated that genotype moderated the indirect effects of relational and overt victimization on child depressive symptoms, such that victimized children with the l/l variation were at an increased risk for depressive symptoms compared to victimized children carrying an s allele. Results highlight the utility of examining process models that incorporate biological and psychological factors contributing to the development of depressive symptomatology, and provide direction toward understanding and promoting resilience among high risk youth from a multiple levels of analysis approach. PMID:23880379

  14. The antifungal plant defensin AhPDF1.1b is a beneficial factor involved in adaptive response to zinc overload when it is expressed in yeast cells

    PubMed Central

    Mith, Oriane; Benhamdi, Asma; Castillo, Teddy; Bergé, Muriel; MacDiarmid, Colin W; Steffen, Janet; Eide, David J; Perrier, Véronique; Subileau, Maeva; Gosti, Françoise; Berthomieu, Pierre; Marquès, Laurence

    2015-01-01

    Antimicrobial peptides represent an expanding family of peptides involved in innate immunity of many living organisms. They show an amazing diversity in their sequence, structure, and mechanism of action. Among them, plant defensins are renowned for their antifungal activity but various side activities have also been described. Usually, a new biological role is reported along with the discovery of a new defensin and it is thus not clear if this multifunctionality exists at the family level or at the peptide level. We previously showed that the plant defensin AhPDF1.1b exhibits an unexpected role by conferring zinc tolerance to yeast and plant cells. In this paper, we further explored this activity using different yeast genetic backgrounds: especially the zrc1 mutant and an UPRE-GFP reporter yeast strain. We showed that AhPDF1.1b interferes with adaptive cell response in the endoplasmic reticulum to confer cellular zinc tolerance. We thus highlighted that, depending on its cellular localization, AhPDF1.1b exerts quite separate activities: when it is applied exogenously, it is a toxin against fungal and also root cells, but when it is expressed in yeast cells, it is a peptide that modulates the cellular adaptive response to zinc overload. PMID:25755096

  15. High Resolution PDF Measurements on Ag Nanoparticles

    SciTech Connect

    Rocha, Tulio C. R.; Martin, Chris; Kycia, Stefan; Zanchet, Daniela

    2009-01-29

    The quantitative analysis of structural defects in Ag nanoparticles was addressed in this work. We performed atomic scale structural characterization by a combination of x-ray diffraction (XRD) using the Pair Distribution Function analysis (PDF) and High Resolution Transmission Electron Microscopy (HRTEM). The XRD measurements were performed using an innovative instrumentation setup to provide high resolution PDF patterns.

  16. Genetic background of extreme violent behavior

    PubMed Central

    Tiihonen, J; Rautiainen, M-R; Ollila, HM; Repo-Tiihonen, E; Virkkunen, M; Palotie, A; Pietiläinen, O; Kristiansson, K; Joukamaa, M; Lauerma, H; Saarela, J; Tyni, S; Vartiainen, H; Paananen, J; Goldman, D; Paunio, T

    2015-01-01

    In developed countries, the majority of all violent crime is committed by a small group of antisocial recidivistic offenders, but no genes have been shown to contribute to recidivistic violent offending or severe violent behavior, such as homicide. Our results, from two independent cohorts of Finnish prisoners, revealed that a monoamine oxidase A (MAOA) low-activity genotype (contributing to low dopamine turnover rate) as well as the CDH13 gene (coding for neuronal membrane adhesion protein) are associated with extremely violent behavior (at least 10 committed homicides, attempted homicides or batteries). No substantial signal was observed for either MAOA or CDH13 among non-violent offenders, indicating that findings were specific for violent offending, and not largely attributable to substance abuse or antisocial personality disorder. These results indicate both low monoamine metabolism and neuronal membrane dysfunction as plausible factors in the etiology of extreme criminal violent behavior, and imply that at least about 5–10% of all severe violent crime in Finland is attributable to the aforementioned MAOA and CDH13 genotypes. PMID:25349169

  17. Pdf - Transport equations for chemically reacting flows

    NASA Technical Reports Server (NTRS)

    Kollmann, W.

    1989-01-01

    The closure problem for the transport equations for pdf and the characteristic functions of turbulent, chemically reacting flows is addressed. The properties of the linear and closed equations for the characteristic functional for Eulerian and Lagrangian variables are established, and the closure problem for the finite-dimensional case is discussed for pdf and characteristic functions. It is shown that the closure for the scalar dissipation term in the pdf equation developed by Dopazo (1979) and Kollmann et al. (1982) results in a single integral, in contrast to the pdf, where double integration is required. Some recent results using pdf methods obtained for turbulent flows with combustion, including effects of chemical nonequilibrium, are discussed.

  18. PDF turbulence modeling and DNS

    NASA Technical Reports Server (NTRS)

    Hsu, A. T.

    1992-01-01

    The problem of time discontinuity (or jump condition) in the coalescence/dispersion (C/D) mixing model is addressed in probability density function (pdf). A C/D mixing model continuous in time is introduced. With the continuous mixing model, the process of chemical reaction can be fully coupled with mixing. In the case of homogeneous turbulence decay, the new model predicts a pdf very close to a Gaussian distribution, with finite higher moments also close to that of a Gaussian distribution. Results from the continuous mixing model are compared with both experimental data and numerical results from conventional C/D models. The effect of Coriolis forces on compressible homogeneous turbulence is studied using direct numerical simulation (DNS). The numerical method used in this study is an eight order compact difference scheme. Contrary to the conclusions reached by previous DNS studies on incompressible isotropic turbulence, the present results show that the Coriolis force increases the dissipation rate of turbulent kinetic energy, and that anisotropy develops as the Coriolis force increases. The Taylor-Proudman theory does apply since the derivatives in the direction of the rotation axis vanishes rapidly. A closer analysis reveals that the dissipation rate of the incompressible component of the turbulent kinetic energy indeed decreases with a higher rotation rate, consistent with incompressible flow simulations (Bardina), while the dissipation rate of the compressible part increases; the net gain is positive. Inertial waves are observed in the simulation results.

  19. Recent progress in the joint velocity-scalar PDF method

    NASA Technical Reports Server (NTRS)

    Anand, M. S.

    1995-01-01

    This viewgraph presentation discusses joint velocity-scalar PDF method; turbulent combustion modeling issues for gas turbine combustors; PDF calculations for a recirculating flow; stochastic dissipation model; joint PDF calculations for swirling flows; spray calculations; reduced kinetics/manifold methods; parallel processing; and joint PDF focus areas.

  20. Genetics Home Reference: alpha-methylacyl-CoA racemase deficiency

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions AMACR deficiency alpha-methylacyl-CoA racemase deficiency Enable Javascript to view ... boxes. Download PDF Open All Close All Description Alpha-methylacyl-CoA racemase (AMACR) deficiency is a disorder ...

  1. Genetics Home Reference: collagen VI-related myopathy

    MedlinePlus

    ... Genetics Home Health Conditions collagen VI-related myopathy collagen VI-related myopathy Enable Javascript to view the ... boxes. Download PDF Open All Close All Description Collagen VI-related myopathy is a group of disorders ...

  2. Genetics Home Reference: myoclonic epilepsy myopathy sensory ataxia

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions MEMSA myoclonic epilepsy myopathy sensory ataxia Enable Javascript to view the ... Download PDF Open All Close All Description Myoclonic epilepsy myopathy sensory ataxia , commonly called MEMSA , is part ...

  3. Genetics Home Reference: Duchenne and Becker muscular dystrophy

    MedlinePlus

    ... Duchenne and Becker muscular dystrophy Duchenne and Becker muscular dystrophy Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Muscular dystrophies are a group of genetic conditions characterized by ...

  4. Genetics Home Reference: hand-foot-genital syndrome

    MedlinePlus

    ... Genetics Home Health Conditions hand-foot-genital syndrome hand-foot-genital syndrome Enable Javascript to view the ... boxes. Download PDF Open All Close All Description Hand-foot-genital syndrome is a rare condition that ...

  5. Genetics Home Reference: Smith-Lemli-Opitz syndrome

    MedlinePlus

    ... Genetics Home Health Conditions Smith-Lemli-Opitz syndrome Smith-Lemli-Opitz syndrome Enable Javascript to view the ... boxes. Download PDF Open All Close All Description Smith-Lemli-Opitz syndrome is a developmental disorder that ...

  6. Genetics Home Reference: D-bifunctional protein deficiency

    MedlinePlus

    ... Genetics Home Health Conditions D-bifunctional protein deficiency D-bifunctional protein deficiency Enable Javascript to view the ... boxes. Download PDF Open All Close All Description D-bifunctional protein deficiency is a disorder that causes ...

  7. Genetic background of novel sequence types of CTX-M-8- and CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae from public wastewater treatment plants in São Paulo, Brazil.

    PubMed

    Dropa, Milena; Lincopan, Nilton; Balsalobre, Livia C; Oliveira, Danielle E; Moura, Rodrigo A; Fernandes, Miriam Rodriguez; da Silva, Quézia Moura; Matté, Glavur R; Sato, Maria I Z; Matté, Maria H

    2016-03-01

    The release of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae to the environment is a public health issue worldwide. The aim of this study was to investigate the genetic background of genes encoding ESBLs in wastewater treatment plants (WWTPs) in São Paulo, southeastern Brazil. In 2009, during a local surveillance study, seven ESBL-producing Enterobacteriaceae strains were recovered from five WWTPs and screened for ESBL genes and mobile genetic elements. Multilocus sequence typing (MLST) was carried out, and wild plasmids were transformed into electrocompetent Escherichia coli. S1-PFGE technique was used to verify the presence of high molecular weight plasmids in wild-type strains and in bla ESBL-containing E. coli transformants. Strains harbored bla CTX-M-8, bla CTX-M-15, and/or bla SHV-28. Sequencing results showed that bla CTX-M-8 and bla CTX-M-15 genes were associated with IS26. MLST revealed new sequence types for E. coli (ST4401, ST4402, ST4403, and ST4445) and Klebsiella pneumoniae (ST1574), except for one K. pneumoniae from ST307 and Enterobacter cloacae from ST131. PCR and S1-PFGE results showed CTX-M-producing E. coli transformants carried heavy plasmids sizing 48.5-209 kb, which belonged to IncI1, IncF, and IncM1 incompatibility groups. This is the first report of CTX-M-8 and SHV-28 enzymes in environmental samples, and the present results demonstrate the plasmid-mediated spread of CTX-M-encoding genes through five WWTPs in São Paulo, Brazil, suggesting WWTPs are hotspots for the transfer of ESBL genes and confirming the urgent need to improve the management of sewage in order to minimize the dissemination of resistance genes to the environment. PMID:26782324

  8. Genetic background of novel sequence types of CTX-M-8- and CTX-M-15-producing Escherichia coli and Klebsiella pneumoniae from public wastewater treatment plants in São Paulo, Brazil.

    PubMed

    Dropa, Milena; Lincopan, Nilton; Balsalobre, Livia C; Oliveira, Danielle E; Moura, Rodrigo A; Fernandes, Miriam Rodriguez; da Silva, Quézia Moura; Matté, Glavur R; Sato, Maria I Z; Matté, Maria H

    2016-03-01

    The release of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae to the environment is a public health issue worldwide. The aim of this study was to investigate the genetic background of genes encoding ESBLs in wastewater treatment plants (WWTPs) in São Paulo, southeastern Brazil. In 2009, during a local surveillance study, seven ESBL-producing Enterobacteriaceae strains were recovered from five WWTPs and screened for ESBL genes and mobile genetic elements. Multilocus sequence typing (MLST) was carried out, and wild plasmids were transformed into electrocompetent Escherichia coli. S1-PFGE technique was used to verify the presence of high molecular weight plasmids in wild-type strains and in bla ESBL-containing E. coli transformants. Strains harbored bla CTX-M-8, bla CTX-M-15, and/or bla SHV-28. Sequencing results showed that bla CTX-M-8 and bla CTX-M-15 genes were associated with IS26. MLST revealed new sequence types for E. coli (ST4401, ST4402, ST4403, and ST4445) and Klebsiella pneumoniae (ST1574), except for one K. pneumoniae from ST307 and Enterobacter cloacae from ST131. PCR and S1-PFGE results showed CTX-M-producing E. coli transformants carried heavy plasmids sizing 48.5-209 kb, which belonged to IncI1, IncF, and IncM1 incompatibility groups. This is the first report of CTX-M-8 and SHV-28 enzymes in environmental samples, and the present results demonstrate the plasmid-mediated spread of CTX-M-encoding genes through five WWTPs in São Paulo, Brazil, suggesting WWTPs are hotspots for the transfer of ESBL genes and confirming the urgent need to improve the management of sewage in order to minimize the dissemination of resistance genes to the environment.

  9. Widespread receptivity to neuropeptide PDF throughout the neuronal circadian clock network of Drosophila revealed by real-time cyclic AMP imaging

    PubMed Central

    Shafer, Orie T.; Kim, Dong Jo; Dunbar-Yaffe, Richard; Nikolaev, Viacheslav O.; Lohse, Martin J.; Taghert, Paul H.

    2008-01-01

    Summary The neuropeptide PDF is released by sixteen clock neurons in Drosophila and helps maintain circadian activity rhythms by coordinating a network of ~150 neuronal clocks. Whether PDF acts directly on elements of this neural network remains unknown. We address this question by adapting Epac1-camps, a genetically encoded cAMP FRET sensor, for use in the living brain. We find that a subset of the PDF-expressing neurons respond to PDF with long-lasting cAMP increases, and confirm that such responses require the PDF receptor. In contrast, an unrelated Drosophila neuropeptide, DH 31, stimulates large cAMP increases in all PDF-expressing clock neurons. Thus the network of ~150 clock neurons displays widespread, though not uniform, PDF receptivity. This work introduces a sensitive means of measuring cAMP changes in a living brain with sub-cellular resolution. Specifically, it experimentally confirms the longstanding hypothesis that PDF is a direct modulator of most neurons in the Drosophila clock network. PMID:18439407

  10. The pdf approach to turbulent flow

    NASA Technical Reports Server (NTRS)

    Kollmann, W.

    1990-01-01

    This paper provides a detailed discussion of the theory and application of probability density function (pdf) methods, which provide a complete statistical description of turbulent flow fields at a single point or a finite number of points. The basic laws governing the flow of Newtonian fluids are set up in the Eulerian and the Lagrangian frame, and the exact and linear equations for the characteristic functionals in those frames are discussed. Pdf equations in both frames are derived as Fourier transforms of the equations of the characteristic functions. Possible formulations for the nonclosed terms in the pdf equation are discussed, their properties are assessed, and closure modes for the molecular-transport and the fluctuating pressure-gradient terms are reviewed. The application of pdf methods to turbulent combustion flows, supersonic flows, and the interaction of turbulence with shock waves is discussed.

  11. PDF methods for turbulent reactive flows

    NASA Technical Reports Server (NTRS)

    Hsu, Andrew T.

    1995-01-01

    Viewgraphs are presented on computation of turbulent combustion, governing equations, closure problem, PDF modeling of turbulent reactive flows, validation cases, current projects, and collaboration with industry and technology transfer.

  12. Application and Evaluation of Interactive 3D PDF for Presenting and Sharing Planning Results for Liver Surgery in Clinical Routine

    PubMed Central

    Newe, Axel; Becker, Linda; Schenk, Andrea

    2014-01-01

    Background & Objectives The Portable Document Format (PDF) is the de-facto standard for the exchange of electronic documents. It is platform-independent, suitable for the exchange of medical data, and allows for the embedding of three-dimensional (3D) surface mesh models. In this article, we present the first clinical routine application of interactive 3D surface mesh models which have been integrated into PDF files for the presentation and the exchange of Computer Assisted Surgery Planning (CASP) results in liver surgery. We aimed to prove the feasibility of applying 3D PDF in medical reporting and investigated the user experience with this new technology. Methods We developed an interactive 3D PDF report document format and implemented a software tool to create these reports automatically. After more than 1000 liver CASP cases that have been reported in clinical routine using our 3D PDF report, an international user survey was carried out online to evaluate the user experience. Results Our solution enables the user to interactively explore the anatomical configuration and to have different analyses and various resection proposals displayed within a 3D PDF document covering only a single page that acts more like a software application than like a typical PDF file (“PDF App”). The new 3D PDF report offers many advantages over the previous solutions. According to the results of the online survey, the users have assessed the pragmatic quality (functionality, usability, perspicuity, efficiency) as well as the hedonic quality (attractiveness, novelty) very positively. Conclusion The usage of 3D PDF for reporting and sharing CASP results is feasible and well accepted by the target audience. Using interactive PDF with embedded 3D models is an enabler for presenting and exchanging complex medical information in an easy and platform-independent way. Medical staff as well as patients can benefit from the possibilities provided by 3D PDF. Our results open the door for a

  13. Assumed PDF modeling in rocket combustor simulations

    NASA Astrophysics Data System (ADS)

    Lempke, M.; Gerlinger, P.; Aigner, M.

    2013-03-01

    In order to account for the interaction between turbulence and chemistry, a multivariate assumed PDF (Probability Density Function) approach is used to simulate a model rocket combustor with finite-rate chemistry. The reported test case is the PennState preburner combustor with a single shear coaxial injector. Experimental data for the wall heat flux is available for this configuration. Unsteady RANS (Reynolds-averaged Navier-Stokes) simulation results with and without the assumed PDF approach are analyzed and compared with the experimental data. Both calculations show a good agreement with the experimental wall heat flux data. Significant changes due to the utilization of the assumed PDF approach can be observed in the radicals, e. g., the OH mass fraction distribution, while the effect on the wall heat flux is insignificant.

  14. Relationship between hemodynamics and atherosclerosis in aortic arches of apolipoprotein E-null mice on 129S6/SvEvTac and C57BL/6J genetic backgrounds

    PubMed Central

    Tomita, Hirofumi; Hagaman, John; Friedman, Morton H.; Maeda, Nobuyo

    2011-01-01

    Objective We investigated the relationships between hemodynamics and differential plaque development at the aortic arch of apolipoprotein E (apoE)-null mice on 129S6/SvEvTac (129) and C57BL/6J (B6) genetic backgrounds. Methods Mean flow velocities at the ascending and descending aorta (mVAA and mVDA) were measured by Doppler ultrasound in wild type and apoE-null male mice at 3 and 9 months of age. Following dissection of the aortic arches, anatomical parameters and plaque areas were evaluated. Results Arch plaques were five times bigger in 129-apoE than in B6-apoE mice at 3 months, and twice as large at 9 months. The geometric differences, namely larger vessel diameter in the B6 strain and broader inner curvature of the aortic arch in the 129 strain, were exaggerated in 9-month-old apoE-null mice. Cardiac output and heart rate under anesthesia were significantly higher in the B6 strain than in the 129 strain. The values of mVAA were similar in the two strains, while mVDA was lower in the 129 strain. However, there was a 129-apoE-specific reduction of flow velocities with age, and both mVAA and mVDA were significantly lower in 129-apoE than in B6-apoE mice at 9 months. The mean relative wall shear stress (rWSS) over the aortic arch in 129-apoE and B6-apoE mice were not different, but animals with lower mean rWSS had larger arch plaques within each strain. Conclusions The plaque formation in the arch of apoE-null mice is accompanied by strain-dependent changes in both arch geometry and hemodynamics. While arch plaque sizes negatively correlate with mean rWSS, additional factors are necessary to account for the strain differences in arch plaque development. PMID:22078246

  15. Recent advances in PDF modeling of turbulent reacting flows

    NASA Technical Reports Server (NTRS)

    Leonard, Andrew D.; Dai, F.

    1995-01-01

    This viewgraph presentation concludes that a Monte Carlo probability density function (PDF) solution successfully couples with an existing finite volume code; PDF solution method applied to turbulent reacting flows shows good agreement with data; and PDF methods must be run on parallel machines for practical use.

  16. Building Background Knowledge

    ERIC Educational Resources Information Center

    Neuman, Susan B.; Kaefer, Tanya; Pinkham, Ashley

    2014-01-01

    This article make a case for the importance of background knowledge in children's comprehension. It suggests that differences in background knowledge may account for differences in understanding text for low- and middle-income children. It then describes strategies for building background knowledge in the age of common core standards.

  17. The PDF method for turbulent combustion

    NASA Technical Reports Server (NTRS)

    Pope, S. B.

    1991-01-01

    Probability Density Function (PDF) methods provide a means of calculating the properties of turbulent reacting flows. They have been successfully applied to many turbulent flames, including some with finite rate kinetic effects. Here the methods are reviewed with an emphasis on computational issues and their application to turbulent combustion.

  18. Datamatrix and PDF417 data integrity test

    SciTech Connect

    Fales, J.F.; Vincent, R.S.

    1993-09-01

    We conducted a test to evaluate data integrity of selected two-dimensional, high-density, high-capacity coding symbologies for use in selected automatic identification applications. The test was part ot the US Army`s Project Manager for Annnunition Logistics Automatic Ammunition Identification Technology Project. Specific symbologies tested were Datamatrix, from International Data Matrix, Inc., and PDF417, from Symbol Technologies, Inc. As a reference, Code 39 symbology was also evaluated under the same conditions. The statistical objective of the test was to determine if Datamatrix and/or PDF417 symbologies could be expected to exhibit one error or less in two million characters scanned and decoded. The level of confidence was set to 95%. Symbols for Datamatrix and PDF417 included 50, 100, 250, and 350 encoded characters for each of three levels or error correction. Each Code 39 symbol contained 15 to 25 characters. Based on a population of 1080 symbols per symbology, sample size was calculated to be 31,438,998 characters per symbology. An automated test apparatus was used to assure uniformity of test conditions. The apparatus included robotic loading and unloading of carrier sheets onto scanning stations. Scanning for Datamatrix symbols was performed using fixed mounted RS-170 CCD cameras. PDF417 and Code 39 symbols were scanned using hand-held rastering visible laser scanners mounted in fixed positions and software triggered. Decoding of all symbols occurred in decoders supplied with the scanners using the respective manufacturer`s proprietary decoding algorithms. Over 94 million characters were decoded during the test. Analysis of test results indicate no errors attributable to either Datamatrix or PDF417 symbologies. Eleven errors were recorded for Code 39.

  19. Genetics Home Reference: Ehlers-Danlos syndrome

    MedlinePlus

    ... Understand Genetics Home Health Conditions Ehlers-Danlos syndrome Ehlers-Danlos syndrome Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Ehlers-Danlos syndrome is a group of disorders that affect the ...

  20. Genetics Home Reference: phosphoglycerate kinase deficiency

    MedlinePlus

    ... the expand/collapse boxes. Download PDF Open All Close All Description Phosphoglycerate kinase deficiency is a genetic disorder that affects the body's ability to break down the simple sugar glucose, which is the primary energy source for most cells. Researchers have described two major ...

  1. Layout-aware text extraction from full-text PDF of scientific articles

    PubMed Central

    2012-01-01

    Background The Portable Document Format (PDF) is the most commonly used file format for online scientific publications. The absence of effective means to extract text from these PDF files in a layout-aware manner presents a significant challenge for developers of biomedical text mining or biocuration informatics systems that use published literature as an information source. In this paper we introduce the ‘Layout-Aware PDF Text Extraction’ (LA-PDFText) system to facilitate accurate extraction of text from PDF files of research articles for use in text mining applications. Results Our paper describes the construction and performance of an open source system that extracts text blocks from PDF-formatted full-text research articles and classifies them into logical units based on rules that characterize specific sections. The LA-PDFText system focuses only on the textual content of the research articles and is meant as a baseline for further experiments into more advanced extraction methods that handle multi-modal content, such as images and graphs. The system works in a three-stage process: (1) Detecting contiguous text blocks using spatial layout processing to locate and identify blocks of contiguous text, (2) Classifying text blocks into rhetorical categories using a rule-based method and (3) Stitching classified text blocks together in the correct order resulting in the extraction of text from section-wise grouped blocks. We show that our system can identify text blocks and classify them into rhetorical categories with Precision1 = 0.96% Recall = 0.89% and F1 = 0.91%. We also present an evaluation of the accuracy of the block detection algorithm used in step 2. Additionally, we have compared the accuracy of the text extracted by LA-PDFText to the text from the Open Access subset of PubMed Central. We then compared this accuracy with that of the text extracted by the PDF2Text system, 2commonly used to extract text from PDF. Finally, we discuss

  2. The Cosmic Background Explorer.

    ERIC Educational Resources Information Center

    Gulkis, Samuel; And Others

    1990-01-01

    Outlines the Cosmic Background Explorer (COBE) mission to measure celestial radiation. Describes the instruments used and experiments involving differential microwave radiometers, and a far infrared absolute spectrophotometer. (YP)

  3. Electrical silencing of PDF neurons advances the phase of non-PDF clock neurons in Drosophila.

    PubMed

    Wu, Ying; Cao, Guan; Nitabach, Michael N

    2008-04-01

    Drosophila clock neurons exhibit self-sustaining cellular oscillations that rely in part on rhythmic transcriptional feedback loops. We have previously determined that electrical silencing of the pigment dispersing factor (PDF)-expressing lateral-ventral (LN(V)) pacemaker subset of fly clock neurons via expression of an inward-rectifier K(+) channel (Kir2.1) severely disrupts free-running rhythms of locomotor activity-most flies are arrhythmic and those that are not exhibit weak short-period rhythms-and abolishes LN(V) molecular oscillation in constant darkness. PDF is known to be an important LN(V) output signal. Here we examine the effects of electrical silencing of the LN(V) pacemakers on molecular rhythms in other, nonsilenced, subsets of clock neurons. In contrast to previously described cell-autonomous abolition of free-running molecular rhythms, we find that electrical silencing of the LN(V) pacemakers via Kir2.1 expression does not impair molecular rhythms in LN(D), DN1, and DN2 subsets of clock neurons. However, free-running molecular rhythms in these non-LN(V) clock neurons occur with advanced phase. Electrical silencing of LN(V)s phenocopies PDF null mutation (pdf (01) ) at both behavioral and molecular levels except for the complete abolition of free-running cellular oscillation in the LN(V)s themselves. LN(V) electrically silenced or pdf 01 flies exhibit weak free-running behavioral rhythms with short period, and the molecular oscillation in non-LN(V) neurons phase advances in constant darkness. That LN( V) electrical silencing leads to the same behavioral and non-LN( V) molecular phenotypes as pdf 01 suggests that persistence of LN(V) molecular oscillation in pdf 01 flies has no functional effect, either on behavioral rhythms or on non-LN(V) molecular rhythms. We thus conclude that functionally relevant signals from LN(V)s to non-LN(V) clock neurons and other downstream targets rely both on PDF signaling and LN(V) electrical activity, and that LN( V

  4. Genetic Testing: What It Means for Your Health and Your Family's Health

    MedlinePlus

    ... Center – http://rarediseases.info.nih.gov/GARD National Human Genome Research Institute – Genetic Testing – http:// www.genome.gov/Pages/Health/PatientsPublicInfo/GeneticTestingFactSheet.pdf National Human Genome Research Institute – Genetic Information Nondiscrimination Act (GINA) – http:// ...

  5. Correlators in nontrivial backgrounds

    SciTech Connect

    Mello Koch, Robert de; Ives, Norman; Stephanou, Michael

    2009-01-15

    Operators in N=4 super Yang-Mills theory with an R-charge of O(N{sup 2}) are dual to backgrounds which are asymtotically AdS{sub 5}xS{sup 5}. In this article we develop efficient techniques that allow the computation of correlation functions in these backgrounds. We find that (i) contractions between fields in the string words and fields in the operator creating the background are the field theory accounting of the new geometry, (ii) correlation functions of probes in these backgrounds are given by the free field theory contractions but with rescaled propagators and (iii) in these backgrounds there are no open string excitations with their special end point interactions; we have only closed string excitations.

  6. Extra Dimensions: 3D in PDF Documentation

    NASA Astrophysics Data System (ADS)

    Graf, Norman A.

    2012-12-01

    Experimental science is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universal 3D (U3D) and the ISO PRC file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. Until recently, Adobe's Acrobat software was also capable of incorporating 3D content into PDF files from a variety of 3D file formats, including proprietary CAD formats. However, this functionality is no longer available in Acrobat X, having been spun off to a separate company. Incorporating 3D content now requires the additional purchase of a separate plug-in. In this talk we present alternatives based on open source libraries which allow the programmatic creation of 3D content in PDF format. While not providing the same level of access to CAD files as the commercial software, it does provide physicists with an alternative path to incorporate 3D content into PDF files from such disparate applications as detector geometries from Geant4, 3D data sets, mathematical surfaces or tesselated volumes.

  7. A GPU accelerated PDF transparency engine

    NASA Astrophysics Data System (ADS)

    Recker, John; Lin, I.-Jong; Tastl, Ingeborg

    2011-01-01

    As commercial printing presses become faster, cheaper and more efficient, so too must the Raster Image Processors (RIP) that prepare data for them to print. Digital press RIPs, however, have been challenged to on the one hand meet the ever increasing print performance of the latest digital presses, and on the other hand process increasingly complex documents with transparent layers and embedded ICC profiles. This paper explores the challenges encountered when implementing a GPU accelerated driver for the open source Ghostscript Adobe PostScript and PDF language interpreter targeted at accelerating PDF transparency for high speed commercial presses. It further describes our solution, including an image memory manager for tiling input and output images and documents, a PDF compatible multiple image layer blending engine, and a GPU accelerated ICC v4 compatible color transformation engine. The result, we believe, is the foundation for a scalable, efficient, distributed RIP system that can meet current and future RIP requirements for a wide range of commercial digital presses.

  8. Deep PDF parsing to extract features for detecting embedded malware.

    SciTech Connect

    Munson, Miles Arthur; Cross, Jesse S.

    2011-09-01

    The number of PDF files with embedded malicious code has risen significantly in the past few years. This is due to the portability of the file format, the ways Adobe Reader recovers from corrupt PDF files, the addition of many multimedia and scripting extensions to the file format, and many format properties the malware author may use to disguise the presence of malware. Current research focuses on executable, MS Office, and HTML formats. In this paper, several features and properties of PDF Files are identified. Features are extracted using an instrumented open source PDF viewer. The feature descriptions of benign and malicious PDFs can be used to construct a machine learning model for detecting possible malware in future PDF files. The detection rate of PDF malware by current antivirus software is very low. A PDF file is easy to edit and manipulate because it is a text format, providing a low barrier to malware authors. Analyzing PDF files for malware is nonetheless difficult because of (a) the complexity of the formatting language, (b) the parsing idiosyncrasies in Adobe Reader, and (c) undocumented correction techniques employed in Adobe Reader. In May 2011, Esparza demonstrated that PDF malware could be hidden from 42 of 43 antivirus packages by combining multiple obfuscation techniques [4]. One reason current antivirus software fails is the ease of varying byte sequences in PDF malware, thereby rendering conventional signature-based virus detection useless. The compression and encryption functions produce sequences of bytes that are each functions of multiple input bytes. As a result, padding the malware payload with some whitespace before compression/encryption can change many of the bytes in the final payload. In this study we analyzed a corpus of 2591 benign and 87 malicious PDF files. While this corpus is admittedly small, it allowed us to test a system for collecting indicators of embedded PDF malware. We will call these indicators features throughout

  9. A PDF closure model for compressible turbulent chemically reacting flows

    NASA Technical Reports Server (NTRS)

    Kollmann, W.

    1992-01-01

    The objective of the proposed research project was the analysis of single point closures based on probability density function (pdf) and characteristic functions and the development of a prediction method for the joint velocity-scalar pdf in turbulent reacting flows. Turbulent flows of boundary layer type and stagnation point flows with and without chemical reactions were be calculated as principal applications. Pdf methods for compressible reacting flows were developed and tested in comparison with available experimental data. The research work carried in this project was concentrated on the closure of pdf equations for incompressible and compressible turbulent flows with and without chemical reactions.

  10. Optimization of background subtraction for image enhancement

    NASA Astrophysics Data System (ADS)

    Venetsky, Larry; Boczar, Ross; Lee-Own, Robert

    2013-05-01

    Analysis of foreground objects in scenery via image processing often involves a background subtraction process. This process aims to improve blob (connected component) content in the image. Quality blob content is often needed for defining regions of interest for object recognition and tracking. Three techniques are examined which optimize the background to be subtracted - genetic algorithm, an analytic solution based on convex optimization, and a related application of the CVX solver toolbox. These techniques are applied to a set of images and the results are compared. Additionally, a possible implementation architecture that uses multiple optimization techniques with subsequent arbitration to produce the best background subtraction is considered.

  11. The GLAST Background Model

    SciTech Connect

    Ormes, J.F.; Atwood, W.; Burnett, T.; Grove, E.; Longo, F.; McEnery, J.; Mizuno, T.; Ritz, S.; /NASA, Goddard

    2007-10-17

    In order to estimate the ability of the GLAST/LAT to reject unwanted background of charged particles, optimize the on-board processing, size the required telemetry and optimize the GLAST orbit, we developed a detailed model of the background particles that would affect the LAT. In addition to the well-known components of the cosmic radiation, we included splash and reentrant components of protons, electrons (e+ and e-) from 10 MeV and beyond as well as the albedo gamma rays produced by cosmic ray interactions with the atmosphere. We made estimates of the irreducible background components produced by positrons and hadrons interacting in the multilayered micrometeorite shield and spacecraft surrounding the LAT and note that because the orbital debris has increased, the shielding required and hence the background are larger than were present in EGRET. Improvements to the model are currently being made to include the east-west effect.

  12. Selected Readings in Genetic Engineering

    ERIC Educational Resources Information Center

    Mertens, Thomas R.; Robinson, Sandra K.

    1973-01-01

    Describes different sources of readings for understanding issues and concepts of genetic engineering. Broad categories of reading materials are: concerns about genetic engineering; its background; procedures; and social, ethical and legal issues. References are listed. (PS)

  13. The Cosmic Background Explorer

    NASA Technical Reports Server (NTRS)

    Gulkis, Samuel; Lubin, Philip M.; Meyer, Stephan S.; Silverberg, Robert F.

    1990-01-01

    The Cosmic Background Explorer (CBE), NASA's cosmological satellite which will observe a radiative relic of the big bang, is discussed. The major questions connected to the big bang theory which may be clarified using the CBE are reviewed. The satellite instruments and experiments are described, including the Differential Microwave Radiometer, which measures the difference between microwave radiation emitted from two points on the sky, the Far-Infrared Absolute Spectrophotometer, which compares the spectrum of radiation from the sky at wavelengths from 100 microns to one cm with that from an internal blackbody, and the Diffuse Infrared Background Experiment, which searches for the radiation from the earliest generation of stars.

  14. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1991-01-01

    Recent limits on spectral distortions and angular anisotropies in the cosmic microwave background are reviewed. The various backgrounds are described, and the theoretical implications are assessed. Constraints on inflationary cosmology dominated by cold dark matter (CDM) and on open cosmological models dominated by baryonic dark matter (BDM), with, respectively, primordial random phase scale-invariant curvature fluctuations or non-gaussian isocurvature fluctuations are described. More exotic theories are addressed, and I conclude with the 'bottom line': what theorists expect experimentalists to be measuring within the next two to three years without having to abandon their most cherished theories.

  15. Mice from a genetically resistant background lacking the interferon gamma receptor are susceptible to infection with Leishmania major but mount a polarized T helper cell 1-type CD4+ T cell response

    PubMed Central

    1995-01-01

    Mice with homologous disruption of the gene coding for the ligand- binding chain of the interferon (IFN) gamma receptor and derived from a strain genetically resistant to infection with Leishmania major have been used to study further the role of this cytokine in the differentiation of functional CD4+ T cell subsets in vivo and resistance to infection. Wild-type 129/Sv/Ev mice are resistant to infection with this parasite, developing only small lesions, which resolve spontaneously within 6 wk. In contrast, mice lacking the IFN- gamma receptor develop large, progressing lesions. After infection, lymph nodes (LN) and spleens from both wild-type and knockout mice showed an expansion of CD4+ cells producing IFN-gamma as revealed by measuring IFN-gamma in supernatants of specifically stimulated CD4+ T cells, by enumerating IFN-gamma-producing T cells, and by Northern blot analysis of IFN-gamma transcripts. No biologically active interleukin (IL) 4 was detected in supernatants of in vitro-stimulated LN or spleen cells from infected wild-type or deficient mice. Reverse transcription polymerase chain reaction analysis with primers specific for IL-4 showed similar IL-4 message levels in LN from both types of mice. The IL-4 message levels observed were comparable to those found in similarly infected C57BL/6 mice and significantly lower than the levels found in BALB/c mice. Anti-IFN-gamma treatment of both types of mice failed to alter the pattern of cytokines produced after infection. These data show that even in the absence of IFN-gamma receptors, T helper cell (Th) 1-type responses still develop in genetically resistant mice with no evidence for the expansion of Th2 cells. PMID:7869054

  16. Improvements and new features in the PDF module

    NASA Technical Reports Server (NTRS)

    Norris, Andrew T.

    1995-01-01

    This viewgraph presentation discusses what models are used in this package and what their advantages and disadvantages are, how the probability density function (PDF) model is implemented and the features of the program, and what can be expected in the future from the NASA Lewis PDF code.

  17. Berkeley Low Background Facility

    SciTech Connect

    Thomas, K. J.; Norman, E. B.; Smith, A. R.; Poon, A. W. P.; Chan, Y. D.; Lesko, K. T.

    2015-08-17

    The Berkeley Low Background Facility (BLBF) at Lawrence Berkeley National Laboratory (LBNL) in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background laboratory on the surface at LBNL and at the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic/anthropogenic products; active screening via neutron activation analysis for U,Th, and K as well as a variety of stable isotopes; and neutron flux/beam characterization measurements through the use of monitors. A general overview of the facilities, services, and sensitivities will be presented. Recent activities and upgrades will also be described including an overview of the recently installed counting system at SURF (recently relocated from Oroville, CA in 2014), the installation of a second underground counting station at SURF in 2015, and future plans. The BLBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  18. Nonthermal cosmic neutrino background

    NASA Astrophysics Data System (ADS)

    Chen, Mu-Chun; Ratz, Michael; Trautner, Andreas

    2015-12-01

    We point out that, for Dirac neutrinos, in addition to the standard thermal cosmic neutrino background (C ν B ), there could also exist a nonthermal neutrino background with comparable number density. As the right-handed components are essentially decoupled from the thermal bath of standard model particles, relic neutrinos with a nonthermal distribution may exist until today. The relic density of the nonthermal (nt) background can be constrained by the usual observational bounds on the effective number of massless degrees of freedom Neff and can be as large as nν nt≲0.5 nγ. In particular, Neff can be larger than 3.046 in the absence of any exotic states. Nonthermal relic neutrinos constitute an irreducible contribution to the detection of the C ν B and, hence, may be discovered by future experiments such as PTOLEMY. We also present a scenario of chaotic inflation in which a nonthermal background can naturally be generated by inflationary preheating. The nonthermal relic neutrinos, thus, may constitute a novel window into the very early Universe.

  19. School Law: Background Checks.

    ERIC Educational Resources Information Center

    Splitt, David A.

    1988-01-01

    In an Oklahoma case, the district court ruled that the school district had failed to investigate the background of a teacher convicted of a second sexual abuse charge. School districts should examine personnel polices and practices, and the school lawyer should review state laws, regulations, and court cases. (MLF)

  20. Foregrounding the Background.

    ERIC Educational Resources Information Center

    Robbins, Bruce

    1998-01-01

    Argues that when introductory activities to the classics begin with background information, it can upstage or confine the life of the story, and shows little faith in the students as readers or in the literature itself. Suggests sometimes letting the literature begin, and then helping students make sense of it. Discusses examples from "To Kill a…

  1. China: Background Notes Series.

    ERIC Educational Resources Information Center

    Reams, Joanne Reppert

    Concise background information on the People's Republic of China is provided. The publication begins with a profile of the country, outlining the people, geography, economy, and membership in international organizations. The bulk of the document then discusses in more detail China's people, geography, history, government, education, economy, and…

  2. Thermal background noise limitations

    NASA Technical Reports Server (NTRS)

    Gulkis, S.

    1982-01-01

    Modern detection systems are increasingly limited in sensitivity by the background thermal photons which enter the receiving system. Expressions for the fluctuations of detected thermal radiation are derived. Incoherent and heterodyne detection processes are considered. References to the subject of photon detection statistics are given.

  3. Pdf prediction of supersonic hydrogen flames

    NASA Technical Reports Server (NTRS)

    Eifler, P.; Kollmann, W.

    1993-01-01

    A hybrid method for the prediction of supersonic turbulent flows with combustion is developed consisting of a second order closure for the velocity field and a multi-scalar pdf method for the local thermodynamic state. It is shown that for non-premixed flames and chemical equilibrium mixture fraction, the logarithm of the (dimensionless) density, internal energy per unit mass and the divergence of the velocity have several advantages over other sets of scalars. The closure model is applied to a supersonic non-premixed flame burning hydrogen with air supplied by a supersonic coflow and the results are compared with a limited set of experimental data.

  4. PDF4LHC recommendations for LHC Run II

    NASA Astrophysics Data System (ADS)

    Butterworth, Jon; Carrazza, Stefano; Cooper-Sarkar, Amanda; De Roeck, Albert; Feltesse, Joël; Forte, Stefano; Gao, Jun; Glazov, Sasha; Huston, Joey; Kassabov, Zahari; McNulty, Ronan; Morsch, Andreas; Nadolsky, Pavel; Radescu, Voica; Rojo, Juan; Thorne, Robert

    2016-02-01

    We provide an updated recommendation for the usage of sets of parton distribution functions (PDFs) and the assessment of PDF and PDF+{α }s uncertainties suitable for applications at the LHC Run II. We review developments since the previous PDF4LHC recommendation, and discuss and compare the new generation of PDFs, which include substantial information from experimental data from the Run I of the LHC. We then propose a new prescription for the combination of a suitable subset of the available PDF sets, which is presented in terms of a single combined PDF set. We finally discuss tools which allow for the delivery of this combined set in terms of optimized sets of Hessian eigenvectors or Monte Carlo replicas, and their usage, and provide some examples of their application to LHC phenomenology. This paper is dedicated to the memory of Guido Altarelli (1941-2015), whose seminal work made possible the quantitative study of PDFs.

  5. PDF4LHC recommendations for LHC Run II

    DOE PAGES

    Butterworth, Jon; Carrazza, Stefano; Cooper-Sarkar, Amanda; Roeck, Albert De; Feltesse, Joel; Forte, Stefano; Gao, Jun; Glazov, Sasha; Huston, Joey; Kassabov, Zahari; et al

    2016-01-06

    We provide an updated recommendation for the usage of sets of parton distribution functions (PDFs) and the assessment of PDF and PDF+αs uncertainties suitable for applications at the LHC Run II. We review developments since the previous PDF4LHC recommendation, and discuss and compare the new generation of PDFs, which include substantial information from experimental data from the Run I of the LHC. We then propose a new prescription for the combination of a suitable subset of the available PDF sets, which is presented in terms of a single combined PDF set. Lastly, we finally discuss tools which allow for themore » delivery of this combined set in terms of optimized sets of Hessian eigenvectors or Monte Carlo replicas, and their usage, and provide some examples of their application to LHC phenomenology.« less

  6. Diffuse UV Background Radiation

    NASA Astrophysics Data System (ADS)

    Conn Henry, Richard; Murthy, J.

    2012-01-01

    The diffuse UV sky is expected to glow with significant amounts of starlight that is scattered from the interstellar dust. The albedo and scattering pattern of the dust in the ultraviolet are both well established, and are both fairly independent of wavelength from 912 Å to 3000 Å. We present 1943 Voyager spectra of the diffuse cosmic background radiation from 500 Å to 1200 Å, and we compare their brightnesses, and their distribution on the sky, to those observed (Murthy et al., ApJ 724, 1389, 2010) from the GALEX mission at longer wavelengths (1530 Å). Significant differences appear, suggesting that background radiation components in addition to dust-scattered starlight may be present in both spectral regions.

  7. The cosmic microwave background

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1989-01-01

    Recent observational and theoretical investigations of the cosmic microwave background radiation (CMBR) are reviewed. Particular attention is given to spectral distortions and CMBR temperature anisotropies at large, intermediate, and small angular scales. The implications of the observations for inflationary cosmological models with curvature fluctuation are explored, and it is shown that the limits determined for intermediate-scale CMBR anisotropy almost rule out a baryon-dominated cosmology.

  8. Executive Summary: Background

    NASA Technical Reports Server (NTRS)

    1983-01-01

    Background information on, and the objectives of, the NASA Global Biology Research Program are given. The following issues were addressed: (1) geographic distribution of wetland parameters, (2) the processes of wetland material fluxes, and (3) the relation of local fluxes with global processes. Wetland inventorying and categorizing, gas-phase exchanges with the atmosphere, material exchange with the aquatic environment, and material storage in wetland sediments were identified as topics requiring further research.

  9. Time course of cytokine upregulation in the lacrimal gland and presence of autoantibodies in a predisposed mouse model of Sjögren's Syndrome: the influence of sex hormones and genetic background.

    PubMed

    Czerwinski, Stefanie; Mostafa, Safinaz; Rowan, Vanessa Seamon; Azzarolo, Ana Maria

    2014-11-01

    Sjögren's Syndrome (SS) is a chronic, inflammatory autoimmune disease characterized by lacrimal gland lymphocytic infiltration and epithelial cell death, as well as by the presence of serum autoantibodies. Although the symptoms of this syndrome are well characterized, patients are not diagnosed until 5-10 years into disease progression; furthermore, the early series of events leading to the initiation of SS are not well understood. In order to better understand the early events of the disease, we have been using ovariectomized (OVX) NOD.B10.H2(b) mice as a genetically predisposed model of SS. Previously, we have shown that removal of ovarian hormones through ovariectomy accelerated the symptoms of this disease, and in early events of SS in the lacrimal glands, lymphocytic infiltration preceded acinar cell apoptosis. To further elucidate the earlier events of this disease in the SS animal model, we investigated the expression and concentration of pro-inflammatory cytokines in the lacrimal glands as well as the presence of autoantibodies in both lacrimal glands and serum. Six weeks old NOD.B10.H2(b) and C57BL/10 control mice were either sham-operated, OVX, OVX and treated with 17β-estradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected at 3, 7, 21, and 30 days after surgery and analyzed for cytokines IL-1β, TNF-α, IFN-γ, IL-10, and IL-4 gene expression by using quantitative RT-PCR and for cytokine levels using ELISA. Furthermore, anti-Ro/SSA and anti-La/SSB autoantibodies were measured in the serum and lacrimal glands supernatants using ELISA. The results of this study showed that OVX caused a significant increase in the expression and levels of the cytokines IL-1β, TNF-α, and IL-4 in the lacrimal glands of the NOD.B10.H2(b) mice starting at 3 days after OVX, while a significant increase of IL-10 gene expression and levels was observed only at later experimental time points. A small but significant increase in the

  10. Time course of cytokine upregulation in the lacrimal gland and presence of autoantibodies in a predisposed mouse model of Sjögren’s Syndrome: the influence of sex hormones and genetic background

    PubMed Central

    Czerwinski, Stefanie; Mostafa, Safinaz; Rowan, Vanessa Seamon; Azzarolo, Ana Maria

    2014-01-01

    Sjögren’s Syndrome (SS) is a chronic, inflammatory autoimmune disease characterized by lacrimal gland lymphocytic infiltration and epithelial cell death, as well as by the presence of serum autoantibodies. Although the symptoms of this syndrome are well characterized, patients are not diagnosed until 5–10 years into disease progression; furthermore, the early series of events leading to the initiation of SS are not well understood. In order to better understand the early events of the disease, we have been using ovariectomized (OVX) NOD.B10.H2b mice as a genetically predisposed model of SS. Previously, we have shown that removal of ovarian hormones through ovariectomy accelerated the symptoms of this disease, and in early events of SS in the lacrimal glands, lymphocytic infiltration preceded acinar cell apoptosis. To further elucidate the earlier events of this disease in the SS animal model, we investigated the expression and concentration of pro-inflammatory cytokines in the lacrimal glands as well as the presence of autoantibodies in both lacrimal glands and serum. Six weeks old NOD.B10.H2b and C57BL/10 control mice were either sham-operated, OVX, OVX and treated with 17β-estradiol (E2), or OVX and treated with dihydrotestosterone (DHT). Lacrimal glands were collected at 3, 7, 21, and 30 days after surgery and analyzed for cytokines IL-1β, TNF-α, IFN-γ, IL-10, and IL-4 gene expression by using quantitative RT-PCR and for cytokine levels using ELISA. Furthermore, anti-Ro/SSA and anti-La/SSB autoantibodies were measured in the serum and lacrimal glands supernatants using ELISA. The results of this study showed that OVX caused a significant increase in the expression and levels of the cytokines IL-1β, TNF-α, and IL-4 in the lacrimal glands of the NOD.B10.H2b mice starting at 3 days after OVX, while a significant increase of IL-10 gene expression and levels was observed only at later experimental time points. A small but significant increase in the

  11. Background level care.

    PubMed

    Pitts, N B

    2009-01-01

    The framework enabled by the International Caries Detection and Assessment System to allow appropriate, patient-centred caries management includes a frequently encountered scenario in which a comprehensive assessment of the teeth and the patient reveals no lesions in need of active preventive or operative care. The issue addressed here is: what background care is appropriate for patients attending a dental practice for routine caries care who, at present, appear to have no active or progressing caries lesions? It is proposed that, in addition to the use of criteria for lesion extent, treatment planning systems should also express the results of lesion assessments in terms of background level care (BLC), preventive treatment options and operative treatment options. The specific treatment options recommended for specific lesions and patients will depend upon a variety of other factors, including lesion activity, monitoring lesion behaviour over time and a range of other prognostic factors. Over recent decades, there has been comparatively little focus on appropriate BLC in a general practice setting. There are a range of issues around the need to support caries prevention and health maintenance from a behavioural and patient-focussed perspective. Even if a patient is deemed to be at low risk of future caries at a particular examination, there is a need for maintenance care. Intrinsic issues which need to be managed for both patients and their caries lesions in this patient group are: (1) the possibility of a change in caries risk status and (2) the impact of incorrect lesion assessments/diagnoses.

  12. The Backgrounds Data Center

    NASA Technical Reports Server (NTRS)

    Snyder, W. A.; Gursky, H.; Heckathorn, H. M.; Lucke, R. L.; Berg, S. L.; Dombrowski, E. G.; Kessel, R. A.

    1993-01-01

    The Strategic Defense Initiative Organization has created data centers for midcourse, plumes, and backgrounds phenomenologies. The Backgrounds Data Center (BDC) has been designated as the prime archive for data collected by SDIO programs. The BDC maintains a Summary Catalog that contains 'metadata,' that is, information about data, such as when the data were obtained, what the spectral range of the data is, and what region of the Earth or sky was observed. Queries to this catalog result in a listing of all data sets (from all experiments in the Summary Catalog) that satisfy the specified criteria. Thus, the user can identify different experiments that made similar observations and order them from the BDC for analysis. On-site users can use the Science Analysis Facility (SAFE for this purpose. For some programs, the BDC maintains a Program Catalog, which can classify data in as many ways as desired (rather than just by position, time, and spectral range as in the Summary Catalog). For example, data sets could be tagged with such diverse parameters as solar illumination angle, signal level, or the value of a particular spectral ratio, as long as these quantities can be read from the digital record or calculated from it by the ingest program. All unclassified catalogs and unclassified data will be remotely accessible.

  13. Backgrounds Data Center

    NASA Astrophysics Data System (ADS)

    Snyder, William A.; Gursky, Herbert; Heckathorn, Harry M.; Lucke, Bob L.; Dorland, Bryan N.; Kessel, R. A.; Berg, S. L.; Dombrowski, E. G.

    1994-09-01

    The Backgrounds Data Center (BDC) is the designated archive for backgrounds data collected by Ballistic Missile Defense Organization (BMDO) programs, some of which include ultraviolet sensors. Currently, the BDC holds ultraviolet data from the IBSS, UVPI, UVLIM, and FUVCAM sensors. The BDC will also be the prime archive for Midcourse Space Experiment (MSX) data and is prepared to negotiate with program managers to handle other datasets. The purpose of the BDC is to make data accessible to users and to assist them in analyzing it. The BDC maintains the Science Catalog Information Exchange System (SCIES) allowing remote users to log in, read or post notices about current programs, search the catalogs for datasets of interest, and submit orders for data. On-site facilities are also available for the analysis of data, and consist of VMS and UNIX workstations with access to software analysis packages such as IDL, IRAF, and Khoros. Either on-site or remotely, users can employ the BDC-developed graphical user interface called the Visual Interface for Space and Terrestrial Analysis (VISTA) to generate catalog queries and to display and analyze data. SCIES and VISTA permit nearly complete access to BDC services and capabilities without the need to be physically present at the data center.

  14. Design and application of PDF model for extracting

    NASA Astrophysics Data System (ADS)

    Xiong, Lei

    2013-07-01

    In order to change the steps of contributions in editorial department system from two steps to one, this paper advocates that the technology of extracting the information of PDF files should be transplanted from PDF reader into IEEE Xplore contribution system and that it should be combined with uploading in batch skillfully to enable editors to upload PDF files about 1GB in batch for once. Computers will extract the information of the title, author, address, mailbox, abstract and key words of thesis voluntarily for later retrieval so as to save plenty of labor, material and finance for editorial department.

  15. PDF approach for turbulent scalar field: Some recent developments

    NASA Technical Reports Server (NTRS)

    Gao, Feng

    1993-01-01

    The probability density function (PDF) method has been proven a very useful approach in turbulence research. It has been particularly effective in simulating turbulent reacting flows and in studying some detailed statistical properties generated by a turbulent field There are, however, some important questions that have yet to be answered in PDF studies. Our efforts in the past year have been focused on two areas. First, a simple mixing model suitable for Monte Carlo simulations has been developed based on the mapping closure. Secondly, the mechanism of turbulent transport has been analyzed in order to understand the recently observed abnormal PDF's of turbulent temperature fields generated by linear heat sources.

  16. Genetics Home Reference: 22q11.2 duplication

    MedlinePlus

    ... Genetics Home Health Conditions 22q11.2 duplication 22q11.2 duplication Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description 22q11.2 duplication is a condition caused by an extra ...

  17. Genetics Home Reference: 16p11.2 duplication

    MedlinePlus

    ... Genetics Home Health Conditions 16p11.2 duplication 16p11.2 duplication Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description 16p11.2 duplication is a chromosomal change in which a ...

  18. Genetics Home Reference: 1q21.1 microduplication

    MedlinePlus

    ... Genetics Home Health Conditions 1q21.1 microduplication 1q21.1 microduplication Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description 1q21.1 microduplication is a chromosomal change in which a ...

  19. Genetics Home Reference: 9q22.3 microdeletion

    MedlinePlus

    ... Genetics Home Health Conditions 9q22.3 microdeletion 9q22.3 microdeletion Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description 9q22.3 microdeletion is a chromosomal change in which a ...

  20. Cosmic microwave background theory.

    PubMed

    Bond, J R

    1998-01-01

    A long-standing goal of theorists has been to constrain cosmological parameters that define the structure formation theory from cosmic microwave background (CMB) anisotropy experiments and large-scale structure (LSS) observations. The status and future promise of this enterprise is described. Current band-powers in -space are consistent with a DeltaT flat in frequency and broadly follow inflation-based expectations. That the levels are approximately (10(-5))2 provides strong support for the gravitational instability theory, while the Far Infrared Absolute Spectrophotometer (FIRAS) constraints on energy injection rule out cosmic explosions as a dominant source of LSS. Band-powers at 100 suggest that the universe could not have re-ionized too early. To get the LSS of Cosmic Background Explorer (COBE)-normalized fluctuations right provides encouraging support that the initial fluctuation spectrum was not far off the scale invariant form that inflation models prefer: e.g., for tilted Lambda cold dark matter sequences of fixed 13-Gyr age (with the Hubble constant H0 marginalized), ns = 1.17 +/- 0.3 for Differential Microwave Radiometer (DMR) only; 1.15 +/- 0.08 for DMR plus the SK95 experiment; 1.00 +/- 0.04 for DMR plus all smaller angle experiments; 1.00 +/- 0.05 when LSS constraints are included as well. The CMB alone currently gives weak constraints on Lambda and moderate constraints on Omegatot, but theoretical forecasts of future long duration balloon and satellite experiments are shown which predict percent-level accuracy among a large fraction of the 10+ parameters characterizing the cosmic structure formation theory, at least if it is an inflation variant.

  1. Ultraviolet Background Radiation

    NASA Astrophysics Data System (ADS)

    Henry, R. C.; Murthy, J.

    1993-12-01

    The UVX experiment was carried on the Space Shuttle Columbia between 1986 January 12 and 19 (STS-61C). Several ultraviolet spectrometers were used to obtain measurements of the diffuse ultraviolet background at 8 locations in the sky. We have reanalysed the UVX measurements of the surface brightness of the diffuse ultraviolet background above b = 40 using the dust-scattering model of Onaka & Kodaira (1991), which explicitly takes into account the variation of the source function with galactic longitude. The range of allowed values of interstellar grain albedoJa, and scattering asymmetry parameter g, is considerably expanded over those of a previous analysis. The new chi square probability contours come close to, but do not include, the values of a and g found for the interstellar grains by Witt et al. (1992) using the Ultraviolet Imaging Telescope (UIT) on the Astro mission. If we hypothesize in additon to the dust-scattered light an extragalactic component, of 300 1 100 photons cm-2 s-1 sr-1 A-1, attenuated by a cosecant b law, the new reduction of the UVX data gives complete consistency with the Witt et al. determination of the optical parameters of the grains in the ultraviolet. This work was supported by United States Air Force Contract F19628-93-K-0004, and by National Aeronautics and Space Administration grant NASA NAG5-619. We are grateful for the encouragement of Dr. Stephan Price, and we thank Dr. L. Danly for information. Onaka, T., & Kodaira, K. 1991, ApJ, 379, 532 Witt, A. N., Petersohn, J. K., Bohlin, R. C., O'Connell, R. W., Roberts, M. S., Smith, A. M., & Stecher, T. P. 1992, ApJ, 395, L5

  2. [Genetics and genetic counseling].

    PubMed

    Izzi, Claudia; Liut, Francesca; Dallera, Nadia; Mazza, Cinzia; Magistroni, Riccardo; Savoldi, Gianfranco; Scolari, Francesco

    2016-01-01

    Autosomal Dominant Polycystic Kidney Disease (ADPKD) is the most frequent genetic disease, characterized by progressive development of bilateral renal cysts. Two causative genes have been identified: PKD1 and PKD2. ADPKD phenotype is highly variable. Typically, ADPKD is an adult onset disease. However, occasionally, ADPKD manifests as very early onset disease. The phenotypic variability of ADPKD can be explained at three genetic levels: genic, allelic and gene modifier effects. Recent advances in molecular screening for PKD gene mutations and the introduction of the new next generation sequencing (NGS)- based genotyping approach have generated considerable improvement regarding the knowledge of genetic basis of ADPKD. The purpose of this article is to provide a comprehensive review of the genetics of ADPKD, focusing on new insights in genotype-phenotype correlation and exploring novel clinical approach to genetic testing. Evaluation of these new genetic information requires a multidisciplinary approach involving a nephrologist and a clinical geneticist. PMID:27067213

  3. Pressure algorithm for elliptic flow calculations with the PDF method

    NASA Technical Reports Server (NTRS)

    Anand, M. S.; Pope, S. B.; Mongia, H. C.

    1991-01-01

    An algorithm to determine the mean pressure field for elliptic flow calculations with the probability density function (PDF) method is developed and applied. The PDF method is a most promising approach for the computation of turbulent reacting flows. Previous computations of elliptic flows with the method were in conjunction with conventional finite volume based calculations that provided the mean pressure field. The algorithm developed and described here permits the mean pressure field to be determined within the PDF calculations. The PDF method incorporating the pressure algorithm is applied to the flow past a backward-facing step. The results are in good agreement with data for the reattachment length, mean velocities, and turbulence quantities including triple correlations.

  4. Multi-variate joint PDF for non-Gaussianities: exact formulation and generic approximations

    SciTech Connect

    Verde, Licia; Jimenez, Raul; Alvarez-Gaume, Luis; Heavens, Alan F.; Matarrese, Sabino E-mail: raul.jimenez@icc.ub.edu E-mail: a.heavens@imperial.ac.uk

    2013-06-01

    We provide an exact expression for the multi-variate joint probability distribution function of non-Gaussian fields primordially arising from local transformations of a Gaussian field. This kind of non-Gaussianity is generated in many models of inflation. We apply our expression to the non-Gaussianity estimation from Cosmic Microwave Background maps and the halo mass function where we obtain analytical expressions. We also provide analytic approximations and their range of validity. For the Cosmic Microwave Background we give a fast way to compute the PDF which is valid up to more than 7σ for f{sub NL} values (both true and sampled) not ruled out by current observations, which consists of expressing the PDF as a combination of bispectrum and trispectrum of the temperature maps. The resulting expression is valid for any kind of non-Gaussianity and is not limited to the local type. The above results may serve as the basis for a fully Bayesian analysis of the non-Gaussianity parameter.

  5. The cosmic background explorer

    SciTech Connect

    Gulkis, G. ); Lubin, P.M. ); Meyer, S.S. ); Silverberg, R.F.

    1990-01-01

    Late last year the National Aeronautics and Space Administration launched its first satellite dedicated to the study of phenomena related to the origins of the universe. The satellite, called the Cosmic Background Explorer (COBE), carries three complementary detectors that will make fundamental measurements of the celestial radiation. Part of that radiation is believed to have originated in processes that occurred at the very dawn of the universe. By measuring the remnant radiation at wavelengths from one micrometer to one centimeter across the entire sky, scientists hope to be able to solve many mysteries regarding the origin and evolution of the early universe. Unfortunately, these radiative relics of the early universe are weak and veiled by local astrophysical and terrestrial sources of radiation. The wavelengths of the various cosmic components may also overlap, thereby making the understanding of the diffuse celestial radiation a challenge. Nevertheless, the COBE instruments, with their full-sky coverage, high sensitivity to a wide range of wavelengths and freedom from interference from the earth's atmosphere, will constitute for astrophysicists an observatory of unprecedented sensitivity and scope. The interesting cosmic signals will then be separated from one another and from noncosmic radiation sources by a comprehensive analysis of the data.

  6. Biological aerosol background characterization

    NASA Astrophysics Data System (ADS)

    Blatny, Janet; Fountain, Augustus W., III

    2011-05-01

    To provide useful information during military operations, or as part of other security situations, a biological aerosol detector has to respond within seconds or minutes to an attack by virulent biological agents, and with low false alarms. Within this time frame, measuring virulence of a known microorganism is extremely difficult, especially if the microorganism is of unknown antigenic or nucleic acid properties. Measuring "live" characteristics of an organism directly is not generally an option, yet only viable organisms are potentially infectious. Fluorescence based instruments have been designed to optically determine if aerosol particles have viability characteristics. Still, such commercially available biological aerosol detection equipment needs to be improved for their use in military and civil applications. Air has an endogenous population of microorganisms that may interfere with alarm software technologies. To design robust algorithms, a comprehensive knowledge of the airborne biological background content is essential. For this reason, there is a need to study ambient live bacterial populations in as many locations as possible. Doing so will permit collection of data to define diverse biological characteristics that in turn can be used to fine tune alarm algorithms. To avoid false alarms, improving software technologies for biological detectors is a crucial feature requiring considerations of various parameters that can be applied to suppress alarm triggers. This NATO Task Group will aim for developing reference methods for monitoring biological aerosol characteristics to improve alarm algorithms for biological detection. Additionally, they will focus on developing reference standard methodology for monitoring biological aerosol characteristics to reduce false alarm rates.

  7. Background sources in optical communications

    NASA Technical Reports Server (NTRS)

    Vilnrotter, V. A.

    1983-01-01

    The characterization and measurement of background radiation relevant to optical communications system performance is addressed. The necessary optical receiver parameters are described, and radiometric concepts required for the calculation of collected background power are developed. The most important components of optical background power are discussed, and their contribution to the total collected background power in various communications scenarios is examined.

  8. Medical genetics

    SciTech Connect

    Nora, J.J.; Fraser, F.C.

    1989-01-01

    This book presents a discussion of medical genetics for the practitioner treating or counseling patients with genetic disease. It includes a discussion of the relationship of heredity and diseases, the chromosomal basis for heredity, gene frequencies, and genetics of development and maldevelopment. The authors also focus on teratology, somatic cell genetics, genetics and cancer, genetics of behavior.

  9. A computer simulated phantom study of tomotherapy dose optimization based on probability density functions (PDF) and potential errors caused by low reproducibility of PDF

    SciTech Connect

    Sheng, Ke; Cai Jing; Brookeman, James; Molloy, Janelle; Christopher, John; Read, Paul

    2006-09-15

    Lung tumor motion trajectories measured by four-dimensional CT or dynamic MRI can be converted to a probability density function (PDF), which describes the probability of the tumor at a certain position, for PDF based treatment planning. Using this method in simulated sequential tomotherapy, we study the dose reduction of normal tissues and more important, the effect of PDF reproducibility on the accuracy of dosimetry. For these purposes, realistic PDFs were obtained from two dynamic MRI scans of a healthy volunteer within a 2 week interval. The first PDF was accumulated from a 300 s scan and the second PDF was calculated from variable scan times from 5 s (one breathing cycle) to 300 s. Optimized beam fluences based on the second PDF were delivered to the hypothetical gross target volume (GTV) of a lung phantom that moved following the first PDF. The reproducibility between two PDFs varied from low (78%) to high (94.8%) when the second scan time increased from 5 s to 300 s. When a highly reproducible PDF was used in optimization, the dose coverage of GTV was maintained; phantom lung receiving 10%-20% prescription dose was reduced by 40%-50% and the mean phantom lung dose was reduced by 9.6%. However, optimization based on PDF with low reproducibility resulted in a 50% underdosed GTV. The dosimetric error increased nearly exponentially as the PDF error increased. Therefore, although the dose of the tumor surrounding tissue can be theoretically reduced by PDF based treatment planning, the reliability and applicability of this method highly depend on if a reproducible PDF exists and is measurable. By correlating the dosimetric error and PDF error together, a useful guideline for PDF data acquisition and patient qualification for PDF based planning can be derived.

  10. Cosmic microwave background images

    NASA Astrophysics Data System (ADS)

    Herranz, D.; Vielva, P.

    2010-01-01

    Cosmology concerns itself with the fundamental questions about the formation, structure, and evolution of the Universe as a whole. Cosmic microwave background (CMB) radiation is one of the foremost pillars of physical cosmology. Joint analyses of CMB and other astronomical observations are able to determine with ever increasing precision the value of the fundamental cosmological parameters and to provide us with valuable insight about the dynamics of the Universe in evolution. The CMB radiation is a relic of the hot and dense first moments of the Universe: a extraordinarily homogeneous and isotropic blackbody radiation, which shows small temperature anisotropies that are the key for understanding the conditions of the primitive Universe, testing cosmological models and probing fundamental physics at the very dawn of time. CMB observations are obtained by imaging of the sky at microwave wavelengths. However, the CMB signal is mixed with other astrophysical signals of both Galactic and extragalactic origin. To properly exploit the cosmological information contained in CMB images, they must be cleansed of these other astrophysical emissions first. Blind source separation (BSS) has been a very active field in the last few years. Conversely, the term "compact sources" is often used in the CMB literature referring to spatially bounded, small features in the images, such as galaxies and galaxy clusters. Compact sources and diffuse sources are usually treated separately in CMB image processing. We devote this tutorial to the case of compact sources. Many of the compact source-detection techniques that are widespread inmost fields of astronomy are not easily applicable to CMB images. In this tutorial, we present an overview of the fundamentals of compact object detection theory keeping in mind at every moment these particularities. Throughout the article, we briefly consider Bayesian object detection, model selection, optimal linear filtering, nonlinear filtering, and

  11. Extra dimensions: 3D in PDF documentation

    SciTech Connect

    Graf, Norman A.

    2011-01-11

    Experimental science is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universal 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide, non-technical audience. We discuss how the field of radiation imaging could benefit from incorporating full 3D information about not only the detectors, but also the results of the experimental analyses, in its electronic publications. In this article, we present examples drawn from high-energy physics, mathematics and molecular biology which take advantage of this functionality. Furthermore, we demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input.

  12. Extra dimensions: 3D in PDF documentation

    DOE PAGES

    Graf, Norman A.

    2011-01-11

    Experimental science is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universalmore » 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide, non-technical audience. We discuss how the field of radiation imaging could benefit from incorporating full 3D information about not only the detectors, but also the results of the experimental analyses, in its electronic publications. In this article, we present examples drawn from high-energy physics, mathematics and molecular biology which take advantage of this functionality. Furthermore, we demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input.« less

  13. The Drosophila neuropeptides PDF and sNPF have opposing electrophysiological and molecular effects on central neurons.

    PubMed

    Vecsey, Christopher G; Pírez, Nicolás; Griffith, Leslie C

    2014-03-01

    Neuropeptides have widespread effects on behavior, but how these molecules alter the activity of their target cells is poorly understood. We employed a new model system in Drosophila melanogaster to assess the electrophysiological and molecular effects of neuropeptides, recording in situ from larval motor neurons, which transgenically express a receptor of choice. We focused on two neuropeptides, pigment-dispersing factor (PDF) and small neuropeptide F (sNPF), which play important roles in sleep/rhythms and feeding/metabolism. PDF treatment depolarized motor neurons expressing the PDF receptor (PDFR), increasing excitability. sNPF treatment had the opposite effect, hyperpolarizing neurons expressing the sNPF receptor (sNPFR). Live optical imaging using a genetically encoded fluorescence resonance energy transfer (FRET)-based sensor for cyclic AMP (cAMP) showed that PDF induced a large increase in cAMP, whereas sNPF caused a small but significant decrease in cAMP. Coexpression of pertussis toxin or RNAi interference to disrupt the G-protein Gαo blocked the electrophysiological responses to sNPF, showing that sNPFR acts via Gαo signaling. Using a fluorescent sensor for intracellular calcium, we observed that sNPF-induced hyperpolarization blocked spontaneous waves of activity propagating along the ventral nerve cord, demonstrating that the electrical effects of sNPF can cause profound changes in natural network activity in the brain. This new model system provides a platform for mechanistic analysis of how neuropeptides can affect target cells at the electrical and molecular level, allowing for predictions of how they regulate brain circuits that control behaviors such as sleep and feeding.

  14. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  15. Beam induced backgrounds: CDF experience

    SciTech Connect

    Tesarek, R.J.; /Fermilab

    2008-05-01

    We summarize the experiences of the Collider Detector at Fermilab (CDF) experiment in the presence of backgrounds originating from the counter circulating beams in the Fermilab Tevatron. These backgrounds are measured and their sources identified. Finally, we outline the strategies employed to reduce the effects of these backgrounds on the experiment.

  16. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

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

  17. Background issues for defensive interceptors

    SciTech Connect

    Canavan, G.H.

    1991-03-01

    Mean nuclear backgrounds are large, but are arguably amenable to frame-to-frame subtraction. Striated backgrounds on the sensors for defensive interceptors could, however, cause clutter leak-through, which could make detection and track difficult. Nominal motions and backgrounds give signal to clutter ratios too low to be useful. Clutter leakage due to line-of-sight drift can be reduced by stabilizing the line of sight around the background clutter itself. Current interceptors have detector arrays large enough for operation independent of nuclear backgrounds in their fields of view. 6 refs., 2 figs.

  18. Automodel solutions for Lévy flight-based transport on a uniform background

    NASA Astrophysics Data System (ADS)

    Kukushkin, A. B.; Sdvizhenskii, P. A.

    2016-06-01

    A wide class of non-stationary superdiffusive transport on a uniform background with a power-law decay at large distances of the step-length probability distribution function (PDF) is shown to possess an approximate automodel solution. The solution for the Green’s function is constructed using the scaling laws for the propagation front (relevant-to-superdiffusion average displacement) and asymptotic solutions far beyond and far in advance of the propagation front. These scaling laws are determined essentially by the long-free-path carriers (Lévy flights). The validity of the suggested automodel solution is proved by its comparison with numerical solutions in the one-dimensional (1D) case of the transport equation with a simple long-tailed PDF with various power-law exponents and in the 3D case of the Biberman-Holstein equation of the resonance radiation transfer for various (Doppler, Lorentz, Voigt and Holtsmark) spectral line shapes.

  19. Galaxy clustering with photometric surveys using PDF redshift information

    NASA Astrophysics Data System (ADS)

    Asorey, J.; Carrasco Kind, M.; Sevilla-Noarbe, I.; Brunner, R. J.; Thaler, J.

    2016-06-01

    Photometric surveys produce large-area maps of the galaxy distribution, but with less accurate redshift information than is obtained from spectroscopic methods. Modern photometric redshift (photo-z) algorithms use galaxy magnitudes, or colours, that are obtained through multiband imaging to produce a probability density function (PDF) for each galaxy in the map. We used simulated data to study the effect of using different photo-z estimators to assign galaxies to redshift bins in order to compare their effects on angular clustering and galaxy bias measurements. We found that if we use the entire PDF, rather than a single-point (mean or mode) estimate, the deviations are less biased, especially when using narrow redshift bins. When the redshift bin widths are Δz = 0.1, the use of the entire PDF reduces the typical measurement bias from 5 per cent, when using single point estimates, to 3 per cent.

  20. Galaxy clustering with photometric surveys using PDF redshift information

    DOE PAGES

    Asorey, J.; Carrasco Kind, M.; Sevilla-Noarbe, I.; Brunner, R. J.; Thaler, J.

    2016-03-28

    Here, photometric surveys produce large-area maps of the galaxy distribution, but with less accurate redshift information than is obtained from spectroscopic methods. Modern photometric redshift (photo-z) algorithms use galaxy magnitudes, or colors, that are obtained through multi-band imaging to produce a probability density function (PDF) for each galaxy in the map. We used simulated data to study the effect of using different photo-z estimators to assign galaxies to redshift bins in order to compare their effects on angular clustering and galaxy bias measurements. We found that if we use the entire PDF, rather than a single-point (mean or mode) estimate, the deviations are less biased, especially when using narrow redshift bins. When the redshift bin widths aremore » $$\\Delta z=0.1$$, the use of the entire PDF reduces the typical measurement bias from 5%, when using single point estimates, to 3%.« less

  1. New Genetics

    MedlinePlus

    ... human genome, behavioral genetics, pharmacogenetics, drug resistance, biofilms, computer modeling. » more Chapter 5: 21st-Century Genetics Covers systems biology, GFP, genetic testing, privacy concerns, DNA forensics, ...

  2. Genetic Counseling

    MedlinePlus

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...

  3. Genetic Counseling

    MedlinePlus

    ... Articles Genetic Counseling Information For... Media Policy Makers Genetic Counseling Language: English Español (Spanish) Recommend on Facebook ... informed decisions about testing and treatment. Reasons for Genetic Counseling There are many reasons that people go ...

  4. Reference and PDF-manager software: complexities, support and workflow.

    PubMed

    Mead, Thomas L; Berryman, Donna R

    2010-10-01

    In the past, librarians taught reference management by training library users to use established software programs such as RefWorks or EndNote. In today's environment, there is a proliferation of Web-based programs that are being used by library clientele that offer a new twist on the well-known reference management programs. Basically, these new programs are PDF-manager software (e.g., Mendeley or Papers). Librarians are faced with new questions, issues, and concerns, given the new workflows and pathways that these PDF-manager programs present. This article takes a look at some of those.

  5. A study of hydrogen diffusion flames using PDF turbulence model

    NASA Technical Reports Server (NTRS)

    Hsu, Andrew T.

    1991-01-01

    The application of probability density function (pdf) turbulence models is addressed in this work. For the purpose of accurate prediction of turbulent combustion, an algorithm that combines a conventional CFD flow solver with the Monte Carlo simulation of the pdf evolution equation has been developed. The algorithm has been validated using experimental data for a heated turbulent plane jet. The study of H2-F2 diffusion flames has been carried out using this algorithm. Numerical results compared favorably with experimental data. The computuations show that the flame center shifts as the equivalence ratio changes, and that for the same equivalence ratio, similarity solutions for flames exist.

  6. A study of hydrogen diffusion flames using PDF turbulence model

    NASA Technical Reports Server (NTRS)

    Hsu, Andrew T.

    1991-01-01

    The application of probability density function (pdf) turbulence models is addressed. For the purpose of accurate prediction of turbulent combustion, an algorithm that combines a conventional computational fluid dynamic (CFD) flow solver with the Monte Carlo simulation of the pdf evolution equation was developed. The algorithm was validated using experimental data for a heated turbulent plane jet. The study of H2-F2 diffusion flames was carried out using this algorithm. Numerical results compared favorably with experimental data. The computations show that the flame center shifts as the equivalence ratio changes, and that for the same equivalence ratio, similarity solutions for flames exist.

  7. PDF methods for combustion in high-speed turbulent flows

    NASA Technical Reports Server (NTRS)

    Pope, Stephen B.

    1995-01-01

    This report describes the research performed during the second year of this three-year project. The ultimate objective of the project is extend the applicability of probability density function (pdf) methods from incompressible to compressible turbulent reactive flows. As described in subsequent sections, progress has been made on: (1) formulation and modelling of pdf equations for compressible turbulence, in both homogeneous and inhomogeneous inert flows; and (2) implementation of the compressible model in various flow configurations, namely decaying isotropic turbulence, homogeneous shear flow and plane mixing layer.

  8. [Genetic information and future medicine].

    PubMed

    Sakurai, Akihiro

    2012-11-01

    Rapid technological advances in genetic analysis have revealed the genetic 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, early diagnosis and management of at-risk family members can be made by identification of a genetic disease in the proband. On the other hand, genetic issues often cause psychological distress to the family. To perform genetic testing appropriately and to protect patients and family members from any harm, guidelines for genetic testing were released from the alliance of Japanese genetics-related academic societies in 2003. As genetic 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.

  9. Diffuse Cosmic Infrared Background Radiation

    NASA Technical Reports Server (NTRS)

    Dwek, Eli

    2002-01-01

    The diffuse cosmic infrared background (CIB) consists of the cumulative radiant energy released in the processes of structure formation that have occurred since the decoupling of matter and radiation following the Big Bang. In this lecture I will review the observational data that provided the first detections and limits on the CIB, and the theoretical studies explaining the origin of this background. Finally, I will also discuss the relevance of this background to the universe as seen in high energy gamma-rays.

  10. Genetic predisposition, non-genetic risk factors and coronary infarct

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Using a genetic predisposition score (GPS), additively integrating the associations of 11 polymorphisms with coronary heart disease (CHD), we examined the consequences of joint presence of high GPS and non-genetic CHD risk factors. Methods: Within the European Prospective Investigation i...

  11. Background Reduction in Cryogenic Detectors

    SciTech Connect

    Bauer, Daniel A.

    2005-09-08

    This paper discusses the background reduction and rejection strategy of the Cryogenic Dark Matter Search (CDMS) experiment. Recent measurements of background levels from CDMS II at Soudan are presented, along with estimates for future improvements in sensitivity expected for a proposed SuperCDMS experiment at SNOLAB.

  12. Lattice QCD in Background Fields

    SciTech Connect

    William Detmold, Brian Tiburzi, Andre Walker-Loud

    2009-06-01

    Electromagnetic properties of hadrons can be computed by lattice simulations of QCD in background fields. We demonstrate new techniques for the investigation of charged hadron properties in electric fields. Our current calculations employ large electric fields, motivating us to analyze chiral dynamics in strong QED backgrounds, and subsequently uncover surprising non-perturbative effects present at finite volume.

  13. Background reduction in cryogenic detectors

    SciTech Connect

    Bauer, Daniel A.; /Fermilab

    2005-04-01

    This paper discusses the background reduction and rejection strategy of the Cryogenic Dark Matter Search (CDMS) experiment. Recent measurements of background levels from CDMS II at Soudan are presented, along with estimates for future improvements in sensitivity expected for a proposed SuperCDMS experiment at SNOLAB.

  14. Background Television and Reading Performance.

    ERIC Educational Resources Information Center

    Armstrong, G. Blake; And Others

    1991-01-01

    Tests G. Armstrong's and B. Greenberg's model of the effect of background television on cognitive performance, applied to reading comprehension and memory. Finds significant deleterious effects of background television, stronger and more consistent effects when testing immediately after reading, and more consistently negative effects resulting…

  15. Progress in the development of PDF turbulence models for combustion

    NASA Technical Reports Server (NTRS)

    Hsu, Andrew T.

    1991-01-01

    A combined Monte Carlo-computational fluid dynamic (CFD) algorithm was developed recently at Lewis Research Center (LeRC) for turbulent reacting flows. In this algorithm, conventional CFD schemes are employed to obtain the velocity field and other velocity related turbulent quantities, and a Monte Carlo scheme is used to solve the evolution equation for the probability density function (pdf) of species mass fraction and temperature. In combustion computations, the predictions of chemical reaction rates (the source terms in the species conservation equation) are poor if conventional turbulence modles are used. The main difficulty lies in the fact that the reaction rate is highly nonlinear, and the use of averaged temperature produces excessively large errors. Moment closure models for the source terms have attained only limited success. The probability density function (pdf) method seems to be the only alternative at the present time that uses local instantaneous values of the temperature, density, etc., in predicting chemical reaction rates, and thus may be the only viable approach for more accurate turbulent combustion calculations. Assumed pdf's are useful in simple problems; however, for more general combustion problems, the solution of an evolution equation for the pdf is necessary.

  16. Low background counting at the LBNL low background facility

    SciTech Connect

    Thomas, K. J.; Norman, E. B.; Smith, A. R.; Chan, Y. D.; Hurley, D. L.; Wang, B. S.

    2013-08-08

    The Low Background Facility (LBF) at the Lawrence Berkeley National Laboratory (LBNL) in Berkeley, California provides low background gamma spectroscopy services to end-users in two unique facilities: locally within a carefully-constructed, low background laboratory space; and a satellite underground station (600 m.w.e) in Oroville, CA. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic and anthropogenic products, as well as active screening via neutron activation analysis for specific applications. A general overview of the facilities, services, and capabilities will be discussed. Recent activities will also be presented, including the recent installation of a 3π muon veto at the surface facility, cosmogenic activation studies of TeO{sub 2} for CUORE, and environmental monitoring of Fukushima fallout.

  17. Non-Gaussianity in the Cosmic Microwave Background temperature fluctuations from cosmic (super-)strings

    SciTech Connect

    Takahashi, Keitaro; Naruko, Atsushi; Sendouda, Yuuiti; Yamauchi, Daisuke; Sasaki, Misao; Yoo, Chul-Moon E-mail: naruko@yukawa.kyoto-u.ac.jp E-mail: yamauchi@yukawa.kyoto-u.ac.jp E-mail: misao@yukawa.kyoto-u.ac.jp

    2009-10-01

    We compute analytically the small-scale temperature fluctuations of the cosmic microwave background from cosmic (super-)strings and study the dependence on the string intercommuting probability P. We develop an analytical model which describes the evolution of a string network and calculate the numbers of string segments and kinks in a horizon volume. Then we derive the probability distribution function (pdf) which takes account of finite angular resolution of observation. The resultant pdf consists of a Gaussian part due to frequent scatterings by long string segments and a non-Gaussian tail due to close encounters with kinks. The dispersion of the Gaussian part is reasonably consistent with that obtained by numerical simulations by Fraisse et al.. On the other hand, the non-Gaussian tail contains two phenomenological parameters which are determined by comparison with the numerical results for P = 1. Extrapolating the pdf to the cases with P < 1, we predict that the non-Gaussian feature is suppressed for small P.

  18. Genetic background, gender, age, body temperature, and arterial blood pH have a major impact on myocardial infarct size in the mouse and need to be carefully measured and/or taken into account: results of a comprehensive analysis of determinants of infarct size in 1,074 mice.

    PubMed

    Guo, Yiru; Flaherty, Michael P; Wu, Wen-Jian; Tan, Wei; Zhu, Xiaoping; Li, Qianhong; Bolli, Roberto

    2012-09-01

    In order to determine whether the myocardial response to ischemia/reperfusion (I/R) injury varies depending on genetic background, gender, age, body temperature, and arterial blood pH, we studied 1,074 mice from 19 strains (including 129S6/SvEvTac (129S6), B6/129P2-Ptgs2(tm1Unc), B6/129SvF(2)/J, B6/129/D2, B6/CBAF1, B6/DBA/1JNcr, BALB/c, BPH2/J, C57BL/6/J (B6/J), C3H/DBA, C3H/FB/FF, C3H/HeJ-Pde6b(rd1), FVB/N/J [FVB/N], FVB/B6, FVB/ICR and Crl:ICR/H [ICR]) and distributed them into 69 groups depending on strain and: (1) two phases of ischemic preconditioning (PC); (2) coronary artery occlusion (O) time; (3) gender; (4) age; (5) blood transfusion; (6) core body temperature; and (7) arterial blood pH. Mice underwent O either without (non-preconditioned [naive]) or with prior cyclic O/reperfusion (R) (PC stimulus) consisting of six 4-min O/4-min R cycles 10 min (early PC, EPC) or 24 h (late PC, LPC) prior to 30 or 45-min O and 24 h R. In B6/J and B6/129/D2 mice, almost the entire risk region was infarcted after a 60-min O. Of the naive mouse hearts, B6/ecSOD(WT) and FVB/N mice had infarct sizes significantly smaller than those of the other mice. All strains except FVB/N benefited from the cardioprotection afforded by the early phase of PC; in contrast, development of LPC was inconsistent amongst groups and was strain-dependent. Female gender (1) was associated with reduced infarct size in ICR mice, (2) determined whether LPC developed in ICR mice, and (3) limited the protection afforded by EPC in 129S6 mice. Importantly, mild hypothermia (1 °C decrease in core temperature) and mild acidosis (0.18 decrease in blood pH) resulted in a striking cardioprotective effect in ICR mice: 67.5 and 43.0 % decrease in infarct size, respectively. Replacing blood losses with crystalloid fluids (instead of blood) during surgery also reduced infarct size. To our knowledge, this is the largest analysis of the determinants of infarct size in mice ever published. The results

  19. Low background techniques in XMASS

    SciTech Connect

    Takeda, Atsushi

    2011-04-27

    The XMASS project aims to detect pp and {sup 7}Be solar neutrinos, neutrino-less double beta decay, and dark matter searches using ultra-pure liquid xenon. The first stage of XMASS project is concentrated on dark matter searches using 800 kg liquid xenon detector which requires low background and low threshold. Several techniques applied to XMASS detector for low background will be presented.

  20. Low Background Counting at LBNL

    DOE PAGES

    Smith, A. R.; Thomas, K. J.; Norman, E. B.; Chan, Y. D.; Lesko, K. T.; Hurley, D. L.

    2015-03-24

    The Low Background Facility (LBF) at Lawrence Berkeley National Laboratory in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background cave and remotely at an underground location that historically has operated underground in Oroville, CA, but has recently been relocated to the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K)more » or common cosmogenic/anthropogenic products, as well as active screening via Neutron Activation Analysis for specific applications. The LBF also provides hosting services for general R&D testing in low background environments on the surface or underground for background testing of detector systems or similar prototyping. A general overview of the facilities, services, and sensitivities is presented. Recent activities and upgrades will also be presented, such as the completion of a 3π anticoincidence shield at the surface station and environmental monitoring of Fukushima fallout. The LBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.« less

  1. Low Background Counting at LBNL

    SciTech Connect

    Smith, A. R.; Thomas, K. J.; Norman, E. B.; Chan, Y. D.; Lesko, K. T.; Hurley, D. L.

    2015-03-24

    The Low Background Facility (LBF) at Lawrence Berkeley National Laboratory in Berkeley, California provides low background gamma spectroscopy services to a wide array of experiments and projects. The analysis of samples takes place within two unique facilities; locally within a carefully-constructed, low background cave and remotely at an underground location that historically has operated underground in Oroville, CA, but has recently been relocated to the Sanford Underground Research Facility (SURF) in Lead, SD. These facilities provide a variety of gamma spectroscopy services to low background experiments primarily in the form of passive material screening for primordial radioisotopes (U, Th, K) or common cosmogenic/anthropogenic products, as well as active screening via Neutron Activation Analysis for specific applications. The LBF also provides hosting services for general R&D testing in low background environments on the surface or underground for background testing of detector systems or similar prototyping. A general overview of the facilities, services, and sensitivities is presented. Recent activities and upgrades will also be presented, such as the completion of a 3π anticoincidence shield at the surface station and environmental monitoring of Fukushima fallout. The LBF is open to any users for counting services or collaboration on a wide variety of experiments and projects.

  2. Evaluation of the reproducibility of lung motion probability distribution function (PDF) using dynamic MRI

    NASA Astrophysics Data System (ADS)

    Cai, Jing; Read, Paul W.; Altes, Talissa A.; Molloy, Janelle A.; Brookeman, James R.; Sheng, Ke

    2007-01-01

    Treatment planning based on probability distribution function (PDF) of patient geometries has been shown a potential off-line strategy to incorporate organ motion, but the application of such approach highly depends upon the reproducibility of the PDF. In this paper, we investigated the dependences of the PDF reproducibility on the imaging acquisition parameters, specifically the scan time and the frame rate. Three healthy subjects underwent a continuous 5 min magnetic resonance (MR) scan in the sagittal plane with a frame rate of approximately 10 f s-1, and the experiments were repeated with an interval of 2 to 3 weeks. A total of nine pulmonary vessels from different lung regions (upper, middle and lower) were tracked and the dependences of their displacement PDF reproducibility were evaluated as a function of scan time and frame rate. As results, the PDF reproducibility error decreased with prolonged scans and appeared to approach equilibrium state in subjects 2 and 3 within the 5 min scan. The PDF accuracy increased in the power function with the increase of frame rate; however, the PDF reproducibility showed less sensitivity to frame rate presumably due to the randomness of breathing which dominates the effects. As the key component of the PDF-based treatment planning, the reproducibility of the PDF affects the dosimetric accuracy substantially. This study provides a reference for acquiring MR-based PDF of structures in the lung.

  3. Genetic Mapping

    MedlinePlus

    ... Genetic Education Resources for Teachers Genomic Careers National DNA Day Online Education Kit Online Genetics Education Resources ... prevalent. Using various laboratory techniques, the scientists isolate DNA from these samples and examine it for unique ...

  4. Genetic Disorders

    MedlinePlus

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  5. Genetic modification and genetic determinism

    PubMed Central

    Resnik, David B; Vorhaus, Daniel B

    2006-01-01

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions. PMID:16800884

  6. Low Background Micromegas in CAST

    NASA Astrophysics Data System (ADS)

    Garza, J. G.; Aune, S.; Aznar, F.; Calvet, D.; Castel, J. F.; Christensen, F. E.; Dafni, T.; Davenport, M.; Decker, T.; Ferrer-Ribas, E.; Galán, J.; García, J. A.; Giomataris, I.; Hill, R. M.; Iguaz, F. J.; Irastorza, I. G.; Jakobsen, A. C.; Jourde, D.; Mirallas, H.; Ortega, I.; Papaevangelou, T.; Pivovaroff, M. J.; Ruz, J.; Tomás, A.; Vafeiadis, T.; Vogel, J. K.

    2015-11-01

    Solar axions could be converted into x-rays inside the strong magnetic field of an axion helioscope, triggering the detection of this elusive particle. Low background x-ray detectors are an essential component for the sensitivity of these searches. We report on the latest developments of the Micromegas detectors for the CERN Axion Solar Telescope (CAST), including technological pathfinder activities for the future International Axion Observatory (IAXO). The use of low background techniques and the application of discrimination algorithms based on the high granularity of the readout have led to background levels below 10-6 counts/keV/cm2/s, more than a factor 100 lower than the first generation of Micromegas detectors. The best levels achieved at the Canfranc Underground Laboratory (LSC) are as low as 10-7 counts/keV/cm2/s, showing good prospects for the application of this technology in IAXO. The current background model, based on underground and surface measurements, is presented, as well as the strategies to further reduce the background level. Finally, we will describe the R&D paths to achieve sub-keV energy thresholds, which could broaden the physics case of axion helioscopes.

  7. Genetic principles.

    PubMed

    Abuelo, D

    1987-01-01

    The author discusses the basic principles of genetics, including the classification of genetic disorders and a consideration of the rules and mechanisms of inheritance. The most common pitfalls in clinical genetic diagnosis are described, with emphasis on the problem of the negative or misleading family history.

  8. Imaging Genetics

    ERIC Educational Resources Information Center

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  9. Genetic Testing

    MedlinePlus

    ... genetic tests for several reasons. These include Finding genetic diseases in unborn babies Finding out if people carry a gene for a disease and might pass it on to their children Screening embryos for disease Testing for genetic diseases in adults before they cause ...

  10. Background simulations and shielding calculations

    SciTech Connect

    Kudryavtsev, Vitaly A.

    2011-04-27

    Key improvements in the sensitivity of the underground particle astrophysics experiments can only be achieved if the radiation causing background events in detectors is well understood and proper measures are taken to suppress it. The background radiation arising from radioactivity and cosmic-ray muons is discussed here together with the methods of its suppression. Different shielding designs are considered to attenuate gamma-rays and neutrons coming from radioactivity in rock and lab walls. Purity of materials used in detector construction is analysed and the background event rates due to the presence of radioactive isotopes in detector components are discussed. Event rates in detectors caused by muon-induced neutrons with and without active veto systems are presented leading to the requirements for the depth of an underground laboratory and the efficiency of the veto system.

  11. Generative electronic background music system

    SciTech Connect

    Mazurowski, Lukasz

    2015-03-10

    In this short paper-extended abstract the new approach to generation of electronic background music has been presented. The Generative Electronic Background Music System (GEBMS) has been located between other related approaches within the musical algorithm positioning framework proposed by Woller et al. The music composition process is performed by a number of mini-models parameterized by further described properties. The mini-models generate fragments of musical patterns used in output composition. Musical pattern and output generation are controlled by container for the mini-models - a host-model. General mechanism has been presented including the example of the synthesized output compositions.

  12. The cosmic microwave background radiation

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1992-01-01

    A review the implications of the spectrum and anisotropy of the cosmic microwave background for cosmology. Thermalization and processes generating spectral distortions are discussed. Anisotropy predictions are described and compared with observational constraints. If the evidence for large-scale power in the galaxy distribution in excess of that predicted by the cold dark matter model is vindicated, and the observed structure originated via gravitational instabilities of primordial density fluctuations, the predicted amplitude of microwave background anisotropies on angular scales of a degree and larger must be at least several parts in 10 exp 6.

  13. Exotic branes and nongeometric backgrounds.

    PubMed

    de Boer, Jan; Shigemori, Masaki

    2010-06-25

    When string or M theory is compactified to lower dimensions, the U-duality symmetry predicts so-called exotic branes whose higher-dimensional origin cannot be explained by the standard string or M-theory branes. We argue that exotic branes can be understood in higher dimensions as nongeometric backgrounds or U folds, and that they are important for the physics of systems which originally contain no exotic charges, since the supertube effect generically produces such exotic charges. We discuss the implications of exotic backgrounds for black hole microstate (non-)geometries. PMID:20867363

  14. Reflowing-driven paragraph recognition for electronic books in PDF

    NASA Astrophysics Data System (ADS)

    Fang, Jing; Tang, Zhi; Gao, Liangcai

    2011-01-01

    When reading electronic books on handheld devices, content sometimes should be reflowed and recomposed to adapt for small-screen mobile devices. According to people's reading practice, it is reasonable to reflow the text content based on paragraphs. Hence, this paper addresses the requirement and proposes a set of novel methods on paragraph recognition for electronic books in PDF. The proposed methods consist of three steps, namely, physical structure analysis, paragraph segmentation, and reading order detection. We make use of locally ordered property of PDF documents and layout style of books to improve traditional page recognition results. In addition, we employ the optimal matching of Bipartite Graph technology to detect paragraphs' reading order. Experiments show that our methods achieve high accuracy. It is noteworthy that, the research has been applied in a commercial software package for Chinese E-book production.

  15. PDF Lecture Materials for Online and ``Flipped'' Format Astronomy Courses

    NASA Astrophysics Data System (ADS)

    Kary, D. M.; Eisberg, J.

    2013-04-01

    Online astronomy courses typically rely on students reading the textbook and/or a set of text-based lecture notes to replace the “lecture” material. However, many of our students report that this is much less engaging than in-person lectures, especially given the amount of interactive work such as “think-pair-share” problems done in many astronomy classes. Students have similarly criticized direct lecture-capture. To address this, we have developed a set of PowerPoint-style presentations with embedded lecture audio combined with prompts for student interaction including think-pair-share questions. These are formatted PDF packages that can be used on a range of different computers using free software. The presentations are first developed using Microsoft PowerPoint software. Audio recordings of scripted lectures are then synchronized with the presentations and the entire package is converted to PDF using Adobe Presenter. This approach combines the ease of editing that PowerPoint provides along with the platform-independence of PDF. It's easy to add, remove, or edit individual slides as needed, and PowerPoint supports internal links so that think-pair-share questions can be inserted with links to feedback based on the answers selected. Modern PDF files support animated visuals with synchronized audio and they can be read using widely available free software. Using these files students in an online course can get many of the benefits of seeing and hearing the course material presented in an in-person lecture format. Students needing extra help in traditional lecture classes can use these presentations to help review the materials covered in lecture. Finally, the presentations can be used in a “flipped” format in which students work through the presentations outside of class time while spending the “lecture” time on in-class interaction.

  16. Chemically reacting supersonic flow calculation using an assumed PDF model

    NASA Technical Reports Server (NTRS)

    Farshchi, M.

    1990-01-01

    This work is motivated by the need to develop accurate models for chemically reacting compressible turbulent flow fields that are present in a typical supersonic combustion ramjet (SCRAMJET) engine. In this paper the development of a new assumed probability density function (PDF) reaction model for supersonic turbulent diffusion flames and its implementation into an efficient Navier-Stokes solver are discussed. The application of this model to a supersonic hydrogen-air flame will be considered.

  17. Obtaining genetic testing in pediatric epilepsy.

    PubMed

    Ream, Margie A; Patel, Anup D

    2015-10-01

    The steps from patient evaluation to genetic diagnosis remain complicated. We discuss some of the genetic testing methods available along with their general advantages and disadvantages. We briefly review common pediatric epilepsy syndromes with strong genetic association and provide a potentially useful algorithm for genetic testing in drug-resistant epilepsy. We performed an extensive literature review of available information as it pertains to genetic testing and genetics in pediatric epilepsy. If a genetic disorder is suspected as the cause of epilepsy, based on drug resistance, family history, or clinical phenotype, timely diagnosis may reduce overall cost, limit the diagnostic odyssey that can bring much anxiety to families, improve prognostic accuracy, and lead to targeted therapy. Interpretation of complicated results should be performed only in collaboration with geneticists and genetic counselors, unless the ordering neurologist has a strong background in and understanding of genetics. Genetic testing can play an important role in the care provided to patients with epilepsy.

  18. Finite rate chemistry and presumed PDF models for premixed turbulent combustion

    SciTech Connect

    Bray, K.N.C.; Swaminathan, N.; Champion, M.; Libby, P.A.

    2006-09-15

    The sensitivity of the prediction of mean reaction rates in turbulent premixed flames to presumed PDF shape is studied. Three different presumed PDF shapes are considered: (i) a beta function PDF, (ii) a twin delta function PDF, and (iii) a PDF based on unstrained laminar flame properties. The unstrained laminar flame has the same thermochemistry as the turbulent flame. Emphasis is placed on capturing the finite rate chemistry effects and obtaining a simple expression for the mean reaction rate. It is shown that, as the PDFs approach their bimodal limit, the mean reaction rate expressions obtained using the above three PDFs reduce to a common form. These expressions differ only in the numerical value of a multiplying factor. Predictions are compared with DNS data. Under the conditions of this comparison, the beta function and twin delta function PDFs lead to significant errors, while the PDF based on properties of an unstrained laminar flame gives good agreement with the DNS. (author)

  19. A time dependent mixing model to close PDF equations for transport in heterogeneous aquifers

    NASA Astrophysics Data System (ADS)

    Schüler, L.; Suciu, N.; Knabner, P.; Attinger, S.

    2016-10-01

    Probability density function (PDF) methods are a promising alternative to predicting the transport of solutes in groundwater under uncertainty. They make it possible to derive the evolution equations of the mean concentration and the concentration variance, used in moment methods. The mixing model, describing the transport of the PDF in concentration space, is essential for both methods. Finding a satisfactory mixing model is still an open question and due to the rather elaborate PDF methods, a difficult undertaking. Both the PDF equation and the concentration variance equation depend on the same mixing model. This connection is used to find and test an improved mixing model for the much easier to handle concentration variance. Subsequently, this mixing model is transferred to the PDF equation and tested. The newly proposed mixing model yields significantly improved results for both variance modelling and PDF modelling.

  20. Extraction and labeling high-resolution images from PDF documents

    NASA Astrophysics Data System (ADS)

    Chachra, Suchet K.; Xue, Zhiyun; Antani, Sameer; Demner-Fushman, Dina; Thoma, George R.

    2013-12-01

    Accuracy of content-based image retrieval is affected by image resolution among other factors. Higher resolution images enable extraction of image features that more accurately represent the image content. In order to improve the relevance of search results for our biomedical image search engine, Open-I, we have developed techniques to extract and label high-resolution versions of figures from biomedical articles supplied in the PDF format. Open-I uses the open-access subset of biomedical articles from the PubMed Central repository hosted by the National Library of Medicine. Articles are available in XML and in publisher supplied PDF formats. As these PDF documents contain little or no meta-data to identify the embedded images, the task includes labeling images according to their figure number in the article after they have been successfully extracted. For this purpose we use the labeled small size images provided with the XML web version of the article. This paper describes the image extraction process and two alternative approaches to perform image labeling that measure the similarity between two images based upon the image intensity projection on the coordinate axes and similarity based upon the normalized cross-correlation between the intensities of two images. Using image identification based on image intensity projection, we were able to achieve a precision of 92.84% and a recall of 82.18% in labeling of the extracted images.

  1. Extra Dimensions: 3D and Time in PDF Documentation

    SciTech Connect

    Graf, Norman A.; /SLAC

    2011-11-10

    High energy physics is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universal 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide audience. In this talk, we present examples of HEP applications which take advantage of this functionality. We demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input. Using this technique, higher dimensional data, such as LEGO plots or time-dependent information can be included in PDF files. In principle, a complete event display, with full interactivity, can be incorporated into a PDF file. This would allow the end user not only to customize the view and representation of the data, but to access the underlying data itself.

  2. Graph-based layout analysis for PDF documents

    NASA Astrophysics Data System (ADS)

    Xu, Canhui; Tang, Zhi; Tao, Xin; Li, Yun; Shi, Cao

    2013-03-01

    To increase the flexibility and enrich the reading experience of e-book on small portable screens, a graph based method is proposed to perform layout analysis on Portable Document Format (PDF) documents. Digital born document has its inherent advantages like representing texts and fractional images in explicit form, which can be straightforwardly exploited. To integrate traditional image-based document analysis and the inherent meta-data provided by PDF parser, the page primitives including text, image and path elements are processed to produce text and non text layer for respective analysis. Graph-based method is developed in superpixel representation level, and page text elements corresponding to vertices are used to construct an undirected graph. Euclidean distance between adjacent vertices is applied in a top-down manner to cut the graph tree formed by Kruskal's algorithm. And edge orientation is then used in a bottom-up manner to extract text lines from each sub tree. On the other hand, non-textual objects are segmented by connected component analysis. For each segmented text and non-text composite, a 13-dimensional feature vector is extracted for labelling purpose. The experimental results on selected pages from PDF books are presented.

  3. The study of PDF turbulence models in combustion

    NASA Technical Reports Server (NTRS)

    Hsu, Andrew T.

    1991-01-01

    In combustion computations, it is known that the predictions of chemical reaction rates are poor if conventional turbulence models are used. The probability density function (pdf) method seems to be the only alternative that uses local instantaneous values of the temperature, density, etc., in predicting chemical reaction rates, and thus is the only viable approach for more accurate turbulent combustion calculations. The fact that the pdf equation has a very large dimensionality renders finite difference schemes extremely demanding on computer memories and thus impractical. A logical alternative is the Monte Carlo scheme. Since CFD has a certain maturity as well as acceptance, it seems that the use of a combined CFD and Monte Carlo scheme is more beneficial. Therefore, a scheme is chosen that uses a conventional CFD flow solver in calculating the flow field properties such as velocity, pressure, etc., while the chemical reaction part is solved using a Monte Carlo scheme. The discharge of a heated turbulent plane jet into quiescent air was studied. Experimental data for this problem shows that when the temperature difference between the jet and the surrounding air is small, buoyancy effect can be neglected and the temperature can be treated as a passive scalar. The fact that jet flows have a self-similar solution lends convenience in the modeling study. Futhermore, the existence of experimental data for turbulent shear stress and temperature variance make the case ideal for the testing of pdf models wherein these values can be directly evaluated.

  4. Sparse PDF Volumes for Consistent Multi-Resolution Volume Rendering

    PubMed Central

    Sicat, Ronell; Krüger, Jens; Möller, Torsten; Hadwiger, Markus

    2015-01-01

    This paper presents a new multi-resolution volume representation called sparse pdf volumes, which enables consistent multi-resolution volume rendering based on probability density functions (pdfs) of voxel neighborhoods. These pdfs are defined in the 4D domain jointly comprising the 3D volume and its 1D intensity range. Crucially, the computation of sparse pdf volumes exploits data coherence in 4D, resulting in a sparse representation with surprisingly low storage requirements. At run time, we dynamically apply transfer functions to the pdfs using simple and fast convolutions. Whereas standard low-pass filtering and down-sampling incur visible differences between resolution levels, the use of pdfs facilitates consistent results independent of the resolution level used. We describe the efficient out-of-core computation of large-scale sparse pdf volumes, using a novel iterative simplification procedure of a mixture of 4D Gaussians. Finally, our data structure is optimized to facilitate interactive multi-resolution volume rendering on GPUs. PMID:26146475

  5. APFEL: A PDF evolution library with QED corrections

    NASA Astrophysics Data System (ADS)

    Bertone, Valerio; Carrazza, Stefano; Rojo, Juan

    2014-06-01

    Quantum electrodynamics and electroweak corrections are important ingredients for many theoretical predictions at the LHC. This paper documents APFEL, a new PDF evolution package that allows for the first time to perform DGLAP evolution up to NNLO in QCD and to LO in QED, in the variable-flavor-number scheme and with either pole or MS bar heavy quark masses. APFEL consistently accounts for the QED corrections to the evolution of quark and gluon PDFs and for the contribution from the photon PDF in the proton. The coupled QCD ⊗ QED equations are solved in x-space by means of higher order interpolation, followed by Runge-Kutta solution of the resulting discretized evolution equations. APFEL is based on an innovative and flexible methodology for the sequential solution of the QCD and QED evolution equations and their combination. In addition to PDF evolution, APFEL provides a module that computes Deep-Inelastic Scattering structure functions in the FONLL general-mass variable-flavor-number scheme up to O(αs2) . All the functionalities of APFEL can be accessed via a Graphical User Interface, supplemented with a variety of plotting tools for PDFs, parton luminosities and structure functions. Written in FORTRAN 77, APFEL can also be used via the C/C++ and Python interfaces, and is publicly available from the HepForge repository.

  6. Atmospheric Neutrinos: Background and Signal

    SciTech Connect

    Mocioiu, Irina

    2010-11-24

    We discuss a brief history of atmospheric neutrinos, from background to proton decay searches to proving neutrino oscillations. We then discuss how high statistics atmospheric neutrino measurements in the IceCube Deep Core Array can provide useful information about neutrino oscillation parameters and other neutrino properties.

  7. Low background techniques in CANDLES

    NASA Astrophysics Data System (ADS)

    Nakajima, K.; Iida, T.; Kishimoto, T.; Matsuoka, K.; Nomachi, M.; Umehara, S.; Chan, W. M.; Kakubata, H.; Li, X.; Maeda, T.; Ohata, T.; Temuge, B.; Tetsuno, K.; Trang, V. T. T.; Uehara, T.; Yoshida, S.; Morishita, K.; Ogawa, I.; Sakamoto, K.; Tamagawa, Y.; Yoshizawa, M.; Fushimi, K.; Hazama, R.; Naktani, N.; Suzuki, K.

    2015-08-01

    CANDLES is a double beta decay experiment using 48Ca in CaF2 crystals. The measurement is being performed with prototype detector (CANDLES III) for high sensitive measurement in the future. Recent status of detector improvements and background reduction techniques are described in this paper.

  8. Integrated Global Background Monitoring Network

    SciTech Connect

    Wiersma, G.B.; Franklin, J.F.; Kohler, A.; Croze, H.; Boelcke, C.

    1986-12-01

    One of the more significant problems when trying to determine what impact is having on global cycles is not knowing what ''natural'' levels should be for both abiotic (gases, trace elements) and biotic (ecosystem functions) processes. The authors believe that a well designed, coordinated network of baseline stations in remote areas around the world can provide a data base will allow best current estimates to be made of biotic and abiotic baseline conditions. These baseline conditions will then help us make better comparisons with more impacted areas, and thus help us more fully understand the impact man is having on his world. This paper examines the history of background pollution monitoring at the international level, describes current activities in the field of ''integrated'' background monitoring, and proposes criteria for the development of a global network of baseline stations to coordinate background monitoring for the presence, accumulation and behavior of pollutants in remote ecosystems. In this paper, this network is called the Integrated Global Background Monitoring Network.

  9. Educational Choice. A Background Paper.

    ERIC Educational Resources Information Center

    Quality Education for Minorities Network, Washington, DC.

    This paper addresses school choice, one proposal to address parental involvement concerns, focusing on historical background, definitions, rationale for advocating choice, implementation strategies, and implications for minorities and low-income families. In the past, transfer payment programs such as tuition tax credits and vouchers were…

  10. Regional Background Fine Particulate Matter

    EPA Science Inventory

    A modeling system composed of the global model GEOS-Chem providing hourly lateral boundary conditions to the regional model CMAQ was used to calculate the policy relevant background level of fine particulate: matter. Simulations were performed for the full year of 2004 over the d...

  11. Low background techniques in CANDLES

    SciTech Connect

    Nakajima, K. E-mail: nkyohei@u-fukui.ac.jp; Iida, T.; Matsuoka, K.; Nomachi, M.; Umehara, S.; Kishimoto, T.; Chan, W. M.; Kakubata, H.; Li, X.; Maeda, T.; Ohata, T.; Temuge, B.; Tetsuno, K.; Trang, V. T. T.; Uehara, T.; Yoshida, S.; Morishita, K.; Ogawa, I.; Sakamoto, K.; Tamagawa, Y.; and others

    2015-08-17

    CANDLES is a double beta decay experiment using {sup 48}Ca in CaF{sub 2} crystals. The measurement is being performed with prototype detector (CANDLES III) for high sensitive measurement in the future. Recent status of detector improvements and background reduction techniques are described in this paper.

  12. Teaching about Natural Background Radiation

    ERIC Educational Resources Information Center

    Al-Azmi, Darwish; Karunakara, N.; Mustapha, Amidu O.

    2013-01-01

    Ambient gamma dose rates in air were measured at different locations (indoors and outdoors) to demonstrate the ubiquitous nature of natural background radiation in the environment and to show that levels vary from one location to another, depending on the underlying geology. The effect of a lead shield on a gamma radiation field was also…

  13. Teacher Pensions: A Background Paper

    ERIC Educational Resources Information Center

    Hansen, Janet S.

    2008-01-01

    Pensions are an important but comparatively unexamined component of human resource policies in education. In an increasingly competitive world where employees are more mobile than ever, pension policies that were designed in the last century may be out of step with the needs of both individuals and schools. This background paper aims to foster…

  14. Ambient background particulate composition, outdoor natural background: interferents/clutter

    NASA Astrophysics Data System (ADS)

    Paterno, Dorothea

    2012-06-01

    It has proven a very difficult task to discriminate an actual BW threat from the natural occurring ambient particulate aerosol, which includes a significant fraction of particles consisting of mixed mineral and biological material. The interferent particles [clutter] (bio and non bio) concentration varies widely both by location, weather and season and diurnally. Naturally occurring background particulates are composed of fungal and bacterial spores both fragments and components, plant fragments and debris, animal fragments and debris, all of which may be associated with inert dust or combustion material. Some or all of which could also be considered to be an interferent to a biological warfare detector and cause these biodector systems to cause False Alarms by non specific BW bio detectors. I will share analysis of current long term background data sets.

  15. The Cosmic Infrared Background Experiment

    NASA Astrophysics Data System (ADS)

    Bock, James; Battle, J.; Cooray, A.; Hristov, V.; Kawada, M.; Keating, B.; Lee, D.; Matsumoto, T.; Matsuura, S.; Nam, U.; Renbarger, T.; Sullivan, I.; Tsumura, K.; Wada, T.; Zemcov, M.

    2009-01-01

    We are developing the Cosmic Infrared Background ExpeRiment (CIBER) to search for signatures of first-light galaxy emission in the extragalactic background. The first generation of stars produce characteristic signatures in the near-infrared extragalactic background, including a redshifted Ly-cutoff feature and a characteristic fluctuation power spectrum, that may be detectable with a specialized instrument. CIBER consists of two wide-field cameras to measure the fluctuation power spectrum, and a low-resolution and a narrow-band spectrometer to measure the absolute background. The cameras will search for fluctuations on angular scales from 7 arcseconds to 2 degrees, where the first-light galaxy spatial power spectrum peaks. The cameras have the necessary combination of sensitivity, wide field of view, spatial resolution, and multiple bands to make a definitive measurement. CIBER will determine if the fluctuations reported by Spitzer arise from first-light galaxies. The cameras observe in a single wide field of view, eliminating systematic errors associated with mosaicing. Two bands are chosen to maximize the first-light signal contrast, at 1.6 um near the expected spectral maximum, and at 1.0 um; the combination is a powerful discriminant against fluctuations arising from local sources. We will observe regions of the sky surveyed by Spitzer and Akari. The low-resolution spectrometer will search for the redshifted Lyman cutoff feature in the 0.7 - 1.8 um spectral region. The narrow-band spectrometer will measure the absolute Zodiacal brightness using the scattered 854.2 nm Ca II Fraunhofer line. The spectrometers will test if reports of a diffuse extragalactic background in the 1 - 2 um band continues into the optical, or is caused by an under estimation of the Zodiacal foreground. We report performance of the assembled and tested instrument as we prepare for a first sounding rocket flight in early 2009. CIBER is funded by the NASA/APRA sub-orbital program.

  16. Modeling of turbulent supersonic H2-air combustion with a multivariate beta PDF

    NASA Technical Reports Server (NTRS)

    Baurle, R. A.; Hassan, H. A.

    1993-01-01

    Recent calculations of turbulent supersonic reacting shear flows using an assumed multivariate beta PDF (probability density function) resulted in reduced production rates and a delay in the onset of combustion. This result is not consistent with available measurements. The present research explores two possible reasons for this behavior: use of PDF's that do not yield Favre averaged quantities, and the gradient diffusion assumption. A new multivariate beta PDF involving species densities is introduced which makes it possible to compute Favre averaged mass fractions. However, using this PDF did not improve comparisons with experiment. A countergradient diffusion model is then introduced. Preliminary calculations suggest this to be the cause of the discrepancy.

  17. Applying molecular genetic tools to tiger conservation.

    PubMed

    Luo, Shu-Jin; Johnson, Warren E; O'Brien, Stephen J

    2010-12-01

    The utility of molecular genetic approaches in conservation of endangered taxa is now commonly recognized. Over the past decade, conservation genetic analyses based on mitochondrial DNA sequencing and microsatellite genotyping have provided powerful tools to resolve taxonomy uncertainty of tiger subspecies, to define conservation units, to reconstruct phylogeography and demographic history, to examine the genetic ancestry of extinct subspecies, to assess population genetic status non-invasively, and to verify genetic background of captive tigers worldwide. The genetic status of tiger subspecies and populations and implications for developing strategies for the survival of this charismatic species both in situ and ex situ are discussed.

  18. Applying molecular genetic tools to tiger conservation.

    PubMed

    Luo, Shu-Jin; Johnson, Warren E; O'Brien, Stephen J

    2010-12-01

    The utility of molecular genetic approaches in conservation of endangered taxa is now commonly recognized. Over the past decade, conservation genetic analyses based on mitochondrial DNA sequencing and microsatellite genotyping have provided powerful tools to resolve taxonomy uncertainty of tiger subspecies, to define conservation units, to reconstruct phylogeography and demographic history, to examine the genetic ancestry of extinct subspecies, to assess population genetic status non-invasively, and to verify genetic background of captive tigers worldwide. The genetic status of tiger subspecies and populations and implications for developing strategies for the survival of this charismatic species both in situ and ex situ are discussed. PMID:21392353

  19. Background stratospheric aerosol reference model

    NASA Technical Reports Server (NTRS)

    Mccormick, M. P.; Wang, P.

    1989-01-01

    In this analysis, a reference background stratospheric aerosol optical model is developed based on the nearly global SAGE 1 satellite observations in the non-volcanic period from March 1979 to February 1980. Zonally averaged profiles of the 1.0 micron aerosol extinction for the tropics and the mid- and high-altitudes for both hemispheres are obtained and presented in graphical and tabulated form for the different seasons. In addition, analytic expressions for these seasonal global zonal means, as well as the yearly global mean, are determined according to a third order polynomial fit to the vertical profile data set. This proposed background stratospheric aerosol model can be useful in modeling studies of stratospheric aerosols and for simulations of atmospheric radiative transfer and radiance calculations in atmospheric remote sensing.

  20. WFC3/UVIS Sky Backgrounds

    NASA Astrophysics Data System (ADS)

    Baggett, Sylvia; Anderson, Jay

    2012-06-01

    This report summarizes the on-orbit background levels present in WFC3/UVIS full-frame images. The results are based on nearly all standard readout images taken since the installation of WFC3 on HST in May 2009, with a relatively small number of exclusions e.g. images with obvious anomalous backgrounds (such as extended targets filling the field of view) or those taken with the quad filters (different bandpass in each amp). Comparisons are provided to estimates from the Exposure Time Calculator (ETC). We anticipate these results to be helpful in fine-tuning the level of post-flash required to achieve the optimum balance of charge transfter efficiency (CTE) loss mitigation versus noise penalty. Observers considering the use of post-flash should refer to the White Paper (MacKenty & Smith 2012) on the CTE WWW page (http://www.stsci.edu/hst/wfc3/ins_performance/CTE/).

  1. Quantum chromodynamics in background fields

    NASA Astrophysics Data System (ADS)

    Huang, Tao; Huang, Zheng

    1989-02-01

    We try to build a framework for quantum chromodynamics in background fields. The nonvanishing vacuum condensates are described by the classical fields, while the corresponding quantum fields are quantized in the Furry representation and the physical states are defined in the physical QCD vacuum. The complete quark and gluon propagators are discussed in this framework and running condensate parameters are introduced by the renormalization requirement. A modified Callan-Symanzik equation is derived by taking account of the nonperturbative corrections.

  2. The Cosmic Background Explorer /COBE/

    NASA Technical Reports Server (NTRS)

    Mather, J. C.

    1982-01-01

    The Cosmic Background Explorer (COBE) satellite, under study by NASA since 1976, will map the spectrum and the angular distribution of diffuse radiation from the universe over the entire wavelength range from 1 micron to 1.3 cm. It carries three instruments: a set of differential microwave radiometers (DMR) at 23.5, 31.4, 53, and 90GHz, a far infrared absolute spectrophotometer (FIRAS) covering 1 to 100 per cm, and a diffuse infrared background experiment (DIRBE) covering 1 to 300 microns. They will use the ideal space environment, a one year lifetime, and standard instrument techniques to achieve orders of magnitude improvements in sensitivity and accuracy, providing a fundamental data base for cosmology. The instruments are united by common purpose as well as similar environmental and orbital requirements. The data from all three experiments will be analyzed together, to distinguish nearby sources of radiation from the cosmologically interesting diffuse background radiations. Construction is planned to begin in 1982 for a launch in 1988.

  3. The isotropic radio background revisited

    SciTech Connect

    Fornengo, Nicolao; Regis, Marco; Lineros, Roberto A.

    2014-04-01

    We present an extensive analysis on the determination of the isotropic radio background. We consider six different radio maps, ranging from 22 MHz to 2.3 GHz and covering a large fraction of the sky. The large scale emission is modeled as a linear combination of an isotropic component plus the Galactic synchrotron radiation and thermal bremsstrahlung. Point-like and extended sources are either masked or accounted for by means of a template. We find a robust estimate of the isotropic radio background, with limited scatter among different Galactic models. The level of the isotropic background lies significantly above the contribution obtained by integrating the number counts of observed extragalactic sources. Since the isotropic component dominates at high latitudes, thus making the profile of the total emission flat, a Galactic origin for such excess appears unlikely. We conclude that, unless a systematic offset is present in the maps, and provided that our current understanding of the Galactic synchrotron emission is reasonable, extragalactic sources well below the current experimental threshold seem to account for the majority of the brightness of the extragalactic radio sky.

  4. Plutonium measurements near background levels

    SciTech Connect

    Not Available

    1992-01-01

    The Rocky Flats Plant (RFP) is part of a nationwide nuclear weapons research, development, and production complex administered by the United States Department of Energy (DOE). Low-levels of environmental Plutonium occurs in and about RFP as a result of plant operations. Plutonium is a key element in remediation investigations and surface water discharge limits. Most of the plutonium analyses at RFP measure concentrations at or near background levels. Measurements often show little, if any, plutonium in the media being sampled, except at known contamination sites. Many plutonium results are less than the calculated minimum detectable-level (MDL). (MDL is an a priori estimate of the activity concentration that can be practically achieved under a specified set of typical measurement conditions.) This paper investigates the relationship between plutonium concentrations and the counting uncertainty when measurements are near background, and suggests why the MDL should not be used as a criteria for limiting data. Issues with defining site background and determining attainment of standards are presented.

  5. Plutonium measurements near background levels

    SciTech Connect

    Not Available

    1992-08-01

    The Rocky Flats Plant (RFP) is part of a nationwide nuclear weapons research, development, and production complex administered by the United States Department of Energy (DOE). Low-levels of environmental Plutonium occurs in and about RFP as a result of plant operations. Plutonium is a key element in remediation investigations and surface water discharge limits. Most of the plutonium analyses at RFP measure concentrations at or near background levels. Measurements often show little, if any, plutonium in the media being sampled, except at known contamination sites. Many plutonium results are less than the calculated minimum detectable-level (MDL). (MDL is an a priori estimate of the activity concentration that can be practically achieved under a specified set of typical measurement conditions.) This paper investigates the relationship between plutonium concentrations and the counting uncertainty when measurements are near background, and suggests why the MDL should not be used as a criteria for limiting data. Issues with defining site background and determining attainment of standards are presented.

  6. Background independence in a background dependent renormalization group

    NASA Astrophysics Data System (ADS)

    Labus, Peter; Morris, Tim R.; Slade, Zöe H.

    2016-07-01

    Within the derivative expansion of conformally reduced gravity, the modified split Ward identities are shown to be compatible with the flow equations if and only if either the anomalous dimension vanishes or the cutoff profile is chosen to have a power-law form. No solutions exist if the Ward identities are incompatible. In the compatible case, a clear reason is found for why Ward identities can still forbid the existence of fixed points; however, for any cutoff profile, a background independent (and parametrization independent) flow equation is uncovered. Finally, expanding in vertices, the combined equations are shown generically to become either overconstrained or highly redundant beyond the six-point level.

  7. Genetic barcodes

    DOEpatents

    Weier, Heinz -Ulrich G

    2015-08-04

    Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

  8. Paleopopulation genetics.

    PubMed

    Wall, Jeffrey D; Slatkin, Montgomery

    2012-01-01

    Paleopopulation genetics is a new field that focuses on the population genetics of extinct groups and ancestral populations (i.e., populations ancestral to extant groups). With recent advances in DNA sequencing technologies, we now have unprecedented ability to directly assay genetic variation from fossils. This allows us to address issues, such as past population structure, changes in population size, and evolutionary relationships between taxa, at a much greater resolution than can traditional population genetics studies. In this review, we discuss recent developments in this emerging field as well as prospects for the future. PMID:22994357

  9. A joint velocity-concentration PDF method for tracer flow in heterogeneous porous media

    NASA Astrophysics Data System (ADS)

    Meyer, Daniel W.; Jenny, Patrick; Tchelepi, Hamdi A.

    2010-12-01

    The probability density function (PDF) of the local concentration of a contaminant, or tracer, is an important component of risk assessment in applications that involve flow in heterogeneous subsurface formations. In this paper, a novel joint velocity-concentration PDF method for tracer flow in highly heterogeneous porous media is introduced. The PDF formalism accounts for advective transport, pore-scale dispersion (PSD), and molecular diffusion. Low-order approximations (LOAs), which are usually obtained using a perturbation expansion, typically lead to Gaussian one-point velocity PDFs. Moreover, LOAs provide reasonable approximations for small log conductivity variances (i.e., σY2 < 1). For large σY2, however, the one-point velocity PDFs deviate significantly from the Gaussian distribution as demonstrated convincingly by several Monte Carlo (MC) simulation studies. Furthermore, the Lagrangian velocity statistics exhibit complex correlations that span a wide range of scales, including long-range correlations due to the formation of preferential flow paths. Both non-Gaussian PDFs and complex long-range correlations are accurately represented using Markovian velocity processes (MVPs) in the proposed joint PDF method. LOA methods can be generalized to some extent by presuming a certain shape for the concentration PDF (e.g., a β PDF fully characterized by the concentration mean and variance). The joint velocity-concentration PDF method proposed here does not require any closure assumptions on the shape of the marginal concentration PDF. The Eulerian joint PDF transport equation is solved numerically using a computationally efficient particle-based approach. The PDF method is validated with high-resolution MC reference data from Caroni and Fiorotto (2005) for saturated transport in velocity fields, which are stationary in space and time, for domains with σY2 = 0.05, 1, and 2 and Péclet numbers ranging from 100 to 10,000. PSD is modeled using constant anisotropic

  10. An Eulerian joint velocity-concentration PDF method for solute dispersion in highly heterogeneous porous media

    NASA Astrophysics Data System (ADS)

    Meyer, Daniel W.; Tchelepi, Hamdi A.; Jenny, Patrick

    2010-05-01

    In risk analysis applications involving heterogeneous formations, the knowledge of the solute concentration probability density function (PDF) at different spatial locations and times is crucial. We propose a new joint velocity-concentration PDF method applicable for highly heterogeneous porous media that accounts for advective transport, pore-scale dispersion and molecular diffusion. Unlike in low order approximation (LOA) methods that are valid for low conductivity variances ?Y 2 and where the one-point velocity PDF is typically assumed to be a Gaussian, the proposed joint PDF method honors the increasingly non-Gaussian velocity one-point PDF and the long-term velocity correlations that were reported in different Monte Carlo (MC) studies for ?Y 2 > 0.5 [e.g., Salandin, P. and V. Fiorotto, WRR, 1998. 34(5) and Trefry, M.G., F.P. Ruan, and D. McLaughlin, WRR, 2003. 39(3)]. Furthermore, the new joint PDF method does not involve any a-priori assumption about the shape of the resulting marginal concentration PDF. LOA methods that provide information on the concentration mean and variance [Fiori, A. and G. Dagan, Journal of Contaminant Hydrology, 2000. 45(1-2)] on the other hand are typically complemented by assuming that the concentration PDF has a β-PDF shape [Bellin, A. and D. Tonina, Journal of Contaminant Hydrology, 2007. 94(1-2)]. The Eulerian joint velocity-concentration PDF transport equation in our model is numerically solved with a computationally efficient particle method. The suggested joint PDF method is validated by comparison with MC data reported by Caroni and Fiorotto for Péclet numbers ranging from 10 to 104 and ?Y 2 = 1 and 2 [Caroni, E. and V. Fiorotto, Transport in Porous Media, 2005. 59(1)].

  11. A PDF/NPF neuropeptide signaling circuitry of male Drosophila melanogaster controls rival-induced prolonged mating.

    PubMed

    Kim, Woo Jae; Jan, Lily Yeh; Jan, Yuh Nung

    2013-12-01

    A primary function of males for many species involves mating with females for reproduction. Drosophila melanogaster males respond to the presence of other males by prolonging mating duration to increase the chance of passing on their genes. To understand the basis of such complex behaviors, we examine the genetic network and neural circuits that regulate rival-induced Longer-Mating-Duration (LMD). Here, we identify a small subset of clock neurons in the male brain that regulate LMD via neuropeptide signaling. LMD requires the function of pigment-dispersing factor (PDF) in four s-LNv neurons and its receptor PDFR in two LNd neurons per hemisphere, as well as the function of neuropeptide F (NPF) in two neurons within the sexually dimorphic LNd region and its receptor NPFR1 in four s-LNv neurons per hemisphere. Moreover, rival exposure modifies the neuronal activities of a subset of clock neurons involved in neuropeptide signaling for LMD. PMID:24314729

  12. Functional PDF Signaling in the Drosophila Circadian Neural Circuit Is Gated by Ral A-Dependent Modulation.

    PubMed

    Klose, Markus; Duvall, Laura B; Li, Weihua; Liang, Xitong; Ren, Chi; Steinbach, Joe Henry; Taghert, Paul H

    2016-05-18

    The neuropeptide PDF promotes the normal sequencing of circadian behavioral rhythms in Drosophila, but its signaling mechanisms are not well understood. We report daily rhythmicity in responsiveness to PDF in critical pacemakers called small LNvs. There is a daily change in potency, as great as 10-fold higher, around dawn. The rhythm persists in constant darkness and does not require endogenous ligand (PDF) signaling or rhythmic receptor gene transcription. Furthermore, rhythmic responsiveness reflects the properties of the pacemaker cell type, not the receptor. Dopamine responsiveness also cycles, in phase with that of PDF, in the same pacemakers, but does not cycle in large LNv. The activity of RalA GTPase in s-LNv regulates PDF responsiveness and behavioral locomotor rhythms. Additionally, cell-autonomous PDF signaling reversed the circadian behavioral effects of lowered RalA activity. Thus, RalA activity confers high PDF responsiveness, providing a daily gate around the dawn hours to promote functional PDF signaling. PMID:27161526

  13. Teaching about natural background radiation

    NASA Astrophysics Data System (ADS)

    Al-Azmi, Darwish; Karunakara, N.; Mustapha, Amidu O.

    2013-07-01

    Ambient gamma dose rates in air were measured at different locations (indoors and outdoors) to demonstrate the ubiquitous nature of natural background radiation in the environment and to show that levels vary from one location to another, depending on the underlying geology. The effect of a lead shield on a gamma radiation field was also demonstrated to emphasize the important role of shielding in radiation protection. The measurements were carried out with a Geiger-Muller (GM)-based dosimeter and a NaI scintillation gamma-ray spectrometer, which are normally available in physics laboratories. Radioactivity in household materials was demonstrated using a gas mantle as an example.

  14. [Toothache with a neuropathic background].

    PubMed

    Khatchaturian, V; de Wijer, A; Kalaykova, S I; Steenks, M H

    2015-03-01

    A 48-year old woman in good general health was referred to the orofacial pain clinic in a centre for special dentistry with a toothache in the premolar region of the left maxillary quadrant. The complaints had existed for 15 years and various dental treatments, including endodontic treatments, apical surgery, extraction and splint therapy, had not helped to alleviate the complaints. As a result of the fact that anti-epileptic drugs were able to reduce the pain it was concluded that this 'toothache' satisfied the criteria of an atypical odontalgia: 'toothache' with a neuropathic background. PMID:26181392

  15. Genetic Engineering

    ERIC Educational Resources Information Center

    Phillips, John

    1973-01-01

    Presents a review of genetic engineering, in which the genotypes of plants and animals (including human genotypes) may be manipulated for the benefit of the human species. Discusses associated problems and solutions and provides an extensive bibliography of literature relating to genetic engineering. (JR)

  16. Computerized background-oriented schlieren

    NASA Astrophysics Data System (ADS)

    Meier, G. E. A.

    2002-06-01

    A schlieren measurement technique based on computer evaluation of image variations due to refractive index variations in the propagation medium is presented; in what follows, this concept is referred to as the "background-oriented schlieren" (BOS) method. The differences between BOS and other optical techniques for refractive index measurement are the governing role of numerical methods, the extremely small amount of optical equipment, the high accuracy, the bidirectional sensitivity, the fast evaluation, and the missing field limitations. The principle of the method is the numerical comparison of a schlieren distorted and an undistorted image of a deliberate background. The method has become usable in practice owing to the immense progress in computing power and to newly developed fast-correlation algorithms. The extension of this method to space resolving techniques is possible. Some experimental studies show the applicability. Examples are a mixing turbulent jet, a supersonic jet, a shed vortex, and the sound wave of a gun shot. These few results underline the encouraging prospect for the future applicability of this technique. The BOS method offers not only the possibility of qualitative and quantitative schlieren investigations but also has the potential to determine density fields by integration of the measured gradient fields.

  17. Video coding with dynamic background

    NASA Astrophysics Data System (ADS)

    Paul, Manoranjan; Lin, Weisi; Lau, Chiew Tong; Lee, Bu-Sung

    2013-12-01

    Motion estimation (ME) and motion compensation (MC) using variable block size, sub-pixel search, and multiple reference frames (MRFs) are the major reasons for improved coding performance of the H.264 video coding standard over other contemporary coding standards. The concept of MRFs is suitable for repetitive motion, uncovered background, non-integer pixel displacement, lighting change, etc. The requirement of index codes of the reference frames, computational time in ME & MC, and memory buffer for coded frames limits the number of reference frames used in practical applications. In typical video sequences, the previous frame is used as a reference frame with 68-92% of cases. In this article, we propose a new video coding method using a reference frame [i.e., the most common frame in scene (McFIS)] generated by dynamic background modeling. McFIS is more effective in terms of rate-distortion and computational time performance compared to the MRFs techniques. It has also inherent capability of scene change detection (SCD) for adaptive group of picture (GOP) size determination. As a result, we integrate SCD (for GOP determination) with reference frame generation. The experimental results show that the proposed coding scheme outperforms the H.264 video coding with five reference frames and the two relevant state-of-the-art algorithms by 0.5-2.0 dB with less computational time.

  18. [Cosmic Microwave Background (CMB) Anisotropies

    NASA Astrophysics Data System (ADS)

    Silk, Joseph

    1998-01-01

    One of the main areas of research is the theory of cosmic microwave background (CMB) anisotropies and analysis of CMB data. Using the four year COBE data we were able to improve existing constraints on global shear and vorticity. We found that, in the flat case (which allows for greatest anisotropy), (omega/H)0 less than 10-7, where omega is the vorticity and H is the Hubble constant. This is two orders of magnitude lower than the tightest, previous constraint. We have defined a new set of statistics which quantify the amount of non-Gaussianity in small field cosmic microwave background maps. By looking at the distribution of power around rings in Fourier space, and at the correlations between adjacent rings, one can identify non-Gaussian features which are masked by large scale Gaussian fluctuations. This may be particularly useful for identifying unresolved localized sources and line-like discontinuities. Levin and collaborators devised a method to determine the global geometry of the universe through observations of patterns in the hot and cold spots of the CMB. We have derived properties of the peaks (maxima) of the CMB anisotropies expected in flat and open CDM models. We represent results for angular resolutions ranging from 5 arcmin to 20 arcmin (antenna FWHM), scales that are relevant for the MAP and COBRA/SAMBA space missions and the ground-based interferometer. Results related to galaxy formation and evolution are also discussed.

  19. [Cosmic Microwave Background (CMB) Anisotropies

    NASA Technical Reports Server (NTRS)

    Silk, Joseph

    1998-01-01

    One of the main areas of research is the theory of cosmic microwave background (CMB) anisotropies and analysis of CMB data. Using the four year COBE data we were able to improve existing constraints on global shear and vorticity. We found that, in the flat case (which allows for greatest anisotropy), (omega/H)0 less than 10(exp -7), where omega is the vorticity and H is the Hubble constant. This is two orders of magnitude lower than the tightest, previous constraint. We have defined a new set of statistics which quantify the amount of non-Gaussianity in small field cosmic microwave background maps. By looking at the distribution of power around rings in Fourier space, and at the correlations between adjacent rings, one can identify non-Gaussian features which are masked by large scale Gaussian fluctuations. This may be particularly useful for identifying unresolved localized sources and line-like discontinuities. Levin and collaborators devised a method to determine the global geometry of the universe through observations of patterns in the hot and cold spots of the CMB. We have derived properties of the peaks (maxima) of the CMB anisotropies expected in flat and open CDM models. We represent results for angular resolutions ranging from 5 arcmin to 20 arcmin (antenna FWHM), scales that are relevant for the MAP and COBRA/SAMBA space missions and the ground-based interferometer. Results related to galaxy formation and evolution are also discussed.

  20. PDF modeling of turbulent flows on unstructured grids

    NASA Astrophysics Data System (ADS)

    Bakosi, Jozsef

    In probability density function (PDF) methods of turbulent flows, the joint PDF of several flow variables is computed by numerically integrating a system of stochastic differential equations for Lagrangian particles. Because the technique solves a transport equation for the PDF of the velocity and scalars, a mathematically exact treatment of advection, viscous effects and arbitrarily complex chemical reactions is possible; these processes are treated without closure assumptions. A set of algorithms is proposed to provide an efficient solution of the PDF transport equation modeling the joint PDF of turbulent velocity, frequency and concentration of a passive scalar in geometrically complex configurations. An unstructured Eulerian grid is employed to extract Eulerian statistics, to solve for quantities represented at fixed locations of the domain and to track particles. All three aspects regarding the grid make use of the finite element method. Compared to hybrid methods, the current methodology is stand-alone, therefore it is consistent both numerically and at the level of turbulence closure without the use of consistency conditions. Since both the turbulent velocity and scalar concentration fields are represented in a stochastic way, the method allows for a direct and close interaction between these fields, which is beneficial in computing accurate scalar statistics. Boundary conditions implemented along solid bodies are of the free-slip and no-slip type without the need for ghost elements. Boundary layers at no-slip boundaries are either fully resolved down to the viscous sublayer, explicitly modeling the high anisotropy and inhomogeneity of the low-Reynolds-number wall region without damping or wall-functions or specified via logarithmic wall-functions. As in moment closures and large eddy simulation, these wall-treatments provide the usual trade-off between resolution and computational cost as required by the given application. Particular attention is focused on

  1. [Genetics of pediatric obesity].

    PubMed

    Peralta-Romero, José de Jesús; Gómez-Zamudio, Jaime Héctor; Estrada-Velasco, Bárbara; Karam-Araujo, Roberto; Cruz-López, Miguel

    2014-01-01

    Obesity is a major health problem around the globe. The statistics of overweight and obesity at early ages have reached alarming levels and placed our country in the first place in regard to childhood obesity. In the development of obesity two major factors take part, one genetic and the other one environmental. From the perspective of environmental changes both overweight and obesity result from the imbalance in the energy balance: people ingest more energy than they expend. Despite people live in the same obesogenic environment not all of them develop obesity; it requires genetic factors for this to happen. This review focuses on the description of the main methodologies to find genetic markers, as well as the main loci in candidate genes, whose single nucleotide polymorphisms (SNPs) are associated with obesity and its comorbidities in children, highlighting the association of these genes in the Mexican population. Knowledge of the genetic markers associated with obesity will help to understand the molecular and physiological mechanisms, the genetic background and changes in body mass index in the Mexican population. This information is useful for the planning of new hypotheses in the search for new biomarkers that can be used in a predictive and preventive way, as well as for the development of new therapeutic strategies.

  2. Revised estimates for continuous shoreline fumigation: a PDF approach.

    PubMed

    Nazir, Muddassir; Khan, Faisal I; Husain, Tahir

    2005-02-14

    A probability density function (PDF) fumigation model is presented here to study the dispersion of air pollutants emitted from a tall stack on the shoreline. This work considers dispersion of the pollutants in the stable layer and within the thermal internal boundary layer (TIBL) proceeds independently. The growth of TIBL is considered parabolic with distance inland. Turbulence is taken as homogeneous and stationary. Dispersion of particles (contaminant) in lateral and vertical directions is assumed independent of each other. This assumption allows us to consider the position of particles in both directions as independent random variables. The lateral dispersion distribution within the TIBL is considered as Gaussian and independent of height. A skewed bi-Gaussian vertical velocity PDF is used to account for the physics of dispersion due to different characteristics of updrafts and downdrafts within the TIBL. We have used Weil (J.C. Weil, A diagnosis of the asymmetry in top-down and bottom-up diffusion using a Lagrangian stochastic model, J. Atmos. Sci., 47 (1990) 501-515) solutions to find out the parameters of this PDF. Incorporating finite Lagrangian integral time scale for the vertical velocity component, it is observed that it reduces the vertical dispersion in the beginning and moves the point of maximum concentration further downwind. Due to little dispersion in the beginning, there is more plume to be dispersed causing higher concentrations at large distances. The model has considered Weil and Brower's (J.C. Weil, P.R. Brower, Estimating convective boundary layer parameters for diffusion applications, Maryland Power Plant Siting Program Rep. PPSP-MP-48, Department of Natural Resources, Annapolis, MD, 1985, 37 pp.) convective limit to analyze dispersion characteristics within TIBL. The revised model discussed here is evaluated with the data available from the Nanticoke field experiment on fumigation conducted in summer of 1978 in Ontario, Canada. The results

  3. Modeling of turbulent supersonic H2-air combustion with an improved joint beta PDF

    NASA Technical Reports Server (NTRS)

    Baurle, R. A.; Hassan, H. A.

    1991-01-01

    Attempts at modeling recent experiments of Cheng et al. indicated that discrepancies between theory and experiment can be a result of the form of assumed probability density function (PDF) and/or the turbulence model employed. Improvements in both the form of the assumed PDF and the turbulence model are presented. The results are again used to compare with measurements. Initial comparisons are encouraging.

  4. PDF uncertainties at large x and gauge boson production

    SciTech Connect

    Accardi, Alberto

    2012-10-01

    I discuss how global QCD fits of parton distribution functions can make the somewhat separated fields of high-energy particle physics and lower energy hadronic and nuclear physics interact to the benefit of both. In particular, I will argue that large rapidity gauge boson production at the Tevatron and the LHC has the highest short-term potential to constrain the theoretical nuclear corrections to DIS data on deuteron targets necessary for up/down flavor separation. This in turn can considerably reduce the PDF uncertainty on cross section calculations of heavy mass particles such as W' and Z' bosons.

  5. The study of PDF turbulence models in combustion

    NASA Technical Reports Server (NTRS)

    Hsu, Andrew T.

    1991-01-01

    The accurate prediction of turbulent combustion is still beyond reach for today's computation techniques. It is the consensus of the combustion profession that the predictions of chemically reacting flow were poor if conventional turbulence models were used. The main difficulty lies in the fact that the reaction rate is highly nonlinear, and the use of averaged temperature, pressure, and density produces excessively large errors. The probability density function (PDF) method is the only alternative at the present time that uses local instant values of the temperature, density, etc. in predicting chemical reaction rate, and thus it is the only viable approach for turbulent combustion calculations.

  6. The present state and future directions of PDF methods

    NASA Technical Reports Server (NTRS)

    Pope, S. B.

    1992-01-01

    The objectives of the workshop are presented in viewgraph format, as is this entire article. The objectives are to discuss the present status and the future direction of various levels of engineering turbulence modeling related to Computational Fluid Dynamics (CFD) computations for propulsion; to assure that combustion is an essential part of propulsion; and to discuss Probability Density Function (PDF) methods for turbulent combustion. Essential to the integration of turbulent combustion models is the development of turbulent model, chemical kinetics, and numerical method. Some turbulent combustion models typically used in industry are the k-epsilon turbulent model, the equilibrium/mixing limited combustion, and the finite volume codes.

  7. 77 FR 23754 - Notice Pursuant to the National Cooperative Research and Production Act of 1993-3D PDF Consortium...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-20

    ... Antitrust Division Notice Pursuant to the National Cooperative Research and Production Act of 1993--3D PDF... Cooperative Research and Production Act of 1993, 15 U.S.C. 4301 et seq. (``the Act''), 3D PDF Consortium, Inc. (``3D PDF'') has filed written notifications simultaneously with the Attorney General and the...

  8. [Genetic evaluation of male homosexuality].

    PubMed

    Gasztonyi, Z

    1998-02-01

    The family trees of 16 homosexual males are evaluated in the material of their Genetic Counselling Clinic. The familial cluster of three cases corresponded to the X-linked recessive inheritance. The results of family, twin and adoption studies are reviewed and the recent findings of molecular genetic and brain researches are summarised. Male homosexuality comprises of different subgroups, but one major entity is caused by X-linked recessive gene(s). This genetic background represent a predisposition which is triggered or suppressed by external factors.

  9. The cosmic microwave background radiation

    NASA Technical Reports Server (NTRS)

    Silk, J.

    1981-01-01

    Because angular anisotropies and spectral distortions of the cosmic microwave background radiation are judged to be inevitable at some level, in a realistic cosmological model, the evidence for spectral distortions and its theoretical implications are described. The evidence for anisotropy is then discussed, and theoretical predictions of radiation anisotropy are summarized and compared with the data available. It is found that spectral distortions at the 3-sigma level near the peak of the blackbody spectrum, although inconsistent with the predicted distortions due to Compton scattering in the early universe, are elegantly interpreted in terms of radiation from an early, pregalactic generation of massive stars which had been thermalized by a modest amount of dust at high redshift. The quadrupole anisotropy at the 4-sigma level is most simply interpreted in terms of the large-scale structure of the universe.

  10. Deleterious background selection with recombination

    SciTech Connect

    Hudson, R.R.; Kaplan, N.L.

    1995-12-01

    An analytic expression for the expected nucleotide diversity is obtained for a neutral locus in a region with deleterious mutation and recombination. Our analytic results are used to predict levels of variation for the entire third chromosome of Drosophila melanogaster. The predictions are consistent with the low levels of variation that have been observed at loci near the centromeres of the third chromosome of D. melanogaster. However, the low levels of variation observed near the tips of this chromosome are not predicted using currently available estimates of the deleterious mutation rate and of selection coefficients. If considerably smaller selection coefficients are assumed, the low observed levels of variation at the tips of the third chromosome are consistent with the background selection model. 33 refs., 4 figs., 1 tab.

  11. Low background aspects of GERDA

    SciTech Connect

    Simgen, Hardy

    2011-04-27

    The GERDA experiment operates bare Germanium diodes enriched in {sup 76}Ge in an environment of pure liquid argon to search for neutrinoless double beta decay. A very low radioactive background is essential for the success of the experiment. We present here the research done in order to remove radio-impurities coming from the liquid argon, the stainless steel cryostat and the front-end electronics. We found that liquid argon can be purified efficiently from {sup 222}Rn. The main source of {sup 222}Rn in GERDA is the cryostat which emanates about 55 mBq. A thin copper shroud in the center of the cryostat was implemented to prevent radon from approaching the diodes. Gamma ray screening of radio-pure components for front-end electronics resulted in the development of a pre-amplifier with a total activity of less than 1 mBq {sup 228}Th.

  12. Low Background Counting At SNOLAB

    SciTech Connect

    Lawson, Ian; Cleveland, Bruce

    2011-04-27

    It is a continuous and ongoing effort to maintain radioactivity in materials and in the environment surrounding most underground experiments at very low levels. These low levels are required so that experiments can achieve the required detection sensitivities for the detection of low-energy neutrinos, searches for dark matter and neutrinoless double-beta decay. SNOLAB has several facilities which are used to determine these low background levels in the materials and the underground environment. This proceedings will describe the SNOLAB High Purity Germanium Detector which has been in continuous use for the past five years and give results of many of the items that have been counted over that period. Brief descriptions of SNOLAB's alpha-beta and electrostatic counters will be given, and the radon levels at SNOLAB will be discussed.

  13. Texture induced microwave background anisotropies

    SciTech Connect

    Borrill, Julian; Copeland, Edmund J.; Liddle, Andrew R.; Stebbins, Albert; Veeraraghavan, Shoba

    1994-03-01

    We use numerical simulations to calculate the cosmic microwave background anisotropy induced by the evolution of a global texture field, with special emphasis on individual textures. Both spherically symmetric and general configurations are analyzed, and in the latter case we consider field configurations which exhibit unwinding events and also ones which do not. We compare the results given by evolving the field numerically under both the expanded core (XCORE) and non-linear sigma model (NLSM) approximations with the analytic predictions of the NLSM exact solution for a spherically symmetric self-similar (SSSS) unwinding. We find that the random unwinding configuration spots' typical peak height is 60-75\\% and angular size typically only 10% of those of the SSSS unwinding, and that random configurations without an unwinding event nonetheless may generate indistinguishable hot and cold spots. A brief comparison is made with other work.

  14. Background canceling surface alpha detector

    DOEpatents

    MacArthur, Duncan W.; Allander, Krag S.; Bounds, John A.

    1996-01-01

    A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone.

  15. Background canceling surface alpha detector

    DOEpatents

    MacArthur, D.W.; Allander, K.S.; Bounds, J.A.

    1996-06-11

    A background canceling long range alpha detector which is capable of providing output proportional to both the alpha radiation emitted from a surface and to radioactive gas emanating from the surface. The detector operates by using an electrical field between first and second signal planes, an enclosure and the surface or substance to be monitored for alpha radiation. The first and second signal planes are maintained at the same voltage with respect to the electrically conductive enclosure, reducing leakage currents. In the presence of alpha radiation and radioactive gas decay, the signal from the first signal plane is proportional to both the surface alpha radiation and to the airborne radioactive gas, while the signal from the second signal plane is proportional only to the airborne radioactive gas. The difference between these two signals is proportional to the surface alpha radiation alone. 5 figs.

  16. Demonstration of thin film pair distribution function analysis (tfPDF) for the study of local structure in amorphous and crystalline thin films.

    PubMed

    Jensen, Kirsten M Ø; Blichfeld, Anders B; Bauers, Sage R; Wood, Suzannah R; Dooryhée, Eric; Johnson, David C; Iversen, Bo B; Billinge, Simon J L

    2015-09-01

    By means of normal-incidence, high-flux and high-energy X-rays, total scattering data for pair distribution function (PDF) analysis have been obtained from thin films (tf), suitable for local structure analysis. By using amorphous substrates as support for the films, the standard Rapid Acquisition PDF setup can be applied and the scattering signal from the film can be isolated from the total scattering data through subtraction of an independently measured background signal. No angular corrections to the data are needed, as would be the case for grazing incidence measurements. The 'tfPDF' method is illustrated through studies of as-deposited (i.e. amorphous) and crystalline FeSb3 films, where the local structure analysis gives insight into the stabilization of the metastable skutterudite FeSb3 phase. The films were prepared by depositing ultra-thin alternating layers of Fe and Sb, which interdiffuse and after annealing crystallize to form the FeSb3 structure. The tfPDF data show that the amorphous precursor phase consists of corner-sharing FeSb6 octahedra with motifs highly resembling the local structure in crystalline FeSb3. Analysis of the amorphous structure allows the prediction of whether the final crystalline product will form the FeSb3 phase with or without excess Sb present. The study thus illustrates how analysis of the local structure in amorphous precursor films can help to understand crystallization processes of metastable phases and opens for a range of new local structure studies of thin films.

  17. The microwave background anisotropies: observations.

    PubMed

    Wilkinson, D

    1998-01-01

    Most cosmologists now believe that we live in an evolving universe that has been expanding and cooling since its origin about 15 billion years ago. Strong evidence for this standard cosmological model comes from studies of the cosmic microwave background radiation (CMBR), the remnant heat from the initial fireball. The CMBR spectrum is blackbody, as predicted from the hot Big Bang model before the discovery of the remnant radiation in 1964. In 1992 the cosmic background explorer (COBE) satellite finally detected the anisotropy of the radiation-fingerprints left by tiny temperature fluctuations in the initial bang. Careful design of the COBE satellite, and a bit of luck, allowed the 30 microK fluctuations in the CMBR temperature (2.73 K) to be pulled out of instrument noise and spurious foreground emissions. Further advances in detector technology and experiment design are allowing current CMBR experiments to search for predicted features in the anisotropy power spectrum at angular scales of 1 degrees and smaller. If they exist, these features were formed at an important epoch in the evolution of the universe--the decoupling of matter and radiation at a temperature of about 4,000 K and a time about 300,000 years after the bang. CMBR anisotropy measurements probe directly some detailed physics of the early universe. Also, parameters of the cosmological model can be measured because the anisotropy power spectrum depends on constituent densities and the horizon scale at a known cosmological epoch. As sophisticated experiments on the ground and on balloons pursue these measurements, two CMBR anisotropy satellite missions are being prepared for launch early in the next century.

  18. What Use Is Population Genetics?

    PubMed

    Charlesworth, Brian

    2015-07-01

    The Genetic Society of America's Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. For over 40 years, 2015 recipient Brian Charlesworth has been a leader in both theoretical and empirical evolutionary genetics, making substantial contributions to our understanding of how evolution acts on genetic variation. Some of the areas in which Charlesworth's research has been most influential are the evolution of sex chromosomes, transposable elements, deleterious mutations, sexual reproduction, and life history. He also developed the influential theory of background selection, whereby the recurrent elimination of deleterious mutations reduces variation at linked sites, providing a general explanation for the correlation between recombination rate and genetic variation.

  19. What Use Is Population Genetics?

    PubMed Central

    Charlesworth, Brian

    2015-01-01

    The Genetic Society of America’s Thomas Hunt Morgan Medal is awarded to an individual GSA member for lifetime achievement in the field of genetics. For over 40 years, 2015 recipient Brian Charlesworth has been a leader in both theoretical and empirical evolutionary genetics, making substantial contributions to our understanding of how evolution acts on genetic variation. Some of the areas in which Charlesworth’s research has been most influential are the evolution of sex chromosomes, transposable elements, deleterious mutations, sexual reproduction, and life history. He also developed the influential theory of background selection, whereby the recurrent elimination of deleterious mutations reduces variation at linked sites, providing a general explanation for the correlation between recombination rate and genetic variation. PMID:26170438

  20. [Oligodendrogliomas: historical background of classifications].

    PubMed

    Nataf, F; Tucker, M-L; Varlet, P; Koziak, M; Beuvon, F; Daumas-Duport, C; Roux, F-X

    2005-09-01

    The story of the classifications for gliomas is related to the development of the techniques used for cytological and histological examination of brain parenchyma. After a review of these techniques and the progressive discovery of the central nervous system cell types, the main classifications are presented. The first classification is due to Bailey and Cushing in 1926. It was based on histoembryogenetic theory. Then Kernohan introduced, in 1938, the concept of anaplasia. The WHO classification was published in 1979, then revised in 1993 and 2000. It took into account some data from both previous systems and introduced gradually the notion of histological criteria of malignancy. More recently; molecular genetics data and clinical evolution were retained. The Sainte-Anne classification for oligodendrogliomas is based on both histological and imaging data. It includes the notion of spatial histological structure of oligodendrogliomas. Contrast enhancement is closely related to endotheliocapillary hyperplasia. Gliomas classifications are changing and confusions can be made because of lack of reproductibility and misinterpretations of samples. PMID:16292165

  1. An Overview of the NCC Spray/Monte-Carlo-PDF Computations

    NASA Technical Reports Server (NTRS)

    Raju, M. S.; Liu, Nan-Suey (Technical Monitor)

    2000-01-01

    This paper advances the state-of-the-art in spray computations with some of our recent contributions involving scalar Monte Carlo PDF (Probability Density Function), unstructured grids and parallel computing. It provides a complete overview of the scalar Monte Carlo PDF and Lagrangian spray computer codes developed for application with unstructured grids and parallel computing. Detailed comparisons for the case of a reacting non-swirling spray clearly highlight the important role that chemistry/turbulence interactions play in the modeling of reacting sprays. The results from the PDF and non-PDF methods were found to be markedly different and the PDF solution is closer to the reported experimental data. The PDF computations predict that some of the combustion occurs in a predominantly premixed-flame environment and the rest in a predominantly diffusion-flame environment. However, the non-PDF solution predicts wrongly for the combustion to occur in a vaporization-controlled regime. Near the premixed flame, the Monte Carlo particle temperature distribution shows two distinct peaks: one centered around the flame temperature and the other around the surrounding-gas temperature. Near the diffusion flame, the Monte Carlo particle temperature distribution shows a single peak. In both cases, the computed PDF's shape and strength are found to vary substantially depending upon the proximity to the flame surface. The results bring to the fore some of the deficiencies associated with the use of assumed-shape PDF methods in spray computations. Finally, we end the paper by demonstrating the computational viability of the present solution procedure for its use in 3D combustor calculations by summarizing the results of a 3D test case with periodic boundary conditions. For the 3D case, the parallel performance of all the three solvers (CFD, PDF, and spray) has been found to be good when the computations were performed on a 24-processor SGI Origin work-station.

  2. Arthropod Genetics.

    ERIC Educational Resources Information Center

    Zumwalde, Sharon

    2000-01-01

    Introduces an activity on arthropod genetics that involves phenotype and genotype identification of the creature and the construction process. Includes a list of required materials and directions to build a model arthropod. (YDS)

  3. Genetic Discrimination

    MedlinePlus

    ... Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care ... genetic discrimination. April 25, 2007, Statement of Administration Policy, Office of Management and Budget Official Statement from the Office of ...

  4. The Diffuse Extreme Ultraviolet Background

    NASA Technical Reports Server (NTRS)

    Vallerga, John; Slavin, Jonathan

    1996-01-01

    Observations of the diffuse EUV background towards 138 different directions using the spectrometers aboard the Extreme Ultraviolet Explorer satellite (EUVE) have been combined into a spectrum from 150A to 730A and represent an effective exposure of 18 million seconds. There is no significant evidence of any non-local line flux in the resultant spectrum such as that from a hot coronal plasma. These results are inconsistent with the Wisconsin C and B broad-band surveys assuming the source is a logT = 5.8 - 6.1 hot plasma in ionization equilibrium with solar abundances, confirming the previous result of Jelinksy, Vallerga and Edelstein) (hereafter Paper 1) using an observation along the ecliptic with the same instrument. To make these results consistent with the previous broad-band surveys, the plasma responsible for the emission must either be depleted in Fe by a factor of approximately 6, be behind an absorbing slab of neutral H with a column of 2 x 10(exp 19)/sq cm, or not be in collisional ionization equilibrium (CIE). One such non-CIE model (Breitswerdt and Schmutzier) that explains the soft x-ray results is also inconsistent with this EUV data.

  5. Acid rain: a background report

    SciTech Connect

    Glustrom, L.; Stolzenberg, J.

    1982-07-08

    This Staff Brief was prepared for the Wisconsin Legislative Council's Special Committee on Acid Rain to provide an introduction to the issue of acid rain. It is divided into four parts. Part I provides an overview on the controversies surrounding the measurement, formation and effects of acid rain. As described in Part I, the term acid rain is used to describe the deposition of acidic components through both wet deposition (e.g., rain or snow) and dry deposition (e.g., direct contact between atmospheric constituents and the land, water or vegetation of the earth). Part II presents background information on state agency activities relating to acid rain in Wisconsin, describes what is known about the occurrence of, susceptibility to and effects of acid rain in Wisconsin, and provides information related to man-made sources of sulfur and nitrogen oxides in Wisconsin. Part III describes major policies and regulations relating to acid rain which have been or are being developed jointly by the United States and Canadian governments, by the United States government and by the State of Wisconsin. Part IV briefly discusses possible areas for Committee action.

  6. DarkLight radiation backgrounds

    SciTech Connect

    Kalantarians, Narbe

    2013-11-01

    We report measurements of photon and neutron radiation levels observed while transmitting a 0.43 MW electron beam through millimeter-sized apertures and during beam-on, but accelerating gradient RF-on, operation. These measurements were conducted at the Free-Electron Laser (FEL) facility of the Jefferson National Accelerator Laboratory (JLab) using a 100 MeV electron beam from an energy-recovery linear accelerator. The beam was directed successively through 6 mm, 4 mm, and 2 mm diameter apertures of length 127 mm in aluminum at a maximum current of 4.3 mA (430 kW beam power). This study was conducted to characterize radiation levels for experiments that need to operate in this environment, such as the proposed DarkLight Experiment. We find that sustained transmission of a 430 kW CW beam through a 2 mm aperture is feasible with manageable beam-related backgrounds. We also find that during beam-off, RF-on operation, field emission inside the niobium cavities of the accelerator cryomodules is the primary source of ambient radiation.

  7. Human Heredity: Genetic Mechanisms in Humans.

    ERIC Educational Resources Information Center

    Blank, C. E.

    1988-01-01

    Discussed are some of the uncertainties in human genetic mechanisms that are often presented as dogma in Biology textbooks. Presented is a brief historical background and illustrations involving chromosome abnormality in humans and linkage studies in humans. (CW)

  8. Ciona Genetics

    PubMed Central

    Veeman, Michael T.; Chiba, Shota; Smith, William C.

    2010-01-01

    Ascidians, such as Ciona, are invertebrate chordates with simple embryonic body plans and small, relatively non-redundant genomes. Ciona genetics is in its infancy compared to many other model systems, but it provides a powerful method for studying this important vertebrate outgroup. Here we give basic methods for genetic analysis of Ciona, including protocols for controlled crosses both by natural spawning and by the surgical isolation of gametes; the identification and propagation of mutant lines; and strategies for positional cloning. PMID:21805273

  9. Cosmic Microwave Background Data Analysis

    NASA Astrophysics Data System (ADS)

    Paykari, Paniez; Starck, Jean-Luc Starck

    2012-03-01

    About 400,000 years after the Big Bang the temperature of the Universe fell to about a few thousand degrees. As a result, the previously free electrons and protons combined and the Universe became neutral. This released a radiation which we now observe as the cosmic microwave background (CMB). The tiny fluctuations* in the temperature and polarization of the CMB carry a wealth of cosmological information. These so-called temperature anisotropies were predicted as the imprints of the initial density perturbations which gave rise to the present large-scale structures such as galaxies and clusters of galaxies. This relation between the present-day Universe and its initial conditions has made the CMB radiation one of the most preferred tools to understand the history of the Universe. The CMB radiation was discovered by radio astronomers Arno Penzias and Robert Wilson in 1965 [72] and earned them the 1978 Nobel Prize. This discovery was in support of the Big Bang theory and ruled out the only other available theory at that time - the steady-state theory. The crucial observations of the CMB radiation were made by the Far-Infrared Absolute Spectrophotometer (FIRAS) instrument on the Cosmic Background Explorer (COBE) satellite [86]- orbited in 1989-1996. COBE made the most accurate measurements of the CMB frequency spectrum and confirmed it as being a black-body to within experimental limits. This made the CMB spectrum the most precisely measured black-body spectrum in nature. The CMB has a thermal black-body spectrum at a temperature of 2.725 K: the spectrum peaks in the microwave range frequency of 160.2 GHz, corresponding to a 1.9mmwavelength. The results of COBE inspired a series of ground- and balloon-based experiments, which measured CMB anisotropies on smaller scales over the next decade. During the 1990s, the first acoustic peak of the CMB power spectrum (see Figure 5.1) was measured with increasing sensitivity and by 2000 the BOOMERanG experiment [26] reported

  10. Background field removal technique using regularization enabled sophisticated harmonic artifact reduction for phase data with varying kernel sizes.

    PubMed

    Kan, Hirohito; Kasai, Harumasa; Arai, Nobuyuki; Kunitomo, Hiroshi; Hirose, Yasujiro; Shibamoto, Yuta

    2016-09-01

    An effective background field removal technique is desired for more accurate quantitative susceptibility mapping (QSM) prior to dipole inversion. The aim of this study was to evaluate the accuracy of regularization enabled sophisticated harmonic artifact reduction for phase data with varying spherical kernel sizes (REV-SHARP) method using a three-dimensional head phantom and human brain data. The proposed REV-SHARP method used the spherical mean value operation and Tikhonov regularization in the deconvolution process, with varying 2-14mm kernel sizes. The kernel sizes were gradually reduced, similar to the SHARP with varying spherical kernel (VSHARP) method. We determined the relative errors and relationships between the true local field and estimated local field in REV-SHARP, VSHARP, projection onto dipole fields (PDF), and regularization enabled SHARP (RESHARP). Human experiment was also conducted using REV-SHARP, VSHARP, PDF, and RESHARP. The relative errors in the numerical phantom study were 0.386, 0.448, 0.838, and 0.452 for REV-SHARP, VSHARP, PDF, and RESHARP. REV-SHARP result exhibited the highest correlation between the true local field and estimated local field. The linear regression slopes were 1.005, 1.124, 0.988, and 0.536 for REV-SHARP, VSHARP, PDF, and RESHARP in regions of interest on the three-dimensional head phantom. In human experiments, no obvious errors due to artifacts were present in REV-SHARP. The proposed REV-SHARP is a new method combined with variable spherical kernel size and Tikhonov regularization. This technique might make it possible to be more accurate backgroud field removal and help to achive better accuracy of QSM.

  11. Background field removal technique using regularization enabled sophisticated harmonic artifact reduction for phase data with varying kernel sizes.

    PubMed

    Kan, Hirohito; Kasai, Harumasa; Arai, Nobuyuki; Kunitomo, Hiroshi; Hirose, Yasujiro; Shibamoto, Yuta

    2016-09-01

    An effective background field removal technique is desired for more accurate quantitative susceptibility mapping (QSM) prior to dipole inversion. The aim of this study was to evaluate the accuracy of regularization enabled sophisticated harmonic artifact reduction for phase data with varying spherical kernel sizes (REV-SHARP) method using a three-dimensional head phantom and human brain data. The proposed REV-SHARP method used the spherical mean value operation and Tikhonov regularization in the deconvolution process, with varying 2-14mm kernel sizes. The kernel sizes were gradually reduced, similar to the SHARP with varying spherical kernel (VSHARP) method. We determined the relative errors and relationships between the true local field and estimated local field in REV-SHARP, VSHARP, projection onto dipole fields (PDF), and regularization enabled SHARP (RESHARP). Human experiment was also conducted using REV-SHARP, VSHARP, PDF, and RESHARP. The relative errors in the numerical phantom study were 0.386, 0.448, 0.838, and 0.452 for REV-SHARP, VSHARP, PDF, and RESHARP. REV-SHARP result exhibited the highest correlation between the true local field and estimated local field. The linear regression slopes were 1.005, 1.124, 0.988, and 0.536 for REV-SHARP, VSHARP, PDF, and RESHARP in regions of interest on the three-dimensional head phantom. In human experiments, no obvious errors due to artifacts were present in REV-SHARP. The proposed REV-SHARP is a new method combined with variable spherical kernel size and Tikhonov regularization. This technique might make it possible to be more accurate backgroud field removal and help to achive better accuracy of QSM. PMID:27114339

  12. [Genetics of contact allergy].

    PubMed

    Schnuch, A

    2011-10-01

    The genetics of contact allergy (CA) is still only partly understood, despite decades of research. This might be due to inadequately defined phenotypes used in the past. Therefore we suggested studying an extreme phenotype, namely, polysensitization (sensitization to 3 or more unrelated allergens). Another approach to unravel the genetics of CA has been the study of candidate genes. In this review, we summarize studies on the associations between genetic variation (e.g. SNPs) in certain candidate genes and CA. The following polymorphisms and mutations were studied: (1) filaggrin, (2) N-acetyltransferase (NAT1 and 2), (3) glutathione-S-transferase (GST M and T), (4) manganese superoxide dismutase, (5) angiotensin-converting enzyme (ACE), (6) tumor necrosis factor (TNF), and (7) interleukin-16 (IL16). The polymorphisms of NAT1/2, GST M/T, ACE, TNF, and IL16 were shown to be associated with an increased risk of CA. In one of our studies, the increased risk conferred by the TNF and IL16 polymorphisms was confined to polysensitized individuals. Other relevant candidate genes may be identified by studying diseases related to CA in terms of clinical symptoms, a more general pathology (inflammation) and possibly an overlapping genetic background, such as irritant contact dermatitis. PMID:21904893

  13. The new genetics

    SciTech Connect

    Jaroff, L.

    1991-01-01

    Knowing the location and make-up of each of the 50,000 to 100,000 human genes will revolutionize the practice of medicine. This knowledge will lead to tailor-made therapies not only for treating disease but also for preventing it - in short, to a new concept of patient care. The Human Genome Project, a 15-year, $3 billion quest to determine the nucleotide sequence of the entire human genome, will make this possible. In The New Genetics, Leon Jaroff recounts the long path of discovery thatt has led to this huge new scientific venture - from the theory of heredity put forth by Aristotle more than 2,000 years ago to the current attempts to treat adenosine deaminase (ADA) deficiency and malignant melanoma via gene therapy. Against this background, the geneticists, molecular biologists, clinicians, and ethicists involved in the Human Genome Project describe their work and how it will provide physicians with ever more precise and effective tools to treat human disease. Jaroff also reveals the other, more problematic side of the story. Patients with an undesirable genetic profile may be subject to discrimination by private insurers. Physicians who fail to recommend genetic screening may find themselves victims of malpractice or wrongful-life suits. Indeed, these issues and others have already begun to affect physicians. The New Genetics makes it abundantly clear tha a revolution has arrived, and that physicians must be prepared to cope with the new order.

  14. Genetic and Environmental Influences on Adolescent Attachment

    ERIC Educational Resources Information Center

    Fearon, Pasco; Shmueli-Goetz, Yael; Viding, Essi; Fonagy, Peter; Plomin, Robert

    2014-01-01

    Background: Twin studies consistently point to limited genetic influence on attachment security in the infancy period, but no study has examined whether this remains the case in later development. This study presents the findings from a twin study examining the relative importance of genetic and environmental influences on attachment in…

  15. The antifungal plant defensin AtPDF2.3 from Arabidopsis thaliana blocks potassium channels.

    PubMed

    Vriens, Kim; Peigneur, Steve; De Coninck, Barbara; Tytgat, Jan; Cammue, Bruno P A; Thevissen, Karin

    2016-01-01

    Scorpion toxins that block potassium channels and antimicrobial plant defensins share a common structural CSαβ-motif. These toxins contain a toxin signature (K-C4-X-N) in their amino acid sequence, and based on in silico analysis of 18 plant defensin sequences, we noted the presence of a toxin signature (K-C5-R-G) in the amino acid sequence of the Arabidopsis thaliana defensin AtPDF2.3. We found that recombinant (r)AtPDF2.3 blocks Kv1.2 and Kv1.6 potassium channels, akin to the interaction between scorpion toxins and potassium channels. Moreover, rAtPDF2.3[G36N], a variant with a KCXN toxin signature (K-C5-R-N), is more potent in blocking Kv1.2 and Kv1.6 channels than rAtPDF2.3, whereas rAtPDF2.3[K33A], devoid of the toxin signature, is characterized by reduced Kv channel blocking activity. These findings highlight the importance of the KCXN scorpion toxin signature in the plant defensin sequence for blocking potassium channels. In addition, we found that rAtPDF2.3 inhibits the growth of Saccharomyces cerevisiae and that pathways regulating potassium transport and/or homeostasis confer tolerance of this yeast to rAtPDF2.3, indicating a role for potassium homeostasis in the fungal defence response towards rAtPDF2.3. Nevertheless, no differences in antifungal potency were observed between the rAtPDF2.3 variants, suggesting that antifungal activity and Kv channel inhibitory function are not linked. PMID:27573545

  16. The antifungal plant defensin AtPDF2.3 from Arabidopsis thaliana blocks potassium channels

    PubMed Central

    Vriens, Kim; Peigneur, Steve; De Coninck, Barbara; Tytgat, Jan; Cammue, Bruno P. A.; Thevissen, Karin

    2016-01-01

    Scorpion toxins that block potassium channels and antimicrobial plant defensins share a common structural CSαβ-motif. These toxins contain a toxin signature (K-C4-X-N) in their amino acid sequence, and based on in silico analysis of 18 plant defensin sequences, we noted the presence of a toxin signature (K-C5-R-G) in the amino acid sequence of the Arabidopsis thaliana defensin AtPDF2.3. We found that recombinant (r)AtPDF2.3 blocks Kv1.2 and Kv1.6 potassium channels, akin to the interaction between scorpion toxins and potassium channels. Moreover, rAtPDF2.3[G36N], a variant with a KCXN toxin signature (K-C5-R-N), is more potent in blocking Kv1.2 and Kv1.6 channels than rAtPDF2.3, whereas rAtPDF2.3[K33A], devoid of the toxin signature, is characterized by reduced Kv channel blocking activity. These findings highlight the importance of the KCXN scorpion toxin signature in the plant defensin sequence for blocking potassium channels. In addition, we found that rAtPDF2.3 inhibits the growth of Saccharomyces cerevisiae and that pathways regulating potassium transport and/or homeostasis confer tolerance of this yeast to rAtPDF2.3, indicating a role for potassium homeostasis in the fungal defence response towards rAtPDF2.3. Nevertheless, no differences in antifungal potency were observed between the rAtPDF2.3 variants, suggesting that antifungal activity and Kv channel inhibitory function are not linked. PMID:27573545

  17. Specific Genetic Disorders

    MedlinePlus

    ... of Genetic Terms Definitions for genetic terms Specific Genetic Disorders Many human diseases have a genetic component. ... Condition in an Adult The Undiagnosed Diseases Program Genetic Disorders Achondroplasia Alpha-1 Antitrypsin Deficiency Antiphospholipid Syndrome ...

  18. Non-Gaussian PDF Modeling of Turbulent Boundary Layer Fluctuating Pressure Excitation

    NASA Technical Reports Server (NTRS)

    Steinwolf, Alexander; Rizzi, Stephen A.

    2003-01-01

    The purpose of the study is to investigate properties of the probability density function (PDF) of turbulent boundary layer fluctuating pressures measured on the exterior of a supersonic transport aircraft. It is shown that fluctuating pressure PDFs differ from the Gaussian distribution even for surface conditions having no significant discontinuities. The PDF tails are wider and longer than those of the Gaussian model. For pressure fluctuations upstream of forward-facing step discontinuities and downstream of aft-facing step discontinuities, deviations from the Gaussian model are more significant and the PDFs become asymmetrical. Various analytical PDF distributions are used and further developed to model this behavior.

  19. A hybrid Reynolds averaged/PDF closure model for supersonic turbulent combustion

    NASA Technical Reports Server (NTRS)

    Frankel, Steven H.; Hassan, H. A.; Drummond, J. Philip

    1990-01-01

    A hybrid Reynolds averaged/assumed pdf approach has been developed and applied to the study of turbulent combustion in a supersonic mixing layer. This approach is used to address the 'laminar-like' treatment of the thermochemical terms that appear in the conservation equations. Calculations were carried out for two experiments involving H2-air supersonic turbulent mixing. Two different forms of the pdf were implemented. In general, the results show modest improvement from previous calculations. Moreover, the results appear to be somewhat independent of the form of the assumed pdf.

  20. PDF calculation of scalar mixing layer with simple chemical reactions

    NASA Astrophysics Data System (ADS)

    Kanzaki, Takao; Pope, Stephen B.

    1999-11-01

    A joint velocity-composition-turbulent frequency PDF(JPDF) model is used to simulate reactive mixing layer in a grid-generated turbulence with the influence of second-order irreversible chemical reactions. To investigate the effects of molecular mixing, a gas flow and a liquid flow are simulated. For a gas flow, the oxidation reaction (NO+ O3 arrow NO2 +O2 ) between nitricoxide (NO) and ozone (O3 ) is used. For a liquid flow, the saponification reaction(NaOH+HCOOCH3 arrow HCOONa+CH_3OH) between sodiumhydroxide(NaOH) and methylformate(HCOOCH_3) is used. The both cases are moderately fast reactions. Therefore, reactive scalar statistics are affected by turbulent mixing. The results of caliculation are compared with experimental data of Komori et al.(1994) and Bilger et al.(1991)

  1. CDF and PDF Comparison Between Humacao, Puerto Rico and Florida

    NASA Technical Reports Server (NTRS)

    Gonzalez-Rodriguez, Rosana

    2004-01-01

    The knowledge of the atmospherics phenomenon is an important part in the communication system. The principal factor that contributes to the attenuation in a Ka band communication system is the rain attenuation. We have four years of tropical region observations. The data in the tropical region was taken in Humacao, Puerto Rico. Previous data had been collected at various climate regions such as desserts, template area and sub-tropical regions. Figure 1 shows the ITU-R rain zone map for North America. Rain rates are important to the rain attenuation prediction models. The models that predict attenuation generally are of two different kinds. The first one is the regression models. By using a data set these models provide an idea of the observed attenuation and rain rates distribution in the present, past and future. The second kinds of models are physical models which use the probability density functions (PDF).

  2. A k-omega-multivariate beta PDF for supersonic combustion

    NASA Technical Reports Server (NTRS)

    Alexopoulos, G. A.; Baurle, R. A.; Hassan, H. A.

    1992-01-01

    In an attempt to study the interaction between combustion and turbulence in supersonic flows, an assumed PDF has been employed. This makes it possible to calculate the time average of the chemical source terms that appear in the species conservation equations. In order to determine the averages indicated in an equation, two transport equations, one for the temperature (enthalpy) variance and one for Q, are required. Model equations are formulated for such quantities. The turbulent time scale controls the evolution. An algebraic model similar to that used by Eklund et al was used in an attempt to predict the recent measurements of Cheng et al. Predictions were satisfactory before ignition but were less satisfactory after ignition. One of the reasons for this behavior is the inadequacy of the algebraic turbulence model employed. Because of this, the objective of this work is to develop a k-omega model to remedy the situation.

  3. Genetic haemochromatosis.

    PubMed

    Rosalki, S B

    2002-10-01

    Genetic haemochromatosis is an autosomal recessive inherited disorder of iron metabolism due to mutation of the HFE gene. In homozygotes (1 in 300 of the UK population), this results in excessive iron absorption from the gut and its deposition in major body organs. This may give rise to fatigue, arthritis, cardiac failure, diabetes mellitus, hepatic cirrhosis or skin pigmentation, occurring predominantly in males over 50 years of age. Identification uses measurement of serum iron, iron-binding capacity (or transferrin) and ferritin, together with initial or confirmatory genetic DNA studies.

  4. The probability density function (PDF) of Lagrangian Turbulence

    NASA Astrophysics Data System (ADS)

    Birnir, B.

    2012-12-01

    The statistical theory of Lagrangian turbulence is derived from the stochastic Navier-Stokes equation. Assuming that the noise in fully-developed turbulence is a generic noise determined by the general theorems in probability, the central limit theorem and the large deviation principle, we are able to formulate and solve the Kolmogorov-Hopf equation for the invariant measure of the stochastic Navier-Stokes equations. The intermittency corrections to the scaling exponents of the structure functions require a multiplicative (multipling the fluid velocity) noise in the stochastic Navier-Stokes equation. We let this multiplicative noise, in the equation, consists of a simple (Poisson) jump process and then show how the Feynmann-Kac formula produces the log-Poissonian processes, found by She and Leveque, Waymire and Dubrulle. These log-Poissonian processes give the intermittency corrections that agree with modern direct Navier-Stokes simulations (DNS) and experiments. The probability density function (PDF) plays a key role when direct Navier-Stokes simulations or experimental results are compared to theory. The statistical theory of turbulence is determined, including the scaling of the structure functions of turbulence, by the invariant measure of the Navier-Stokes equation and the PDFs for the various statistics (one-point, two-point, N-point) can be obtained by taking the trace of the corresponding invariant measures. Hopf derived in 1952 a functional equation for the characteristic function (Fourier transform) of the invariant measure. In distinction to the nonlinear Navier-Stokes equation, this is a linear functional differential equation. The PDFs obtained from the invariant measures for the velocity differences (two-point statistics) are shown to be the four parameter generalized hyperbolic distributions, found by Barndorff-Nilsen. These PDF have heavy tails and a convex peak at the origin. A suitable projection of the Kolmogorov-Hopf equations is the

  5. Genetic modifiers and oligogenic inheritance.

    PubMed

    Kousi, Maria; Katsanis, Nicholas

    2015-06-01

    Despite remarkable progress in the identification of mutations that drive genetic disorders, progress in understanding the effect of genetic background on the penetrance and expressivity of causal alleles has been modest, in part because of the methodological challenges in identifying genetic modifiers. Nonetheless, the progressive discovery of modifier alleles has improved both our interpretative ability and our analytical tools to dissect such phenomena. In this review, we analyze the genetic properties and behaviors of modifiers as derived from studies in patient populations and model organisms and we highlight conceptual and technological tools used to overcome some of the challenges inherent in modifier mapping and cloning. Finally, we discuss how the identification of these modifiers has facilitated the elucidation of biological pathways and holds the potential to improve the clinical predictive value of primary causal mutations and to develop novel drug targets.

  6. Genetic Disorders

    MedlinePlus

    ... of pregnancy loss. How do I know which tests to have? Your health care provider or a genetic counselor can discuss all of the testing options with you and help you decide based on your individual risk factors. Do I have to have these tests? Whether you want to be tested is a ...

  7. Genetic Recombination

    ERIC Educational Resources Information Center

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  8. An assumed joint-Beta PDF approach for supersonic turbulent combustion

    SciTech Connect

    Baurle, R.A.; Alexopoulos, G.A.; Hassan, H.A.; Drummond, J.P. NASA, Langley Research Center, Hampton, VA )

    1992-07-01

    In a recent experiment, Cheng et al. (1991) used ultraviolet spontaneous vibrational Raman scattering and laser-induced predissociative fluorescence techniques for simultaneous measurements of temperature and concentrations of O2, H2, H2O, OH, and N2 (and their rms) in supersonic turbulent reacting shear layers. Because present computational techniques are not suited for prediction of all of the above measurements, a new approach has been developed and is being used to predict all relevant flow properties and their rms (where appropriate). The approach explores the use of a joint-Beta PDF for concentrations. It was found that the general expression of this PDF was impractical because of decoding problems resulting from determining the various parameters of the PDF. Thus, a special case of this general expression was considered. Calculations using this simplified version of the joint-Beta PDF were not consistent with the available data from the experiment. 9 refs.

  9. Disk diffusion quality control guidelines for NVP-PDF 713: a novel peptide deformylase inhibitor.

    PubMed

    Anderegg, Tamara R; Jones, Ronald N

    2004-01-01

    NVP-PDF713 is a peptide deformylase inhibitor that has emerged as a candidate for treating Gram-positive infections and selected Gram-negative species that commonly cause community-acquired respiratory tract infections. This report summarizes the results of a multi-center (seven participants) disk diffusion quality control (QC) investigation for NVP PDF-713 using guidelines of the National Committee for Clinical Laboratory Standards and the standardized disk diffusion method. A total of 420 NVP-PDF 713 zone diameter values were generated for each QC organism. The proposed zone diameter ranges contained 97.6-99.8% of the reported participant results and were: Staphylococcus aureus ATCC 25923 (25-35 mm), Streptococcus pneumoniae ATCC 49619 (30-37 mm), and Haemophilus influenzae ATCC 49247 (24-32 mm). These QC criteria for the disk diffusion method should be applied during the NVP-PDF 713 clinical trials to maximize test accuracy.

  10. Evaluation of a Consistent LES/PDF Method Using a Series of Experimental Spray Flames

    NASA Astrophysics Data System (ADS)

    Heye, Colin; Raman, Venkat

    2012-11-01

    A consistent method for the evolution of the joint-scalar probability density function (PDF) transport equation is proposed for application to large eddy simulation (LES) of turbulent reacting flows containing evaporating spray droplets. PDF transport equations provide the benefit of including the chemical source term in closed form, however, additional terms describing LES subfilter mixing must be modeled. The recent availability of detailed experimental measurements provide model validation data for a wide range of evaporation rates and combustion regimes, as is well-known to occur in spray flames. In this work, the experimental data will used to investigate the impact of droplet mass loading and evaporation rates on the subfilter scalar PDF shape in comparison with conventional flamelet models. In addition, existing model term closures in the PDF transport equations are evaluated with a focus on their validity in the presence of regime changes.

  11. Using Interactive 3D PDF for Exploring Complex Biomedical Data: Experiences and Solutions.

    PubMed

    Newe, Axel; Becker, Linda

    2016-01-01

    The Portable Document Format (PDF) is the most commonly used file format for the exchange of electronic documents. A lesser-known feature of PDF is the possibility to embed three-dimensional models and to display these models interactively with a qualified reader. This technology is well suited to present, to explore and to communicate complex biomedical data. This applies in particular for data which would suffer from a loss of information if it was reduced to a static two-dimensional projection. In this article, we present applications of 3D PDF for selected scholarly and clinical use cases in the biomedical domain. Furthermore, we present a sophisticated tool for the generation of respective PDF documents. PMID:27577484

  12. Combined PDF and Rietveld studies of ADORable zeolites and the disordered intermediate IPC-1P.

    PubMed

    Morris, Samuel A; Wheatley, Paul S; Položij, Miroslav; Nachtigall, Petr; Eliášová, Pavla; Čejka, Jiří; Lucas, Tim C; Hriljac, Joseph A; Pinar, Ana B; Morris, Russell E

    2016-09-28

    The disordered intermediate of the ADORable zeolite UTL has been structurally confirmed using the pair distribution function (PDF) technique. The intermediate, IPC-1P, is a disordered layered compound formed by the hydrolysis of UTL in 0.1 M hydrochloric acid solution. Its structure is unsolvable by traditional X-ray diffraction techniques. The PDF technique was first benchmarked against high-quality synchrotron Rietveld refinements of IPC-2 (OKO) and IPC-4 (PCR) - two end products of IPC-1P condensation that share very similar structural features. An IPC-1P starting model derived from density functional theory was used for the PDF refinement, which yielded a final fit of Rw = 18% and a geometrically reasonable structure. This confirms the layers do stay intact throughout the ADOR process and shows PDF is a viable technique for layered zeolite structure determination. PMID:27527381

  13. An assumed joint-Beta PDF approach for supersonic turbulent combustion

    NASA Technical Reports Server (NTRS)

    Baurle, R. A.; Alexopoulos, G. A.; Hassan, H. A.; Drummond, J. P.

    1992-01-01

    In a recent experiment, Cheng et al. (1991) used ultraviolet spontaneous vibrational Raman scattering and laser-induced predissociative fluorescence techniques for simultaneous measurements of temperature and concentrations of O2, H2, H2O, OH, and N2 (and their rms) in supersonic turbulent reacting shear layers. Because present computational techniques are not suited for prediction of all of the above measurements, a new approach has been developed and is being used to predict all relevant flow properties and their rms (where appropriate). The approach explores the use of a joint-Beta PDF for concentrations. It was found that the general expression of this PDF was impractical because of decoding problems resulting from determining the various parameters of the PDF. Thus, a special case of this general expression was considered. Calculations using this simplified version of the joint-Beta PDF were not consistent with the available data from the experiment.

  14. Multipurpose background for standardization in medical photography.

    PubMed

    Hallock, G G

    1985-08-01

    A dual photography background system consisting of a quadrilled format on one side and a plain background on the other is described. It is mobile and efficient as a space- and time-saving device for medical photography.

  15. Modeling Interactions Among Turbulence, Gas-Phase Chemistry, Soot and Radiation Using Transported PDF Methods

    NASA Astrophysics Data System (ADS)

    Haworth, Daniel

    2013-11-01

    The importance of explicitly accounting for the effects of unresolved turbulent fluctuations in Reynolds-averaged and large-eddy simulations of chemically reacting turbulent flows is increasingly recognized. Transported probability density function (PDF) methods have emerged as one of the most promising modeling approaches for this purpose. In particular, PDF methods provide an elegant and effective resolution to the closure problems that arise from averaging or filtering terms that correspond to nonlinear point processes, including chemical reaction source terms and radiative emission. PDF methods traditionally have been associated with studies of turbulence-chemistry interactions in laboratory-scale, atmospheric-pressure, nonluminous, statistically stationary nonpremixed turbulent flames; and Lagrangian particle-based Monte Carlo numerical algorithms have been the predominant method for solving modeled PDF transport equations. Recent advances and trends in PDF methods are reviewed and discussed. These include advances in particle-based algorithms, alternatives to particle-based algorithms (e.g., Eulerian field methods), treatment of combustion regimes beyond low-to-moderate-Damköhler-number nonpremixed systems (e.g., premixed flamelets), extensions to include radiation heat transfer and multiphase systems (e.g., soot and fuel sprays), and the use of PDF methods as the basis for subfilter-scale modeling in large-eddy simulation. Examples are provided that illustrate the utility and effectiveness of PDF methods for physics discovery and for applications to practical combustion systems. These include comparisons of results obtained using the PDF method with those from models that neglect unresolved turbulent fluctuations in composition and temperature in the averaged or filtered chemical source terms and/or the radiation heat transfer source terms. In this way, the effects of turbulence-chemistry-radiation interactions can be isolated and quantified.

  16. Cancer Genetics Services Directory

    MedlinePlus

    ... Overview–for health professionals Research NCI Cancer Genetics Services Directory This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic ...

  17. The impact of the photon PDF and electroweak corrections on t bar{t} distributions

    NASA Astrophysics Data System (ADS)

    Pagani, D.; Tsinikos, I.; Zaro, M.

    2016-09-01

    We discuss the impact of EW corrections on differential distributions in top-quark pair production at the LHC and future hadron colliders, focussing on the effects of initial-state photons. Performing a calculation at Next-to-Leading Order QCD+EW accuracy, we investigate in detail the impact of photon-initiated channels on central values as well as PDF and scale uncertainties, both at order α _sα and α _s^2α . We present predictions at 13 and 100 TeV, and provide results for the 8 TeV differential measurements performed by ATLAS and CMS. A thorough comparison of results obtained with the NNPDF2.3QED and CT14QED PDF sets is performed. While contributions due to the photon PDF are negligible with CT14QED, this is not the case for NNPDF2.3QED, where such contributions are sizeable and show large PDF uncertainties. On the one hand, we show that differential observables in top-pair production, in particular top-quark and tbar{t} rapidities, can be used to improve the determination of the photon PDF within the NNPDF approach. On the other hand, with current PDF sets, we demonstrate the necessity of including EW corrections and photon-induced contributions for a correct determination of both the central value and the uncertainties of theoretical predictions.

  18. Accurate and computationally efficient mixing models for the simulation of turbulent mixing with PDF methods

    NASA Astrophysics Data System (ADS)

    Meyer, Daniel W.; Jenny, Patrick

    2013-08-01

    Different simulation methods are applicable to study turbulent mixing. When applying probability density function (PDF) methods, turbulent transport, and chemical reactions appear in closed form, which is not the case in second moment closure methods (RANS). Moreover, PDF methods provide the entire joint velocity-scalar PDF instead of a limited set of moments. In PDF methods, however, a mixing model is required to account for molecular diffusion. In joint velocity-scalar PDF methods, mixing models should also account for the joint velocity-scalar statistics, which is often under appreciated in applications. The interaction by exchange with the conditional mean (IECM) model accounts for these joint statistics, but requires velocity-conditional scalar means that are expensive to compute in spatially three dimensional settings. In this work, two alternative mixing models are presented that provide more accurate PDF predictions at reduced computational cost compared to the IECM model, since no conditional moments have to be computed. All models are tested for different mixing benchmark cases and their computational efficiencies are inspected thoroughly. The benchmark cases involve statistically homogeneous and inhomogeneous settings dealing with three streams that are characterized by two passive scalars. The inhomogeneous case clearly illustrates the importance of accounting for joint velocity-scalar statistics in the mixing model. Failure to do so leads to significant errors in the resulting scalar means, variances and other statistics.

  19. A New LES/PDF Method for Computational Modeling of Turbulent Reacting Flows

    NASA Astrophysics Data System (ADS)

    Turkeri, Hasret; Muradoglu, Metin; Pope, Stephen B.

    2013-11-01

    A new LES/PDF method is developed for computational modeling of turbulent reacting flows. The open source package, OpenFOAM, is adopted as the LES solver and combined with the particle-based Monte Carlo method to solve the LES/PDF model equations. The dynamic Smagorinsky model is employed to account for the subgrid-scale motions. The LES solver is first validated for the Sandia Flame D using a steady flamelet method in which the chemical compositions, density and temperature fields are parameterized by the mean mixture fraction and its variance. In this approach, the modeled transport equations for the mean mixture fraction and the square of the mixture fraction are solved and the variance is then computed from its definition. The results are found to be in a good agreement with the experimental data. Then the LES solver is combined with the particle-based Monte Carlo algorithm to form a complete solver for the LES/PDF model equations. The in situ adaptive tabulation (ISAT) algorithm is incorporated into the LES/PDF method for efficient implementation of detailed chemical kinetics. The LES/PDF method is also applied to the Sandia Flame D using the GRI-Mech 3.0 chemical mechanism and the results are compared with the experimental data and the earlier PDF simulations. The Scientific and Technical Research Council of Turkey (TUBITAK), Grant No. 111M067.

  20. Genetics of inherited cardiomyopathy

    PubMed Central

    Jacoby, Daniel; McKenna, William J.

    2012-01-01

    During the past two decades, numerous disease-causing genes for different cardiomyopathies have been identified. These discoveries have led to better understanding of disease pathogenesis and initial steps in the application of mutation analysis in the evaluation of affected individuals and their family members. As knowledge of the genetic abnormalities, and insight into cellular and organ biology has grown, so has appreciation of the level of complexity of interaction between genotype and phenotype across disease states. What were initially thought to be one-to-one gene-disease correlates have turned out to display important relational plasticity dependent in large part on the genetic and environmental backgrounds into which the genes of interest express. The current state of knowledge with regard to genetics of cardiomyopathy represents a starting point to address the biology of disease, but is not yet developed sufficiently to supplant clinically based classification systems or, in most cases, to guide therapy to any significant extent. Future work will of necessity be directed towards elucidation of the biological mechanisms of both rare and common gene variants and environmental determinants of plasticity in the genotype–phenotype relationship with the ultimate goal of furthering our ability to identify, diagnose, risk stratify, and treat this group of disorders which cause heart failure and sudden death in the young. PMID:21810862

  1. Genetic testing, genetic medicine, and managed care.

    PubMed

    Rothstein, M A; Hoffman, S

    1999-01-01

    As modern human genetics moves from the research setting to the clinical setting, it will encounter the managed care system. Issues of cost, access, and quality of care will affect the availability and nature of genetic testing, genetic counseling, and genetic therapies. This Article will explore such issues as professional education, coverage of genetic services, privacy and confidentiality, and liability. It will conclude with a series of recommendations for the practice of genetic medicine in the age of managed care.

  2. The PDF4LHC report on PDFs and LHC data: Results from Run I and preparation for Run II

    DOE PAGES

    Rojo, Juan; Accardi, Alberto; Ball, Richard D.; Cooper-Sarkar, Amanda; Roeck, Albert de; Farry, Stephen; Ferrando, James; Forte, Stefano; Gao, Jun; Harland-Lang, Lucian; et al

    2015-09-16

    The accurate determination of the Parton Distribution Functions (PDFs) of the proton is an essential ingredient of the Large Hadron Collider (LHC) program. PDF uncertainties impact a wide range of processes, from Higgs boson characterisation and precision Standard Model measurements to New Physics searches. A major recent development in modern PDF analyses has been to exploit the wealth of new information contained in precision measurements from the LHC Run I, as well as progress in tools and methods to include these data in PDF fits. In this report we summarise the information that PDF-sensitive measurements at the LHC have providedmore » so far, and review the prospects for further constraining PDFs with data from the recently started Run II. Lastly, this document aims to provide useful input to the LHC collaborations to prioritise their PDF-sensitive measurements at Run II, as well as a comprehensive reference for the PDF-fitting collaborations.« less

  3. The PDF4LHC report on PDFs and LHC data: Results from Run I and preparation for Run II

    SciTech Connect

    Rojo, Juan; Accardi, Alberto; Ball, Richard D.; Cooper-Sarkar, Amanda; de Roeck, Albert; Farry, Stephen; Ferrando, James; Forte, Stefano; Gao, Jun; Harland-Lang, Lucian; Huston, Joey; Glazov, Alexander; Gouzevitch, Maxime; Gwenlan, Claire; Lipka, Katerina; Lisovyi, Mykhailo; Mangano, Michelangelo; Nadolsky, Pavel; Perrozzi, Luca; Plačakytė, Ringaile; Radescu, Voica; Salam, Gavin P.; Thorne, Robert

    2015-09-16

    The accurate determination of Parton Distribution Functions (PDFs) of the proton is an essential ingredient of the Large Hadron Collider (LHC) program. PDF uncertainties impact a wide range of processes, from Higgs boson characterization and precision Standard Model measurements to New Physics searches. A major recent development in modern PDF analyses has been to exploit the wealth of new information contained in precision measurements from the LHC Run I, as well as progress in tools and methods to include these data in PDF fits. In this report we summarize the information that PDF-sensitive measurements at the LHC have provided so far, and review the prospects for further constraining PDFs with data from the recently started Run II. As a result, this document aims to provide useful input to the LHC collaborations to prioritize their PDF-sensitive measurements at Run II, as well as a comprehensive reference for the PDF-fitting collaborations.

  4. The PDF4LHC report on PDFs and LHC data: Results from Run I and preparation for Run II

    DOE PAGES

    Rojo, Juan; Accardi, Alberto; Ball, Richard D.; Cooper-Sarkar, Amanda; de Roeck, Albert; Farry, Stephen; Ferrando, James; Forte, Stefano; Gao, Jun; Harland-Lang, Lucian; et al

    2015-09-16

    The accurate determination of Parton Distribution Functions (PDFs) of the proton is an essential ingredient of the Large Hadron Collider (LHC) program. PDF uncertainties impact a wide range of processes, from Higgs boson characterization and precision Standard Model measurements to New Physics searches. A major recent development in modern PDF analyses has been to exploit the wealth of new information contained in precision measurements from the LHC Run I, as well as progress in tools and methods to include these data in PDF fits. In this report we summarize the information that PDF-sensitive measurements at the LHC have provided somore » far, and review the prospects for further constraining PDFs with data from the recently started Run II. As a result, this document aims to provide useful input to the LHC collaborations to prioritize their PDF-sensitive measurements at Run II, as well as a comprehensive reference for the PDF-fitting collaborations.« less

  5. Human genetics

    SciTech Connect

    Carlson, E.A.

    1984-01-01

    This text provides full and balanced coverage of the concepts requisite for a thorough understanding of human genetics. Applications to both the individual and society are integrated throughout the lively and personal narrative, and the essential principles of heredity are clearly presented to prepare students for informed participation in public controversies. High-interest, controversial topics, including recombinant DNA technology, oncogenes, embryo transfer, environmental mutagens and carcinogens, IQ testing, and eugenics encourage understanding of important social issues.

  6. Mitochondrial genetics

    PubMed Central

    Chinnery, Patrick Francis; Hudson, Gavin

    2013-01-01

    Introduction In the last 10 years the field of mitochondrial genetics has widened, shifting the focus from rare sporadic, metabolic disease to the effects of mitochondrial DNA (mtDNA) variation in a growing spectrum of human disease. The aim of this review is to guide the reader through some key concepts regarding mitochondria before introducing both classic and emerging mitochondrial disorders. Sources of data In this article, a review of the current mitochondrial genetics literature was conducted using PubMed (http://www.ncbi.nlm.nih.gov/pubmed/). In addition, this review makes use of a growing number of publically available databases including MITOMAP, a human mitochondrial genome database (www.mitomap.org), the Human DNA polymerase Gamma Mutation Database (http://tools.niehs.nih.gov/polg/) and PhyloTree.org (www.phylotree.org), a repository of global mtDNA variation. Areas of agreement The disruption in cellular energy, resulting from defects in mtDNA or defects in the nuclear-encoded genes responsible for mitochondrial maintenance, manifests in a growing number of human diseases. Areas of controversy The exact mechanisms which govern the inheritance of mtDNA are hotly debated. Growing points Although still in the early stages, the development of in vitro genetic manipulation could see an end to the inheritance of the most severe mtDNA disease. PMID:23704099

  7. Genetic Testing (For Parents)

    MedlinePlus

    ... Story" 5 Things to Know About Zika & Pregnancy Genetic Testing KidsHealth > For Parents > Genetic Testing Print A ... blood, skin, bone, or other tissue is needed. Genetic Testing During Pregnancy For genetic testing before birth, ...

  8. Cancer Genetics Services Directory

    MedlinePlus

    ... Services Directory Cancer Prevention Overview Research NCI Cancer Genetics Services Directory This directory lists professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, ...

  9. Explanatory Models of Genetics and Genetic Risk among a Selected Group of Students.

    PubMed

    Goltz, Heather Honoré; Bergman, Margo; Goodson, Patricia

    2016-01-01

    This exploratory qualitative study focuses on how college students conceptualize genetics and genetic risk, concepts essential for genetic literacy (GL) and genetic numeracy (GN), components of overall health literacy (HL). HL is dependent on both the background knowledge and culture of a patient, and lower HL is linked to increased morbidity and mortality for a number of chronic health conditions (e.g., diabetes and cancer). A purposive sample of 86 students from three Southwestern universities participated in eight focus groups. The sample ranged in age from 18 to 54 years, and comprised primarily of female (67.4%), single (74.4%), and non-White (57%) participants, none of whom were genetics/biology majors. A holistic-content approach revealed broad categories concerning participants' explanatory models (EMs) of genetics and genetic risk. Participants' EMs were grounded in highly contextualized narratives that only partially overlapped with biomedical models. While higher education levels should be associated with predominately knowledge-based EM of genetic risk, this study shows that even in well-educated populations cultural factors can dominate. Study findings reveal gaps in how this sample of young adults obtains, processes, and understands genetic/genomic concepts. Future studies should assess how individuals with low GL and GN obtain and process genetics and genetic risk information and incorporate this information into health decision making. Future work should also address the interaction of communication between health educators, providers, and genetic counselors, to increase patient understanding of genetic risk. PMID:27376052

  10. Explanatory Models of Genetics and Genetic Risk among a Selected Group of Students

    PubMed Central

    Goltz, Heather Honoré; Bergman, Margo; Goodson, Patricia

    2016-01-01

    This exploratory qualitative study focuses on how college students conceptualize genetics and genetic risk, concepts essential for genetic literacy (GL) and genetic numeracy (GN), components of overall health literacy (HL). HL is dependent on both the background knowledge and culture of a patient, and lower HL is linked to increased morbidity and mortality for a number of chronic health conditions (e.g., diabetes and cancer). A purposive sample of 86 students from three Southwestern universities participated in eight focus groups. The sample ranged in age from 18 to 54 years, and comprised primarily of female (67.4%), single (74.4%), and non-White (57%) participants, none of whom were genetics/biology majors. A holistic-content approach revealed broad categories concerning participants’ explanatory models (EMs) of genetics and genetic risk. Participants’ EMs were grounded in highly contextualized narratives that only partially overlapped with biomedical models. While higher education levels should be associated with predominately knowledge-based EM of genetic risk, this study shows that even in well-educated populations cultural factors can dominate. Study findings reveal gaps in how this sample of young adults obtains, processes, and understands genetic/genomic concepts. Future studies should assess how individuals with low GL and GN obtain and process genetics and genetic risk information and incorporate this information into health decision making. Future work should also address the interaction of communication between health educators, providers, and genetic counselors, to increase patient understanding of genetic risk. PMID:27376052

  11. Dragon Genetics.

    ERIC Educational Resources Information Center

    Harrell, Pamela Esprivalo

    1997-01-01

    Describes an activity that combines Mendel's Postulates with Morgan's Chromosome theory of inheritance. Students pair up the mother's and father's genes and learn how the genes line up with each other. Background information on the theories is provided and tips that can be used to aid student understanding are included. (DDR)

  12. Demonstration of thin film pair distribution function analysis (tfPDF) for the study of local structure in amorphous and crystalline thin films

    SciTech Connect

    Jensen, K. M.Ø.; Blichfeld, A. B.; Bauers, S. R.; Wood, S. R.; Dooryhee, E.; Johnson, D. C.; Iversen, B. B.; Billinge, S.

    2015-07-05

    By means of normal incidence, high flux and high energy x-rays, we have obtained total scattering data for Pair Distribution Function (PDF) analysis from thin films (tf), suitable for local structure analysis. By using amorphous substrates as support for the films, the standard Rapid Acquisition PDF setup can be applied and the scattering signal from the film can be isolated from the total scattering data through subtraction of an independently measured background signal. No angular corrections to the data are needed, as would be the case for grazing incidence measurements. We illustrate the ‘tfPDF’ method through studies of as deposited (i.e. amorphous) and crystalline FeSb3 films, where the local structure analysis gives insight into the stabilization of the metastable skutterudite FeSb3 phase. The films were prepared by depositing ultra-thin alternating layers of Fe and Sb, which interdiffuse and after annealing crystallize to form the FeSb3 structure. The tfPDF data show that the amorphous precursor phase consists of corner-sharing FeSb6 octahedra with motifs highly resembling the local structure in crystalline FeSb3. Analysis of the amorphous structure allows predicting whether the final crystalline product will form the FeSb3 phase with or without excess Sb present. The study thus illustrates how analysis of the local structure in amorphous precursor films can help to understand crystallization processes of metastable phases and opens for a range of new local structure studies of thin films.

  13. Demonstration of thin film pair distribution function analysis (tfPDF) for the study of local structure in amorphous and crystalline thin films

    DOE PAGES

    Jensen, K. M.Ø.; Blichfeld, A. B.; Bauers, S. R.; Wood, S. R.; Dooryhee, E.; Johnson, D. C.; Iversen, B. B.; Billinge, S.

    2015-07-05

    By means of normal incidence, high flux and high energy x-rays, we have obtained total scattering data for Pair Distribution Function (PDF) analysis from thin films (tf), suitable for local structure analysis. By using amorphous substrates as support for the films, the standard Rapid Acquisition PDF setup can be applied and the scattering signal from the film can be isolated from the total scattering data through subtraction of an independently measured background signal. No angular corrections to the data are needed, as would be the case for grazing incidence measurements. We illustrate the ‘tfPDF’ method through studies of as depositedmore » (i.e. amorphous) and crystalline FeSb3 films, where the local structure analysis gives insight into the stabilization of the metastable skutterudite FeSb3 phase. The films were prepared by depositing ultra-thin alternating layers of Fe and Sb, which interdiffuse and after annealing crystallize to form the FeSb3 structure. The tfPDF data show that the amorphous precursor phase consists of corner-sharing FeSb6 octahedra with motifs highly resembling the local structure in crystalline FeSb3. Analysis of the amorphous structure allows predicting whether the final crystalline product will form the FeSb3 phase with or without excess Sb present. The study thus illustrates how analysis of the local structure in amorphous precursor films can help to understand crystallization processes of metastable phases and opens for a range of new local structure studies of thin films.« less

  14. Extra dimensions: 3D and time in PDF documentation

    NASA Astrophysics Data System (ADS)

    Graf, N. A.

    2011-01-01

    Experimental science is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universal 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide, non-technical audience. We discuss how the field of radiation imaging could benefit from incorporating full 3D information about not only the detectors, but also the results of the experimental analyses, in its electronic publications. In this article, we present examples drawn from high-energy physics, mathematics and molecular biology which take advantage of this functionality. We demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input.

  15. Extra Dimensions: 3D and Time in PDF Documentation

    SciTech Connect

    Graf, N.A.; /SLAC

    2012-04-11

    Experimental science is replete with multi-dimensional information which is often poorly represented by the two dimensions of presentation slides and print media. Past efforts to disseminate such information to a wider audience have failed for a number of reasons, including a lack of standards which are easy to implement and have broad support. Adobe's Portable Document Format (PDF) has in recent years become the de facto standard for secure, dependable electronic information exchange. It has done so by creating an open format, providing support for multiple platforms and being reliable and extensible. By providing support for the ECMA standard Universal 3D (U3D) file format in its free Adobe Reader software, Adobe has made it easy to distribute and interact with 3D content. By providing support for scripting and animation, temporal data can also be easily distributed to a wide, non-technical audience. We discuss how the field of radiation imaging could benefit from incorporating full 3D information about not only the detectors, but also the results of the experimental analyses, in its electronic publications. In this article, we present examples drawn from high-energy physics, mathematics and molecular biology which take advantage of this functionality. We demonstrate how 3D detector elements can be documented, using either CAD drawings or other sources such as GEANT visualizations as input.

  16. eMeteorNews: website and PDF journal

    NASA Astrophysics Data System (ADS)

    Roggemans, P.; Kacerek, R.; Koukal, J.; Miskotte, K.; Piffl, R.

    2016-01-01

    Amateur meteor workers have always been interested to exchange information and experience. In the past this was only possible via personal contacts by letter or by specialized journals. With internet a much faster medium became available and plenty of websites, mailing lists, Facebook groups, etc., have been created in order to communicate about meteors. Today there is a wealth of meteor data circulating on internet, but the information is very scattered and not directly available to everyone. The authors have been considering how to organize an easy access to the many different meteor related publications. The best solution for the current needs of amateur meteor observers proved to be a dedicated website combined with a PDF journal, both being free available without any subscription fee or registration requirement. The authors decided to start with this project and in March 2016 the website meteornews.org has been created. A first issue of eMeteorNews was prepared in April 2016. The year 2016 will be a test period for this project. The mission statement of this project is: "Minimizing overhead and editorial constraints to assure a swift exchange of information dedicated to all fields of active amateur meteor work."

  17. Cosmic Background Explorer (COBE) press kit

    NASA Technical Reports Server (NTRS)

    1989-01-01

    COBE, the Cosmic Background Explorer spacecraft, and its mission are described. COBE was designed to study the origin and dynamics of the universe including the theory that the universe began with a cataclysmic explosion referred to as the Big Bang. To this end, earth's cosmic background - the infrared radiation that bombards earth from every direction - will be measured by three sophisticated instruments: the Differential Microwave Radiometer (DMR), the Far Infrared Absolute Spectrophotometer (FIRAS), and the Diffuse Infrared Background Experiment (DIRBE).

  18. Color gradient background oriented schlieren imaging

    NASA Astrophysics Data System (ADS)

    Mier, Frank Austin; Hargather, Michael

    2015-11-01

    Background oriented schlieren (BOS) imaging is a method of visualizing refractive disturbances through the comparison of digital images. By comparing images with and without a refractive disturbance visualizations can be achieved via a range of image processing methods. Traditionally, backgrounds consist of random distributions of high contrast speckle patterns. To image a refractive disturbance, a digital image correlation algorithm is used to identify the location and magnitude of apparent pixel shifts in the background pattern. Here a novel method of using color gradient backgrounds is explored as an alternative. The gradient background eliminates the need to perform an image correlation between the two digital images, as simple image subtraction can be used to identify the location, magnitude, and direction of the image distortions. This allows for quicker processing. Two-dimensional gradient backgrounds using multiple colors are shown. The gradient backgrounds are demonstrated to provide quantitative data limited only by the camera's pixel resolution, whereas speckle backgrounds limit resolution to the size of the random pattern features and image correlation window size. Additional results include the use of a computer screen as a background.

  19. Color gradient background-oriented schlieren imaging

    NASA Astrophysics Data System (ADS)

    Mier, Frank Austin; Hargather, Michael J.

    2016-06-01

    Background-oriented schlieren is a method of visualizing refractive disturbances by comparing digital images with and without a refractive disturbance distorting a background pattern. Traditionally, backgrounds consist of random distributions of high-contrast color transitions or speckle patterns. To image a refractive disturbance, a digital image correlation algorithm is used to identify the location and magnitude of apparent pixel shifts in the background pattern between the two images. Here, a novel method of using color gradient backgrounds is explored as an alternative that eliminates the need to perform a complex image correlation between the digital images. A simple image subtraction can be used instead to identify the location, magnitude, and direction of the image distortions. Gradient backgrounds are demonstrated to provide quantitative data only limited by the camera's pixel resolution, whereas speckle backgrounds limit resolution to the size of the random pattern features and image correlation window size. Quantitative measurement of density in a thermal boundary layer is presented. Two-dimensional gradient backgrounds using multiple colors are demonstrated to allow measurement of two-dimensional refractions. A computer screen is used as the background, which allows for rapid modification of the gradient to tune sensitivity for a particular application.

  20. Genetic toxicology.

    PubMed

    Kramer, P J

    1998-04-01

    Systems for testing genetic toxicology are components of carcinogenic and genetic risk assessment. Present routine genotoxicity-testing is based on at least 20 years of development during which many different test systems have been introduced and used. Today, it is clear that no single test is capable of detecting all genotoxic agents. Therefore, the usual approach is to perform a standard battery of in-vitro and in-vivo tests for genotoxicity. Work-groups of the European Union (EU), the Organization for Economic Co-operation and Development (OECD), and, very recently, the work-group of the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) have defined such standard battery tests. These and some currently used supplementary or confirmatory tests are briefly discussed here. Additional test systems for the assessment of genotoxic and carcinogenic hazard and risk are seriously needed. These tests must be more relevant to man than are current assays and less demanding in respect of cost, time and number of animals. Another aspect for reassessment derives from the actual situation in the pharmaceutical industry. Companies have to prepare for the world economy of the 21st century. Therefore, pharmaceutical research is speeding up tremendously by use of tools such as genomics, combinatorial chemistry, high throughput screening and proteomics. Toxicology and genotoxicology need to re-evaluate their changing environment and must find ways to respond to these needs. In conclusion, genetic toxicology needs to answer questions coming from two major directions: hazard and risk identification and high throughput testing. PMID:9625484