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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. Bringing genetic background into focus.

    PubMed

    Chow, Clement Y

    2016-02-01

    Researchers should embrace differences in genetic background to build richer disease models that more accurately reflect the level of variation in the human population, posits Clement Chow. PMID:26659016

  3. 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

  4. Genetic background of supernumerary teeth.

    PubMed

    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

  5. 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.

  6. Genetic background of hyperphenylalaninemia in Nagasaki, Japan.

    PubMed

    Dateki, Sumito; Watanabe, Satoshi; Nakatomi, Akiko; Kinoshita, Eiichi; Matsumoto, Tadashi; Yoshiura, Koh-Ichiro; Moriuchi, Hiroyuki

    2016-05-01

    Phenylketonuria (PKU) and related hyperphenylalaninemia (HPA) are caused by a deficiency in hepatic phenylalanine hydroxylase (PAH). The incidence of PKU in Nagasaki prefecture is higher than that in all parts of Japan (1/15 894 vs 1/120 000). To investigate the genetic background of patients with HPA in Nagasaki prefecture, mutation analysis was done in 14 patients with PKU or mild HPA. Homozygous or compound heterozygous PAH mutations were identified in all the patients. The spectrum of PAH mutations in the cohort was broad and similar to those in all parts of Japan and East Asian countries. R53H is the most common mutation in patients with mild HPA. The present results provide further support for genotype-phenotype correlations in patients with HPA. The high incidence of PKU in Nagasaki, the westernmost part of Japan, might be due to migration of people with PAH mutations from China and Korea, and geographic factors. PMID:27173423

  7. [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

  8. Distinguishing Hypertrophic Cardiomyopathy-Associated Mutations from Background Genetic Noise

    PubMed Central

    Kapplinger, Jamie D.; Landstrom, Andrew P.; Bos, J. Martijn; Salisbury, Benjamin A.; Callis, Thomas E.; Ackerman, Michael J.

    2014-01-01

    Despite the significant progress that has been made in identifying disease-associated mutations, the utility of the Hypertrophic Cardiomyopathy (HCM) genetic test is limited by a lack of understanding of the background genetic variation inherent to these sarcomeric genes in seemingly healthy subjects. This study represents the first comprehensive analysis of genetic variation in 427 ostensibly healthy individuals for the HCM genetic test using the “Gold Standard” Sanger sequencing method validating the background rate identified in the publically available exomes. While mutations are clearly over-represented in disease, a background rate as high as ~5% among healthy individuals prevents diagnostic certainty. To this end, we have identified a number of estimated predictive value-based associations including gene-specific, topology, and conservation methods generating an algorithm aiding in the probabilistic interpretation of an HCM genetic test. PMID:24510615

  9. 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

  10. 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

  11. Empathy is moderated by genetic background in mice.

    PubMed

    Chen, QiLiang; Panksepp, Jules B; 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

  12. Cancer morphology, carcinogenesis and genetic instability: a background.

    PubMed

    Bignold, Leon P; Coghlan, B L D; Jersmann, H P A

    2006-01-01

    tumour cells, a field which was pioneered in the 1970s mainly by Loeb. Here these discoveries are traced, beginning with "nuclear instability" though mitotic-and-chromosomal theories, single somatic mutation theories, "multi-hit" somatic theories, "somatic, non-chromosomal, genetic instability" and epigenetic mechanisms in tumour cells as a background to the chapters which follow. PMID:16383012

  13. Genetic background strongly influences the severity of glomerulosclerosis in mice.

    PubMed

    Nishino, Tomohiro; Sasaki, Nobuya; Nagasaki, Ken-Ichi; Ahmad, Zulkifli; Agui, Takashi

    2010-10-01

    The ICGN mouse strain is a glomerulosclerosis (GS) model that shows characteristic proteinuria, podocyte morphological abnormalities and increased extracellular matrix accumulation in the glomeruli, which are the final common pathology associated with a variety of kidney diseases leading to end-stage renal failure. Previously, we performed a quantitative trait locus (QTL) analysis to identify the causative genes for GS in ICGN mice and found the deletion mutation of the tensin2 (Tns2) gene that creates both a premature stop codon and dramatically decreases mRNA expression levels within the region of the major QTL (this mutation was designated Tns2(nep)). The severity of GS varies considerably in humans and other animals, indicating the influence of several genes controlling the disease phenotype. In this study, to identify the modifier/resistant gene(s) for GS, we produced congenic strains carrying the Tns2(nep) mutation on the C57BL/6J (B6) genetic background and analyzed GS severity. Interestingly, the B6 congenic mice exhibited milder phenotypes than the ICGN strain mice. The results suggest that B6 mice have a modifier(s) of GS resistance. Therefore, identification of the modifier loci in B6 mice will provide important new information regarding gene interactions controlling GS. PMID:20484839

  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. 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

  18. 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

  19. 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...

  20. No Influence of Indy on Lifespan in Drosophila after Correction for Genetic and Cytoplasmic Background Effects

    PubMed Central

    Toivonen, Janne M; Walker, Glenda A; Martinez-Diaz, Pedro; Bjedov, Ivana; Driege, Yasmine; Jacobs, Howard T; Gems, David; Partridge, Linda

    2007-01-01

    To investigate whether alterations in mitochondrial metabolism affect longevity in Drosophila melanogaster, we studied lifespan in various single gene mutants, using inbred and outbred genetic backgrounds. As positive controls we included the two most intensively studied mutants of Indy, which encodes a Drosophila Krebs cycle intermediate transporter. It has been reported that flies heterozygous for these Indy mutations, which lie outside the coding region, show almost a doubling of lifespan. We report that only one of the two mutants lowers mRNA levels, implying that the lifespan extension observed is not attributable to the Indy mutations themselves. Moreover, neither Indy mutation extended lifespan in female flies in any genetic background tested. In the original genetic background, only the Indy mutation associated with altered RNA expression extended lifespan in male flies. However, this effect was abolished by backcrossing into standard outbred genetic backgrounds, and was associated with an unidentified locus on the X chromosome. The original Indy line with long-lived males is infected by the cytoplasmic symbiont Wolbachia, and the longevity of Indy males disappeared after tetracycline clearance of this endosymbiont. These findings underscore the critical importance of standardisation of genetic background and of cytoplasm in genetic studies of lifespan, and show that the lifespan extension previously claimed for Indy mutants was entirely attributable to confounding variation from these two sources. In addition, we saw no effects on lifespan of expression knockdown of the Indy orthologues nac-2 and nac-3 in the nematode Caenorhabditis elegans. PMID:17571923

  1. Analysis of non-Gaussian cosmic microwave background maps based on the N-pdf. Application to Wilkinson Microwave Anisotropy Probe data

    NASA Astrophysics Data System (ADS)

    Vielva, P.; Sanz, J. L.

    2009-08-01

    We present a new method based on the N-point probability distribution function (N-pdf) to study non-Gaussianity in cosmic microwave background maps. Likelihood and Bayesian estimation are applied to a local non-linear perturbed model up to third order, characterized by a linear term which is described by a Gaussian N-pdf, and a second- and third-order terms which are proportional to the square and the cube of the linear one. We also explore a set of model selection techniques (the Akaike and the Bayesian information criteria, the minimum description length, the Bayesian evidence and the generalized likelihood ratio test) and their application to decide whether a given data set is better described by the proposed local non-Gaussian model, rather than by the standard Gaussian temperature distribution. As an application, we consider the analysis of the Wilkinson Microwave Anisotropy Probe 5-year data at a resolution of ~2°. At this angular scale (the Sachs-Wolfe regime), the non-Gaussian description proposed in this work defaults (under certain conditions) to an approximative local form of the weak non-linear coupling inflationary model previously addressed in the literature. For this particular case, we obtain an estimation for the non-linear coupling parameter of -94 < fNL < 154 at 95 per cent confidence level. Equally, model selection criteria also indicate that the Gaussian hypothesis is favoured against the particular local non-Gaussian model proposed in this work. This result is in agreement with previous findings obtained for equivalent non-Gaussian models and with different non-Gaussian estimators. However, our estimator based on the N-pdf is more efficient than previous estimators and, therefore, provides tighter constraints on the coupling parameter at degree scale.

  2. 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

  3. 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...

  4. Tuberculin skin test reactivity is dependent on host genetic background in Colombian tuberculosis household contacts.

    PubMed

    Cobat, Aurélie; Barrera, Luis F; Henao, Hanna; Arbeláez, Patricia; Abel, Laurent; García, Luis F; Schurr, Erwin; Alcaïs, Alexandre

    2012-04-01

    The tuberculin skin test (TST) measures the intensity of antimycobacterial acquired immunity and is used to diagnose latent infection with Mycobacterium tuberculosis. We report evidence for a codominant gene explaining ∼65% of the TST variability. Disregarding the host genetic background may lead to misclassifications of TST-based diagnosis of latent M. tuberculosis infection. PMID:22291100

  5. [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

  6. 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. PMID:26994290

  7. 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

  8. 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. PMID:26373338

  9. Genetic Background Modulates Impaired Excitability of Inhibitory Neurons in a Mouse Model of Dravet Syndrome

    PubMed Central

    Rubinstein, Moran; Westenbroek, Ruth E.; Yu, Frank H.; Jones, Christina J.; Scheuer, Todd; Catterall, William A.

    2014-01-01

    Dominant loss-of-function mutations in voltage-gated sodium channel NaV1.1 cause Dravet Syndrome, an intractable childhood-onset epilepsy. NaV1.1+/− Dravet Syndrome mice in C57BL/6 genetic background exhibit severe seizures, cognitive and social impairments, and premature death. Here we show that Dravet Syndrome mice in pure 129/SvJ genetic background have many fewer seizures and much less premature death than in pure C57BL/6 background. These mice also have a higher threshold for thermally induced seizures, fewer myoclonic seizures, and no cognitive impairment, similar to patients with Genetic Epilepsy with Febrile Seizures Plus. Consistent with this mild phenotype, mutation of NaV1.1 channels has much less physiological effect on neuronal excitability in 129/SvJ mice. In hippocampal slices, the excitability of CA1 Stratum Oriens interneurons is selectively impaired, while the excitability of CA1 pyramidal cells is unaffected. NaV1.1 haploinsufficiency results in increased rheobase and threshold for action potential firing and impaired ability to sustain high-frequency firing. Moreover, deletion of NaV1.1 markedly reduces the amplification and integration of synaptic events, further contributing to reduced excitability of interneurons. Excitability is less impaired in inhibitory neurons of Dravet Syndrome mice in 129/SvJ genetic background. Because specific deletion of NaV1.1 in forebrain GABAergic interneuons is sufficient to cause the symptoms of Dravet Syndrome in mice, our results support the conclusion that the milder phenotype in 129/SvJ mice is caused by lesser impairment of sodium channel function and electrical excitability in their forebrain interneurons. This mild impairment of excitability of interneurons leads to a milder disease phenotype in 129/SvJ mice, similar to Genetic Epilepsy with Febrile Seizures Plus in humans. PMID:25281316

  10. 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

  11. T cell genetic background determines default T helper phenotype development in vitro

    PubMed Central

    1995-01-01

    A host's ability to resist certain pathogens such as Leishmania major can depend upon the phenotype of T helper (Th) subset that develops. Different murine genetic backgrounds are known to significantly alter the direction of Th subset development, although the cellular basis of this influence is poorly understood. To examine the basis of this effect we used an in vitro alpha/beta-T cell receptor (TCR) transgenic system for analysis of Th phenotype development. To control for TCR usage, we derived the DO11.10 alpha/beta-TCR transgene in several genetic backgrounds. Our findings suggest that the effects of genetic background on Th phenotype development reside within the T cell, and not the antigen-presenting cell compartment. Transgenic T cells from both the B10.D2 and BALB/c backgrounds showed development toward either the Th1 or Th2 phenotype under the strong directing influence of interleukin (IL) 12 and IL4, respectively. However, when T cells were activated in vitro under neutral conditions in which exogenous cytokines were not added, B10.D2-derived T cells acquired a significantly stronger Th1 phenotype than T cells from the BALB/c background, correspondent with in vivo Th responses to Leishmania in these strains. Importantly, these cytokine differences resulted in distinct functional properties, because B10.D2- but not BALB/c-derived T cells could induce macrophage production of nitric oxide, an important antimicrobial factor. Thus, the genetically determined default Th phenotype development observed in vitro may correspond to in vivo Th subset responses for pathogens such as Leishmania which do not initiate strong Th phenotype-directing signals. PMID:7836924

  12. [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. PMID:26654542

  13. Induced neural stem cells from distinct genetic backgrounds exhibit different reprogramming status.

    PubMed

    Kim, Sung Min; Lim, Kyung Tae; Kwak, Tae Hwan; Lee, Seung Chan; Im, Jung Hyun; Hali, Sai; In Hwang, Seon; Kim, Dajeong; Hwang, Jeongho; Kim, Kee-Pyo; Chung, Hak-Jae; Kim, Jeong Beom; Ko, Kinarm; Chung, Hyung-Min; Lee, Hoon Taek; Schöler, Hans R; Han, Dong Wook

    2016-03-01

    Somatic cells could be directly converted into induced neural stem cells (iNSCs) by ectopic expression of defined transcription factors. However, the underlying mechanism of direct lineage transition into iNSCs is largely unknown. In this study, we examined the effect of genetic background on the direct conversion process into an iNSC state. The iNSCs from two different mouse strains exhibited the distinct efficiency of lineage conversion as well as clonal expansion. Furthermore, the expression levels of endogenous NSC markers, silencing of transgenes, and in vitro differentiation potential were also different between iNSC lines from different strains. Therefore, our data suggest that the genetic background of starting cells influences the conversion efficiency as well as reprogramming status of directly converted iNSCs. PMID:26930613

  14. Destabilizing Protein Polymorphisms in the Genetic Background Direct Phenotypic Expression of Mutant SOD1 Toxicity

    PubMed Central

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

    2009-01-01

    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

  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 Central

    Zeng, Kai; Charlesworth, Brian

    2011-01-01

    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. PMID:21705759

  17. Antibody-mediated glomerulonephritis in mice: the role of endotoxin, complement and genetic background

    PubMed Central

    ROBSON, M G; COOK, H T; PUSEY, C D; WALPORT, M J; DAVIES, K A

    2003-01-01

    Antibody-mediated glomerulonephritis in man may be exacerbated by infection and this effect may be mediated by bacterial endotoxin. There is evidence supporting a role for endotoxin in heterologous nephrotoxic nephritis in rats, but the role of endotoxin in this model in mice has not previously been explored. Previous data in mice on the role of complement in this model are conflicting and this may be due to the mixed genetic background of mice used in these studies. We used the model of heterologous nephrotoxic nephritis in mice and explored the role of endotoxin, complement and genetic background. In this study we show a synergy between antibody and endotoxin in causing a neutrophil influx. We also show that C1q-deficient mice have an increased susceptibility to glomerular inflammation but this is seen only on a mixed 129/Sv × C57BL/6 genetic background. On a C57BL/6 background we did not find any differences in disease susceptibility when wildtype, C1q, factor B or factor B/C2 deficient mice were compared. We also demonstrate that C57BL/6 mice are more susceptible to glomerular inflammation than 129/Sv mice. These results show that endotoxin is required in this model in mice, and that complement does not play a major role in glomerular inflammation in C57BL/6 mice. C1q may play a protective role in mixed-strain 129/Sv × C57BL/6 mice, but the data may also be explained by systematic bias in background genes, as there is a large difference in disease susceptibility between C57BL/6 and 129/Sv mice. PMID:12930357

  18. 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

  19. RNAi phenotypes are influenced by the genetic background of the injected strain

    PubMed Central

    2013-01-01

    Background RNA interference (RNAi) is a powerful tool to study gene function in organisms that are not amenable to classical forward genetics. Hence, together with the ease of comprehensively identifying genes by new generation sequencing, RNAi is expanding the scope of animal species and questions that can be addressed in terms of gene function. In the case of genetic mutants, the genetic background of the strains used is known to influence the phenotype while this has not been described for RNAi experiments. Results Here we show in the red flour beetle Tribolium castaneum that RNAi against Tc-importin α1 leads to different phenotypes depending on the injected strain. We rule out off target effects and show that sequence divergence does not account for this difference. By quantitatively comparing phenotypes elicited by RNAi knockdown of four different genes we show that there is no general difference in RNAi sensitivity between these strains. Finally, we show that in case of Tc-importin α1 the difference depends on the maternal genotype. Conclusions These results show that in RNAi experiments strain specific differences have to be considered and that a proper documentation of the injected strain is required. This is especially important for the increasing number of emerging model organisms that are being functionally investigated using RNAi. In addition, our work shows that RNAi is suitable to systematically identify the differences in the gene regulatory networks present in populations of the same species, which will allow novel insights into the evolution of animal diversity. PMID:23324472

  20. 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

  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. 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

  3. 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

  4. 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

  5. Mouse genetic background is associated with variation in secondary complications after subarachnoid hemorrhage.

    PubMed

    D'Abbondanza, Josephine A; Lass, Elliot; Ai, Jinglu; Loch Macdonald, R

    2015-01-01

    Spontaneous subarachnoid hemorrhage (SAH) is a form of hemorrhagic stroke that accounts for approximately 7 % of all strokes worldwide and is associated with mortality in approximately 35 % of cases and morbidity in many of the survivors. Studies have suggested that genetic variations may affect the pathophysiology of SAH. The goal of this study was to investigate the effect of mouse genetic background on brain injury and large artery vasospasm after SAH. SAH was induced in seven inbred strains of mice, and the degree of large artery vasospasm and brain injury was assessed. After 48 h, SAH mice showed a significant reduction in middle cerebral artery diameter and increased neuronal injury in the cerebral cortex compared with sham-operated controls. Mouse strains also demonstrated variable degrees of vasospasm and brain injury. This data suggests that different genetic factors influence how much brain injury and vasospasm occur after SAH. Future investigations may provide insight into the causes of these differences between strains and into which genetic contributors may be responsible for vasospasm and brain injury after SAH. PMID:25366595

  6. Ethnic Background and Genetic Variation in the Evaluation of Cancer Risk: A Systematic Review

    PubMed Central

    Jing, Lijun; Su, Li; Ring, Brian Z.

    2014-01-01

    The clinical use of genetic variation in the evaluation of cancer risk is expanding, and thus understanding how determinants of cancer susceptibility identified in one population can be applied to another is of growing importance. However there is considerable debate on the relevance of ethnic background in clinical genetics, reflecting both the significance and complexity of genetic heritage. We address this via a systematic review of reported associations with cancer risk for 82 markers in 68 studies across six different cancer types, comparing association results between ethnic groups and examining linkage disequilibrium between risk alleles and nearby genetic loci. We find that the relevance of ethnic background depends on the question. If asked whether the association of variants with disease risk is conserved across ethnic boundaries, we find that the answer is yes, the majority of markers show insignificant variability in association with cancer risk across ethnic groups. However if the question is whether a significant association between a variant and cancer risk is likely to reproduce, the answer is no, most markers do not validate in an ethnic group other than the discovery cohort’s ancestry. This lack of reproducibility is not attributable to studies being inadequately populated due to low allele frequency in other ethnic groups. Instead, differences in local genomic structure between ethnic groups are associated with the strength of association with cancer risk and therefore confound interpretation of the implied physiologic association tracked by the disease allele. This suggest that a biological association for cancer risk alleles may be broadly consistent across ethnic boundaries, but reproduction of a clinical study in another ethnic group is uncommon, in part due to confounding genomic architecture. As clinical studies are increasingly performed globally this has important implications for how cancer risk stratifiers should be studied and

  7. 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

  8. 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

  9. Impact of Genetic Background on Neonatal Lethality of Gga2 Gene-Trap Mice

    PubMed Central

    Doray, Balraj; Govero, Jennifer; Kornfeld, Stuart

    2014-01-01

    The functional redundancy of the three mammalian Golgi-localized, γ-ear–containing, ADP-ribosylation factor-binding proteins (GGAs) was addressed in a previous study. Using insertional mutagenesis, we found that Gga1 or Gga3 homozygous knockout mice were for the most part normal, whereas mice homozygous for two different Gga2 gene-trap alleles exhibited either embryonic or neonatal lethality in the C57BL/6 background, depending on the source of the vector utilized (Byg vs. Tigm, respectively). We now show that the Byg strain harbors a disrupted Gga2 allele that is hypomorphic, indicating that the Byg lethality is attributable to a mechanism independent of GGA2. This is in contrast to the Tigm Gga2 allele, which is a true knockout and establishes a role for GGA2 during the neonatal period. Placement of the Tigm Gga2 allele into the C57BL6/Ola129Sv mixed background results in a lower incidence of neonatal lethality, showing the importance of genetic background in determining the requirement for GGA2 during this period. The Gga2−/− mice that survive have reduced body weight at birth and this runted phenotype is maintained through adulthood. PMID:24637350

  10. 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

  11. 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

  12. Severe ocular phenotypes in Rbp4-deficient mice in the C57BL/6 genetic background.

    PubMed

    Shen, Jingling; Shi, Dan; Suzuki, Tomohiro; Xia, Zunping; Zhang, Hanli; Araki, Kimi; Wakana, Shigeharu; Takeda, Naoki; Yamamura, Ken-Ichi; Jin, Shoude; Li, Zhenghua

    2016-06-01

    Retinol-binding protein 4 (RBP4) is a specific carrier for retinol in the blood. In hepatocytes, newly synthesized RBP4 associates with retinol and transthyretin and is secreted into the blood. The ternary transthyretin-RBP4-retinol complex transports retinol in the circulation and delivers it to target tissues. Rbp4-deficient mice in a mixed genetic background (129xC57BL/6J) have decreased sensitivity to light in the b-wave amplitude on electroretinogram. Sensitivity progressively improves and approaches that of wild-type mice at 24 weeks of age. In the present study, we produced Rbp4-deficient mice in the C57BL/6 genetic background. These mice displayed more severe phenotypes. They had decreased a- and b-wave amplitudes on electroretinograms. In accordance with these abnormalities, we found structural changes in these mice, such as loss of the peripheral choroid and photoreceptor layer in the peripheral retinas. In the central retinas, the distance between the inner limiting membrane and the outer plexiform layer was much shorter with fewer ganglion cells and fewer synapses in the inner plexiform layer. Furthermore, ocular developmental defects of retinal depigmentation, optic disc abnormality, and persistent hyaloid artery were also observed. All these abnormalities had not recovered even at 40 weeks of age. Our Rbp4-deficient mice accumulated retinol in the liver but it was undetectable in the serum, indicating an inverse relation between serum and liver retinol levels. Our results suggest that RBP4 is critical for the mobilization of retinol from hepatic storage pools, and that such mobilization is necessary for ocular development and visual function. PMID:26974396

  13. 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

  14. 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

  15. 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. PMID:27097329

  16. 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

  17. Mouse genetic background impacts both on iron and non-iron metals parameters and on their relationships.

    PubMed

    Cavey, Thibault; Ropert, Martine; de Tayrac, Marie; Bardou-Jacquet, Edouard; Island, Marie-Laure; Leroyer, Patricia; Bendavid, Claude; Brissot, Pierre; Loréal, Olivier

    2015-08-01

    Iron is reported to interact with other metals. In addition, it has been shown that genetic background may impact iron metabolism. Our objective was to characterize, in mice of three genetic backgrounds, the links between iron and several non-iron metals. Thirty normal mice (C57BL/6, Balb/c and DBA/2; n = 10 for each group), fed with the same diet, were studied. Quantification of iron, zinc, cobalt, copper, manganese, magnesium and rubidium was performed by ICP/MS in plasma, erythrocytes, liver and spleen. Transferrin saturation was determined. Hepatic hepcidin1 mRNA level was evaluated by quantitative RT-PCR. As previously reported, iron parameters were modulated by genetic background with significantly higher values for plasma iron parameters and liver iron concentration in DBA/2 and Balb/c strains. Hepatic hepcidin1 mRNA level was lower in DBA/2 mice. No iron parameter was correlated with hepcidin1 mRNA levels. Principal component analysis of the data obtained for non-iron metals indicated that metals parameters stratified the mice according to their genetic background. Plasma and tissue metals parameters that are dependent or independent of genetic background were identified. Moreover, relationships were found between plasma and tissue content of iron and some other metals parameters. Our data: (i) confirms the impact of the genetic background on iron parameters, (ii) shows that genetic background may also play a role in the metabolism of non-iron metals, (iii) identifies links between iron and other metals parameters which may have implications in the understanding and, potentially, the modulation of iron metabolism. PMID:26041486

  18. 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

  19. Molecular Mechanisms of Drug Resistance in Natural Leishmania Populations Vary with Genetic Background

    PubMed Central

    Decuypere, Saskia; Vanaerschot, Manu; Brunker, Kirstyn; Imamura, Hideo; Müller, Sylke; Khanal, Basudha; Rijal, Suman; Dujardin, Jean-Claude; Coombs, Graham H.

    2012-01-01

    The evolution of drug-resistance in pathogens is a major global health threat. Elucidating the molecular basis of pathogen drug-resistance has been the focus of many studies but rarely is it known whether a drug-resistance mechanism identified is universal for the studied pathogen; it has seldom been clarified whether drug-resistance mechanisms vary with the pathogen's genotype. Nevertheless this is of critical importance in gaining an understanding of the complexity of this global threat and in underpinning epidemiological surveillance of pathogen drug resistance in the field. This study aimed to assess the molecular and phenotypic heterogeneity that emerges in natural parasite populations under drug treatment pressure. We studied lines of the protozoan parasite Leishmania (L.) donovani with differential susceptibility to antimonial drugs; the lines being derived from clinical isolates belonging to two distinct genetic populations that circulate in the leishmaniasis endemic region of Nepal. Parasite pathways known to be affected by antimonial drugs were characterised on five experimental levels in the lines of the two populations. Characterisation of DNA sequence, gene expression, protein expression and thiol levels revealed a number of molecular features that mark antimonial-resistant parasites in only one of the two populations studied. A final series of in vitro stress phenotyping experiments confirmed this heterogeneity amongst drug-resistant parasites from the two populations. These data provide evidence that the molecular changes associated with antimonial-resistance in natural Leishmania populations depend on the genetic background of the Leishmania population, which has resulted in a divergent set of resistance markers in the Leishmania populations. This heterogeneity of parasite adaptations provides severe challenges for the control of drug resistance in the field and the design of molecular surveillance tools for widespread applicability. PMID:22389733

  20. Testing an 'aging gene' in long-lived drosophila strains: increased longevity depends on sex and genetic background.

    PubMed

    Spencer, Christine C; Howell, Christine E; Wright, Amber R; Promislow, Daniel E L

    2003-04-01

    Molecular advances of the past decade have led to the discovery of a myriad of 'aging genes' (methuselah, Indy, InR, Chico, superoxide dismutase) that extend Drosophila lifespan by up to 85%. Despite this life extension, these mutants are no longer lived than at least some recently wild-caught strains. Typically, long-lived mutants are identified in relatively short-lived genetic backgrounds, and their effects are rarely tested in genetic backgrounds other than the one in which they were isolated or derived. However, the mutant's high-longevity phenotype may be dependent on interactions with alleles that are common in short-lived laboratory strains. Here we set out to determine whether one particular mutant could extend lifespan in long-lived genetic backgrounds in the fruit fly, Drosophila melanogaster. We measured longevity and resistance to thermal stress in flies that were transgenically altered to overexpress human superoxide dismutase (SOD) in the motorneurones in each of 10 genotypes. Each genotype carried the genetic background from a different naturally long-lived wild-caught Drosophila strain. While SOD increased lifespan on average, the effect was genotype- and sex-specific. Our results indicate that naturally segregating genes interact epistatically with the aging gene superoxide dismutase to modify its ability to extend longevity. This study points to the need to identify mutants that increase longevity not only in the lab strain of origin but also in naturally long-lived genetic backgrounds. PMID:12882325

  1. Deletion of liaR Reverses Daptomycin Resistance in Enterococcus faecium Independent of the Genetic Background

    PubMed Central

    Panesso, Diana; Reyes, Jinnethe; Gaston, Elizabeth P.; Deal, Morgan; Londoño, Alejandra; Nigo, Masayuki; Munita, Jose M.; Miller, William R.; Shamoo, Yousif; Tran, Truc T.

    2015-01-01

    We have shown previously that changes in LiaFSR, a three-component regulatory system predicted to orchestrate the cell membrane stress response, are important mediators of daptomycin (DAP) resistance in enterococci. Indeed, deletion of the gene encoding the response regulator LiaR in a clinical strain of Enterococcus faecalis reversed DAP resistance (DAP-R) and produced a strain hypersusceptible to antimicrobial peptides. Since LiaFSR is conserved in Enterococcus faecium, we investigated the role of LiaR in a variety of clinical E. faecium strains representing the most common DAP-R genetic backgrounds. Deletion of liaR in DAP-R E. faecium R446F (DAP MIC of 16 μg/ml) and R497F (MIC of 24 μg/ml; harboring changes in LiaRS) strains fully reversed resistance (DAP MICs decreasing to 0.25 and 0.094 μg/ml, respectively). Moreover, DAP at concentrations of 13 μg/ml (achieved with human doses of 12 mg/kg body weight) retained bactericidal activity against the mutants. Furthermore, the liaR deletion derivatives of these two DAP-R strains exhibited increased binding of boron-dipyrromethene difluoride (BODIPY)-daptomycin, suggesting that high-level DAP-R mediated by LiaR in E. faecium involves repulsion of the calcium-DAP complex from the cell surface. In DAP-tolerant strains HOU503F and HOU515F (DAP MICs within the susceptible range but bacteria not killed by DAP concentrations of 5× the MIC), deletion of liaR not only markedly decreased the DAP MICs (0.064 and 0.047 μg/ml, respectively) but also restored the bactericidal activity of DAP at concentrations as low as 4 μg/ml (achieved with human doses of 4 mg/kg). Our results suggest that LiaR plays a relevant role in the enterococcal cell membrane adaptive response to antimicrobial peptides independent of the genetic background and emerges as an attractive target to restore the activity of DAP against multidrug-resistant strains. PMID:26369959

  2. 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

  3. 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

  4. The genetic tumor background is an important determinant for heterogeneous MYCN-amplified neuroblastoma.

    PubMed

    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; Ambros, Peter F; Ambros, Inge M

    2016-07-01

    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

  5. 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

  6. 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. PMID:25896609

  7. Effects of Vendor and Genetic Background on the Composition of the Fecal Microbiota of Inbred Mice

    PubMed Central

    Ericsson, Aaron C.; Davis, J. Wade; Spollen, William; Bivens, Nathan; Givan, Scott; Hagan, Catherine E.; McIntosh, Mark; Franklin, Craig L.

    2015-01-01

    The commensal gut microbiota has been implicated as a determinant in several human diseases and conditions. There is mounting evidence that the gut microbiota of laboratory mice (Mus musculus) similarly modulates the phenotype of mouse models used to study human disease and development. While differing model phenotypes have been reported using mice purchased from different vendors, the composition and uniformity of the fecal microbiota in mice of various genetic backgrounds from different vendors is unclear. Using culture-independent methods and robust statistical analysis, we demonstrate significant differences in the richness and diversity of fecal microbial populations in mice purchased from two large commercial vendors. Moreover, the abundance of many operational taxonomic units, often identified to the species level, as well as several higher taxa, differed in vendor- and strain-dependent manners. Such differences were evident in the fecal microbiota of weanling mice and persisted throughout the study, to twenty-four weeks of age. These data provide the first in-depth analysis of the developmental trajectory of the fecal microbiota in mice from different vendors, and a starting point from which researchers may be able to refine animal models affected by differences in the gut microbiota and thus possibly reduce the number of animals required to perform studies with sufficient statistical power. PMID:25675094

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

    DOE PAGESBeta

    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

  9. Effects of vendor and genetic background on the composition of the fecal microbiota of inbred mice.

    PubMed

    Ericsson, Aaron C; Davis, J Wade; Spollen, William; Bivens, Nathan; Givan, Scott; Hagan, Catherine E; McIntosh, Mark; Franklin, Craig L

    2015-01-01

    The commensal gut microbiota has been implicated as a determinant in several human diseases and conditions. There is mounting evidence that the gut microbiota of laboratory mice (Mus musculus) similarly modulates the phenotype of mouse models used to study human disease and development. While differing model phenotypes have been reported using mice purchased from different vendors, the composition and uniformity of the fecal microbiota in mice of various genetic backgrounds from different vendors is unclear. Using culture-independent methods and robust statistical analysis, we demonstrate significant differences in the richness and diversity of fecal microbial populations in mice purchased from two large commercial vendors. Moreover, the abundance of many operational taxonomic units, often identified to the species level, as well as several higher taxa, differed in vendor- and strain-dependent manners. Such differences were evident in the fecal microbiota of weanling mice and persisted throughout the study, to twenty-four weeks of age. These data provide the first in-depth analysis of the developmental trajectory of the fecal microbiota in mice from different vendors, and a starting point from which researchers may be able to refine animal models affected by differences in the gut microbiota and thus possibly reduce the number of animals required to perform studies with sufficient statistical power. PMID:25675094

  10. 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

  11. 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

  12. The Adiponectin Variants Contribute to the Genetic Background of Type 2 Diabetes in Turkish Population.

    PubMed

    Arikoglu, Hilal; Ozdemir, Hulya; Kaya, Dudu Erkoc; Ipekci, Suleyman Hilmi; Arslan, Ahmet; Kayis, Seyit Ali; Gonen, Mustafa Sait

    2013-10-26

    Adiponectin, an adipose tissue specific protein encoded by the Adiponectin gene, modulates insulin sensitivity and plays an important role in regulating energy homeostasis. Many studies have shown that single nucleotide polymorphisms (SNPs) in the Adiponectin gene are associated with low plasma adiponectin levels, insulin resistance and an increased risk of type 2 diabetes mellitus. The aim of the present study was to evaluate the contribution of the Adiponectin gene polymorphisms in genetic background of type 2 diabetes in a Turkish population. In total, 169 unrelated and non-obese diabetic patients and 119 age- and BMI-matched non-diabetic individuals with no family history of diabetes were enrolled in this study. We detected a significant association between type 2 diabetes and two SNPs: SNP -11391G>A, which is located in the promoter region of the Adiponectin gene, and SNP +276G>T, which is found in intron 2 of the gene (P<0.05). The silence SNP G15G (+45T>G) in exon 1 and SNP +349A>G in intron 2 also showed a weak association with type 2 diabetes (P=0.06 and P=0.07, respectively), while SNPs -3971A>G in intron 1 and Y111H, R112C and H241P in exon 3 showed no association (P>0.05). In conclusion, these findings suggest that Adiponectin gene polymorphisms might be effective on susceptibility for type 2 diabetes development which emerged from the interactions between multiple genes, variants and environmental factors. PMID:24513330

  13. 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

  14. Blood pressure, heart rate, and tubuloglomerular feedback in A1AR-deficient mice with different genetic backgrounds

    PubMed Central

    Kim, Soo Mi; Mizel, Diane; Qin, Yan; Huang, Yuning; Schnermann, Jurgen

    2014-01-01

    Aim Differences in genetic background between control mice and mice with targeted gene mutations have been recognized as a potential cause for phenotypic differences. In the present study we have used A1AR-deficient mice in a C57Bl/6 and SWR/J congenic background to assess the influence of background on the effect of A1AR-deficiency on cardiovascular and renal functional parameters. Methods In A1AR+/+ and A1AR−/− mice in C57Bl/6 and SWR/J congenic backgrounds we assessed blood pressure and heart rate using radio-telemetry, plasma renin concentrations, and tubuloglomerular feedback. Results We did not detect significant differences in arterial blood pressure (MAP) and heart rates (HR) between A1AR+/+ and A1AR−/− mice in either C57Bl/6, SWR/J, or mixed backgrounds. MAP and HR were significantly higher in SWR/J than in C57Bl/6 mice. A high NaCl intake increased MAP in A1AR−/− mice on C57Bl/6 background while there was less or no salt sensitivity in the SWR/J background. No significant differences in plasma renin concentration were detected between A1AR−/− and A1AR+/+ mice in any of the strains. Tubuloglomerular feedback was found to be absent in A1AR−/− mice with SWR/J genetic background. Conclusions While this study confirmed important differences between inbred mouse strains, we did not identify phenotypic modifications of A1AR-related effects on blood pressure, heart rate, and plasma renin by differences in genetic background. PMID:25182861

  15. Response to Dietary Phosphate Deficiency is Affected by Genetic Background in Growing Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concern over the environmental impact of phosphate (P) excretion from pig production has led to reduced dietary P supplementation. To examine how genetics influence P utilization, 94 gilts sired by 2 genetic lines (PIC337 and PIC280) were fed either a P adequate diet (PA) or a 20% P deficient diet ...

  16. Genetic-Background Modulation of Core and Variable Autistic-Like Symptoms in Fmr1 Knock-Out Mice

    PubMed Central

    Pietropaolo, Susanna; Guilleminot, Aurélie; Martin, Benoît; D'Amato, Francesca R.; Crusio, Wim E.

    2011-01-01

    Background No animal models of autism spectrum disorders (ASD) with good construct validity are currently available; using genetic models of pathologies characterized by ASD-like deficits, but with known causes, may be therefore a promising strategy. The Fmr1-KO mouse is an example of this approach, modeling Fragile X syndrome, a well-known genetic disorder presenting ASD symptoms. The Fmr1-KO is available on different genetic backgrounds (FVB versus C57BL/6), which may explain some of the conflicting results that have been obtained with these mutants up till now. Methods Fmr1 KO and their wild-type littermates on both the FVB and C57BL/6 genetic backgrounds were examined on a battery of tests modeling the clinical symptoms of ASD, including the triad of core symptoms (alterations in social interaction and communication, presence of repetitive behaviors), as well as the secondary symptoms (disturbances in sensori-motor reactivity and in circadian patterns of activity, epileptic events). Results Fmr1-KO mice displayed autistic-like core symptoms of altered social interaction and occurrence of repetitive behaviors with additional hyperactivity. The genetic background modulated the effects of the Fmr1 deletion and it appears that the C57BL/6 background may be more suitable for further research on core autistic-like symptoms. Conclusions The Fmr1-mouse line does not recapitulate all of the main core and secondary ASD symptoms, but still can be useful to elucidate the neurobiological mechanisms underlying specific ASD-like endophenotypes. PMID:21364941

  17. Testing the Role of Genetic Background in Parallel Evolution Using the Comparative Experimental Evolution of Antibiotic Resistance

    PubMed Central

    Vogwill, Tom; Kojadinovic, Mila; Furió, Victoria; MacLean, R. Craig

    2014-01-01

    Parallel evolution is the independent evolution of the same phenotype or genotype in response to the same selection pressure. There are examples of parallel molecular evolution across divergent genetic backgrounds, suggesting that genetic background may not play an important role in determining the outcome of adaptation. Here, we measure the influence of genetic background on phenotypic and molecular adaptation by combining experimental evolution with comparative analysis. We selected for resistance to the antibiotic rifampicin in eight strains of bacteria from the genus Pseudomonas using a short term selection experiment. Adaptation occurred by 47 mutations at conserved sites in rpoB, the target of rifampicin, and due to the high diversity of possible mutations the probability of within-strain parallel evolution was low. The probability of between-strain parallel evolution was only marginally lower, because different strains substituted similar rpoB mutations. In contrast, we found that more than 30% of the phenotypic variation in the growth rate of evolved clones was attributable to among-strain differences. Parallel molecular evolution across strains resulted in divergent phenotypic evolution because rpoB mutations had different effects on growth rate in different strains. This study shows that genetic divergence between strains constrains parallel phenotypic evolution, but had little detectable impact on the molecular basis of adaptation in this system. PMID:25228081

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

    NASA Astrophysics Data System (ADS)

    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.

  19. Enhanced biofilm formation and multi‐host transmission evolve from divergent genetic backgrounds in C ampylobacter jejuni

    PubMed Central

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

    2015-01-01

    Summary Multicellular biofilms are an ancient bacterial adaptation that offers a protective environment for survival in hostile habitats. In microaerophilic organisms such as C ampylobacter, 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 C ampylobacter 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. PMID:26373338

  20. Genetic background of skin barrier dysfunction in the pathogenesis of psoriasis vulgaris

    PubMed Central

    Szczerkowska-Dobosz, Aneta; Rębała, Krzysztof; Purzycka-Bohdan, Dorota

    2015-01-01

    Psoriasis is a common inflammatory skin disease. It is known to be a complex condition with multifactorial mode of inheritance, however the associations between particular pathogenic pathways remain unclear. A novel report on the pathogenesis of psoriasis has recently included the genetic determination of the skin barrier dysfunction. In this paper, we focus on specific genetic variants associated with formation of the epidermal barrier and their role in the complex pathogenesis of the disease. PMID:26015782

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

    PubMed Central

    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. PMID:26751950

  2. Patients' Attitudes Towards Disclosure of Genetic Test Results to Family Members: The Impact of Patients' Sociodemographic Background and Counseling Experience.

    PubMed

    Gilbar, Roy; Shalev, Stavit; Spiegel, Ronen; Pras, Elon; Berkenstadt, Michal; Sagi, Michal; Ben-Yehuda, Adi; Mor, Pnina; Perry, Shlomit; Zaccai, Tzipora Falik; Borochowitz, Zvi; Barnoy, Sivia

    2016-04-01

    Many factors predict the intention to disclose genetic information to relatives. The article examines the impact of patients' socio-demographic factors on their intention to disclose genetic testing results to their relatives. Data were collected in eight genetic clinics in Israel. Patients were requested to fill in a questionnaire after counseling. A convenience sample of 564 participants who visited these clinics was collected for a response rate of 85 %. Of them, 282 participants came for susceptibility testing for hereditary cancers (cancer group), and 282 for genetic screening tests (prenatal group). In the cancer group, being secular and having more years of education correlated positively with the intention to disclose test results to relatives. In the prenatal group, being married and female correlated positively with the intention to disclose. In the cancer group, being religious and with less years of education correlated positively with the view that the clinician should deliver the results to the family. In the prenatal group, being male and unmarried correlated positively with this belief. In both groups, being of young age correlated with the perception that genetic information is private. Varied sociodemographic factors affect the intention to inform family members. Thus, knowing the social background of patients will shed light on people's attitudes to genetic information and will help clinicians provide effective counseling in discussions with patients about the implications of test results for relatives. PMID:26371363

  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. PMID:26021277

  4. 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...

  5. 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...

  6. 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

  7. Genetic background and environmental conditions drive metabolic variation in wild type and transgenic soybean (Glycine max) seeds.

    PubMed

    Cohen, Hagai; Shir, Ofer M; Yu, Yang; Hou, Wensheng; Sun, Shi; Han, Tianfu; Amir, Rachel

    2016-08-01

    The metabolic profiles and composition of storage reserves of agricultural crop seeds are strongly regulated by heritable and environmental factors. Yet, very little is known about the genetic and environmental determinants of adaptive metabolic variation amongst wild type as well as transgenic seed populations derived from the same genetic background, grown under natural field conditions. The goal of the current study was to investigate the effects of natural environmental conditions on wild type and transgenic soybean seeds expressing a feedback-insensitive form of cystathionine γ-synthase, a methionine main regulatory enzyme. The seeds were grown in four geographically distinct habitats in China and then assayed for primary metabolic profiles using gas chromatography mass spectrometry, morphological traits and storage reserve accumulation. The analyses revealed changes in the levels of primary metabolites which evidently exhibited high correlation to methionine regardless of changes in environmental conditions. The environment, however, constituted a major determinant of metabolic profiles amongst seeds, as much more metabolites were observed to be affected by this variable, particularly along the north-to-south latitudinal gradient. The observations suggest that metabolic variation amongst seeds grown under natural field conditions depends upon the complex relationships existing amongst their genetic background and the environmental conditions characterizing their cultivation areas. PMID:27038216

  8. 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

  9. 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

  10. Genetic Background and Antibiotic Resistance of Staphylococcus aureus Strains Isolated in the Republic of Georgia

    PubMed Central

    Revazishvili, Tamara; Bakanidze, Lela; Gomelauri, Tsaro; Zhgenti, Ekaterine; Chanturia, Gvantsa; Kekelidze, Merab; Rajanna, Chythanya; Kreger, Arnold; Sulakvelidze, Alexander

    2006-01-01

    The genetic composition and antibiotic sensitivities of 50 clinical isolates of Staphylococcus aureus obtained from various clinics in the Republic of Georgia were characterized. S. aureus strains ATCC 700699 and ATCC 29737 were included as reference standards in all analyses. All 52 strains had identical 16S rRNA profiles. In contrast, pulsed-field gel electrophoresis (PFGE) identified 20 distinct PFGE types among the 52 strains examined, which indicates that PFGE is more discriminating than is 16S rRNA sequence analysis for differentiating S. aureus strains. The results of our PFGE typing also suggest that multiple genetic subpopulations (related at the ca. 85% similarity level, based on their SmaI PFGE patterns) exist among the Georgian S. aureus strains. Twenty-two of the 50 Georgian strains were methicillin resistant and PCR positive for mecA, and 5 strains were methicillin sensitive even though they possessed mecA. None of the strains were vancomycin resistant or contained vanA. The nucleotide sequences of mecA fragments obtained from all mecA-containing strains were identical. Our data indicate that the population of S. aureus strains in Georgia is fairly homogeneous and that the prevalence of methicillin-resistant, mecA-positive strains is relatively high in that country. PMID:17021070

  11. Silver-Russell Syndrome - Part I: Clinical Characteristics and Genetic Background.

    PubMed

    Marczak-Hałupka, Anna; Kalina, Maria A; Tańska, Anna; Chrzanowska, Krystyna H

    2015-01-01

    Silver-Russell syndrome (SRS) is a rare, clinically and genetically heterogeneous entity, caused by (epi)genetic alternations. It is characterized by prenatal and postnatal growth retardation, relative macrocephaly, the triangular face and body asymmetry. About 40-60% of cases are caused by hypomethylation of 11p.15.5 Imprinting Centre Region 1 (ICR1) on the paternal chromosome, and maternal uniparental disomy for chromosome 7 (UPD(7)mat) is found in 5-10% of cases. There are suggested correlations between genotype and the phenotype. Psychomotor development may be delayed, usually mildly, with school difficulties and speech delay more common in patients with UPD(7)mat. Children with 11p15 hypomethylation are shorter and lighter at birth in comparison to children with UPD(7)mat, however further deceleration tends to be more apparent in the latter group. The onset of puberty tends to occur early, with acceleration of bone age, resulting in less apparent growth spurt. Failure to thrive and feeding problems are characteristic for the infant period, and further development of a child may be conditioned by additional congenital defects. PMID:26615046

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

    PubMed

    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

  13. Influence of Genetic Background on Anthocyanin and Copigment Composition and Behavior during Thermoalkaline Processing of Maize.

    PubMed

    Collison, Amy; Yang, Liyi; Dykes, Linda; Murray, Seth; Awika, Joseph M

    2015-06-10

    Visual color is a primary quality factor for foods purchase; identifying factors that influence in situ color quality of pigmented maize during processing is important. Twenty-four genetically distinct pigmented maize hybrids (red/blue, blue, red, and purple) were used to investigate the effect of pigment and copigment composition on color stability during nixtamalization and tortilla chip processing. The red/blue and blue samples generally contained higher proportions of acylated anthocyanins (mainly cyanidin-3-(6″-malonylglucoside)) than the red and purple color classes. Phenolic amides were the major extractable copigments in all samples (450-764 μg/g), with red samples containing the most putrescines and blue samples containing the most spermidines. Even though samples with higher proportions of acylated anthocyanins retained more pigments during processing, this did not relate to final product color quality. In general, the red/blue samples retained their color quality the best and thus are good candidates for genetic improvement for direct processing into alkalized products. PMID:26010030

  14. Inherited disorders in the black population of southern Africa. Part I. Historical and demographic background; genetic haematological conditions.

    PubMed

    Beighton, P; Botha, M C

    1986-02-15

    Genetic, geographic and socio-economic diversity has resulted in disparity in the relative prevalence of many inherited disorders and congenital conditions in the populations of southern Africa. In the first section of a 3-part article an account is given of the historical and demographic background in relation to factors which influence the presence and frequency of faulty genes in the black community. In addition, inherited haematological conditions--in particular haemoglobinopathies, red-cell enzyme and membrane defects--are discussed in terms of their clinical, genetic and anthropological significance. The conditions transmitted by simple genetic mechanisms are documented in Part II, with discussion of those notable for their unusually high or low prevalence. In the final section multifactorial, chromosomal and non-genetic congenital disorders are reviewed and a number of unusual conditions of obscure aetiology are mentioned. In this 3-part overview an attempt has been made to document present knowledge and to provide a bibliography for inherited and congenital disorders in the black population. PMID:3485313

  15. 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

  16. PKCε overexpression, irrespective of genetic background, sensitizes skin to ultraviolet radiation-induced development of squamous cell carcinomas

    PubMed Central

    Sand, Jordan Marshall; Aziz, Moammir Hasan; Dreckschmidt, Nancy Ellen; Havighurst, Thomas; Kim, KyungMann; Verma, Ajit Kumar

    2009-01-01

    Chronic exposure to ultraviolet radiation (UVR) is the major etiologic factor in the development of human skin cancers including squamous cell carcinoma (SCC). We have shown that PKCε transgenic mice on FVB/N background, which overexpress PKCε protein approximately 8-fold over endogenous levels in epidermis, exhibit about 3-fold more sensitivity than wild-type littermates to UVR-induced development of SCC (Cancer Research, 64, 7756, 2004). To determine whether it is PKCε and not the mouse genetic background, that determines susceptibility to UVR carcinogenesis, we cross-bred PKCε FVB/N transgenic mice with SKH-1 hairless mice to generate PKCε overexpressing SKH-1 hairless mice. To evaluate the susceptibility of PKCε SKH-1 hairless transgenic mice to UVR carcinogenesis, the mice were exposed to UVR (1–2 KJ/m2) three times weekly from a bank of six kodacel-filtered FS40 sunlamps. As compared to the wild-type hairless mice, PKCε overexpression in SKH-1 hairless mice decreased the latency (12 weeks) while increased the incidence (2-fold) and multiplicity (4-fold) of SCC. The SKH hairless transgenic mice were observed to be as sensitive as FVB/N transgenic mice to UVR-induced development of SCC and expression of proliferative markers (PCNA, Stat3 and ERK1/2). The results indicate that PKCε level dictates susceptibility, irrespective of genetic background, to UVR carcinogenesis. PMID:19626035

  17. Genetic background of claw disorders in the course of lactation and their relationships with type traits.

    PubMed

    Gernand, E; Döhne, D A; König, S

    2013-12-01

    Random regression threshold animal models were applied to binary longitudinal claw disorder data for studying genetic parameters of all claw disorders (ACD), as well as to claw disorders divided into different categories: non-purulent claw disorders (NPCD), purulent claw disorders (PCD), dermatitis digitalis (DD), sole ulcer (SU), phlegmona (PH), laminitis (LAM) and interdigital hyperplasia (IH) in the course of lactation. Claw disorder data were obtained from 26,651 Holstein cows kept in 15 large-scale contract herds in the region of Thuringia over a period of 5 years from 2007 to 2012. If a cow had one or more entries of the same disorder, for example, sole ulcer, within an interval of 30 days, she was scored with a '1', and otherwise, she received a score of '0' for healthy. Heritabilities for the same disorder were relatively stable between DIM 50 and DIM 300, but they tended to increase in early and late lactation. Highest heritabilities in the range from 0.20 to 0.34 were estimated for IH, and lowest heritabilities were realized for LAM (~ 0.05). Genetic correlations for same traits between different DIMs were high for adjacent test days, but close to zero for distant test days. The relationship between the sire EBVs for claw disorders and official sire EBVs for the type traits 'foot angle' was slightly antagonistic with correlation coefficients in the range from 0.05 (DD) to 0.33 (PH). Correlations between lactation EBVs for hock quality, rear leg rear view and the feet and leg index with EBVs for claw disorders were slightly favourable and ranged between -0.01 (rear leg rear view correlated with SU) and -0.43 (hock quality correlated with PH). Regarding daily EBVs for claw disorders, the strongest correlation coefficient was of value -0.46 (LAM early in lactation correlated with the feet and leg index). Genetic parameters from the random regression model were verified by applying a single-trait repeatability model. Correlation coefficients between lactation

  18. 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. PMID:26410018

  19. [Clinical and genetic background of familial myelodysplasia and acute myeloid leukemia].

    PubMed

    Király, Péter Attila; Kállay, Krisztián; Marosvári, Dóra; Benyó, Gábor; Szőke, Anita; Csomor, Judit; Bödör, Csaba

    2016-02-21

    Myelodysplastic syndrome and acute myeloid leukaemia are mainly sporadic diseases, however, rare familial cases exist. These disorders are considered rare, but are likely to be more common than currently appreciated, and are characterized by the autosomal dominant mutations of hematopoietic transcription factors. These syndromes have typical phenotypic features and are associated with an increased risk for developing overt malignancy. Currently, four recognized syndromes could be separated: familial acute myeloid leukemia with mutated CEBPA, familial myelodysplastic syndrome/acute myeloid leukemia with mutated GATA2, familial platelet disorder with propensity to myeloid malignancy with RUNX1 mutations, and telomere biology disorders due to mutations of TERC or TERT. Furthermore, there are new, emerging syndromes associated with germline mutations in novel genes including ANKRD26, ETV6, SRP72 or DDX41. This review will discuss the current understanding of the genetic basis and clinical presentation of familial leukemia and myelodysplasia. PMID:26876264

  20. 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

  1. 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

  2. Multiple effects of genetic background on variegated transgene expression in mice.

    PubMed Central

    Opsahl, Margaret L; McClenaghan, Margaret; Springbett, Anthea; Reid, Sarah; Lathe, Richard; Colman, Alan; Whitelaw, C Bruce A

    2002-01-01

    BLG/7 transgenic mice express an ovine beta-lactoglobulin transgene during lactation. Unusually, transgene expression levels in milk differ between siblings. This variable expression is due to variegated transgene expression in the mammary gland and is reminiscent of position-effect variegation. The BLG/7 line was created and maintained on a mixed CBA x C57BL/6 background. We have investigated the effect on transgene expression of backcrossing for 13 generations into these backgrounds. Variable transgene expression was observed in all populations examined, confirming that it is an inherent property of the transgene array at its site of integration. There were also strain-specific effects on transgene expression that appear to be independent of the inherent variegation. The transgene, compared to endogenous milk protein genes, is specifically susceptible to inbreeding depression. Outcrossing restored transgene expression levels to that of the parental population; thus suppression was not inherited. Finally, no generation-dependent decrease in mean expression levels was observed in the parental population. Thus, although the BLG/7 transgene is expressed in a variegated manner, there was no generation-associated accumulated silencing of transgene expression. PMID:11901126

  3. Zinc, oxidative stress, genetic background and immunosenescence: implications for healthy ageing

    PubMed Central

    Mocchegiani, Eugenio; Malavolta, Marco; Marcellini, Fiorella; Pawelec, Graham

    2006-01-01

    The relevance of zinc for proper functioning of the entire immune system is already well documented. However, the identification of individuals who really need zinc supplementation is still debated in view of the fact that excessive zinc may also be toxic. The risk of developing zinc deficiency in people from industrialized countries is relatively low, except for elderly subjects where zinc intake may be suboptimal and inflammation is chronic. Thus, the role of zinc on the immune system and on the health of European elderly people is becoming of paramount importance, considering also that the elderly population is rapidly increasing. In particular, the factors contributing to and the biochemical markers of zinc deficiency in the elderly are still remain to be established. Epidemiological, functional, and genetic studies aimed at formulating a rationale for the promotion of healthy ageing through zinc supplementation was the subject of an International Conference held in Madrid from 11–13 February 2006 (3rd ZincAge Meeting) at the CNIO Institute (local organizer: Maria Blasco, partner of ZincAge) PMID:16800874

  4. Genetic and environmental backgrounds responsible for the changes in the phenotype of MS in Japanese subjects.

    PubMed

    Kira, Jun-Ichi

    2012-10-01

    There are two distinct phenotypes of multiple sclerosis (MS) in Asians, manifesting as opticospinal (OSMS) and conventional (CMS) forms. In Japan, the results of four nationwide surveys of MS conducted between 1972 and 2004 have revealed a four-fold increase in the estimated number of clinically definite MS patients in 2003 compared with 1972; a shift in the peak age at onset from the early 30s in 1989 to the early 20s in 2003; a successive proportional decrease in optic-spinal involvement in clinically definite MS patients; an increase in the number of CMS patients with Barkhof brain lesions with advancing birth year and a decrease in the number of OSMS patients with LESCLs. These findings suggest that MS phenotypes are drastically altered by environmental factors such as latitude and "Westernization". Helicobacter pylori infection rates, reflecting sanitary conditions in infancy, are significantly different between CMS and OSMS patients. Both phenotypes show distinct HLA class II gene associations. Therefore, changes in environmental factors may have differentially influenced susceptibility to each disease subtype, given that disease susceptibility is only partly genetically determined. PMID:25877266

  5. 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

  6. 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

  7. 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

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

    PubMed

    Vogwill, T; Kojadinovic, M; MacLean, R C

    2016-05-11

    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

  9. 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

  10. 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

  11. Genetic Background of Immune Complications after Allogeneic Hematopoietic Stem Cell Transplantation in Children.

    PubMed

    Skoczen, Szymon; Bik-Multanowski, Miroslaw; Pietrzyk, Jacek J; Grabowska, Agnieszka; Fijorek, Kamil; Strojny, Wojciech; Klus-Kwiecinska, Kinga; Balwierz, Walentyna; Siedlar, Maciej

    2016-01-01

    Immune reactions are among the most serious complications observed after hematopoietic stem cell transplantation (HSCT) in children. Microarray technique allows for simultaneous assessment of expression of nearly all human genes. The objective of the study was to compare the whole genome expression in children before and after HSCT. A total of 33 children referred for HSCT were enrolled in the study. In 70% of the patients HSCT was performed for the treatment of neoplasms. Blood samples were obtained before HSCT and six months after the procedure. Subsequently, the whole genome expression was assessed in leukocytes using GeneChip Human Gene 1.0 ST microarray. The analysis of genomic profiles before and after HSCT revealed altered expression of 124 genes. Pathway enrichment analysis revealed upregulation of five pathways after HSCT: allograft rejection, graft-versus-host disease, type I diabetes mellitus, autoimmune thyroid disease, and viral myocarditis. The activation of those pathways seems to be related to immune reactions commonly observed after HSCT. Our results contribute to better understanding of the genomic background of the immunologic complications of HSCT. PMID:26880945

  12. 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

  13. Comparative analysis of genetic background in eight near-isogenic wheat lines with different H genes conferring resistance to Hessian fly

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Near-isogenic lines (NILs) are useful tools for investigating gene expression, detecting closely linked markers, or cloning the genes. However, the reliability of using NILs for genetic and genomic analysis relies on the homogeneity of the genetic background. In this study, a set of eight NILs (Car...

  14. 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

  15. 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

  16. The effects of cocaine self-administration on dendritic spine density in the rat hippocampus are dependent on genetic background.

    PubMed

    Miguéns, Miguel; Kastanauskaite, Asta; Coria, Santiago M; Selvas, Abraham; Ballesteros-Yañez, Inmaculada; DeFelipe, Javier; Ambrosio, Emilio

    2015-01-01

    Chronic exposure to cocaine induces modifications to neurons in the brain regions involved in addiction. Hence, we evaluated cocaine-induced changes in the hippocampal CA1 field in Fischer 344 (F344) and Lewis (LEW) rats, 2 strains that have been widely used to study genetic predisposition to drug addiction, by combining intracellular Lucifer yellow injection with confocal microscopy reconstruction of labeled neurons. Specifically, we examined the effects of cocaine self-administration on the structure, size, and branching complexity of the apical dendrites of CA1 pyramidal neurons. In addition, we quantified spine density in the collaterals of the apical dendritic arbors of these neurons. We found differences between these strains in several morphological parameters. For example, CA1 apical dendrites were more branched and complex in LEW than in F344 rats, while the spine density in the collateral dendrites of the apical dendritic arbors was greater in F344 rats. Interestingly, cocaine self-administration in LEW rats augmented the spine density, an effect that was not observed in the F344 strain. These results reveal significant structural differences in CA1 pyramidal cells between these strains and indicate that cocaine self-administration has a distinct effect on neuron morphology in the hippocampus of rats with different genetic backgrounds. PMID:23966583

  17. 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

  18. [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

  19. Shared Genetic Background for Regulation of Mood and Sleep: Association of GRIA3 with Sleep Duration in Healthy Finnish Women

    PubMed Central

    Utge, Siddheshwar; Kronholm, Erkki; Partonen, Timo; Soronen, Pia; Ollila, Hanna M.; Loukola, Anu; Perola, Markus; Salomaa, Veikko; Porkka-Heiskanen, Tarja; Paunio, Tiina

    2011-01-01

    Study Objectives: Sleeping 7 to 8 hours per night appears to be optimal, since both shorter and longer sleep times are related to increased morbidity and mortality. Depressive disorder is almost invariably accompanied by disturbed sleep, leading to decreased sleep duration, and disturbed sleep may be a precipitating factor in the initiation of depressive illness. Here, we examined whether, in healthy individuals, sleep duration is associated with genes that we earlier found to be associated with depressive disorder. Design: Population-based molecular genetic study. Setting: Regression analysis of 23 risk variants for depressive disorder from 12 genes to sleep duration in healthy individuals. Participants: Three thousand, one hundred, forty-seven individuals (25–75 y) from population-based Health 2000 and FINRISK 2007 samples. Measurements and Results: We found a significant association of rs687577 from GRIA3 on the X-chromosome with sleep duration in women (permutation-based corrected empirical P = 0.00001, β = 0.27; Bonferroni corrected P = 0.0052; f = 0.11). The frequency of C/C genotype previously found to increase risk for depression in women was highest among those who slept for 8 hours or less in all age groups younger than 70 years. Its frequency decreased with the lengthening of sleep duration, and those who slept for 9 to 10 hours showed a higher frequency of C/A or A/A genotypes, when compared with the midrange sleepers (7-8 hours) (permutation-based corrected empirical P = 0.0003, OR = 1.81). Conclusions: The GRIA3 polymorphism that was previously found to be associated with depressive disorder in women showed an association with sleep duration in healthy women. Mood disorders and short sleep may share a common genetic background and biologic mechanisms that involve glutamatergic neurotransmission. Citation: Utge S; Kronholm E; Partonen T; Soronen P; Ollila HM; Loukola A; Perola M; Salomaa V; Porkka-Heiskanen T; Paunio T. Shared genetic background for

  20. Borna disease virus-induced neuronal degeneration dependent on host genetic background and prevented by soluble factors

    PubMed Central

    Wu, Yuan-Ju; Schulz, Herbert; Lin, Chia-Ching; Saar, Kathrin; Patone, Giannino; Fischer, Heike; Hübner, Norbert; Heimrich, Bernd; Schwemmle, Martin

    2013-01-01

    Infection of newborn rats with Borne disease virus (BDV) results in selective degeneration of granule cell neurons of the dentate gyrus (DG). To study cellular countermechanisms that might prevent this pathology, we screened for rat strains resistant to this BDV-induced neuronal degeneration. To this end, we infected hippocampal slice cultures of different rat strains with BDV and analyzed for the preservation of the DG. Whereas infected cultures of five rat strains, including Lewis (LEW) rats, exhibited a disrupted DG cytoarchitecture, slices of three other rat strains, including Sprague–Dawley (SD), were unaffected. However, efficiency of viral replication was comparable in susceptible and resistant cultures. Moreover, these rat strain–dependent differences in vulnerability were replicated in vivo in neonatally infected LEW and SD rats. Intriguingly, conditioned media from uninfected cultures of both LEW and SD rats could prevent BDV-induced DG damage in infected LEW hippocampal cultures, whereas infection with BDV suppressed the availability of these factors from LEW but not in SD hippocampal cultures. To gain further insights into the genetic basis for this rat strain–dependent susceptibility, we analyzed DG granule cell survival in BDV-infected cultures of hippocampal neurons derived from the F1 and F2 offspring of the crossing of SD and LEW rats. Genome-wide association analysis revealed one resistance locus on chromosome (chr) 6q16 in SD rats and, surprisingly, a locus on chr3q21-23 that was associated with susceptibility. Thus, BDV-induced neuronal degeneration is dependent on the host genetic background and is prevented by soluble protective factors in the disease-resistant SD rat strain. PMID:23319640

  1. 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

  2. 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.

  3. 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.

  4. Phenolic Contents and Compositions in Skins of Red Wine Grape Cultivars among Various Genetic Backgrounds and Originations

    PubMed Central

    Zhu, Lei; Zhang, Yali; Lu, Jiang

    2012-01-01

    In order to analyze and compare the phenolic characteristics of red wine grapes with diverse genetic backgrounds, skin phenolics among 21 different cultivars belonging to Vitis vinifera L., East Asian and North American Vitis species and hybrids, as well as 2 varieties of muscadine grapes were estimated by HPLC-MS/MS. There were 45 anthocyanins, 28 flavonols, 8 flavan-3-ols, 9 cinnamic acids, 5 benzoic acids, 5 ellagic acids and 2 stilbenes detected in all the samples. Total contents of each phenolic type varied significantly among the different grape cultivars investigated. There was also a large variability in the phenolic compositions of different grape groups. The differences in anthocyanin composition were obvious between V. vinifera and non-V. vinifera grapes and also between the grapes originating from Eurasia and North America. Quercetin-3-glucuronide and quercetin-3-glucoside were marker flavonol compounds for Euvitis grape skins. Flavan-3-ol monomers were dominant in the skins of muscadine and non-V. amurensis East Asian grapes, whereas polymers were more common in V. vinifera and North American grapes. The muscadine grapes were very rich in flavonols, flavan-3-ols and ellagic acids. Via principal component analysis, these grape cultivars were clustered into three groups according to their characteristic phenolic content and composition. PMID:22489164

  5. 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

  6. 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

  7. Impact of the genetic background on the composition of the chicken plasma MiRNome in response to a stress.

    PubMed

    Ahanda, Marie-Laure Endale; Zerjal, Tatiana; Dhorne-Pollet, Sophie; Rau, Andrea; Cooksey, Amanda; Giuffra, Elisabetta

    2014-01-01

    Circulating extra-cellular microRNAs (miRNAs) have emerged as promising minimally invasive markers in human medicine. We evaluated miRNAs isolated from total plasma as biomarker candidates of a response to an abiotic stress (feed deprivation) in a livestock species. Two chicken lines selected for high (R+) and low (R-) residual feed intake were chosen as an experimental model because of their extreme divergence in feed intake and energy metabolism. Adult R+ and R- cocks were sampled after 16 hours of feed deprivation and again four hours after re-feeding. More than 292 million sequence reads were generated by small RNA-seq of total plasma RNA. A total of 649 mature miRNAs were identified; after quality filtering, 148 miRNAs were retained for further analyses. We identified 23 and 19 differentially abundant miRNAs between feeding conditions and between lines respectively, with only two miRNAs identified in both comparisons. We validated a panel of six differentially abundant miRNAs by RT-qPCR on a larger number of plasma samples and checked their response to feed deprivation in liver. Finally, we evaluated the conservation and tissue distribution of differentially abundant miRNAs in plasma across a variety of red jungle fowl tissues. We show that the chicken plasma miRNome reacts promptly to the alteration of the animal physiological condition driven by a feed deprivation stress. The plasma content of stress-responsive miRNAs is strongly influenced by the genetic background, with differences reflecting the phenotypic divergence acquired through long-term selection, as evidenced by the profiles of conserved miRNAs with a regulatory role in energy metabolism (gga-miR-204, gga-miR-let-7f-5p and gga-miR-122-5p). These results reinforce the emerging view in human medicine that even small genetic differences can have a considerable impact on the resolution of biomarker studies, and provide support for the emerging interest in miRNAs as potential novel and minimally

  8. Impact of the Genetic Background on the Composition of the Chicken Plasma MiRNome in Response to a Stress

    PubMed Central

    Dhorne-Pollet, Sophie; Rau, Andrea; Cooksey, Amanda; Giuffra, Elisabetta

    2014-01-01

    Circulating extra-cellular microRNAs (miRNAs) have emerged as promising minimally invasive markers in human medicine. We evaluated miRNAs isolated from total plasma as biomarker candidates of a response to an abiotic stress (feed deprivation) in a livestock species. Two chicken lines selected for high (R+) and low (R−) residual feed intake were chosen as an experimental model because of their extreme divergence in feed intake and energy metabolism. Adult R+ and R− cocks were sampled after 16 hours of feed deprivation and again four hours after re-feeding. More than 292 million sequence reads were generated by small RNA-seq of total plasma RNA. A total of 649 mature miRNAs were identified; after quality filtering, 148 miRNAs were retained for further analyses. We identified 23 and 19 differentially abundant miRNAs between feeding conditions and between lines respectively, with only two miRNAs identified in both comparisons. We validated a panel of six differentially abundant miRNAs by RT-qPCR on a larger number of plasma samples and checked their response to feed deprivation in liver. Finally, we evaluated the conservation and tissue distribution of differentially abundant miRNAs in plasma across a variety of red jungle fowl tissues. We show that the chicken plasma miRNome reacts promptly to the alteration of the animal physiological condition driven by a feed deprivation stress. The plasma content of stress-responsive miRNAs is strongly influenced by the genetic background, with differences reflecting the phenotypic divergence acquired through long-term selection, as evidenced by the profiles of conserved miRNAs with a regulatory role in energy metabolism (gga-miR-204, gga-miR-let-7f-5p and gga-miR-122-5p). These results reinforce the emerging view in human medicine that even small genetic differences can have a considerable impact on the resolution of biomarker studies, and provide support for the emerging interest in miRNAs as potential novel and minimally

  9. 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

  10. The TaDREB3 transgene transferred by conventional crossings to different genetic backgrounds of bread wheat improves drought tolerance.

    PubMed

    Shavrukov, Yuri; Baho, Manahil; Lopato, Sergiy; Langridge, Peter

    2016-01-01

    Drought tolerance of the wheat cultivar Bobwhite was previously enhanced by transformation with a construct containing the wheat DREB3 gene driven by the stress-inducible maize Rab17 promoter. Progeny of a single T2 transgenic line were used as pollinators in crosses with four elite bread wheat cultivars from Western Australia: Bonnie Rock, IGW-2971, Magenta and Wyalkatchem, with the aim of evaluating transgene performance in different genetic backgrounds. The selected pollinator line, BW8-9-10-3, contained multiple transgene copies, had significantly improved drought tolerance compared with wild-type plants and showed no growth and development penalties or abnormalities. A single hybrid plant was selected from each cross-combination for three rounds of backcrossing with the corresponding maternal wheat cultivar. The transgene was detected in all four F1 BC3 combinations, but stress-inducible transgene expression was found in only three of the four combinations. Under well-watered conditions, the phenotypes and grain yield components of the F2 BC3 transgene-expressing lines were similar to those of corresponding recurrent parents and null-segregants. Under severe drought conditions, the backcross lines demonstrated 12-18% higher survival rates than the corresponding control plants. Two from four F3 BC3 transgenic lines showed significantly higher yield (18.9% and 21.5%) than control plants under limited water conditions. There was no induction of transgene expression under cold stress, and therefore, no improvement of frost tolerance observed in the progenies of drought-tolerant F3 BC3 lines. PMID:25940960

  11. 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

  12. 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)...

  13. 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

  14. 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

  15. 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

  16. 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

  17. qDTY1.1, a major QTL for rice grain yield under reproductive-stage drought stress with a consistent effect in multiple elite genetic backgrounds

    PubMed Central

    2011-01-01

    Background Drought is one of the most important abiotic stresses causing drastic reductions in yield in rainfed rice environments. The suitability of grain yield (GY) under drought as a selection criterion has been reported in the past few years. Most of the quantitative trait loci (QTLs) for GY under drought in rice reported so far has been in the background of low-yielding susceptible varieties. Such QTLs have not shown a similar effect in multiple high- yielding drought-susceptible varieties, thus limiting their use in marker-assisted selection. Genetic control of GY under reproductive-stage drought stress (RS) in elite genetic backgrounds was studied in three F3:4 mapping populations derived from crosses of N22, a drought-tolerant aus cultivar, with Swarna, IR64, and MTU1010, three high-yielding popular mega-varieties, with the aim to identify QTLs for GY under RS that show a consistent effect in multiple elite genetic backgrounds. Three populations were phenotyped under RS in the dry seasons (DS) of 2009 and 2010 at IRRI. For genotyping, whole-genome scans for N22/MTU1010 and bulked segregant analysis for N22/Swarna and N22/IR64 were employed using SSR markers. Results A major QTL for GY under RS, qDTY1.1, was identified on rice chromosome 1 flanked by RM11943 and RM431 in all three populations. In combined analysis over two years, qDTY1.1 showed an additive effect of 29.3%, 24.3%, and 16.1% of mean yield in N22/Swarna, N22/IR64, and N22/MTU1010, respectively, under RS. qDTY1.1 also showed a positive effect on GY in non-stress (NS) situations in N22/Swarna, N22/IR64 over both years, and N22/MTU1010 in DS2009. Conclusions This is the first reported QTL in rice with a major and consistent effect in multiple elite genetic backgrounds under both RS and NS situations. Consistency of the QTL effect across different genetic backgrounds makes it a suitable candidate for use in marker-assisted breeding. PMID:22008150

  18. Genetic background strongly modifies the severity of symptoms of Hirschsprung disease, but not hearing loss in rats carrying Ednrb(sl) mutations.

    PubMed

    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 Ednrb(sl) 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

  19. Antibacterial resistance, genes encoding toxins and genetic background among Staphylococcus aureus isolated from community-acquired skin and soft tissue infections in France: a national prospective survey.

    PubMed

    Lamy, B; Laurent, F; Gallon, O; Doucet-Populaire, F; Etienne, J; Decousser, J-W

    2012-06-01

    The epidemiology of staphylococcal community-acquired skin and soft tissues infections (CA-SSTIs) has changed dramatically. We described prospectively the characteristics of the Staphylococcus aureus isolated from 71 non-teaching French hospitals and implicated in CA-SSTIs: antimicrobial susceptibility (mecA polymerase chain reaction [PCR], disk diffusion method), virulence factor gene (sea, tst, pvl) prevalence and genetic background (agr allele). During November 2006, 235 strains were collected (wound infection: 51%, abscess: 21%, whitlow: 8%, diabetic foot: 7%, furunculosis: 3%). sea, tst and pvl were identified in 22.1, 13.2 and 8.9% strains, respectively. agr allele 1 was the most frequently encountered genetic background, whatever the methicillin susceptibility. Among the 34 methicillin-resistant S. aureus (MRSA, 14.5% of all S. aureus), only one strain (2.9%) harboured pvl (belonging to the European ST80 clone), four (11.8%) tst (belonging to two endemic French clones) and 18 (52.9%) sea gene (mainly the Lyon clone). According to their in vitro activity, pristinamycin or trimethoprim/sulfamethoxazole could be considered as first-choice antibiotics. To date, the international pvl-positive MRSA clones have not spread in France. MRSA strains isolated from putative CA-SSTIs exhibited a genetic and phenotypic background of hospital-acquired (HA) clones. National survey should be continued, in order to monitor the emergence of virulent clones. PMID:21997773

  20. Effects of Cu/Zn Superoxide Dismutase (sod1) Genotype and Genetic Background on Growth, Reproduction and Defense in Biomphalaria glabrata

    PubMed Central

    Bonner, Kaitlin M.; Bayne, Christopher J.; Larson, Maureen K.; Blouin, Michael S.

    2012-01-01

    Resistance of the snail Biomphalaria glabrata to the trematode Schistosoma mansoni is correlated with allelic variation at copper-zinc superoxide dismutase (sod1). We tested whether there is a fitness cost associated with carrying the most resistant allele in three outbred laboratory populations of snails. These three populations were derived from the same base population, but differed in average resistance. Under controlled laboratory conditions we found no cost of carrying the most resistant allele in terms of fecundity, and a possible advantage in terms of growth and mortality. These results suggest that it might be possible to drive resistant alleles of sod1 into natural populations of the snail vector for the purpose of controlling transmission of S. mansoni. However, we did observe a strong effect of genetic background on the association between sod1 genotype and resistance. sod1 genotype explained substantial variance in resistance among individuals in the most resistant genetic background, but had little effect in the least resistant genetic background. Thus, epistatic interactions with other loci may be as important a consideration as costs of resistance in the use of sod1 for vector manipulation. PMID:22724037

  1. Non-alcoholic fatty liver disease and metabolic syndrome in adolescents: pathogenetic role of genetic background and intrauterine environment.

    PubMed

    Alisi, Anna; Cianfarani, Stefano; Manco, Melania; Agostoni, Carlo; Nobili, Valerio

    2012-02-01

    In the last three decades the incidence of metabolic syndrome (MetS) has been growing worldwide along with an increase of obesity, type 2 diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). In children and adolescents such epidemics are particularly worrisome, since the metabolic consequences in adulthood will significantly burden the health care system. Although the definition of MetS in childhood is still controversial, there is agreement with respect to NAFLD being the hepatic manifestation of MetS. However, the molecular pathogenesis of MetS and its contribution to NAFLD is complex and closely related to the pre- and postnatal environment as well as to genetic predisposing factors. The analysis of the possible relationships between NAFLD and MetS is particularly interesting, not only from an epidemiological point of view, but also to better understand the genetic and environmental factors contributing to the development of both diseases. We here summarize the most recent epidemiological data on the incidence of both diseases in adolescents, and several aspects linking MetS with NAFLD, discussing the possible role played by genetics and intrauterine environment. PMID:21355790

  2. 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. PMID:27233215

  3. Genetic background effects on disease onset and lifespan of the mutant dynactin p150Glued mouse model of motor neuron disease.

    PubMed

    Heiman-Patterson, Terry D; Blankenhorn, Elizabeth P; Sher, Roger B; Jiang, Juliann; Welsh, Priscilla; Dixon, Meredith C; Jeffrey, Jeremy I; Wong, Philip; Cox, Gregory A; Alexander, Guillermo M

    2015-01-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease primarily affecting motor neurons in the central nervous system. Although most cases of ALS are sporadic, about 5-10% of cases are familial (FALS) with approximately 20% of FALS caused by mutations in the Cu/Zn superoxide dismutase (SOD1) gene. We have reported that hSOD1-G93A transgenic mice modeling this disease show a more severe phenotype when the transgene is bred on a pure SJL background and a milder phenotype when bred on a pure B6 background and that these phenotype differences link to a region on mouse Chromosome 17.To examine whether other models of motor neuron degeneration are affected by genetic background, we bred the mutant human dynactin p150Glued (G59S-hDCTN1) transgene onto inbred SJL and B6 congenic lines. This model is based on an autosomal dominant lower motor neuron disease in humans linked to a mutation in the p150Glued subunit of the dynactin complex. As seen in hSOD1-G93A mice, we observed a more severe phenotype with earlier disease onset (p<0.001) and decreased survival (p<0.00001) when the G59S-hDCTN1 transgene was bred onto the SJL background and delayed onset (p<0.0001) with increased survival (p<0.00001) when bred onto the B6 background. Furthermore, B6 mice with an SJL derived chromosome 17 interval previously shown to delay disease onset in hSOD1-G93A mice also showed delays onset in G59S-hDCTN1 mice suggesting that at least some genetic modifiers are shared. We have shown that genetic background influences phenotype in G59S-hDCTN1 mice, in part through a region of chromosome 17 similar to the G93-hSOD1 ALS mouse model. These results support the presence of genetic modifiers in both these models some of which may be shared. Identification of these modifiers will highlight intracellular pathways involved in motor neuron disease and provide new therapeutic targets that may be applicable to motor neuron degeneration. PMID:25763819

  4. Genetics

    MedlinePlus

    Homozygous; 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 ...

  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. Contribution of Genetic Background and Clinical Risk Factors to Low-Trauma Fractures in Human Immunodeficiency Virus (HIV)-Positive Persons: The Swiss HIV Cohort Study

    PubMed Central

    Junier, Thomas; Rotger, Margalida; Biver, Emmanuel; Ledergerber, Bruno; Barceló, Catalina; Bartha, Istvan; Kovari, Helen; Schmid, Patrick; Fux, Christoph; Bernasconi, Enos; Brun del Re, Claudia; Weber, Rainer; Fellay, Jacques; Tarr, Philip E.

    2016-01-01

    Background. The impact of human genetic background on low-trauma fracture (LTF) risk has not been evaluated in the context of human immunodeficiency virus (HIV) and clinical LTF risk factors. Methods. In the general population, 6 common single-nucleotide polymorphisms (SNPs) associate with LTF through genome-wide association study. Using genome-wide SNP arrays and imputation, we genotyped these SNPs in HIV-positive, white Swiss HIV Cohort Study participants. We included 103 individuals with a first, physician-validated LTF and 206 controls matched on gender, whose duration of observation and whose antiretroviral therapy start dates were similar using incidence density sampling. Analyses of nongenetic LTF risk factors were based on 158 cases and 788 controls. Results. A genetic risk score built from the 6 LTF-associated SNPs did not associate with LTF risk, in both models including and not including parental hip fracture history. The contribution of clinical LTF risk factors was limited in our dataset. Conclusions. Genetic LTF markers with a modest effect size in the general population do not improve fracture prediction in persons with HIV, in whom clinical LTF risk factors are prevalent in both cases and controls. PMID:27419173

  7. Effectiveness of vaccination with recombinant HpaA from Helicobacter pylori is influenced by host genetic background.

    PubMed

    Sutton, Philip; Doidge, Christopher; Pinczower, Gideon; Wilson, John; Harbour, Stacey; Swierczak, Agnieszka; Lee, Adrian

    2007-07-01

    Several studies have explored the production and immunogenicity of HpaA as a potential protective antigen against Helicobacter pylori but little is known regarding its protective capabilities. We therefore evaluated the protective efficacy of recombinant HpaA (rHpaA) as a candidate vaccine antigen against H. pylori. To explore the impact of genetic diversity, inbred and outbred mice were prophylactically and therapeutically immunized with rHpaA adjuvanted with cholera toxin (CT). Prophylactic immunization induced a reduction in bacterial colonization in BALB/c and QS mice, but was ineffective in C57BL/6 mice, despite induction of antigen-specific antibodies. By contrast, therapeutic immunization was effective in all three strains of mice. Prophylactic immunization with CT-adjuvanted rHpaA was more effective when delivered via the nasal route than following intragastric delivery in BALB/c mice. However, HpaA-mediated protection was inferior to that induced by bacterial lysate. Hence, protective efficacy is inducible with vaccines containing HpaA, most relevantly shown in an outbred population of mice. The effectiveness of protection induced by HpaA antigen was influenced by host genetics and was less effective than lysate. HpaA therefore has potential for the development of effective immunization against H. pylori but this would probably entail the antigen to be one component of a multiantigenic vaccine. PMID:17567282

  8. 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

  9. The Role of CD1d-Restricted NKT Cells in the Clearance of Pseudomonas aeruginosa from the Lung Is Dependent on the Host Genetic Background

    PubMed Central

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

    2015-01-01

    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

  10. 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…

  11. Npc1 deficiency in the C57BL/6J genetic background enhances Niemann-Pick disease type C spleen pathology.

    PubMed

    Parra, Julio; Klein, Andrés D; Castro, Juan; Morales, María Gabriela; Mosqueira, Matías; Valencia, Ilse; Cortés, Victor; Rigotti, Attilio; Zanlungo, Silvana

    2011-09-30

    Niemann-Pick type C (NPC) disease is an autosomal recessive neurovisceral lipid storage disorder. The affected genes are NPC1 and NPC2. Mutations in either gene lead to intracellular cholesterol accumulation. There are three forms of the disease, which are categorized based on the onset and severity of the disease: the infantile form, in which the liver and spleen are severely affected, the juvenile form, in which the liver and brain are affected, and the adult form, which affects the brain. In mice, a spontaneous mutation in the Npc1 gene originated in the BALB/c inbred strain mimics the juvenile form of the disease. To study the influence of genetic background on the expression of NPC disease in mice, we transferred the Npc1 mutation from the BALB/c to C57BL/6J inbred background. We found that C57BL/6J-Npc1(-/-) mice present with a much more aggressive form of the disease, including a shorter lifespan than BALB/c-Npc1(-/-) mice. Surprisingly, there was no difference in the amount of cholesterol in the brains of Npc1(-/-) mice of either mouse strain. However, Npc1(-/-) mice with the C57BL/6J genetic background showed striking spleen damage with a marked buildup of cholesterol and phospholipids at an early age, which correlated with large foamy cell clusters. In addition, C57BL/6J Npc1(-/-) mice presented red cell abnormalities and abundant ghost erythrocytes that correlated with a lower hemoglobin concentration. We also found abnormalities in white cells, such as cytoplasmic granulation and neutrophil hypersegmentation that included lymphopenia and atypias. In conclusion, Npc1 deficiency in the C57BL6/J background is associated with spleen, erythrocyte, and immune system abnormalities that lead to a reduced lifespan. PMID:21910975

  12. 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).

  13. 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

  14. 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

  15. The mecA Homolog mecC Confers Resistance against β-Lactams in Staphylococcus aureus Irrespective of the Genetic Strain Background

    PubMed Central

    Ballhausen, Britta; Kriegeskorte, André; Schleimer, Nina; Peters, Georg

    2014-01-01

    In staphylococci, methicillin resistance is mediated by mecA-encoded penicillin-binding protein 2a (PBP2a), which has a low affinity for beta-lactams. Recently, a novel PBP2a homolog was described as being encoded by mecC, which shares only 70% similarity to mecA. To prove that mecC is the genetic determinant that confers methicillin resistance in Staphylococcus aureus, a mecC knockout strain was generated. The S. aureus ΔmecC strain showed considerably reduced oxacillin and cefoxitin MICs (0.25 and 4 μg/ml, respectively) compared to those of the corresponding wild-type methicillin-resistant S. aureus (MRSA) strain (8 and 16 μg/ml, respectively). Complementing the mutant in trans with wild-type mecC restored the resistance to oxacillin and cefoxitin. By expressing mecC and mecA in different S. aureus clonal lineages, we found that mecC mediates resistance irrespective of the genetic strain background, yielding oxacillin and cefoxitin MIC values comparable to those with mecA. In addition, we showed that mecC expression is inducible by oxacillin, which supports the assumption that a functional beta-lactam-dependent regulatory system is active in MRSA strains possessing staphylococcal cassette chromosome mec (SCCmec) type XI. In summary, we showed that mecC is inducible by oxacillin and mediates beta-lactam resistance in SCCmec type XI-carrying strains as well as in different S. aureus genetic backgrounds. Furthermore, our results could explain the comparatively low MICs for clinical mecC-harboring S. aureus isolates. PMID:24752255

  16. The mecA homolog mecC confers resistance against β-lactams in Staphylococcus aureus irrespective of the genetic strain background.

    PubMed

    Ballhausen, Britta; Kriegeskorte, André; Schleimer, Nina; Peters, Georg; Becker, Karsten

    2014-07-01

    In staphylococci, methicillin resistance is mediated by mecA-encoded penicillin-binding protein 2a (PBP2a), which has a low affinity for beta-lactams. Recently, a novel PBP2a homolog was described as being encoded by mecC, which shares only 70% similarity to mecA. To prove that mecC is the genetic determinant that confers methicillin resistance in Staphylococcus aureus, a mecC knockout strain was generated. The S. aureus ΔmecC strain showed considerably reduced oxacillin and cefoxitin MICs (0.25 and 4 μg/ml, respectively) compared to those of the corresponding wild-type methicillin-resistant S. aureus (MRSA) strain (8 and 16 μg/ml, respectively). Complementing the mutant in trans with wild-type mecC restored the resistance to oxacillin and cefoxitin. By expressing mecC and mecA in different S. aureus clonal lineages, we found that mecC mediates resistance irrespective of the genetic strain background, yielding oxacillin and cefoxitin MIC values comparable to those with mecA. In addition, we showed that mecC expression is inducible by oxacillin, which supports the assumption that a functional beta-lactam-dependent regulatory system is active in MRSA strains possessing staphylococcal cassette chromosome mec (SCCmec) type XI. In summary, we showed that mecC is inducible by oxacillin and mediates beta-lactam resistance in SCCmec type XI-carrying strains as well as in different S. aureus genetic backgrounds. Furthermore, our results could explain the comparatively low MICs for clinical mecC-harboring S. aureus isolates. PMID:24752255

  17. The mineralization phenotype in Abcc6 ( -/- ) mice is affected by Ggcx gene deficiency and genetic background--a model for pseudoxanthoma elasticum.

    PubMed

    Li, Qiaoli; Uitto, Jouni

    2010-02-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by ectopic mineralization of connective tissues and shows considerable intra- and inter-familial phenotypic variability. PXE is caused by mutations in the ABCC6 gene, and targeted ablation of Abcc6 in mouse recapitulates PXE. In this study, we examined the hypothesis that the GGCX gene encoding gamma-glutamyl carboxylase may interfere with the mineralization process in Abcc6 ( -/- ) mice. Thus, Abcc6 ( -/- ) and Ggcx (+/-) mice were generated on 129S1;C57 and 129S1;129X1;C57 genetic backgrounds, respectively, and backcrossed with C57BL/6J for five generations. Thus, these strains differ by the 129X1 contribution to the background of the mice. We then generated Abcc6 ( -/- ) ;Ggcx (+/+) and Abcc6 ( -/- ) ;Ggcx (+/-) mice by crossing Abcc6 ( -/- ) and Ggcx (+/-) mice. The degree of mineralization of connective capsule of vibrissae, a biomarker of the mineralization process in PXE, was evaluated by computerized morphometric analysis and quantified colorimetrically by calcium and phosphate levels in tissues. The mineralization of the vibrissae in Abcc6 ( -/- ) mice takes place at approximately 5-6 weeks of age and is significantly enhanced at 3 months of age in comparison to wild-type mice (>10-fold, p < 0.001). However, the onset of mineralization in Abcc6 ( -/- ) ;Ggcx (+/+) mice was delayed until between 3 and 4 months of age, suggesting that the genetic background plays a role in modifying the mineralization process. The mineralization in the Abcc6 ( -/- ) ;Ggcx (+/- ) mice was accelerated in comparison with age-matched Abcc6 ( -/- ) ;Ggcx (+/+) mice, with approximately 3-fold difference at 3, 4, and 9 months of age (p < 0.01). The mineralization process was also accelerated in these mice by a special custom-designed diet with mineral modifications. These findings suggest a role for both the GGCX gene and the genetic background as well as dietary factors in modulating the phenotypic

  18. 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. PMID:26210294

  19. 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

  20. 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

  1. 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

  2. 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

  3. ACS Quicklook PDF products

    NASA Astrophysics Data System (ADS)

    Suchkov, Anatoly

    1999-12-01

    This report details the features of the ACS quicklook PDF products produced by the HST data pipeline. The requirements closely follow the design of paper products recommended by the Data Quality Committee, with appropriate changes required to fully support ACS.

  4. 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.

  5. Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line

    PubMed Central

    Krentz, Anthony D.; Murphy, Mark W.; Zhang, Teng; Sarver, Aaron L.; Jain, Sanjay; Griswold, Michael D.; Bardwell, Vivian J.; Zarkower, David

    2013-01-01

    Dmrt1(doublesex and mab-3 related transcription factor 1) is a regulator of testis development in vertebrates that has been implicated in testicular germ cell tumors of mouse and human. In the fetal mouse testis Dmrt1 regulates germ cell pluripotency in a strain-dependent manner. Loss of Dmrt1 in 129Sv strain mice results in a >90% incidence of testicular teratomas, tumors consisting cells of multiple germ layers; by contrast, these tumors have never been observed in Dmrt1 mutants of C57BL/6J (B6) or mixed genetic backgrounds. To further investigate the interaction between Dmrt1 and genetic background we compared mRNA expression in wild type and Dmrt1 mutant fetal testes of 129Sv and B6 mice at embryonic day 15.5 (E15.5), prior to overt tumorigenesis. Loss of Dmrt1 caused misexpression of overlapping but distinct sets of mRNAs in the two strains. The mRNAs that were selectively affected included some that changed expression only in one strain or the other and some that changed in both strains but to a greater degree in one versus the other. In particular, loss of Dmrt1 in 129Sv testes caused a more severe failure to silence regulators of pluripotency than in B6 testes. A number of genes misregulated in 129Sv mutant testes also are misregulated in human testicular germ cell tumors (TGCTs), suggesting similar etiology between germ cell tumors in mouse and man. Expression profiling showed that DMRT1 also regulates pluripotency genes in the fetal ovary, although Dmrt1 mutant females do not develop teratomas. Pathway analysis indicated disruption of several signaling pathways in Dmrt1 mutant fetal testes, including Nodal, Notch, and GDNF. We used a Nanos3-cre knock-in allele to perform conditional gene targeting, testing the GDNF coreceptors Gfra1 and Ret for effects on teratoma susceptibility. Conditional deletion of Gfra1 but not Ret in fetal germ cells of animals outcrossed to 129Sv caused a modest but significant elevation in tumor incidence. Despite some

  6. 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

  7. 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 ( ...

  8. Genetics Home Reference: Waardenburg syndrome

    MedlinePlus

    ... Me Understand Genetics Home Health Conditions Waardenburg syndrome Waardenburg syndrome Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Waardenburg syndrome is a group of genetic conditions that can ...

  9. 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 ...

  10. Early post-myocardial infarction survival in MRL mice is mediated by attenuated apoptosis and inflammation but depends on genetic background

    PubMed Central

    Hunt, Darlene L.; Campbell, Patrick H.; Zambon, Alexander C.; Vranizan, Karen; Evans, Sylvia M.; Kuo, Hai-Chien; Yamaguchi, Ken D.; Omens, Jeffrey H.; McCulloch, Andrew D.

    2011-01-01

    The Murphy Roths Large (MRL) mouse, a strain capable of regenerating right ventricular myocardium, has a high post-myocardial infarction (MI) survival rate compared with C57BL/6J (C57) mice. The biological processes responsible for this survival advantage are unknown. To assess the effect of genetic background, the LG/J strain, which harbors 75% of the MRL composite genome, was included in the study. The MRL survival advantage versus C57 mice (92% vs. 68%, P < 0.05) occurred primarily in the first 5 days; LG/J survival was intermediate (P = NS). Microarray data analysis revealed an attenuation of apoptotic (P < 0.05) and stress response transcripts in MRL hearts compared with C57 hearts after MI. Supporting the microarray results, there were fewer TUNEL-positive cells 1 day post-MI in MRL infarcts compared with C57 infarcts (P = 0.001) and fewer CD45-positive cells in the MRL infarct border zone 2 days post-MI (P < 0.01). LG/J results were intermediate (P = NS). MRL hearts had smaller infarct scars and attenuated ventricular dilation 30 days post-MI compared with C57 hearts (P < 0.05). We conclude that the early post-MI survival advantage of MRL mice over the C57 strain is mediated at least in part by reductions in apoptosis and inflammatory infiltration, and that these reductions may influence chronic remodeling. The intermediate survival, apoptosis and inflammation profile of LG/J mice suggests this high tolerance for MI in the MRL could be derived from its shared genetic background with the LG/J. PMID:21967898

  11. Impact of CCR5delta32 host genetic background and disease progression on HIV-1 intrahost evolutionary processes: efficient hypothesis testing through hierarchical phylogenetic models.

    PubMed

    Edo-Matas, Diana; Lemey, Philippe; Tom, Jennifer A; Serna-Bolea, Cèlia; van den Blink, Agnes E; van 't Wout, Angélique B; Schuitemaker, Hanneke; Suchard, Marc A

    2011-05-01

    The interplay between C-C chemokine receptor type 5 (CCR5) host genetic background, disease progression, and intrahost HIV-1 evolutionary dynamics remains unclear because differences in viral evolution between hosts limit the ability to draw conclusions across hosts stratified into clinically relevant populations. Similar inference problems are proliferating across many measurably evolving pathogens for which intrahost sequence samples are readily available. To this end, we propose novel hierarchical phylogenetic models (HPMs) that incorporate fixed effects to test for differences in dynamics across host populations in a formal statistical framework employing stochastic search variable selection and model averaging. To clarify the role of CCR5 host genetic background and disease progression on viral evolutionary patterns, we obtain gp120 envelope sequences from clonal HIV-1 variants isolated at multiple time points in the course of infection from populations of HIV-1-infected individuals who only harbored CCR5-using HIV-1 variants at all time points. Presence or absence of a CCR5 wt/Δ32 genotype and progressive or long-term nonprogressive course of infection stratify the clinical populations in a two-way design. As compared with the standard approach of analyzing sequences from each patient independently, the HPM provides more efficient estimation of evolutionary parameters such as nucleotide substitution rates and d(N)/d(S) rate ratios, as shown by significant shrinkage of the estimator variance. The fixed effects also correct for nonindependence of data between populations and results in even further shrinkage of individual patient estimates. Model selection suggests an association between nucleotide substitution rate and disease progression, but a role for CCR5 genotype remains elusive. Given the absence of clear d(N)/d(S) differences between patient groups, delayed onset of AIDS symptoms appears to be solely associated with lower viral replication rates rather

  12. The role of the immunological background of mice in the genetic variability of Schistosoma mansoni as detected by random amplification of polymorphic DNA.

    PubMed

    Cossa-Moiane, I L; Mendes, T; Ferreira, T M; Mauricio, I; Calado, M; Afonso, A; Belo, S

    2015-11-01

    Schistosomiasis is a parasitic disease caused by flatworms of the genus Schistosoma. Among the Schistosoma species known to infect humans, S. mansoni is the most frequent cause of intestinal schistosomiasis in sub-Saharan Africa and South America: the World Health Organization estimates that about 200,000 deaths per year result from schistosomiasis in sub-Saharan Africa alone. The Schistosoma life cycle requires two different hosts: a snail as intermediate host and a mammal as definitive host. People become infected when they come into contact with water contaminated with free-living larvae (e.g. when swimming, fishing, washing). Although S. mansoni has mechanisms for escaping the host immune system, only a minority of infecting larvae develop into adults, suggesting that strain selection occurs at the host level. To test this hypothesis, we compared the Belo Horizonte (BH) strain of S. mansoni recovered from definitive hosts with different immunological backgrounds using random amplification of polymorphic DNA-polymerase chain reaction (RAPD-PCR). Schistosoma mansoni DNA profiles of worms obtained from wild-type (CD1 and C57BL/6J) and mutant (Jα18- / - and TGFβRIIdn) mice were analysed. Four primers produced polymorphic profiles, which can therefore potentially be used as reference biomarkers. All male worms were genetically distinct from females isolated from the same host, with female worms showing more specific fragments than males. Of the four host-derived schistosome populations, female and male adults recovered from TGFβRIIdn mice showed RAPD-PCR profiles that were most similar to each other. Altogether, these data indicate that host immunological backgrounds can influence the genetic diversity of parasite populations. PMID:24991919

  13. G (VP7) serotype-dependent preferential VP7 gene selection detected in the genetic background of simian rotavirus SA11.

    PubMed

    Kobayashi, N; Taniguchi, K; Kojima, K; Urasawa, T; Urasawa, S

    1996-01-01

    We previously found the preferential selection of VP7 gene from a parent rotavirus strain SA11 with G serotype 3 (G3) in the sequential passages after mixed infection of simian rotavirus SA11 and SA11-human rotavirus single-VP7 gene-substitution reassortants with G1, G2, or G4 specificity. However, it has not been known whether or not VP7 genes derived from other strains with G3 specificity (G3-VP7 gene) are preferentially selected in the genetic background of SA11. To address this question, mixed infections followed by multiple passages were performed with a reassortant SA11-L2/KU-R1 (SKR1) (which possesses VP7 gene derived from G1 human rotavirus KU and other 10 genes of SA11 origin) and one of the five G3-rotaviruses, RRV, K9, YO, AK35, and S3. After the 10th passage, selection rates of SA11-L2/KU-R1 gene 9 (G1-VP7 gene) and gene 5 (NSP1 gene) reduced considerably (0 to 20.4%) in the clones obtained from all the coinfection experiments, while all or some of other segments were preferentially selected from SKR1 depending on the pairs of coinfection. When viral growth kinetics was examined, SKR1 exhibited better growth and reached a higher titer than any G3 viruses. Although the generated reassortants with VP7 gene and NSP1 gene derived from G3 viruses showed almost similar growth kinetics to that of SKR1 during the first 20 h of replication, the titers of these reassortants were higher than that of SKR1 after 36 h postinfection. The results obtained in this study suggested that G3-VP7 gene is functionally more adapted to the genetic background of SA11. PMID:8774679

  14. 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

  15. 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

  16. Evaluation of a Method Using Three Genomic Guided Escherichia coli Markers for Phylogenetic Typing of E. coli Isolates of Various Genetic Backgrounds.

    PubMed

    Hamamoto, Kouta; Ueda, Shuhei; Yamamoto, Yoshimasa; Hirai, Itaru

    2015-06-01

    Genotyping and characterization of bacterial isolates are essential steps in the identification and control of antibiotic-resistant bacterial infections. Recently, one novel genotyping method using three genomic guided Escherichia coli markers (GIG-EM), dinG, tonB, and dipeptide permease (DPP), was reported. Because GIG-EM has not been fully evaluated using clinical isolates, we assessed this typing method with 72 E. coli collection of reference (ECOR) environmental E. coli reference strains and 63 E. coli isolates of various genetic backgrounds. In this study, we designated 768 bp of dinG, 745 bp of tonB, and 655 bp of DPP target sequences for use in the typing method. Concatenations of the processed marker sequences were used to draw GIG-EM phylogenetic trees. E. coli isolates with identical sequence types as identified by the conventional multilocus sequence typing (MLST) method were localized to the same branch of the GIG-EM phylogenetic tree. Sixteen clinical E. coli isolates were utilized as test isolates without prior characterization by conventional MLST and phylogenetic grouping before GIG-EM typing. Of these, 14 clinical isolates were assigned to a branch including only isolates of a pandemic clone, E. coli B2-ST131-O25b, and these results were confirmed by conventional typing methods. Our results suggested that the GIG-EM typing method and its application to phylogenetic trees might be useful tools for the molecular characterization and determination of the genetic relationships among E. coli isolates. PMID:25809972

  17. 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

  18. Genome-wide association mapping and biochemical markers reveal that seed ageing and longevity are intricately affected by genetic background and developmental and environmental conditions in barley.

    PubMed

    Nagel, Manuela; Kranner, Ilse; Neumann, Kerstin; Rolletschek, Hardy; Seal, Charlotte E; Colville, Louise; Fernández-Marín, Beatriz; Börner, Andreas

    2015-06-01

    Globally, over 7.4 million accessions of crop seeds are stored in gene banks, and conservation of genotypic variation is pivotal for breeding. We combined genetic and biochemical approaches to obtain a broad overview of factors that influence seed storability and ageing in barley (Hordeum vulgare). Seeds from a germplasm collection of 175 genotypes from four continents grown in field plots with different nutrient supply were subjected to two artificial ageing regimes. Genome-wide association mapping revealed 107 marker trait associations, and hence, genotypic effects on seed ageing. Abiotic and biotic stresses were found to affect seed longevity. To address aspects of abiotic, including oxidative, stress, two major antioxidant groups were analysed. No correlation was found between seed deterioration and the lipid-soluble tocochromanols, nor with oil, starch and protein contents. Conversely, the water-soluble glutathione and related thiols were converted to disulphides, indicating a strong shift towards more oxidizing intracellular conditions, in seeds subjected to long-term dry storage at two temperatures or to two artificial ageing treatments. The data suggest that intracellular pH and (bio)chemical processes leading to seed deterioration were influenced by the type of ageing or storage. Moreover, seed response to ageing or storage treatment appears to be significantly influenced by both maternal environment and genetic background. PMID:25328120

  19. 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

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

    NASA Astrophysics Data System (ADS)

    Lee, Samuel K.; Ando, Shin'ichiro; Kamionkowski, Marc

    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⊕, 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.

  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. 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 ...

  3. Bothrops jararaca venom (BjV) induces differential leukocyte accumulation in mice genetically selected for acute inflammatory reaction: the role of host genetic background on expression of adhesion molecules and release of endogenous mediators.

    PubMed

    Carneiro, Adriana S; Ribeiro, Orlando G; Cabrera, Wafa H K; Vorraro, Francisca; De Franco, Marcelo; Ibañez, Olga M; Starobinas, Nancy

    2008-10-01

    The dynamics of the local inflammatory events induced by Bothrops jararaca venom (BjV) inoculation in footpad of mice genetically selected for maximal (AIRmax) and minimal (AIRmin) acute inflammatory reactivity (AIR) was investigated. The BjV injection induced a marked inflammatory cell infiltrate with predominance of neutrophils, with increased blood cell numbers before its accumulation, suggesting a stimulatory action of BjV on mechanisms of cell mobilization from bone marrow. The process of cell migration is regulated by different cell-adhesion molecules (CAM). Our results showed that neutrophil cells from both lines had the same pattern of response concerning CAMs expression, presenting the involvement of l-selectin, Mac-1 and PECAM-1 adhesion molecules in BjV-induced neutrophil accumulation. The effect of BjV on the release of pro-inflammatory cytokines and chemokines related with cellular migration was also studied and IL-1beta, IL-6, TNF-alpha and MIP-2 levels could be detected after venom injection. The AIRmax mice were shown to be more responsive than AIRmin with respect to leukocyte influx, expression of MIP-2 and release of IL-1beta and IL-6. These results demonstrate the importance of host genetic background in the local response and the involvement of alleles accumulated in AIRmax mice in the inflammatory events induced by BjV. PMID:18723041

  4. 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

  5. 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

  6. Var Gene promoter activation in clonal Plasmodium falciparum isolates follows a hierarchy and suggests a conserved switching program that is independent of genetic background.

    PubMed

    Enderes, Corinna; Kombila, Davy; Dal-Bianco, Matthias; Dzikowski, Ron; Kremsner, Peter; Frank, Matthias

    2011-11-15

    Antigenic variation of Plasmodium falciparum is mediated by a mutually exclusive expression mechanism that limits expression to an individual member of the multicopy var gene family. This process determines the antigenic and adhesive phenotype of the infected red blood cell. Previously, we showed that var gene switching is influenced by chromosomal position. Here, we address whether var gene transcription follows a general conserved pattern in long-term laboratory parasites and in recently culture-adapted field parasites. Activation of the var gene family was monitored in biological replicates in each parasite isolate every 3-5 generations for up to 3 months. We used transgenic parasites carrying a drug-selectable marker at a defined var locus to characterize var gene activation after the exclusive expression of the transgene. Transgenic parasites exhibited a repeatable hierarchy of var gene activation and a fluctuating transcriptional activity of the transgenic var locus. Transcriptional profiling of wild-type laboratory and field parasites showed a universal bias toward transcription of UpsC var genes and a fluctuating transcriptional activity of the dominant var promoter. The data suggest the existence of an intrinsic var gene transcription program that is independent of genetic background. PMID:21926380

  7. Genetic adaptation of Pseudomonas aeruginosa during chronic lung infection of patients with cystic fibrosis: strong and weak mutators with heterogeneous genetic backgrounds emerge in mucA and/or lasR mutants.

    PubMed

    Ciofu, Oana; Mandsberg, Lotte F; Bjarnsholt, Thomas; Wassermann, Tina; Høiby, Niels

    2010-04-01

    During the chronic lung infection of patients with cystic fibrosis (CF), Pseudomonas aeruginosa can survive for long periods due to adaptive evolution mediated by genetic variation. Hypermutability is considered to play an important role in this adaptive evolution and it has been demonstrated that mutator populations are amplified in the CF lung by hitchhiking with adaptive mutations. Two of the genes that are frequently mutated in isolates from chronic infection are mucA and lasR. Loss-of-function mutations in these genes determine the phenotypic switch to mucoidy and loss of quorum sensing, which are considered hallmarks of chronic virulence. The aims of our study were to investigate (1) the genetic background of the P. aeruginosa subpopulations with non-mutator, weak or strong mutator phenotype and their dynamics during the chronic lung infection, and (2) the time sequence in which the hypermutable, mucoid and quorum-sensing-negative phenotypes emerge during chronic lung infection. For these purposes the sequences of mutS, mutL, uvrD, mutT, mutY and mutM anti-mutator genes as well as of mucA and lasR were analysed in 70 sequential P. aeruginosa isolates obtained from the respiratory secretions of 10 CF patients (one to three isolates per time point). Analysis of the genetic background of the mutator phenotype showed that mutS was the most commonly affected gene followed by mutL in isolates with strong mutator phenotype. The mutT, mutY, mutM genes were affected in isolates with low fold-changes in the mutation frequencies compared to the reference strain PAO1. Isolates with non-mutator, weak or strong mutator phenotype were represented at all time points showing co-existence of these subpopulations, which suggests parallel evolution of the various mutators in the different focal niches of infection in the CF lung. Mutations in mucA and lasR occurred earlier than mutations in the anti-mutator genes, showing that hypermutability is not a prerequisite for the

  8. 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 ...

  9. 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...

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. 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 ...

  18. 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 ...

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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 ( ...

  6. 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 ...

  7. 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

  8. 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

  9. Randomized Controlled Trial of the Effectiveness of Genetic Counseling and a Distance, Computer-Based, Lifestyle Intervention Program for Adult Offspring of Patients with Type 2 Diabetes: Background, Study Protocol, and Baseline Patient Characteristics

    PubMed Central

    Nishigaki, M.; Tokunaga-Nakawatase, Y.; Nishida, J.; Taru, C.; Miyawaki, I.; Sanada, H.; Kazuma, K.

    2012-01-01

    Relatives of type 2 diabetic patients are at a high risk of developing type 2 diabetes and should be regarded as target of intervention for diabetes prevention. However, it is usually hard to motivate them to implement preventive lifestyle changes, because of lack of opportunity to take advises from medical professionals, inadequate risk perception, and low priority for preventive behavior. Prevention strategy for them therefore should be highly acceptable and suited for them. The parallel, three-group trial is now being conducted to investigate the effects of genetic counseling and/or a computerized behavioral program on the prevention of type 2 diabetes in that population. The preventive strategies used in this study could provide a novel solution to the numbers of genetically high-risk individuals, if found to be effective. The objective of this paper is to describe the background, protocol, and baseline patient characteristics of the trial. PMID:22619705

  10. Diversity of murine norovirus strains isolated from asymptomatic mice of different genetic backgrounds within a single U.S. research institute.

    PubMed

    Barron, Elyssa L; Sosnovtsev, Stanislav V; Bok, Karin; Prikhodko, Victor; Sandoval-Jaime, Carlos; Rhodes, Crystal R; Hasenkrug, Kim; Carmody, Aaron B; Ward, Jerrold M; Perdue, Kathy; Green, Kim Y

    2011-01-01

    Antibody prevalence studies in laboratory mice indicate that murine norovirus (MNV) infections are common, but the natural history of these viruses has not been fully established. This study examined the extent of genetic diversity of murine noroviruses isolated from healthy laboratory mice housed in multiple animal facilities within a single, large research institute- the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIAID-NIH) in Bethesda, Maryland, U.S. Ten distinct murine norovirus strains were isolated from various tissues and feces of asymptomatic wild type sentinel mice as well as asymptomatic immunodeficient (RAG 2(-/-)) mice. The NIH MNV isolates showed little cytopathic effect in permissive RAW264.7 cells in early passages, but all isolates examined could be adapted to efficient growth in cell culture by serial passage. The viruses, although closely related in genome sequence, were distinguishable from each other according to facility location, likely due to the introduction of new viruses into each facility from separate sources or vendors at different times. Our study indicates that the murine noroviruses are widespread in these animal facilities, despite rigorous guidelines for animal care and maintenance. PMID:21738664

  11. 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. PMID:26058953

  12. Urethral Obstruction by Seminal Coagulum is Associated with Medetomidine–Ketamine Anesthesia in Male Mice on C57BL/6J and Mixed Genetic Backgrounds

    PubMed Central

    Wells, Sara; Trower, Chris; Hough, Tertius A; Stewart, Michelle; Cheeseman, Michael T

    2009-01-01

    Male and female mice were anesthetized by intraperitoneal injection with a mixture delivering 0.5 mg/kg medetomidine and 50 mg/kg ketamine to achieve immobilization for whole-body radiographs and bone densitometry, as part of a phenotypic screen for bone and mineral disorders in mice carrying genetic modifications induced through mutagenesis with N′-ethyl-N′-nitrosourea. Morbidity and mortality occurred in 19 of 628 (3%) of male mice 24 to 72 h after a seemingly uneventful recovery from anesthesia. No morbidity or mortality occurred in 1564 female mice that were similar in age to the affected male mice and that underwent the same procedure. Of the 7 male mice that underwent postmortem examinations, 5 had urinary bladders grossly distended with urine and 1 had ascites. In addition, the pelvic or penile urethra in 5 of the examined male mice was obstructed with seminal coagulum associated with varying degrees of erosion of the urothelial lining and inflammation of the urethra. In 2 of these animals, from which plasma samples were recovered, azotemia, hyperphosphatemia, and hyperkalemia were present. The predilection for delayed morbidity and mortality in males after anesthesia suggests that anesthesia with 0.5 mg/kg medetomidine and 50 mg/kg ketamine is a potential risk factor for obstructive uropathy due to release of seminal coagulum. This adverse effect did not recur when we altered our anesthesia protocol to 10 mg/kg xylazine and 100 mg/kg ketamine. PMID:19476720

  13. Immune responses to human factor IX in haemophilia B mice of different genetic backgrounds are distinct and modified by TLR4

    PubMed Central

    Sack, B K; Wang, X; Sherman, A; Rogers, G L; Markusic, D M

    2015-01-01

    Our laboratory develops protocols to prevent or reverse ongoing anti-hFIX IgG inhibitors in haemophilia B mice with a F9 gene deletion on BALB/c and C3H/HeJ backgrounds. C3H/HeJ F9−/Y mice develop high titre anti-hFIX IgG1 inhibitors and anaphylaxis, whereas most BALB/c F9−/Y mice have mild anti-hFIX IgG1 inhibitors and no anaphylaxis. Our aim was to determine if hFIX-specific B- and T-cell responses in BALB/c and C3H/HeJ F9−/Y mice trigger the difference in anti-hFIX immune responses. BALB/c and C3H/HeJ F9−/Y mice were challenged weekly with recombinant hFIX protein. Humoral immune responses were determined by IgG1 and IgG2a anti-hFIX ELISA, Bethesda assay for inhibitors and B-cell ELISpot on bone marrow and spleen cells. T-cell studies measured the TH1 (IFN-γ) and TH2 (IL-4) cytokine responses in splenocytes at the mRNA and protein level in response to hFIX protein. Antibody responses were also measured in C3H/HeJ/OuJ F9−/Y mice with restored toll-like receptor 4 (TLR4) function. BALB/c F9−/Y mice have a TH2 skewed response and a reduction in anti-hFIX secreting plasma cells in the bone marrow. Independent antigen challenge revealed both strains generated equivalent IgG1 antibody titres to an intravenously delivered antigen. C3H/HeJ F9−/Y mice have a mixed TH1 and TH2 response (mainly TH2). Importantly, TLR4 signalling has a modulatory role in the C3H background on the levels of anti-hFIX IgG1 and incidence of anaphylaxis. The background strain strongly impacts the immune response to hFIX, which can be significantly impacted by mutations in innate immune sensors. PMID:25417755

  14. 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

  15. 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. PMID:26113523

  16. 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

  17. 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

  18. Metabolic and clinical response to Escherichia coli lipopolysaccharide in layer pullets of different genetic backgrounds supplied with graded dietary L-arginine.

    PubMed

    Lieboldt, M A; Frahm, J; Halle, I; Görs, S; Schrader, L; Weigend, S; Preisinger, R; Metges, C C; Breves, G; Dänicke, S

    2016-03-01

    L-arginine (Arg) is an essential amino acid in birds that plays a decisive role in avian protein synthesis and immune response. Effects of graded dietary Arg supply on metabolic and clinical response to Escherichia coli lipopolysaccharide (LPS) were studied over 48 hours after a single intramuscular LPS injection in 18-week-old genetically diverse purebred pullets. LPS induced a genotype-specific fever response within 4 hours post injectionem. Whereas brown genotypes showed an initial hypothermia followed by longer-lasting moderate hyperthermia, white genotypes exhibited a biphasic hyperthermia without initial hypothermia. Furthermore, within 2 hours after LPS injection, sickness behavior characterized by lethargy, anorexia, intensified respiration, and ruffled feathers appeared, persisted for 3 to 5 hours and recovered 12 hours post injectionem. The varying grades of Arg did not alter the examined traits named above, whereas insufficient Arg reduced body growth and increased relative weights of liver and pancreas significantly. At 48 hours post injectionem, increased relative weights of liver and spleen were also found in LPS treated pullets, whereas LPS decreased those of pancreas, bursa, thymus, and cecal tonsils. Moreover, LPS lowered the sum of plasma amino acids and decreased plasma concentrations of Arg, citrulline, glutamate, methionine, ornithine, phenylalanine, proline, tryptophan, and tyrosine, and increased those of aspartate, glutamine, lysine, 1- and 3-methyl-histidine. Elevating concentrations of dietary Arg led to increasing plasma concentrations of Arg, citrulline, ornithine, and 3-methyl-histidine subsequently. As quantitative expression of LPS-induced anorexia, proteolysis, and the following changes in plasma amino acids, pullets showed a significant decrease of feed and nitrogen intake and catabolic metabolism characterized by negative nitrogen balance and body weight loss in the first 24 hours post injectionem. Pullets recovered from the

  19. 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 ...

  20. 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 ...

  1. 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 ...

  2. 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 ...

  3. 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 ...

  4. 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 ...

  5. 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 ...

  6. 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 ...

  7. 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 ...

  8. 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 ...

  9. 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 ...

  10. 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 ...

  11. Genetics Home Reference: factor V deficiency

    MedlinePlus

    ... Genetics Home Health Conditions factor V deficiency factor V deficiency Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Factor V deficiency is a rare bleeding disorder. The signs ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. Temporal and Anatomical Host Resistance to Chronic Salmonella Infection Is Quantitatively Dictated by Nramp1 and Influenced by Host Genetic Background

    PubMed Central

    Loomis, Wendy P.; Johnson, Matthew L.; Brasfield, Alicia; Blanc, Marie-Pierre; Yi, Jaehun; Miller, Samuel I.; Cookson, Brad T.; Hajjar, Adeline M.

    2014-01-01

    The lysosomal membrane transporter, Nramp1, plays a key role in innate immunity and resistance to infection with intracellular pathogens such as non-typhoidal Salmonella (NTS). NTS-susceptible C57BL/6 (B6) mice, which express the mutant Nramp1D169 allele, are unable to control acute infection with Salmonella enterica serovar Typhimurium following intraperitoneal or oral inoculation. Introducing functional Nramp1G169 into the B6 host background, either by constructing a congenic strain carrying Nramp1G169 from resistant A/J mice (Nramp-Cg) or overexpressing Nramp1G169 from a transgene (Nramp-Tg), conferred equivalent protection against acute Salmonella infection. In contrast, the contributions of Nramp1 for controlling chronic infection are more complex, involving temporal and anatomical differences in Nramp1-dependent host responses. Nramp-Cg, Nramp-Tg and NTS-resistant 129×1/SvJ mice survived oral Salmonella infection equally well for the first 2–3 weeks, providing evidence that Nramp1 contributes to the initial control of NTS bacteremia preceding establishment of chronic Salmonella infection. By day 30, increased host Nramp1 expression (Tg>Cg) provided greater protection as indicated by decreased splenic bacterial colonization (Tg

  17. Loss of MOR-1 on different genetic backgrounds leads to increased BrdU labeling in the dentate gyrus only after repeated injection

    PubMed Central

    Cominski, Tara P.; Turchin, Carol E.; Hsu, Ming-Sing; Ansonoff, Michael A.

    2012-01-01

    The endogenous opioid system is involved in various physiological processes including neurogenesis in the dentate gyrus (DG) of the hippocampus. In the current study, we investigated the role of the mu opioid receptor (MOR-1) on DG neurogenesis and measured glucocorticoid levels following several injection paradigms to supplement the neurogenesis experiments. MOR-1 knockout (KO) mice on C57BL/6 and 129S6 backgrounds were injected with BrdU using either a single injection or two different repeated injection protocols and then sacrificed at different time points. The total number of BrdU and PCNA positive cells in the DG is significantly increased in MOR-1 KO mice compared to WT on both strains after repeated injection, but not after a single injection. Plasma corticosterone (CORT) levels increased similarly in MOR-1 KO and WT mice following both single and repeated injection, indicating that the stress response is activated following any injection protocol, but that the mechanism responsible for the increase in BrdU labeling in MOR-1 KO mice is CORT-level independent. Finally, WT 129S6 mice, independent of genotype, showed higher levels of plasma CORT compared to WT C57BL/6 mice in both non-injected controls and following injection at two separate time points; these levels were inversely correlated with low numbers of BrdU cells in the DG in 129S6 mice compared to C57BL/6 mice. In summary, these data demonstrate that loss of MOR-1 increases BrdU labeling in the DG independent of CORT levels, but only following a repeated injection, illustrating the capability of injection paradigms to influence cell proliferative responses in a genotype-dependent manner. PMID:22280973

  18. 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.

  19. 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.

  20. 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

  1. Genetic background of extreme violent behavior.

    PubMed

    Tiihonen, J; Rautiainen, M-R; Ollila, H M; 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

    2015-06-01

    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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. Rapid vascular responses to anthrax lethal toxin in mice containing a segment of chromosome 11 from the CAST/Ei strain on a C57BL/6 genetic background.

    PubMed

    Weigel, Kelsey J; Rues, Laura; Doyle, Edward J; Buchheit, Cassandra L; Wood, John G; Gallagher, Ryan J; Kelly, Laura E; Radel, Jeffrey D; Bradley, Kenneth A; LeVine, Steven M

    2012-01-01

    Host allelic variation controls the response to B. anthracis and the disease course of anthrax. Mouse strains with macrophages that are responsive to anthrax lethal toxin (LT) show resistance to infection while mouse strains with LT non-responsive macrophages succumb more readily. B6.CAST.11M mice have a region of chromosome 11 from the CAST/Ei strain (a LT responsive strain) introgressed onto a LT non-responsive C57BL/6J genetic background. Previously, B6.CAST.11M mice were found to exhibit a rapid inflammatory reaction to LT termed the early response phenotype (ERP), and displayed greater resistance to B. anthracis infection compared to C57BL/6J mice. Several ERP features (e.g., bloat, hypothermia, labored breathing, dilated pinnae vessels) suggested vascular involvement. To test this, Evan's blue was used to assess vessel leakage and intravital microscopy was used to monitor microvascular blood flow. Increased vascular leakage was observed in lungs of B6.CAST.11M mice compared to C57BL/6J mice 1 hour after systemic administration of LT. Capillary blood flow was reduced in the small intestine mesentery without concomitant leukocyte emigration following systemic or topical application of LT, the latter suggesting a localized tissue mechanism in this response. Since LT activates the Nlrp1b inflammasome in B6.CAST.11M mice, the roles of inflammasome products, IL-1β and IL-18, were examined. Topical application to the mesentery of IL-1β but not IL-18 revealed pronounced slowing of blood flow in B6.CAST.11M mice that was not present in C57BL/6J mice. A neutralizing anti-IL-1β antibody suppressed the slowing of blood flow induced by LT, indicating a role for IL-1β in the response. Besides allelic differences controlling Nlrp1b inflammasome activation by LT observed previously, evidence presented here suggests that an additional genetic determinant(s) could regulate the vascular response to IL-1β. These results demonstrate that vessel leakage and alterations to

  8. 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 ...

  9. 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 ...

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. Background sources at PEP

    SciTech Connect

    Lynch, H.; Schwitters, R.F.; Toner, W.T.

    1988-01-01

    Important sources of background for PEP experiments are studied. Background particles originate from high-energy electrons and positrons which have been lost from stable orbits, ..gamma..-rays emitted by the primary beams through bremsstrahlung in the residual gas, and synchrotron radiation x-rays. The effect of these processes on the beam lifetime are calculated and estimates of background rates at the interaction region are given. Recommendations for the PEP design, aimed at minimizing background are presented. 7 figs., 4 tabs.

  1. 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.

  2. GW182 controls Drosophila circadian behavior and PDF-receptor signaling.

    PubMed

    Zhang, Yong; Emery, Patrick

    2013-04-10

    The neuropeptide PDF is crucial for Drosophila circadian behavior: it keeps circadian neurons synchronized. Here, we identify GW182 as a key regulator of PDF signaling. Indeed, GW182 downregulation results in phenotypes similar to those of Pdf and Pdf-receptor (Pdfr) mutants. gw182 genetically interacts with Pdfr and cAMP signaling, which is essential for PDFR function. GW182 mediates miRNA-dependent gene silencing through its interaction with AGO1. Consistently, GW182's AGO1 interaction domain is required for GW182's circadian function. Moreover, our results indicate that GW182 modulates PDFR signaling by silencing the expression of the cAMP phosphodiesterase DUNCE. Importantly, this repression is under photic control, and GW182 activity level--which is limiting in circadian neurons--influences the responses of the circadian neural network to light. We propose that GW182's gene silencing activity functions as a rheostat for PDFR signaling and thus profoundly impacts the circadian neural network and its response to environmental inputs. PMID:23583112

  3. 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.

  4. Neurobiological background of negative symptoms.

    PubMed

    Galderisi, Silvana; Merlotti, Eleonora; Mucci, Armida

    2015-10-01

    Studies investigating neurobiological bases of negative symptoms of schizophrenia failed to provide consistent findings, possibly due to the heterogeneity of this psychopathological construct. We tried to review the findings published to date investigating neurobiological abnormalities after reducing the heterogeneity of the negative symptoms construct. The literature in electronic databases as well as citations and major articles are reviewed with respect to the phenomenology, pathology, genetics and neurobiology of schizophrenia. We searched PubMed with the keywords "negative symptoms," "deficit schizophrenia," "persistent negative symptoms," "neurotransmissions," "neuroimaging" and "genetic." Additional articles were identified by manually checking the reference lists of the relevant publications. Publications in English were considered, and unpublished studies, conference abstracts and poster presentations were not included. Structural and functional imaging studies addressed the issue of neurobiological background of negative symptoms from several perspectives (considering them as a unitary construct, focusing on primary and/or persistent negative symptoms and, more recently, clustering them into factors), but produced discrepant findings. The examined studies provided evidence suggesting that even primary and persistent negative symptoms include different psychopathological constructs, probably reflecting the dysfunction of different neurobiological substrates. Furthermore, they suggest that complex alterations in multiple neurotransmitter systems and genetic variants might influence the expression of negative symptoms in schizophrenia. On the whole, the reviewed findings, representing the distillation of a large body of disparate data, suggest that further deconstruction of negative symptomatology into more elementary components is needed to gain insight into underlying neurobiological mechanisms. PMID:25797499

  5. 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 ...

  6. 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 ...

  7. 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)

  8. 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.

  9. Virtual Libraries and Valuable .pdf Downloads.

    ERIC Educational Resources Information Center

    Van Horn, Royal

    2002-01-01

    Describes educational resources available as free downloads on the Internet. Includes, for example, websites for downloads of the "Digest of Education Statistics 2001," ERIC Digests, and other educational resources available in .pdf format from such organizations as the Educational Testing Service, Phi Delta Kappa, and the Association of…

  10. 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)

  11. 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.

  12. Backgrounds in Language.

    ERIC Educational Resources Information Center

    Maxwell, John C.; Long, Barbara K.

    "Backgrounds in Language," a field-tested inservice course designed for use by groups of 15 or 25 language arts teachers, provides the subject matter background teachers need to make informed decisions about what curriculum materials to use in what way, at what time, and with which students. The course is comprised of eight 2-hour sessions,…

  13. 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.

  14. 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:// ...

  15. Background Underground at WIPP

    NASA Astrophysics Data System (ADS)

    Esch, Ernst-Ingo; Hime, A.; Bowles, T. J.

    2001-04-01

    Recent interest to establish a dedicated underground laboratory in the United States prompted an experimental program at to quantify the enviromental backgrounds underground at the Waste Isolation Pilot Plant (WIPP) in Carlsbad, New Mexico. An outline of this program is provided along with recent experimental data on the cosmic ray muon flux at the 650 meter level of WIPP. The implications of the cosmic ray muon and fast neutron background at WIPP will be discussed in the context of new generation, low background experiments envisioned in the future.

  16. The cosmic neutrino background

    NASA Technical Reports Server (NTRS)

    Dar, Arnon

    1991-01-01

    The cosmic neutrino background is expected to consist of relic neutrinos from the big bang, of neutrinos produced during nuclear burning in stars, of neutrinos released by gravitational stellar collapse, and of neutrinos produced by cosmic ray interactions with matter and radiation in the interstellar and intergalactic medium. Formation of baryonic dark matter in the early universe, matter-antimatter annihilation in a baryonic symmetric universe, and dark matter annihilation could have also contributed significantly to the cosmic neutrino background. The purpose of this paper is to review the properties of these cosmic neutrino backgrounds, the indirect evidence for their existence, and the prospects for their detection.

  17. Adaptive background model

    NASA Astrophysics Data System (ADS)

    Lu, Xiaochun; Xiao, Yijun; Chai, Zhi; Wang, Bangping

    2007-11-01

    An adaptive background model aiming at outdoor vehicle detection is presented in this paper. This model is an improved model of PICA (pixel intensity classification algorithm), it classifies pixels into K-distributions by color similarity, and then a hypothesis that the background pixel color appears in image sequence with a high frequency is used to evaluate all the distributions to determine which presents the current background color. As experiments show, the model presented in this paper is a robust, adaptive and flexible model, which can deal with situations like camera motions, lighting changes and so on.

  18. 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.

  19. 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.

  20. The GLAST Background Model

    SciTech Connect

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

    2007-07-12

    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.

  1. 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

  2. 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.

  3. 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.

  4. Immunopathogenic Background of Pars Planitis.

    PubMed

    Przeździecka-Dołyk, Joanna; Węgrzyn, Agnieszka; Turno-Kręcicka, Anna; Misiuk-Hojło, Marta

    2016-04-01

    Pars planitis is defined as an intermediate uveitis of unknown background of systemic disease with characteristic formations such as vitreous snowballs, snowbanks and changes in peripheral retina. The incidence of pars planitis varies 2.4-15.4 % of the uveitis patients. The pathogenesis of the disease is to be determined in future. Clinical and histopathological findings suggest an autoimmune etiology, most likely as a reaction to endogenous antigen of unknown source, with T cells predominant in both vitreous and pars plana infiltrations. T cells subsets play an important role as a memory-effector peripheral cell. Snowbanks are formed as an effect of post inflammatory glial proliferation of fibrous astrocytes. There is also a genetic predisposition for pars planitis by human leukocyte antigen and several other genes. A coexistence of multiple sclerosis and optic neuritis has been described in numerous studies. Epiretinal membrane, cataract, cystoid macular edema, retinal detachment, retinal vasculitis, neovascularization, vitreous peripheral traction, peripheral hole formation, vitreous hemorrhage, disc edema are common complications observed in pars planitis. There is a need to expand the knowledge of the pathogenic and immunologic background of the pars planitis to create an accurate pharmacological treatment. PMID:26438050

  5. 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.

  6. [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

  7. 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

  8. Daily rhythms in locomotor circuits in Drosophila involve PDF.

    PubMed

    Pírez, Nicolás; Christmann, Bethany L; Griffith, Leslie C

    2013-08-01

    The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep. PMID:23678016

  9. 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…

  10. 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.

  11. Berkeley Low Background Facility

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

    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.

  12. 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.

  13. 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…

  14. Monitored background radiometer

    NASA Technical Reports Server (NTRS)

    Ruel, C.; Larouche, M.; Donato, M.

    1986-01-01

    The infrared (IR) testing of the Olympus thermal model has provided a capability to perform cost effective thermal balance testing of satellites and satellite components. A high-accuracy monitored background radiometer was developed for the measurement of absorbed radiation heat flux encountered during IR thermal vacuum testing of spacecraft. The design, development, and calibration of this radiometer is described.

  15. A compression algorithm for the combination of PDF sets

    NASA Astrophysics Data System (ADS)

    Carrazza, Stefano; Latorre, José I.; Rojo, Juan; Watt, Graeme

    2015-10-01

    The current PDF4LHC recommendation to estimate uncertainties due to parton distribution functions (PDFs) in theoretical predictions for LHC processes involves the combination of separate predictions computed using PDF sets from different groups, each of which comprises a relatively large number of either Hessian eigenvectors or Monte Carlo (MC) replicas. While many fixed-order and parton shower programs allow the evaluation of PDF uncertainties for a single PDF set at no additional CPU cost, this feature is not universal, and, moreover, the a posteriori combination of the predictions using at least three different PDF sets is still required. In this work, we present a strategy for the statistical combination of individual PDF sets, based on the MC representation of Hessian sets, followed by a compression algorithm for the reduction of the number of MC replicas. We illustrate our strategy with the combination and compression of the recent NNPDF3.0, CT14 and MMHT14 NNLO PDF sets. The resulting compressed Monte Carlo PDF sets are validated at the level of parton luminosities and LHC inclusive cross sections and differential distributions. We determine that around 100 replicas provide an adequate representation of the probability distribution for the original combined PDF set, suitable for general applications to LHC phenomenology.

  16. PDF for Healthcare and Child Health Data Forms.

    PubMed

    Zuckerman, Alan E; Schneider, Joseph H; Miller, Ken

    2008-01-01

    PDF-H is a new best practices standard that uses XFA forms and embedded JavaScript to combine PDF forms with XML data. Preliminary experience with AAP child health forms shows that the combination of PDF with XML is a more effective method to visualize familiar data on paper and the web than the traditional use of XML and XSLT. Both PDF-H and HL7 Clinical Document Architecture can co-exist using the same data for different display formats. PMID:18999257

  17. 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

  18. 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.

  19. Background illumination simulator

    SciTech Connect

    Towry, E.R.

    1992-05-12

    This patent describes a testing apparatus for testing and evaluating the performance of laser seeking warheads for missiles, under simulated weather conditions. It comprises support means for supporting a warhead seeker; laser means for generating a laser beam and for directing a laser beam towards the seeker; a diffusion screen interposed between the seeker support means and the laser means for diffusing the laser beam; a collimating lens interposed between the diffusion screen and the seeker support means for collimating the diffused laser beam and for directing the collimated laser beam onto a warhead seeker, supported in the seeker support; background illuminator means for illuminating the seeker support and a seeker disposed therein, supported for movement into and out of an operating position between the diffusion means and the collimating lens for providing background lighting in simulation of weather lighting conditions; and control means for controlling the intensity of the light provided by the illuminator means to simulate various weather conditions.

  20. Some background about satellites

    NASA Technical Reports Server (NTRS)

    Burns, Joseph A.

    1986-01-01

    Four tables of planetary and satellite data are presented which list satellite discoveries, planetary parameters, satellite orbits, and satellite physical properties respectively. A scheme for classifying the satellites is provided and it is noted that most known moons fall into three general classes: regular satellites, collisional shards, and irregular satellites. Satellite processes are outlined with attention given to origins, dynamical and thermal evolution, surface processes, and composition and cratering. Background material is provided for each family of satellites.

  1. 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.

  2. PDF Modeling of Turbulent Lean Premixed Combustion

    SciTech Connect

    Yilmaz, S.L.; •Givi, P.; Strakey, P.A.

    2007-10-01

    The joint velocity-scalar-frequency probability density function (PDF) methodology is employed for prediction of a bluff-body stabilized lean premixed methane-air flame. A reduced mechanism with CO and NO chemistry is used to describe fuel oxidation. The predicted mean and rms values of the velocity, temperature and concentrations of major and minor species are compared with laboratory measurements. This technical effort was performed in support of the National Energy Technology Laboratory’s on-going research in “Assessment of Turbo-Chemistry Models for Gas Turbine Combustion Emissions” under the RDS contract DE-AC26-04NT41817.

  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. 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.

  5. 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.

  6. 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.

  7. Graphic composite segmentation for PDF documents with complex layouts

    NASA Astrophysics Data System (ADS)

    Xu, Canhui; Tang, Zhi; Tao, Xin; Shi, Cao

    2013-01-01

    Converting the PDF books to re-flowable format has recently attracted various interests in the area of e-book reading. Robust graphic segmentation is highly desired for increasing the practicability of PDF converters. To cope with various layouts, a multi-layer concept is introduced to segment graphic composites including photographic images, drawings with text insets or surrounded with text elements. Both image based analysis and inherent digital born document advantages are exploited in this multi-layer based layout analysis method. By combining low-level page elements clustering applied on PDF documents and connected component analysis on synthetically generated PNG image document, graphic composites can be segmented for PDF documents with complex layouts. The experimental results on graphic composite segmentation of PDF document pages have shown satisfactory performance.

  8. 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.

  9. PDF4LHC recommendations for LHC Run II

    DOE PAGESBeta

    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

  10. 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.

  11. 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.

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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.

  17. Maritime infrared background clutter

    NASA Astrophysics Data System (ADS)

    Schwering, Piet B. W.

    1996-06-01

    The detection of small targets in maritime infrared surveillance is hampered by the presence of clutter. Sea surface structure, reflection and emission changes related to incident angle variations and surface effects are standard features governing the clutter behavior. Also special effects as sun glint and horizon effects play an important role for clutter. In order to optimize the detection process, quantitative clutter estimates are of use for filter settings. We have recorded a large amount of infrared backgrounds in the last few years, during common NATO trials. A large amount of different meteorological conditions took place during the various experiments. A first set of these data have been analyzed to obtain statistical data that represent the infrared scene. We have derived vertical temperature profiles, vertical fluctuation profiles, horizontal correlation coefficients and temporal correlation functions. In this paper we present the first analysis of these data. We are in the process of obtaining a condensed database of information to regenerate clutter images from bulk meteo parameters, and clutter parameters. The clutter and meteo parameters have been used to simulate various infrared scenes. Examples of this simulation process are shown in the presentation. The simulated images are statistically similar to the original images that were used to derive the parameters. A description of the image- generation is presented. Future expansions of the model are discussed.

  18. 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.

  19. 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, ...

  20. 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 ...

  1. Genetic background of clinical homogeneity of phenylketonuria in Poland.

    PubMed Central

    Jaruzelska, J; Matuszak, R; Lyonnet, S; Rey, F; Rey, J; Filipowicz, J; Borski, K; Munnich, A

    1993-01-01

    In order to elucidate the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland, a total of 71 children with typical phenylketonuria (PKU) originating from western and northern Poland were screened for 13 mutations in the phenylalanine hydroxylase (PAH) gene. Eighty percent of all PKU alleles tested were found to carry an identified mutation. One mutation, namely the R408W mutation, accounted for more than 63% of mutant PAH alleles in Poland, the other 27% being accounted for by six mutations: IVS12nt1 (5%), IVSnt546 (5%), Y414C (4%), R252W (1.5%), R261Q (< 1%), and G272ter (< 1%). The predominance of the R408W mutation resulted in a high rate of homozygotes (35.2%) and compound heterozygotes for this mutation in children from western and northern Poland. The frequency and deleterious nature of this mutation probably accounts for the clinical homogeneity and severity of the hyperphenylalaninaemias in Poland. In addition, the high rate of the R408W mutation and its association with mutant haplotype 2 at the PAH locus in Poland give additional support to the Balto-Slavic origin of this mutant gene. PMID:8097262

  2. Mutations in metabolic pathways, what role does genetic background play?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ornithine transcarbamylase (OTC) is a key enzyme for the synthesis of urea and the endogenous synthesis of arginine. OTC is present in hepatocytes and enterocytes and catalyzes the synthesis of citrulline. Although the spf-ash mutation results in a reduction in enzyme abundance, ureagenesis is maint...

  3. 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.

  4. 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.

  5. Optimal reconstruction value for DCT dequantization using Laplacian pdf model

    NASA Astrophysics Data System (ADS)

    Kang, So-Yeon; Lee, Byung-Uk

    2004-01-01

    Many image compression standards such as JPEG, MPEG or H.263 are based on the discrete cosine transform (DCT), quantization, and Huffman coding. Quantization error is the major source of image quality degradation. The current dequantization method assumes the uniform distribution of DCT coefficients. Therefore the reconstruction value is the center of each quantization interval. However DCT coefficients are regarded to follow Laplacian probability density function (pdf). We derive an optimal reconstruction value in closed form assuming Laplacian pdf, and show the effect of the correction on image quality. We estimate the Laplacian pdf parameter for each DCT coefficient, and obtain a correction for reconstruction value from the proposed theoretical predictions. The corrected value depends on the Laplacian pdf parameter and the quantization step size Q. The effect of PSNR improvement due to the change in dequantization value is about 0.2 ~ 0.4 dB. We also analyze the reason for the limited improvements.

  6. 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.

  7. 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...

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

    NASA Astrophysics Data System (ADS)

    Verde, Licia; Jimenez, Raul; Alvarez-Gaume, Luis; Heavens, Alan F.; Matarrese, Sabino

    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 fNL 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.

  9. 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.

  10. 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.

  11. Extra dimensions: 3D in PDF documentation

    DOE PAGESBeta

    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

  12. 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.

  13. 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.

  14. 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 ...

  15. Genetic counseling

    MedlinePlus

    ... this page: //medlineplus.gov/ency/patientinstructions/000510.htm Genetic counseling To use the sharing features on this ... cystic fibrosis or Down syndrome. Who May Want Genetic Counseling? It is up to you whether or ...

  16. Genetic counseling

    MedlinePlus

    Genetics is the study of heredity, the process of a parent passing certain genes on to their ... certain diseases are also often determined by genes. Genetic counseling is the process where parents can learn ...

  17. 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 ...

  18. 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

  19. 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.

  20. 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.

  1. 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. PMID:24353297

  2. Identification of embedded mathematical formulas in PDF documents using SVM

    NASA Astrophysics Data System (ADS)

    Lin, Xiaoyan; Gao, Liangcai; Tang, Zhi; Hu, Xuan; Lin, Xiaofan

    2012-01-01

    With the tremendous popularity of PDF format, recognizing mathematical formulas in PDF documents becomes a new and important problem in document analysis field. In this paper, we present a method of embedded mathematical formula identification in PDF documents, based on Support Vector Machine (SVM). The method first segments text lines into words, and then classifies each word into two classes, namely formula or ordinary text. Various features of embedded formulas, including geometric layout, character and context content, are utilized to build a robust and adaptable SVM classifier. Embedded formulas are then extracted through merging the words labeled as formulas. Experimental results show good performance of the proposed method. Furthermore, the method has been successfully incorporated into a commercial software package for large-scale e-Book production.

  3. Galaxy clustering with photometric surveys using PDF redshift information

    DOE PAGESBeta

    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

  4. 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.

  5. Computerized Placement Tests: Background Readings.

    ERIC Educational Resources Information Center

    College Entrance Examination Board, Princeton, NJ.

    This document is a compilation of background readings for the user of Computerized Placement Tests (CPTs) developed by the College Board for student placement purposes. CPTs are computerized adaptive tests that test the individual abilities and backgrounds of examinees. CPTs are part of the ACCUPLACER student information management system. The…

  6. FAMILY BACKGROUND OF RURAL YOUTH.

    ERIC Educational Resources Information Center

    COPP, JAMES H.

    FAMILY BACKGROUNDS OF RURAL YOUTH ARE DISCUSSED. THE BACKGROUND PROVIDED BY THE FAMILY HAS IMPLICATIONS FOR THE ADJUSTMENT OF RURAL YOUTH IN AN URBANIZED, HIGHLY TECHNICAL SOCIETY. THE BASIC ECOLOGICAL CONDITIONS OF RURAL AREAS INFLUENCE THE RATE OF SOCIAL CHANGE, THE IMPORTANCE OF THE FAMILY AS A SOCIAL UNIT, AND THE ORIENTATION TOWARD LEGAL…

  7. 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.

  8. 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.

  9. 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…

  10. 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. PMID:26345167

  11. Background events in microchannel plates

    NASA Technical Reports Server (NTRS)

    Siegmund, O. H. W.; Vallerga, J.; Wargelin, B.

    1988-01-01

    Measurements have been made to assess the characteristics and origins of background events in microchannel plates (MCPs). An overall background rate of about 0.4 events/sq cm persec has been achieved consistently for MCPs that have been baked and scrubbed. The temperature and gain of the MCPs are found to have no significant effect on the background rate. Detection of 1.46-MeV gamma rays from the MCP glass confirms the presence of K-40, with a concentration of 0.0007 percent, in MCP glass. It is shown that beta decay from K-40 is sufficient to cause the background rate and spectrum observed. Anticoincidence measurements indicate the the background rate caused by cosmic ray interactions is small (less than 0.016 events/sq cm per sec).

  12. 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. PMID:21058181

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. MiniCLEAN surface backgrounds

    NASA Astrophysics Data System (ADS)

    Wang, Boqian; Schnee, Richard; Deap/Clean Collaboration

    2011-04-01

    MiniCLEAN is a dark matter experiment using 150kg fiducial mass of liquid cryogen (argon or neon) to search for Weakly Interacting Massive Particles (WIMPs). MiniCLEAN seeks to detect scintillation photons from WIMP-induced argon recoils. A potentially dominant background is from alpha decays on the inner surfaces of the containment vessel. Such events can mimic the prompt signal characteristic of nuclear recoils. This talk will show the expected background rates, methods of background discrimination, and their expected effectiveness.

  18. 17 CFR 232.104 - Unofficial PDF copies included in an electronic submission.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 17 Commodity and Securities Exchanges 2 2011-04-01 2011-04-01 false Unofficial PDF copies included... Filing Requirements § 232.104 Unofficial PDF copies included in an electronic submission. (a) An... (§ 249.101 of this chapter) or a Form D (§ 239.500 of this chapter), may include one unofficial PDF...

  19. Statistics for Learning Genetics

    NASA Astrophysics Data System (ADS)

    Charles, Abigail Sheena

    This study investigated the knowledge and skills that biology students may need to help them understand statistics/mathematics as it applies to genetics. The data are based on analyses of current representative genetics texts, practicing genetics professors' perspectives, and more directly, students' perceptions of, and performance in, doing statistically-based genetics problems. This issue is at the emerging edge of modern college-level genetics instruction, and this study attempts to identify key theoretical components for creating a specialized biological statistics curriculum. The goal of this curriculum will be to prepare biology students with the skills for assimilating quantitatively-based genetic processes, increasingly at the forefront of modern genetics. To fulfill this, two college level classes at two universities were surveyed. One university was located in the northeastern US and the other in the West Indies. There was a sample size of 42 students and a supplementary interview was administered to a select 9 students. Interviews were also administered to professors in the field in order to gain insight into the teaching of statistics in genetics. Key findings indicated that students had very little to no background in statistics (55%). Although students did perform well on exams with 60% of the population receiving an A or B grade, 77% of them did not offer good explanations on a probability question associated with the normal distribution provided in the survey. The scope and presentation of the applicable statistics/mathematics in some of the most used textbooks in genetics teaching, as well as genetics syllabi used by instructors do not help the issue. It was found that the text books, often times, either did not give effective explanations for students, or completely left out certain topics. The omission of certain statistical/mathematical oriented topics was seen to be also true with the genetics syllabi reviewed for this study. Nonetheless

  20. 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.

  1. Background suppression in MAS NMR

    NASA Astrophysics Data System (ADS)

    White, Jeffery L.; Beck, Larry W.; Ferguson, David B.; Haw, James F.

    Pulse sequences for suppressing background signals from spinning modules used in magic-angle spinning NMR are described. These pulse sequences are based on spatially selective composite 90° pulses originally reported by Bax, which provide for no net excitation of spins outside the homogeneous region of the coil. We have achieved essentially complete suppression of background signals originating from our Vespel spinning module (which uses a free-standing coil) in both 1H and 13C spectra without notable loss in signal intensity. Successful modification of both Bloch decay and cross-polarization pulse sequences to include spatially selective pulses was essential to acquire background-free spectra for weak samples. Background suppression was also found to be particularly valuable for both T1 and T1 ϱ, relaxation measurements.

  2. Low Background Counting at LBNL

    DOE PAGESBeta

    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

  3. 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.

  4. Low Background Counting at LBNL

    NASA Astrophysics Data System (ADS)

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

    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.

  5. SIMPLE PDF MODELS FOR CONVECTIVELY DRIVEN VERTICAL DIFFUSION

    EPA Science Inventory

    The mode of vertical velocity in convective boundary layers is usually negative and the probability distribution function(PDF) of w, pw is rarely symmetrlc. Consequently, vertical diffusion from elevated sources is usually asymmetric and exhibits a descending mode of concentratio...

  6. 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.

  7. Parameterization and Monte Carlo solutions to PDF evolution equations

    NASA Astrophysics Data System (ADS)

    Suciu, Nicolae; Schüler, Lennart; Attinger, Sabine; Knabner, Peter

    2015-04-01

    The probability density function (PDF) of the chemical species concentrations transported in random environments is governed by unclosed evolution equations. The PDF is transported in the physical space by drift and diffusion processes described by coefficients derived by standard upscaling procedures. Its transport in the concentration space is described by a drift determined by reaction rates, in a closed form, as well as a term accounting for the sub-grid mixing process due to molecular diffusion and local scale hydrodynamic dispersion. Sub-grid mixing processes are usually described by models of the conditionally averaged diffusion flux or models of the conditional dissipation rate. We show that in certain situations mixing terms can also be derived, in the form of an Itô process, from simulated or measured concentration time series. Monte Carlo solutions to PDF evolution equations are usually constructed with systems of computational particles, which are well suited for highly dimensional advection-dominated problems. Such solutions require the fulfillment of specific consistency conditions relating the statistics of the random concentration field, function of both space and time, to that of the time random function describing an Itô process in physical and concentration spaces which governs the evolution of the system of particles. We show that the solution of the Fokker-Planck equation for the concentration-position PDF of the Itô process coincides with the solution of the PDF equation only for constant density flows in spatially statistically homogeneous systems. We also find that the solution of the Fokker-Planck equation is still equivalent to the solution of the PDF equation weighted by the variable density or by other conserved scalars. We illustrate the parameterization of the sub-grid mixing by time series and the Monte Carlo solution for a problem of contaminant transport in groundwater. The evolution of the system of computational particles whose

  8. Analysis of genetic data on Jewish populations. I. Historical background, demographic features, and genetic markers.

    PubMed Central

    Bonné-Tamir, B; Karlin, S; Kenett, R

    1979-01-01

    Part I describes the data sets on which the analysis of Part II is based. This covers the nature of the populations sampled, the extent to which the samples are representative, and a brief review of historical and demographic facts on the populations involved. PMID:380329

  9. Springtime trans-pacific atmospheric transport from east Asia: a transit-time-pdf approach

    NASA Astrophysics Data System (ADS)

    Holzer, M.; McKendry, I.; Jaffe, D.

    2003-04-01

    The atmosphere is known to episodically transport aerosols, dust, and gaseous pollutants from industrialized south-east Asia, the Gobi desert, and Siberian wild fires to western North America. We give a novel characterization of the ever-present background transport from these regions and of the probability of transport ``events", that is, long-range transport of high concentrations with minimal dispersion. Our primary transport diagnostic is the transit-time probability density function (pdf), {\\cal G}, which is a tracer-independent measure of the flow that allows us to isolate the role of transport from other factors such as source variability and chemistry. The pdf approach, unlike typical back-trajectory analyses, captures transport due to all possible paths and accounts for both resolved advection and subgrid processes. We use a numerical model of the global atmosphere (MATCH), driven by NCEP reananlysis data, to establish the springtime statistics of daily averages of {\\cal G}. A suitably defined average of {\\cal G} quantifies the mass fraction of background air of a given transit time, or age, from the source regions. An analysis of the variability of {\\cal G} at fixed transit time allows us to identify transport events and to estimate their probability of occurrence. This is illustrated for transport events to the ``Pacific-North-West" (PNW) region of North America, defined as (43.8o-53.3o{N}) × (115.3o-124.7o{W}). Correlations between {\\cal G} averaged over the PNW and the winds at any point in the atmosphere identify large-scale anomaly structures of the flow that correspond to favorable transport to the PNW.

  10. 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)

  11. 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.

  12. Genetic counseling.

    PubMed

    Fraser, F C

    1974-09-01

    A workshop was sponsored by the National Genetics Foundation to evaluate and make recommendations about the status of genetic counseling, its goals, nature, achievements, and needs. The process of genetic workup and counseling is divided into 5 stages: validation of the diagnosis; obtaining family history; estimation of the risk of recurrence; helping the family make a decision and take appropriate action; and extending counseling to other members of the family. Counseling can be directed at individuals or at special groups with the potential of carrying such diseases as sickle cell amenia or Tay-Sachs. No consensus exists on an optimal counseling approach. Genetic counseling is regarded as a team effort, requiring, in addition to the counselor, laboratory facilities and a variety of specialists. The source of payment for genetic counseling services is regarded as a problem of increasing concern. Generally, the fee paid rarely covers the cost of the many procedures and it is suggested that the cost, like that of other public health services, should be subsidized by the state. Considerable argument exists over whether a genetic counselor must have a M.D. degree or whether a Ph. D. in medical genetics is suitable enough. The quality of much genetic counseling, which is often done in the office of doctors unskilled in the field, would be increased if better training in genetics were offered to medical students and if physicians were informed of the existence of counseling centers. Further, there is a growing feeling that some sort of accreditation of genetic counselors is desirable. PMID:4609197

  13. Gravitino condensation in fivebrane backgrounds

    NASA Astrophysics Data System (ADS)

    Kitazawa, Noriaki

    2002-04-01

    We calculate the tension of the D3-brane in the fivebrane background which is described by the exactly solvable SU(2)k×U(1) world-sheet conformal field theory with large Kač-Moody level k. The D3-brane tension is extracted from the amplitude of one closed string exchange between two parallel D3-branes, and the amplitude is calculated by utilizing the open-closed string duality. The tension of the D3-brane in the background does not coincide with the one in the flat space-time even in the flat space-time limit: k-->∞. The finite curvature effect should vanish in the flat space-time limit and only the topological effect can remain. Therefore, the deviation suggests the condensation of the gravitino and/or dilatino which has been expected in the fivebrane background as a gravitational instanton.

  14. 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.

  15. Background music and cognitive performance.

    PubMed

    Angel, Leslie A; Polzella, Donald J; Elvers, Greg C

    2010-06-01

    The present experiment employed standardized test batteries to assess the effects of fast-tempo music on cognitive performance among 56 male and female university students. A linguistic processing task and a spatial processing task were selected from the Criterion Task Set developed to assess verbal and nonverbal performance. Ten excerpts from Mozart's music matched for tempo were selected. Background music increased the speed of spatial processing and the accuracy of linguistic processing. The findings suggest that background music can have predictable effects on cognitive performance. PMID:20865993

  16. 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.

  17. Detector Background at Muon Colliders

    SciTech Connect

    Mokhov, N.V.; Striganov, S.I.; /Fermilab

    2011-09-01

    Physics goals of a Muon Collider (MC) can only be reached with appropriate design of the ring, interaction region (IR), high-field superconducting magnets, machine-detector interface (MDI) and detector. Results of the most recent realistic simulation studies are presented for a 1.5-TeV MC. It is shown that appropriately designed IR and MDI with sophisticated shielding in the detector have a potential to substantially suppress the background rates in the MC detector. The main characteristics of backgrounds are studied.

  18. 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

  19. Genetic Susceptibility to Lymphoma

    PubMed Central

    Skibola, Christine F.; Curry, John D.; Nieters, Alexandra

    2010-01-01

    BACKGROUND Genetic susceptibility studies of lymphoma may serve to identify at risk populations and to elucidate important disease mechanisms. METHODS This review considered all studies published through October 2006 on the contribution of genetic polymorphisms in the risk of lymphoma. RESULTS Numerous studies implicate the role of genetic variants that promote B-cell survival and growth with increased risk of lymphoma. Several reports including a large pooled study by InterLymph, an international consortium of non-Hodgkin lymphoma (NHL) case-control studies, found positive associations between variant alleles in TNF -308G>A and IL10 -3575T>A genes and risk of diffuse large B-cell lymphoma. Four studies reported positive associations between a GSTT1 deletion and risk of Hodgkin and non-Hodgkin lymphoma. Genetic studies of folate-metabolizing genes implicate folate in NHL risk, but further studies that include folate and alcohol assessments are needed. Links between NHL and genes involved in energy regulation and hormone production and metabolism may provide insights into novel mechanisms implicating neuro- and endocrine-immune cross-talk with lymphomagenesis, but will need replication in larger populations. CONCLUSIONS Numerous studies suggest that common genetic variants with low penetrance influence lymphoma risk, though replication studies will be needed to eliminate false positive associations. PMID:17606447

  20. Genetic High-Cholesterol Condition More Common Than Thought

    MedlinePlus

    ... nlm.nih.gov/medlineplus/news/fullstory_157755.html Genetic High-Cholesterol Condition More Common Than Thought Researchers ... the United States, she said. Rates of the genetic disorder vary based on racial/ethnic background, but ...

  1. Signaling of pigment-dispersing factor (PDF) in the Madeira cockroach Rhyparobia maderae.

    PubMed

    Wei, Hongying; Yasar, Hanzey; Funk, Nico W; Giese, Maria; Baz, El-Sayed; Stengl, Monika

    2014-01-01

    The insect neuropeptide pigment-dispersing factor (PDF) is a functional ortholog of vasoactive intestinal polypeptide, the coupling factor of the mammalian circadian pacemaker. Despite of PDF's importance for synchronized circadian locomotor activity rhythms its signaling is not well understood. We studied PDF signaling in primary cell cultures of the accessory medulla, the circadian pacemaker of the Madeira cockroach. In Ca²⁺ imaging studies four types of PDF-responses were distinguished. In regularly bursting type 1 pacemakers PDF application resulted in dose-dependent long-lasting increases in Ca²⁺ baseline concentration and frequency of oscillating Ca²⁺ transients. Adenylyl cyclase antagonists prevented PDF-responses in type 1 cells, indicating that PDF signaled via elevation of intracellular cAMP levels. In contrast, in type 2 pacemakers PDF transiently raised intracellular Ca²⁺ levels even after blocking adenylyl cyclase activity. In patch clamp experiments the previously characterized types 1-4 could not be identified. Instead, PDF-responses were categorized according to ion channels affected. Application of PDF inhibited outward potassium or inward sodium currents, sometimes in the same neuron. In a comparison of Ca²⁺ imaging and patch clamp experiments we hypothesized that in type 1 cells PDF-dependent rises in cAMP concentrations block primarily outward K⁺ currents. Possibly, this PDF-dependent depolarization underlies PDF-dependent phase advances of pacemakers. Finally, we propose that PDF-dependent concomitant modulation of K⁺ and Na⁺ channels in coupled pacemakers causes ultradian membrane potential oscillations as prerequisite to efficient synchronization via resonance. PMID:25269074

  2. Cultural Backgrounds and Textual Appropriation

    ERIC Educational Resources Information Center

    Shi, Ling

    2006-01-01

    This study examines interviews with 46 undergraduates to explore if participants with differing language and cultural backgrounds view plagiarism or textual appropriation primarily as a) a language problem because of a lack of words of one's own, or b) a cultural challenge as a result of either some first language (L1) cultural training to…

  3. 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…

  4. 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.

  5. Mathematical background of Parrondo's paradox

    NASA Astrophysics Data System (ADS)

    Behrends, Ehrhard

    2004-05-01

    Parrondo's paradox states that there are losing gambling games which, when being combined stochastically or in a suitable deterministic way, give rise to winning games. Here we investigate the probabilistic background. We show how the properties of the equilibrium distributions of the Markov chains under consideration give rise to the paradoxical behavior, and we provide methods how to find the best a priori strategies.

  6. 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.

  7. 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…

  8. 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...

  9. 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.

  10. Hot Universe Background Explorer (HUBE)

    NASA Astrophysics Data System (ADS)

    Henry, R. C.; Murthy, J.; Ford, H.; Peacock, K.; Burrows, D. N.; Smith, B. W.; Bloch, J. J.

    1998-05-01

    The study of diffuse backgrounds has played an important role in the recent history of astronomy. From the microwave discovery of the 2.7 K background to the soft X-ray detection of coronal gas to the diffuse H2 emission from warm interstellar gas in our galaxy to the infrared mapping of wisps of dust at high galactic latitudes, diffuse background astronomy has provided fundamental insights into the nature of the universe. As the various regions of the electromagnetic spectrum have been explored, their diffuse backgrounds have been found to arise from the widest possible range of sources: from the local interstellar medium to the farthest reaches of the observable universe; from the wrinkled echo of the Big Bang to the million degree plasma between the stars. Most astronomers are ``point-source" astronomers, and the history of astronomy space missions is that few have been dedicated to the elucidation of the nature of the truly diffuse radiation. And yet a large fraction of the total electromagnetic energy in the universe occurs in the form of diffuse radiation. In some spectral ranges, we do not yet know the fraction of radiation that is diffuse; we are dealing with genuinely unexplored frontiers. We will describe the extraordinary science that can be obtained through a MIDEX mission that is dedicated to the exploration of the diffuse emission in the far ultraviolet and soft X-ray regions of the spectrum, where the diffuse radiation is dominated by emission from the hottest components of the interstellar medium and, perhaps, from the intergalactic medium. HUBE currently enjoys the status of being NASA's MIDEX Alternate Astrophysics Mission. We are re-proposing HUBE in the current MIDEX competition with a much broader scientific set of goals, aiming at a definitive spectroscopic survey of the diffuse background over a greatly-expanded spectral range. Our HUBE proposal effort is being supported by Ball Aerospace Corporation.

  11. 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. PMID:26170438

  12. 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

  13. 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.

  14. [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. PMID:9489379

  15. 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 ...

  16. RNA genetics

    SciTech Connect

    Domingo, E. ); Holland, J.J. . Dept. of Biology); Ahlquist, P. . Dept. of Plant Pathology)

    1988-01-01

    This book contains the proceedings on RNA genetics: Retroviruses, Viroids, and RNA recombination, Volume 2. Topics covered include: Replication of retrovirus genomes, Hepatitis B virus replication, and Evolution of RNA viruses.

  17. 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)

  18. The evolutionary genetics of canalization.

    PubMed

    Flatt, Thomas

    2005-09-01

    Evolutionary genetics has recently made enormous progress in understanding how genetic variation maps into phenotypic variation. However why some traits are phenotypically invariant despite apparent genetic and environmental changes has remained a major puzzle. In the 1940s, Conrad Hal Waddington coined the concept and term "canalization" to describe the robustness of phenotypes to perturbation; a similar concept was proposed by Waddington's contemporary Ivan Ivanovich Schmalhausen. This paper reviews what has been learned about canalization since Waddington. Canalization implies that a genotype's phenotype remains relatively invariant when individuals of a particular genotype are exposed to different environments (environmental canalization) or when individuals of the same single- or multilocus genotype differ in their genetic background (genetic canalization). Consequently, genetic canalization can be viewed as a particular kind of epistasis, and environmental canalization and phenotypic plasticity are two aspects of the same phenomenon. Canalization results in the accumulation of phenotypically cryptic genetic variation, which can be released after a "decanalizing" event. Thus, canalized genotypes maintain a cryptic potential for expressing particular phenotypes, which are only uncovered under particular decanalizing environmental or genetic conditions. Selection may then act on this newly released genetic variation. The accumulation of cryptic genetic variation by canalization may therefore increase evolvability at the population level by leading to phenotypic diversification under decanalizing conditions. On the other hand, under canalizing conditions, a major part of the segregating genetic variation may remain phenotypically cryptic; canalization may therefore, at least temporarily, constrain phenotypic evolution. Mechanistically, canalization can be understood in terms of transmission patterns, such as epistasis, pleiotropy, and genotype by environment

  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. Application of PDF417 symbology for 'DNA Barcoding'.

    PubMed

    Kumar, N Pradeep; Rajavel, A R; Jambulingam, P

    2008-05-01

    DNA sequences consisting of about 600 base pairs of the 5' region of the cytochrome c oxidase subunit 1 (COI) gene has been proposed as DNA Barcodes for taxonomical identification of species in different animals. We evaluated the application of two-dimensional barcodes for 'DNA Barcoding'. 'PDF417' symbology was applied to convert DNA Barcode sequences already proposed [N. Pradeep Kumar, A.R. Rajavel, R. Natarajan, P. Jambulingam, DNA Barcodes can distinguish species of Indian mosquitoes (Diptera: Culicidae). J. Med. Entomol. 77 (2007) 1-7.] for 10 different species of mosquitoes prevalent in India. Decoding of these digital images using 2-D scanner and a suitable software reproduced the input DNA sequences unchanged. This analysis indicated the utility of PDF417 for 'DNA Barcoding', which could be of definite use for taxonomic documentation of animals. PMID:18282635

  1. 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.

  2. Research on Optimization of Encoding Algorithm of PDF417 Barcodes

    NASA Astrophysics Data System (ADS)

    Sun, Ming; Fu, Longsheng; Han, Shuqing

    The purpose of this research is to develop software to optimize the data compression of a PDF417 barcode using VC++6.0. According to the different compression mode and the particularities of Chinese, the relevant approaches which optimize the encoding algorithm of data compression such as spillage and the Chinese characters encoding are proposed, a simple approach to compute complex polynomial is introduced. After the whole data compression is finished, the number of the codeword is reduced and then the encoding algorithm is optimized. The developed encoding system of PDF 417 barcodes will be applied in the logistics management of fruits, therefore also will promote the fast development of the two-dimensional bar codes.

  3. Genetic Screening

    PubMed Central

    Burke, Wylie; Tarini, Beth; Press, Nancy A.; Evans, James P.

    2011-01-01

    Current approaches to genetic screening include newborn screening to identify infants who would benefit from early treatment, reproductive genetic screening to assist reproductive decision making, and family history assessment to identify individuals who would benefit from additional prevention measures. Although the traditional goal of screening is to identify early disease or risk in order to implement preventive therapy, genetic screening has always included an atypical element—information relevant to reproductive decisions. New technologies offer increasingly comprehensive identification of genetic conditions and susceptibilities. Tests based on these technologies are generating a different approach to screening that seeks to inform individuals about all of their genetic traits and susceptibilities for purposes that incorporate rapid diagnosis, family planning, and expediting of research, as well as the traditional screening goal of improving prevention. Use of these tests in population screening will increase the challenges already encountered in genetic screening programs, including false-positive and ambiguous test results, overdiagnosis, and incidental findings. Whether this approach is desirable requires further empiric research, but it also requires careful deliberation on the part of all concerned, including genomic researchers, clinicians, public health officials, health care payers, and especially those who will be the recipients of this novel screening approach. PMID:21709145

  4. Perfluorocarbon background concentrations in Europe

    NASA Astrophysics Data System (ADS)

    Straume, Anne Grete; Dietz, Russel N.; Koffı̀, Ernest N.'dri; Nodop, Katrin

    Five studies of the background level of several perfluorocarbon compounds in Europe are here presented together with measurements from the European Tracer Experiment (ETEX). The tracers used during the two ETEX tracer releases were the perfluorocarbons (PFCs); perfluoromethylcyclohexane (C 7F 14, PMCH) and perfluoromethylcyclopentane (C 6F 12, PMCP). Their background concentrations were detected by using both passive and active sampling techniques, to define the spatial and temporal variation of the PFCs over Europe. Also the background variations of four isomers of the PFC compound perfluorodimethylcyclohexane (C 8F 16, PDCH) were studied. The results were compared to other PFC tracer studies in the U.S.A. and Europe. The mean and median values of the measured PFCs were found to vary slightly and randomly in space and time. They were found to be higher and to have a larger standard deviation than the measurements from the American studies. The background concentrations were still found to be low and stable enough for PFCs to be highly suitable for use in tracer studies. The following concentrations were found: PMCP; 4.6±0.3 fl ℓ -1, PMCH: 4.6±0.8 fl ℓ -1, ocPDCH: 0.96±0.33 fl ℓ -1, mtPDCH: 9.3±0.8 fl ℓ -1, mcPDCH: 8.8±0.8 fl ℓ -1, ptPDCH: 6.1±0.8 fl ℓ -1. A study of the correlation between the measured PFC compounds showed a significant correlation between most of the compounds, which indicate that there are no major PFC sources in Europe.

  5. 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.

  6. PDF orientations in shocked quartz grains around the Chicxulub crater

    NASA Astrophysics Data System (ADS)

    Nakano, Yoichiro; Goto, Kazuhisa; Matsui, Takafumi; Tada, Ryuji; Tajika, Eiichi

    2008-04-01

    We measured 852 sets of planar deformation features (PDFs) in shocked quartz grains in impactite samples of the Yaxcopoil (YAX-1) core and from 4 Cretaceous/Tertiary (K/T) boundary deposits: the Monaca, the Cacarajícara, and the Peñalver formations in Cuba, and DSDP site 536, within 800 km of the Chicxulub crater, in order to investigate variations of PDF orientations in the proximity of the crater.

  7. The photon PDF in events with rapidity gaps

    NASA Astrophysics Data System (ADS)

    Harland-Lang, L. A.; Khoze, V. A.; Ryskin, M. G.

    2016-05-01

    We consider photon-initiated events with large rapidity gaps in proton-proton collisions, where one or both protons may break up. We formulate a modified photon PDF that accounts for the specific experimental rapidity gap veto, and demonstrate how the soft survival probability for these gaps may be implemented consistently. Finally, we present some phenomenological results for the two-photon induced production of lepton and W boson pairs.

  8. 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.

  9. TMD PDF's: gauge invariance, RG properties and Wilson lines

    SciTech Connect

    Cherednikov, I. O.; Stefanis, N. G.

    2009-03-23

    The UV divergences associated with transverse-momentum dependent (TMD) parton distribution functions (PDF) are calculated together with the ensuing one-loop anomalous dimensions in the light-cone gauge. Time-reversal-odd effects in the anomalous dimensions are observed and the role of Glauber gluons is discussed. A generalized renormalization procedure of TMD PDFs is proposed, relying upon the renormalization of contour-dependent operators with obstructions.

  10. 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.

  11. 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.

  12. Cross-reference identification within a PDF document

    NASA Astrophysics Data System (ADS)

    Li, Sida; Gao, Liangcai; Tang, Zhi; Yu, Yinyan

    2015-01-01

    Cross-references, such like footnotes, endnotes, figure/table captions, references, are a common and useful type of page elements to further explain their corresponding entities in the target document. In this paper, we focus on cross-reference identification in a PDF document, and present a robust method as a case study of identifying footnotes and figure references. The proposed method first extracts footnotes and figure captions, and then matches them with their corresponding references within a document. A number of novel features within a PDF document, i.e., page layout, font information, lexical and linguistic features of cross-references, are utilized for the task. Clustering is adopted to handle the features that are stable in one document but varied in different kinds of documents so that the process of identification is adaptive with document types. In addition, this method leverages results from the matching process to provide feedback to the identification process and further improve the algorithm accuracy. The primary experiments in real document sets show that the proposed method is promising to identify cross-reference in a PDF document.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Extra dimensions: 3d and time in pdf documentation

    NASA Astrophysics Data System (ADS)

    Graf, N. A.

    2008-07-01

    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.

  18. 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.

  19. Genetic screening

    PubMed Central

    Andermann, Anne; Blancquaert, Ingeborg

    2010-01-01

    Abstract OBJECTIVE To provide a primer for primary care professionals who are increasingly called upon to discuss the growing number of genetic screening services available and to help patients make informed decisions about whether to participate in genetic screening, how to interpret results, and which interventions are most appropriate. QUALITY OF EVIDENCE As part of a larger research program, a wide literature relating to genetic screening was reviewed. PubMed and Internet searches were conducted using broad search terms. Effort was also made to identify the gray literature. MAIN MESSAGE Genetic screening is a type of public health program that is systematically offered to a specified population of asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Ensuring an added benefit from screening, as compared with standard clinical care, and preventing unintended harms, such as undue anxiety or stigmatization, depends on the design and implementation of screening programs, including the recruitment methods, education and counseling provided, timing of screening, predictive value of tests, interventions available, and presence of oversight mechanisms and safeguards. There is therefore growing apprehension that economic interests might lead to a market-driven approach to introducing and expanding screening before program effectiveness, acceptability, and feasibility have been demonstrated. As with any medical intervention, there is a moral imperative for genetic screening to do more good than harm, not only from the perspective of individuals and families, but also for the target population and society as a whole. CONCLUSION Primary care professionals have an important role to play in helping their patients navigate the rapidly changing terrain of genetic screening services by informing them about the benefits and risks of new genetic and genomic technologies and empowering them to

  20. 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 ...

  1. 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)

  2. Background stratospheric aerosol reference model

    NASA Astrophysics Data System (ADS)

    McCormick, M. P.; Wang, Pi-Huan

    Nearly global SAGE I satellite observations in the nonvolcanic period from March 1979 to February 1980 are used to produce a reference background stratospheric aerosol optical model. Zonally average profiles of the 1.0-micron aerosol extinction for the tropics, midlatitudes, and high latitudes for both hemispheres are given in graphical and tabulated form for the different seasons. A third order polynomial fit to the vertical profile data set is used to derive analytic expressions for the seasonal global means and the yearly global mean. The results have application to the simulation of atmospheric radiative transfer and radiance calculations in atmospheric remote sensing.

  3. High background photon counting lidar

    NASA Technical Reports Server (NTRS)

    Lentz, W. J.

    1992-01-01

    Photon counting with lidar returns is usually limited to low light levels, while wide dynamic range is achieved by counting for long times. The broad emission spectrum of inexpensive high-power semiconductor lasers makes receiver filters pass too much background light for traditional photon counting in daylight. Very high speed photon counting is possible, however, at more than 500 MHz which allows the construction of eyesafe lidar operating in the presence of bright clouds. Detector improvements are possible to count to 20 GHz producing a single shot dynamic range of ten decades.

  4. [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

  5. 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.

  6. 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.

  7. A Matrix Isolation and Computational Study of Molecular Palladium Fluorides: Does PdF6 Exist?

    PubMed

    Wilson, Antony V; Nguyen, Timothy; Brosi, Felix; Wang, Xuefeng; Andrews, Lester; Riedel, Sebastian; Bridgeman, Adam J; Young, Nigel A

    2016-02-01

    Palladium atoms generated by thermal evaporation and laser ablation were reacted with and trapped in F2/Ar, F2/Ne, and neat F2 matrices. The products were characterized by electronic absorption and infrared spectroscopy, together with relativistic density functional theory calculations as well as coupled cluster calculations. Vibrational modes at 540 and 617 cm(-1) in argon matrices were assigned to molecular PdF and PdF2, and a band at 692 cm(-1) was assigned to molecular PdF4. A band at 624 cm(-1) can be assigned to either PdF3 or PdF6, with the former preferred from experimental considerations. Although calculations might support the latter assignment, our conclusion is that in these detailed experiments there is no convincing evidence for PdF6. PMID:26745551

  8. 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)

  9. 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.

  10. [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.

  11. [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.

  12. Genetic basis of hyperlysinemia

    PubMed Central

    2013-01-01

    Background Hyperlysinemia is an autosomal recessive inborn error of L-lysine degradation. To date only one causal mutation in the AASS gene encoding α-aminoadipic semialdehyde synthase has been reported. We aimed to better define the genetic basis of hyperlysinemia. Methods We collected the clinical, biochemical and molecular data in a cohort of 8 hyperlysinemia patients with distinct neurological features. Results We found novel causal mutations in AASS in all affected individuals, including 4 missense mutations, 2 deletions and 1 duplication. In two patients originating from one family, the hyperlysinemia was caused by a contiguous gene deletion syndrome affecting AASS and PTPRZ1. Conclusions Hyperlysinemia is caused by mutations in AASS. As hyperlysinemia is generally considered a benign metabolic variant, the more severe neurological disease course in two patients with a contiguous deletion syndrome may be explained by the additional loss of PTPRZ1. Our findings illustrate the importance of detailed biochemical and genetic studies in any hyperlysinemia patient. PMID:23570448

  13. 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…

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Confusion background from compact binaries

    NASA Astrophysics Data System (ADS)

    Regimbau, T.; Hughes, Scott A.

    2010-05-01

    Double neutron stars are one of the most promizing sources for terrestrial gravitational wave interferometers. For actual interferometers and their planned upgrades, the probability of having a signal present in the data is small, but as the sensitivity improves, the detection rate increases and the waveforms may start to overlap, creating a confusion background, ultimately limiting the capabilities of future detectors. The third generation Einstein Telescope, with an horizon of z > 1 and very low frequency "seismic wall" may be affected by such confusion noise. At a minimum, careful data analysis will be require to separate signals which will appear confused. This result should be borne in mind when designing highly advanced future instruments.

  19. Polarization of Cosmic Microwave Background

    NASA Astrophysics Data System (ADS)

    Buzzelli, A.; Cabella, P.; de Gasperis, G.; Vittorio, N.

    2016-02-01

    In this work we present an extension of the ROMA map-making code for data analysis of Cosmic Microwave Background polarization, with particular attention given to the inflationary polarization B-modes. The new algorithm takes into account a possible cross- correlated noise component among the different detectors of a CMB experiment. We tested the code on the observational data of the BOOMERanG (2003) experiment and we show that we are provided with a better estimate of the power spectra, in particular the error bars of the BB spectrum are smaller up to 20% for low multipoles. We point out the general validity of the new method. A possible future application is the LSPE balloon experiment, devoted to the observation of polarization at large angular scales.

  20. Recognizing foreground-background interaction

    NASA Astrophysics Data System (ADS)

    Jenkins, Jeffrey; Szu, Harold

    2010-04-01

    Can the background affect a foreground target in distant, low-quality imagery? If it does, it might occur in our mind, or perhaps it may represent a snapshot of our early vision. An affirmative answer, one way or another, may affect our current understanding of this phenomena and potentially for related applications. How can we be sure about this in the psycho-physical sense? We begin with the physiology of our brain's homeostasis, of which an isothermal equilibrium is characterized by the minimum of Helmholtz isothermal Free Energy: A = U - T0S >= 0, where T0 = 37°C, the Boltzmann Entropy S = KB1n(W), and U is the unknown internal energy to be computed.

  1. 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.

  2. 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.

  3. 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.

  4. 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. PMID:9419320

  5. 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 ...

  6. 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)

  7. Simulation appraisal of the adequacy of numbers of background markers for relationship estimation in association mapping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The number of background markers and sample size are two common issues that need to be addressed in many association mapping studies. Our objectives were (1) to investigate the robustness of genetic relatedness estimates based on different numbers of background markers via model testing and variance...

  8. Combined PDF/SPH method for compressible turbulent flows

    NASA Astrophysics Data System (ADS)

    Welton, Walter Christian

    A particle method which applies the probability density function (PDF) method to compressible turbulent flows is presented. Solution of the PDF equation is achieved using a Lagrangian/Monte Carlo approach which combines techniques borrowed from the field of smoothed particle hydrodynamics (SPH). This combination gives the method a unique ability to extract mean quantities, including the mean pressure gradient, directly from the particles using a grid-free approach. Two algorithms which greatly reduce the computational work for SPH in 1D and 2D have been developed to implement the method; for a simulation with N particles the computational work scales purely as {cal O}(N). The particle method has also been combined with a variance-reduction technique which can significantly reduce statistical error in first and second moments of selected mean flow quantities. When used with a second-order accurate predictor/corrector scheme, the resulting particle method provides a feasible way to obtain accurate PDF solutions to compressible turbulent flow problems. Results are presented for a variety of quasi-1D and 2D flows to demonstrate the method's robustness. These include solutions to both statistically stationary and nonstationary problems, and use both periodic and characteristic-based inflow/outflow boundary conditions. A 2D plane wake simulation also includes comparisons with experimental data and shows good agreement in spite of the simple turbulence model used. Comprehensive studies of numerical errors have also been performed, including a convergence study of the method. Detailed results are presented which confirm the expected behavior of each error.

  9. 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 ...

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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

  18. 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

  19. 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.

  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. Cancer Genetics Services Directory

    MedlinePlus

    ... Prevention 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 counseling, genetic susceptibility testing, ...

  2. 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, ...

  3. Genetically engineered foods

    MedlinePlus

    ... plants or animals) inserted into their genetic codes. Genetic engineering can be done with plants, animals, or bacteria ... have been genetically engineering plants since the 1990s. Genetic engineering allows scientists to speed this process up by ...

  4. Cosmological implications of the PSCz PDF and its moments

    NASA Astrophysics Data System (ADS)

    Plionis, Manolis; Basilakos, Spyros

    2001-10-01

    We compare the probability density function (PDF) and its low-order moments (variance and skewness) of the smoothed IRAS Point Source Catalogue Redshift Survey (PSCz) galaxy density field and of the corresponding simulated PSCz look-alikes, generated from N-body simulations of six different dark matter models: four structure-normalized with Γ=0.25 and σ8=0.55Ω0-0.6, one COBE-normalized, and the old standard cold dark matter model. The galaxy distributions are smoothed with a Gaussian window at three different smoothing scales, Rsm=5, 10 and 15h-1Mpc. We find that the simulation PSCz look-alike PDFs are sensitive only to the normalization of the power spectrum, probably owing to the shape similarity of the simulated galaxy power spectrum on the relevant scales. We find that the only models that are consistent, at a high significance level, with the observed PSCz PDF are models with a relatively low power spectrum normalization (σ8=0.83). From the phenomenologically derived σ8-moments relation, fitted from the simulation data, we find that the PSCz moments suggest σ8~=0.7.

  5. PDF receptor signaling in Drosophila contributes to both circadian and geotactic behaviors.

    PubMed

    Mertens, Inge; Vandingenen, Anick; Johnson, Erik C; Shafer, Orie T; Li, W; Trigg, J S; De Loof, Arnold; Schoofs, Liliane; Taghert, Paul H

    2005-10-20

    The neuropeptide Pigment-Dispersing Factor (PDF) is a principle transmitter regulating circadian locomotor rhythms in Drosophila. We have identified a Class II (secretin-related) G protein-coupled receptor (GPCR) that is specifically responsive to PDF and also to calcitonin-like peptides and to PACAP. In response to PDF, the PDF receptor (PDFR) elevates cAMP levels when expressed in HEK293 cells. As predicted by in vivo studies, cotransfection of Neurofibromatosis Factor 1 significantly improves coupling of PDFR to adenylate cyclase. pdfr mutant flies display increased circadian arrhythmicity, and also display altered geotaxis that is epistatic to that of pdf mutants. PDFR immunosignals are expressed by diverse neurons, but only by a small subset of circadian pacemakers. These data establish the first synapse within the Drosophila circadian neural circuit and underscore the importance of Class II peptide GPCR signaling in circadian neural systems. PMID:16242402

  6. PDF-modulated visual inputs and cryptochrome define diurnal behavior in Drosophila.

    PubMed

    Cusumano, Paola; Klarsfeld, André; Chélot, Elisabeth; Picot, Marie; Richier, Benjamin; Rouyer, François

    2009-11-01

    Morning and evening circadian oscillators control the bimodal activity of Drosophila in light-dark cycles. The lateral neurons evening oscillator (LN-EO) is important for promoting diurnal activity at dusk. We found that the LN-EO autonomously synchronized to light-dark cycles through either the cryptochrome (CRY) that it expressed or the visual system. In conditions in which CRY was not activated, flies depleted for pigment-dispersing factor (PDF) or its receptor lost the evening activity and displayed reversed PER oscillations in the LN-EO. Rescue experiments indicated that normal PER cycling and the presence of evening activity relied on PDF secretion from the large ventral lateral neurons and PDF receptor function in the LN-EO. The LN-EO thus integrates light inputs and PDF signaling to control Drosophila diurnal behavior, revealing a new clock-independent function for PDF. PMID:19820704

  7. 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

  8. 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

  9. 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.

  10. 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)

  11. 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. PMID:26306190

  12. Image segmentation by background extraction refinements

    NASA Technical Reports Server (NTRS)

    Rodriguez, Arturo A.; Mitchell, O. Robert

    1990-01-01

    An image segmentation method refining background extraction in two phases is presented. In the first phase, the method detects homogeneous-background blocks and estimates the local background to be extracted throughout the image. A block is classified homogeneous if its left and right standard deviations are small. The second phase of the method refines background extraction in nonhomogeneous blocks by recomputing the shoulder thresholds. Rules that predict the final background extraction are derived by observing the behavior of successive background statistical measurements in the regions under the presence of dark and/or bright object pixels. Good results are shown for a number of outdoor scenes.

  13. Selection Components in Background Replacement Lines of Drosophila

    PubMed Central

    Clark, Andrew G.; Bundgaard, Jørgen

    1984-01-01

    Selection components analysis was performed in lines of Drosophila melanogaster at three times during substitution backcrossing. The initial two lines were inbred isofemale lines from natural populations in California, and one had the spread wing mutation eagle. The selection components analysis revealed aspects of the genetic structure of the determinants of fitness by demonstrating changes in the marginal fitnesses of the eagle locus. Differences among backgrounds essentially disappeared by the 20th generation of backcrossing, suggesting that the previously observed differences were attributable to linkage disequilibrium. The method of bootstrapping was used as a novel means of determining statistical confidence in selection components. PMID:17246226

  14. Mapping Quantitative Trait Loci by Controlling Polygenic Background Effects

    PubMed Central

    Xu, Shizhong

    2013-01-01

    A new mixed-model method was developed for mapping quantitative trait loci (QTL) by incorporating multiple polygenic covariance structures. First, we used genome-wide markers to calculate six different kinship matrices. We then partitioned the total genetic variance into six variance components, one corresponding to each kinship matrix, including the additive, dominance, additive × additive, dominance × dominance, additive × dominance, and dominance × additive variances. The six different kinship matrices along with the six estimated polygenic variances were used to control the genetic background of a QTL mapping model. Simulation studies showed that incorporating epistatic polygenic covariance structure can improve QTL mapping resolution. The method was applied to yield component traits of rice. We analyzed four traits (yield, tiller number, grain number, and grain weight) using 278 immortal F2 crosses (crosses between recombinant inbred lines) and 1619 markers. We found that the relative importance of each type of genetic variance varies across different traits. The total genetic variance of yield is contributed by additive × additive (18%), dominance × dominance (14%), additive × dominance (48%), and dominance × additive (15%) variances. Tiller number is contributed by additive (17%), additive × additive (22%), and dominance × additive (43%) variances. Grain number is mainly contributed by additive (42%), additive × additive (19%), and additive × dominance (31%) variances. Grain weight is almost exclusively contributed by the additive (73%) variance plus a small contribution from the additive × additive (10%) variance. Using the estimated genetic variance components to capture the polygenic covariance structure, we detected 39 effects for yield, 39 effects for tiller number, 24 for grain number, and 15 for grain weight. The new method can be directly applied to polygenic-effect-adjusted genome-wide association studies (GWAS) in human and other

  15. 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).

  16. 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.

  17. The Background of PER People: A Survey

    NASA Astrophysics Data System (ADS)

    McCullough, Laura

    2006-12-01

    Data from a survey given to about 50 PER community members were analyzed to determine the backgrounds of the members. The type of college attended, the type of graduate school, when they chose physics, when they chose PER, and other interesting background information will be presented. Also presented will be gender analyses of background differences. Remarkably little difference in background was found between men and women in the sample.

  18. 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

  19. 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

  20. 25 CFR 556.4 - Background investigations.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS BACKGROUND INVESTIGATIONS FOR PRIMARY MANAGEMENT OFFICIALS AND KEY EMPLOYEES § 556.4 Background investigations. A tribe shall perform a background investigation for each primary management official and for each key employee of a gaming operation. (a) A...

  1. 25 CFR 556.4 - Background investigations.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS BACKGROUND INVESTIGATIONS FOR PRIMARY MANAGEMENT OFFICIALS AND KEY EMPLOYEES § 556.4 Background investigations. A tribe shall perform a background investigation for each primary management official and for each key employee of a gaming operation. (a) A...

  2. 25 CFR 556.4 - Background investigations.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS BACKGROUND INVESTIGATIONS FOR PRIMARY MANAGEMENT OFFICIALS AND KEY EMPLOYEES § 556.4 Background investigations. A tribe shall perform a background investigation for each primary management official and for each key employee of a gaming operation. (a) A...

  3. 25 CFR 556.4 - Background investigations.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS BACKGROUND INVESTIGATIONS FOR PRIMARY MANAGEMENT OFFICIALS AND KEY EMPLOYEES § 556.4 Background investigations. A tribe shall perform a background investigation for each primary management official and for each key employee of a gaming operation. (a) A...

  4. 25 CFR 556.4 - Background investigations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false Background investigations. 556.4 Section 556.4 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GAMING LICENSES AND BACKGROUND INVESTIGATIONS FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS BACKGROUND INVESTIGATIONS FOR PRIMARY MANAGEMENT OFFICIALS AND KEY EMPLOYEES §...

  5. 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.

  6. 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.

  7. 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

  8. Adaptive sensor fusion using genetic algorithms

    SciTech Connect

    Fitzgerald, D.S.; Adams, D.G.

    1994-08-01

    Past attempts at sensor fusion have used some form of Boolean logic to combine the sensor information. As an alteniative, an adaptive ``fuzzy`` sensor fusion technique is described in this paper. This technique exploits the robust capabilities of fuzzy logic in the decision process as well as the optimization features of the genetic algorithm. This paper presents a brief background on fuzzy logic and genetic algorithms and how they are used in an online implementation of adaptive sensor fusion.

  9. Genetic risks and genetic model specification.

    PubMed

    Zheng, Gang; Zhang, Wei; Xu, Jinfeng; Yuan, Ao; Li, Qizhai; Gastwirth, Joseph L

    2016-08-21

    Genetic risks and genetic models are often used in design and analysis of genetic epidemiology studies. A genetic model is defined in terms of two genetic risk measures: genotype relative risk and odds ratio. The impacts of choosing a risk measure on the resulting genetic models are studied in the power to detect association and deviation from Hardy-Weinberg equilibrium in cases using genetic relative risk. Extensive simulations demonstrate that the power of a study to detect associations using odds ratio is lower than that using relative risk with the same value when other parameters are fixed. When the Hardy-Weinberg equilibrium holds in the general population, the genetic model can be inferred by the deviation from Hardy-Weinberg equilibrium in only cases. Furthermore, it is more efficient than that based on the deviation from Hardy-Weinberg equilibrium in all cases and controls. PMID:27181372

  10. Medical genetics and genetic counseling in Chile.

    PubMed

    Margarit, Sonia B; Alvarado, Mónica; Alvarez, Karin; Lay-Son, Guillermo

    2013-12-01

    In the South American Republic of Chile genetic counseling is not currently recognized as an independent clinical discipline, and in general is provided by physicians with training in clinical genetics. At present only one genetic counselor and 28 clinical geneticists practice in this country of over 16 million inhabitants. Pediatric dysmorphology constitutes the primary area of practice in clinical genetics. Although the country has a universal health care system and an adequate level of health care, genetic conditions are not considered a health care priority and there is a lack of clinical and laboratory resources designated for clinical genetics services. Multiple educational, cultural and financial barriers exist to the growth and development of genetic counseling services in Chile. However, during the last 10 years increased awareness of the importance of identifying individuals at risk for inherited cancer syndromes led to growing interest in the practice of cancer genetics. PMID:23744184

  11. Applying the New Genetics

    ERIC Educational Resources Information Center

    Sorenson, James

    1976-01-01

    New developments in the prediction and treatment of genetic diseases are presented. Genetic counseling and the role of the counselor, and rights of individuals to reproduce versus societal impact of genetic disorders, are discussed. (RW)

  12. Genetic Differences in Intelligence

    ERIC Educational Resources Information Center

    Intellect, 1977

    1977-01-01

    The Genetics Society of America has released a statement saying that the possibility of a "genetic difference in intelligence between races" is still an open question and warning against "the misuse of genetics for political purposes". (Editor)

  13. Genetic Testing for ALS

    MedlinePlus

    ... Involved Donate Familial Amyotrophic Lateral Sclerosis (FALS) and Genetic Testing By Deborah Hartzfeld, MS, CGC, Certified Genetic ... guarantee a person will develop symptoms of ALS. Genetic Counseling If there is more than one person ...

  14. Effects of Streptococcus pneumoniae Strain Background on Complement Resistance

    PubMed Central

    Hyams, Catherine; Opel, Sophia; Hanage, William; Yuste, Jose; Bax, Katie; Henriques-Normark, Birgitta; Spratt, Brian G.; Brown, Jeremy S.

    2011-01-01

    Background Immunity to infections caused by Streptococcus pneumoniae is dependent on complement. There are wide variations in sensitivity to complement between S. pneumoniae strains that could affect their ability to cause invasive infections. Although capsular serotype is one important factor causing differences in complement resistance between strains, there is also considerable other genetic variation between S. pneumoniae strains that may affect complement-mediated immunity. We have therefore investigated whether genetically distinct S. pneumoniae strains with the same capsular serotype vary in their sensitivity to complement mediated immunity. Methodology and Principal Findings C3b/iC3b deposition and neutrophil association were measured using flow cytometry assays for S. pneumoniae strains with different genetic backgrounds for each of eight capsular serotypes. For some capsular serotypes there was marked variation in C3b/iC3b deposition between different strains that was independent of capsule thickness and correlated closely to susceptibility to neutrophil association. C3b/iC3b deposition results also correlated weakly with the degree of IgG binding to each strain. However, the binding of C1q (the first component of the classical pathway) correlated more closely with C3b/iC3b deposition, and large differences remained in complement sensitivity between strains with the same capsular serotype in sera in which IgG had been cleaved with IdeS. Conclusions These data demonstrate that bacterial factors independent of the capsule and recognition by IgG have strong effects on the susceptibility of S. pneumoniae to complement, and could therefore potentially account for some of the differences in virulence between strains. PMID:22022358

  15. 17 CFR 232.104 - Unofficial PDF copies included in an electronic submission.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... electronic submission. An unofficial PDF copy may contain graphic and image material (but not animated... tabular representation of any omitted graphic or image material. (c) If a filer omits an unofficial...

  16. 17 CFR 232.104 - Unofficial PDF copies included in an electronic submission.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... electronic submission. An unofficial PDF copy may contain graphic and image material (but not animated... tabular representation of any omitted graphic or image material. (c) If a filer omits an unofficial...

  17. Abundance, Grain Size and PDF Orientations of Shocked Quartz Grains Around the Chicxulub Crater

    NASA Astrophysics Data System (ADS)

    Goto, K.; Nakano, Y.; Matsui, T.; Tada, R.; Tajika, E.

    2011-03-01

    We measured abundance, grain size, and PDF orientations of shocked quartz grains around the Chicxulub crater in order to investigate the distribution and variation of shocked quartz grains produced by the Chicxulub impact.

  18. 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

  19. Gravity Transect Profile and PDF/PF Comparisons from the Bee Bluff Structure

    NASA Astrophysics Data System (ADS)

    Jurena, D. J.; French, B. M.; Gaffey, M. J.

    2003-03-01

    Support for an impact origin of this structure includes an anomaly profile similar to other impact structures. PDF orientations support this as well and also indicate a distinct separate source for PDFs outside the structure.

  20. 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