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Sample records for susceptible individuals specific

  1. Individual Genetic Susceptibility

    Energy Technology Data Exchange (ETDEWEB)

    Eric J. Hall

    2008-12-08

    Risk estimates derived from epidemiological studies of exposed populations, as well as the maximum permissible doses allowed for occupational exposure and exposure of the public to ionizing radiation are all based on the assumption that the human population is uniform in its radiosensitivity, except for a small number of individuals, such as ATM homozygotes who are easily identified by their clinical symptoms. The hypothesis upon which this proposal is based is that the human population is not homogeneous in radiosensitiviry, but that radiosensitive sub-groups exist which are not easy to identify. These individuals would suffer an increased incidence of detrimental radiation effects, and distort the shape of the dose response relationship. The radiosensitivity of these groups depend on the expression levels of specific proteins. The plan was to investigate the effect of 3 relatively rare, high penetrate genes available in mice, namely Atm, mRad9 & Brca1. The purpose of radiation protection is to prevent! deterministic effects of clinical significance and limit stochastic effects to acceptable levels. We plan, therefore to compare with wild type animals the radiosensitivity of mice heterozygous for each of the genes mentioned above, as well as double heterozygotes for pairs of genes, using two biological endpoints: a) Ocular cataracts as an important and relevant deterministic effect, and b) Oncogenic transformation in cultured embryo fibroblasts, as a surrogate for carcinogenesis, the most relevant stochastic effect.

  2. Individual Differences in Susceptibility to Inattentional Blindness

    Science.gov (United States)

    Seegmiller, Janelle K.; Watson, Jason M.; Strayer, David L.

    2011-01-01

    Inattentional blindness refers to the finding that people do not always see what appears in their gaze. Though inattentional blindness affects large percentages of people, it is unclear if there are individual differences in susceptibility. The present study addressed whether individual differences in attentional control, as reflected by…

  3. Individual Susceptibility to Hypobaric Environments: An Update

    Science.gov (United States)

    Law, Jennifer; Watkins, Sharmi

    2009-01-01

    Astronauts are at risk for developing decompression sickness (DCS) while exposed to the hypobaric environment of the extravehicular suit in space, in terrestrial hypobaric chambers, and during ascent from neutral buoyancy training dives. There is increasing recognition that DCS risk is different between diving and altitude exposures, with many individual parameters and environmental factors implicated as risk factors for development of DCS in divers but are not recognized as risk factors in altitude exposures. Much of the literature to date has focused on patent foramen ovale (PFO), which has long been considered a major risk factor for DCS in diving exposures, but its link to serious DCS in altitude exposures remains unclear. Knowledge of those risk factors specific to hypobaric DCS may help identify susceptible individuals and aid in astronaut selection, crew assignment, and mission planning. This paper reviews the current literature pertaining to these risk factors, including PFO, anthropometric parameters, gender, menstrual cycle, lifetime diving experience, physical fitness, biochemical levels, complement activation, cigarette smoking, fluid balance, and ambient temperature. Further research to evaluate pertinent risk factors for DCS in altitude exposures is recommended.

  4. Individual differences in susceptibility to inattentional blindness.

    Science.gov (United States)

    Seegmiller, Janelle K; Watson, Jason M; Strayer, David L

    2011-05-01

    Inattentional blindness refers to the finding that people do not always see what appears in their gaze. Though inattentional blindness affects large percentages of people, it is unclear if there are individual differences in susceptibility. The present study addressed whether individual differences in attentional control, as reflected by variability in working memory capacity, modulate susceptibility to inattentional blindness. Participants watched a classic inattentional blindness video (Simons & Chabris, 1999) and were instructed to count passes among basketball players, wherein 58% noticed the unexpected: a person wearing a gorilla suit. When participants were accurate with their pass counts, individuals with higher working memory capacity were more likely to report seeing the gorilla (67%) than those with lesser working memory capacity (36%). These results suggest that variability in attentional control is a potential mechanism underlying the apparent modulation of inattentional blindness across individuals.

  5. Why do Individuals Differ in Viral Susceptibility?

    NARCIS (Netherlands)

    Sluijs, van L.; Pijlman, G.P.; Kammenga, J.E.

    2017-01-01

    Viral susceptibility and disease progression is determined by host genetic variation that underlies individual differences. Genetic polymorphisms that affect the phenotype upon infection have been well-studied for only a few viruses, such as HIV-1 and Hepatitis C virus. However, even for

  6. Genetic susceptibility for specific cancers. Medical liability of the clinician.

    Science.gov (United States)

    Severin, M J

    1999-12-01

    The use of genetic profiling techniques to detect individuals with an increased susceptibility to heritable cancers has provoked recent legal interest in the duties of the attending physician and in the rights of patients and their families. In the current study specific prima facie and recently litigated cases are presented and explored to delineate the issues facing physicians and to illustrate the prerogatives of patients who are caught up in a heritable cancer enigma. Various courts have attempted to answer questions involving lawsuits in which incidents of breast/ovarian carcinoma and colon carcinoma have provoked claims of negligence against health care providers. Health care workers involved in the care of these patients have specific duties to these individuals. It would appear that physicians are being forced to assume the additional duty of delving into a patient's family history of cancer through multiple generations. This duty is followed by a responsibility to provide detailed counseling to those patients in whom such activity impacts the diagnosis and management of familial cancer.

  7. Temperature alters host genotype-specific susceptibility to chytrid infection

    NARCIS (Netherlands)

    Gsell, A.S.; De Senerpont Domis, L.N.; Van Donk, E.; Ibelings, B.W.

    2013-01-01

    The cost of parasitism often depends on environmental conditions and host identity. Therefore, variation in the biotic and abiotic environment can have repercussions on both, species-level host-parasite interaction patterns but also on host genotype-specific susceptibility to disease. We exposed

  8. Entropy, specific heat, susceptibility, and Rushbrooke inequality in percolation

    Science.gov (United States)

    Hassan, M. K.; Alam, D.; Jitu, Z. I.; Rahman, M. M.

    2017-11-01

    We investigate percolation, a probabilistic model for continuous phase transition, on square and weighted planar stochastic lattices. In its thermal counterpart, entropy is minimally low where order parameter (OP) is maximally high and vice versa. In addition, specific heat, OP, and susceptibility exhibit power law when approaching the critical point and the corresponding critical exponents α ,β ,γ respectably obey the Rushbrooke inequality (RI) α +2 β +γ ≥2 . Their analogs in percolation, however, remain elusive. We define entropy and specific heat and redefine susceptibility for percolation and show that they behave exactly in the same way as their thermal counterpart. We also show that RI holds for both the lattices albeit they belong to different universality classes.

  9. Susceptibility and reactivity in polysensitized individuals following controlled induction

    DEFF Research Database (Denmark)

    Bangsgaard, Nannie; Carlsen, Berit C; Johansen, Jeanne Duus

    2010-01-01

    It is uncertain whether polysensitized patients acquire multiple allergies only because of a high degree of exposure to environmental allergens, or because of being highly susceptible to developing contact allergy.......It is uncertain whether polysensitized patients acquire multiple allergies only because of a high degree of exposure to environmental allergens, or because of being highly susceptible to developing contact allergy....

  10. The Identification of Fatigue Resistant and Fatigue Susceptible Individuals

    Science.gov (United States)

    2008-05-01

    normalized and compared 38 to normalized SAFTE predictions. See text for details. Figure 3 Fatigue plots for fatigue susceptible vs. fatigue...has 5 seconds to press the button to get points for successful signal detections. Lower tones are given with greater frequency and responses to...address the first question, and we use predictions of the Sleep Activity Fatigue Task Effectiveness, or SAFTE model (Hursh, Redmond, Johnson, Thorne

  11. Murine glomerular transcriptome links endothelial cell-specific molecule-1 deficiency with susceptibility to diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Xiaoyi Zheng

    Full Text Available Diabetic nephropathy (DN is the leading cause of kidney disease; however, there are no early biomarkers and no cure. Thus, there is a large unmet need to predict which individuals will develop nephropathy and to understand the molecular mechanisms that govern this susceptibility. We compared the glomerular transcriptome from mice with distinct susceptibilities to DN at four weeks after induction of diabetes, but before histologic injury, and identified differential regulation of genes that modulate inflammation. From these genes, we identified endothelial cell specific molecule-1 (Esm-1, as a glomerular-enriched determinant of resistance to DN. Glomerular Esm-1 mRNA and protein were lower in DN-susceptible, DBA/2, compared to DN-resistant, C57BL/6, mice. We demonstrated higher Esm-1 secretion from primary glomerular cultures of diabetic mice, and high glucose was sufficient to increase Esm-1 mRNA and protein secretion in both strains of mice. However, induction was significantly attenuated in DN-susceptible mice. Urine Esm-1 was also significantly higher only in DN-resistant mice. Moreover, using intravital microscopy and a biomimetic microfluidic assay, we showed that Esm-1 inhibited rolling and transmigration in a dose-dependent manner. For the first time we have uncovered glomerular-derived Esm-1 as a potential non-invasive biomarker of DN. Esm-1 inversely correlates with disease susceptibility and inhibits leukocyte infiltration, a critical factor in protecting the kidney from DN.

  12. Landslide susceptibility and risk assessment: specificities for road networks

    Science.gov (United States)

    Pellicani, Roberta; Argentiero, Ilenia; Parisi, Alessandro; Spilotro, Giuseppe

    2017-04-01

    A regional-scale assessment of landslide susceptibility and risk along the main road corridors crossing the provincial territory of Matera (Basilicata Region, Southern Italy) was carried out. The entire provincial road network extends for about 1,320 km through a territory, of which represents the main connection infrastructure among thirty-one municipalities due to the lack of an efficient integrated transportation system through the whole regional territory. For this reason, the strategic importance of these roads consists in their uniqueness in connecting every urban center with the socio-economic surrounding context. These roads and their vehicular traffic are continuously exposed to instability processes (about the 40% of the total length is disrupted by landslides), characterized both by high intensity and low frequency and by low intensity and high frequency. This last typology, consisting in small shallow landslides, is particularly hazardous for the roads since it is widespread along the road network, its occurrence is connected to rainfalls and determines high vulnerability conditions for the road in terms of interruption of vehicular traffic. A GIS-based heuristic-bivariate statistical predictive model was performed to assess and map the landslide susceptibility in the study area, by using a polynomial function of eight predisposing factors, weighted according to their influence on the landslide phenomena, recognized and collected in an inventory. Susceptibility associated to small shallow phenomena was assessed by using a polynomial function of specific factors, such as slope angle and aspect, lithological outcrops, rainfalls, etc. In absence of detailed input data, the spatial distribution of landslide risk along the road corridors was assessed and mapped using a qualitative hazard-consequence matrix approach, by which risk is obtained by combining hazard categories with consequence classes pairwise in a two-dimensional table or matrix. Landslide

  13. Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

    Science.gov (United States)

    Yurgelun, Matthew B; Kulke, Matthew H; Fuchs, Charles S; Allen, Brian A; Uno, Hajime; Hornick, Jason L; Ukaegbu, Chinedu I; Brais, Lauren K; McNamara, Philip G; Mayer, Robert J; Schrag, Deborah; Meyerhardt, Jeffrey A; Ng, Kimmie; Kidd, John; Singh, Nanda; Hartman, Anne-Renee; Wenstrup, Richard J; Syngal, Sapna

    2017-04-01

    Purpose Hereditary factors play an important role in colorectal cancer (CRC) risk, yet the prevalence of germline cancer susceptibility gene mutations in patients with CRC unselected for high-risk features (eg, early age at diagnosis, personal/family history of cancer or polyps, tumor microsatellite instability [MSI], mismatch repair [MMR] deficiency) is unknown. Patients and Methods We recruited 1,058 participants who received CRC care in a clinic-based setting without preselection for age at diagnosis, personal/family history, or MSI/MMR results. All participants underwent germline testing for mutations in 25 genes associated with inherited cancer risk. Each gene was categorized as high penetrance or moderate penetrance on the basis of published estimates of the lifetime cancer risks conferred by pathogenic germline mutations in that gene. Results One hundred five (9.9%; 95% CI, 8.2% to 11.9%) of 1,058 participants carried one or more pathogenic mutations, including 33 (3.1%) with Lynch syndrome (LS). Twenty-eight (96.6%) of 29 available LS CRCs demonstrated abnormal MSI/MMR results. Seventy-four (7.0%) of 1,058 participants carried non-LS gene mutations, including 23 (2.2%) with mutations in high-penetrance genes (five APC, three biallelic MUTYH, 11 BRCA1/2, two PALB2, one CDKN2A, and one TP53), 15 of whom lacked clinical histories suggestive of their underlying mutation. Thirty-eight (3.6%) participants had moderate-penetrance CRC risk gene mutations (19 monoallelic MUTYH, 17 APC*I1307K, two CHEK2). Neither proband age at CRC diagnosis, family history of CRC, nor personal history of other cancers significantly predicted the presence of pathogenic mutations in non-LS genes. Conclusion Germline cancer susceptibility gene mutations are carried by 9.9% of patients with CRC. MSI/MMR testing reliably identifies LS probands, although 7.0% of patients with CRC carry non-LS mutations, including 1.0% with BRCA1/2 mutations.

  14. Endothelial dilatory function predicts individual susceptibility to renal damage in the 5/6 nephrectomized rat

    NARCIS (Netherlands)

    Gschwend, S; Buikema, H; Navis, G; Henning, RH; De Zeeuw, D; Van Dokkum, RPE

    2002-01-01

    In experimental animal models of renal disease the degree of renal damage varies between individuals. This could be caused by variation in the noxious event or by differences in individual susceptibility. Intact endothelial function is assumed to provide a defense mechanism against progressive renal

  15. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: findings from the Breast Cancer Association Consortium

    National Research Council Canada - National Science Library

    Broeks, A; Schmidt, M.K; Sherman, M.E; Couch, F.J; Hopper, J.L; Dite, G.S; Apicella, C; Smith, L.D; Hammet, F; Southey, M.C; Veer, L.J. van 't; Groot, R. de; Smit, V.T; Fasching, P.A; Beckmann, M.W; Jud, S; Ekici, A.B; Hartmann, A; Hein, A; Schulz-Wendtland, R; Burwinkel, B; Marme, F; Schneeweiss, A; Sinn, H.P; Sohn, C; Tchatchou, S; Bojesen, S.E; Nordestgaard, B.G; Flyger, H; Orsted, D.D; Kaur-Knudsen, D; Milne, R.L; Perez, J.I; Zamora, P; Roiguez, P.M; Benitez, J; Brauch, H; Justenhoven, C; Ko, Y.D; Hamann, U; Fischer, H.P; Bruning, T; Pesch, B; Chang-Claude, J; Wang-Gohrke, S; Bremer, M; Karstens, J.H; Hillemanns, P; Dork, T; Nevanlinna, H.A; Heikkinen, T; Heikkila, P; Blomqvist, C; Aittomaki, K; Aaltonen, K; Lindblom, A; Margolin, S; Mannermaa, A; Kosma, V.M; Kauppinen, J.M; Kataja, V; Auvinen, P; Eskelinen, M; Soini, Y; Chenevix-Trench, G; Spurdle, A.B; Beesley, J; Chen, X; Holland, H; Lambrechts, D; Claes, B; Vandorpe, T; Neven, P; Wildiers, H; Flesch-Janys, D; Hein, R; Loning, T; Kosel, M; Fredericksen, Z.S; Wang, X; Giles, G.G; Baglietto, L; Severi, G; McLean, C; Haiman, C.A; Henderson, B.E; Marchand, L. le; Kolonel, L.N; Alnaes, G.G; Kristensen, V; Borresen-Dale, A.L; Hunter, D.J; Hankinson, S.E; Anulis, I.L; Mulligan, A.M; O'Malley, F.P; Devilee, P; Huijts, P.E; Tollenaar, R.A.E.M; Asperen, C.J. van

    2011-01-01

    .... We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes...

  16. Why do Individuals Differ in Viral Susceptibility? A Story Told by Model Organisms

    Directory of Open Access Journals (Sweden)

    Lisa van Sluijs

    2017-09-01

    Full Text Available Viral susceptibility and disease progression is determined by host genetic variation that underlies individual differences. Genetic polymorphisms that affect the phenotype upon infection have been well-studied for only a few viruses, such as HIV-1 and Hepatitis C virus. However, even for well-studied viruses the genetic basis of individual susceptibility differences remains elusive. Investigating the effect of causal polymorphisms in humans is complicated, because genetic methods to detect rare or small-effect polymorphisms are limited and genetic manipulation is not possible in human populations. Model organisms have proven a powerful experimental platform to identify and characterize polymorphisms that underlie natural variations in viral susceptibility using quantitative genetic tools. We summarize and compare the genetic tools available in three main model organisms, Mus musculus, Drosophila melanogaster, and Caenorhabditis elegans, and illustrate how these tools can be applied to detect polymorphisms that determine the viral susceptibility. Finally, we analyse how candidate polymorphisms from model organisms can be used to shed light on the underlying mechanism of individual variation. Insights in causal polymorphisms and mechanisms underlying individual differences in viral susceptibility in model organisms likely provide a better understanding in humans.

  17. Modulation of the Genome and Epigenome of Individuals Susceptible to Autism by Environmental Risk Factors

    Directory of Open Access Journals (Sweden)

    Costas Koufaris

    2015-04-01

    Full Text Available Diverse environmental factors have been implicated with the development of autism spectrum disorders (ASD. Genetic factors also underlie the differential vulnerability to environmental risk factors of susceptible individuals. Currently the way in which environmental risk factors interact with genetic factors to increase the incidence of ASD is not well understood. A greater understanding of the metabolic, cellular, and biochemical events involved in gene x environment interactions in ASD would have important implications for the prevention and possible treatment of the disorder. In this review we discuss various established and more alternative processes through which environmental factors implicated in ASD can modulate the genome and epigenome of genetically-susceptible individuals.

  18. Social-psychological specific of individual adaptation

    OpenAIRE

    Olga Ovsyanik

    2012-01-01

    There is analyzing of specific of social-psychological adaptation person by model of adaptation. Structure model of adaptation of women of our age group, which was named “adaptation complex” was made by theoretic analyzes of problem of adaptation adult.

  19. Species distribution & antifungal susceptibility pattern of oropharyngeal Candida isolates from human immunodeficiency virus infected individuals

    Directory of Open Access Journals (Sweden)

    Partha Pratim Das

    2016-01-01

    Results: From the 59 culture positive HIV seropositive cases, 61 Candida isolates were recovered; Candidaalbicans (n=47, 77.0%, C. dubliniensis (n=9, 14.7%, C. parapsilosis (n=2, 3.2%, C. glabrata (n=2, 3.2%, and C. famata (n=1, 1.6%. Candida colonization in HIV-seropositive individuals was significantly higher than that of HIV-seronegative (control group. Antifungal susceptibility testing revealed (n=6, 9.3% C. albicans isolates resistant to voriconazole and fluconazole by disk-diffusion method whereas no resistance was seen by Fungitest method. Interpretation & conclusions: C. albicans was the commonest Candida species infecting or colonizing HIV seropositive individuals. Oropharyngeal Candida isolates had high level susceptibility to all the major antifungals commonly in use. Increased level of immunosuppression in HIV-seropositives and drug resistance of non-albicans Candida species makes identification and susceptibility testing of Candida species necessary in different geographical areas of the country.

  20. Mind the gap: glucocorticoids modulate hippocampal glutamate tone underlying individual differences in stress susceptibility.

    Science.gov (United States)

    Nasca, C; Bigio, B; Zelli, D; Nicoletti, F; McEwen, B S

    2015-06-01

    Why do some individuals succumb to stress and develop debilitating psychiatric disorders, whereas others adapt well in the face of adversity? There is a gap in understanding the neural bases of individual differences in the responses to environmental factors on brain development and functions. Here, using a novel approach for screening an inbred population of laboratory animals, we identified two subpopulations of mice: susceptible mice that show mood-related abnormalities compared with resilient mice, which cope better with stress. This approach combined with molecular and behavioral analyses, led us to recognize, in hippocampus, presynaptic mGlu2 receptors, which inhibit glutamate release, as a stress-sensitive marker of individual differences to stress-induced mood disorders. Indeed, genetic mGlu2 deletion in mice results in a more severe susceptibility to stress, mimicking the susceptible mouse sub-population. Furthermore, we describe an underlying mechanism by which glucocorticoids, acting via mineralocorticoid receptors (MRs), decrease resilience to stress via downregulation of mGlu2 receptors. We also provide a mechanistic link between MRs and an epigenetic control of the glutamatergic synapse that underlies susceptibility to stressful experiences. The approach and the epigenetic allostasis concept introduced here serve as a model for identifying individual differences based upon biomarkers and underlying mechanisms and also provide molecular features that may be useful in translation to human behavior and psychopathology.

  1. Global lung cancer risk from PAH exposure highly depends on emission sources and individual susceptibility

    Science.gov (United States)

    Shen, Huizhong; Tao, Shu; Liu, Junfeng; Huang, Ye; Chen, Han; Li, Wei; Zhang, Yanyan; Chen, Yuanchen; Su, Shu; Lin, Nan; Xu, Yinyin; Li, Bengang; Wang, Xilong; Liu, Wenxin

    2014-10-01

    The health impacts of polycyclic aromatic hydrocarbons (PAHs), the most concerning organic pollutants, depend not only on the locations and strengths of emission sources, but also on individual susceptibility. Moreover, trans-boundary transport makes them a global concern. In this study, a comprehensive analysis of the global health impacts of polycyclic aromatic hydrocarbons (PAHs) in ambient air is presented. Model resolution is critical in exposure modelling. Globally, incremental lifetime lung cancer risk (ILCR) induced by ambient PAH exposure is 3.1 × 10-5. If the individual susceptibility was not taken into consideration, the overall risk would be underestimated by 55% and the proportion of highly vulnerable population would be underestimated by more than 90%. Emphasizing on individual susceptibility, our study provides an instrumental revision of current risk assessment methodology. In terms of lung cancer risk, the most important sources are combustion of biomass fuels (40%) and fossil fuels (14%) in the residential/commercial sector, coke (13%) and aluminium (12%) production, and motor vehicles (9%). PAHs can travel long distance globally especially within the Eurasian continent. Still, the risk is dominantly contributed by local.

  2. Prediction Equations Overestimate the Energy Requirements More for Obesity-Susceptible Individuals.

    Science.gov (United States)

    McLay-Cooke, Rebecca T; Gray, Andrew R; Jones, Lynnette M; Taylor, Rachael W; Skidmore, Paula M L; Brown, Rachel C

    2017-09-13

    Predictive equations to estimate resting metabolic rate (RMR) are often used in dietary counseling and by online apps to set energy intake goals for weight loss. It is critical to know whether such equations are appropriate for those susceptible to obesity. We measured RMR by indirect calorimetry after an overnight fast in 26 obesity susceptible (OSI) and 30 obesity resistant (ORI) individuals, identified using a simple 6-item screening tool. Predicted RMR was calculated using the FAO/WHO/UNU (Food and Agricultural Organisation/World Health Organisation/United Nations University), Oxford and Miflin-St Jeor equations. Absolute measured RMR did not differ significantly between OSI versus ORI (6339 vs. 5893 kJ·d -1 , p = 0.313). All three prediction equations over-estimated RMR for both OSI and ORI when measured RMR was ≤5000 kJ·d -1 . For measured RMR ≤7000 kJ·d -1 there was statistically significant evidence that the equations overestimate RMR to a greater extent for those classified as obesity susceptible with biases ranging between around 10% to nearly 30% depending on the equation. The use of prediction equations may overestimate RMR and energy requirements particularly in those who self-identify as being susceptible to obesity, which has implications for effective weight management.

  3. Individual differences underlying susceptibility to addiction: Role for the endogenous oxytocin system.

    Science.gov (United States)

    Buisman-Pijlman, Femke T A; Sumracki, Nicole M; Gordon, Jake J; Hull, Philip R; Carter, C Sue; Tops, Mattie

    2014-04-01

    Recent research shows that the effects of oxytocin are more diverse than initially thought and that in some cases oxytocin can directly influence the response to drugs and alcohol. Large individual differences in basal oxytocin levels and reactivity of the oxytocin system exist. This paper will review the literature to explore how individual differences in the oxytocin system arise and examine the hypothesis that this may mediate some of the individual differences in susceptibility to addiction and relapse. Differences in the oxytocin system can be based on individual factors, e.g. genetic variation especially in the oxytocin receptor, age or gender, or be the result of early environmental influences such as social experiences, stress or trauma. The paper addresses the factors that cause individual differences in the oxytocin system and the environmental factors that have been identified to induce long-term changes in the developing oxytocin system during different life phases. Individual differences in the oxytocin system can influence effects of drugs and alcohol directly or indirectly. The oxytocin system has bidirectional interactions with the stress-axis, autonomic nervous system, neurotransmitter systems (e.g. dopamine, serotonin and GABA/glutamate) and the immune system. These systems are all important, even vital, in different phases of addiction. It is suggested that early life adversity can change the development of the oxytocin system and the way it modulates other systems. This in turn could minimise the negative feedback loops that would normally exist. Individuals may show only minor differences in behaviour and function unless subsequent stressors or drug use challenges the system. It is postulated that at that time individual differences in oxytocin levels, reactivity of the system or interactions with other systems can influence general resilience, drug effects and the susceptibility to develop problematic drug and alcohol use. © 2013. Published

  4. Women Are More Susceptible to Caries but Individuals Born with Clefts Are Not

    Science.gov (United States)

    Jindal, Aditi; McMeans, Michelle; Narayanan, Somnya; Rose, Erin K.; Jain, Shilpa; Marazita, Mary L.; Menezes, Renato; Letra, Ariadne; Carvalho, Flavia M.; Brandon, Carla A.; Resick, Judith M.; Mereb, Juan C.; Poletta, Fernando A.; Lopez-Camelo, Jorge S.; Castilla, Eduardo E.; Orioli, Iêda M.; Vieira, Alexandre R.

    2011-01-01

    The identification of individuals at a higher risk of developing caries is of great interest. Isolated forms of cleft lip and palate are among the most common craniofacial congenital anomalies in humans. Historically, several reports suggest that individuals born with clefts have a higher risk for caries. Caries continues to be the most common infectious noncontagious disease worldwide and a great burden to any health system. The identification of individuals of higher susceptibility to caries is of great interest. In this paper, we assessed caries experience of 1,593 individuals from three distinct populations. The study included individuals born with clefts, their unaffected relatives, and unrelated unaffected controls that were recruited from areas with similar cultural pressures and limited access to dental care. DMFT/dmft scores were obtained, and caries experience rates were compared among the three groups in each geographic area. Individuals born with clefts did not present higher caries experience in comparison to their unaffected relatives or unrelated unaffected controls. Women tend to present higher caries rates in comparison to men. Our work provides strong evidence that individuals born with clefts are not at higher risk to caries; however, women tend to have more severe caries experience. PMID:21747859

  5. Sex-specific differences in pathogen susceptibility in honey bees (Apis mellifera).

    Science.gov (United States)

    Retschnig, Gina; Williams, Geoffrey R; Mehmann, Marion M; Yañez, Orlando; de Miranda, Joachim R; Neumann, Peter

    2014-01-01

    Sex-related differences in susceptibility to pathogens are a common phenomenon in animals. In the eusocial Hymenoptera the two female castes, workers and queens, are diploid and males are haploid. The haploid susceptibility hypothesis predicts that haploid males are more susceptible to pathogen infections compared to females. Here we test this hypothesis using adult male (drone) and female (worker) honey bees (Apis mellifera), inoculated with the gut endoparasite Nosema ceranae and/or black queen cell virus (BQCV). These pathogens were chosen due to previously reported synergistic interactions between Nosema apis and BQCV. Our data do not support synergistic interactions between N. ceranae and BQCV and also suggest that BQCV has limited effect on both drone and worker health, regardless of the infection level. However, the data clearly show that, despite lower levels of N. ceranae spores in drones than in workers, Nosema-infected drones had both a higher mortality and a lower body mass than non-infected drones, across all treatment groups, while the mortality and body mass of worker bees were largely unaffected by N. ceranae infection, suggesting that drones are more susceptible to this pathogen than workers. In conclusion, the data reveal considerable sex-specific differences in pathogen susceptibility in honey bees and highlight the importance of ultimate measures for determining susceptibility, such as mortality and body quality, rather than mere infection levels.

  6. Sex-specific differences in pathogen susceptibility in honey bees (Apis mellifera.

    Directory of Open Access Journals (Sweden)

    Gina Retschnig

    Full Text Available Sex-related differences in susceptibility to pathogens are a common phenomenon in animals. In the eusocial Hymenoptera the two female castes, workers and queens, are diploid and males are haploid. The haploid susceptibility hypothesis predicts that haploid males are more susceptible to pathogen infections compared to females. Here we test this hypothesis using adult male (drone and female (worker honey bees (Apis mellifera, inoculated with the gut endoparasite Nosema ceranae and/or black queen cell virus (BQCV. These pathogens were chosen due to previously reported synergistic interactions between Nosema apis and BQCV. Our data do not support synergistic interactions between N. ceranae and BQCV and also suggest that BQCV has limited effect on both drone and worker health, regardless of the infection level. However, the data clearly show that, despite lower levels of N. ceranae spores in drones than in workers, Nosema-infected drones had both a higher mortality and a lower body mass than non-infected drones, across all treatment groups, while the mortality and body mass of worker bees were largely unaffected by N. ceranae infection, suggesting that drones are more susceptible to this pathogen than workers. In conclusion, the data reveal considerable sex-specific differences in pathogen susceptibility in honey bees and highlight the importance of ultimate measures for determining susceptibility, such as mortality and body quality, rather than mere infection levels.

  7. High miR-124-3p expression identifies smoking individuals susceptible to atherosclerosis.

    Science.gov (United States)

    de Ronde, Maurice W J; Kok, Maayke G M; Moerland, Perry D; Van den Bossche, Jan; Neele, Annette E; Halliani, Amalia; van der Made, Ingeborg; de Winther, Menno P J; Meijers, Joost C M; Creemers, Esther E; Pinto-Sietsma, Sara-Joan

    2017-08-01

    The risk of developing cardiovascular disease (CVD) is twice as high among smoking individuals compared to non-smokers. Monocytes are involved in smoking-related atherosclerotic plaque formation. In this study, we investigated whether smokers with an increased risk of developing CVD can be identified on the basis of monocyte-derived miRNA expression levels. We performed a miRNA microarray experiment on isolated monocytes from smoking, former smoking and non-smoking individuals in a cohort of patients with premature CVD and healthy controls (Cohort I, n = 76). We found miR-124-3p to be heterogeneously expressed among all smoking individuals, whereas expression was low in non-smokers. Subsequently, RT-qPCR measurements on whole blood showed that among smoking individuals an increase in miR-124-3p is associated with an increased risk for advanced atherosclerotic disease (cohort II, n = 24) (OR 11.72 95% CI 1.09-126.53) and subclinical atherosclerosis (coronary artery calcium score ≥ 80(th) percentile, cohort III n = 138) (OR 2.71, 95% CI 1.05-7.01). This was not observed among former smokers or non-smoking individuals. Flow cytometric analysis demonstrated that high miR-124-3p expression was associated with upregulation of the monocyte surface markers CD45RA, CD29 and CD206, indicating an altered monocyte phenotype. Finally, overexpression of miR-124-3p resulted in an upregulation of CD206 surface expression on monocytes. High miR-124-3p expression is associated with an increased risk of subclinical atherosclerosis in smoking individuals and with an altered monocyte phenotype. This may suggest that miR-124-3p identifies which smoking individuals are susceptible to the atherogenic effects of smoking. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Ethical, social, and legal issues surrounding studies of susceptible populations and individuals.

    Science.gov (United States)

    Soskolne, C L

    1997-01-01

    Calls for professional accountability have resulted in the development of ethics guidelines by numerous specialty and subspecialty groups of scientists. Indeed, guidelines among some health professions now address vulnerable and dependent groups: but these are silent on issues related to biomarkers. In parallel, attention has been drawn to human rights concerns associated with attempts to detect hypersusceptible workers, especially in democratic countries. Despite this, concern for vulnerable populations grows as advances in biomarker technology make the identification of genetic predisposition and susceptibility markers of both exposure and outcome more attainable. In this article, the principles derived from the ethical theory of utilitarianism provide the basis for principle-based ethical analysis. In addition, the four principles of biomedical ethics--respect for autonomy, beneficence, nonmaleficence, and social justice--are considered for biomarker studies. The need for a context in which ethical analysis is conducted and from which prevailing social values are shown to drive decisions of an ethical nature is emphasized; these include statutory regulation and law. Because biomarker studies can result in more harm than good, special precautions to inform research participants prior to any involvement in the use of biomarkers are needed. In addition, safeguards to maintain the privacy of data derived from biomarker studies must be developed and implemented prior to the application of these new technologies. Guidelines must be expanded to incorporate ethical, social, and legal considerations surrounding the introduction of new technologies for studying susceptible populations and individuals who may be vulnerable to environmental exposures. PMID:9255569

  9. Cell-Type-Specific Epigenetic Editing at the Fosb Gene Controls Susceptibility to Social Defeat Stress.

    Science.gov (United States)

    Hamilton, Peter J; Burek, Dominika J; Lombroso, Sonia I; Neve, Rachael L; Robison, Alfred J; Nestler, Eric J; Heller, Elizabeth A

    2018-01-01

    Chronic social defeat stress regulates the expression of Fosb in the nucleus accumbens (NAc) to promote the cell-type-specific accumulation of ΔFosB in the two medium spiny neuron (MSN) subtypes in this region. ΔFosB is selectively induced in D1-MSNs in the NAc of resilient mice, and in D2-MSNs of susceptible mice. However, little is known about the consequences of such selective induction, particularly in D2-MSNs. This study examined how cell-type-specific control of the endogenous Fosb gene in NAc regulates susceptibility to social defeat stress. Histone post-translational modifications (HPTMs) were targeted specifically to Fosb using engineered zinc-finger proteins (ZFPs). Fosb-ZFPs were fused to either the transcriptional repressor, G9a, which promotes histone methylation or the transcriptional activator, p65, which promotes histone acetylation. These ZFPs were expressed in D1- vs D2-MSNs using Cre-dependent viral expression in the NAc of mice transgenic for Cre recombinase in these MSN subtypes. We found that stress susceptibility is oppositely regulated by the specific cell type and HPTM targeted. We report that Fosb-targeted histone acetylation in D2-MSNs or histone methylation in D1-MSNs promotes a stress-susceptible, depressive-like phenotype, while histone methylation in D2-MSNs or histone acetylation in D1-MSNs increases resilience to social stress as quantified by social interaction behavior and sucrose preference. This work presents the first demonstration of cell- and gene-specific targeting of histone modifications, which model naturally occurring transcriptional phenomena that control social defeat stress behavior. This epigenetic-editing approach, which recapitulates physiological changes in gene expression, reveals clear differences in the social defeat phenotype induced by Fosb gene manipulation in MSN subtypes.

  10. Individual behavioral characteristics of wild-type rats predict susceptibility to experimental autoimmune encephalomyelitis

    NARCIS (Netherlands)

    Kavelaars, A; Heijnen, CJ; Tennekes, R; Bruggink, JE; Koolhaas, JM

    1999-01-01

    Neuroendocrine-immune interactions are thought to be important in determining susceptibility to autoimmune disease. Animal studies have revealed that differences in susceptibility to experimental autoimmune encephalomyelitis (EAE) are related to:reactivity in the hypothalamo-pituitary-adrenal axis.

  11. AIRE polymorphism, melanoma antigen-specific T cell immunity, and susceptibility to melanoma.

    Science.gov (United States)

    Conteduca, Giuseppina; Fenoglio, Daniela; Parodi, Alessia; Battaglia, Florinda; Kalli, Francesca; Negrini, Simone; Tardito, Samuele; Ferrera, Francesca; Salis, Annalisa; Millo, Enrico; Pasquale, Giuseppe; Barra, Giusi; Damonte, Gianluca; Indiveri, Francesco; Ferrone, Soldano; Filaci, Gilberto

    2016-09-20

    AIRE is involved in susceptibility to melanoma perhaps regulating T cell immunity against melanoma antigens (MA). To address this issue, AIRE and MAGEB2 expressions were measured by real time PCR in medullary thymic epithelial cells (mTECs) from two strains of C57BL/6 mice bearing either T or C allelic variant of the rs1800522 AIRE SNP. Moreover, the extent of apoptosis induced by mTECs in MAGEB2-specific T cells and the susceptibility to in vivo melanoma B16F10 cell challenge were compared in the two mouse strains.The C allelic variant, protective in humans against melanoma, induced lower AIRE and MAGEB2 expression in C57BL/6 mouse mTECs than the T allele. Moreover, mTECs expressing the C allelic variant induced lower extent of apoptosis in MAGEB2-specific syngeneic T cells than mTECs bearing the T allelic variant (p AIRE genotype than in those bearing the TT one (p AIRE SNP may differentially shape the MA-specific T cell repertoire potentially influencing susceptibility to melanoma.

  12. Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.

    Science.gov (United States)

    Yu, Min; Bardia, Aditya; Aceto, Nicola; Bersani, Francesca; Madden, Marissa W; Donaldson, Maria C; Desai, Rushil; Zhu, Huili; Comaills, Valentine; Zheng, Zongli; Wittner, Ben S; Stojanov, Petar; Brachtel, Elena; Sgroi, Dennis; Kapur, Ravi; Shioda, Toshihiro; Ting, David T; Ramaswamy, Sridhar; Getz, Gad; Iafrate, A John; Benes, Cyril; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A

    2014-07-11

    Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease. Copyright © 2014, American Association for the Advancement of Science.

  13. Specific adjustments in grapevine leaf proteome discriminating resistant and susceptible grapevine genotypes to Plasmopara viticola.

    Science.gov (United States)

    Figueiredo, Andreia; Martins, Joana; Sebastiana, Mónica; Guerreiro, Ana; Silva, Anabela; Matos, Ana Rita; Monteiro, Filipa; Pais, Maria Salomé; Roepstorff, Peter; Coelho, Ana Varela

    2017-01-30

    Grapevine downy mildew is an important disease affecting crop production leading to severe yield losses. This study aims to identify the grapevine cultivar-specific adjustments of leaf proteome that allow the discrimination between resistance and susceptibility towards P. viticola (constitutive (0h) and in after inoculation (6, 12 and 24h). Leaf proteome analysis was performed using 2D difference gel electrophoresis followed by protein identification via mass spectrometry. In addition, we analysed ROS production, antioxidant capacity, lipid peroxidation and gene expression. Proteins related to photosynthesis and metabolism allowed the discrimination of resistant and susceptible grapevine cultivars prior to P. viticola inoculation. Following inoculation increase of hydrogen peroxide levels, cellular redox regulation, establishment of ROS signalling and plant cell death seem to be key points differentiating the resistant genotype. Lipid associated signalling events, particularly related to jasmonates appear also to play a major role in the establishment of resistance. The findings from this study contribute to a better understanding of genotype-specific differences that account for a successful establishment of a defence response to the downy mildew pathogen. Here, we present for the first time grapevine cultivar-specific adjustments of leaf proteome that allow the discrimination between resistance and susceptibility towards P. viticola (constitutive (0h) and in after inoculation (6, 12 and 24h). We have highlighted that, following inoculation, the major factors differentiating the resistant from the susceptible grapevine cultivars are the establishment of effective ROS signalling together with lipid-associated signalling events, particularly related to jasmonates. It is believed that plants infected with biotrophic pathogens suppress JA-mediated responses, however recent evidences shown that jasmonic acid signalling pathway in grapevine resistance against Plasmopara

  14. Region-specific disturbed iron distribution in early idiopathic Parkinson's disease measured by quantitative susceptibility mapping.

    Science.gov (United States)

    He, Naying; Ling, Huawei; Ding, Bei; Huang, Juan; Zhang, Yong; Zhang, Zhongping; Liu, Chunlei; Chen, Kemin; Yan, Fuhua

    2015-11-01

    In Parkinson's disease (PD), iron elevation in specific brain regions as well as selective loss of dopaminergic neurons is a major pathologic feature. A reliable quantitative measure of iron deposition is a potential biomarker for PD and may contribute to the investigation of iron-mediated PD. The primary purpose of this study is to assess iron variations in multiple deep grey matter nuclei in early PD with a novel MRI technique, quantitative susceptibility mapping (QSM). The inter-group differences of susceptibility and R2* value in deep grey matter nuclei, namely head of caudate nucleus (CN), putamen (PUT), global pallidus (GP), substantia nigra (SN), and red nucleus (RN), and the correlations between regional iron deposition and the clinical features were explored in forty-four early PD patients and 35 gender and age-matched healthy controls. Susceptibility values were found to be elevated within bilateral SN and RN contralateral to the most affected limb in early PD compared with healthy controls (HCs). The finding of increased susceptibility in bilateral SN is consistent with work on a subgroup of patients at the earliest clinical detectable state (Hoehn and Yahr [1967]: Neurology 17:427-442; Stage I). However, increased R2* values were only seen within SN contralateral to the most affected limb in the PD group when compared with controls. Furthermore, bilateral SN magnetic susceptibility positively correlated with disease duration and UPDRS-III scores in early PD. This finding supports the potential value of QSM as a non-invasive quantitative biomarker of early PD. © 2015 Wiley Periodicals, Inc.

  15. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations......3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ≤ 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor...

  16. Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

    DEFF Research Database (Denmark)

    Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

    2011-01-01

    Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations......3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P = 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor...

  17. Epitope-Specific Tolerance Modes Differentially Specify Susceptibility to Proteolipid Protein-Induced Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Lei Wang

    2017-11-01

    Full Text Available Immunization with myelin components can elicit experimental autoimmune encephalomyelitis (EAE. EAE susceptibility varies between mouse strains, depending on the antigen employed. BL/6 mice are largely resistant to EAE induction with proteolipid protein (PLP, probably a reflection of antigen-specific tolerance. However, the extent and mechanism(s of tolerance to PLP remain unclear. Here, we identified three PLP epitopes in PLP-deficient BL/6 mice. PLP-sufficient mice did not respond against two of these, whereas tolerance was “leaky” for an epitope with weak predicted MHCII binding, and only this epitope was encephalitogenic. In TCR transgenic mice, the “EAE-susceptibility-associated” epitope was “ignored” by specific CD4 T cells, whereas the “resistance-associated” epitope induced clonal deletion and Treg induction in the thymus. Central tolerance was autoimmune regulator dependent and required expression and presentation of PLP by thymic epithelial cells (TECs. TEC-specific ablation of PLP revealed that peripheral tolerance, mediated by dendritic cells through recessive tolerance mechanisms (deletion and anergy, could largely compensate for a lack of central tolerance. However, adoptive EAE was exacerbated in mice lacking PLP in TECs, pointing toward a non-redundant role of the thymus in dominant tolerance to PLP. Our findings reveal multiple layers of tolerance to a central nervous system autoantigen that vary among epitopes and thereby specify disease susceptibility. Understanding how different modalities of tolerance apply to distinct T cell epitopes of a target in autoimmunity has implications for antigen-specific strategies to therapeutically interfere with unwanted immune reactions against self.

  18. Recapitulation of Clinical Individual Susceptibility to Drug-Induced QT Prolongation in Healthy Subjects Using iPSC-Derived Cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Tadahiro Shinozawa

    2017-02-01

    Full Text Available To predict drug-induced serious adverse events (SAE in clinical trials, a model using a panel of cells derived from human induced pluripotent stem cells (hiPSCs of individuals with different susceptibilities could facilitate major advancements in translational research in terms of safety and pharmaco-economics. However, it is unclear whether hiPSC-derived cells can recapitulate interindividual differences in drug-induced SAE susceptibility in populations not having genetic disorders such as healthy subjects. Here, we evaluated individual differences in SAE susceptibility based on an in vitro model using hiPSC-derived cardiomyocytes (hiPSC-CMs as a pilot study. hiPSCs were generated from blood samples of ten healthy volunteers with different susceptibilities to moxifloxacin (Mox-induced QT prolongation. Different Mox-induced field potential duration (FPD prolongation values were observed in the hiPSC-CMs from each individual. Interestingly, the QT interval was significantly positively correlated with FPD at clinically relevant concentrations (r > 0.66 in multiple analyses including concentration-QT analysis. Genomic analysis showed no interindividual significant differences in known target-binding sites for Mox and other drugs such as the hERG channel subunit, and baseline QT ranges were normal. The results suggest that hiPSC-CMs from healthy subjects recapitulate susceptibility to Mox-induced QT prolongation and provide proof of concept for in vitro preclinical trials.

  19. EEG quantification of alertness: methods for early identification of individuals most susceptible to sleep deprivation

    Science.gov (United States)

    Berka, Chris; Levendowski, Daniel J.; Westbrook, Philip; Davis, Gene; Lumicao, Michelle N.; Olmstead, Richard E.; Popovic, Miodrag; Zivkovic, Vladimir T.; Ramsey, Caitlin K.

    2005-05-01

    Electroencephalographic (EEG) and neurocognitive measures were simultaneously acquired to quantify alertness from 24 participants during 44-hours of sleep deprivation. Performance on a three-choice vigilance task (3C-VT), paired-associate learning/memory task (PAL) and modified Maintenance of Wakefulness Test (MWT), and sleep technician-observed drowsiness (eye-closures, head-nods, EEG slowing) were quantified. The B-Alert system automatically classifies each second of EEG on an alertness/drowsiness continuum. B-Alert classifications were significantly correlated with technician-observations, visually scored EEG and performance measures. B-Alert classifications during 3C-VT, and technician observations and performance during the 3C-VT and PAL evidenced progressively increasing drowsiness as a result of sleep deprivation with a stabilizing effect observed at the batteries occurring between 0600 and 1100 suggesting a possible circadian effect similar to those reported in previous sleep deprivation studies. Participants were given an opportunity to take a 40-minute nap approximately 24-hours into the sleep deprivation portion of the study (i.e., 7 PM on Saturday). The nap was followed by a transient period of increased alertness. Approximately 8 hours after the nap, behavioral and physiological measures of drowsiness returned to levels prior to the nap. Cluster analysis was used to stratify individuals into three groups based on their level of impairment as a result of sleep deprivation. The combination of B-Alert and neuro-behavioral measures may identify individuals whose performance is most susceptible to sleep deprivation. These objective measures could be applied in an operational setting to provide a "biobehavioral assay" to determine vulnerability to sleep deprivation.

  20. Fnip1 regulates skeletal muscle fiber type specification, fatigue resistance, and susceptibility to muscular dystrophy.

    Science.gov (United States)

    Reyes, Nicholas L; Banks, Glen B; Tsang, Mark; Margineantu, Daciana; Gu, Haiwei; Djukovic, Danijel; Chan, Jacky; Torres, Michelle; Liggitt, H Denny; Hirenallur-S, Dinesh K; Hockenbery, David M; Raftery, Daniel; Iritani, Brian M

    2015-01-13

    Mammalian skeletal muscle is broadly characterized by the presence of two distinct categories of muscle fibers called type I "red" slow twitch and type II "white" fast twitch, which display marked differences in contraction strength, metabolic strategies, and susceptibility to fatigue. The relative representation of each fiber type can have major influences on susceptibility to obesity, diabetes, and muscular dystrophies. However, the molecular factors controlling fiber type specification remain incompletely defined. In this study, we describe the control of fiber type specification and susceptibility to metabolic disease by folliculin interacting protein-1 (Fnip1). Using Fnip1 null mice, we found that loss of Fnip1 increased the representation of type I fibers characterized by increased myoglobin, slow twitch markers [myosin heavy chain 7 (MyH7), succinate dehydrogenase, troponin I 1, troponin C1, troponin T1], capillary density, and mitochondria number. Cultured Fnip1-null muscle fibers had higher oxidative capacity, and isolated Fnip1-null skeletal muscles were more resistant to postcontraction fatigue relative to WT skeletal muscles. Biochemical analyses revealed increased activation of the metabolic sensor AMP kinase (AMPK), and increased expression of the AMPK-target and transcriptional coactivator PGC1α in Fnip1 null skeletal muscle. Genetic disruption of PGC1α rescued normal levels of type I fiber markers MyH7 and myoglobin in Fnip1-null mice. Remarkably, loss of Fnip1 profoundly mitigated muscle damage in a murine model of Duchenne muscular dystrophy. These results indicate that Fnip1 controls skeletal muscle fiber type specification and warrant further study to determine whether inhibition of Fnip1 has therapeutic potential in muscular dystrophy diseases.

  1. Ketamine and Imipramine Reverse Transcriptional Signatures of Susceptibility and Induce Resilience-Specific Gene Expression Profiles.

    Science.gov (United States)

    Bagot, Rosemary C; Cates, Hannah M; Purushothaman, Immanuel; Vialou, Vincent; Heller, Elizabeth A; Yieh, Lynn; LaBonté, Benoit; Peña, Catherine J; Shen, Li; Wittenberg, Gayle M; Nestler, Eric J

    2017-02-15

    Examining transcriptional regulation by antidepressants in key neural circuits implicated in depression and understanding the relation to transcriptional mechanisms of susceptibility and natural resilience may help in the search for new therapeutic agents. Given the heterogeneity of treatment response in human populations, examining both treatment response and nonresponse is critical. We compared the effects of a conventional monoamine-based tricyclic antidepressant, imipramine, and a rapidly acting, non-monoamine-based antidepressant, ketamine, in mice subjected to chronic social defeat stress, a validated depression model, and used RNA sequencing to analyze transcriptional profiles associated with susceptibility, resilience, and antidepressant response and nonresponse in the prefrontal cortex (PFC), nucleus accumbens, hippocampus, and amygdala. We identified similar numbers of responders and nonresponders after ketamine or imipramine treatment. Ketamine induced more expression changes in the hippocampus; imipramine induced more expression changes in the nucleus accumbens and amygdala. Transcriptional profiles in treatment responders were most similar in the PFC. Nonresponse reflected both the lack of response-associated gene expression changes and unique gene regulation. In responders, both drugs reversed susceptibility-associated transcriptional changes and induced resilience-associated transcription in the PFC. We generated a uniquely large resource of gene expression data in four interconnected limbic brain regions implicated in depression and its treatment with imipramine or ketamine. Our analyses highlight the PFC as a key site of common transcriptional regulation by antidepressant drugs and in both reversing susceptibility- and inducing resilience-associated molecular adaptations. In addition, we found region-specific effects of each drug, suggesting both common and unique effects of imipramine versus ketamine. Copyright © 2016 Society of Biological

  2. Individual differences in renal ACE activity in healthy rats predict susceptibility to adriamycin-induced renal damage

    NARCIS (Netherlands)

    Rook, M; Lely, AT; Kramer, AB; van Goor, H; Navis, G

    Background. In man, differences in angiotensin converting enzyme (ACE) levels, related to ACE (I/D) genotype, are associated with renal prognosis. This raises the hypothesis that individual differences in renal ACE activity are involved in renal susceptibility to inflicted damage. Therefore, we

  3. Are Some Individuals Diagnosed with ADHD Prone to Alcohol Abuse?: Consideration of Two Possible Mediating Factors for this Susceptibility

    Science.gov (United States)

    Maxwell, Allison

    2013-01-01

    Some studies conducted on ADHD have found a statistically significant relationship between those diagnosed with the disorder and a higher susceptibility to abuse alcohol. However, other studies have found no such correlation, or have found this to be true of only a nonstatistically significant subset of the population of individuals with ADHD.…

  4. Alcohol induces sensitization to gluten in genetically susceptible individuals: a case control study.

    Directory of Open Access Journals (Sweden)

    Stuart Currie

    Full Text Available BACKGROUND: The mechanisms of cerebellar degeneration attributed to prolonged and excessive alcohol intake remain unclear. Additional or even alternative causes of cerebellar degeneration are often overlooked in suspected cases of alcohol-related ataxia. The objectives of this study were two fold: (1 to investigate the prevalence of gluten-related serological markers in patients with alcohol-related ataxia and; (2 to compare the pattern of brain involvement on magnetic resonance imaging between patients with alcohol and gluten ataxias. MATERIALS & METHODS: Patients diagnosed with alcohol and gluten ataxias were identified from a retrospective review of patients attending a tertiary clinic. HLA genotype and serological markers of gluten-related disorders were recorded. Cerebellar volumetry, MR spectroscopy and voxel-based morphometric analyses were performed on patients and compared with matched control data. RESULTS: Of 904 registered patients, 104 had alcohol ataxia and 159 had gluten ataxia. 61% of the alcohol ataxia group and 70% of the gluten ataxia group had HLA DQ2/DQ8 genotype compared to 30% in healthy local blood donors. 44% of patients with alcohol ataxia had antigliadin antibodies compared to 12% in the healthy local population and 10% in patients with genetically confirmed ataxias. None of the patients with alcohol ataxia and antigliadin antibodies had celiac disease compared to 40% in patients with gluten ataxia. The pattern of structural brain abnormality in patients with alcohol ataxia who had antigliadin antibodies differed from gluten ataxia and was identical to that of alcohol ataxia. CONCLUSIONS: Alcohol related cerebellar degeneration may, in genetically susceptible individuals, induce sensitization to gluten. Such sensitization may result from a primary cerebellar insult, but a more systemic effect is also possible. The duration and amount of exposure to alcohol may not be the only factors responsible for the cerebellar

  5. Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity

    OpenAIRE

    Robinson, Mike JF; Burghardt, Paul R; Patterson, Christa M.; Nobile, Cameron W; Akil, Huda; Watson, Stanley J.; Berridge, Kent C.; Ferrario, Carrie R.

    2015-01-01

    Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty foods), like the smell of brownies, can elicit craving to eat and increase the amount of food consumed. People who are more susceptible to these motivational effects of food cues may have a higher risk for becoming obese. Further, overconsumption of junk-foods leading to the development of obesity may itself heighten attraction to food cues. Here, we used a model of individual susceptibility to junk-foods diet-indu...

  6. Addiction memory as a specific, individually learned memory imprint.

    Science.gov (United States)

    Böning, J

    2009-05-01

    The construct of "addiction memory" (AM) and its importance for relapse occurrence has been the subject of discussion for the past 30 years. Neurobiological findings from "social neuroscience" and biopsychological learning theory, in conjunction with construct-valid behavioral pharmacological animal models, can now also provide general confirmation of addiction memory as a pathomorphological correlate of addiction disorders. Under multifactorial influences, experience-driven neuronal learning and memory processes of emotional and cognitive processing patterns in the specific individual "set" and "setting" play an especially pivotal role in this connection. From a neuropsychological perspective, the episodic (biographical) memory, located at the highest hierarchical level, is of central importance for the formation of the AM in certain structural and functional areas of the brain and neuronal networks. Within this context, neuronal learning and conditioning processes take place more or less unconsciously and automatically in the preceding long-term-memory systems (in particular priming and perceptual memory). They then regulate the individually programmed addiction behavior implicitly and thus subsequently stand for facilitated recollection of corresponding, previously stored cues or context situations. This explains why it is so difficult to treat an addiction memory, which is embedded above all in the episodic memory, from the molecular carrier level via the neuronal pattern level through to the psychological meaning level, and has thus meanwhile become a component of personality.

  7. Individual differences in the brain are associated with resilience versus susceptibility to lipopolysaccharide-induced memory impairment.

    Science.gov (United States)

    Tang, Hui; Ji, Muhuo; Zong, Manman; Jia, Min; Luo, Dan; Zhou, Zhiqiang; Yang, Jianjun

    2018-01-01

    Sepsis impairs learning and memory function, yet marked interindividual variability exists in the degree to which sepsis compromises learning and memory function. Thus, testing resilience versus susceptibility to systemic inflammation induced-memory impairment and the underlying mechanism is needed. In the present study, we firstly used lipopolysaccharide (LPS) to induce memory impairment, and then evaluated cognitive function on days 4-7 after the first LPS challenge. Subjects' scores on both behavioral measures were subjected to a hierarchical cluster analysis, identifying two clusters that differed notably on the Y-maze and fear conditioning tests. This analysis divided these subjects into two groups, one cluster (13 of 34 subjects) displayed impaired working and associative memory, named "Susceptive". The remaining cluster (21 of 34 subjects) showed normal memory, named "Resilient". We have also included another group receiving normal saline to serve as the control group. The three groups underwent a battery of biochemical detections. In addition, we investigated whether the individual differences would disappear between the "Resilient" and "Susceptive" groups by using microglia inhibitor minocycline. We showed that as compared with the "Resilient" or control group, the "Susceptive" group was accompanied by increased tumor necrosis factor-alpha, interleukin-1beta (IL-1β), IL-6, and biomarkers of microglia activation ionized calcium binding adaptor molecule-1 and cluster of differentiation 68. Notably, after decreasing the activation of microglia, the differences in cognitive function between the "Resilient" and "Susceptive" groups disappeared. Collectively, our study suggests that individual differences in the brain are associated with resilience versus susceptibility to LPS-induced memory impairment. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Specific dysregulation of IFNγ production by natural killer cells confers susceptibility to viral infection.

    Directory of Open Access Journals (Sweden)

    Nassima Fodil

    2014-12-01

    Full Text Available Natural Killer (NK cells contribute to the control of viral infection by directly killing target cells and mediating cytokine release. In C57BL/6 mice, the Ly49H activating NK cell receptor plays a key role in early resistance to mouse cytomegalovirus (MCMV infection through specific recognition of the MCMV-encoded MHC class I-like molecule m157 expressed on infected cells. Here we show that transgenic expression of Ly49H failed to provide protection against MCMV infection in the naturally susceptible A/J mouse strain. Characterization of Ly49H(+ NK cells from Ly49h-A transgenic animals showed that they were able to mount a robust cytotoxic response and proliferate to high numbers during the course of infection. However, compared to NK cells from C57BL/6 mice, we observed an intrinsic defect in their ability to produce IFNγ when challenged by either m157-expressing target cells, exogenous cytokines or chemical stimulants. This effect was limited to NK cells as T cells from C57BL/6 and Ly49h-A mice produced comparable cytokine levels. Using a panel of recombinant congenic strains derived from A/J and C57BL/6 progenitors, we mapped the genetic basis of defective IFNγ production to a single 6.6 Mb genetic interval overlapping the Ifng gene on chromosome 10. Inspection of the genetic interval failed to reveal molecular differences between A/J and several mouse strains showing normal IFNγ production. The chromosome 10 locus is independent of MAPK signalling or decreased mRNA stability and linked to MCMV susceptibility. This study highlights the existence of a previously uncovered NK cell-specific cis-regulatory mechanism of Ifnγ transcript expression potentially relevant to NK cell function in health and disease.

  9. Tools for Protecting the Privacy of Specific Individuals in Video

    Directory of Open Access Journals (Sweden)

    Chen Datong

    2007-01-01

    Full Text Available This paper presents a system for protecting the privacy of specific individuals in video recordings. We address the following two problems: automatic people identification with limited labeled data, and human body obscuring with preserved structure and motion information. In order to address the first problem, we propose a new discriminative learning algorithm to improve people identification accuracy using limited training data labeled from the original video and imperfect pairwise constraints labeled from face obscured video data. We employ a robust face detection and tracking algorithm to obscure human faces in the video. Our experiments in a nursing home environment show that the system can obtain a high accuracy of people identification using limited labeled data and noisy pairwise constraints. The study result indicates that human subjects can perform reasonably well in labeling pairwise constraints with the face masked data. For the second problem, we propose a novel method of body obscuring, which removes the appearance information of the people while preserving rich structure and motion information. The proposed approach provides a way to minimize the risk of exposing the identities of the protected people while maximizing the use of the captured data for activity/behavior analysis.

  10. Individual differences in susceptibility to large portion sizes among obese and normal‐weight children

    National Research Council Canada - National Science Library

    Mooreville, Mira; Davey, Adam; Orloski, Alexandria; Hannah, Elizabeth L; Mathias, Kevin C; Birch, Leann L; Kral, Tanja V.E; Zakeri, Issa F; Fisher, Jennifer O

    2015-01-01

    ... and satiety among children by promoting energy intake at and across meals . Such conditions do not have uniform effects on children, however, as evidenced by the observation that a majority of youth are not obese in the current environment . Whether heavier children are more susceptible to large food portion sizes is unclear. The notion of ...

  11. Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity

    Science.gov (United States)

    Robinson, Mike JF; Burghardt, Paul R; Patterson, Christa M; Nobile, Cameron W; Akil, Huda; Watson, Stanley J; Berridge, Kent C; Ferrario, Carrie R

    2015-01-01

    Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty foods), like the smell of brownies, can elicit craving to eat and increase the amount of food consumed. People who are more susceptible to these motivational effects of food cues may have a higher risk for becoming obese. Further, overconsumption of junk-foods leading to the development of obesity may itself heighten attraction to food cues. Here, we used a model of individual susceptibility to junk-foods diet-induced obesity to determine whether there are pre-existing and/or diet-induced increases in attraction to and motivation for sucrose-paired cues (ie, incentive salience or ‘wanting’). We also assessed diet- vs obesity-associated alterations in mesolimbic function and receptor expression. We found that rats susceptible to diet-induced obesity displayed heightened conditioned approach prior to the development of obesity. In addition, after junk-food diet exposure, those rats that developed obesity also showed increased willingness to gain access to a sucrose cue. Heightened ‘wanting’ was not due to individual differences in the hedonic impact (‘liking’) of sucrose. Neurobiologically, Mu opioid receptor mRNA expression was lower in striatal ‘hot-spots’ that generate eating or hedonic impact only in those rats that became obese. In contrast, prolonged exposure to junk-food resulted in cross-sensitization to amphetamine-induced locomotion and downregulation of striatal D2R mRNA regardless of the development of obesity. Together these data shed light on individual differences in behavioral and neurobiological consequences of exposure to junk-food diets and the potential contribution of incentive sensitization in susceptible individuals to greater food cue-triggered motivation. PMID:25761571

  12. Individual Differences in Cue-Induced Motivation and Striatal Systems in Rats Susceptible to Diet-Induced Obesity.

    Science.gov (United States)

    Robinson, Mike J F; Burghardt, Paul R; Patterson, Christa M; Nobile, Cameron W; Akil, Huda; Watson, Stanley J; Berridge, Kent C; Ferrario, Carrie R

    2015-08-01

    Pavlovian cues associated with junk-foods (caloric, highly sweet, and/or fatty foods), like the smell of brownies, can elicit craving to eat and increase the amount of food consumed. People who are more susceptible to these motivational effects of food cues may have a higher risk for becoming obese. Further, overconsumption of junk-foods leading to the development of obesity may itself heighten attraction to food cues. Here, we used a model of individual susceptibility to junk-foods diet-induced obesity to determine whether there are pre-existing and/or diet-induced increases in attraction to and motivation for sucrose-paired cues (ie, incentive salience or 'wanting'). We also assessed diet- vs obesity-associated alterations in mesolimbic function and receptor expression. We found that rats susceptible to diet-induced obesity displayed heightened conditioned approach prior to the development of obesity. In addition, after junk-food diet exposure, those rats that developed obesity also showed increased willingness to gain access to a sucrose cue. Heightened 'wanting' was not due to individual differences in the hedonic impact ('liking') of sucrose. Neurobiologically, Mu opioid receptor mRNA expression was lower in striatal 'hot-spots' that generate eating or hedonic impact only in those rats that became obese. In contrast, prolonged exposure to junk-food resulted in cross-sensitization to amphetamine-induced locomotion and downregulation of striatal D2R mRNA regardless of the development of obesity. Together these data shed light on individual differences in behavioral and neurobiological consequences of exposure to junk-food diets and the potential contribution of incentive sensitization in susceptible individuals to greater food cue-triggered motivation.

  13. Individual differences in susceptibility to motion sickness among six Skylab astronauts

    Science.gov (United States)

    Graybiel, A.; Miller, E. F., II; Homick, J. L.

    1975-01-01

    Motion sickness was studied in Skylab crewmen. By mission-day 8 (MD 8), astronauts were virtually free of motion sickness symptoms after rotation and linear acceleration tests. None of the Skylab-II astronauts (crewmen 1-3) was motion sick aloft, but astronaut 6 of the Skylab-III crew experienced motion sickness within an hour after transition into orbit. All three astronauts (4-6) of Skylab-III experienced motion sickness in the workshop, where astronaut 6 was most susceptible and astronaut 4 least susceptible. The higher susceptibility of SL-III crewmen in the workshop, as compared with SL-II crewmen, may be attributable to the fact that they were based in the command module (CM) less than one-third as long as were SL-II astronauts. I.e., the unnatural movements permitted in the open spaces of the workshop entrained more complex interactions of unusual vestibular and visual stimuli than did those in the CM. The observed reduced liability to kinetosis relative to earth may be due to absence of the gravity stimulus to the otolith organs.

  14. Incremental susceptibility of individual tooth surfaces to dental caries in Scottish adolescents.

    Science.gov (United States)

    Chestnutt, I G; Schafer, F; Jacobson, A P; Stephen, K W

    1996-02-01

    This study reports on the caries susceptibility of tooth surfaces in 4294 adolescents (mean age 12.5 yr) during a 3-yr, double-blind clinical caries trial, conducted in Lanarkshire, Scotland, between 1988 and 1992. Children were selected on the grounds of dental maturity and past caries experience. Clinical examinations with mirror, CPITN probe and fibre optic trans-illumination were carried out on the permanent dentition, with the buccal pits of mandibular molars and palatal pits of maxillary molars being recorded as separate sites. At baseline 6061 surfaces were decayed (1.0% of 601 160 surfaces examined), 20 160 (3.4%) filled, and 10 909 (1.8%) missing due to caries. The number of surfaces recorded as sound at baseline in subjects completing the study was 454 663. Of these 8176 (1.8%) new surfaces were decayed, 14 832 (3.3%) filled and 4000 (0.9%) missing at the final examination. Molar occlusal surfaces showed greatest susceptibility to attack, 35.8%) of those at risk becoming carious in the course of the study. All buccal and lingual smooth surfaces showed a low susceptibility, but 8.8% of buccal and palatal pits developed caries. At the final clinical-only examination, pit and fissure caries accounted for 48%, interproximal surfaces for 39%, and smooth surfaces for 13% of caries prevalence. However, overall the contribution of these surfaces to 3-yr increments was, 40%, 47% and 13%, respectively.

  15. Theta-specific susceptibility in a model of adaptive synaptic plasticity.

    Science.gov (United States)

    Albers, Christian; Schmiedt, Joscha T; Pawelzik, Klaus R

    2013-01-01

    Learning and memory formation are processes which are still not fully understood. It is widely believed that synaptic plasticity is the most important neural substrate for both. However, it has been observed that large-scale theta band oscillations in the mammalian brain are beneficial for learning, and it is not clear if and how this is linked to synaptic plasticity. Also, the underlying dynamics of synaptic plasticity itself have not been completely uncovered yet, especially for non-linear interactions between multiple spikes. Here, we present a new and simple dynamical model of synaptic plasticity. It incorporates novel contributions to synaptic plasticity including adaptation processes. We test its ability to reproduce non-linear effects on four different data sets of complex spike patterns, and show that the model can be tuned to reproduce the observed synaptic changes in great detail. When subjected to periodically varying firing rates, already linear pair based spike timing dependent plasticity (STDP) predicts a specific susceptibility of synaptic plasticity to pre- and postsynaptic firing rate oscillations in the theta-band. Our model retains this band-pass property, while for high firing rates in the non-linear regime it modifies the specific phase relation required for depression and potentiation. For realistic parameters, maximal synaptic potentiation occurs when the postsynaptic is trailing the presynaptic activity slightly. Anti-phase oscillations tend to depress it. Our results are well in line with experimental findings, providing a straightforward and mechanistic explanation for the importance of theta oscillations for learning.

  16. Behavior of susceptible-vaccinated--infected--recovered epidemics with diversity in the infection rate of the individuals

    CERN Document Server

    Cai, Chao-Ran; Guan, Jian-Yue

    2013-01-01

    We study a susceptible-vaccinated--infected--recovered (SVIR) epidemic-spreading model with diversity of infection rate of the individuals. By means of analytical arguments as well as extensive computer simulations, we demonstrate that the heterogeneity in infection rate can either impede or accelerate the epidemic spreading, which depends on the amount of vaccinated individuals introduced in the population as well as the contact pattern among the individuals. Remarkably, as long as the individuals with different capability of acquiring the disease interact with unequal frequency, there always exist a cross point for the fraction of vaccinated, below which the diversity of infection rate hinders the epidemic spreading and above which expedites it. The overall results are robust to the SVIR dynamics defined on different population models; the possible applications of the results are discussed.

  17. Individual variation in contagious yawning susceptibility is highly stable and largely unexplained by empathy or other known factors.

    Directory of Open Access Journals (Sweden)

    Alex J Bartholomew

    Full Text Available The contagious aspect of yawning is a well-known phenomenon that exhibits variation in the human population. Despite the observed variation, few studies have addressed its intra-individual reliability or the factors modulating differences in the susceptibility of healthy volunteers. Due to its obvious biological basis and impairment in diseases like autism and schizophrenia, a better understanding of this trait could lead to novel insights into these conditions and the general biological functioning of humans. We administered 328 participants a 3-minute yawning video stimulus, a cognitive battery, and a comprehensive questionnaire that included measures of empathy, emotional contagion, circadian energy rhythms, and sleepiness. Individual contagious yawning measurements were found to be highly stable across testing sessions, both in a lab setting and if administered remotely online, confirming that certain healthy individuals are less susceptible to contagious yawns than are others. Additionally, most individuals who failed to contagiously yawn in our study were not simply suppressing their reaction, as they reported not even feeling like yawning in response to the stimulus. In contrast to previous studies indicating that empathy, time of day, or intelligence may influence contagious yawning susceptibility, we found no influence of these variables once accounting for the age of the participant. Participants were less likely to show contagious yawning as their age increased, even when restricting to ages of less than 40 years. However, age was only able to explain 8% of the variability in the contagious yawn response. The vast majority of the variability in this extremely stable trait remained unexplained, suggesting that studies of its inheritance are warranted.

  18. Differential functional connectivity within an emotion regulation neural network among individuals resilient and susceptible to the depressogenic effects of early life stress.

    Science.gov (United States)

    Cisler, J M; James, G A; Tripathi, S; Mletzko, T; Heim, C; Hu, X P; Mayberg, H S; Nemeroff, C B; Kilts, C D

    2013-03-01

    Early life stress (ELS) is a significant risk factor for depression. The effects of ELS exposure on neural network organization have not been differentiated from the effect of depression. Furthermore, many individuals exposed to ELS do not develop depression, yet the network organization patterns differentiating resiliency versus susceptibility to the depressogenic effects of ELS are not clear. Women aged 18-44 years with either a history of ELS and no history of depression (n = 7), a history of ELS and current or past depression (n = 19), or a history of neither ELS nor depression (n = 12) underwent a resting-state 3-T functional magnetic resonance imaging (fMRI) scan. An emotion regulation brain network consisting of 21 nodes was described using graph analyses and compared between groups. Group differences in network topology involved decreased global connectivity and hub-like properties for the right ventrolateral prefrontal cortex (vlPFC) and decreased local network connectivity for the dorsal anterior cingulate cortex (dACC) among resilient individuals. Decreased local connectivity and increased hub-like properties of the left amygdala, decreased hub-like properties of the dACC and decreased local connectivity of the left vlPFC were observed among susceptible individuals. Regression analyses suggested that the severity of ELS (measured by self-report) correlated negatively with global connectivity and hub-like qualities for the left dorsolateral PFC (dlPFC). These preliminary results suggest functional neural connectivity patterns specific to ELS exposure and resiliency versus susceptibility to the depressogenic effects of ELS exposure.

  19. On individual-specific prediction of hidden inbreeding depression load.

    Science.gov (United States)

    Casellas, J

    2018-02-01

    Inbreeding depression is caused by increased homozygosity in the genome and merges two genetic mechanisms, a higher impact from recessive mutations and the waste of overdominance contributions. It is of major concern for the conservation of endangered populations of plants and animals, as major abnormalities are more frequent in inbred families than in outcrosses. Nevertheless, we lack appropriate analytical methods to estimate the hidden inbreeding depression load (IDL) in the genome of each individual. Here, a new mixed linear model approach has been developed to account for the inbreeding depression-related background of each individual in the pedigree. Within this context, inbred descendants contributed relevant information to predict the IDL contained in the genome of a given ancestor; moreover, known relationships spread these predictions to the remaining individuals in the pedigree, even if not contributing inbred offspring. Results obtained from the analysis of weaning weight in the MARET rabbit population demonstrated that the genetic background of inbreeding depression distributed heterogeneously across individuals and inherited generation by generation. Moreover, this approach was clearly preferred in terms of model fit and complexity when compared with classical approaches to inbreeding depression. This methodology must be viewed as a new tool for a better understanding of inbreeding in domestic and wild populations. © 2017 Blackwell Verlag GmbH.

  20. Specific adjustments in grapevine leaf proteome discriminating resistant and susceptible grapevine genotypes to Plasmopara viticola

    DEFF Research Database (Denmark)

    Figueiredo, Andreia; Martins, Joana; Sebastiana, Mónica

    2017-01-01

    Grapevine downy mildew is an important disease affecting crop production leading to severe yield losses. This study aims to identify the grapevine cultivar-specific adjustments of leaf proteome that allow the discrimination between resistance and susceptibility towards P. viticola (constitutive (...

  1. Monitoring the growth and drug susceptibility of individual bacteria using asynchronous magnetic bead rotation sensors.

    Science.gov (United States)

    Kinnunen, Paivo; Sinn, Irene; McNaughton, Brandon H; Newton, Duane W; Burns, Mark A; Kopelman, Raoul

    2011-01-15

    Continuous growth of individual bacteria has been previously studied by direct observation using optical imaging. However, optical microscopy studies are inherently diffraction limited and limited in the number of individual cells that can be continuously monitored. Here we report on the use of the asynchronous magnetic bead rotation (AMBR) sensor, which is not diffraction limited. The AMBR sensor allows for the measurement of nanoscale growth dynamics of individual bacterial cells, over multiple generations. This torque-based magnetic bead sensor monitors variations in drag caused by the attachment and growth of a single bacterial cell. In this manner, we observed the growth and division of individual Escherichia coli, with 80-nm sensitivity to the cell length. Over the life cycle of a cell, we observed up to a 300% increase in the rotational period of the biosensor due to increased cell volume. In addition, we observed single bacterial cell growth response to antibiotics. This work demonstrates the non-microscopy limited AMBR biosensor for monitoring individual cell growth dynamics, including cell elongation, generation time, lag time, and division, as well as their sensitivity to antibiotics. Copyright © 2010 Elsevier B.V. All rights reserved.

  2. Skin fibroblasts from individuals hemizygous for the familial adenopolyposis susceptibility gene show delayed crisis in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Chen, S.; Kazim, D.; Kraveka, J.; Pollack, R.E. (Columbia Univ., New York, NY (USA))

    1989-03-01

    Normal human fibroblast cells have not been reported to escape crisis--that is they die after about 24 doublings in culture. The authors have been studying the growth properties of skin fibroblast cells from persons in families with familial adenopolyposis of the colon (FAP). An individual hemizygous at the FAP locus will develop hyperplasia of the colonic epithelium followed by colonic polyps, both at an early age. Polyps themselves still retain a single functional FAP allele. A mutation or deletion in this allele in a polyp is hypothesized to lead to further loss of growth control; thus, a tumor is formed. They found that the in vitro life-span of skin fibroblast cells from FAP individuals and from some asymptomatic children were markedly extended when compared with normal individuals.

  3. [CZECANCA: CZEch CAncer paNel for Clinical Application-- Design and Optimization of the Targeted Sequencing Panel for the Identification of Cancer Susceptibility in High-risk Individuals from the Czech Republic].

    Science.gov (United States)

    Soukupová, J; Zemánková, P; Kleiblová, P; Janatová, M; Kleibl, Z

    2016-01-01

    Individuals with hereditary cancer syndromes form a minor but clinically important subgroup of oncology patients, comprising several thousand cases in the Czech Republic annually. In these patients, the identification of pathogenic mutations in cancer susceptibility genes has an important predictive and, in some cases, prognostic value. It also enables rational preventive strategies in asymptomatic carriers from affected families. More than 150 cancer susceptibility genes have been described so far; however, mutations in most of them are very rare, occurring with substantial population variability, and hence their clinical interpretation is very complicated. Diagnostics of mutations in cancer susceptibility genes have benefited from the broad availability of next-generation sequencing analyses using targeted gene panels. In order to rationalize the diagnostics of hereditary cancer syndromes in the Czech Republic, we have prepared the sequence capture panel "CZECANCA", targeting 219 cancer susceptibility genes. Besides more than 50 clinically important high- and moderate-penetrance susceptibility genes, the panel also targets less common candidate genes with uncertain clinical relevance. Alongside the panel design, we have optimized the analytical and bioinformatics pipeline, which will facilitate establishing a collective nationwide database of genotypes and clinical data from the analyzed individuals. The key objective of this project is to provide diagnostic laboratories in the Czech Republic with a reliable procedure and collective database improving the clinical utility of next-generation sequencing analyses in high-risk patients, which would help improve the interpretation of rare or population-specific variants in cancer susceptibility genes.

  4. Individual differences underlying susceptibility to addiction: role for the endogenous oxytocin system

    NARCIS (Netherlands)

    Buisman-Pijlman, F.T.A; Sumracki, N.M.; Gordon, J.J.; Hull, P.R.; Carter, C.S.; Tops, M.

    2014-01-01

    Recent research shows that the effects of oxytocin are more diverse than initially thought and that in some cases oxytocin can directly influence the response to drugs and alcohol. Large individual differences in basal oxytocin levels and reactivity of the oxytocin system exist. This paper will

  5. Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress

    NARCIS (Netherlands)

    G.E. Hodes (Georgia E.); M.L. Pfau (Madeline L.); M. Leboeuf (Marylene); S.A. Golden (Sam A.); D.J. Christoffel (Daniel J.); D. Bregman (Dana); N. Rebusi (Nicole); M. Heshmati (Mitra); H. Aleyasin (Hossein); B.L. Warren (Brandon L.); B. Lebonté (Benoit); S. Horn (Sarah); K.A. Lapidus (Kyle A.); V. Stelzhammer (Viktoria); E.H.F. Wong (Erik H. F.); S. Bahn (Sabine); V. Krishnan (Vaishnav); C.A. Bolaños-Guzman (Carlos A.); J.W. Murrough (James W.); M. Merad (Miriam); S.J. Russo (Scott J.)

    2014-01-01

    textabstractDepression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that

  6. Recognition specificity of individual EH domains of mammals and yeast

    DEFF Research Database (Denmark)

    Paoluzi, S; Castagnoli, L; Lauro, I

    1998-01-01

    The Eps homology (EH) domain is a recently described protein binding module that is found, in multiple or single copies, in several proteins in species as diverse as human and yeast. In this work, we have investigated the molecular details of recognition specificity mediated by this domain family...... by characterizing the peptide-binding preference of 11 different EH domains from mammal and yeast proteins. Ten of the eleven EH domains could bind at least some peptides containing an Asn-Pro-Phe (NPF) motif. By contrast, the first EH domain of End3p preferentially binds peptides containing an His-Thr/Ser-Phe (HT...

  7. Sex-specific effects of NLRP6/AVR and ADM loci on susceptibility to essential hypertension in a Sardinian population.

    Directory of Open Access Journals (Sweden)

    Nicola Glorioso

    Full Text Available Coronary artery disease, heart failure, fatal arrhythmias, stroke, and renal disease are the most common causes of mortality for humans, and essential hypertension remains a major risk factor. Elucidation of susceptibility loci for essential hypertension has been difficult because of its complex, multifactorial nature involving genetic, environmental, and sex- and age-dependent nature. We investigated whether the 11p15.5 region syntenic to rat chromosome 1 region containing multiple blood pressure quantitative trait loci (QTL detected in Dahl rat intercrosses harbors polymorphisms that contribute to susceptibility/resistance to essential hypertension in a Sardinian population. Initial testing performed using microsatellite markers spanning 18 Mb of 11p15.5 detected a strong association between D11S1318 (at 2.1 Mb, P = 0.004 and D11S1346 (at 10.6 Mb, P = 0.00000004, suggesting that loci in close proximity to these markers may contribute to susceptibility in our Sardinian cohort. NLR family, pyrin domain containing 6/angiotensin-vasopressin receptor (NLRP6/AVR, and adrenomedullin (ADM are in close proximity to D11S1318 and D11S1346, respectively; thus we tested single nucleotide polymorphisms (SNPs within NLRP6/AVR and ADM for their association with hypertension in our Sardinian cohort. Upon sex stratification, we detected one NLRP6/AVR SNP associated with decreased susceptibility to hypertension in males (rs7948797G, P = 0.029; OR = 0.73 [0.57-0.94]. For ADM, sex-specific analysis showed a significant association between rs4444073C, with increased susceptibility to essential hypertension only in the male population (P = 0.006; OR = 1.44 [1.13-1.84]. Our results revealed an association between NLRP6/AVR and ADM loci with male essential hypertension, suggesting the existence of sex-specific NLRP6/AVR and ADM variants affecting male susceptibility to essential hypertension.

  8. Differential Gene Expression Profile in the Rat Caudal Vestibular Nucleus is Associated with Individual Differences in Motion Sickness Susceptibility.

    Directory of Open Access Journals (Sweden)

    Jun-Qin Wang

    molecular basis for individual differences in MS susceptibility and provide information for the development of new therapeutic strategies for MSS individuals.

  9. A Locus at 5q33.3 Confers Resistance to Tuberculosis in Highly Susceptible Individuals

    Science.gov (United States)

    Sobota, Rafal S.; Stein, Catherine M.; Kodaman, Nuri; Scheinfeldt, Laura B.; Maro, Isaac; Wieland-Alter, Wendy; Igo, Robert P.; Magohe, Albert; Malone, LaShaunda L.; Chervenak, Keith; Hall, Noemi B.; Modongo, Chawangwa; Zetola, Nicola; Matee, Mecky; Joloba, Moses; Froment, Alain; Nyambo, Thomas B.; Moore, Jason H.; Scott, William K.; Lahey, Timothy; Boom, W. Henry; von Reyn, C. Fordham; Tishkoff, Sarah A.; Sirugo, Giorgio; Williams, Scott M.

    2016-01-01

    Immunosuppression resulting from HIV infection increases the risk of progression to active tuberculosis (TB) both in individuals newly exposed to Mycobacterium tuberculosis (MTB) and in those with latent infections. We hypothesized that HIV-positive individuals who do not develop TB, despite living in areas where it is hyperendemic, provide a model of natural resistance. We performed a genome-wide association study of TB resistance by using 581 HIV-positive Ugandans and Tanzanians enrolled in prospective cohort studies of TB; 267 of these individuals developed active TB, and 314 did not. A common variant, rs4921437 at 5q33.3, was significantly associated with TB (odds ratio = 0.37, p = 2.11 × 10−8). This variant lies within a genomic region that includes IL12B and is embedded in an H3K27Ac histone mark. The locus also displays consistent patterns of linkage disequilibrium across African populations and has signals of strong selection in populations from equatorial Africa. Along with prior studies demonstrating that therapy with IL-12 (the cytokine encoded in part by IL12B, associated with longer survival following MTB infection in mice deficient in CD4 T cells), our results suggest that this pathway might be an excellent target for the development of new modalities for treating TB, especially for HIV-positive individuals. Our results also indicate that studying extreme disease resistance in the face of extensive exposure can increase the power to detect associations in complex infectious disease. PMID:26942285

  10. Increased susceptibility of blood type O individuals to develop anemia in Plasmodium vivax infection.

    Science.gov (United States)

    Resende, Sarah Stela; Milagres, Vanessa Gonçalves; Chaves, Daniel Gonçalves; Fontes, Cor Jesus Fernandes; Carvalho, Luzia Helena; Sousa, Tais Nobrega; Brito, Cristiana Ferreira Alves de

    2017-06-01

    Plasmodium vivax has been reported to cause severe malaria, and one of the main resulting complications is anemia. Considering that P. vivax infects only young erythrocytes, anemia has been associated with the destruction of infected and non-infected erythrocytes. However, few studies have focused on understanding the relationship between the pathogenesis of P. vivax malaria and human genetic polymorphisms. Although ABO groups seem to influence the outcome of Plasmodium falciparum malaria, the association between P. vivax and ABO blood groups has been minimally investigated. Thus, we investigate the correlation between ABO blood groups and anemia induced by P. vivax infection. Five single nucleotide polymorphisms at the ABO gene were genotyped by PCR-RFLP and Real-Time PCR in P. vivax-infected subjects. The ABO blood types were associated with the hematological data of the patients. Our main finding was that type O infected-individuals showed lower levels of hemoglobin and hematocrit compared to type A-infected individuals. The correlation between ABO blood groups and hemoglobin levels remained significant when a multiple linear regression was applied with the possible confounding effects of clinical-epidemiologic variables taken into account. The finding that type O individuals have a higher frequency of anemia is a first step to understand the mechanisms involved in malaria anemia, which could be associated to increased destruction of type O erythrocytes. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Untangling the neurobiology of coping styles in rodents: Towards neural mechanisms underlying individual differences in disease susceptibility.

    Science.gov (United States)

    de Boer, Sietse F; Buwalda, Bauke; Koolhaas, Jaap M

    2017-03-01

    Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding of coping style variation is fundamental for biobehavioral neurosciences in probing individual disease susceptibility. This review outlines individual differences in trait-aggressiveness as an adaptive component of the natural sociobiology of rats and mice, and highlights that these reflect the general style of coping that varies from proactive (aggressive) to reactive (docile). We propose that this qualitative coping style can be disentangled into multiple quantitative behavioral domains, e.g., flexibility/impulse control, emotional reactivity and harm avoidance/reward processing, that each are encoded into selective neural circuitries. Since functioning of all these brain circuitries rely on fine-tuned serotonin signaling, autoinhibitory control mechanisms of serotonergic neuron (re)activity are crucial in orchestrating general coping style. Untangling the precise neuromolecular mechanisms of different coping styles will provide a roadmap for developing better therapeutic strategies of stress-related diseases. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.

    Science.gov (United States)

    Johnston, Jennifer J; Rubinstein, Wendy S; Facio, Flavia M; Ng, David; Singh, Larry N; Teer, Jamie K; Mullikin, James C; Biesecker, Leslie G

    2012-07-13

    Genome- and exome-sequencing costs are continuing to fall, and many individuals are undergoing these assessments as research participants and patients. The issue of secondary (so-called incidental) findings in exome analysis is controversial, and data are needed on methods of detection and their frequency. We piloted secondary variant detection by analyzing exomes for mutations in cancer-susceptibility syndromes in subjects ascertained for atherosclerosis phenotypes. We performed exome sequencing on 572 ClinSeq participants, and in 37 genes, we interpreted variants that cause high-penetrance cancer syndromes by using an algorithm that filtered results on the basis of mutation type, quality, and frequency and that filtered mutation-database entries on the basis of defined categories of causation. We identified 454 sequence variants that differed from the human reference. Exclusions were made on the basis of sequence quality (26 variants) and high frequency in the cohort (77 variants) or dbSNP (17 variants), leaving 334 variants of potential clinical importance. These were further filtered on the basis of curation of literature reports. Seven participants, four of whom were of Ashkenazi Jewish descent and three of whom did not meet family-history-based referral criteria, had deleterious BRCA1 or BRCA2 mutations. One participant had a deleterious SDHC mutation, which causes paragangliomas. Exome sequencing, coupled with multidisciplinary interpretation, detected clinically important mutations in cancer-susceptibility genes; four of such mutations were in individuals without a significant family history of disease. We conclude that secondary variants of high clinical importance will be detected at an appreciable frequency in exomes, and we suggest that priority be given to the development of more efficient modes of interpretation with trials in larger patient groups. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights

  13. 19p13.1 Is a triple-negative-specific breast cancer susceptibility locus

    NARCIS (Netherlands)

    K. Stevens (Kristen); Z. Fredericksen (Zachary); C. Vachon (Celine); X. Wang (Xing); S. Margolin (Sara); A. Lindblom (Annika); H. Nevanlinna (Heli); D. Greco (Dario); K. Aittomäki (Kristiina); C. Blomqvist (Carl); J. Chang-Claude (Jenny); A. Vrieling (Alina); D. Flesch-Janys (Dieter); H.-P. Sinn (Hans-Peter); S. Wang-Gohrke (Shan); S. Nickels (Stefan); H. Brauch (Hiltrud); Y-D. Ko (Yon-Dschun); H.-P. Fischer; R.K. Schmutzler (Rita); A. Meindl (Alfons); C.R. Bartram (Claus); S. Schott (Sarah); C. Engel (Christoph); A.K. Godwin (Andrew); J. Weaver (JoEllen); S.S. Pathak; P. Sharma (Pankaj); H. Brenner (Hermann); H. Mul̈ler (Heiko); V. Arndt (Volker); C. Stegmaier (Christa); P. Miron (Penelope); D. Yannoukakos (Drakoulis); A. Stavropoulou (Alexandra); G. Fountzilas (George); H. Gogas (Helen); R. Swann (Ruth); M. Dwek (Miriam); A. Perkins (Annie); R.L. Milne (Roger); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); S.E. Bojesen (Stig); S.F. Nielsen (Sune); B.G. Nordestgaard (Børge); H. Flyger (Henrik); P. Guénel (Pascal); T. Truong (Thérèse); F. Menegaux (Florence); E. Cordina-Duverger (Emilie); B. Burwinkel (Barbara); F. Marme (Federick); A. Schneeweiss (Andreas); C. Sohn (Christof); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); J. Peto (Julian); N. Johnson (Nichola); O. Fletcher (Olivia); I. dos Santos Silva (Isabel); P.A. Fasching (Peter); M.W. Beckmann (Matthias); A. Hartmann; A.B. Ekici (Arif); A. Lophatananon (Artitaya); K.R. Muir (Kenneth); P. Puttawibul (Puttisak); S. Wiangnon (Surapon); M.K. Schmidt (Marjanka); A. Broeks (Annegien); L.M. Braaf (Linde); E.H. Rosenberg (Efraim); J.L. Hopper (John); C. Apicella (Carmel); D.J. Park (Daniel); M.C. Southey (Melissa); A.J. Swerdlow (Anthony ); A. Ashworth (Alan); O. Nicholas (Orr); M. Schoemaker (Minouk); H. Anton-Culver (Hoda); A. Ziogas (Argyrios); L. Bernstein (Leslie); C.C. Dur (Christina Clarke); C-Y. Shen (Chen-Yang); J-C. Yu (Jyh-Cherng); H.-M. Hsu (Huan-Ming); C.-N. Hsiung (Chia-Ni); U. Hamann (Ute); T. Dun̈nebier (Thomas); T. Rud̈iger (Thomas); H.U. Ulmer (Hans); P.D.P. Pharoah (Paul); A.M. Dunning (Alison); M.K. Humphreys (Manjeet); Q. Wang (Qing); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); P. Hall (Per); K. Czene (Kamila); C.B. Ambrosone (Christine); F. Ademuyiwa (Foluso); H. Hwang (Helena); D. Eccles (Diana); M. García-Closas (Montserrat); J.D. Figueroa (Jonine); M.E. Sherman (Mark); J. Lissowska (Jolanta); P. Devilee (Peter); C.M. Seynaeve (Caroline); R.A.E.M. Tollenaar (Rob); M.J. Hooning (Maartje); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.M. Mulligan (Anna Marie); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); E.M. John (Esther); A. Miron (Alexander); G.G. Alnæs (Grethe); V. Kristensen (Vessela); A.-L. Brøresen-Dale (Anne-Lise); G.G. Giles (Graham); L. Baglietto (Laura); C.A. McLean (Catriona Ann); G. Severi (Gianluca); M. Kosel (Matthew); V.S. Pankratz (Shane); S. Slager (Susan); J.E. Olson (Janet); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); M. Barile (Monica); D. Lambrechts (Diether); S. Hatse (Sigrid); A.-S. Dieudonné (Anne-Sophie); M.R. Christiaens (Marie Rose); G. Chenevix-Trench (Georgia); J. Beesley (Jonathan); X. Chen (Xiaoqing); A. Mannermaa (Arto); V-M. Kosma (Veli-Matti); J. Hartikainen (Jaana); Y. Soini (Ylermi); D.F. Easton (Douglas); F.J. Couch (Fergus)

    2012-01-01

    textabstractThe 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER),

  14. Susceptibility of Grapholita molesta (Busck, 1916) to formulations of Bacillus thuringiensis, individual toxins and their mixtures.

    Science.gov (United States)

    Ricietto, Ana Paula Scaramal; Gomis-Cebolla, Joaquín; Vilas-Bôas, Gislayne Trindade; Ferré, Juan

    2016-11-01

    The Oriental fruit moth, Grapholita molesta (Lepidoptera: Tortricidae), is a major pest of fruit trees worldwide, such as peach and apple. Bacillus thuringiensis has been shown to be an efficient alternative to synthetic insecticides in the control of many agricultural pests. The objective of this study was to evaluate the effectiveness of B. thuringiensis individual toxins and their mixtures for the control of G. molesta. Bioassays were performed with Cry1Aa, Cry1Ac, Cry1Ca, Vip3Aa, Vip3Af and Vip3Ca, as well as with the commercial products DiPel® and XenTari®. The most active proteins were Vip3Aa and Cry1Aa, with LC 50 values of 1.8 and 7.5ng/cm 2 , respectively. Vip3Ca was nontoxic to this insect species. Among the commercial products, DiPel® was slightly, but significantly, more toxic than XenTari®, with LC 50 values of 13 and 33ng commercial product/cm 2 , respectively. Since Vip3A and Cry1 proteins are expressed together in some insect-resistant crops, we evaluated possible synergistic or antagonistic interactions among them. The results showed moderate to high antagonism in the combinations of Vip3Aa with Cry1Aa and Cry1Ca. Copyright © 2016. Published by Elsevier Inc.

  15. Short-term effects of air temperature on blood markers of coagulation and inflammation in potentially susceptible individuals.

    Science.gov (United States)

    Schäuble, Claudia Luise; Hampel, Regina; Breitner, Susanne; Rückerl, Regina; Phipps, Richard; Diaz-Sanchez, David; Devlin, Robert B; Carter, Jacqueline D; Soukup, Joleen; Silbajoris, Robert; Dailey, Lisa; Koenig, Wolfgang; Cyrys, Josef; Geruschkat, Uta; Belcredi, Petra; Kraus, Ute; Peters, Annette; Schneider, Alexandra E

    2012-09-01

    Changes in air temperature are associated with an increase in cardiovascular events, but the role of procoagulant and proinflammatory blood markers is still poorly understood. The authors investigated the association between air temperature and fibrinogen, plasminogen activator inhibitor type 1, interleukin-6 and high-sensitivity C reactive protein in two potentially susceptible groups. This prospective panel study was conducted between March 2007 and December 2008 in Augsburg, Germany. The study population comprised 187 participants with type 2 diabetes mellitus or impaired glucose tolerance and 87 participants with genetic polymorphisms on the detoxification and inflammation pathways. Overall, 1766 repeated blood measurements were collected. Hourly meteorology data were available from a central measurement site. The association between temperature and blood markers was analysed with additive mixed models. For type 2 diabetes mellitus and impaired glucose tolerance participants, the authors observed immediate, lagged and cumulative increases in fibrinogen (range of percentage changes in geometric mean: 0.6%-0.8%) and plasminogen activator inhibitor type 1 (6.0%-10.1%) in association with a 5°C temperature decrement. Participants with a body mass index above 30 kg/m(2) as well as females showed particularly strong fibrinogen effects. In participants with the special genetic background, 5°C decreases in the 5-day average of temperature led to a change of 8.0% (95% CI 0.5% to 16.2%) in interleukin-6 and of -8.4% (95% CI -15.8% to -0.3%) in high-sensitivity C reactive protein, the latter driven by physically active individuals. The authors observed different temperature effects on blood markers in two potentially susceptible groups probably indicating varying underlying biological mechanisms. This study results might provide a link between temperature and cardiovascular events.

  16. The accumulation of DNA demethylation in Sat α in normal gastric tissues with Helicobacter pylori infection renders susceptibility to gastric cancer in some individuals.

    Science.gov (United States)

    Saito, Masaaki; Suzuki, Koichi; Maeda, Takafumi; Kato, Takaharu; Kamiyama, Hidenori; Koizumi, Kei; Miyaki, Yuichiro; Okada, Shinichiro; Kiyozaki, Hirokazu; Konishi, Fumio

    2012-06-01

    Helicobacter pylori (HP) infection is widely recognized as a risk factor for gastric cancer, but only a minority of infected individuals develop gastric cancer. The aim of this study was to determine whether DNA demethylation in non-cancerous gastric mucosa (NGM) significantly enhances susceptibility to gastric cancer. A total of 165 healthy volunteers, including 83 HP-positive and 82-negative individuals, as well as 83 patients with single and 18 with synchronous double gastric cancer (GC) were enrolled in this study. The relative demethylation levels (RDLs) of repetitive sequences, including Alu, LINE-1 and Sat α, were quantified by real-time methylation-specific polymerase chain reaction. The Alu RDL did not exhibit any differences within each respective group, whereas LINE-1 RDL was significantly elevated in cancer tissues compared with the NGM in the other groups (PSat α RDL correlated with HP infection and cancer development. Sat α RDL was significantly elevated in the NGM in HP-positive compared with HP-negative (PSat α RDL of the NGM in the total population increased in an age-dependent manner, it was significantly increased in a fraction of younger GC patients (Sat α RDL in the NGM compared with single GC (P=0.0014). In these two fractions, Sat α RDL in the NGM exhibited an inverse correlation with age. In conclusion, the present study demonstrated that the accumulation of DNA demethylation in Sat α RDL in the NGM with HP infection potentially renders susceptibility to gastric cancer in a fraction of GC patients younger than 45 years or in patients with multiple cancers.

  17. Short-term effects of air temperature on blood pressure and pulse pressure in potentially susceptible individuals.

    Science.gov (United States)

    Lanzinger, Stefanie; Hampel, Regina; Breitner, Susanne; Rückerl, Regina; Kraus, Ute; Cyrys, Josef; Geruschkat, Uta; Peters, Annette; Schneider, Alexandra

    2014-09-01

    Only few epidemiological studies have investigated the association between air temperature and blood pressure (BP) or pulse pressure (PP), with inconsistent findings. We examined whether short-term changes in air temperature were associated with changes in BP or PP in three different populations. Between March 2007 and December 2008, 371 systolic and diastolic BP measurements were collected in 30 individuals with type-2 diabetes mellitus (T2D), 30 persons with impaired glucose tolerance and 42 healthy individuals without a metabolic disorder from Augsburg, Germany. Hourly means of ambient meteorological data were obtained from a fixed measurement station. Personal temperature measurements were conducted using data loggers. Temperature effects were evaluated using additive mixed models adjusting for time trend and relative humidity. Decreases in air temperature were associated with an increase in systolic BP, diastolic BP and PP in individuals with T2D. For example, a 1°C decrease in ambient temperature was associated with an immediate increase in systolic BP of 1.0 mmHg (95%-confidence interval: [0.5;1.4]mmHg). Effects of personally measured air temperature were similar. Temperature effects were modified by age, body mass index, gender, antihypertensive medication and whereabouts, such as being indoors. We observed associations between decreases in air temperature and increases in BP as well as PP in persons with T2D indicating that these people might be potentially more susceptible to changes in air temperature. Our findings may provide a hypothesis for a mechanism between air temperature decreases and short-term increases of cardiovascular events. Copyright © 2014 Elsevier GmbH. All rights reserved.

  18. The Jewish people: their ethnic history, genetic disorders and specific cancer susceptibility.

    Science.gov (United States)

    Kedar-Barnes, Inbal; Rozen, Paul

    2004-01-01

    The Jews are an ancient and unique group of people linked by language, religion and customs in spite of their major geographical shifts, expulsions, forced conversions and massacres throughout their entire history. As a result of these historical events that led to repeated migration, the Jewish people became dispersed into various ethnic sub-groups. Between these ethnic groups exists heterogeneity, as well as some similarities, to the populations amongst whom they lived. Rare genetic diseases have been reported to be prevalent among the different groups of Jews, which for the most part can be explained by random genetic drift together with intra-familial marriages. In this publication, we will briefly discuss the origin of the various ethnic groups and some of the genetic diseases commonly found in them, with emphasis on the Ashkenazim, their prevalent genetic diseases and cancer susceptibility.

  19. Monocot and dicot MLO powdery mildew susceptibility factors are functionally conserved in spite of the evolution of class-specific molecular features

    NARCIS (Netherlands)

    Appiano, M.; Catalano, D.; Santillan Martinez, M.I.; Lotti, C.; Zheng Zheng, Zheng; Visser, R.G.F.; Ricciardi, L.; Bai, Y.; Pavan, S.N.C.

    2015-01-01

    Background Specific members of the plant Mildew Locus O (MLO) protein family act as susceptibility factors towards powdery mildew (PM), a worldwide-spread fungal disease threatening many cultivated species. Previous studies indicated that monocot and dicot MLO susceptibility proteins are

  20. Individual and sex-specific differences in intrinsic growth rate covary with consistent individual differences in behaviour.

    Science.gov (United States)

    Biro, Peter A; Adriaenssens, Bart; Sampson, Portia

    2014-09-01

    The evolutionary causes of consistent individual differences in behaviour are currently a source of debate. A recent hypothesis suggests that consistent individual differences in life-history productivity (growth and/or fecundity) may covary with behavioural traits that contribute to growth-mortality trade-offs, such as risk-proneness (boldness) and foraging activity (voraciousness). It remains unclear, however, to what extent individual behavioural and life-history profiles are set early in life, or are a more flexible result of specific environmental or developmental contexts that allow bold and active individuals to acquire more resources. Longitudinal studies of individually housed animals under controlled conditions can shed light on this question. Since growth and behaviour can both vary within individuals (they are labile), studying between-individual correlations in behaviour and growth rate requires repeated scoring for both variables over an extended period of time. However, such a study has not yet been done. Here, we repeatedly measured individual mass seven times each, boldness 40 times each and voracity eight times each during the first 4 months of life on 90 individually housed crayfish (Cherax destructor). Animals were fed ad libitum, generating a context where individuals can express their intrinsic growth rate (i.e. growth capacity), but in which bold and voracious behaviour is not necessary for high resource acquisition (crayfish can and do hoard food back to their burrow). We show that individuals that were consistently bold over time during the day were also bolder at night, were more voracious and maintained higher growth rates over time than shy individuals. Independent of individual differences, we also observed that males were faster-growing, bolder and more voracious than females. Our findings imply that associations between bold behaviour and fast growth can occur in unlimited food contexts where there is no necessary link between bold

  1. Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer’s disease

    Science.gov (United States)

    Lambert, Jean-Charles; Ibrahim-Verbaas, Carla A; Harold, Denise; Naj, Adam C; Sims, Rebecca; Bellenguez, Céline; Jun, Gyungah; DeStefano, Anita L; Bis, Joshua C; Beecham, Gary W; Grenier-Boley, Benjamin; Russo, Giancarlo; Thornton-Wells, Tricia A; Jones, Nicola; Smith, Albert V; Chouraki, Vincent; Thomas, Charlene; Ikram, M Arfan; Zelenika, Diana; Vardarajan, Badri N; Kamatani, Yoichiro; Lin, Chiao-Feng; Gerrish, Amy; Schmidt, Helena; Kunkle, Brian; Dunstan, Melanie L; Ruiz, Agustin; Bihoreau, Marie-Thérèse; Choi, Seung-Hoan; Reitz, Christiane; Pasquier, Florence; Hollingworth, Paul; Ramirez, Alfredo; Hanon, Olivier; Fitzpatrick, Annette L; Buxbaum, Joseph D; Campion, Dominique; Crane, Paul K; Baldwin, Clinton; Becker, Tim; Gudnason, Vilmundur; Cruchaga, Carlos; Craig, David; Amin, Najaf; Berr, Claudine; Lopez, Oscar L; De Jager, Philip L; Deramecourt, Vincent; Johnston, Janet A; Evans, Denis; Lovestone, Simon; Letenneur, Luc; Morón, Francisco J; Rubinsztein, David C; Eiriksdottir, Gudny; Sleegers, Kristel; Goate, Alison M; Fiévet, Nathalie; Huentelman, Matthew J; Gill, Michael; Brown, Kristelle; Kamboh, M Ilyas; Keller, Lina; Barberger-Gateau, Pascale; McGuinness, Bernadette; Larson, Eric B; Green, Robert; Myers, Amanda J; Dufouil, Carole; Todd, Stephen; Wallon, David; Love, Seth; Rogaeva, Ekaterina; Gallacher, John; St George-Hyslop, Peter; Clarimon, Jordi; Lleo, Alberto; Bayer, Anthony; Tsuang, Debby W; Yu, Lei; Tsolaki, Magda; Bossù, Paola; Spalletta, Gianfranco; Proitsi, Petroula; Collinge, John; Sorbi, Sandro; Sanchez-Garcia, Florentino; Fox, Nick C; Hardy, John; Deniz Naranjo, Maria Candida; Bosco, Paolo; Clarke, Robert; Brayne, Carol; Galimberti, Daniela; Mancuso, Michelangelo; Matthews, Fiona; Moebus, Susanne; Mecocci, Patrizia; Zompo, Maria Del; Maier, Wolfgang; Hampel, Harald; Pilotto, Alberto; Bullido, Maria; Panza, Francesco; Caffarra, Paolo; Nacmias, Benedetta; Gilbert, John R; Mayhaus, Manuel; Lannfelt, Lars; Hakonarson, Hakon; Pichler, Sabrina; Carrasquillo, Minerva M; Ingelsson, Martin; Beekly, Duane; Alvarez, Victoria; Zou, Fanggeng; Valladares, Otto; Younkin, Steven G; Coto, Eliecer; Hamilton-Nelson, Kara L; Gu, Wei; Razquin, Cristina; Pastor, Pau; Mateo, Ignacio; Owen, Michael J; Faber, Kelley M; Jonsson, Palmi V; Combarros, Onofre; O’Donovan, Michael C; Cantwell, Laura B; Soininen, Hilkka; Blacker, Deborah; Mead, Simon; Mosley, Thomas H; Bennett, David A; Harris, Tamara B; Fratiglioni, Laura; Holmes, Clive; de Bruijn, Renee F A G; Passmore, Peter; Montine, Thomas J; Bettens, Karolien; Rotter, Jerome I; Brice, Alexis; Morgan, Kevin; Foroud, Tatiana M; Kukull, Walter A; Hannequin, Didier; Powell, John F; Nalls, Michael A; Ritchie, Karen; Lunetta, Kathryn L; Kauwe, John S K; Boerwinkle, Eric; Riemenschneider, Matthias; Boada, Mercè; Hiltunen, Mikko; Martin, Eden R; Schmidt, Reinhold; Rujescu, Dan; Wang, Li-san; Dartigues, Jean-François; Mayeux, Richard; Tzourio, Christophe; Hofman, Albert; Nöthen, Markus M; Graff, Caroline; Psaty, Bruce M; Jones, Lesley; Haines, Jonathan L; Holmans, Peter A; Lathrop, Mark; Pericak-Vance, Margaret A; Launer, Lenore J; Farrer, Lindsay A; van Duijn, Cornelia M; Van Broeckhoven, Christine; Moskvina, Valentina; Seshadri, Sudha; Williams, Julie; Schellenberg, Gerard D; Amouyel, Philippe

    2013-01-01

    Eleven susceptibility loci for late-onset Alzheimer’s disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer’s disease cases and 37,154 controls. In stage 2,11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer’s disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer’s disease. PMID:24162737

  2. [Antibiotic susceptibility of Staphylococcus aureus and Streptococcus pneumoniae in healthy carrier individuals in primary care in Barcelona area].

    Science.gov (United States)

    Llor, Carles; Boada, Albert; Pons-Vigués, Mariona; Grenzner, Elisabet; Juvé, Rosa; Almeda, Jesús

    2018-01-01

    The information available on antibiotic resistance patterns are generally based on specimens from hospitalised individuals. This study was aimed at evaluating the antibiotic resistance rate of nasal carriage strains of Staphylococcus aureus and Streptococcus pneumoniae in healthy individuals, in accordance with age and gender, attended in Primary Care Centres (PCC). Cross-sectional study. Seven PCC in the Barcelona area. Healthy nasal carriers aged 4years or more who did not present with any sign of infectious disease, and had not taken any antibiotic or had been hospitalised in the previous 3months. A total of 3,969 nasal swabs valid for identification were collected between 2010 and 2011 and were sent to one central microbiological laboratory for isolation of both pathogens. Resistance to common antibiotics was determined on the basis of the current European Committee on Antimicrobial Susceptibility Testing guidelines on cut-off points. The prevalence of methicillin-resistant S.aureus was 1.3% (95%CI: 0.5-2.1%), with resistance rates of 87.1% to phenoxymethylpenicillin and 11.6% to azithromycin, with no significant differences with age and gender. A total of 2.4% (95CI%: 0.1-4.7%) of the pneumococcal strains were highly resistant to both phenoxymethylpenicillin and macrolides, whereas the highest resistance rates were to cefaclor (53.3%), followed by tetracycline (20%) and cefuroxime (12.1%). These pathogens have lower resistance rates in the community than in the hospital setting. Primary Care physicians must be more aware of the current antimicrobial resistance, in order to ensure prudent use of antibiotics. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  3. Whole-brain connectivity dynamics reflect both task-specific and individual-specific modulation: A multitask study.

    Science.gov (United States)

    Xie, Hua; Calhoun, Vince D; Gonzalez-Castillo, Javier; Damaraju, Eswar; Miller, Robyn; Bandettini, Peter A; Mitra, Sunanda

    2017-05-23

    Functional connectivity (FC) has been widely used to study the functional organization of temporally correlated and spatially distributed brain regions. Recent studies of FC dynamics, quantified by windowed correlations, provide new insights to analyze dynamic, context-dependent reconfiguration of brain networks. A set of reoccurring whole-brain connectivity patterns at rest, referred to as FC states, have been identified, hypothetically reflecting underlying cognitive processes or mental states. We posit that the mean FC information for a given subject represents a significant contribution to the group-level FC dynamics. We show that the subject-specific FC profile, termed as FC individuality, can be removed to increase sensitivity to cognitively relevant FC states. To assess the impact of the FC individuality and task-specific FC modulation on the group-level FC dynamics analysis, we generate and analyze group studies of four subjects engaging in four cognitive conditions (rest, simple math, two-back memory, and visual attention task). We also propose a model to quantitatively evaluate the effect of two factors, namely, subject-specific and task-specific modulation on FC dynamics. We show that FC individuality is a predominant factor in group-level FC variability, and the embedded cognitively relevant FC states are clearly visible after removing the individual's connectivity profile. Our results challenge the current understanding of FC states and emphasize the importance of individual heterogeneity in connectivity dynamics analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Bone quantitative susceptibility mapping using a chemical species-specific R2* signal model with ultrashort and conventional echo data.

    Science.gov (United States)

    Dimov, Alexey V; Liu, Zhe; Spincemaille, Pascal; Prince, Martin R; Du, Jiang; Wang, Yi

    2017-03-05

    To develop quantitative susceptibility mapping (QSM) of bone using an ultrashort echo time (UTE) gradient echo (GRE) sequence for signal acquisition and a bone-specific effective transverse relaxation rate ( R2*) to model water-fat MR signals for field mapping. Three-dimensional radial UTE data (echo times ≥ 40 μs) was acquired on a 3 Tesla scanner and fitted with a bone-specific signal model to map the chemical species and susceptibility field. Experiments were performed ex vivo on a porcine hoof and in vivo on healthy human subjects (n = 7). For water-fat separation, a bone-specific model assigning R2* decay mostly to water was compared with the standard models that assigned the same decay for both fat and water. In the ex vivo experiment, bone QSM was correlated with CT. Compared with standard models, the bone-specific R2* method significantly reduced errors in the fat fraction within the cortical bone in all tested data sets, leading to reduced artifacts in QSM. Good correlation was found between bone CT and QSM values in the porcine hoof (R(2)  = 0.77). Bone QSM was successfully generated in all subjects. The QSM of bone is feasible using UTE with a conventional echo time GRE acquisition and a bone-specific R2* signal model. Magn Reson Med 000:000-000, 2017. © 2017 International Society for Magnetic Resonance in Medicine. © 2017 International Society for Magnetic Resonance in Medicine.

  5. Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice

    Data.gov (United States)

    U.S. Environmental Protection Agency — Datasets in Gene Expression Omnibus used in the study ORD-020969: Genomic effects of androstenedione and sex-specific liver cancer susceptibility in mice. This...

  6. Evaluation of Veterinary-Specific Interpretive Criteria for Susceptibility Testing of Streptococcus equi Subspecies with Trimethoprim-Sulfamethoxazole and Trimethoprim-Sulfadiazine

    DEFF Research Database (Denmark)

    Sadaka, Carmen; Kanellos, Theo; Guardabassi, Luca

    2017-01-01

    Antimicrobial susceptibility test results for trimethoprim-sulfadiazine with Streptococcus equi subspecies are interpreted based on human data for trimethoprim-sulfamethoxazole. The veterinary-specific data generated in this study support a single breakpoint for testing trimethoprim...

  7. Expression levels of pituitary tumor transforming 1 and glutathione-S-transferase theta 3 are associated with the individual susceptibility to D-galactosamine-induced hepatotoxicity.

    Science.gov (United States)

    Yun, Jun-Won; Kim, Chae-Wook; Bae, Il-Hong; Park, Young-Ho; Chung, Jin-Ho; Lim, Kyung-Min; Kang, Kyung-Sun

    2010-01-01

    Although drug-induced liver injury (DILI) is frequently observed, individual variation in the susceptibility to DILI is hard to predict. Intrinsic genetic variation is considered a key element for this variation but little is known about the identity of the genes associated with DILI. In this study, pre-biopsy method was applied to uncover the key genes for D-galactosamine (GalN)-induced liver injury and a cause and effect study was conducted to elucidate the correlation between the expression of uncovered genes and GalN-induced hepatotoxicity. To identify the genes determining the susceptibility to GalN-induced hepatotoxicity, we compared the innate gene expression profiles in the liver tissue pre-biopsied before GalN treatment of the SD rats susceptible and resistant to GalN-induced hepatotoxicity, using microarray. Eight genes including Pttg1, Ifit1 and Gstt3 were lower or higher in the susceptible animals than the resistant and RT-PCR analysis confirmed it. To determine if these genes are associated with the susceptibility to GalN-induced hepatotoxicity indeed, expression levels were measured using real-time PCR in a new set of animals and the correlation with GalN-induced hepatotoxicity were analyzed. Notably, the expression of Pttg1 was significantly correlated with the severity of GalN-induced hepatotoxicity (p<0.01) and the animals with lowest and highest level of Gstt3 turned out to be the most susceptible and resistant, respectively, demonstrating that the expression of Pttg1 and Gstt3 could predict inter-individual susceptibility to GalN-induced hepatotoxicity. More importantly, this study showed the utility of pre-biopsy method in the identification of the gene for the chemical-induced hepatotoxicity.

  8. The utilize facilities of individual education plan by children with specific learning difficulties

    OpenAIRE

    Jehličková, Hana

    2013-01-01

    The topic of the thesis are the special educational needs of pupils with specific learning difficulties. The aim of this paper is to explore the awareness of parents about the possibility of using individual educational plan for the education of children with learning disabilities and support the role of parents in educational process. The theoretical base of the thesis discusses the concept of specific learning disorders, their etiology, classification, diagnosis. It also defines individual ...

  9. Integrated genetic and epigenetic analysis identifies haplotype-specific methylation in the FTO type 2 diabetes and obesity susceptibility locus.

    Directory of Open Access Journals (Sweden)

    Christopher G Bell

    Full Text Available Recent multi-dimensional approaches to the study of complex disease have revealed powerful insights into how genetic and epigenetic factors may underlie their aetiopathogenesis. We examined genotype-epigenotype interactions in the context of Type 2 Diabetes (T2D, focussing on known regions of genomic susceptibility. We assayed DNA methylation in 60 females, stratified according to disease susceptibility haplotype using previously identified association loci. CpG methylation was assessed using methylated DNA immunoprecipitation on a targeted array (MeDIP-chip and absolute methylation values were estimated using a Bayesian algorithm (BATMAN. Absolute methylation levels were quantified across LD blocks, and we identified increased DNA methylation on the FTO obesity susceptibility haplotype, tagged by the rs8050136 risk allele A (p = 9.40×10(-4, permutation p = 1.0×10(-3. Further analysis across the 46 kb LD block using sliding windows localised the most significant difference to be within a 7.7 kb region (p = 1.13×10(-7. Sequence level analysis, followed by pyrosequencing validation, revealed that the methylation difference was driven by the co-ordinated phase of CpG-creating SNPs across the risk haplotype. This 7.7 kb region of haplotype-specific methylation (HSM, encapsulates a Highly Conserved Non-Coding Element (HCNE that has previously been validated as a long-range enhancer, supported by the histone H3K4me1 enhancer signature. This study demonstrates that integration of Genome-Wide Association (GWA SNP and epigenomic DNA methylation data can identify potential novel genotype-epigenotype interactions within disease-associated loci, thus providing a novel route to aid unravelling common complex diseases.

  10. Species-Specific and Drug-Specific Differences in Susceptibility of Candida Biofilms to Echinocandins: Characterization of Less Common Bloodstream Isolates

    Science.gov (United States)

    Simitsopoulou, Maria; Peshkova, Pavla; Tasina, Efthymia; Katragkou, Aspasia; Kyrpitzi, Daniela; Velegraki, Aristea; Walsh, Thomas J.

    2013-01-01

    Candida species other than Candida albicans are increasingly recognized as causes of biofilm-associated infections. This is a comprehensive study that compared the in vitro activities of all three echinocandins against biofilms formed by different common and infrequently identified Candida isolates. We determined the activities of anidulafungin (ANID), caspofungin (CAS), and micafungin (MFG) against planktonic cells and biofilms of bloodstream isolates of C. albicans (15 strains), Candida parapsilosis (6 strains), Candida lusitaniae (16 strains), Candida guilliermondii (5 strains), and Candida krusei (12 strains) by XTT [2,3-bis(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. Planktonic and biofilm MICs were defined as ≥50% fungal damage. Planktonic cells of all Candida species were susceptible to the three echinocandins, with MICs of ≤1 mg/liter. By comparison, differences in the MIC profiles of biofilms in response to echinocandins existed among the Candida species. Thus, C. lusitaniae and C. guilliermondii biofilms were highly recalcitrant to all echinocandins, with MICs of ≥32 mg/liter. In contrast, the MICs of all three echinocandins for C. albicans and C. krusei biofilms were relatively low (MICs ≤ 1 mg/liter). While echinocandins exhibited generally high MICs against C. parapsilosis biofilms, MFG exhibited the lowest MICs against these isolates (4 mg/liter). A paradoxical growth effect was observed with CAS concentrations ranging from 8 to 64 mg/liter against C. albicans and C. parapsilosis biofilms but not against C. krusei, C. lusitaniae, or C. guilliermondii. While non-albicans Candida planktonic cells were susceptible to all echinocandins, there were drug- and species-specific differences in susceptibility among biofilms of the various Candida species, with C. lusitaniae and C. guilliermondii exhibiting profiles of high MICs of the three echinocandins. PMID:23529739

  11. A Major Susceptibility Locus for Specific Language Impairment Is Located on 13q21

    OpenAIRE

    Bartlett, Christopher W.; Flax, Judy F.; Logue, Mark W.; Vieland, Veronica J.; Bassett, Anne S.; Tallal, Paula; Brzustowicz, Linda M.

    2002-01-01

    Children who fail to develop language normally—in the absence of explanatory factors such as neurological disorders, hearing impairment, or lack of adequate opportunity—are clinically described as having specific language impairment (SLI). SLI has a prevalence of ∼7% in children entering school and is associated with later difficulties in learning to read. Research indicates that genetic factors are important in the etiology of SLI. Studies have consistently demonstrated that SLI aggregates i...

  12. The brain-specific factor FEZ1 is a determinant of neuronal susceptibility to HIV-1 infection.

    LENUS (Irish Health Repository)

    Haedicke, Juliane

    2009-08-18

    Neurons are one of the few cell types in the human body that do not support HIV type-1 (HIV-1) replication. Although the lack of key receptors is a major obstacle to infection, studies suggest that additional functions inhibit virus replication to explain the exquisite resistance of neurons to HIV-1. However, specific neuronal factors that may explain this resistance remain to be discovered. In a screen for antiviral factors using a fibroblast line chemically mutagenized and selected for resistance to retroviral infection, we recently identified induction of rat FEZ1 (fasciculation and elongation protein zeta-1), a brain-specific protein, as the cause of this resistance. When exogenously expressed in nonneuronal cell lines rat FEZ1 blocked nuclear entry of retroviral DNA. Here, we demonstrate that among human brain cells, neurons naturally express high levels of FEZ1 compared to astrocytes or microglia cells and are correspondingly less susceptible to infection with pseudotyped HIV-1 that bypasses receptor-mediated viral entry. Demonstrating that endogenous FEZ1 was functionally important in the resistance of neurons to HIV-1 infection, siRNA-mediated knockdown of endogenous FEZ1 increased the infectivity of neurons while sensitive brain cell types like microglia became more resistant upon FEZ1 overexpression. In addition, FEZ1 expression was not induced in response to IFN treatment. As such, in contrast to other widely expressed, IFN-inducible antiviral factors, FEZ1 appears to represent a unique neuron-specific determinant of cellular susceptibility to infection in a cell type that is naturally resistant to HIV-1.

  13. Individual-specific features of brain systems identified with resting state functional correlations.

    Science.gov (United States)

    Gordon, Evan M; Laumann, Timothy O; Adeyemo, Babatunde; Gilmore, Adrian W; Nelson, Steven M; Dosenbach, Nico U F; Petersen, Steven E

    2017-02-01

    Recent work has made important advances in describing the large-scale systems-level organization of human cortex by analyzing functional magnetic resonance imaging (fMRI) data averaged across groups of subjects. However, new findings have emerged suggesting that individuals' cortical systems are topologically complex, containing small but reliable features that cannot be observed in group-averaged datasets, due in part to variability in the position of such features along the cortical sheet. This previous work has reported only specific examples of these individual-specific system features; to date, such features have not been comprehensively described. Here we used fMRI to identify cortical system features in individual subjects within three large cross-subject datasets and one highly sampled within-subject dataset. We observed system features that have not been previously characterized, but 1) were reliably detected across many scanning sessions within a single individual, and 2) could be matched across many individuals. In total, we identified forty-three system features that did not match group-average systems, but that replicated across three independent datasets. We described the size and spatial distribution of each non-group feature. We further observed that some individuals were missing specific system features, suggesting individual differences in the system membership of cortical regions. Finally, we found that individual-specific system features could be used to increase subject-to-subject similarity. Together, this work identifies individual-specific features of human brain systems, thus providing a catalog of previously unobserved brain system features and laying the foundation for detailed examinations of brain connectivity in individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Pitx2 prevents susceptibility to atrial arrhythmias by inhibiting left-sided pacemaker specification.

    Science.gov (United States)

    Wang, Jun; Klysik, Elzbieta; Sood, Subeena; Johnson, Randy L; Wehrens, Xander H T; Martin, James F

    2010-05-25

    Atrial fibrillation (AF), the most prevalent sustained cardiac arrhythmia, often coexists with the related arrhythmia atrial flutter (AFL). Limitations in effectiveness and safety of current therapies make an understanding of the molecular mechanism underlying AF more urgent. Genome-wide association studies implicated a region of human chromosome 4q25 in familial AF and AFL, approximately 150 kb distal to the Pitx2 homeobox gene, a developmental left-right asymmetry (LRA) gene. To investigate the significance of the 4q25 variants, we used mouse models to investigate Pitx2 in atrial arrhythmogenesis directly. When challenged by programmed stimulation, Pitx2(null+/-) adult mice had atrial arrhythmias, including AFL and atrial tachycardia, indicating that Pitx2 haploinsufficiency predisposes to atrial arrhythmias. Microarray and in situ studies indicated that Pitx2 suppresses sinoatrial node (SAN)-specific gene expression, including Shox2, in the left atrium of embryos and young adults. In vivo ChIP and transfection experiments indicated that Pitx2 directly bound Shox2 in vivo, supporting the notion that Pitx2 directly inhibits the SAN-specific genetic program in left atrium. Our findings implicate Pitx2 and Pitx2-mediated LRA-signaling pathways in prevention of atrial arrhythmias.

  15. Changes in Predicted Muscle Coordination with Subject-Specific Muscle Parameters for Individuals after Stroke

    Directory of Open Access Journals (Sweden)

    Brian A. Knarr

    2014-01-01

    Full Text Available Muscle weakness is commonly seen in individuals after stroke, characterized by lower forces during a maximal volitional contraction. Accurate quantification of muscle weakness is paramount when evaluating individual performance and response to after stroke rehabilitation. The objective of this study was to examine the effect of subject-specific muscle force and activation deficits on predicted muscle coordination when using musculoskeletal models for individuals after stroke. Maximum force generating ability and central activation ratio of the paretic plantar flexors, dorsiflexors, and quadriceps muscle groups were obtained using burst superimposition for four individuals after stroke with a range of walking speeds. Two models were created per subject: one with generic and one with subject-specific activation and maximum isometric force parameters. The inclusion of subject-specific muscle data resulted in changes in the model-predicted muscle forces and activations which agree with previously reported compensation patterns and match more closely the timing of electromyography for the plantar flexor and hamstring muscles. This was the first study to create musculoskeletal simulations of individuals after stroke with subject-specific muscle force and activation data. The results of this study suggest that subject-specific muscle force and activation data enhance the ability of musculoskeletal simulations to accurately predict muscle coordination in individuals after stroke.

  16. Vocal Imitation in Parrots Allows Addressing of Specific Individuals in a Dynamic Communication Network

    DEFF Research Database (Denmark)

    Balsby, T.J.S.; Momberg, J.V.; Dabelsteen, T.

    2012-01-01

    Parrots in captivity are known for their ability to vocally imitate humans and recently it has been shown that wild-living orange-fronted conures are able to immediately imitate other individuals´ contact calls. The function of this exceptional ability to imitate remains unclear. However, orangeâ......€“fronted conures live in fission-fusion flocks where they encounter many different individuals every day, and it is possible that their vocal imitation ability is a flexible means to address a specific individual within a flock. We tested this via playback to short-term captive wild conures. Test birds were placed...... together in pairs in outdoor aviaries to form simple flocks. To simulate imitation of a specific individual these pairs received playback of contact calls that primarily imitate one of the two birds. Overall, individuals that received simulated vocal imitations of its calls responded more frequently...

  17. Technical Note: Evaluation of individual ultraviolet radiation dosimeter sensitivity and specificity for assessing shade use.

    Science.gov (United States)

    Holcomb, K E; Stull, C L

    2017-09-01

    The effects of solar or UV radiation on livestock are often evaluated in research focused on heat stress, dermatological conditions, and other topics, with radiation measurements recorded by instrumentation at a field or local weather station for a general geographical location. Individual sensors would be valuable for quantifying an individual animal's exposure, especially as they move about in a heterogeneous environment. Individual commercially available UV dosimeters were evaluated for specificity and sensitivity and found to be potentially valuable research tools for assessing and comparing the UV radiation exposure of individual animals.

  18. Presence of a central vein within white matter lesions on susceptibility weighted imaging: a specific finding for multiple sclerosis?

    Energy Technology Data Exchange (ETDEWEB)

    Lummel, Nina; Boeckh-Behrens, Tobias; Brueckmann, Hartmut; Linn, Jennifer [University of Munich, Department of Neuroradiology, Munich (Germany); Schoepf, Veronika [University of Munich, Department of Neuroradiology, Munich (Germany); Medical University of Vienna, MR Centre of Excellence, Vienna (Austria); Burke, Michael [GE Healthcare, Solingen (Germany)

    2011-05-15

    Susceptibility weighted imaging depicts the perivenous extent of multiple sclerosis white matter lesions (MS-WML) in vivo by directly visualizing their centrally running vein. The aim of this study was to investigate the specificity of this finding for MS. Fifteen patients with MS and 15 patients with microangiopathic white matter lesions (mWML) underwent 3T MRI, including a fluid-attenuated inversion recovery sequence (FLAIR) and a susceptibility weighted angiography (SWAN). All WMLs were identified on FLAIR and assigned to one of the following localizations: supratentorial peripheral, supratentorial periventricular, or infratentorial. Subsequently, the presence of a central vein within these lesions was assessed on SWAN. A total of 711 MS-WMLs and 1,119 m-WMLs were identified on FLAIR, all of which could also be visualized on SWAN. A central vein was detectable in 80% of the MS-WMLs and in 78% of the m-WMLs (in 73% and 76% of the peripheral, in 92% and 94% of the periventricular, and in 71% and 75% of the infratentorial MS-WMLs and m-WMLs, respectively). With regard to the supratentorial peripheral lesions, significantly more m-WMLs showed a central vein compared to the MS-WMLs. For the other localizations, there was no significant difference between the groups with regard to the percentage of lesions with central vein. Our results indicate that the detection of a central vein within a WML should not be considered a specific finding for MS; it is also found in WMLs of other etiologies. (orig.)

  19. Triheptanoin reduces seizure susceptibility in a syndrome-specific mouse model of generalized epilepsy.

    Science.gov (United States)

    Kim, Tae Hwan; Borges, Karin; Petrou, Steven; Reid, Christopher A

    2013-01-01

    Triheptanoin is a triglyceride containing heptanoate, an odd-chained medium fatty acid that is metabolized to produce propionyl-CoA and subsequently C4 intermediates of the citric acid cycle and therefore capable of anaplerosis. These metabolic products are believed to underlie triheptanoin's anticonvulsant effects in rodent seizure models. Here we investigate the anticonvulsive effects of oral triheptanoin in a syndrome-specific genetic mouse model of generalized epilepsy based on the GABA(A)γ2(R43Q) mutation. Mice were fed a diet supplemented with triheptanoin from weaning for three weeks prior to electrocortical recordings. Occurrence and durations of spike and wave discharges (SWDs) were measured. Triheptanoin did not alter body weight or basal blood glucose levels suggesting that it was well tolerated. Triheptanoin supplementation halved the time spent in seizures due to a reduction in both SWD occurrence and duration. An injection of insulin was used to reduce blood glucose, a metabolic stress known to precipitate seizures in the GABA(A)γ2(R43Q) mouse. The reduction in seizure count was also evident following insulin induced hypoglycemia with the triheptanoin treated group having significantly less SWDs than control animals under similar low blood glucose conditions. In summary, triheptanoin may be an effective and well tolerated dietary therapy for generalized epilepsy. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  20. Vocal imitation in parrots allows addressing of specific individuals in a dynamic communication network.

    Directory of Open Access Journals (Sweden)

    Thorsten J S Balsby

    Full Text Available Parrots in captivity are known for their ability to vocally imitate humans and recently it has been shown that wild-living orange-fronted conures are able to immediately imitate other individuals' contact calls. The function of this exceptional ability to imitate remains unclear. However, orange-fronted conures live in fission-fusion flocks where they encounter many different individuals every day, and it is possible that their vocal imitation ability is a flexible means to address a specific individual within a flock. We tested this via playback to short-term captive wild conures. Test birds were placed together in pairs in outdoor aviaries to form simple flocks. To simulate imitation of a specific individual these pairs received playback of contact calls that primarily imitate one of the two birds. Overall, individuals that received simulated vocal imitations of its calls responded more frequently and faster than the other individual. This suggests that orange-fronted conures can use imitations of contact calls to address specific individuals of a flock. In the discussion we argue that the fission-fusion flock dynamics of many parrot species has been an important factor in evolving conures' and other parrots' exceptional ability to imitate.

  1. Vocal imitation in parrots allows addressing of specific individuals in a dynamic communication network.

    Science.gov (United States)

    Balsby, Thorsten J S; Momberg, Jane Vestergaard; Dabelsteen, Torben

    2012-01-01

    Parrots in captivity are known for their ability to vocally imitate humans and recently it has been shown that wild-living orange-fronted conures are able to immediately imitate other individuals' contact calls. The function of this exceptional ability to imitate remains unclear. However, orange-fronted conures live in fission-fusion flocks where they encounter many different individuals every day, and it is possible that their vocal imitation ability is a flexible means to address a specific individual within a flock. We tested this via playback to short-term captive wild conures. Test birds were placed together in pairs in outdoor aviaries to form simple flocks. To simulate imitation of a specific individual these pairs received playback of contact calls that primarily imitate one of the two birds. Overall, individuals that received simulated vocal imitations of its calls responded more frequently and faster than the other individual. This suggests that orange-fronted conures can use imitations of contact calls to address specific individuals of a flock. In the discussion we argue that the fission-fusion flock dynamics of many parrot species has been an important factor in evolving conures' and other parrots' exceptional ability to imitate.

  2. A meta-analysis of 87,040 individuals identifies 23 new susceptibility loci for prostate cancer

    DEFF Research Database (Denmark)

    Al Olama, Ali Amin; Kote-Jarai, Zsofia; Berndt, Sonja I

    2014-01-01

    Genome-wide association studies (GWAS) have identified 76 variants associated with prostate cancer risk predominantly in populations of European ancestry. To identify additional susceptibility loci for this common cancer, we conducted a meta-analysis of > 10 million SNPs in 43,303 prostate cancer...

  3. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    NARCIS (Netherlands)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael J.; Maranian, Mel J.; Bolla, Manjeet K.; Wang, Qin; Shah, Mitul; Perkins, Barbara J.; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S.; Bojesen, Stig E.; Nordestgaard, Borge G.; Flyger, Henrik; Nielsen, Sune F.; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A.; Aittomaki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G.; Whittemore, Alice S.; John, Esther M.; Malone, Kathleen E.; Gammon, Marilie D.; Santella, Regina M.; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F.; Casey, Graham; Hunter, David J.; Gapstur, Susan M.; Gaudet, Mia M.; Diver, W. Ryan; Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.; Le Marchand, Loic; Berg, Christine D.; Chanock, Stephen J.; Figueroa, Jonine; Hoover, Robert N.; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K.; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A.; van der Luijt, Rob B.|info:eu-repo/dai/nl/153170824; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guenel, Pascal; Truong, Therese; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H.; Tseng, Chiu-chen; Van den Berg, David; Stram, Daniel O.; Gonzalez-Neira, Anna; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; Tan, Gie-Hooi; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; Collee, J. Margriet; Blot, William; Signorello, Lisa B.; Cai, Qiuyin; Hopper, John L.; Southey, Melissa C.; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N.; Nord, Silje; Alnaes, Grethe I. Grenaker; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Canzian, Federico; Trichopoulos, Dimitrios; Peeters, Petra|info:eu-repo/dai/nl/074099655; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J.; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K.; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A.; Hein, Alexander; Beckmann, Matthias W.; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J.; Swerdlow, Anthony J.; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L.; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S.; Labreche, France; Dumont, Martine; Winqvist, Robert; Pylkas, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Bruening, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V.; Doerk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Devilee, Peter; Tollenaar, Robert A. E. M.; Seynaeve, Caroline; Van Asperen, Christi J.; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; Mckay, James; Slager, Susan; Toland, Amanda E.; Ambrosone, Christine B.; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L.; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S.; Tessier, Daniel C.; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Rosario Alonso, M.; Alvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul P. D. P.; Kraft, Peter; Dunning, Alison M.; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F.

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining similar to 14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising

  4. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    NARCIS (Netherlands)

    K. Michailidou (Kyriaki); J. Beesley (Jonathan); S. Lindstrom (Stephen); S. Canisius (Sander); J. Dennis (Joe); M. Lush (Michael); M. Maranian (Melanie); M.K. Bolla (Manjeet); Q. Wang (Qing); M. Shah (Mitul); B. Perkins (Barbara); K. Czene (Kamila); M. Eriksson (Mikael); H. Darabi (Hatef); J.S. Brand (Judith S.); S.E. Bojesen (Stig); B.G. Nordestgaard (Børge); H. Flyger (Henrik); S.F. Nielsen (Sune); N. Rahman (Nazneen); C. Turnbull (Clare); O. Fletcher (Olivia); J. Peto (Julian); L.J. Gibson (Lorna); I. dos Santos Silva (Isabel); J. Chang-Claude (Jenny); D. Flesch-Janys (Dieter); A. Rudolph (Anja); U. Eilber (Ursula); T.W. Behrens (Timothy); H. Nevanlinna (Heli); T.A. Muranen (Taru); K. Aittomäki (Kristiina); C. Blomqvist (Carl); S. Khan (Sofia); K. Aaltonen (Kirsimari); H. Ahsan (Habibul); M.G. Kibriya (Muhammad); A.S. Whittemore (Alice S.); E.M. John (Esther M.); K.E. Malone (Kathleen E.); M.D. Gammon (Marilie); R.M. Santella (Regina M.); G. Ursin (Giske); E. Makalic (Enes); D.F. Schmidt (Daniel); G. Casey (Graham); D.J. Hunter (David J.); S.M. Gapstur (Susan M.); M.M. Gaudet (Mia); W.R. Diver (Ryan); C.A. Haiman (Christopher A.); F.R. Schumacher (Fredrick); B.E. Henderson (Brian); L. Le Marchand (Loic); C.D. Berg (Christine); S.J. Chanock (Stephen); J.D. Figueroa (Jonine); R.N. Hoover (Robert N.); D. Lambrechts (Diether); P. Neven (Patrick); H. Wildiers (Hans); E. van Limbergen (Erik); M.K. Schmidt (Marjanka); A. Broeks (Annegien); S. Verhoef; S. Cornelissen (Sten); F.J. Couch (Fergus); J.E. Olson (Janet); B. Hallberg (Boubou); C. Vachon (Celine); Q. Waisfisz (Quinten); E.J. Meijers-Heijboer (Hanne); M.A. Adank (Muriel); R.B. van der Luijt (Rob); J. Li (Jingmei); J. Liu (Jianjun); M.K. Humphreys (Manjeet); D. Kang (Daehee); J.-Y. Choi (Ji-Yeob); S.K. Park (Sue K.); K.Y. Yoo; K. Matsuo (Keitaro); H. Ito (Hidemi); H. Iwata (Hiroji); K. Tajima (Kazuo); P. Guénel (Pascal); T. Truong (Thérèse); C. Mulot (Claire); M. Sanchez (Marie); B. Burwinkel (Barbara); F. Marme (Federick); H. Surowy (Harald); C. Sohn (Christof); A.H. Wu (Anna H); C.-C. Tseng (Chiu-chen); D. Van Den Berg (David); D.O. Stram (Daniel O.); A. González-Neira (Anna); J. Benítez (Javier); M.P. Zamora (Pilar); J.I.A. Perez (Jose Ignacio Arias); X.-O. Shu (Xiao-Ou); W. Lu (Wei); Y. Gao; H. Cai (Hui); A. Cox (Angela); S.S. Cross (Simon); M.W.R. Reed (Malcolm); I.L. Andrulis (Irene); J.A. Knight (Julia); G. Glendon (Gord); A.-M. Mulligan (Anna-Marie); E.J. Sawyer (Elinor); I.P. Tomlinson (Ian); M. Kerin (Michael); N. Miller (Nicola); A. Lindblom (Annika); S. Margolin (Sara); S.H. Teo (Soo Hwang); C.H. Yip (Cheng Har); N.A.M. Taib (Nur Aishah Mohd); G.-H. Tan (Gie-Hooi); M.J. Hooning (Maartje); A. Hollestelle (Antoinette); J.W.M. Martens (John); J. Margriet Collée; W.J. Blot (William); L.B. Signorello (Lisa B.); Q. Cai (Qiuyin); J. Hopper (John); M.C. Southey (Melissa); H. Tsimiklis (Helen); C. Apicella (Carmel); C-Y. Shen (Chen-Yang); C.-N. Hsiung (Chia-Ni); P.-E. Wu (Pei-Ei); M.-F. Hou (Ming-Feng); V. Kristensen (Vessela); S. Nord (Silje); G.G. Alnæs (Grethe); G.G. Giles (Graham G.); R.L. Milne (Roger); C.A. McLean (Catriona Ann); F. Canzian (Federico); D. Trichopoulos (Dimitrios); P.H.M. Peeters; E. Lund (Eiliv); R. Sund (Reijo); K.T. Khaw; M.J. Gunter (Marc J.); D. Palli (Domenico); L.M. Mortensen (Lotte Maxild); L. Dossus (Laure); J.-M. Huerta (Jose-Maria); A. Meindl (Alfons); R.K. Schmutzler (Rita); C. Sutter (Christian); R. Yang (Rongxi); K. Muir (Kenneth); A. Lophatananon (Artitaya); S. Stewart-Brown (Sarah); P. Siriwanarangsan (Pornthep); J.M. Hartman (Joost); X. Miao; K.S. Chia (Kee Seng); C.W. Chan (Ching Wan); P.A. Fasching (Peter); R. Hein (Rebecca); M.W. Beckmann (Matthias W.); L. Haeberle (Lothar); H. Brenner (Hermann); A.K. Dieffenbach (Aida Karina); V. Arndt (Volker); C. Stegmaier (Christa); A. Ashworth (Alan); N. Orr (Nick); M. Schoemaker (Minouk); A.J. Swerdlow (Anthony ); L.A. Brinton (Louise); M. García-Closas (Montserrat); W. Zheng (Wei); S.L. Halverson (Sandra L.); M. Shrubsole (Martha); J. Long (Jirong); M.S. Goldberg (Mark); F. Labrèche (France); M. Dumont (Martine); R. Winqvist (Robert); K. Pykäs (Katri); A. Jukkola-Vuorinen (Arja); M. Grip (Mervi); H. Brauch (Hiltrud); U. Hamann (Ute); T. Brüning (Thomas); P. Radice (Paolo); P. Peterlongo (Paolo); S. Manoukian (Siranoush); L. Bernard (Loris); N.V. Bogdanova (Natalia); T. Dörk (Thilo); A. Mannermaa (Arto); V. Kataja (Vesa); V-M. Kosma (Veli-Matti); J.M. Hartikainen (J.); P. Devilee (Peter); R.A.E.M. Tollenaar (Rob); C.M. Seynaeve (Caroline); C.J. van Asperen (Christi); A. Jakubowska (Anna); J. Lubinski (Jan); K. Jaworska (Katarzyna); T. Huzarski (Tomasz); S. Sangrajrang (Suleeporn); V. Gaborieau (Valerie); P. Brennan (Paul); J.D. McKay (James); S. Slager (Susan); A.E. Toland (Amanda); C.B. Ambrosone (Christine); D. Yannoukakos (Drakoulis); M. Kabisch (Maria); D. Torres (Diana); S.L. Neuhausen (Susan); H. Anton-Culver (Hoda); C. Luccarini (Craig); C. Baynes (Caroline); S. Ahmed (Shahana); S. Healey (Sue); D.C. Tessier (Daniel C.); D. Vincent (Daniel); F. Bacot (Francois); G. Pita (G.); M.R. Alonso (Rosario); N. Álvarez (Nuria); D. Herrero (Daniel); J. Simard (Jacques); P.P.D.P. Pharoah (Paul P.D.P.); P. Kraft (Peter); A.M. Dunning (Alison); G. Chenevix-Trench (Georgia); P. Hall (Per); D.F. Easton (Douglas)

    2015-01-01

    textabstractGenome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS,

  5. Monocot and dicot MLO powdery mildew susceptibility factors are functionally conserved in spite of the evolution of class-specific molecular features.

    Science.gov (United States)

    Appiano, Michela; Catalano, Domenico; Santillán Martínez, Miguel; Lotti, Concetta; Zheng, Zheng; Visser, Richard G F; Ricciardi, Luigi; Bai, Yuling; Pavan, Stefano

    2015-10-26

    Specific members of the plant Mildew Locus O (MLO) protein family act as susceptibility factors towards powdery mildew (PM), a worldwide-spread fungal disease threatening many cultivated species. Previous studies indicated that monocot and dicot MLO susceptibility proteins are phylogenetically divergent. A bioinformatic approach was followed to study the type of evolution of Angiosperm MLO susceptibility proteins. Transgenic complementation tests were performed for functional analysis. Our results show that monocot and dicot MLO susceptibility proteins evolved class-specific conservation patterns. Many of them appear to be the result of negative selection and thus are likely to provide an adaptive value. We also tested whether different molecular features between monocot and dicot MLO proteins are specifically required by PM fungal species to cause pathogenesis. To this aim, we transformed a tomato mutant impaired for the endogenous SlMLO1 gene, and therefore resistant to the tomato PM species Oidium neolycopersici, with heterologous MLO susceptibility genes from the monocot barley and the dicot pea. In both cases, we observed restoration of PM symptoms. Finally, through histological observations, we demonstrate that both monocot and dicot susceptibility alleles of the MLO genes predispose to penetration of a non-adapted PM fungal species in plant epidermal cells. With this study, we provide insights on the evolution and function of MLO genes involved in the interaction with PM fungi. With respect to breeding research, we show that transgenic complementation assays involving phylogenetically distant plant species can be used for the characterization of novel MLO susceptibility genes. Moreover, we provide an overview of MLO protein molecular features predicted to play a major role in PM susceptibility. These represent ideal targets for future approaches of reverse genetics, addressed to the selection of loss-of-function resistant mutants in cultivated species.

  6. Determination of susceptibility and specific heat critical exponents for weak itinerant-electron ferromagnets from vibrating reed experiments

    Science.gov (United States)

    Balakrishnan, K.; Kaul, S. N.

    2002-04-01

    We report the observation of a linear relationship between the magnetic contribution to Young's modulus, ΔE/E0, and inverse magnetic susceptibility χ-1 for amorphous weak itinerant-electron ferromagnets Fe90Zr10 and Fe91Zr9 in the asymptotic critical region near the ferromagnetic-paramagnetic phase transition. The proportionality ΔE(T)/E0~χ-1(T) is shown to provide as accurate a means of determining the asymptotic critical exponent γ and the leading ``correction-to-scaling'' amplitudes for susceptibilty from the ΔE/E0 data as a direct measurement of magnetic susceptibilty does. Similarly, the well-known relation between the magnetic contributions to sound velocity and specific heat is fully exploited to extract accurate estimates for the universal critical amplitude ratio A+/A- and the asymptotic critical exponents α+/- for the specific heat from the sound velocity data. The presently determined values of α+/- and γ, together with the reported value for spontaneous magnetization critical exponent β, not only obey the scaling equalities α+=α- and α+2β+γ=2 but also assert that the atomic magnetic moments in the alloys in question interact with one another through an attractive interaction which decays faster than 1/r5 with the interatomic spacing, r.

  7. Leishmania major-specific B cells are necessary for Th2 cell development and susceptibility to L. major LV39 in BALB/c mice.

    Science.gov (United States)

    Ronet, Catherine; Voigt, Heike; Himmelrich, Hayo; Doucey, Marie-Agnès; Hauyon-La Torre, Yazmin; Revaz-Breton, Mélanie; Tacchini-Cottier, Fabienne; Bron, Claude; Louis, Jacques; Launois, Pascal

    2008-04-01

    B lymphocytes are considered to play a minimal role in host defense against Leishmania major. In this study, the contribution of B cells to susceptibility to infection with different strains of L. major was investigated in BALB/c mice lacking mature B cells due to the disruption of the IgM transmembrane domain (microMT). Whereas BALB/c microMT remained susceptible to infection with L. major IR173 and IR75, they were partially resistant to infection with L. major LV39. Adoptive transfer of naive B cells into BALB/c microMT mice before infection restored susceptibility to infection with L. major LV39, demonstrating a role for B cells in susceptibility to infection with this parasite. In contrast, adoptive transfer of B cells that express an IgM/IgD specific for hen egg lysozyme (HEL), an irrelevant Ag, did not restore disease progression in BALB/c microMT mice infected with L. major LV39. This finding was likely due to the inability of HEL Tg B cells to internalize and present Leishmania Ags to specific T cells. Furthermore, specific Ig did not contribute to disease progression as assessed by transfer of immune serum in BALB/c microMT mice. These data suggest that direct Ag presentation by specific B cells and not Ig effector functions is involved in susceptibility of BALB/c mice to infection with L. major LV39.

  8. Clonal complex 398 methicillin susceptible Staphylococcus aureus: a frequent unspecialized human pathogen with specific phenotypic and genotypic characteristics.

    Directory of Open Access Journals (Sweden)

    Tomasz Chroboczek

    Full Text Available Clonal complex 398 livestok-associated-MRSA (CC398 LA-MRSA clone is described as a major animal pathogen that can also colonize and infect humans. CC398 methicillin susceptible Staphylococcus aureus (CC398 MSSA is less described. We identified 126 CC398 MSSA strains of human origin within 6380 S. aureus isolates gathered between 2009 and 2011, from the French National Reference Centre for Staphylococci. They were characterized using antimicrobial susceptibility testing, spa typing, DNA microarrays (Identibac S. aureus Genotyping ®, Alere, CC398-specific sequence PCR, ermT (encoding macrolides résistance PCR. Fifty-three CC398 LA-MRSA collected from French pigs and veal were used as comparators, and phylogenetic relations between human CC398 MSSA and animal CC398 MRSA populations were explored on the basis of spa-typing and DNA microarrays. CC398 MSSA were able to induce a large spectrum of infections (especially skin, bloodstream, and pneumonias. The prevalence rate of this clone was high in MSSA population, i.e., 24.7% in a local prospective study on nasal colonization, and 7.5% in a national prospective study on infective endocarditis. CC398 MSSA isolates were frequently (89% erythromycin resistant, due to the presence of the ermT gene, a gene not detected in erythromycin resistant CC398 LA-MRSA strains. Expression of staphylococcal complement inhibitor (scn and the chemotaxis inhibitory protein (chp, was also specific to this population. The CC398 MRSA signature included also a panel of antibiotic resistance genes, especially a type IV or V cassette mec and tetM. CC398 MSSA and CC398 LA-MRSA populations were closely related based on spa-typing and DNA microarrays, with the MRSA strains forming the most derived lineage in phylogenic trees. Both MSSA and MRSA populations may come from common ancestors, which would have evolved in the settings of different selective pressures, explaining the acquisition of ermT, chp and scn for MSSA, and

  9. Glycaemic threshold for diabetes-specific retinopathy among individuals from Saudi Arabia, Algeria and Portugal

    DEFF Research Database (Denmark)

    Almdal, Thomas Peter; Handlos, Line Neerup; Vistisen, Dorte

    2014-01-01

    We studied the glycaemic threshold and prevalence of diabetic retinopathy in screen-detected diabetes in Saudi Arabia, Algeria and Portugal. The prevalence of diabetes-specific retinopathy started to increase at an HbA1c level of 6-6.4% and in individuals with HbA1c >7.0% the prevalence was 6.0%....

  10. Individually specific call feature is not used to neighbour-stranger discrimination: the corncrake case.

    Directory of Open Access Journals (Sweden)

    Michał Budka

    Full Text Available In various contexts, animals rely on acoustic signals to differentiate between conspecifics. Currently, studies examining vocal signatures use two main approaches. In the first approach, researchers search for acoustic characteristics that have the potential to be individual specific. This approach yields information on variation in signal parameters both within and between individuals and generates practical tools that can be used in population monitoring. In the second approach, playback experiments with natural calls are conducted to discern whether animals are capable of discriminating among the vocal signatures of different individuals. However, both approaches do not reveal the exact signal characteristics that are being used in the discrimination process. In this study, we tested whether an individual-specific call characteristic--namely the length of the intervals between successive maximal amplitude peaks within syllables (PPD--is crucial in neighbour-stranger discrimination by males of the nocturnal and highly secretive bird species, the corncrake (Crex crex. We conducted paired playback experiments in which corncrakes (n = 47 were exposed to artificial calls with PPD characteristics of neighbour and stranger birds. These artificial calls differed only in PPD structure. The calls were broadcast from a speaker, and we recorded the birds' behavioural responses. Although corncrakes have previously been experimentally shown to discriminate between neighbours and strangers, we found no difference in the responses to the artificial calls representing neighbours versus strangers. This finding demonstrates that even if vocal signatures are individual specific within a species, it does not automatically mean that said signatures are being crucial in discrimination among individuals. At the same time, the birds' aggressive responses to the artificial calls indicated that the information transmitted by PPDs is important in species-specific

  11. Individually specific call feature is not used to neighbour-stranger discrimination: the corncrake case.

    Science.gov (United States)

    Budka, Michał; Osiejuk, Tomasz S

    2014-01-01

    In various contexts, animals rely on acoustic signals to differentiate between conspecifics. Currently, studies examining vocal signatures use two main approaches. In the first approach, researchers search for acoustic characteristics that have the potential to be individual specific. This approach yields information on variation in signal parameters both within and between individuals and generates practical tools that can be used in population monitoring. In the second approach, playback experiments with natural calls are conducted to discern whether animals are capable of discriminating among the vocal signatures of different individuals. However, both approaches do not reveal the exact signal characteristics that are being used in the discrimination process. In this study, we tested whether an individual-specific call characteristic--namely the length of the intervals between successive maximal amplitude peaks within syllables (PPD)--is crucial in neighbour-stranger discrimination by males of the nocturnal and highly secretive bird species, the corncrake (Crex crex). We conducted paired playback experiments in which corncrakes (n = 47) were exposed to artificial calls with PPD characteristics of neighbour and stranger birds. These artificial calls differed only in PPD structure. The calls were broadcast from a speaker, and we recorded the birds' behavioural responses. Although corncrakes have previously been experimentally shown to discriminate between neighbours and strangers, we found no difference in the responses to the artificial calls representing neighbours versus strangers. This finding demonstrates that even if vocal signatures are individual specific within a species, it does not automatically mean that said signatures are being crucial in discrimination among individuals. At the same time, the birds' aggressive responses to the artificial calls indicated that the information transmitted by PPDs is important in species-specific call recognition

  12. Individual differences and specificity of prefrontal gamma frequency-tACS on fluid intelligence capabilities.

    Science.gov (United States)

    Santarnecchi, E; Muller, T; Rossi, S; Sarkar, A; Polizzotto, N R; Rossi, A; Cohen Kadosh, R

    2016-02-01

    Emerging evidence suggests that transcranial alternating current stimulation (tACS) is an effective, frequency-specific modulator of endogenous brain oscillations, with the potential to alter cognitive performance. Here, we show that reduction in response latencies to solve complex logic problem indexing fluid intelligence is obtained through 40 Hz-tACS (gamma band) applied to the prefrontal cortex. This improvement in human performance depends on individual ability, with slower performers at baseline receiving greater benefits. The effect could have not being explained by regression to the mean, and showed task and frequency specificity: it was not observed for trials not involving logical reasoning, as well as with the application of low frequency 5 Hz-tACS (theta band) or non-periodic high frequency random noise stimulation (101-640 Hz). Moreover, performance in a spatial working memory task was not affected by brain stimulation, excluding possible effects on fluid intelligence enhancement through an increase in memory performance. We suggest that such high-level cognitive functions are dissociable by frequency-specific neuromodulatory effects, possibly related to entrainment of specific brain rhythms. We conclude that individual differences in cognitive abilities, due to acquired or developmental origins, could be reduced during frequency-specific tACS, a finding that should be taken into account for future individual cognitive rehabilitation studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Genome-wide association study using the ethnicity-specific Japonica array: identification of new susceptibility loci for cold medicine-related Stevens-Johnson syndrome with severe ocular complications.

    Science.gov (United States)

    Ueta, Mayumi; Sawai, Hiromi; Shingaki, Ryosei; Kawai, Yusuke; Sotozono, Chie; Kojima, Kaname; Yoon, Kyung-Chul; Kim, Mee Kum; Seo, Kyoung Yul; Joo, Choun-Ki; Nagasaki, Masao; Kinoshita, Shigeru; Tokunaga, Katsushi

    2017-04-01

    A genome-wide association study (GWAS) for cold medicine-related Stevens-Johnson syndrome (CM-SJS) with severe ocular complications (SOC) was performed in a Japanese population. A recently developed ethnicity-specific array with genome-wide imputation that was based on the whole-genome sequences of 1070 unrelated Japanese individuals was used. Validation analysis with additional samples from Japanese individuals and replication analysis using samples from Korean individuals identified two new susceptibility loci on chromosomes 15 and 16. This study might suggest the usefulness of GWAS using the ethnicity-specific array and genome-wide imputation based on large-scale whole-genome sequences. Our findings contribute to the understanding of genetic predisposition to CM-SJS with SOC.

  14. Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study

    Science.gov (United States)

    Fisher, Diana E.; Li, Chuan-Ming; Hoffman, Howard J.; Chiu, May S.; Themann, Christa L.; Petersen, Hannes; Jonsson, Palmi V.; Jonsson, Helgi; Jonasson, Fridbert; Sverrisdottir, Johanna Eyrun; Launer, Lenore J.; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances

    2015-01-01

    Objective We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. Design Population-based cohort study. Study sample A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. Results Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. Conclusions Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women. PMID:25816699

  15. Sex-specific predictors of hearing-aid use in older persons: The age, gene/environment susceptibility - Reykjavik study.

    Science.gov (United States)

    Fisher, Diana E; Li, Chuan-Ming; Hoffman, Howard J; Chiu, May S; Themann, Christa L; Petersen, Hannes; Jonsson, Palmi V; Jonsson, Helgi; Jonasson, Fridbert; Sverrisdottir, Johanna Eyrun; Launer, Lenore J; Eiriksdottir, Gudny; Gudnason, Vilmundur; Cotch, Mary Frances

    2015-01-01

    We estimate the prevalence of hearing-aid use in Iceland and identify sex-specific factors associated with use. Population-based cohort study. A total of 5172 age, gene/environment susceptibility - Reykjavik study (AGES-RS) participants, aged 67 to 96 years (mean age 76.5 years), who completed air-conduction and pure-tone audiometry. Hearing-aid use was reported by 23.0% of men and 15.9% of women in the cohort, although among participants with at least moderate hearing loss in the better ear (pure-tone average [PTA] of thresholds at 0.5, 1, 2, and 4 kHz ≥ 35 dB hearing level [HL]) it was 49.9% and did not differ by sex. Self-reported hearing loss was the strongest predictor of hearing-aid use in men [OR: 2.68 (95% CI: 1.77, 4.08)] and women [OR: 3.07 (95% CI: 1.94, 4.86)], followed by hearing loss severity based on audiometry. Having diabetes or osteoarthritis were significant positive predictors of use in men, whereas greater physical activity and unimpaired cognitive status were important in women. Hearing-aid use was comparable in Icelandic men and women with moderate or greater hearing loss. Self-recognition of hearing loss was the factor most predictive of hearing-aid use; other influential factors differed for men and women.

  16. Gender- and ethnic-specific associations with obesity: individual and neighborhood-level factors.

    Science.gov (United States)

    Zeigler-Johnson, Charnita; Weber, Anita; Glanz, Karen; Spangler, Elaine; Rebbeck, Timothy R

    2013-01-01

    Gender- and ethnicity-specific groups face different risks for obesity, but little is understood about the factors that predict group-specific risks. We evaluated individual and neighborhood factors in relation to obesity. Cross-sectional surveys of adults (ages 18-100 years) from southeastern Pennsylvania were analyzed. Individual- and neighborhood-level factors were included in fully-adjusted regression models to estimate relationships with obesity for specific gender-ethnic groups. The study included 679 Asian women, 655 Asian men, 4190 African-American women, 1568 African-American men, 1248 Hispanic women, 586 Hispanic men, 11791 European American women, and 6547 European American men. There were significant differences in the predictors of obesity by gender-ethnic groups. Obesity was differentially associated with age (p obesity (p gender-ethnic group. Inverse neighborhood effects on obesity prevalence were observed in most groups for higher neighborhood education and family income. Direct associations with obesity were observed for neighborhood poverty and neighborhood smoking. We observed that individual- and neighborhood-level variables are associated with obesity. Several individual-level effects differ by gender-ethnic group.

  17. HSV-2 Specifically Down Regulates HLA-C Expression to Render HSV-2-Infected DCs Susceptible to NK Cell Killing

    Science.gov (United States)

    Elboim, Moran; Grodzovski, Inna; Djian, Esther; Wolf, Dana G.; Mandelboim, Ofer

    2013-01-01

    Both NK cells and CTLs kill virus-infected and tumor cells. However, the ways by which these killer cells recognize the infected or the tumorigenic cells are different, in fact almost opposite. CTLs are activated through the interaction of the TCR with MHC class I proteins. In contrast, NK cells are inhibited by MHC class I molecules. The inhibitory NK receptors recognize mainly MHC class I proteins and in this regard practically all of the HLA-C proteins are recognized by inhibitory NK cell receptors, while only certain HLA-A and HLA-B proteins interact with these receptors. Sophisticated viruses developed mechanisms to avoid the attack of both NK cells and CTLs through, for example, down regulation of HLA-A and HLA-B molecules to avoid CTL recognition, leaving HLA-C proteins on the cell surface to inhibit NK cell response. Here we provide the first example of a virus that through specific down regulation of HLA-C, harness the NK cells for its own benefit. We initially demonstrated that none of the tested HSV-2 derived microRNAs affect NK cell activity. Then we show that surprisingly upon HSV-2 infection, HLA-C proteins are specifically down regulated, rendering the infected cells susceptible to NK cell attack. We identified a motif in the tail of HLA-C that is responsible for the HSV-2-meduiated HLA-C down regulation and we show that the HLA-C down regulation is mediated by the viral protein ICP47. Finally we show that HLA-C proteins are down regulated from the surface of HSV-2 infected dendritic cells (DCs) and that this leads to the killing of DC by NK cells. Thus, we propose that HSV-2 had developed this unique and surprising NK cell-mediated killing strategy of infected DC to prevent the activation of the adaptive immunity. PMID:23555244

  18. T helper cell subsets specific for Pseudomonas aeruginosa in healthy individuals and patients with cystic fibrosis.

    Directory of Open Access Journals (Sweden)

    Hannah K Bayes

    Full Text Available We set out to determine the magnitude of antigen-specific memory T helper cell responses to Pseudomonas aeruginosa in healthy humans and patients with cystic fibrosis.Peripheral blood human memory CD4(+ T cells were co-cultured with dendritic cells that had been infected with different strains of Pseudomonas aeruginosa. The T helper response was determined by measuring proliferation, immunoassay of cytokine output, and immunostaining of intracellular cytokines.Healthy individuals and patients with cystic fibrosis had robust antigen-specific memory CD4(+ T cell responses to Pseudomonas aeruginosa that not only contained a Th1 and Th17 component but also Th22 cells. In contrast to previous descriptions of human Th22 cells, these Pseudomonal-specific Th22 cells lacked the skin homing markers CCR4 or CCR10, although were CCR6(+. Healthy individuals and patients with cystic fibrosis had similar levels of Th22 cells, but the patient group had significantly fewer Th17 cells in peripheral blood.Th22 cells specific to Pseudomonas aeruginosa are induced in both healthy individuals and patients with cystic fibrosis. Along with Th17 cells, they may play an important role in the pulmonary response to this microbe in patients with cystic fibrosis and other conditions.

  19. Effects of divorce on Dutch boys' and girls' externalizing behavior in Gene × Environment perspective: diathesis stress or differential susceptibility in the Dutch Tracking Adolescents' Individual Lives Survey study?

    Science.gov (United States)

    Nederhof, Esther; Belsky, Jay; Ormel, Johan; Oldehinkel, Albertine J

    2012-08-01

    The effects of divorce on children's behavioral development have proven to be quite varied across studies, and most developmental and family scholars today appreciate the great heterogeneity in divorce effects. Thus, this inquiry sought to determine whether select dopaminergic genes previously associated with externalizing behavior and/or found to moderate diverse environmental effects (dopamine receptors D2 and D4, catechol-O-methyltransferase) might moderate divorce effects on adolescent self-reported externalizing problems; and, if so, whether evidence of gene-environment (G × E) interaction would prove consistent with diathesis-stress or differential-susceptibility models of environmental action. Data from the first and third wave of the Dutch Tracking Adolescents' Individual Lives Survey (n = 1,134) revealed some evidence of G × E interaction reflecting diathesis-stress but not differential susceptibility. It is intriguing that some evidence pointed to "vantage sensitivity," which are benefits accruing to those with a specific genotype when their parents remained together, the exact opposite of diathesis-stress. The limits of this work are considered, especially with regard to the conditions for testing differential susceptibility, and future directions are outlined.

  20. Activity Recognition in Individuals Walking With Assistive Devices: The Benefits of Device-Specific Models

    Science.gov (United States)

    Gupta, Aakash; Deems-Dluhy, Susan; Hoppe-Ludwig, Shenan; Kording, Konrad; Jayaraman, Arun

    2017-01-01

    Background Wearable sensors gather data that machine-learning models can convert into an identification of physical activities, a clinically relevant outcome measure. However, when individuals with disabilities upgrade to a new walking assistive device, their gait patterns can change, which could affect the accuracy of activity recognition. Objective The objective of this study was to assess whether we need to train an activity recognition model with labeled data from activities performed with the new assistive device, rather than data from the original device or from healthy individuals. Methods Data were collected from 11 healthy controls as well as from 11 age-matched individuals with disabilities who used a standard stance control knee-ankle-foot orthosis (KAFO), and then a computer-controlled adaptive KAFO (Ottobock C-Brace). All subjects performed a structured set of functional activities while wearing an accelerometer on their waist, and random forest classifiers were used as activity classification models. We examined both global models, which are trained on other subjects (healthy or disabled individuals), and personal models, which are trained and tested on the same subject. Results Median accuracies of global and personal models trained with data from the new KAFO were significantly higher (61% and 76%, respectively) than those of models that use data from the original KAFO (55% and 66%, respectively) (Wilcoxon signed-rank test, P=.006 and P=.01). These models also massively outperformed a global model trained on healthy subjects, which only achieved a median accuracy of 53%. Device-specific models conferred a major advantage for activity recognition. Conclusions Our results suggest that when patients use a new assistive device, labeled data from activities performed with the specific device are needed for maximal precision activity recognition. Personal device-specific models yield the highest accuracy in such scenarios, whereas models trained on

  1. Activity Recognition in Individuals Walking With Assistive Devices: The Benefits of Device-Specific Models.

    Science.gov (United States)

    Lonini, Luca; Gupta, Aakash; Deems-Dluhy, Susan; Hoppe-Ludwig, Shenan; Kording, Konrad; Jayaraman, Arun

    2017-08-10

    Wearable sensors gather data that machine-learning models can convert into an identification of physical activities, a clinically relevant outcome measure. However, when individuals with disabilities upgrade to a new walking assistive device, their gait patterns can change, which could affect the accuracy of activity recognition. The objective of this study was to assess whether we need to train an activity recognition model with labeled data from activities performed with the new assistive device, rather than data from the original device or from healthy individuals. Data were collected from 11 healthy controls as well as from 11 age-matched individuals with disabilities who used a standard stance control knee-ankle-foot orthosis (KAFO), and then a computer-controlled adaptive KAFO (Ottobock C-Brace). All subjects performed a structured set of functional activities while wearing an accelerometer on their waist, and random forest classifiers were used as activity classification models. We examined both global models, which are trained on other subjects (healthy or disabled individuals), and personal models, which are trained and tested on the same subject. Median accuracies of global and personal models trained with data from the new KAFO were significantly higher (61% and 76%, respectively) than those of models that use data from the original KAFO (55% and 66%, respectively) (Wilcoxon signed-rank test, P=.006 and P=.01). These models also massively outperformed a global model trained on healthy subjects, which only achieved a median accuracy of 53%. Device-specific models conferred a major advantage for activity recognition. Our results suggest that when patients use a new assistive device, labeled data from activities performed with the specific device are needed for maximal precision activity recognition. Personal device-specific models yield the highest accuracy in such scenarios, whereas models trained on healthy individuals perform poorly and should not be

  2. Untangling the neurobiology of coping styles in rodents : Towards neural mechanisms underlying individual differences in disease susceptibility

    NARCIS (Netherlands)

    de Boer, Sietse F; Buwalda, Bauke; Koolhaas, Jaap M.

    Considerable individual differences exist in trait-like patterns of behavioral and physiological responses to salient environmental challenges. This individual variation in stress coping styles has an important functional role in terms of health and fitness. Hence, understanding the neural embedding

  3. Glycaemic threshold for diabetes-specific retinopathy among individuals from Saudi Arabia, Algeria and Portugal.

    Science.gov (United States)

    Almdal, T P; Handlos, L N; Valerius, M; Juul, E; Nielsen, K E; Vistisen, D; Nielsen, L B; Sheikh, A; Belhadj, M; Nadir, D; Zinai, S; Raposo, J; Lund-Andersen, H; Witte, D R

    2014-03-01

    We studied the glycaemic threshold and prevalence of diabetic retinopathy in screen-detected diabetes in Saudi Arabia, Algeria and Portugal. The prevalence of diabetes-specific retinopathy started to increase at an HbA1c level of 6-6.4% (42-47 mmol/mol) and in individuals with HbA(1c) >7.0% the prevalence was 6.0%. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  4. Assessment of Anopheles salivary antigens as individual exposure biomarkers to species-specific malaria vector bites

    Directory of Open Access Journals (Sweden)

    Ali Zakia M I

    2012-12-01

    Full Text Available Abstract Background Malaria transmission occurs during the blood feeding of infected anopheline mosquitoes concomitant with a saliva injection into the vertebrate host. In sub-Saharan Africa, most malaria transmission is due to Anopheles funestus s.s and to Anopheles gambiae s.l. (mainly Anopheles gambiae s.s. and Anopheles arabiensis. Several studies have demonstrated that the immune response against salivary antigens could be used to evaluate individual exposure to mosquito bites. The aim of this study was to assess the use of secreted salivary proteins as specific biomarkers of exposure to An. gambiae and/or An. funestus bites. Methods For this purpose, salivary gland proteins 6 (SG6 and 5′nucleotidases (5′nuc from An. gambiae (gSG6 and g-5′nuc and An. funestus (fSG6 and f-5′nuc were selected and produced in recombinant form. The specificity of the IgG response against these salivary proteins was tested using an ELISA with sera from individuals living in three Senegalese villages (NDiop, n = 50; Dielmo, n = 38; and Diama, n = 46 that had been exposed to distinct densities and proportions of the Anopheles species. Individuals who had not been exposed to these tropical mosquitoes were used as controls (Marseille, n = 45. Results The IgG responses against SG6 recombinant proteins from these two Anopheles species and against g-5′nucleotidase from An. gambiae, were significantly higher in Senegalese individuals compared with controls who were not exposed to specific Anopheles species. Conversely, an association was observed between the level of An. funestus exposure and the serological immune response levels against the f-5′nucleotidase protein. Conclusion This study revealed an Anopheles salivary antigenic protein that could be considered to be a promising antigenic marker to distinguish malaria vector exposure at the species level. The epidemiological interest of such species-specific antigenic markers is discussed.

  5. Resting-state networks predict individual differences in common and specific aspects of executive function.

    Science.gov (United States)

    Reineberg, Andrew E; Andrews-Hanna, Jessica R; Depue, Brendan E; Friedman, Naomi P; Banich, Marie T

    2015-01-01

    The goal of the present study was to examine relationships between individual differences in resting state functional connectivity as ascertained by fMRI (rs-fcMRI) and performance on tasks of executive function (EF), broadly defined as the ability to regulate thoughts and actions. Unlike most previous research that focused on the relationship between rs-fcMRI and a single behavioral measure of EF, in the current study we examined the relationship of rs-fcMRI with individual differences in subcomponents of EF. Ninety-one adults completed a resting state fMRI scan and three separate EF tasks outside the magnet: inhibition of prepotent responses, task set shifting, and working memory updating. From these three measures, we derived estimates of common aspects of EF, as well as abilities specific to working memory updating and task shifting. Using Independent Components Analysis (ICA), we identified across the group of participants several networks of regions (Resting State Networks, RSNs) with temporally correlated time courses. We then used dual regression to explore how these RSNs covaried with individual differences in EF. Dual regression revealed that increased higher common EF was associated with connectivity of a) frontal pole with an attentional RSN, and b) Crus I and II of the cerebellum with the right frontoparietal RSN. Moreover, higher shifting-specific abilities were associated with increased connectivity of angular gyrus with a ventral attention RSN. The results of the current study suggest that the organization of the brain at rest may have important implications for individual differences in EF, and that individuals higher in EF may have expanded resting state networks as compared to individuals with lower EF. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. A specific brain structural basis for individual differences in reality monitoring.

    Science.gov (United States)

    Buda, Marie; Fornito, Alex; Bergström, Zara M; Simons, Jon S

    2011-10-05

    Much recent interest has centered on understanding the relationship between brain structure variability and individual differences in cognition, but there has been little progress in identifying specific neuroanatomical bases of such individual differences. One cognitive ability that exhibits considerable variability in the healthy population is reality monitoring; the cognitive processes used to introspectively judge whether a memory came from an internal or external source (e.g., whether an event was imagined or actually occurred). Neuroimaging research has implicated the medial anterior prefrontal cortex (PFC) in reality monitoring, and here we sought to determine whether morphological variability in a specific anteromedial PFC brain structure, the paracingulate sulcus (PCS), might underlie performance. Fifty-three healthy volunteers were selected on the basis of MRI scans and classified into four groups according to presence or absence of the PCS in their left or right hemisphere. The group with absence of the PCS in both hemispheres showed significantly reduced reality monitoring performance and ability to introspect metacognitively about their performance when compared with other participants. Consistent with the prediction that sulcal absence might mean greater volume in the surrounding frontal gyri, voxel-based morphometry revealed a significant negative correlation between anterior PFC gray matter and reality monitoring performance. The findings provide evidence that individual differences in introspective abilities like reality monitoring may be associated with specific structural variability in the PFC.

  7. Eleven years of malaria surveillance in a Sudanese village highlights unexpected variation in individual disease susceptibility and outbreak severity

    DEFF Research Database (Denmark)

    Creasey, A; Giha, H; Hamad, A A

    2004-01-01

    An analysis is presented of continuous data collected over 11 years based on 1,902,600 person/days of observation on the malaria experience of the people of Daraweesh, a village in eastern Sudan. Malaria transmission is hypo-endemic: the acquisition of clinical immunity with age is not as obvious...... as in more holo-endemic areas and malaria remained a problem in all age groups throughout the study. However, this population, who are of Fulani origin, showed a distinctly variable level of disease susceptibility. Thirty-two percent of the village never reported malaria symptoms or required malaria...... an interesting question for malaria modelling in this, and in other low transmission zones, such as the burgeoning urban areas of modern Africa....

  8. Individuality in harpsichord performance: Disentangling performer- and piece-specific influences on interpretive choices

    Directory of Open Access Journals (Sweden)

    Bruno eGingras

    2013-11-01

    Full Text Available Although a growing body of research has examined issues related to individuality in music performance, few studies have attempted to quantify markers of individuality that transcend pieces and musical styles. This study aims to identify such meta-markers by discriminating between influences linked to specific pieces or interpretive goals and performer-specific playing styles, using two complementary statistical approaches: linear mixed models (LMMs to estimate fixed (piece and interpretation and random (performer effects, and similarity analyses to compare expressive profiles on a note-by-note basis across pieces and expressive parameters. Twelve professional harpsichordists recorded three pieces representative of the Baroque harpsichord repertoire, including three interpretations of one of these pieces, each emphasizing a different melodic line, on an instrument equipped with a MIDI console. Four expressive parameters were analyzed: articulation, note onset asynchrony, timing, and velocity. LMMs showed that piece-specific influences were much larger for articulation than for other parameters, for which performer-specific effects were predominant, and that piece-specific influences were generally larger than effects associated with interpretive goals. Some performers consistently deviated from the mean values for articulation and velocity across pieces and interpretations, suggesting that global measures of expressivity may in some cases constitute valid markers of artistic individuality. Similarity analyses detected significant associations among the magnitudes of the correlations between the expressive profiles of different performers. These associations were found both when comparing across parameters and within the same piece or interpretation, or on the same parameter and across pieces or interpretations. These findings suggest the existence of expressive meta-strategies that can manifest themselves across pieces, interpretive goals, or

  9. Individuality in harpsichord performance: disentangling performer- and piece-specific influences on interpretive choices.

    Science.gov (United States)

    Gingras, Bruno; Asselin, Pierre-Yves; McAdams, Stephen

    2013-01-01

    Although a growing body of research has examined issues related to individuality in music performance, few studies have attempted to quantify markers of individuality that transcend pieces and musical styles. This study aims to identify such meta-markers by discriminating between influences linked to specific pieces or interpretive goals and performer-specific playing styles, using two complementary statistical approaches: linear mixed models (LMMs) to estimate fixed (piece and interpretation) and random (performer) effects, and similarity analyses to compare expressive profiles on a note-by-note basis across pieces and expressive parameters. Twelve professional harpsichordists recorded three pieces representative of the Baroque harpsichord repertoire, including three interpretations of one of these pieces, each emphasizing a different melodic line, on an instrument equipped with a MIDI console. Four expressive parameters were analyzed: articulation, note onset asynchrony, timing, and velocity. LMMs showed that piece-specific influences were much larger for articulation than for other parameters, for which performer-specific effects were predominant, and that piece-specific influences were generally larger than effects associated with interpretive goals. Some performers consistently deviated from the mean values for articulation and velocity across pieces and interpretations, suggesting that global measures of expressivity may in some cases constitute valid markers of artistic individuality. Similarity analyses detected significant associations among the magnitudes of the correlations between the expressive profiles of different performers. These associations were found both when comparing across parameters and within the same piece or interpretation, or on the same parameter and across pieces or interpretations. These findings suggest the existence of expressive meta-strategies that can manifest themselves across pieces, interpretive goals, or expressive devices.

  10. Impact of diabetes susceptibility loci on progression from pre-diabetes to diabetes in at-risk individuals of the diabetes prevention trial-type 1 (DPT-1).

    Science.gov (United States)

    Butty, Vincent; Campbell, Christopher; Mathis, Diane; Benoist, Christophe

    2008-09-01

    The unfolding of type 1 diabetes involves a number of steps: defective immunological tolerance, priming of anti-islet autoimmunity, and destruction of insulin-producing beta-cells. A number of genetic loci contribute to susceptibility to type 1 diabetes, but it is unclear which stages of the disease are influenced by the different loci. Here, we analyzed the frequency of type 1 diabetes-risk alleles among individuals from the Diabetes Prevention Trial-Type 1 (DPT-1) clinical trial, which tested a preventive effect of insulin in at-risk relatives of diabetic individuals, all of which presented with autoimmune manifestations but only one-third of which eventually progressed to diabetes. In this study, 708 individuals randomized into DPT-1 were genotyped for 37 single nucleotide polymorphisms in diabetes susceptibility loci. Susceptibility alleles at loci expected to influence immunoregulation (PTPN22, CTLA4, and IL2RA) did not differ between progressors and nonprogressors but were elevated in both groups relative to general population frequencies, as was the INS promoter variant. In contrast, HLA DQB1*0302 and DQB1*0301 differed significantly in progressors versus nonprogressors (DQB*0302, 42.6 vs. 34.7%, P = 0.0047; DQB*0301, 8.6 vs. 14.3%, P = 0.0026). Multivariate analysis of the factors contributing to progression demonstrated that initial titers of anti-insulin autoantibodies (IAAs) could account for some (P = 0.0016) but not all of this effect on progression (P = 0.00038 for the independent effect of the number of DQB*0302 alleles). The INS-23 genotype was most strongly associated with anti-IAAs (median IAA levels in TT individuals, 60 nU/ml; AT, 121; and AA, 192; P = 0.000037) and only suggestively to the outcome of oral insulin administration. With the exception of HLA, most susceptibility loci tested condition the risk of autoimmunity rather than the risk of failed immunoregulation that results in islet destruction. Future clinical trials might consider

  11. Depot-specific differences in angiogenic capacity of adipose tissue in differential susceptibility to diet-induced obesity.

    Science.gov (United States)

    Song, Mun-Gyu; Lee, Hye-Jin; Jin, Bo-Yeong; Gutierrez-Aguilar, Ruth; Shin, Kyung-Ho; Choi, Sang-Hyun; Um, Sung Hee; Kim, Dong-Hoon

    2016-11-01

    Adipose tissue (AT) expansion requires AT remodeling, which depends on AT angiogenesis. Modulation of AT angiogenesis could have therapeutic promise for the treatment of obesity. However, it is unclear how the capacity of angiogenesis in each adipose depot is affected by over-nutrition. Therefore, we investigated the angiogenic capacity (AC) of subcutaneous and visceral fats in lean and obese mice. We compared the AC of epididymal fat (EF) and inguinal fat (IF) using an angiogenesis assay in diet-induced obese (DIO) mice and diet-resistant (DR) mice fed a high-fat diet (HFD). Furthermore, we compared the expression levels of genes related to angiogenesis, macrophage recruitment, and inflammation using RT-qPCR in the EF and IF of lean mice fed a low-fat diet (LFD), DIO mice, and DR mice fed a HFD. DIO mice showed a significant increase in the AC of EF only at 22 weeks of age compared to DR mice. The expression levels of genes related to angiogenesis, macrophage recruitment, and inflammation were significantly higher in the EF of DIO mice than in those of LFD mice and DR mice, while expression levels of genes related to macrophages and their recruitment were higher in the IF of DIO mice than in those of LFD and DR mice. Expression of genes related to angiogenesis (including Hif1a, Vegfa, Fgf1, Kdr, and Pecam1), macrophage recruitment, and inflammation (including Emr1, Ccr2, Itgax, Ccl2, Tnf, and Il1b) correlated more strongly with body weight in the EF of HFD-fed obese mice compared to that of IF. These results suggest depot-specific differences in AT angiogenesis and a potential role in the susceptibility to diet-induced obesity.

  12. Colony-specific investigations reveal highly variable responses among individual corals to ocean acidification and warming.

    Science.gov (United States)

    Kavousi, Javid; Reimer, James Davis; Tanaka, Yasuaki; Nakamura, Takashi

    2015-08-01

    As anthropogenic climate change is an ongoing concern, scientific investigations on its impacts on coral reefs are increasing. Although impacts of combined ocean acidification (OA) and temperature stress (T) on reef-building scleractinian corals have been studied at the genus, species and population levels, there are little data available on how individual corals respond to combined OA and anomalous temperatures. In this study, we exposed individual colonies of Acropora digitifera, Montipora digitata and Porites cylindrica to four pCO2-temperature treatments including 400 μatm-28 °C, 400 μatm-31 °C, 1000 μatm-28 °C and 1000 μatm-31 °C for 26 days. Physiological parameters including calcification, protein content, maximum photosynthetic efficiency, Symbiodinium density, and chlorophyll content along with Symbiodinium type of each colony were examined. Along with intercolonial responses, responses of individual colonies versus pooled data to the treatments were investigated. The main results were: 1) responses to either OA or T or their combination were different between individual colonies when considering physiological functions; 2) tolerance to either OA or T was not synonymous with tolerance to the other parameter; 3) tolerance to both OA and T did not necessarily lead to tolerance of OA and T combined (OAT) at the same time; 4) OAT had negative, positive or no impacts on physiological functions of coral colonies; and 5) pooled data were not representative of responses of all individual colonies. Indeed, the pooled data obscured actual responses of individual colonies or presented a response that was not observed in any individual. From the results of this study we recommend improving experimental designs of studies investigating physiological responses of corals to climate change by complementing them with colony-specific examinations. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Evaluation of canine-specific minocycline and doxycycline susceptibility breakpoints for meticillin-resistant Staphylococcus pseudintermedius isolates from dogs.

    Science.gov (United States)

    Hnot, Melanie L; Cole, Lynette K; Lorch, Gwendolen; Papich, Mark G; Rajala-Schultz, Paivi J; Daniels, Joshua B

    2015-10-01

    Using the US Clinical and Laboratory Standards Institute (CLSI) human tetracycline breakpoints to predict minocycline and doxycycline susceptibility of Staphylococcus pseudintermedius (SP) isolates from dogs is not appropriate because they are too high to meet pharmacokinetic/pharmacodynamic data using a standard dose. New breakpoints have been approved for doxycycline and proposed for minocycline. Revised breakpoints are four dilutions lower than tetracycline breakpoints, providing a more conservative standard for classification of isolates. The objectives of this study were to measure minimum inhibitory concentrations (MICs) of minocycline and doxycycline of 100 canine meticillin-resistant SP clinical isolates, compare their susceptibilities to minocycline and doxycycline based on current and revised standards, and document their tetracycline resistance genes. E-test strips were used to determine MICs. PCR was used to identify tet genes. Using the human tetracycline breakpoint of MIC ≤ 4 μg/mL, 76 isolates were susceptible to minocycline and 36 isolates were susceptible to doxycycline. In contrast, using the proposed minocycline breakpoint (MIC ≤ 0.25 μg/mL) and approved doxycycline breakpoint (MIC ≤ 0.125 μg/mL), 31 isolates were susceptible to both minocycline and doxycycline. Thirty-one isolates carried no tet genes, two had tet(K) and 67 had tet(M). Use of the human tetracycline breakpoints misclassified 45 and five of the isolates as susceptible to minocycline and doxycycline, respectively. PCR analysis revealed that 43 and five of the isolates classified as susceptible to minocycline and doxycycline, respectively, possessed the tetracycline resistance gene, tet(M), known to confer resistance to both drugs. These results underscore the importance of utilizing the proposed minocycline and approved doxycycline canine breakpoints in place of human tetracycline breakpoints. © 2015 ESVD and ACVD.

  14. Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.

    Science.gov (United States)

    Handisurya, Alessandra; Day, Patricia M; Thompson, Cynthia D; Bonelli, Michael; Lowy, Douglas R; Schiller, John T

    2014-08-01

    The immunocytes that regulate papillomavirus infection and lesion development in humans and animals remain largely undefined. We found that immunocompetent mice with varying H-2 haplotypes displayed asymptomatic skin infection that produced L1 when challenged with 6×1010 MusPV1 virions, the recently identified domestic mouse papillomavirus (also designated "MmuPV1"), but were uniformly resistant to MusPV1-induced papillomatosis. Broad immunosuppression with cyclosporin A resulted in variable induction of papillomas after experimental infection with a similar dose, from robust in Cr:ORL SENCAR to none in C57BL/6 mice, with lesional outgrowth correlating with early viral gene expression and partly with reported strain-specific susceptibility to chemical carcinogens, but not with H-2 haplotype. Challenge with 1×1012 virions in the absence of immunosuppression induced small transient papillomas in Cr:ORL SENCAR but not in C57BL/6 mice. Antibody-induced depletion of CD3+ T cells permitted efficient virus replication and papilloma formation in both strains, providing experimental proof for the crucial role of T cells in controlling papillomavirus infection and associated disease. In Cr:ORL SENCAR mice, immunodepletion of either CD4+ or CD8+ T cells was sufficient for efficient infection and papillomatosis, although deletion of one subset did not inhibit the recruitment of the other subset to the infected epithelium. Thus, the functional cooperation of CD4+ and CD8+ T cells is required to protect this strain. In contrast, C57BL/6 mice required depletion of both CD4+ and CD8+ T cells for infection and papillomatosis, and separate CD4 knock-out and CD8 knock-out C57BL/6 were also resistant. Thus, in C57BL/6 mice, either CD4+ or CD8+ T cell-independent mechanisms exist that can protect this particular strain from MusPV1-associated disease. These findings may help to explain the diversity of pathological outcomes in immunocompetent humans after infection with a specific

  15. Strain-specific properties and T cells regulate the susceptibility to papilloma induction by Mus musculus papillomavirus 1.

    Directory of Open Access Journals (Sweden)

    Alessandra Handisurya

    2014-08-01

    Full Text Available The immunocytes that regulate papillomavirus infection and lesion development in humans and animals remain largely undefined. We found that immunocompetent mice with varying H-2 haplotypes displayed asymptomatic skin infection that produced L1 when challenged with 6×1010 MusPV1 virions, the recently identified domestic mouse papillomavirus (also designated "MmuPV1", but were uniformly resistant to MusPV1-induced papillomatosis. Broad immunosuppression with cyclosporin A resulted in variable induction of papillomas after experimental infection with a similar dose, from robust in Cr:ORL SENCAR to none in C57BL/6 mice, with lesional outgrowth correlating with early viral gene expression and partly with reported strain-specific susceptibility to chemical carcinogens, but not with H-2 haplotype. Challenge with 1×1012 virions in the absence of immunosuppression induced small transient papillomas in Cr:ORL SENCAR but not in C57BL/6 mice. Antibody-induced depletion of CD3+ T cells permitted efficient virus replication and papilloma formation in both strains, providing experimental proof for the crucial role of T cells in controlling papillomavirus infection and associated disease. In Cr:ORL SENCAR mice, immunodepletion of either CD4+ or CD8+ T cells was sufficient for efficient infection and papillomatosis, although deletion of one subset did not inhibit the recruitment of the other subset to the infected epithelium. Thus, the functional cooperation of CD4+ and CD8+ T cells is required to protect this strain. In contrast, C57BL/6 mice required depletion of both CD4+ and CD8+ T cells for infection and papillomatosis, and separate CD4 knock-out and CD8 knock-out C57BL/6 were also resistant. Thus, in C57BL/6 mice, either CD4+ or CD8+ T cell-independent mechanisms exist that can protect this particular strain from MusPV1-associated disease. These findings may help to explain the diversity of pathological outcomes in immunocompetent humans after infection

  16. Individual differences in personality traits reflect structural variance in specific brain regions.

    Science.gov (United States)

    Gardini, Simona; Cloninger, C Robert; Venneri, Annalena

    2009-06-30

    Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals' personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.

  17. Differential susceptibility to maternal expressed emotion in children with ADHD and their siblings? Investigating plasticity genes, prosocial and antisocial behaviour

    NARCIS (Netherlands)

    Richards, Jennifer S; Hartman, Catharina A; Franke, Barbara; Hoekstra, Pieter J; Heslenfeld, Dirk J; Oosterlaan, Jaap; Arias Vásquez, Alejandro; Buitelaar, Jan K

    The differential susceptibility theory states that children differ in their susceptibility towards environmental experiences, partially due to plasticity genes. Individuals carrying specific variants in such genes will be more disadvantaged in negative but, conversely, more advantaged in positive

  18. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

    Science.gov (United States)

    Michailidou, Kyriaki; Beesley, Jonathan; Lindstrom, Sara; Canisius, Sander; Dennis, Joe; Lush, Michael; Maranian, Mel J; Bolla, Manjeet K; Wang, Qin; Shah, Mitul; Perkins, Barbara J; Czene, Kamila; Eriksson, Mikael; Darabi, Hatef; Brand, Judith S; Bojesen, Stig E; Nordestgaard, Børge G; Flyger, Henrik; Nielsen, Sune F; Rahman, Nazneen; Turnbull, Clare; Fletcher, Olivia; Peto, Julian; Gibson, Lorna; dos-Santos-Silva, Isabel; Chang-Claude, Jenny; Flesch-Janys, Dieter; Rudolph, Anja; Eilber, Ursula; Behrens, Sabine; Nevanlinna, Heli; Muranen, Taru A; Aittomäki, Kristiina; Blomqvist, Carl; Khan, Sofia; Aaltonen, Kirsimari; Ahsan, Habibul; Kibriya, Muhammad G; Whittemore, Alice S; John, Esther M; Malone, Kathleen E; Gammon, Marilie D; Santella, Regina M; Ursin, Giske; Makalic, Enes; Schmidt, Daniel F; Casey, Graham; Hunter, David J; Gapstur, Susan M; Gaudet, Mia M; Diver, W Ryan; Haiman, Christopher A; Schumacher, Fredrick; Henderson, Brian E; Le Marchand, Loic; Berg, Christine D; Chanock, Stephen; Figueroa, Jonine; Hoover, Robert N; Lambrechts, Diether; Neven, Patrick; Wildiers, Hans; van Limbergen, Erik; Schmidt, Marjanka K; Broeks, Annegien; Verhoef, Senno; Cornelissen, Sten; Couch, Fergus J; Olson, Janet E; Hallberg, Emily; Vachon, Celine; Waisfisz, Quinten; Meijers-Heijboer, Hanne; Adank, Muriel A; van der Luijt, Rob B; Li, Jingmei; Liu, Jianjun; Humphreys, Keith; Kang, Daehee; Choi, Ji-Yeob; Park, Sue K; Yoo, Keun-Young; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Tajima, Kazuo; Guénel, Pascal; Truong, Thérèse; Mulot, Claire; Sanchez, Marie; Burwinkel, Barbara; Marme, Frederik; Surowy, Harald; Sohn, Christof; Wu, Anna H; Tseng, Chiu-chen; Van Den Berg, David; Stram, Daniel O; González-Neira, Anna; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Shu, Xiao-Ou; Lu, Wei; Gao, Yu-Tang; Cai, Hui; Cox, Angela; Cross, Simon S; Reed, Malcolm WR; Andrulis, Irene L; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Lindblom, Annika; Margolin, Sara; Teo, Soo Hwang; Yip, Cheng Har; Taib, Nur Aishah Mohd; TAN, Gie-Hooi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John WM; Collée, J Margriet; Blot, William; Signorello, Lisa B; Cai, Qiuyin; Hopper, John L; Southey, Melissa C; Tsimiklis, Helen; Apicella, Carmel; Shen, Chen-Yang; Hsiung, Chia-Ni; Wu, Pei-Ei; Hou, Ming-Feng; Kristensen, Vessela N; Nord, Silje; Alnaes, Grethe I Grenaker; Giles, Graham G; Milne, Roger L; McLean, Catriona; Canzian, Federico; Trichopoulos, Dmitrios; Peeters, Petra; Lund, Eiliv; Sund, Malin; Khaw, Kay-Tee; Gunter, Marc J; Palli, Domenico; Mortensen, Lotte Maxild; Dossus, Laure; Huerta, Jose-Maria; Meindl, Alfons; Schmutzler, Rita K; Sutter, Christian; Yang, Rongxi; Muir, Kenneth; Lophatananon, Artitaya; Stewart-Brown, Sarah; Siriwanarangsan, Pornthep; Hartman, Mikael; Miao, Hui; Chia, Kee Seng; Chan, Ching Wan; Fasching, Peter A; Hein, Alexander; Beckmann, Matthias W; Haeberle, Lothar; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Stegmaier, Christa; Ashworth, Alan; Orr, Nick; Schoemaker, Minouk J; Swerdlow, Anthony J; Brinton, Louise; Garcia-Closas, Montserrat; Zheng, Wei; Halverson, Sandra L; Shrubsole, Martha; Long, Jirong; Goldberg, Mark S; Labrèche, France; Dumont, Martine; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Brauch, Hiltrud; Hamann, Ute; Brüning, Thomas; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Bernard, Loris; Bogdanova, Natalia V; Dörk, Thilo; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Devilee, Peter; Tollenaar, Robert AEM; Seynaeve, Caroline; Van Asperen, Christi J; Jakubowska, Anna; Lubinski, Jan; Jaworska, Katarzyna; Huzarski, Tomasz; Sangrajrang, Suleeporn; Gaborieau, Valerie; Brennan, Paul; McKay, James; Slager, Susan; Toland, Amanda E; Ambrosone, Christine B; Yannoukakos, Drakoulis; Kabisch, Maria; Torres, Diana; Neuhausen, Susan L; Anton-Culver, Hoda; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Healey, Catherine S; Tessier, Daniel C; Vincent, Daniel; Bacot, Francois; Pita, Guillermo; Alonso, M Rosario; Álvarez, Nuria; Herrero, Daniel; Simard, Jacques; Pharoah, Paul PDP; Kraft, Peter; Dunning, Alison M; Chenevix-Trench, Georgia; Hall, Per; Easton, Douglas F

    2015-01-01

    Genome wide association studies (GWAS) and large scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ~14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS comprising of 15,748 breast cancer cases and 18,084 controls, and 46,785 cases and 42,892 controls from 41 studies genotyped on a 200K custom array (iCOGS). Analyses were restricted to women of European ancestry. Genotypes for more than 11M SNPs were generated by imputation using the 1000 Genomes Project reference panel. We identified 15 novel loci associated with breast cancer at P<5×10−8. Combining association analysis with ChIP-Seq data in mammary cell lines and ChIA-PET chromatin interaction data in ENCODE, we identified likely target genes in two regions: SETBP1 on 18q12.3 and RNF115 and PDZK1 on 1q21.1. One association appears to be driven by an amino-acid substitution in EXO1. PMID:25751625

  19. Exploratory study on domain-specific determinants of opiate-dependent individuals' quality of life.

    Science.gov (United States)

    De Maeyer, J; Vanderplasschen, W; Lammertyn, J; van Nieuwenhuizen, C; Broekaert, E

    2011-01-01

    Studies on determinants of quality of life (QoL) among opiate-dependent individuals are scarce. Moreover, findings concerning the role of severity of drug use are inconsistent. This exploratory study investigates the association between domain-specific QoL and demographic, social, person, health and drug-related variables, and potential indirect effects of current heroin use on opiate-dependent individuals' QoL. A cohort of opiate-dependent individuals who started outpatient methadone treatment at least 5 years previously (n = 159) were interviewed about their current QoL, psychological distress, satisfaction with methadone treatment and the severity of drug-related problems using the Lancashire Quality of Life Profile, the Brief Symptom Inventory, the Verona Service Satisfaction Scale for Methadone Treatment and the EuropASI. None of the QoL domains were defined by the same compilation of determinants. No direct effect of current heroin use on QoL was retained, but path analyses demonstrated its indirect effects on the domains of 'living situation', 'finances' and 'leisure and social participation'. These findings illustrate the particularity of each QoL domain and the need for a multidimensional approach to the concept. The relationship between current heroin use and various domains of opiate-dependent individuals' QoL is complex, indirect and mediated by psychosocial and treatment-related variables. Copyright © 2011 S. Karger AG, Basel.

  20. Sex-Specific Heterogeneity in Fixed Morphological Traits Influences Individual Fitness in a Monogamous Bird Population.

    Science.gov (United States)

    Plard, Floriane; Schindler, Susanne; Arlettaz, Raphaël; Schaub, Michael

    2018-01-01

    Theoretical work has emphasized the important role of individual traits on population dynamics, but empirical models are often based on average or stage-dependent demographic rates. In this study on a monogamous bird, the Eurasian hoopoe (Upupa epops), we show how the interactions between male and female fixed and dynamic heterogeneity influence demographic rates and population dynamics. We built an integral projection model including individual sex, age, condition (reflecting dynamic heterogeneity), and fixed morphology (reflecting fixed heterogeneity). Fixed morphology was derived from a principal component analysis of six morphological traits. Our results revealed that reproductive success and survival were linked to fixed heterogeneity, whereas dynamic heterogeneity influenced mainly the timing of reproduction. Fixed heterogeneity had major consequences for the population growth rate, but interestingly, its effect on population dynamics differed between the sexes. Female fixed morphology was directly linked to annual reproductive success, whereas male fixed morphology also influenced annual survival, being twice higher in large than in small males. Even in a monogamous bird with shared parental care, large males can reach 10% higher fitness than females. Including the dynamics of male and female individual traits in population models refines our understanding of the individual mechanisms that influence demographic rates and population dynamics and can help in identifying differences in sex-specific strategies.

  1. Is it more effective group relaxation than individual to reduce anxiety in specific phobias?

    Directory of Open Access Journals (Sweden)

    Julián Carretero Román

    2009-05-01

    Full Text Available Relaxation is a standard technique used by nurses to reduce the level of anxiety. It seems that their implementation on a group can bring certain benefits compared with individual relaxation. This outline is intended to raise this hypothesis in caring for individuals diagnosed with specific phobia, by approaching the problem from the cognitive behavioural therapy perspective. In addition, it seeks to evaluate the usefulness of the nurse intervention relaxation to reduce the level of anxiety, in turn comparing the results obtained using an indicator of the scale of results NOC and the Hamilton Anxiety Scale. The phobia is a specific entity underdiagnosed, whose prevalence is about 10%. Those affected can live a really limited and debilitating, deteriorating quality of life. The community mental health nurses are in a unique position to participate in the cognitive behavioural therapy through relaxation, which will allow them to reduce the level of anxiety when people establish contact with the phobic stimulus. Methodology: quasi-experimental study in specific phobia diagnosed, 20 to 40 years old adults attending for the first time to the mental health facility derived from primary care. Both the control group as the pilot will be treated by conducted cognitive-behavioural psychotherapy individualized according to the therapeutic protocol MSC, except in terms of relaxation, which in the experimental group will be conducted at the group level. The effectiveness of treatment will be assessed with the Hamilton anxiety scale and the likert type scale of outcome indicators NOC "stress level" with 3 measurements, before starting, immediately after completing the sessions of relaxation and three months later, checking the decline in the average level of anxiety.

  2. Long-term evaluation of the antimicrobial susceptibility and microbial profile of subgingival biofilms in individuals with aggressive periodontitis

    Science.gov (United States)

    Lourenço, Talita Gomes Baêta; Heller, Débora; do Souto, Renata Martins; Silva-Senem, Mayra Xavier e; Varela, Victor Macedo; Torres, Maria Cynesia Barros; Feres-Filho, Eduardo Jorge; Colombo, Ana Paula Vieira

    2015-01-01

    This study evaluates the antimicrobial susceptibility and composition of subgingival biofilms in generalized aggressive periodontitis (GAP) patients treated using mechanical/antimicrobial therapies, including chlorhexidine (CHX), amoxicillin (AMX) and metronidazole (MET). GAP patients allocated to the placebo (C, n = 15) or test group (T, n = 16) received full-mouth disinfection with CHX, scaling and root planning, and systemic AMX (500 mg)/MET (250 mg) or placebos. Subgingival plaque samples were obtained at baseline, 3, 6, 9 and 12 months post-therapy from 3–4 periodontal pockets, and the samples were pooled and cultivated under anaerobic conditions. The minimum inhibitory concentrations (MICs) of AMX, MET and CHX were assessed using the microdilution method. Bacterial species present in the cultivated biofilm were identified by checkerboard DNA-DNA hybridization. At baseline, no differences in the MICs between groups were observed for the 3 antimicrobials. In the T group, significant increases in the MICs of CHX (p < 0.05) and AMX (p < 0.01) were detected during the first 3 months; however, the MIC of MET decreased at 12 months (p < 0.05). For several species, the MICs significantly changed over time in both groups, i.e., Streptococci MICs tended to increase, while for several periodontal pathogens, the MICs diminished. A transitory increase in the MIC of the subgingival biofilm to AMX and CHX was observed in GAP patients treated using enhanced mechanical therapy with topical CHX and systemic AMX/MET. Both protocols presented limited effects on the cultivable subgingival microbiota. PMID:26273264

  3. DNA fragile site breakage as a measure of chemical exposure and predictor of individual susceptibility to form oncogenic rearrangements.

    Science.gov (United States)

    Lehman, Christine E; Dillon, Laura W; Nikiforov, Yuri E; Wang, Yuh-Hwa

    2017-03-01

    Chromosomal rearrangements induced by non-radiation causes contribution to the majority of oncogenic fusions found in cancer. Treatment of human thyroid cells with fragile site-inducing laboratory chemicals can cause preferential DNA breakage at the RET gene and generate the RET/PTC1 rearrangement, a common driver mutation in papillary thyroid carcinomas (PTC). Here, we demonstrate that treatment with non-cytotoxic levels of environmental chemicals (benzene and diethylnitrosamine) or chemotherapeutic agents (etoposide and doxorubicin) generates significant DNA breakage within RET at levels similar to those generated by fragile site-inducing laboratory chemicals. This suggests that chronic exposure to these chemicals plays a role in the formation of non-radiation associated RET/PTC rearrangements. We also investigated whether the sensitivity of the fragile RET region could predict the likelihood of rearrangement formation using normal thyroid tissues from patients with and without RET/PTC rearrangements. We found that normal cells of patients with thyroid cancer driven by RET/PTC rearrangements have significantly higher blunt-ended, double-stranded DNA breaks at RET than those of patients without RET/PTC rearrangements. This sensitivity of a cancer driver gene suggests for the first time that a DNA breakage test at the RET region could be utilized to evaluate susceptibility to RET/PTC formation. Further, the significant increase of blunt-ended, double-stranded DNA breaks, but not other types of DNA breaks, in normal cells from patients with RET/PTC-driven tumors suggests that blunt-ended double-stranded DNA breaks are a preferred substrate for rearrangement formation, and implicate involvement of the non-homologous end joining pathway in the formation of RET/PTC rearrangements. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  4. Tomato susceptibility to Alternaria stem canker : Parameters involved in host-specific toxin-induced leaf necrosis

    NARCIS (Netherlands)

    Witsenboer, Hanneke M.A.; Kloosterziel, Karen M.; Hateboer, Guus; Nijkamp, H. John J.; Hille, Jacques

    1992-01-01

    AAL-toxin causes severe necrosis in leaves of susceptible tomato cultivars at nanomolar concentrations. In resistant tomato cultivars harbouring the semi-dominant Alternaria stem canker resistance locus necrosis is also observed, however at much higher toxin concentrations, in both lines the

  5. [Individualized unicondylar knee replacement : Use of patient-specific implants and instruments].

    Science.gov (United States)

    Arnholdt, J; Holzapfel, B M; Sefrin, L; Rudert, M; Beckmann, J; Steinert, A F

    2017-02-01

    Unicompartmental knee replacement in patients with osteoarthritis (OA) of the medial compartment. Individualized instruments and implants with a planning protocol for optimal fit. The individualized instruments and implants (ConforMIS Inc.; Burlington, MA, USA) are manufactured based on a computed tomography scan of the affected lower extremity and are provided together with a planning protocol (iView®) of the surgery. Unicompartmental OA of the knee (Kellgren & Lawrence stage IV) or Morbus Ahlbäck after unsuccessful conservative or joint preserving surgery. Bi- or tricompartmental OA, knee ligament instabilities, knee deformities >15° (varus, valgus, extension deficit). Relative contraindication: body mass index >40. Limited medial arthrotomy, identification of mechanical contact zone of the femoral condyle (linea terminalis); removal of remaining cartilage and all osteophytes that may interfere with the correct placement of the individually designed instruments. Balancing of knee in extension using patient-specific balancing chips of incremental heights. Resection of tibia with a fitted individualized tibial cutting block; confirmation of axial alignment with an extramedullary alignment tower; balancing flexion gap using spacer blocks in 90° flexion. Final femur preparation with the individual cutting instruments. Final tibial preparation with an individual drill jig for the placement of cavities fitting the cement pegs of the prosthesis. Lavage, cementing of implants in 45° of knee flexion, removal of excess cement, and wound closure. Sterile wound dressing, compressive bandage. Unlimited active/passive range of motion. Functional rehabilitation with partial weight bearing first 2 weeks, then transition to full weight bearing. Clinical/radiographic follow-up directly after surgery, at 12 and 52 weeks, then every 1-2 years. In all, 31 patients with medial OA (27 medial knee osteoarthritis, 4 osteonecrosis) were treated. Mean age 60

  6. Paradoxical lower serum triglyceride levels and higher type 2 diabetes mellitus susceptibility in obese individuals with the PNPLA3 148M variant.

    Directory of Open Access Journals (Sweden)

    Colin N A Palmer

    Full Text Available Obesity is highly associated with elevated serum triglycerides, hepatic steatosis and type 2 diabetes (T2D. The I148M (rs738409 genetic variant of patatin-like phospholipase domain-containing 3 gene (PNPLA3 is known to modulate hepatic triglyceride accumulation, leading to steatosis. No association between PNPLA3 I148M genotype and T2D in Europeans has been reported. Aim of this study is to examine the relationship between PNPLA3 I148M genotypes and serum triglycerides, insulin resistance and T2D susceptibility by testing a gene-environment interaction model with severe obesity.PNPLA3 I148M was genotyped in a large obese cohort, the SOS study (n = 3,473 and in the Go-DARTS (n = 15,448, a T2D case-control study. Metabolic parameters were examined across the PNPLA3 I148M genotypes in participants of the SOS study at baseline and at 2- and 10-year follow up after bariatric surgery or conventional therapy. The associations with metabolic parameters were validated in the Go-DARTS study. Serum triglycerides were found to be lower in the PNPLA3 148M carriers from the SOS study at baseline and from the Go-DARTS T2D cohort. An increased risk for T2D conferred by the 148M allele was found in the SOS study (O.R. 1.09, 95% C.I. 1.01-1.39, P = 0.040 and in severely obese individuals in the Go-DARTS study (O.R. 1.37, 95% C.I. 1.13-1.66, P = 0.001. The 148M allele was no longer associated with insulin resistance or T2D after bariatric surgery in the SOS study and no association with the 148M allele was observed in the less obese (BMI<35 individuals in the Go-DARTS study (P for interaction  = 0.002. This provides evidence for the obesity interaction with I48M allele and T2D risk in a large-scale cross-sectional and a prospective interventional study.Severely obese individuals carrying the PNPLA3 148M allele have lower serum triglyceride levels, are more insulin resistant and more susceptible to T2D. This study supports the hypothesis that obesity

  7. PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus.

    LENUS (Irish Health Repository)

    Bowes, John

    2015-04-28

    Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis; it has a higher estimated genetic component than psoriasis alone, however most genetic susceptibility loci identified for PsA to date are also shared with psoriasis. Here we attempt to validate novel single nucleotide polymorphisms selected from our recent PsA Immunochip study and determine specificity to PsA.

  8. Memory and language in middle childhood in individuals with a history of specific language impairment.

    Science.gov (United States)

    Hesketh, Anne; Conti-Ramsden, Gina

    2013-01-01

    This study reports on the sensitivity of sentence repetition as a marker of specific language impairment (SLI) in different subgroups of children in middle childhood and examines the role of memory and grammatical knowledge in the performance of children with and without language difficulties on this task. Eleven year old children, 197 with a history of SLI and 75 typically developing (TD) peers were administered sentence repetition, phonological short term memory (PSTM) and grammatical morphology tasks. Children with a history of SLI were divided into four subgroups: specific language impairment, non-specific language impairment, low cognition with resolved language and resolved. Performance on the sentence repetition task was significantly impaired in all four subgroups of children with a history of SLI when compared to their age peers. Regression analyses revealed grammatical knowledge was predictive of performance for TD children and children with a history of SLI. However, memory abilities were significantly predictive of sentence repetition task performance for children with a history of SLI only. Processes involved in sentence repetition are more taxing of PSTM for individuals with a history of SLI in middle childhood in a way that does not appear to be the case for TD children.

  9. VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Hsiang-Chun Lee

    2016-01-01

    Full Text Available Metabolic syndrome (MetS represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF. We hypothesized that very low density lipoproteins (VLDL in MetS (MetS-VLDL may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL, and MetS-VLDL (msVLDL groups. VLDL (15 µg/g and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 ± 0.23 mm; nVLDL, n = 7, 1.84 ± 0.13 mm; msVLDL, n = 10, 2.18 ± 0.24 mm; p < 0.0001 at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% ± 7.7%, vs. msVLDL, n = 10, 52.9% ± 9.6%; p < 0.05. Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals.

  10. Antioxidant Defense Enzyme Genes and Asthma Susceptibility: Gender-Specific Effects and Heterogeneity in Gene-Gene Interactions between Pathogenetic Variants of the Disease

    Science.gov (United States)

    Polonikov, Alexey V.; Ivanov, Vladimir P.; Bogomazov, Alexey D.; Freidin, Maxim B.; Illig, Thomas; Solodilova, Maria A.

    2014-01-01

    Oxidative stress resulting from an increased amount of reactive oxygen species and an imbalance between oxidants and antioxidants plays an important role in the pathogenesis of asthma. The present study tested the hypothesis that genetic susceptibility to allergic and nonallergic variants of asthma is determined by complex interactions between genes encoding antioxidant defense enzymes (ADE). We carried out a comprehensive analysis of the associations between adult asthma and 46 single nucleotide polymorphisms of 34 ADE genes and 12 other candidate genes of asthma in Russian population using set association analysis and multifactor dimensionality reduction approaches. We found for the first time epistatic interactions between ADE genes underlying asthma susceptibility and the genetic heterogeneity between allergic and nonallergic variants of the disease. We identified GSR (glutathione reductase) and PON2 (paraoxonase 2) as novel candidate genes for asthma susceptibility. We observed gender-specific effects of ADE genes on the risk of asthma. The results of the study demonstrate complexity and diversity of interactions between genes involved in oxidative stress underlying susceptibility to allergic and nonallergic asthma. PMID:24895604

  11. Antioxidant Defense Enzyme Genes and Asthma Susceptibility: Gender-Specific Effects and Heterogeneity in Gene-Gene Interactions between Pathogenetic Variants of the Disease

    Directory of Open Access Journals (Sweden)

    Alexey V. Polonikov

    2014-01-01

    Full Text Available Oxidative stress resulting from an increased amount of reactive oxygen species and an imbalance between oxidants and antioxidants plays an important role in the pathogenesis of asthma. The present study tested the hypothesis that genetic susceptibility to allergic and nonallergic variants of asthma is determined by complex interactions between genes encoding antioxidant defense enzymes (ADE. We carried out a comprehensive analysis of the associations between adult asthma and 46 single nucleotide polymorphisms of 34 ADE genes and 12 other candidate genes of asthma in Russian population using set association analysis and multifactor dimensionality reduction approaches. We found for the first time epistatic interactions between ADE genes underlying asthma susceptibility and the genetic heterogeneity between allergic and nonallergic variants of the disease. We identified GSR (glutathione reductase and PON2 (paraoxonase 2 as novel candidate genes for asthma susceptibility. We observed gender-specific effects of ADE genes on the risk of asthma. The results of the study demonstrate complexity and diversity of interactions between genes involved in oxidative stress underlying susceptibility to allergic and nonallergic asthma.

  12. Transcriptomics and systems biology analysis in identification of specific pathways involved in cacao resistance and susceptibility to witches' broom disease.

    Science.gov (United States)

    da Hora Junior, Braz Tavares; Poloni, Joice de Faria; Lopes, Maíza Alves; Dias, Cristiano Villela; Gramacho, Karina Peres; Schuster, Ivan; Sabau, Xavier; Cascardo, Júlio Cézar De Mattos; Mauro, Sônia Marli Zingaretti Di; Gesteira, Abelmon da Silva; Bonatto, Diego; Micheli, Fabienne

    2012-04-01

    This study reports on expression analysis associated with molecular systems biology of cacao-Moniliophthora perniciosa interaction. Gene expression data were obtained for two cacao genotypes (TSH1188, resistant; Catongo, susceptible) challenged or not with the fungus M. perniciosa and collected at three time points through disease. Using expression analysis, we identified 154 and 227 genes that are differentially expressed in TSH1188 and Catongo, respectively. The expression of some of these genes was confirmed by RT-qPCR. Physical protein-protein interaction (PPPI) networks of Arabidopsis thaliana orthologous proteins corresponding to resistant and susceptible interactions were obtained followed by cluster and gene ontology analyses. The integrated analysis of gene expression and systems biology allowed designing a general scheme of major mechanisms associated with witches' broom disease resistance/susceptibility. In this sense, the TSH1188 cultivar shows strong production of ROS and elicitors at the beginning of the interaction with M. perniciosa followed by resistance signal propagation and ROS detoxification. On the other hand, the Catongo genotype displays defense mechanisms that include the synthesis of some defense molecules but without success in regards to elimination of the fungus. This phase is followed by the activation of protein metabolism which is achieved with the production of proteasome associated with autophagy as a precursor mechanism of PCD. This work also identifies candidate genes for further functional studies and for genetic mapping and marker assisted selection.

  13. Web placement in sympatric linyphiid spiders ( Arachnida, Araneae): Individual foraging decisions reveal inter-specific competition

    Science.gov (United States)

    Herberstein, Marie Elisabeth

    1998-02-01

    The distribution of two sympatric web spiders, Frontinellina frutetorum (C. L. Koch) and Neriene radiata (Walckenaer) (Araneae: Linyphiidae) was studied on an area of forest regrowth in eastern Austria. Both species utilised significantly different heights on young conifer trees to construct their webs. F. frutetorum selected higher vegetation layers, whereas N. radiata constructed its webs, closer to the ground. This distribution may either be evidence of competition for web space or it may reflect specific distribution patterns unrelated to spider density. An experiment showed that when spiders of either species were released onto vacant trees they selected similar vegetation heights for web construction. On trees already occupied by a heterospecific individual however, F. frutetorum placed its webs significantly higher and N. radiata significantly lower compared to web placement on vacant trees suggesting that F. frutetorum and N. radiata compete for web space.

  14. DNA strand breaks in the lymphocytes of workers exposed to diisocyanates: indications of individual differences in susceptibility after low-dose and short-term exposure.

    Science.gov (United States)

    Marczynski, B; Merget, R; Mensing, T; Rabstein, S; Kappler, M; Bracht, A; Haufs, M G; Käfferlein, H U; Brüning, T

    2005-06-01

    Diisocyanates are chemically reactive and induce asthma, but data on genotoxic effects of diisocyanates in humans are limited. The investigation presented here used short term diisocyanate chamber exposure to study DNA strand breaks in lymphocytes of 10 healthy individuals and of 42 workers, with airway symptoms, who had previously been exposed to diisocyanates. The alkaline version of the Comet assay was used to analyse DNA strand breaks in lymphocytes. In addition, blood samples of 10 further control individuals without any exposure to diisocyanates were studied. Substances studied were 4,4'-methylenediphenyldiisocyanate (MDI, n=25), 2,4-toluenediisocynate and 2,6-toluenediisocyanate (TDI, n=5), and 1,6-hexamethylenediisocyanate (HDI, n=12), at concentrations between 5 and 30 ppb for 2 h. Lymphocytes isolated from the subjects before exposure and 30 min and 19 h after were used to evaluate DNA damage. No significant changes in DNA strand-break frequencies were measured, as Olive tail moment (OTM), either between groups or before and after diisocyanate exposure. OTM was similar in subjects with an asthmatic reaction (MDI, n=5; TDI, n=1; HDI, n=1) and in subjects without such a reaction. However, a small and susceptible group (about 10% of the individuals studied) could be identified with higher frequencies of DNA strand breaks in lymphocytes after chamber exposure. The occurrence of DNA damage in this group may be based on indirect mechanisms such as oxidative stress or apoptosis.

  15. The Predictive Role of Difficulties in Emotion Regulation and Self-Control with Susceptibility to Addiction in Drug-Dependent Individuals

    Directory of Open Access Journals (Sweden)

    Mahmoud Shirazi

    2015-06-01

    Full Text Available Objective: The present study aimed to examine the predictive role of difficulties in emotion regulation and self-control in potential for addiction among drug-dependent individuals. Method: This was a correlational study which falls within the category of descriptive studies. The statistical population of the current study included all patients under treatment in outpatient health centers in Bam, among whom 315 individuals were selected through cluster sampling method as the participants of the study. Difficulties in Emotion Regulation Scale, Self-Control Scale, and Addiction Susceptibility Questionnaire were used for data collection purposes. Results: The results indicated that difficulties engaging in goal directed behavior, impulse control difficulties, lack of emotional awareness, and lack of emotional clarity (dimensions of difficulties in emotion regulation had a significant positive correlation with potential for addiction. In addition, there was a negative significant relationship between self-control and potential for addiction among drug-dependent individuals. Conclusion: In addition to common methods of abstinence from drug dependence, teaching self-control and emotional control techniques to addicted patients can help them reduce their dependence.

  16. Gender-specific increase in susceptibility to metabolic syndrome of offspring rats after prenatal caffeine exposure with post-weaning high-fat diet

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jing [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Luo, Hanwen [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Wu, Yimeng; He, Zheng; Zhang, Li; Guo, Yu [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ma, Lu [Department of Epidemiology & Health Statistics, Public Health School of Wuhan University, Wuhan 430071 (China); Magdalou, Jacques [UMR 7561 CNRS-NancyUniversité, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Chen, Liaobin [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China); Wang, Hui, E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Hubei Provincial Key Laboratory of Developmentally Originated Disease, Wuhan 430071 (China)

    2015-05-01

    Prenatal caffeine exposure (PCE) alters the hypothalamic–pituitary–adrenocortical (HPA) axis-associated neuroendocrine metabolic programming and induces an increased susceptibility to metabolic syndrome (MS) in intrauterine growth retardation (IUGR) offspring rats. High-fat diet (HFD) is one of the main environmental factors accounting for the incidence of MS. In this study, we aimed to clarify the gender-specific increase in susceptibility to MS in offspring rats after PCE with post-weaning HFD. Maternal Wistar rats were administered with caffeine (120 mg/kg·d) from gestational day 11 until delivery. The offspring rats with normal diet or HFD were euthanized at postnatal week 24, and blood samples were collected. Results showed that PCE not only reduced serum adrenocorticotropic hormone (ACTH) and corticosterone levels, but also enhanced serum glucose, triglyceride and total cholesterol (TCH) concentrations in the offspring rats. Moreover, several interactions among PCE, HFD and gender were observed by a three-way ANOVA analysis. In PCE offspring, HFD could aggravate the degree of increased serum triglyceride level. Meanwhile, serum corticosterone levels of females were decreased more obviously than those of males in PCE offspring. The results also revealed interactions between HFD and gender in the levels of serum ACTH, triglyceride and TCH, which were changed more evidently in female HFD offspring. These results indicate that HFD could exacerbate the dysfunction of lipid metabolism and the susceptibility to MS induced by PCE, and the female offspring are more sensitive to HFD-induced neuroendocrine metabolic dysfunction than their male counterparts. - Highlights: • Caffeine induced HPA axis dysfunction in offspring rats fed by high-fat diet (HFD). • Caffeine induced an increased susceptibility to metabolic syndrome. • HFD aggravated susceptibility to metabolic syndrome induced by caffeine. • Female was more sensitive to HFD-induced neuroendocrine

  17. Use of Noninvasive Bone Structural Measurements to Evaluate Stress Fracture Susceptibility Among Female Recruits in U.S. Marine Corps Basic Training: Individual Profiles of Stress Fracture Susceptibility Among Female Recruits in U.S. Marine Corps Basic Training

    National Research Council Canada - National Science Library

    Shaffer, Rick

    1996-01-01

    The objective of this study was to derive predictive models of stress fracture susceptibility in female military recruits by administering a questionnaire highlighting exercise and health habits prior...

  18. Respiratory characteristics of individuals with non-specific low back pain: A cross-sectional study.

    Science.gov (United States)

    Mohan, Vikram; Paungmali, Aatit; Sitilerpisan, Patraporn; Hashim, Ummi F; Mazlan, Munifa B; Nasuha, Tuan N

    2018-02-08

    Non-specific low back pain (NS-LBP) is known to cause respiratory dysfunction. In this study, we investigated alterations in breathing, respiratory strength and endurance, core stability, diaphragm mobility, and chest expansion among patients with NS-LBP and healthy individuals. The specific aim of the study was to correlate between respiratory function and other variables among NS-LBP patients. Thirty four patients with NS-LBP were matched with 34 healthy participants before undergoing total faulty breathing scale, spirometer, respiratory pressure meter, chest expansion, ultrasound, and pressure biofeedback measurements. There were signs of faulty breathing in the NS-LBP patients when compared to the healthy participants. Diaphragmatic mobility and respiratory muscle endurance were lower in the NS-LBP group. Chest expansion exhibited a significant decrease at the level of the fourth intercostal space in the NS-LBP group, but respiratory muscle strength and core stability were not significant between the two groups. Positive correlations were found to be fairly significant regarding respiratory muscle strength. The findings of this study indicated altered respiratory characteristics in the NS-LBP patients, and suggested that they would improve through respiratory exercises. © 2018 John Wiley & Sons Australia, Ltd.

  19. Mycobacterial Cultures Contain Cell Size and Density Specific Sub-populations of Cells with Significant Differential Susceptibility to Antibiotics, Oxidative and Nitrite Stress

    Science.gov (United States)

    Vijay, Srinivasan; Nair, Rashmi Ravindran; Sharan, Deepti; Jakkala, Kishor; Mukkayyan, Nagaraja; Swaminath, Sharmada; Pradhan, Atul; Joshi, Niranjan V.; Ajitkumar, Parthasarathi

    2017-01-01

    The present study shows the existence of two specific sub-populations of Mycobacterium smegmatis and Mycobacterium tuberculosis cells differing in size and density, in the mid-log phase (MLP) cultures, with significant differential susceptibility to antibiotic, oxidative, and nitrite stress. One of these sub-populations (~10% of the total population), contained short-sized cells (SCs) generated through highly-deviated asymmetric cell division (ACD) of normal/long-sized mother cells and symmetric cell divisions (SCD) of short-sized mother cells. The other sub-population (~90% of the total population) contained normal/long-sized cells (NCs). The SCs were acid-fast stainable and heat-susceptible, and contained high density of membrane vesicles (MVs, known to be lipid-rich) on their surface, while the NCs possessed negligible density of MVs on the surface, as revealed by scanning and transmission electron microscopy. Percoll density gradient fractionation of MLP cultures showed the SCs-enriched fraction (SCF) at lower density (probably indicating lipid-richness) and the NCs-enriched fraction (NCF) at higher density of percoll fractions. While live cell imaging showed that the SCs and the NCs could grow and divide to form colony on agarose pads, the SCF, and NCF cells could independently regenerate MLP populations in liquid and solid media, indicating their full genomic content and population regeneration potential. CFU based assays showed the SCF cells to be significantly more susceptible than NCF cells to a range of concentrations of rifampicin and isoniazid (antibiotic stress), H2O2 (oxidative stress),and acidified NaNO2 (nitrite stress). Live cell imaging showed significantly higher susceptibility of the SCs of SC-NC sister daughter cell pairs, formed from highly-deviated ACD of normal/long-sized mother cells, to rifampicin and H2O2, as compared to the sister daughter NCs, irrespective of their comparable growth rates. The SC-SC sister daughter cell pairs, formed

  20. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schäfer, C.; Schwarz, E.

    2008-01-01

    AIM: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development...... of ALD in dependence on the sex of the patients. RESULTS: No significant differences between males and females with ALD were calculated for the intake (per kg body weight/day) of protein, carbohydrates, fat, and the intake (per kg body weight/day) of most micronutrients. In females with ALD, higher...

  1. Is nutrient intake a gender-specific cause for enhanced susceptibility to alcohol-induced liver disease in women?

    DEFF Research Database (Denmark)

    Wagnerberger, S.; Schafer, C.; Schwarz, E.

    2008-01-01

    Aim: Women have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations, but not in alcohol abusers. As certain micronutrients are reported to take influence on the development...... of ALD in dependence on the sex of the patients. Results: No significant differences between males and females with ALD were calculated for the intake (per kg body weight/day) of protein, carbohydrates, fat, and the intake (per kg body weight/day) of most micronutrients. In females with ALD, higher...

  2. Reduced short-term memory span in aphasia and susceptibility to interference: contribution of material-specific maintenance deficits.

    Science.gov (United States)

    Barde, Laura H F; Schwartz, Myrna F; Chrysikou, Evangelia G; Thompson-Schill, Sharon L

    2010-03-01

    Semantic short-term memory (STM) deficits have been traditionally defined as an inability to maintain semantic representations over a delay (Martin et al., 1994b). Yet some patients with semantic STM deficits make numerous intrusions of items from previously presented lists, thus presenting an interesting paradox: why should an inability to maintain semantic representations produce an increase in intrusions from earlier lists? In this study, we investigated the relationship between maintenance deficits and susceptibility to interference in a group of 20 aphasic patients characterized with weak semantic or weak phonological STM. Patients and matched control participants performed a modified item-recognition task designed to elicit semantic or phonological interference from list items located one, two, or three trials back (Hamilton & Martin, 2007). Controls demonstrated significant effects of interference in both versions of the task. Interference in patients was predicted by the type and severity of their STM deficit; that is, shorter semantic spans were associated with greater semantic interference and shorter phonological spans were associated with greater phonological interference. We interpret these results through a new perspective, the reactivation hypothesis, and we discuss their importance for accounts emphasizing the contribution of maintenance mechanisms for STM impairments in aphasia as well as susceptibility to interference. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

  3. Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C

    2009-01-01

    malaria-free period. The GM/KM allotypes of the donors were determined. RESULTS: The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly......-dependent. DISCUSSION: The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible CONCLUSIONS: The GM allotypes have significant influence......BACKGROUND: Plasmodium falciparum malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control. METHODS: In this study, 216 individuals from...

  4. A Smart Insole to Promote Healthy Aging for Frail Elderly Individuals: Specifications, Design, and Preliminary Results.

    Science.gov (United States)

    Piau, Antoine; Charlon, Yoann; Campo, Eric; Vellas, Bruno; Nourhashemi, Fati

    2015-05-25

    Older individuals frequently experience reversible "frailty syndrome,", increasing incidence of disability. Although physical exercise interventions may delay functional decline, there are difficulties in implementing them and performing seamless follow-up at home. Very few technological solutions attempt to address this challenge and improve individual participation. Our objectives are to (1) develop a technological solution designed to support active aging of frail older persons, (2) conduct a first laboratory evaluation of the device, and (3) design a multidimensional clinical trial to validate our solution. We conducted a first phase of multidisciplinary meetings to identify real end users and health professional's unmet needs, and to produce specifications for the architecture of the solution. In a second phase, we performed laboratory tests of the first proposed prototype (a smart insole) with 3 healthy volunteers. We then designed an ongoing clinical trial to finalize the multidimensional evaluation and improvement of the solution. To respond to the needs expressed by the stakeholders (frailty monitoring and adherence improvement), we developed a prototype of smart shoe insole to monitor key parameters of frailty during daily life and promote walking. It is a noninvasive wireless insole, which automatically measures gait parameters and transmits information to a remote terminal via a secure Internet connection. To ensure the solution's autonomy and transparency, we developed an original energy harvesting system, which transforms mechanical energy produced by the user's walking movement into electrical energy. The first laboratory tests of this technological solution showed good reliability measures and also a good acceptability for the users. We have planned an original iterative medical research protocol to validate our solution in real life. Our smart insole could support preventive strategies against disability in primary care by empowering the older

  5. Specific kinematics and associated muscle activation in individuals with scapular dyskinesis.

    Science.gov (United States)

    Huang, Tsun-Shun; Ou, Hsiang-Ling; Huang, Chien-Ying; Lin, Jiu-Jenq

    2015-08-01

    Knowledge of the kinematics and associated muscular activity in individuals with scapular dyskinesis may provide insight into the injury mechanism and inform the planning of treatment strategies. We investigated scapular kinematics and associated muscular activation during arm movements in individuals with scapular dyskinesis. A visual-based palpation method was used to evaluate 82 participants with unilateral shoulder pain. Scapular movements during arm raising/lowering movements were classified as abnormal single pattern (inferior angle prominence, pattern I; medial border prominence, pattern II; excessive/inadequate scapular elevation or upward rotation, pattern III), abnormal mixed patterns, or normal pattern (pattern IV). Scapular kinematics and associated muscular activation were assessed with an electromagnetic motion-capturing system and surface electromyography. More scapular internal rotation was found in pattern II subjects (4°, P = .009) and mixed pattern I and II subjects (4°, P = .023) than in control subjects during arm lowering. Scapular posterior tipping (3°, P = .028) was less in pattern I subjects during arm lowering. Higher upper trapezius activity (14%, P = .01) was found in pattern II subjects during arm lowering. In addition, lower trapezius (5%, P = .025) and serratus anterior activity (10%, P = .004) were less in mixed pattern I and II subjects during arm lowering. Specific alterations of scapular muscular activation and kinematics were found in different patterns of scapular dyskinesis. The findings also validated the use of a comprehensive classification test to assess scapular dyskinesis, especially in the lowering phase of arm elevation. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

  6. Individualized prostate biopsy strategy for Chinese patients with different prostate-specific antigen levels.

    Science.gov (United States)

    Dai, Bo; Ye, Ding-Wei; Kong, Yun-Yi; Shen, Yi-Jin; Wang, Bo-Hua

    2008-03-01

    To evaluate the best individualized prostate biopsy strategies for Chinese patients with suspected prostate cancer. The present study included 221 Chinese patients who underwent transrectal ultrasound guided prostate biopsies for the first time. All patients underwent the same 10-core biopsy protocol. In addition to the Hodge sextant technique, four more biopsies were obtained from the base and middle regions of bilateral peripheral zones. The differences between 10-core and sextant strategies in cancer detection among patients with different prostate specific antigen (PSA) levels were evaluated. The relationship between PSA level, number of positive biopsy cores and organ-confined cancer rate in prostate cancer patients was also analyzed. The overall prostate cancer detection rate was 40.7% in the 221 patients. The 10-core strategy increased cancer detection by 6.67% (6/90) in our patients (P 50 ng/mL (P sextant strategy is recommended for those with PSA > 50 ng/mL. For patients with PSA ranging from 20.1 ng/mL to 50 ng/mL, the 10-core strategy should be applied in patients with life expectancy = or > 10 years and the sextant strategy should be applied in those with life expectancy < 10 years.

  7. Improved quantification of cerebral hemodynamics using individualized time thresholds for assessment of peak enhancement parameters derived from dynamic susceptibility contrast enhanced magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Christian Nasel

    Full Text Available Assessment of cerebral ischemia often employs dynamic susceptibility contrast enhanced magnetic resonance imaging (DSC-MRI with evaluation of various peak enhancement time parameters. All of these parameters use a single time threshold to judge the maximum tolerable peak enhancement delay that is supposed to reliably differentiate sufficient from critical perfusion. As the validity of this single threshold approach still remains unclear, in this study, (1 the definition of a threshold on an individual patient-basis, nevertheless (2 preserving the comparability of the data, was investigated.The histogram of time-to-peak (TTP values derived from DSC-MRI, the so-called TTP-distribution curve (TDC, was modeled using a double-Gaussian model in 61 patients without severe cerebrovascular disease. Particular model-based zf-scores were used to describe the arterial, parenchymal and venous bolus-transit phase as time intervals Ia,p,v. Their durations (delta Ia,p,v, were then considered as maximum TTP-delays of each phase.Mean-R2 for the model-fit was 0.967. Based on the generic zf-scores the proposed bolus transit phases could be differentiated. The Ip-interval reliably depicted the parenchymal bolus-transit phase with durations of 3.4 s-10.1 s (median = 4.3s, where an increase with age was noted (∼30 ms/year.Individual threshold-adjustment seems rational since regular bolus-transit durations in brain parenchyma obtained from the TDC overlap considerably with recommended critical TTP-thresholds of 4 s-8 s. The parenchymal transit time derived from the proposed model may be utilized to individually correct TTP-thresholds, thereby potentially improving the detection of critical perfusion.

  8. Improved Quantification of Cerebral Hemodynamics Using Individualized Time Thresholds for Assessment of Peak Enhancement Parameters Derived from Dynamic Susceptibility Contrast Enhanced Magnetic Resonance Imaging

    Science.gov (United States)

    Nasel, Christian; Kalcher, Klaudius; Boubela, Roland; Moser, Ewald

    2014-01-01

    Purpose Assessment of cerebral ischemia often employs dynamic susceptibility contrast enhanced magnetic resonance imaging (DSC-MRI) with evaluation of various peak enhancement time parameters. All of these parameters use a single time threshold to judge the maximum tolerable peak enhancement delay that is supposed to reliably differentiate sufficient from critical perfusion. As the validity of this single threshold approach still remains unclear, in this study, (1) the definition of a threshold on an individual patient-basis, nevertheless (2) preserving the comparability of the data, was investigated. Methods The histogram of time-to-peak (TTP) values derived from DSC-MRI, the so-called TTP-distribution curve (TDC), was modeled using a double-Gaussian model in 61 patients without severe cerebrovascular disease. Particular model-based zf-scores were used to describe the arterial, parenchymal and venous bolus-transit phase as time intervals Ia,p,v. Their durations (delta Ia,p,v), were then considered as maximum TTP-delays of each phase. Results Mean-R2 for the model-fit was 0.967. Based on the generic zf-scores the proposed bolus transit phases could be differentiated. The Ip-interval reliably depicted the parenchymal bolus-transit phase with durations of 3.4 s–10.1 s (median = 4.3s), where an increase with age was noted (∼30 ms/year). Conclusion Individual threshold-adjustment seems rational since regular bolus-transit durations in brain parenchyma obtained from the TDC overlap considerably with recommended critical TTP-thresholds of 4 s–8 s. The parenchymal transit time derived from the proposed model may be utilized to individually correct TTP-thresholds, thereby potentially improving the detection of critical perfusion. PMID:25521121

  9. Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal.

    Science.gov (United States)

    Silva, Lindsay; Black, Rita; Michaelides, Michael; Hurd, Yasmin L; Dow-Edwards, Diana

    Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P) 29-38) male and female rats, either shipped from a supplier or born in our vivarium, to once daily injections of 3mg/kg THC. Our findings suggest that males are more sensitive to the anxiolytic and antidepressant effects of THC, as measured by the elevated plus maze (EPM) and forced swim test (FST), respectively, than females. Exposure to the FST increased plasma corticosterone levels, regardless of drug treatment or origin and females had higher levels than males overall. Shipping increased THC responses in females (acoustic startle habituation) and in males (latency to immobility in FST). No significant effects of THC or shipping on pre-pulse inhibition were observed. Due to differences in timing of puberty in males and females during the P29-38 period of THC treatment, we also dosed female rats between P21-30 (pre-puberty) and male rats between P39-48 (puberty). Pre-pubertal animals showed reductions in anxiety on the EPM, an effect that was not seen in animals treated during puberty. These results suggest that both sexes are more susceptible to changes in emotional behavior when THC exposure occurs just prior to the onset of puberty. Within the animals dosed from P29-38, THC increased cannabinoid receptor 1 (CB1R) mRNA expression and tended to decrease CP55,940 stimulated [35S]GTPγS binding in the central amygdala only of females. Therefore, early stress enhances THC responses in males (in FST) and females (ASR habituation), THC alters CB1R expression and function in females only and prepubescent rats are generally more responsive to THC than pubertal rats. In summary

  10. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study

    DEFF Research Database (Denmark)

    Smith, Colette; Sabin, Caroline A; Lundgren, Jens D

    2010-01-01

    To investigate any emerging trends in causes of death amongst HIV-positive individuals in the current cART era, and to investigate the factors associated with each specific cause of death.......To investigate any emerging trends in causes of death amongst HIV-positive individuals in the current cART era, and to investigate the factors associated with each specific cause of death....

  11. Preparative chromatography for specific δ13C isotopic analysis of individual carbohydrates in environmental samples

    Science.gov (United States)

    Nouara, Amel; Panagiotopoulos, Christos; Balesdent, Jérôme; Sempéré, Richard

    2017-04-01

    Carbohydrates are among the most abundant organic molecules on the Earth and are present in all geochemical systems. Despite their high abundance in the environment, very few studies assessed their origin using molecular carbohydrate isotopic analyses. In contrast with bulk stable isotope analysis (BSIA), which gives the isotopic signature of the entire sample without any specification about its chemical composition, compound specific 13C isotopic analysis of individual sugars (CSIA) offers valuable information about the origin of single molecules. Previous investigations used gas or liquid chromatography coupled with isotope ratio mass spectroscopy (GC-IRMS; HPLC-IRMS) for CSIA of sugars however the former requires δ13C corrections due to the carbon added to the sugar (derivatization) while the later does not provide always adequate separations among monosaccharides. Here we used cation preparative chromatography (Ca2+, Pb2+ and Na+) with refractive index detection in order to produce pure monosaccharide targets for subsequent EA-IRMS analyses. Milli-Q water was used as eluant at a flow rate 0.6 ml min-1. In general, three successive purifications (Ca2+, Pb2+, Ca2+) were sufficient to produce pure compounds. Pure monosaccharides were compared with authentic monosaccharide standards using 1H NMR and/or mass spectroscopy. The detection limit of our technique was about 1µM/sugar with a precision of 10% (n=6). Blanks run with Milli-Q water after three successive purifications resulted in carbon content of 0.13 to 2.77 µgC per collected sugar. These values are much lower than the minimum required amount (5 µgC) of the EA-IRSMS system with a precision of ± 0.35 ‰. Application of our method to environmental samples resulted in δ13C values of glucose, fructose, and levoglucosan in the range of -24 to -26 ‰ (PM10 atmospheric particles), and -15‰ to -22 ‰ for arabinose, glucose, and xylose (marine high molecular dissolved organic matter). These results fall in

  12. GABAergic neuron-specific loss of Ube3a causes Angelman syndrome-like EEG abnormalities and enhances seizure susceptibility

    Science.gov (United States)

    Judson, Matthew C.; Wallace, Michael L.; Sidorov, Michael S.; Burette, Alain C.; Gu, Bin; van Woerden, Geeske M.; King, Ian F.; Han, Ji Eun; Zylka, Mark J.; Elgersma, Ype; Weinberg, Richard J.; Philpot, Benjamin D.

    2016-01-01

    SUMMARY Loss of maternal UBE3A causes Angelman syndrome (AS), a neurodevelopmental disorder associated with severe epilepsy. We previously implicated GABAergic deficits onto layer (L) 2/3 pyramidal neurons in the pathogenesis of neocortical hyperexcitability, and perhaps epilepsy, in AS model mice. Here we investigate consequences of selective Ube3a loss from either GABAergic or glutamatergic neurons, focusing on the development of hyperexcitability within L2/3 neocortex and in broader circuit and behavioral contexts. We find that GABAergic Ube3a loss causes AS-like increases in neocortical EEG delta power, enhances seizure susceptibility, and leads to presynaptic accumulation of clathrin-coated vesicles (CCVs) – all without decreasing GABAergic inhibition onto L2/3 pyramidal neurons. Conversely, glutamatergic Ube3a loss fails to yield EEG abnormalities, seizures, or associated CCV phenotypes, despite impairing tonic inhibition onto L2/3 pyramidal neurons. These results substantiate GABAergic Ube3a loss as the principal cause of circuit hyperexcitability in AS mice, lending insight into ictogenic mechanisms in AS. PMID:27021170

  13. Biomphalaria glabrata transcriptome: cDNA microarray profiling identifies resistant- and susceptible-specific gene expression in haemocytes from snail strains exposed to Schistosoma mansoni

    Directory of Open Access Journals (Sweden)

    Rollinson David

    2008-12-01

    Full Text Available Abstract Background Biomphalaria glabrata is an intermediate snail host for Schistosoma mansoni, one of the important schistosomes infecting man. B. glabrata/S. mansoni provides a useful model system for investigating the intimate interactions between host and parasite. Examining differential gene expression between S. mansoni-exposed schistosome-resistant and susceptible snail lines will identify genes and pathways that may be involved in snail defences. Results We have developed a 2053 element cDNA microarray for B. glabrata containing clones from ORESTES (Open Reading frame ESTs libraries, suppression subtractive hybridization (SSH libraries and clones identified in previous expression studies. Snail haemocyte RNA, extracted from parasite-challenged resistant and susceptible snails, 2 to 24 h post-exposure to S. mansoni, was hybridized to the custom made cDNA microarray and 98 differentially expressed genes or gene clusters were identified, 94 resistant-associated and 4 susceptible-associated. Quantitative PCR analysis verified the cDNA microarray results for representative transcripts. Differentially expressed genes were annotated and clustered using gene ontology (GO terminology and Kyoto Encyclopaedia of Genes and Genomes (KEGG pathway analysis. 61% of the identified differentially expressed genes have no known function including the 4 susceptible strain-specific transcripts. Resistant strain-specific expression of genes implicated in innate immunity of invertebrates was identified, including hydrolytic enzymes such as cathepsin L, a cysteine proteinase involved in lysis of phagocytosed particles; metabolic enzymes such as ornithine decarboxylase, the rate-limiting enzyme in the production of polyamines, important in inflammation and infection processes, as well as scavenging damaging free radicals produced during production of reactive oxygen species; stress response genes such as HSP70; proteins involved in signalling, such as importin 7

  14. A role for impaired regulatory T cell function in adverse responses to aluminum adjuvant-containing vaccines in genetically susceptible individuals.

    Science.gov (United States)

    Terhune, Todd D; Deth, Richard C

    2014-09-08

    Regulatory T cells play a critical role in the immune response to vaccination, but there is only a limited understanding of the response of regulatory T cells to aluminum adjuvants and the vaccines that contain them. Available studies in animal models show that although induced T regulatory cells may be induced concomitantly with effector T cells following aluminum-adjuvanted vaccination, they are unable to protect against sensitization, suggesting that under the Th2 immune-stimulating effects of aluminum adjuvants, Treg cells may be functionally compromised. Allergic diseases are characterized by immune dysregulation, with increases in IL-4 and IL-6, both of which exert negative effects on Treg function. For individuals with a genetic predisposition, the beneficial influence of adjuvants on immune responsiveness may be accompanied by immune dysregulation, leading to allergic diseases. This review examines aspects of the regulatory T cell response to aluminum-adjuvanted immunization and possible genetic susceptibility factors related to that response. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults.

    Directory of Open Access Journals (Sweden)

    Marielle eYoung-Bernier

    2014-08-01

    Full Text Available Cortical plasticity, including long-term potentiation (LTP-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI, a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. Methods: SAI was first assessed by examining the modulation of motor evoked potentials (MEPs in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 HZ every 200 ms for 2 s with 8 s between trains, repeated 20 times. MEP responses (120% RMT were assessed immediately after iTBS and 5, 10, and 20 min post-application. Results: Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n=13 young and 10 older adults showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Conclusion: Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS.

  16. Short-latency afferent inhibition is a poor predictor of individual susceptibility to rTMS-induced plasticity in the motor cortex of young and older adults

    Science.gov (United States)

    Young-Bernier, Marielle; Tanguay, Annick N.; Davidson, Patrick S. R.; Tremblay, François

    2014-01-01

    Cortical plasticity, including long-term potentiation (LTP)-like plasticity, can be assessed non-invasively with repetitive transcranial magnetic stimulation (rTMS) protocols. In this study, we examined age differences in responses to intermittent theta burst stimulation (iTBS) in a group of 20 young and 18 healthy older adults. Because the cholinergic system plays a role in the neural processes underlying learning and memory, including LTP, we also investigated whether short latency afferent inhibition (SAI), a neurophysiological marker of central cholinergic activity, would be associated with age-related differences in LTP-like plasticity induced by iTBS. Methods: SAI was first assessed by examining the modulation of motor evoked potentials (MEPs) in response to median nerve conditioning 20 ms prior to TMS. Participants then underwent iTBS (3 pulses at 50 Hz every 200 ms for 2 s with 8 s between trains, repeated 20 times). MEP responses (120% resting motor threshold (RMT)) were assessed immediately after iTBS and 5, 10, and 20 min post-application. Results: Responses to iTBS were quite variable in both age groups, with only approximately 60% of the participants (n = 13 young and 10 older adults) showing the expected facilitation of MEP responses. There were no significant age group differences in MEP facilitation following iTBS. Although older adults exhibited reduced SAI, individual variations were not associated with susceptibility to express LTP-like induced plasticity after iTBS. Conclusion: Overall, these results are consistent with reports of high inter-individual variability in responses to iTBS. Although SAI was reduced in older adults, consistent with a deterioration of the cholinergic system with age, SAI levels were not associated with LTP-like plasticity as assessed with iTBS. PMID:25147523

  17. Cause-specific cardiovascular risk associated with nonsteroidal antiinflammatory drugs among healthy individuals

    DEFF Research Database (Denmark)

    Fosbøl, Emil Loldrup; Folke, Fredrik; Jacobsen, Søren

    2010-01-01

    Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals.......Studies have raised concern on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). We studied safety of NSAID therapy in a nationwide cohort of healthy individuals....

  18. Voxel-specific brain arterial input functions from dynamic susceptibility contrast MRI and blind deconvolution in a group of healthy males.

    Science.gov (United States)

    Nordli, Håkon; Taxt, Torfinn; Moen, Gunnar; Grüner, Renate

    2010-04-01

    Arterial input functions may differ between brain regions due to delay and dispersion effects in the vascular supply network. Unless corrected for, these differences may degrade quantitative estimations of cerebral blood flow in dynamic susceptibility contrast magnetic resonance perfusion imaging (DSC-MRI). To investigate in a healthy population (n=44) the properties of voxel-specific arterial input functions that were obtained using a recently published blind estimation approach. The voxel-specific arterial input functions were qualitatively and quantitatively assessed, through visual inspection or by comparing time-to-peak (delays) and peak amplitude (dispersion) values between eight regions of the brain. Furthermore, they were compared to arterial input functions selected manually in the middle cerebral artery (MCA), where normally no delay or dispersion of the contrast agent was expected. The estimated voxel-specific arterial input functions varied between brain regions. Differences in delays and dispersion were larger within one brain region among all participants than between regions in one participant. A good correlation was typically found between the estimated voxel-specific arterial input functions and the manually selected arterial input functions in the MCA region. Given knowledge of neurovascular anatomy, the current blind approach seemingly produced reasonable estimates of voxel-specific arterial input functions. In addition to potentially reducing quantification errors in DSC-MRI, these user-independent voxel-specific arterial input functions could be useful for visualizing abnormal blood supply patterns in patients.

  19. Specific mutations of penicillin-binding protein 1A in 77 clinically acquired amoxicillin-resistant Helicobacter pylori strains in comparison with 77 amoxicillin-susceptible strains.

    Science.gov (United States)

    Kwon, Yong Hwan; Kim, Ji Yeon; Kim, Nayoung; Park, Ji Hyun; Nam, Ryoung Hee; Lee, Sun Min; Kim, Jin-Wook; Kim, Jung Mogg; Park, Jong Youn; Lee, Dong Ho

    2017-08-25

    Amoxicillin (Amx) is one of the most important antibiotics for eradication of Helicobacter pylori (H. pylori). Main determinants of genetically stable Amx resistance are mutations in the C-terminus of penicillin-binding protein 1A (pbp1A). However, contribution of individual mutation remains unclear. 77 Amx-resistant (Amx(R) ) and 77 Amx-susceptible (Amx(S) ) H. pylori strains were isolated from gastric tissues, and DNA sequencing was performed to compare C-terminus sequences of pbp1A gene between Amx(R) and Amx(S) strains. Natural transformation of these mutated genes into amoxicillin-susceptible strains was performed. Among many mutations in pbp1A, D479E (OR: 37.4, 95% CI: 5.53-252.49, P < .001), and T593 mutation (OR: 32.0, 95% CI: 4.04-252.86, P < .001) independently contributed to Amx resistance in H. pylori strains. In the transformation experiment, T593 mutations were identified in their transformants showing Amx resistance. However, PCR product of D479E was not inserted into recipient (ATCC 43504) resulting in transformation failure. Amx resistance is associated with various substitutions in pbp1A and T593 mutation contributes to Amx resistance of H. pylori. © 2017 John Wiley & Sons Ltd.

  20. Comparison of individuals opting for BRCA1/2 or HNPCC genetic susceptibility testing with regard to coping, illness perceptions, illness experiences, family system characteristics and hereditary cancer distress

    NARCIS (Netherlands)

    van Oostrom, Iris; Meijers-Heijboer, Hanne; Duivenvoorden, Hugo J.; Bröcker-Vriends, Annette H. J. T.; van Asperen, Christi J.; Sijmons, Rolf H.; Seynaeve, Caroline; van Gool, Arthur R.; Klijn, Jan G. M.; Tibben, Aad

    2007-01-01

    To study differences between individuals opting for genetic cancer susceptibility testing of a known familial BRCA1/2 and HNPCC related germline mutation. Coping, illness perceptions, experiences with cancer in relatives and family system characteristics were assessed in 271 applicants for genetic

  1. Comparison of individuals opting for BRCA1/2 or HNPCC genetic susceptibility testing with regard to coping, illness perceptions, illness experiences, family system characteristics and hereditary cancer distress

    NARCIS (Netherlands)

    van Oostrom, Iris; Meijers-Heijboer, Hanne; Duivenvoorden, Hugo J.; Brocker-Vriends, Annette H. J. T.; van Asperen, Christi J.; Sijmons, Rolf H.; Seynaeve, Caroline; Van Gool, Arthur R.; Klijn, Jan G. M.; Tibben, Aad

    Objective: To study differences between individuals opting for genetic cancer susceptibility testing of a known familial BRCA1/2 and HNPCC related germline mutation. Methods: Coping, illness perceptions, experiences with cancer in relatives and family system characteristics were assessed in 271

  2. Comparison of individuals opting for BRCA1/2 or HNPCC genetic susceptibility testing with regard to coping, illness perceptions, illness experiences, family system characteristics and hereditary cancer distress.

    NARCIS (Netherlands)

    Oostrom, I.I.H. van; Meijers-Heijboer, H.; Duivenvoorden, H.J.; Brocker-Vriends, A.H.; Asperen, C.J. van; Sijmons, R.H.; Seynaeve, C.; Gool, A.R. van; Klijn, J.G.M.; Tibben, A.

    2007-01-01

    OBJECTIVE: To study differences between individuals opting for genetic cancer susceptibility testing of a known familial BRCA1/2 and HNPCC related germline mutation. METHODS: Coping, illness perceptions, experiences with cancer in relatives and family system characteristics were assessed in 271

  3. Allele-specific analysis of cell fusion-mediated pluripotent reprograming reveals distinct and predictive susceptibilities of human X-linked genes to reactivation.

    Science.gov (United States)

    Cantone, Irene; Dharmalingam, Gopuraja; Chan, Yi-Wah; Kohler, Anne-Celine; Lenhard, Boris; Merkenschlager, Matthias; Fisher, Amanda G

    2017-01-25

    Inactivation of one X chromosome is established early in female mammalian development and can be reversed in vivo and in vitro when pluripotency factors are re-expressed. The extent of reactivation along the inactive X chromosome (Xi) and the determinants of locus susceptibility are, however, poorly understood. Here we use cell fusion-mediated pluripotent reprograming to study human Xi reactivation and allele-specific single nucleotide polymorphisms (SNPs) to identify reactivated loci. We show that a subset of human Xi genes is rapidly reactivated upon re-expression of the pluripotency network. These genes lie within the most evolutionary recent segments of the human X chromosome that are depleted of LINE1 and enriched for SINE elements, predicted to impair XIST spreading. Interestingly, this cadre of genes displays stochastic Xi expression in human fibroblasts ahead of reprograming. This stochastic variability is evident between clones, by RNA-sequencing, and at the single-cell level, by RNA-FISH, and is not attributable to differences in repressive histone H3K9me3 or H3K27me3 levels. Treatment with the DNA demethylating agent 5-deoxy-azacytidine does not increase Xi expression ahead of reprograming, but instead reveals a second cadre of genes that only become susceptible to reactivation upon induction of pluripotency. Collectively, these data not only underscore the multiple pathways that contribute to maintaining silencing along the human Xi chromosome but also suggest that transcriptional stochasticity among human cells could be useful for predicting and engineering epigenetic strategies to achieve locus-specific or domain-specific human Xi gene reactivation.

  4. Individual and Contextual Parameters Associated with Adolescents' Domain Specific Self-Perceptions

    Science.gov (United States)

    Kokkinos, Constantinos M.; Hatzinikolaou, Stamatia

    2011-01-01

    The present study examined the role of adolescents' self-esteem and perceptions of family and classroom contexts on their domain specific self-perceptions. 345 Greek junior high school adolescents aged 14-16 completed measures of domain specific self-perceptions, self-esteem, parenting styles and classroom climate. Hierarchical regression analyses…

  5. CANNABIS USE BY INDIVIDUALS WITH MULTIPLE SCLEROSIS: EFFECTS ON SPECIFIC IMMUNE PARAMETERS

    Science.gov (United States)

    Sexton, Michelle; Cudaback, Eiron; Abdullah, Rehab A.; Finnell, John; Mischley, Laurie K; Rozga, Mary; Lichtman, Aron H.; Stella, Nephi

    2014-01-01

    Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS were similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective from Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study. PMID:25135301

  6. Cannabis use by individuals with multiple sclerosis: effects on specific immune parameters.

    Science.gov (United States)

    Sexton, Michelle; Cudaback, Eiron; Abdullah, Rehab A; Finnell, John; Mischley, Laurie K; Rozga, Mary; Lichtman, Aron H; Stella, Nephi

    2014-10-01

    Cannabinoids affect immune responses in ways that may be beneficial for autoimmune diseases. We sought to determine whether chronic Cannabis use differentially modulates a select number of immune parameters in healthy controls and individuals with multiple sclerosis (MS cases). Subjects were enrolled and consented to a single blood draw, matched for age and BMI. We measured monocyte migration isolated from each subject, as well as plasma levels of endocannabinoids and cytokines. Cases met definition of MS by international diagnostic criteria. Monocyte cell migration measured in control subjects and individuals with MS was similarly inhibited by a set ratio of phytocannabinoids. The plasma levels of CCL2 and IL17 were reduced in non-naïve cannabis users irrespective of the cohorts. We detected a significant increase in the endocannabinoid arachidonoylethanolamine (AEA) in serum from individuals with MS compared to control subjects, and no significant difference in levels of other endocannabinoids and signaling lipids irrespective of Cannabis use. Chronic Cannabis use may affect the immune response to similar extent in individuals with MS and control subjects through the ability of phytocannabinoids to reduce both monocyte migration and cytokine levels in serum. From a panel of signaling lipids, only the levels of AEA are increased in individuals with MS, irrespective of Cannabis use or not. Our results suggest that both MS cases and controls respond similarly to chronic Cannabis use with respect to the immune parameters measured in this study.

  7. The Type 1 Diabetes - HLA Susceptibility Interactome - Identification of HLA Genotype-Specific Disease Genes for Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, C.; Hansen, Niclas Tue; Bergholdt, R.

    2010-01-01

    Background: The individual contribution of genes in the HLA region to the risk of developing type 1 diabetes (T1D) is confounded by the high linkage disequilibrium (LD) in this region. Using a novel approach we have combined genetic association data with information on functional protein......-protein interactions to elucidate risk independent of LD and to place the genetic association into a functional context. Methodology/Principal Findings: Genetic association data from 2300 single nucleotide polymorphisms (SNPs) in the HLA region was analysed in 2200 T1D family trios divided into six risk groups based...... on HLA-DRB1 genotypes. The best SNP signal in each gene was mapped to proteins in a human protein interaction network and their significance of clustering in functional network modules was evaluated. The significant network modules identified through this approach differed between the six HLA risk groups...

  8. Individual differences in implicit motor learning: task specificity in sensorimotor adaptation and sequence learning.

    Science.gov (United States)

    Stark-Inbar, Alit; Raza, Meher; Taylor, Jordan A; Ivry, Richard B

    2017-01-01

    In standard taxonomies, motor skills are typically treated as representative of implicit or procedural memory. We examined two emblematic tasks of implicit motor learning, sensorimotor adaptation and sequence learning, asking whether individual differences in learning are correlated between these tasks, as well as how individual differences within each task are related to different performance variables. As a prerequisite, it was essential to establish the reliability of learning measures for each task. Participants were tested twice on a visuomotor adaptation task and on a sequence learning task, either the serial reaction time task or the alternating reaction time task. Learning was evident in all tasks at the group level and reliable at the individual level in visuomotor adaptation and the alternating reaction time task but not in the serial reaction time task. Performance variability was predictive of learning in both domains, yet the relationship was in the opposite direction for adaptation and sequence learning. For the former, faster learning was associated with lower variability, consistent with models of sensorimotor adaptation in which learning rates are sensitive to noise. For the latter, greater learning was associated with higher variability and slower reaction times, factors that may facilitate the spread of activation required to form predictive, sequential associations. Interestingly, learning measures of the different tasks were not correlated. Together, these results oppose a shared process for implicit learning in sensorimotor adaptation and sequence learning and provide insight into the factors that account for individual differences in learning within each task domain. We investigated individual differences in the ability to implicitly learn motor skills. As a prerequisite, we assessed whether individual differences were reliable across test sessions. We found that two commonly used tasks of implicit learning, visuomotor adaptation and the

  9. Sexual Niche Segregation and Gender-Specific Individual Specialisation in a Highly Dimorphic Marine Mammal.

    Directory of Open Access Journals (Sweden)

    Laëtitia Kernaléguen

    Full Text Available While sexual segregation is expected in highly dimorphic species, the local environment is a major factor driving the degree of resource partitioning within a population. Sexual and individual niche segregation was investigated in the Australian fur seal (Arctocephalus pusillus doriferus, which is a benthic foraging species restricted to the shallow continental shelf region of south-eastern Australia. Tracking data and the isotopic values of plasma, red blood cells and whiskers were combined to document spatial and dietary niche segregation throughout the year. Tracking data indicated that, in winter, males and females overlapped in their foraging habitat. All individuals stayed within central Bass Strait, relatively close (< 220 km to the breeding colony. Accordingly, both genders exhibited similar plasma and red cell δ13C values. However, males exhibited greater δ13C intra-individual variation along the length of their whisker than females. This suggests that males exploited a greater diversity of foraging habitats throughout the year than their female counterparts, which are restricted in their foraging grounds by the need to regularly return to the breeding colony to suckle their pup. The degree of dietary sexual segregation was also surprisingly low, both sexes exhibiting a great overlap in their δ15N values. Yet, males displayed higher δ15N values than females, suggesting they fed upon a higher proportion of higher trophic level prey. Given that males and females exploit different resources (mainly foraging habitats, the degree of individual specialisation might differ between the sexes. Higher degrees of individual specialisation would be expected in males which exploit a greater range of resources. However, comparable levels of inter-individual variation in δ15N whisker values were found in the sampled males and females, and, surprisingly, all males exhibited similar seasonal and inter-annual variation in their δ13C whisker values

  10. Driver drowsiness detection based on non-intrusive metrics considering individual specifics.

    Science.gov (United States)

    Wang, Xuesong; Xu, Chuan

    2016-10-01

    Drowsy driving is a serious highway safety problem. If drivers could be warned before they became too drowsy to drive safely, some drowsiness-related crashes could be prevented. The presentation of timely warnings, however, depends on reliable detection. To date, the effectiveness of drowsiness detection methods has been limited by their failure to consider individual differences. The present study sought to develop a drowsiness detection model that accommodates the varying individual effects of drowsiness on driving performance. Nineteen driving behavior variables and four eye feature variables were measured as participants drove a fixed road course in a high fidelity motion-based driving simulator after having worked an 8-h night shift. During the test, participants were asked to report their drowsiness level using the Karolinska Sleepiness Scale at the midpoint of each of the six rounds through the road course. A multilevel ordered logit (MOL) model, an ordered logit model, and an artificial neural network model were used to determine drowsiness. The MOL had the highest drowsiness detection accuracy, which shows that consideration of individual differences improves the models' ability to detect drowsiness. According to the results, percentage of eyelid closure, average pupil diameter, standard deviation of lateral position and steering wheel reversals was the most important of the 23 variables. The consideration of individual differences on a drowsiness detection model would increase the accuracy of the model's detection accuracy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Sex-specific and individual preferences for hunting strategies in white sharks

    NARCIS (Netherlands)

    Towner, A.V.; Leos-Barajas, V.; Langrock, R.; Schick, R.S.; Smale, M.J.; Kaschke, T.; Jewell, O.J.W; Papastamatiou, Y.P.

    2016-01-01

    1. Fine-scale predator movements may be driven by many factors including sex, habitat anddistribution of resources. There may also be individual preferences for certain movementstrategies within a population which can be hard to quantify.2. Within top predators, movements are also going to be

  12. Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer

    DEFF Research Database (Denmark)

    Zuber, Verena; Bettella, Francesco; Witoelar, Aree

    2017-01-01

    ) and applied to other diseases such as schizophrenia. Conclusions: This is the first study to evaluate the enrichment of epigenetic readers in genome-wide associations studies for SNPs within enhancers, and provides a powerful tool for enriching and prioritizing PC and BC genetic risk loci. Our study......Background: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA elements, acting to determine tissue or cell identity and driving tumor...... progression. Although previous approaches have been tried to explain risk associated with SNPs in regulatory DNA elements, so far epigenetic readers such as bromodomain containing protein 4 (BRD4) and super-enhancers have not been used to annotate SNPs. In prostate cancer (PC), androgen receptor (AR) binding...

  13. A rapid and low-cost microscopic observation drug susceptibility assay for detecting TB and MDR-TB among individuals infected by HIV in South India

    Directory of Open Access Journals (Sweden)

    S Solomon

    2013-01-01

    Full Text Available Background: The converging epidemics of HIV and tuberculosis (TB pose one of the greatest public health challenges of our time. Rapid diagnosis of TB is essential in view of its infectious nature, high burden of cases, and emergence of drug resistance. Objective: The purpose of this present study was to evaluate the feasibility of implementing the microscopic observation drug susceptibility (MODS assay, a novel assay for the diagnosis of TB and multi-drug-resistant tuberculosis (MDR-TB directly from sputum specimens, in the Indian setting. Materials and Methods: This study involved a cross-sectional, blinded assessment of the MODS assay on 1036 suspected cases of pulmonary TB in HIV-positive and HIV-negative patients against the radiometric method, BD-BACTEC TB 460 system. Results: Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of the MODS assay in detecting MTB among TB suspected patients were 89.1%, 99.1%, 94.2%, 95.8%, respectively. In addition, in the diagnosis of drug-resistant TB, the MODS assay was 84.2% sensitive for those specimens reporting MDR, 87% sensitivity for those specimens reporting INH mono-resistance, and 100% sensitive for specimens reporting RIF mono-resistance. The median time to detection of TB in the MODS assay versus BACTEC was 9 versus 21 days (P < 0.001. Conclusion: Costing 5 to 10 times lesser than the automated culture methods, the MODS assay has the potential clinical utility as a simple and rapid method. It could be effectively used as an alternative method for diagnosing TB and detection of MDR-TB in a timely and affordable way in resource-limited settings.

  14. General and species-specific transcriptional responses to downy mildew infection in a susceptible (Vitis vinifera) and a resistant (V. riparia) grapevine species

    Science.gov (United States)

    2010-01-01

    Background Downy mildew is a destructive grapevine disease caused by Plasmopara viticola (Berk. and Curt.) Berl. and de Toni, which can only be controlled by intensive fungicide treatments. Natural sources of resistance from wild grapevine (Vitis) species are used in conventional breeding approaches, but the signals and effectors involved in resistance in this important crop species are not well understood. Results Early transcriptional changes associated with P. viticola infection in susceptible V. vinifera and resistant V. riparia plants were analyzed using the Combimatrix microarray platform. Transcript levels were measured 12 and 24 h post-inoculation, reflecting the time points immediately preceding the onset of resistance in V. riparia, as determined by microscopic analysis. Our data indicate that resistance in V. riparia is induced after infection, and is not based on differences in basal gene expression between the two species. The strong and rapid transcriptional reprogramming involves the induction of pathogenesis-related proteins and enzymes required for the synthesis of phenylpropanoid-derived compounds, many of which are also induced, albeit to a lesser extent, in V. vinifera. More interestingly, resistance in V. riparia also involves the specific modulation of numerous transcripts encoding components of signal transduction cascades, hypersensitive reaction markers and genes involved in jasmonate biosynthesis. The limited transcriptional modulation in V. vinifera represents a weak attempted defense response rather than the activation of compatibility-specific pathways. Conclusions Several candidate resistance genes were identified that could be exploited in future biotechnological approaches to increase disease resistance in susceptible grapevine species. Measurements of jasmonic acid and methyl jasmonate in infected leaves suggest that this hormone may also be involved in V. riparia resistance to P. viticola. PMID:20167053

  15. Emergence of a Homo sapiens-specific gene family and chromosome 16p11.2 CNV susceptibility.

    Science.gov (United States)

    Nuttle, Xander; Giannuzzi, Giuliana; Duyzend, Michael H; Schraiber, Joshua G; Narvaiza, Iñigo; Sudmant, Peter H; Penn, Osnat; Chiatante, Giorgia; Malig, Maika; Huddleston, John; Benner, Chris; Camponeschi, Francesca; Ciofi-Baffoni, Simone; Stessman, Holly A F; Marchetto, Maria C N; Denman, Laura; Harshman, Lana; Baker, Carl; Raja, Archana; Penewit, Kelsi; Janke, Nicolette; Tang, W Joyce; Ventura, Mario; Banci, Lucia; Antonacci, Francesca; Akey, Joshua M; Amemiya, Chris T; Gage, Fred H; Reymond, Alexandre; Eichler, Evan E

    2016-08-11

    Genetic differences that specify unique aspects of human evolution have typically been identified by comparative analyses between the genomes of humans and closely related primates, including more recently the genomes of archaic hominins. Not all regions of the genome, however, are equally amenable to such study. Recurrent copy number variation (CNV) at chromosome 16p11.2 accounts for approximately 1% of cases of autism and is mediated by a complex set of segmental duplications, many of which arose recently during human evolution. Here we reconstruct the evolutionary history of the locus and identify bolA family member 2 (BOLA2) as a gene duplicated exclusively in Homo sapiens. We estimate that a 95-kilobase-pair segment containing BOLA2 duplicated across the critical region approximately 282 thousand years ago (ka), one of the latest among a series of genomic changes that dramatically restructured the locus during hominid evolution. All humans examined carried one or more copies of the duplication, which nearly fixed early in the human lineage--a pattern unlikely to have arisen so rapidly in the absence of selection (P sapiens-specific duplication. In summary, the duplicative transposition of BOLA2 at the root of the H. sapiens lineage about 282 ka simultaneously increased copy number of a gene associated with iron homeostasis and predisposed our species to recurrent rearrangements associated with disease.

  16. Activity Recognition in Individuals Walking With Assistive Devices: The Benefits of Device-Specific Models

    OpenAIRE

    Lonini, Luca; Gupta, Aakash; Deems-Dluhy, Susan; Hoppe-Ludwig, Shenan; Kording, Konrad; Jayaraman, Arun

    2017-01-01

    Background Wearable sensors gather data that machine-learning models can convert into an identification of physical activities, a clinically relevant outcome measure. However, when individuals with disabilities upgrade to a new walking assistive device, their gait patterns can change, which could affect the accuracy of activity recognition. Objective The objective of this study was to assess whether we need to train an activity recognition model with labeled data from activities performed wit...

  17. Workplace accommodations and unmet needs specific to individuals who are deaf or hard of hearing.

    Science.gov (United States)

    Haynes, Scott; Linden, Maureen

    2012-09-01

    The purpose of this paper is to identify the workplace accommodations used by individuals who are deaf or hard of hearing, to report the perceived impact of the accommodations and to identify unmet needs with respect to workplace accommodations. Individuals who are deaf or hard of hearing participated in an online survey. Respondents identified with one of four levels of functional hearing ability and selected from descriptions of workplace accommodations. Each selection was ranked according to perceived importance, satisfaction and frequency of use. Respondents also commented on unmet needs. The most common accommodations were telephone aids (55%), co-worker helps (34%) and electronic communication (31%). Importance and frequency of use ranked high among most respondents (76% and 87%, respectively). However, perceived satisfaction ranked high among only 50% of respondents. The most common unmet needs were effective communication in groups and lack of co-worker support. Workplace accommodations are viewed as important and frequently used by individuals who are deaf or hard of hearing. However, satisfaction with the accommodations is marginal at best. Unmet needs remain in the areas of communication in meetings, support of co-workers and the development of a more universally accessible workplace environment.

  18. Intra-individual gait pattern variability in specific situations: Implications for forensic gait analysis.

    Science.gov (United States)

    Ludwig, Oliver; Dillinger, Steffen; Marschall, Franz

    2016-07-01

    In this study, inter- and intra-individual gait pattern differences are examined in various gait situations by means of phase diagrams of the extremity angles (cyclograms). 8 test subjects walked along a walking distance of 6m under different conditions three times each: barefoot, wearing sneakers, wearing combat boots, after muscular fatigue, and wearing a full-face motorcycle helmet restricting vision. The joint angles of foot, knee, and hip were recorded in the sagittal plane. The coupling of movements was represented by time-adjusted cyclograms, and the inter- and intra-individual differences were captured by calculating the similarity between different gait patterns. Gait pattern variability was often greater between the defined test situations than between the individual test subjects. The results have been interpreted considering neurophysiological regulation mechanisms. Footwear, masking, and fatigue were interpreted as disturbance parameters, each being a cause for gait pattern variability and complicating the inference of identity of persons in video recordings. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  19. A clinical assessment of cochlear implant recipient performance: implications for individualized map settings in specific environments.

    Science.gov (United States)

    Hey, Matthias; Hocke, Thomas; Mauger, Stefan; Müller-Deile, Joachim

    2016-11-01

    Individual speech intelligibility was measured in quiet and noise for cochlear Implant recipients upgrading from the Freedom to the CP900 series sound processor. The postlingually deafened participants (n = 23) used either Nucleus CI24RE or CI512 cochlear implant, and currently wore a Freedom sound processor. A significant group mean improvement in speech intelligibility was found in quiet (Freiburg monosyllabic words at 50 dBSPL) and in noise (adaptive Oldenburger sentences in noise) for the two CP900 series SmartSound programs compared to the Freedom program. Further analysis was carried out on individual's speech intelligibility outcomes in quiet and in noise. Results showed a significant improvement or decrement for some recipients when upgrading to the new programs. To further increase speech intelligibility outcomes when upgrading, an enhanced upgrade procedure is proposed that includes additional testing with different signal-processing schemes. Implications of this research are that future automated scene analysis and switching technologies could provide additional performance improvements by introducing individualized scene-dependent settings.

  20. Quality of life assessment in laryngectomized individuals: do we need additions to standard questionnaires in specific clinical research projects?

    NARCIS (Netherlands)

    Op de Coul, B. M. R.; Ackerstaff, A. H.; van As, C. J.; van den Hoogen, F. J. A.; Meeuwis, C. A.; Manni, J. J.; Hilgers, F. J. M.

    2005-01-01

    To assess, whether the EORTC questionnaires QLQ-C30 and QLQ-H&N35 give enough detailed information to study specific quality of life (QoL) related issues in laryngectomized individuals. Multicentre, prospective clinical trial; baseline measurement with EORTC questionnaires and an additional

  1. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.

    Directory of Open Access Journals (Sweden)

    Terje Raudsepp

    Full Text Available Impaired acrosomal reaction (IAR of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (PA and g.11040379C>A (p.166H>N in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44 and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.

  2. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.

    Science.gov (United States)

    Raudsepp, Terje; McCue, Molly E; Das, Pranab J; Dobson, Lauren; Vishnoi, Monika; Fritz, Krista L; Schaefer, Robert; Rendahl, Aaron K; Derr, James N; Love, Charles C; Varner, Dickson D; Chowdhary, Bhanu P

    2012-01-01

    Impaired acrosomal reaction (IAR) of sperm causes male subfertility in humans and animals. Despite compelling evidence about the genetic control over acrosome biogenesis and function, the genomics of IAR is as yet poorly understood, providing no molecular tools for diagnostics. Here we conducted Equine SNP50 Beadchip genotyping and GWAS using 7 IAR-affected and 37 control Thoroughbred stallions. A significant (Phorse chromosome 13 in FK506 binding protein 6 (FKBP6). The gene belongs to the immunophilins FKBP family known to be involved in meiosis, calcium homeostasis, clathrin-coated vesicles, and membrane fusions. Direct sequencing of FKBP6 exons in cases and controls identified SNPs g.11040315G>A and g.11040379C>A (p.166H>N) in exon 4 that were significantly associated with the IAR phenotype both in the GWAS cohort (n = 44) and in a large multi-breed cohort of 265 horses. All IAR stallions were homozygous for the A-alleles, while this genotype was found only in 2% of controls. The equine FKBP6 was exclusively expressed in testis and sperm and had 5 different transcripts, of which 4 were novel. The expression of this gene in AC/AG heterozygous controls was monoallelic, and we observed a tendency for FKBP6 up-regulation in IAR stallions compared to controls. Because exon 4 SNPs had no effect on the protein structure, it is likely that FKBP6 relates to the IAR phenotype via regulatory or modifying functions. In conclusion, FKBP6 was considered a susceptibility gene of incomplete penetrance for IAR in stallions and a candidate gene for male subfertility in mammals. FKBP6 genotyping is recommended for the detection of IAR-susceptible individuals among potential breeding stallions. Successful use of sperm as a source of DNA and RNA propagates non-invasive sample procurement for fertility genomics in animals and humans.

  3. A NOVel ELISPOT assay to quantify HLA-specific B cells in HLA-immunized individuals

    NARCIS (Netherlands)

    Heidt, S.; Roelen, D.L.; Vaal, Y.J. de; Kester, M.G.; Eijsink, C.; Thomas, S.; Besouw, N.M. van; Volk, H.D.; Weimar, W.; Claas, F.H.; Mulder, A.

    2012-01-01

    Quantification of the humoral alloimmune response is generally achieved by measuring serum HLA antibodies, which provides no information about the cells involved in the humoral immune response. Therefore, we have developed an HLA-specific B-cell ELISPOT assay allowing for quantification of B cells

  4. Individual differences in cognitive reappraisal usage modulate the time course of brain activation during symptom provocation in specific phobia

    Science.gov (United States)

    2013-01-01

    Background Extinction learning is proposed to be one key mechanism of action underlying exposure-based cognitive-behavioral therapy (CBT) in specific phobia. Beyond that, cognitive reappraisal, one important strategy to regulate negative emotions, is a crucial component of CBT interventions, but has been disregarded in previous studies investigating neural change processes in specific phobia. The aim of this study was to investigate the association of individual differences in habitual/dispositional cognitive reappraisal usage and the time course of brain activation during phobic stimulation in specific phobia. Methods Dental phobic patients and healthy control subjects participated in a functional magnetic resonance imaging (fMRI) study whilst being confronted with phobic, disgust, fear and neutral pictures. Individual differences in cognitive reappraisal usage were assessed via a self-report questionnaire and correlated with activation decreases over the course of time. Results Phobic individuals with higher dispositional cognitive reappraisal scores showed a more pronounced activation decline in the right dorsomedial prefrontal cortex (dmPFC) which might be associated with a diminution of explicit cognitive emotion regulation over the course of time. Less decrease of activation in the right ventromedial prefrontal cortex (vmPFC) and the lateral orbitofrontal cortex (lOFC) over time in subjects with higher cognitive reappraisal scores might be related to a stronger automatic regulation of emotions or even emotional relearning. Additionally, phobic subjects compared with healthy controls showed a stronger habituation of the left dmPFC over the course of symptom provocation. Conclusions The results of this study show for the first time that individual differences in cognitive reappraisal usage are associated with the time course of brain activation during symptom provocation in specific phobia. Additionally, the present study gives first indications for the

  5. Visualization of specific gene expression in individual Salmonella typhimurium cells by in situ PCR

    DEFF Research Database (Denmark)

    Tolker-Nielsen, Tim; Holmstrøm, Kim; Molin, Søren

    1997-01-01

    lac mRNA in suboptimally isopropyl-beta-D-thiogalactopyranoside-induced cells was investigated. By use of a single-cell beta-galactosidase assay, it was confirmed that homogeneous suboptimally induced cultures of S. typhimurium F' lacY cells could be established, and the number of functional lac m......RNAs in individual cells was estimated from standard population level beta-galactosidase assays, Cells estimated to contain a single lac mRNA were detected as containing lac mRNA by the in situ PCR method. Conclusively, we demonstrate the potential of in situ PCR for detection of even poorly expressed m...

  6. Inherited susceptibility and radiation exposure

    Energy Technology Data Exchange (ETDEWEB)

    Little, J.B. [Harvard School of Public Health, Boston, MA (United States)

    1997-03-01

    There is continuing concern that some people in the general population may have genetic makeups that place them at particularly high risk for radiation-induced cancer. The existence of such a susceptible subpopulation would have obvious implications for the estimation of risks of radiation exposure. Although it has been long known that familial aggregations of cancer do sometimes occur, recent evidence suggests that a general genetic predisposition to cancer does not exist; most cancers occur sporadically. On the other hand, nearly 10% of the known Mendelian genetic disorders are associated with cancer. A number of these involve a familial predisposition to cancer, and some are characterized by an enhanced susceptibility to the induction of cancer by various physical and chemical carcinogens, including ionizing radiation. Such increased susceptibility will depend on several factors including the frequency of the susceptibility gene in the population and its penetrance, the strength of the predisposition, and the degree to which the cancer incidence in susceptible individuals may be increased by the carcinogen. It is now known that these cancer-predisposing genes may be responsible not only for rare familial cancer syndromes, but also for a proportion of the common cancers. Although the currently known disorders can account for only a small fraction of all cancers, they serve as models for genetic predisposition to carcinogen-induced cancer in the general population. In the present report, the author describes current knowledge of those specific disorders that are associated with an enhanced predisposition to radiation-induced cancer, and discusses how this knowledge may bear on the susceptibility to radiation-induced cancer in the general population and estimates of the risk of radiation exposure.

  7. Individual and contextual parameters associated with adolescents' domain specific self-perceptions.

    Science.gov (United States)

    Kokkinos, Constantinos M; Hatzinikolaou, Stamatia

    2011-04-01

    The present study examined the role of adolescents' self-esteem and perceptions of family and classroom contexts on their domain specific self-perceptions. 345 Greek junior high school adolescents aged 14-16 completed measures of domain specific self-perceptions, self-esteem, parenting styles and classroom climate. Hierarchical regression analyses revealed that both family and classroom contexts predicted students' self-perceptions, after students' demographics, academic achievement and self-esteem were controlled for. However, different patterns emerged in the relationship between family, classroom climate and self-esteem depending on domain specific self-perceptions. Academic self-perceptions (scholastic, mathematics and language competences) were predicted by classroom climate dimensions (order and organization, student involvement, rule clarity), whereas self-perceptions regarding relations with parents, close friends and behaviour conduct, were predicted by parenting styles. Given the fact that adolescence is a period of fluctuation in self-understanding which renders self-perceptions particularly malleable, the results support the critical role of the social environments where adolescents operate. Copyright © 2010 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

  8. [Antifungal susceptibility profiles of Candida species to triazole: application of new CLSI species-specific clinical breakpoints and epidemiological cutoff values for characterization of antifungal resistance].

    Science.gov (United States)

    Karabıçak, Nilgün; Alem, Nihal

    2016-01-01

    The Clinical and Laboratory Standards Institute (CLSI) Subcommittee on Antifungal Susceptibility Testing has newly introduced species-specific clinical breakpoints (CBPs) for fluconazole and voriconazole. When CBPs can not be determined, wild-type minimal inhibitory concentration (MIC) distributions are detected and epidemiological cutoff values (ECVs) provide valuable means for the detection of emerging resistance. The aim of this study is to determine triazole resistance patterns in Candida species by the recently revised CLSI CBPs. A total of 140 Candida strains isolated from blood cultures of patients with invasive candidiasis hospitalized in various intensive care units in Turkey and sent to our reference laboratory between 2011-2012, were included in the study. The isolates were identified by conventional methods, and susceptibility testing was performed against fluconazole, itraconazole and voriconazole, by the 24-h CLSI broth microdilution (BMD) method. Azole resistance rates for all Candida species were determined using the new species-specific CLSI CBPs and ECVs criteria, when appropriate. The species distribution of the isolates were as follows; C.parapsilosis (n= 31 ), C.tropicalis (n= 26 ), C.glabrata (n= 21), C.albicans (n= 18), C.lusitaniae (n= 16), C.krusei (n= 16), C.kefyr (n= 9), C.guilliermondii (n= 2), and C.dubliniensis (n= 1). According to the newly determined CLSI CBPs for fluconazole and C.albicans, C.parapsilosis, C.tropicalis [susceptible (S), ≤ 2 µg/ml; dose-dependent susceptible (SDD), 4 µg/ml; resistant (R), ≥ 8 µg/ml], and C.glabrata (SDD, ≤ 32 µg/ml; R≥ 64 µg/ml) and for voriconazole and C.albicans, C.parapsilosis, C.tropicalis (S, ≤ 0.12 µg/ml; SDD, 0.25-0.5 µg/ml; R, ≥ 1 µg/ml), and C.krusei (S, ≤ 0.5 µg/ml; SDD, 1 µg/ml; R, ≥ 2 µg/ml), it was found that three of C.albicans, one of C.parapsilosis and one of C.glabrata isolates were resistant to fluconazole, while two of C.albicans and two of C

  9. The quantity and quality of α-gal-specific antibodies differ in individuals with and without delayed red meat allergy.

    Science.gov (United States)

    Kollmann, D; Nagl, B; Ebner, C; Emminger, W; Wöhrl, S; Kitzmüller, C; Vrtala, S; Mangold, A; Ankersmit, H-J; Bohle, B

    2017-02-01

    IgG to galactose-α-1,3-galactose (α-gal) are highly abundant natural antibodies (Ab) in humans. α-Gal-specific IgE Ab cause a special form of meat allergy characterized by severe systemic reactions 3-7 h after consumption of red meat. We investigated 20 patients who experienced such reactions and characterized their α-gal-specific IgE and IgG responses in more detail. α-Gal-specific IgE was determined by ImmunoCAP. IgE reactivity to meat extract and bovine gamma globulin (BGG) was assessed by immunoblotting and ELISA, respectively. In some experiments, sera were pre-incubated with α-gal or protein G to deplete IgG Ab. α-Gal-specific IgG1-4 Ab in individuals with and without meat allergy were assessed by ELISA. In immunoblots, BGG was the most frequently recognized meat protein. Binding of IgE and IgG to BGG was confirmed by ELISA and completely abolished after pre-incubation with α-gal. Neither the depletion of autologous α-gal-specific IgG Ab nor the addition of α-gal-specific IgG Ab from nonallergic individuals changed the IgE recognition of BGG of meat-allergic patients. Meat-allergic patients showed significantly higher α-gal-specific IgG1 and IgG3 Ab than nonallergic individuals, whereas the latter showed significantly higher levels of α-gal-specific IgG4 Ab. Patients with delayed meat allergy display IgE and IgG Ab that selectively recognize the α-gal epitope on BGG. Their enhanced α-gal-specific IgE levels are accompanied by high levels of α-gal-specific IgG1 devoid of IgE-blocking activity. This subclass distribution is atypical for food allergies and distinct from natural α-gal IgG responses in nonallergic individuals. © 2016 The Authors. Allergy Published by John Wiley & Sons Ltd.

  10. In-cell PCR method for specific genotyping of genomic DNA from one individual in a mixture of cells from two individuals: a model study with specific relevance to prenatal diagnosis based on fetal cells in maternal blood

    DEFF Research Database (Denmark)

    Hviid, T Vauvert

    2002-01-01

    maternal blood samples, the use of such an approach for genotyping by molecular biology techniques in a more routine setting has been hampered by the large contamination of maternal nucleated blood cells in the cell isolates. Therefore, a new method based on in-cell PCR is described, which may overcome...... this problem. Methods and Results: Mixtures of cells from two different individuals were fixed and permeabilized in suspension. After coamplification of a DNA sequence specific for one of the individuals and the DNA sequence to be genotyped, the two PCR products were linked together in the fixed cells positive...... for both DNA sequences by complementary primer tails and further amplification steps. In a model system of mixtures of male and female CD71-positive cells from umbilical cord blood attached to immunomagnetic particles, a Y-chromosome-specific sequence (TSPY) was linked to a polymorphic HLA-DPB1 sequence...

  11. Individuals with non-specific low back pain use a trunk stiffening strategy to maintain upright posture.

    Science.gov (United States)

    Jones, Stephanie L; Henry, Sharon M; Raasch, Christine C; Hitt, Juvena R; Bunn, Janice Y

    2012-02-01

    There is increasing evidence that individuals with non-specific low back pain (LBP) have altered movement coordination. However, the relationship of this neuromotor impairment to recurrent pain episodes is unknown. To assess coordination while minimizing the confounding influences of pain we characterized automatic postural responses to multi-directional support surface translations in individuals with a history of LBP who were not in an active episode of their pain. Twenty subjects with and 21 subjects without non-specific LBP stood on a platform that was translated unexpectedly in 12 directions. Net joint torques of the ankles, knees, hips, and trunk in the frontal and sagittal planes as well as surface electromyographs of 12 lower leg and trunk muscles were compared across perturbation directions to determine if individuals with LBP responded using a trunk stiffening strategy. Individuals with LBP demonstrated reduced peak trunk torques, and enhanced activation of the trunk and ankle muscle responses following perturbations. These results suggest that individuals with LBP use a strategy of trunk stiffening achieved through co-activation of trunk musculature, aided by enhanced distal responses, to respond to unexpected support surface perturbations. Notably, these neuromotor alterations persisted between active pain periods and could represent either movement patterns that have developed in response to pain or could reflect underlying impairments that may contribute to recurrent episodes of LBP. Copyright © 2011 Elsevier Ltd. All rights reserved.

  12. Individuals with non-specific low back pain use a trunk stiffening strategy to maintain upright posture

    Science.gov (United States)

    Jones, Stephanie L.; Henry, Sharon M.; Raasch, Christine C.; Hitt, Juvena R.; Bunn, Janice Y.

    2011-01-01

    There is increasing evidence that individuals with non-specific low back pain (LBP) have altered movement coordination., hHowever, the relationship of this neuromotor impairment to recurrent pain episodes is unknown. To assess coordination while minimizing the confounding influences of pain we characterized automatic postural responses to multi-directional support surface translations in individuals with a history of LBP who were not in an active episode of their pain. Twenty subjects with and 21 subjects without non-specific LBP stood on a platform that was translated unexpectedly in 12 directions. Net joint torques of the ankles, knees, hips and trunk in the frontal and sagittal planes as well as surface electromyographs of 12 lower leg and trunk muscles were compared across perturbation directions to determine if individuals with LBP responded using a trunk stiffening strategy. Individuals with LBP demonstrated reduced peak trunk torques, and enhanced activation of the trunk and ankle muscle responses following perturbations. These results suggest that individuals with LBP use a strategy of trunk stiffening achieved through co-activation of trunk musculature, aided by enhanced distal responses, to respond to unexpected support surface perturbations. Notably, these neuromotor alterations persisted between active pain periods and could represent either movement patterns that have developed in response to pain or could reflect underlying impairments that maymay contribute to recurrent episodes of LBP. PMID:22100719

  13. Alcohol-Specific Coping Styles of Adult Children of Individuals with Alcohol Use Disorders and Associations with Psychosocial Functioning.

    Science.gov (United States)

    Drapkin, Michelle L; Eddie, David; Buffington, Angela J; McCrady, Barbara S

    2015-07-01

    Parental alcohol use disorders (AUDs) have been conceptualized as a chronic stressor that can lead to deleterious long-term outcomes in children of individuals with AUDs. Yet, while many individuals are detrimentally affected by their parents' problematic alcohol use, and go on to manifest psychological problems, others do not. How individuals cope with the stress of having a parent with an AUD is believed to be an important moderator of this differential outcome. This study assessed whether individuals' alcohol-specific coping styles predicted alcohol use, positive or negative life events, and depression, using a sample of 465 college students, of whom 20% were adult children of individuals with alcohol use disorders, colloquially known as adult children of alcoholics (ACOAs), and a battery of well-validated, self-report measures. Participant ACOAs reported less 'engaged' and 'total' alcohol-specific coping strategies and more 'withdrawal' alcohol-specific coping strategies than their non adult children of alcoholics (NACOAs) counterparts. Across participants, women reported more 'engaged', 'tolerant/inactive', and 'total' coping than men. Although ACOAs reported significantly more negative life events, which predicted more passive coping styles, they did not differ significantly from NACOAs on measures of problematic alcohol use or depression, supporting theories of resilience in ACOAs regardless of their alcohol-specific coping styles. For NACOAs, 'tolerant' coping predicted greater depression and alcohol-related problems; 'engaged' coping predicted fewer alcohol problems. Results suggest that ACOAs cope differently with problematic alcohol use among relatives and friends compared with NACOAs and are more likely to experience negative life events. Additionally, alcohol-related coping strategies have more predictive utility in NACOAs than ACOAs. © The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.

  14. Inter-individual variation in DNA methylation is largely restricted to tissue-specific differentially methylated regions in maize.

    Science.gov (United States)

    Lauria, Massimiliano; Echegoyen-Nava, Rodrigo Antonio; Rodríguez-Ríos, Dalia; Zaina, Silvio; Lund, Gertrud

    2017-02-23

    Variation in DNA methylation across distinct genetic populations, or in response to specific biotic or abiotic stimuli, has typically been studied in leaf DNA from pooled individuals using either reduced representation bisulfite sequencing, whole genome bisulfite sequencing (WGBS) or methylation sensitive amplified polymorphism (MSAP). The latter represents a useful alterative when sample size is large, or when analysing methylation changes in genomes that have yet to be sequenced. In this study we compared variation in methylation across ten individual leaf and endosperm samples from maize hybrid and inbred lines using MSAP. We also addressed the methodological implications of analysing methylation variation using pooled versus individual DNA samples, in addition to the validity of MSAP compared to WGBS. Finally, we analysed a subset of variable and non-variable fragments with respect to genomic location, vicinity to repetitive elements and expression patterns across leaf and endosperm tissues. On average, 30% of individuals showed inter-individual methylation variation, mostly of leaf and endosperm-specific differentially methylated DNA regions. With the exception of low frequency demethylation events, the bulk of inter-individual methylation variation (84 and 80% in leaf and endosperm, respectively) was effectively captured in DNA from pooled individuals. Furthermore, available genome-wide methylation data largely confirmed MSAP leaf methylation profiles. Most variable methylation that mapped within genes was associated with CG methylation, and many of such genes showed tissue-specific expression profiles. Finally, we found that the hAT DNA transposon was the most common class II transposable element found in close proximity to variable DNA regions. The relevance of our results with respect to future studies of methylation variation is the following: firstly, the finding that inter-individual methylation variation is largely restricted to tissue-specific

  15. Site-specific chromatin immunoprecipitation: a selective method to individually analyze neighboring transcription factor binding sites in vivo

    Directory of Open Access Journals (Sweden)

    Schuch Ronaldo

    2012-02-01

    Full Text Available Abstract Background Transcription factors (TFs and their binding sites (TFBSs play a central role in the regulation of gene expression. It is therefore vital to know how the allocation pattern of TFBSs affects the functioning of any particular gene in vivo. A widely used method to analyze TFBSs in vivo is the chromatin immunoprecipitation (ChIP. However, this method in its present state does not enable the individual investigation of densely arranged TFBSs due to the underlying unspecific DNA fragmentation technique. This study describes a site-specific ChIP which aggregates the benefits of both EMSA and in vivo footprinting in only one assay, thereby allowing the individual detection and analysis of single binding motifs. Findings The standard ChIP protocol was modified by replacing the conventional DNA fragmentation, i. e. via sonication or undirected enzymatic digestion (by MNase, through a sequence specific enzymatic digestion step. This alteration enables the specific immunoprecipitation and individual examination of occupied sites, even in a complex system of adjacent binding motifs in vivo. Immunoprecipitated chromatin was analyzed by PCR using two primer sets - one for the specific detection of precipitated TFBSs and one for the validation of completeness of the enzyme digestion step. The method was established exemplary for Sp1 TFBSs within the egfr promoter region. Using this site-specific ChIP, we were able to confirm four previously described Sp1 binding sites within egfr promoter region to be occupied by Sp1 in vivo. Despite the dense arrangement of the Sp1 TFBSs the improved ChIP method was able to individually examine the allocation of all adjacent Sp1 TFBS at once. The broad applicability of this site-specific ChIP could be demonstrated by analyzing these SP1 motifs in both osteosarcoma cells and kidney carcinoma tissue. Conclusions The ChIP technology is a powerful tool for investigating transcription factors in vivo, especially

  16. Specific features of team kinds of sports sportsmen’s individual characteristics

    Directory of Open Access Journals (Sweden)

    V.N. Liashenko

    2016-10-01

    Full Text Available Purpose: to study individual characteristics of personalities of team kinds of sports sportsmen, specializing in football. Material: in the research football players (n=28, age 18 - 20 years participated. Psycho-diagnostic testing by methodic 16PF of Kattel was used. Results: we found high correlation between factors, which were conditioned by caution in choosing partners for communication and active contacts. Such sportsmen express their emotions expressively. It facilitates improvement of relations in conditions of co-operation in little group. It was also found that one of personality’s leading characteristics in sportsmen is their activity in social contacts. The higher is courage the more active is communication. It promotes discussion of common interests and targets for the given group of people. Conclusions: Sportsmen, who have many emotional interests and are ready to risk (or having bent to adventures have to face non understanding of other players. In such case conflict can be inevitable. Especially it manifests, if opposite side has the same indicators in this factor. Just courage, risk and adventurism push them to conflict solution of problem situations.

  17. Spinal Manipulative Therapy Specific Changes In Pain Sensitivity In Individuals With Low Back Pain (NCT01168999)

    Science.gov (United States)

    Bialosky, Joel E; George, Steven Z; Horn, Maggie E; Price, Donald D; Staud, Roland; Robinson, Michael E

    2013-01-01

    Spinal Manipulative Therapy (SMT) is effective for some individuals experiencing low back pain (LBP); however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with LBP to receive SMT, placebo SMT, placebo SMT with the instructional set, “The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people”, or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over two weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following two weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (p= 0.05, partial η2= 0.07). Group dependent differences were not observed for changes in pain intensity and disability at two week. Participant satisfaction was greatest following the enhanced placebo SMT. PMID:24361109

  18. Individual-specific multi-scale finite element simulation of cortical bone of human proximal femur

    Science.gov (United States)

    Ascenzi, Maria-Grazia; Kawas, Neal P.; Lutz, Andre; Kardas, Dieter; Nackenhorst, Udo; Keyak, Joyce H.

    2013-07-01

    We present an innovative method to perform multi-scale finite element analyses of the cortical component of the femur using the individual's (1) computed tomography scan; and (2) a bone specimen obtained in conjunction with orthopedic surgery. The method enables study of micro-structural characteristics regulating strains and stresses under physiological loading conditions. The analysis of the micro-structural scenarios that cause variation of strain and stress is the first step in understanding the elevated strains and stresses in bone tissue, which are indicative of higher likelihood of micro-crack formation in bone, implicated in consequent remodeling or macroscopic bone fracture. Evidence that micro-structure varies with clinical history and contributes in significant, but poorly understood, ways to bone function, motivates the method's development, as does need for software tools to investigate relationships between macroscopic loading and micro-structure. Three applications - varying region of interest, bone mineral density, and orientation of collagen type I, illustrate the method. We show, in comparison between physiological loading and simple compression of a patient's femur, that strains computed at the multi-scale model's micro-level: (i) differ; and (ii) depend on local collagen-apatite orientation and degree of calcification. Our findings confirm the strain concentration role of osteocyte lacunae, important for mechano-transduction. We hypothesize occurrence of micro-crack formation, leading either to remodeling or macroscopic fracture, when the computed strains exceed the elastic range observed in micro-structural testing.

  19. Suicide Attempts Among Individuals With Specific Learning Disorders: An Underrecognized Issue.

    Science.gov (United States)

    Fuller-Thomson, Esme; Carroll, Samara Z; Yang, Wook

    2017-06-01

    Several studies have linked specific learning disorders (SLDs) with suicidal ideation, but less is known about the disorders' association with suicide attempts. This gap in the literature is addressed via the 2012 nationally representative Canadian Community Health Survey ( n = 21,744). The prevalence of lifetime suicide attempts among those with an SLD was much higher than those without (11.1% vs. 2.7%, p attempted suicide, even after adjusting for most known risk factors (e.g., childhood adversities, history of mental illness and substance abuse, sociodemographics; odds ratio = 1.46, 95% CI [1.05, 2.04]). The largest attenuation in the association between SLD and suicidal attempts was accounted for by adverse childhood experiences. Among those with SLDs ( n = 745), a history of witnessing chronic parental domestic violence and ever having had a major depressive disorder were associated with substantially higher odds of suicide attempts.

  20. Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study.

    Science.gov (United States)

    Smith, Colette; Sabin, Caroline A; Lundgren, Jens D; Thiebaut, Rodolphe; Weber, Rainer; Law, Matthew; Monforte, Antonella d'Arminio; Kirk, Ole; Friis-Moller, Nina; Phillips, Andrew; Reiss, Peter; El Sadr, Wafaa; Pradier, Christian; Worm, Signe W

    2010-06-19

    To investigate any emerging trends in causes of death amongst HIV-positive individuals in the current cART era, and to investigate the factors associated with each specific cause of death. An observational multicentre cohort study. All HIV-positive individuals included in one of the cohorts in the Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study were included. The association between HIV-specific and non HIV-specific risk factors and death were studied using multivariable Poisson regression. We observed 2482 deaths in 180,176 person-years (PY) on 33,308 individuals [rate/1000 PY = 13.8 (95% CI 13.2-14.3)]. Primary causes of death were: AIDS (n = 743; rate/1000 PY = 4.12), liver-related (341; 1.89), CVD-related (289; 1.60), non-AIDS malignancy (286; 1.59). The overall rate of death fell from 16.9 in 1999/2000 to 9.6/ 1000 PY in 2007/2008. Smoking was associated with CVD and non-AIDS cancers, HBV and HCV co-infection with liver-related deaths, and hypertension with liver-related and CVD deaths. Diabetes was a risk factor for all specific causes of death except non-AIDS cancers, and higher current HIV RNA for AIDS-related deaths. Lower CD4 cell counts were associated with a higher risk of death from all specific causes of death. Multiple potentially modifiable traditional and HIV-specific risk factors for death of HIV-infected persons were identified. The maximum reduction in mortality in HIV-infected populations will require that each of these factors be appropriately addressed. No trends in terms of emerging causes of unexpected deaths were observed, although monitoring will continue.

  1. Individuals with non-specific low back pain in an active episode demonstrate temporally altered torque responses and direction-specific enhanced muscle activity following unexpected balance perturbations

    Science.gov (United States)

    Jones, Stephanie L.; Hitt, Juvena R.; DeSarno, Michael J.; Henry, Sharon M.

    2012-01-01

    Individuals with a history of non-specific low back pain (LBP) while in a quiescent pain period demonstrate altered automatic postural responses (APRs) characterized by reduced trunk torque contributions and increased co-activation of trunk musculature. However it is unknown whether these changes preceded or resulted from pain. To further delineate the relationship between cyclic pain recurrence and APRs, we quantified postural responses following multi-directional support surface translations, in individuals with non-specific LBP, following an active pain episode. Sixteen subjects with and 16 without LBP stood on two force plates that were translated unexpectedly in 12 directions. Net joint torques of the ankles, knees (sagittal only), hips and trunk, in the frontal and sagittal planes were quantified and activation of 12 muscles of the lower limb unilaterally and the dorsal and ventral trunk, bilaterally, were recorded using surface electromyography (EMG). Peaks and latencies to peak joint torques, rates of torque development (slopes) and integrated EMGs characterizing baseline and active muscle contributions were analysed for group by perturbation direction (torques) and group by perturbation by epoch interaction (EMG) effects. In general, the LBP cohort demonstrated APRs that were of similar torque magnitude and rate but peaked earlier compared to individuals without LBP. Individuals with LBP also demonstrated increased muscle activity following perturbation directions in which the muscle was acting as a prime mover and reduced muscle activity in opposing directions, proximally and distally, with some proximal asymmetries. These altered postural responses may reflect increased muscle spindle sensitivity. Given that these motor alterations are demonstrated proximally and distally, they likely reflect the influence of central nervous system processing in this cohort. PMID:22875027

  2. Rapid and individual-specific glycoprofiling of the low abundance N-glycosylated protein tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Thaysen-Andersen, Morten; Thøgersen, Ida B.; Nielsen, Hans Jørgen

    2007-01-01

    was performed using matrix-assisted laser desorption/ionization MS and MS/MS. The method proved to be fast and sensitive and furthermore yielded a comprehensive site-specific glycan analysis, allowing a differentiation of the glycoprofiles of the two sources of recombinant protein, both comprising N......-glycans of a highly heterogeneous nature. To test the potential of the method, tissue inhibitor of metalloproteinases-1 (TIMP-1), a secreted low abundance N-glycosylated protein and a cancer marker, was purified in an individual-specific manner from plasma of five healthy individuals using IgG depletion...... and immunoaffinity chromatography. The corresponding TIMP-1 glycoprofiles were determined to be highly similar, comprising mainly bi- and triantennary complex oligosaccharides. Additionally it was shown that platelet-derived TIMP-1 displayed a similar glycoprofile. This is the first study to investigate...

  3. Task-specific codes for face recognition: how they shape the neural representation of features for detection and individuation.

    Science.gov (United States)

    Nestor, Adrian; Vettel, Jean M; Tarr, Michael J

    2008-01-01

    The variety of ways in which faces are categorized makes face recognition challenging for both synthetic and biological vision systems. Here we focus on two face processing tasks, detection and individuation, and explore whether differences in task demands lead to differences both in the features most effective for automatic recognition and in the featural codes recruited by neural processing. Our study appeals to a computational framework characterizing the features representing object categories as sets of overlapping image fragments. Within this framework, we assess the extent to which task-relevant information differs across image fragments. Based on objective differences we find among task-specific representations, we test the sensitivity of the human visual system to these different face descriptions independently of one another. Both behavior and functional magnetic resonance imaging reveal effects elicited by objective task-specific levels of information. Behaviorally, recognition performance with image fragments improves with increasing task-specific information carried by different face fragments. Neurally, this sensitivity to the two tasks manifests as differential localization of neural responses across the ventral visual pathway. Fragments diagnostic for detection evoke larger neural responses than non-diagnostic ones in the right posterior fusiform gyrus and bilaterally in the inferior occipital gyrus. In contrast, fragments diagnostic for individuation evoke larger responses than non-diagnostic ones in the anterior inferior temporal gyrus. Finally, for individuation only, pattern analysis reveals sensitivity to task-specific information within the right "fusiform face area". OUR RESULTS DEMONSTRATE: 1) information diagnostic for face detection and individuation is roughly separable; 2) the human visual system is independently sensitive to both types of information; 3) neural responses differ according to the type of task-relevant information

  4. Hue-specific colour memory impairment in an individual with intact colour perception and colour naming.

    Science.gov (United States)

    Jakobson, L S; Pearson, P M; Robertson, B

    2008-01-15

    Cases of hue-selective dyschomatopsias, together with the results of recent optical imaging studies [Xiao, Y., Casti, A. R. R., Xiao, J., & Kaplan, E. (2006). A spatially organized representation of colour in macaque primary visual cortex. Perception, 35, ECVP Abstract Supplement; Xiao, Y., Wang, Y., & Felleman, D. J. (2003). A spatially organized representation of colour in macaque cortical area V2. Nature, 421, 535-539], have provided support for the idea that different colours are processed in spatially distinct regions of extrastriate cortex. In the present report, we provide evidence suggesting that a similar, but distinct, map may exist for representations of colour in memory. This evidence comes from observations of a young woman (QP) who demonstrates an isolated deficit in colour memory secondary to a concussive episode. Despite having normal colour perception and colour naming skills, and above-average memory skills in other domains, QP's ability to recall visually encoded colour information over short retention intervals is dramatically impaired. Her long-term memory for colour and her colour imagery skills are also abnormal. Surprisingly, however, these impairments are not seen with all hues; specifically, her ability to remember or imagine blue shades is spared. This interesting case contributes to the literature suggesting that colour perception, naming, and memory can be clinically dissociated, and provides insights into the organization of colour information in memory.

  5. Bisexual-Specific Minority Stressors, Psychological Distress, and Suicidality in Bisexual Individuals: the Mediating Role of Loneliness.

    Science.gov (United States)

    Mereish, Ethan H; Katz-Wise, Sabra L; Woulfe, Julie

    2017-08-01

    Bisexual individuals are at higher risk for poor mental health outcomes compared to heterosexual as well as lesbian and gay individuals and experience minority stressors, such as discrimination, from both heterosexual and sexual minority communities. However, there is little research examining the negative effects of bisexual-specific minority stressors on bisexual individuals' mental health as well as psychological factors that might help explain minority stressors' deleterious effects. This research examined the effects of distal minority stressors (i.e., anti-bisexual experiences from both heterosexual as well as lesbian and gay people) and proximal stressors (i.e., internalized heterosexism and sexual orientation concealment) on psychological distress and suicidality among bisexual adults (N = 503). Building on the relational framing of the minority stress model, we also tested one relational factor (i.e., loneliness) as a mediator of the associations between distal and proximal minority stressors and poor mental health (i.e., psychological distress and suicidality). Structural equation modeling analyses were used to test the mediating effects of loneliness on the associations between minority stressors and psychological distress and suicidality. Although distal and proximal minority stressors were not associated with each other, loneliness mediated the effects of distal and proximal minority stressors on psychological distress and suicidality. The results of this study underscore the importance of targeting bisexual-specific minority stressors as well as loneliness in preventive interventions to improve the mental health of bisexual individuals.

  6. Specificity of Balance Training in Healthy Individuals: A Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Kümmel, Jakob; Kramer, Andreas; Giboin, Louis-Solal; Gruber, Markus

    2016-09-01

    It has become common practice to incorporate balance tasks into the training program for athletes who want to improve performance and prevent injuries, in rehabilitation programs, and in fall prevention programs for the elderly. However, it is still unclear whether incorporating balance tasks into a training program increases performance only in these specific tasks or if it affects balance in a more general way. The objective of this systematic literature review and meta-analysis was to determine to what extent the training of balance tasks can improve performance in non-trained balance tasks. A systematic literature search was performed in the online databases EMBASE, PubMed, SPORTDiscus and Web of Science. Articles related to balance training and testing in healthy populations published between January 1985 and March 2015 were considered. A total of 3093 articles were systematically evaluated. Randomized controlled trials were included that (i) used only balance tasks during the training, (ii) used at least two balance tests before and after training, and (iii) tested performance in the trained balance tasks and at least one non-trained balance task. Six studies with a total of 102 subjects met these criteria and were included into the meta-analysis. The quality of the studies was evaluated by means of the Physiotherapy Evidence Database (PEDro) scale. A random effect model was used to calculate the between-subject standardized mean differences (SMDbs) in order to quantify the effect of balance training on various kinds of balance measures relative to controls. The tested balance tasks in each study were classified into tasks that had been trained and tasks that had not been trained. For further analyses, the non-trained balance tasks were subdivided into tasks with similar or non-similar body position and similar or non-similar balance perturbation direction compared to the trained task. The effect of balance training on the performance of the trained balance

  7. Specific features of taxation of in-dividuals in relationships with foreign elements.

    Directory of Open Access Journals (Sweden)

    Karina Ponomareva

    2017-01-01

    material benefits, are taken into account. Exceptions to this rule are provided for in Article 217 of the Tax Code, which contains a list of income exempt from taxation.Conclusions. The author comes to the conclusion that the legal regulation of the taxation of residents and non-residents is changing rapidly. Meanwhile, in the Russian legislation, the specifics of creating and terminating the status of a tax resident are not specified in detail. At the same time, several taxation regimes have been established for foreigners. This fact allows them to pay taxes at a general rate.

  8. High-throughput sequencing reveals extensive variation in human-specific L1 content in individual human genomes.

    Science.gov (United States)

    Ewing, Adam D; Kazazian, Haig H

    2010-09-01

    Using high-throughput sequencing, we devised a technique to determine the insertion sites of virtually all members of the human-specific L1 retrotransposon family in any human genome. Using diagnostic nucleotides, we were able to locate the approximately 800 L1Hs copies corresponding specifically to the pre-Ta, Ta-0, and Ta-1 L1Hs subfamilies, with over 90% of sequenced reads corresponding to human-specific elements. We find that any two individual genomes differ at an average of 285 sites with respect to L1 insertion presence or absence. In total, we assayed 25 individuals, 15 of which are unrelated, at 1139 sites, including 772 shared with the reference genome and 367 nonreference L1 insertions. We show that L1Hs profiles recapitulate genetic ancestry, and determine the chromosomal distribution of these elements. Using these data, we estimate that the rate of L1 retrotransposition in humans is between 1/95 and 1/270 births, and the number of dimorphic L1 elements in the human population with gene frequencies greater than 0.05 is between 3000 and 10,000.

  9. Postural instability of extremely obese individuals improves after a body weight reduction program entailing specific balance training.

    Science.gov (United States)

    Maffiuletti, N A; Agosti, F; Proietti, M; Riva, D; Resnik, M; Lafortuna, C L; Sartorio, A

    2005-01-01

    The purposes of this study were to compare postural stability between obese and lean subjects and to investigate the effect of a 3-week body weight reduction (BWR) program entailing specific balance training on postural stability of extremely obese patients. Time of balance maintenance and mean error on the medial-lateral direction at the trunk and lower limb level were assessed during a single limb stance on a movable platform in 19 non-obese and in 20 extremely obese individuals (age range: 20-40 yr). Time of balance maintenance was shorter (obese: 21.1+/-7.7 vs lean: 27.3+/-3.1 sec) and medial-lateral sway of the trunk was larger in obese (5.4+/-3.2 degrees) than in lean (3.2+/-1.1 degrees) subjects (pprogram (energy-restricted diet, moderate physical exercise, nutritional education and psychological counselling) combined with or without 6 sessions of specific balance training on a movable platform. BWR plus specific balance training enhanced time of balance maintenance (pre: 23.8+/-7.2 vs post: 30.0+/-0.0 sec) and reduced the trunk sway (5.2+/-2.8 degrees vs 2.6+/-0.9 degrees ) more than BWR alone (pprogram. It was concluded that balance improvement is an important goal of rehabilitation, that would probably reduce the propensity of overweight individuals to fall while performing everyday activities.

  10. Individualized fetal growth assessment: critical evaluation of key concepts in the specification of third trimester size trajectories.

    Science.gov (United States)

    Deter, Russell L; Lee, Wesley; Sangi-Haghpeykar, Haleh; Tarca, Adi L; Yeo, Lami; Romero, Roberto

    2014-04-01

    To characterize second and third trimester fetal growth using Individualized Growth Assessment methods in a larger cohort of fetuses with normal neonatal growth outcomes. A prospective longitudinal study of 119 pregnancies was performed from 18 weeks, MA, to delivery. Measurements of several 1D and 3D fetal size parameters were obtained from 3D volume data sets at 3-4 week intervals. Regression analyses were used to determine Start Points (SP) and Rossavik model (P = c {t} (k + st)) coefficients c. k and s for each parameter in each fetus. Second trimester growth velocity reference ranges were determined and size model specification functions re-established, the latter used to generate individual size models. Actual measurements were compared to predicted third trimester size trajectories using Percent Deviations. New age-specific reference ranges for the Percent Deviations of each parameter were defined using 2-level statistical modeling. Rossavik models fit the data for all parameters very well (R(2): 99%), with SP's and k values similar to those found in much smaller cohorts. The c* values were strongly related to the second trimester slope (R(2): 97%), as was predicted s* to estimated c* (R(2): 54--95%). Rossavik models predicted third trimester growth with systematic errors close to 0%; random errors (95% range) ranged between 5.7 and 10.9% and 20.0 and 24.3% for 1D and 3D parameters, respectively. IGA procedures for evaluating second and third trimester growth are now established based on a larger cohort (4-6 fold larger). New, more rigorously defined, age-specific standards for the evaluation of third trimester size deviations are now available for nine anatomical parameters and a weight estimation procedure that incorporates a soft tissue parameter (fractional thigh volume). These results provide a means for more reliably assessing fetal growth on an individualized basis, thus minimizing the effect of biological differences in growth.

  11. Individual Differences in Disgust Sensitivity Do Not Influence Moral Reasoning, but a Discipline-Specific Ethics Course Does

    Directory of Open Access Journals (Sweden)

    Lisa M. McCool

    2014-07-01

    Full Text Available The purpose of this research study was to determine undergraduate students’ perceptions of ethical dilemmas as a means of measuring general concern for leadership ethics within the marketplace. With the end goal of identifying best practices for ethics education in business and to further aid our understanding of how individual factors, such as disgust sensitivity, can alter students’ moral assessments, we measured the relationship between emotion and cognition in affecting ethical decision making. We found specific coursework in business ethics can produce a significant gain in moral reasoning. These results suggest that in the absence of strong moral intuitions, discipline-specific ethics coursework can lead to more postconventional moral decision making.

  12. Individual preferences for physical exercise as secondary prevention for non-specific low back pain: A discrete choice experiment.

    Directory of Open Access Journals (Sweden)

    Emmanuel Aboagye

    Full Text Available Exercise is effective in improving non-specific low back pain (LBP. Certain components of physical exercise, such as the type, intensity and frequency of exercise, are likely to influence participation among working adults with non-specific LBP, but the value and relative importance of these components remain unknown. The study's aim was to examine such specific components and their influence on individual preferences for exercise for secondary prevention of non-specific LBP among working adults.In a discrete choice experiment, working individuals with non-specific LBP answered a web-based questionnaire. Each respondent was given ten pairs of hypothetical exercise programs and asked to choose one option from each pair. The choices comprised six attributes of exercise (i.e., type of training, design, intensity, frequency, proximity and incentives, each with either three or four levels. A conditional logit regression that reflected the random utility model was used to analyze the responses.The final study population consisted of 112 participants. The participants' preferred exercise option was aerobic (i.e., cardiovascular rather than strength training, group exercise with trainer supervision, rather than individual or unsupervised exercise. They also preferred high intensity exercise performed at least once or twice per week. The most popular types of incentive were exercise during working hours and a wellness allowance rather than coupons for sports goods. The results show that the relative value of some attribute levels differed between young adults (age ≤ 44 years and older adults (age ≥ 45 years in terms of the level of trainer supervision required, exercise intensity, travel time to exercise location and financial incentives. For active study participants, exercise frequency (i.e., twice per week, 1.15; CI: 0.25; 2.06 influenced choice of exercise. For individuals with more than one child, travel time (i.e., 20 minutes, -0.55; CI: 0

  13. Profiling of Measles-Specific Humoral Immunity in Individuals Following Two Doses of MMR Vaccine Using Proteome Microarrays

    Directory of Open Access Journals (Sweden)

    Iana H. Haralambieva

    2015-03-01

    Full Text Available Introduction: Comprehensive evaluation of measles-specific humoral immunity after vaccination is important for determining new and/or additional correlates of vaccine immunogenicity and efficacy. Methods: We used a novel proteome microarray technology and statistical modeling to identify factors and models associated with measles-specific functional protective immunity in 150 measles vaccine recipients representing the extremes of neutralizing antibody response after two vaccine doses. Results: Our findings demonstrate a high seroprevalence of antibodies directed to the measles virus (MV phosphoprotein (P, nucleoprotein (N, as well as antibodies to the large polymerase (L protein (fragment 1234 to 1900 AA. Antibodies to these proteins, in addition to anti-F antibodies (and, to a lesser extent, anti-H antibodies, were correlated with neutralizing antibody titer and/or were associated with and predictive of neutralizing antibody response. Conclusion: Our results identify antibodies to specific measles virus proteins and statistical models for monitoring and assessment of measles-specific functional protective immunity in vaccinated individuals.

  14. Gender-dependent and age-of-onset-specific association of the rs11675434 single-nucleotide polymorphism near TPO with susceptibility to Graves' ophthalmopathy.

    Science.gov (United States)

    Kuś, Aleksander; Szymański, Konrad; Jurecka-Lubieniecka, Beata; Pawlak-Adamska, Edyta; Kula, Dorota; Miśkiewicz, Piotr; Bolanowski, Marek; Płoski, Rafał; Bossowski, Artur; Daroszewski, Jacek; Jarząb, Barbara; Bednarczuk, Tomasz

    2017-03-01

    The role of TPO gene polymorphism in the susceptibility to Graves' disease (GD) remains unclear. However, single-nucleotide polymorphisms (SNPs) near TPO have been recently associated with serum levels of thyroid peroxidase (TPO) antibody in two independent genome-wide association studies. Moreover, we have observed a strong association between the rs11675434 SNP located near TPO and the presence of clinically evident Graves' ophthalmopathy (GO). The aim of the current study was to reevaluate and dissect this association in an extended group of 1231 well-characterized patients with GD (1043 adults and 188 children) and 1130 healthy controls from the Polish Caucasian population, considering possible gender-dependent and age-of-onset-specific effects of the studied SNP. We found that the T allele of rs11675434 was significantly more frequent in GD patients with than without GO (odds ratio (OR)=1.26, 95% confidence interval (CI)=1.05-1.51, P=0.012), which was consistent with our previous findings. Further analyses performed in subgroups of patients showed that the association with GO was significant in adult patients with age of GD onset ⩾45 years (OR=1.34, 95% CI=1.03-1.75, P=0.031), but not in children and adolescents or adult patients with earlier onset of the disease (OR=1.72, 95% CI=0.77-3.84, P=0.18 and OR=1.05, 95% CI=0.79-1.40, P=0.75, respectively). Moreover, a strong association with GO was present in males (OR=2.06, 95% CI=1.40-3.02, P=0.0002), whereas it was absent in females (OR=1.10, 95% CI=0.90-1.35, P=0.35). The results of our study further suggest that rs11675434 SNP located near TPO is associated with the development of GO, especially in males and patients with later age of GD onset.

  15. Individual susceptibility to UV and ionizing radiations: DNA repair evaluated by the comets test; Susceptibilite individuelle aux radiations ultraviolettes et ionisantes: reparation de l'ADN evaluee par le test des cometes

    Energy Technology Data Exchange (ETDEWEB)

    Alapetite, C

    1999-07-01

    Some patients having a cancer treated by radiotherapy can suffer from an hypersensitivity with respect to UV and ionizing radiations which corresponds to an inter-individual variability of the response to the geno-toxic stress induced by radiations. A predictive approach of this risk has been developed which shows the interest of an analysis of the individual capacities of repair of DNA radio-lesions. This approach uses the alkaline comets test. The application of this test to the patients' lymphocytes shows a high percentage of severe reactions of normal tissues after the radiotherapy course with a high residual level of broken DNA strands which gives evidence for a repair defect. The retrospective application of this test to breast cancers with radiotherapy complications without any genetical predisposition has permitted to validate this test in order to use it as a predictive diagnosis of the individual susceptibility of patients with respect to radiotherapy. (J.S.)

  16. Hypnotic Induction is followed by State-like changes in the organization of EEG Functional Connectivity in the Theta and Beta Frequency bands in high-hypnotically susceptible individuals

    Directory of Open Access Journals (Sweden)

    Graham eJamieson

    2014-07-01

    Full Text Available Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs and 11 low susceptible (lows participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH and the imaginary component of coherence (iCOH, which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1–3.9Hz, theta (4–7.9Hz alpha (8–12.9Hz, beta1 (13–19.9Hz, beta2 (20–29.9Hz and gamma (30–45Hz. The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized hypnotic-state.

  17. Hypnotic induction is followed by state-like changes in the organization of EEG functional connectivity in the theta and beta frequency bands in high-hypnotically susceptible individuals

    Science.gov (United States)

    Jamieson, Graham A.; Burgess, Adrian P.

    2014-01-01

    Altered state theories of hypnosis posit that a qualitatively distinct state of mental processing, which emerges in those with high hypnotic susceptibility following a hypnotic induction, enables the generation of anomalous experiences in response to specific hypnotic suggestions. If so then such a state should be observable as a discrete pattern of changes to functional connectivity (shared information) between brain regions following a hypnotic induction in high but not low hypnotically susceptible participants. Twenty-eight channel EEG was recorded from 12 high susceptible (highs) and 11 low susceptible (lows) participants with their eyes closed prior to and following a standard hypnotic induction. The EEG was used to provide a measure of functional connectivity using both coherence (COH) and the imaginary component of coherence (iCOH), which is insensitive to the effects of volume conduction. COH and iCOH were calculated between all electrode pairs for the frequency bands: delta (0.1–3.9 Hz), theta (4–7.9 Hz) alpha (8–12.9 Hz), beta1 (13–19.9 Hz), beta2 (20–29.9 Hz) and gamma (30–45 Hz). The results showed that there was an increase in theta iCOH from the pre-hypnosis to hypnosis condition in highs but not lows with a large proportion of significant links being focused on a central-parietal hub. There was also a decrease in beta1 iCOH from the pre-hypnosis to hypnosis condition with a focus on a fronto-central and an occipital hub that was greater in high compared to low susceptibles. There were no significant differences for COH or for spectral band amplitude in any frequency band. The results are interpreted as indicating that the hypnotic induction elicited a qualitative change in the organization of specific control systems within the brain for high as compared to low susceptible participants. This change in the functional organization of neural networks is a plausible indicator of the much theorized “hypnotic-state.” PMID:25104928

  18. [Posttraumatic stress disorder (PTSD) as a consequence of the interaction between an individual genetic susceptibility, a traumatogenic event and a social context].

    Science.gov (United States)

    Auxéméry, Y

    2012-10-01

    Why are some individuals more likely than others to develop a posttraumatic stress disorder (PTSD) in the face of similar levels of trauma exposure? Monitoring the traumatic process combining the antecedents, the determinants of the psychic trauma and the acute symptoms can clarify the causes of the final onset of a chronic repetition syndrome. Epidemiologic research has clarified risk factors that increase the likelihood of PTSD after exposure to a potentially traumatic event. PTSD is an interaction between a subject, a traumatogenic factor and a social context. With each epidemiological, psychopathological and more particularly neurogenetic study, we will expand on the impact of these interactions on the therapeutic treatment of psycho-traumatised persons. Most studies have shown that unrelated to the traumatic event, additional risk factors for developing PTSD include younger age at the time of the trauma, female gender, lower social economic statuts, lack of social support, premorbid personality characteristics and preexisting anxiety or depressive disorders increase the risk of PTSD. The psychic trauma is firmly attached to the repetition and the previous traumas are as many risks of developing a subsequent PTSD in the wake of a new trauma: PTSD in adults may represent a prolonged symptomatic reaction to prior traumatic assault, child abuse and childhood adversities. Related to the traumatic event, the organic pain, the traumatic brain injury, but also the sight of blood can lead to a trauma being considered as more serious or more harmful to life. It is useful to recognize the acute reactions of exhaustion stress as they can guide both the pharmacotherapeutic and the psychotherapeutic treatment thanks to debriefings. Even though the majority of people with acute stress disorder subsequently develop PTSD, the current data indicate that too many people can develop PTSD without initially displaying acute stress disorder. Though peritraumatic dissociation and

  19. Immunological changes in human immunodeficiency virus (HIV)-infected individuals during HIV-specific protease inhibitor treatment

    DEFF Research Database (Denmark)

    Ullum, H; Katzenstein, T; Aladdin, H

    1999-01-01

    The present study examines the influence of effective anti-retroviral treatment on immune function, evaluated by a broad array of immunological tests. We followed 12 individuals infected with human immunodeficiency virus (HIV) for 6 months after initiation of combination anti-retroviral treatment...... Vaccinia virus was increased after 3-6 months, whereas the specific HIV-directed CTL activity and the concentration and lytic activity of natural killer (NK) cells were unchanged during follow-up. These results demonstrate that the initiation of a treatment including an HIV protease inhibitor is followed...... count increased mainly due to increases in numbers of CD4+ CD28+ and CD4+ CD45RO+ cells, whereas increases in numbers of CD4+ CD45RA+ cells contributed little to the increase in CD4+ cell count. The total cytotoxic T-cell (CTL) killing of autologous B cells infected with HIV-encoding recombinant...

  20. Immunological changes in human immunodeficiency virus (HIV)-infected individuals during HIV-specific protease inhibitor treatment

    DEFF Research Database (Denmark)

    Ullum, H; Katzenstein, T; Aladdin, H

    1999-01-01

    Vaccinia virus was increased after 3-6 months, whereas the specific HIV-directed CTL activity and the concentration and lytic activity of natural killer (NK) cells were unchanged during follow-up. These results demonstrate that the initiation of a treatment including an HIV protease inhibitor is followed......The present study examines the influence of effective anti-retroviral treatment on immune function, evaluated by a broad array of immunological tests. We followed 12 individuals infected with human immunodeficiency virus (HIV) for 6 months after initiation of combination anti-retroviral treatment...... including a protease inhibitor. Unstimulated and pokeweed mitogen (PWM)-, interleukin (IL)-2- and phytohaemagglutinin (PHA)-stimulated lymphocyte proliferative responses increased during follow-up reaching average levels from 1.3-fold (PHA) to 3.7-fold (PWM) above baseline values. The total CD4+ lymphocyte...

  1. Implicit sexual attitude of heterosexual, gay and bisexual individuals: disentangling the contribution of specific associations to the overall measure.

    Directory of Open Access Journals (Sweden)

    Pasquale Anselmi

    Full Text Available The article aims to measure implicit sexual attitude in heterosexual, gay and bisexual individuals. A Many-Facet Rasch Measurement analysis was used to disentangle the contribution of specific associations to the overall IAT measure. A preference for heterosexuals relative to homosexuals is observed in heterosexual respondents, driven most by associating positive attributes with heterosexuals rather than negative attributes with homosexuals. Differently, neither the negative nor the positive evaluation of any of the target groups play a prominent role in driving the preference for homosexuals observed in gay respondents. A preference for heterosexuals relative to homosexuals is observed in bisexual respondents, that results most from ascribing negative attributes to homosexuals rather than positive attributes to heterosexuals. The results are consistent with the expression of the need for achieving a positive self-image and with the influence of shared social norms concerning sexuality.

  2. Generalization of Context-Specific Training in Individuals with Mild Cognitive Impairment: An Event-Related Potential Study

    Directory of Open Access Journals (Sweden)

    Sam C.C. Chan

    2016-12-01

    Full Text Available Background: This study examined the neural processes associated with the generalization of the effect of context-specific (CS training to noncontextual situations among individuals with mild cognitive impairment (MCI. Methods: Fourteen and 16 participants with MCI were randomly allocated to a Chinese calligraphy writing (CW training or a control group, respectively. The CW participants learned how to write Chinese strokes in a semicursive style to construct characters, tapping on working memory functions. The control group, on the other hand, learned how to use a tablet computer without emphasis on working memory functions. They then performed two 2-back tasks with CS semicursive strokes and non-context-specific (NCS digits. Event-related electroencephalogram signals were concurrently recorded. Results: The CW participants had a significantly shorter reaction time in the CS than in the NCS task (p < 0.05. They showed significantly longer latency in working memory updating (N200; t11 = 4.70, p = 0.05 and shorter latency in the evaluation of visual representation (P300; t12 = 4.67; p = 0.05 than the control group when performing the 2-back CS task. Shorter P300 latency was also revealed in the 2-back NCS task (t12 = 5.15, p = 0.041, suggesting a possible generalization of the training effect among the CW participants. Conclusion: The results suggest that CS working memory is likely to be generalized to NCS domains among individuals with MCI. Future research should extend the scope of the generalization and apply it beyond experimental conditions.

  3. Analysis of individual- and time-specific covariate effects on survival of Serinus serinus in north-eastern Spain

    Science.gov (United States)

    Conroy, M.J.; Senar, J.C.; Domenech, J.

    2002-01-01

    We developed models for the analysis of recapture data for 2678 serins (Serinus serinus) ringed in north-eastern Spain since 1985. We investigated several time- and individual-specific factors as potential predictors of overall mortality and dispersal patterns, and of gender and age differences in these patterns. Time-specific covariates included minimum daily temperature, days below freezing, and abundance of a strong competitor, siskins (Carduelis spinus) during winter, and maximum temperature and rainfall during summer. Individual covariates included body mass (i.e. body condition), and wing length (i.e. flying ability), and interactions between body mass and environmental factors. We found little support of a predictive relationship between environmental factors and survival, but good evidence of relationships between body mass and survival, especially for juveniles. Juvenile survival appears to vary in a curvilinear manner with increasing mass, suggesting that there may exist an optimal mass beyond which increases are detrimental. The mass-survival relationship does seem to be influenced by at least one environmental factor, namely the abundance of wintering siskins. When siskins are abundant, increases in body mass appear to relate strongly to increasing survival. When siskin numbers are average or low the relationship is largely reversed, suggesting that the presence of strong competition mitigates the otherwise largely negative aspects of greater body mass. Wing length in juveniles also appears to be related positively to survival, perhaps largely due to the influence of a few unusually large juveniles with adult-like survival. Further work is needed to test these relationships, ideally under experimentation.

  4. Derivation of gender and age-specific reference intervals from fully normal Japanese individuals and the implications for health screening.

    Science.gov (United States)

    Yamakado, Minoru; Ichihara, Kiyoshi; Matsumoto, Yoshiyuki; Ishikawa, Yoshiki; Kato, Kiminori; Komatsubara, Yusuke; Takaya, Norihide; Tomita, Shohken; Kawano, Reo; Takada, Keisuke; Watanabe, Kiyoaki

    2015-07-20

    With nationwide standardization of laboratory tests among institutions for health screening in Japan, common reference intervals (RIs) were derived from records of 1,500,000 health check attendees. Targets were 20 basic laboratory tests including body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling the following strict criteria were chosen: SBPmediation with no remarkable current/past illnesses. The latent abnormal values exclusion (LAVE) method was applied to ensure fully normal results. RIs were derived by parametric method using modified Box-Cox power transformation. Among all attendees, 23% fulfilled the criteria. Application of the LAVE method further reduced the dataset by 40%-50%. Age-related charts of test results differed greatly between genders in almost all tests. Comparison of derived RIs with clinical decision limits (CDLs) revealed that the upper limits of RIs differed from CDLs according to gender and age. Implementation of gender and age-specific RIs derived from individuals with fully normal health attributes will (1) enable appropriate interpretation of test results in health screening and (2) promote judicious application of CDLs for therapeutic intervention, taking into account gender, age and other health attributes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. A longitudinal study of behavioral, emotional and social difficulties in individuals with a history of specific language impairment (SLI).

    Science.gov (United States)

    St Clair, Michelle C; Pickles, Andrew; Durkin, Kevin; Conti-Ramsden, Gina

    2011-01-01

    Children with specific language impairment (SLI) have often been reported to have associated behavioral, emotional and social difficulties. Most previous studies involve observations at a single time point, or cross sectional designs, and longitudinal evidence of the developmental trajectories of particular difficulties is limited. The Strengths and Difficulties Questionnaire was used to measure behavioral (hyperactivity and conduct), emotional and social (peer) problems in a sample of individuals with a history of SLI at four time points from childhood (age 7) to adolescence (age 16). A decrease in behavioral and emotional problems was observed from childhood to adolescence, although emotional problems were still evident in adolescence. In contrast, there was an increase in social problems. Reading skills and expressive language were related only to behavioral problems. Pragmatic abilities were related to behavioral, emotional and social difficulties. As a group, those with a history of SLI have poorer long term social and, to a lesser extent, emotional outcomes. In contrast, behavioral difficulties appear to decrease to normative levels by adolescence. Different aspects of early language abilities and reading skills exert different types and degrees of influence on behavioral, emotional and social difficulties. Readers will be able to: (1) understand the types of behavioral, emotional and social difficulties present in individuals with a history of SLI; (2) be familiar with the developmental trajectory of these difficulties from childhood to adolescence; and (3) understand the relationships between behavioral, emotional and social difficulties and early language and literacy ability. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. Elephant-Initiated Interactions with Humans: Individual Differences and Specific Preferences in Captive African Elephants (Loxodonta africana

    Directory of Open Access Journals (Sweden)

    Zoë T. Rossman

    2017-04-01

    Full Text Available South Africa has seen a recent increase in the number of African elephants (Loxodonta africana maintained in reserves and parks and managed in free contact, where they may spend a significant amount of time in close proximity to humans. This study investigates how individual elephants choose to initiate interactions with humans by examining whether interaction types and frequencies vary both between elephants and with regards to the category of human involved in the interaction. Observations were made on a herd of seven captive African elephants frequently exposed to elephant handlers (guides, volunteers (who carry out general observations for the park’s research unit, and tourists. The elephants differed in the frequencies with which they initiated interactions with each category of human and in the types of behaviors they used to initiate interactions. However, all of the elephants interacted most frequently with guides. Certain individual elephants showed preferences in interacting with specific guides, indicating particular elephant-guide bonds. This study provides evidence for elephant-handler bonds as well as information on the extent of interactions between humans and African elephants managed in free contact.

  7. Modeling and analysis of individual with lower extremity amputation locomotion using prosthetic feet and running-specific prostheses.

    Science.gov (United States)

    Murai, Akihiko; Hobara, Hiroaki; Hashizume, Satoru; Kobayashi, Yoshiyuki; Tada, Mitsunori

    2017-07-01

    Prostheses have enabled individuals with lower extremity amputation (ILEAs) to accomplish many daily activities. Prosthetic feet allow ILEA to locomote and improves their quality of life. Carbon-fiber running-specific prostheses (RSPs) with energy storing capabilities support ILEAs to perform sprinting by partly providing spring-like properties in their amputated legs. Previous studies declare the spring-like RSP behavior and stiffness regulation during ILEA sprinting using RSP, though little is known about the behavior of the whole system that is a complex combination of human body and prostheses. This paper models this combined system with human and prosthetic foot and RSP using the digital human technology, then, analyzes the ILEA walking using the prosthetic foot and sprinting using RSP. We develop models that are combinations of human and prostheses by individualizing a linkage structure and inertial parameters of the digital human model. Then, locomotion of ILEA is analyzed based on measurements with optical motion capture system and force plates, and kinematics and dynamics computation. This modeling and computational technique can be applied to the locomotion of ILEA as well as a human motion using tools, and expanded to an analysis and improvement of system involving human.

  8. Temperament Alters Susceptibility to Negative Peer Influence in Early Adolescence

    Science.gov (United States)

    Mrug, Sylvie; Madan, Anjana; Windle, Michael

    2012-01-01

    The role of deviant peers in adolescent antisocial behavior has been well documented, but less is known about individual differences in susceptibility to negative peer influence. This study examined whether specific temperament dimensions moderate the prospective relationship between peer deviance and delinquent behavior in early adolescence.…

  9. Sex-specific effects of naturally occurring variants in the dopamine receptor D2 locus on insulin secretion and Type 2 diabetes susceptibility

    DEFF Research Database (Denmark)

    Guigas, B; de Leeuw van Weenen, J E; van Leeuwen, N

    2014-01-01

    AIMS: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. METHODS: Four potentially...

  10. Highly specific detection of myostatin prodomain by an immunoradiometric sandwich assay in serum of healthy individuals and patients.

    Directory of Open Access Journals (Sweden)

    Astrid Breitbart

    Full Text Available BACKGROUND: Myostatin is a muscle derived factor that functions as a negative regulator of skeletal muscle growth. Induction of myostatin expression was observed in rodent models of muscle wasting and in cachectic patients with cancer or pulmonary disease. Therefore, there is an increasing interest to use serum myostatin as a biomarker. METHODS: We established an immunoradiometric sandwich assay (IRMA, which uses a commercially available chicken polyclonal, affinity purified antibody directed against human myostatin prodomain. We determined the serum concentrations of myostatin prodomain in 249 healthy individuals as well as 169 patients with heart failure, 53 patients with cancer and 44 patients with chronic pulmonary disease. RESULTS: The IRMA had a detection limit of 0.7ng/ml, an intraassay imprecision of ≤14.1% and an interassay imprecision of ≤ 18.9%. The specificity of our assay was demonstrated by size exclusion chromatography, detection of myostatin by Western-blotting and a SMAD-dependent transcriptional-reporter assay in the signal-rich serum fractions, as well as lack of interference by unspecific substances like albumin, hemoglobin or lipids. Myostatin prodomain was stable at room temperature and resistant to freeze-thaw cycles. Apparently healthy individuals over the age of 55 had a median myostatin prodomain serum concentration of 3.9ng/ml (25(th-75(th percentiles, 2-7ng/ml and we could not detect increased levels in patients with stable chronic heart failure or cancer related weight loss. In contrast, we found strongly elevated concentrations of myostatin prodomain (median 26.9ng/ml, 25(th-75(th percentiles, 7-100ng/ml in the serum of underweight patients with chronic pulmonary disease. CONCLUSIONS: We established a highly specific IRMA for the quantification of myostatin prodomain concentration in human serum. Our assay could be useful to study myostatin as a biomarker for example in patients with chronic pulmonary disease

  11. Variation in Metabolic Rate among Individuals Is Related to Tissue-Specific Differences in Mitochondrial Leak Respiration.

    Science.gov (United States)

    Salin, Karine; Auer, Sonya K; Rudolf, Agata M; Anderson, Graeme J; Selman, Colin; Metcalfe, Neil B

    Standard metabolic rate (SMR) and maximum metabolic rate (MMR) typically vary two- or threefold among conspecifics, with both traits assumed to significantly impact fitness. However, the underlying mechanisms that determine such intraspecific variation are not well understood. We examined the influence of mitochondrial properties on intraspecific variation in SMR and MMR and hypothesized that if SMR supports the cost of maintaining the metabolic machinery required for MMR, then the mitochondrial properties underlying these traits should be shared. Mitochondrial respiratory capacity (leak and phosphorylating respiration) and mitochondrial content (cytochrome c oxidase activity) were determined in the liver and white muscle of brown trout Salmo trutta of similar age and maintenance conditions. SMR and MMR were uncorrelated across individuals and were not associated with the same mitochondrial properties, suggesting that they are under the control of separate physiological processes. Moreover, tissue-specific relationships between mitochondrial properties and whole-organism metabolic traits were observed. Specifically, SMR was positively associated with leak respiration in liver mitochondria, while MMR was positively associated with muscle mitochondrial leak respiration and mitochondrial content. These results suggest that a high SMR or MMR, rather than signaling a higher ability for respiration-driven ATP synthesis, may actually reflect greater dissipation of energy, driven by proton leak across the mitochondrial inner membrane. Knowledge of these links should aid interpretation of the potential fitness consequences of such variation in metabolism, given the importance of mitochondria in the utilization of resources and their allocation to performance.

  12. Microsatellite interruptions stabilize primate genomes and exist as population-specific single nucleotide polymorphisms within individual human genomes.

    Science.gov (United States)

    Ananda, Guruprasad; Hile, Suzanne E; Breski, Amanda; Wang, Yanli; Kelkar, Yogeshwar; Makova, Kateryna D; Eckert, Kristin A

    2014-07-01

    Interruptions of microsatellite sequences impact genome evolution and can alter disease manifestation. However, human polymorphism levels at interrupted microsatellites (iMSs) are not known at a genome-wide scale, and the pathways for gaining interruptions are poorly understood. Using the 1000 Genomes Phase-1 variant call set, we interrogated mono-, di-, tri-, and tetranucleotide repeats up to 10 units in length. We detected ∼26,000-40,000 iMSs within each of four human population groups (African, European, East Asian, and American). We identified population-specific iMSs within exonic regions, and discovered that known disease-associated iMSs contain alleles present at differing frequencies among the populations. By analyzing longer microsatellites in primate genomes, we demonstrate that single interruptions result in a genome-wide average two- to six-fold reduction in microsatellite mutability, as compared with perfect microsatellites. Centrally located interruptions lowered mutability dramatically, by two to three orders of magnitude. Using a biochemical approach, we tested directly whether the mutability of a specific iMS is lower because of decreased DNA polymerase strand slippage errors. Modeling the adenomatous polyposis coli tumor suppressor gene sequence, we observed that a single base substitution interruption reduced strand slippage error rates five- to 50-fold, relative to a perfect repeat, during synthesis by DNA polymerases α, β, or η. Computationally, we demonstrate that iMSs arise primarily by base substitution mutations within individual human genomes. Our biochemical survey of human DNA polymerase α, β, δ, κ, and η error rates within certain microsatellites suggests that interruptions are created most frequently by low fidelity polymerases. Our combined computational and biochemical results demonstrate that iMSs are abundant in human genomes and are sources of population-specific genetic variation that may affect genome stability. The

  13. Individual Polychlorinated Biphenyl (PCB) Congeners Produce Tissue- and Gene-Specific Effects on Thyroid Hormone Signaling during Development

    Science.gov (United States)

    Giera, Stefanie; Bansal, Ruby; Ortiz-Toro, Theresa M.; Taub, Daniel G.

    2011-01-01

    Polychlorinated biphenyls (PCB) are industrial chemicals linked to developmental deficits that may be caused in part by disrupting thyroid hormone (TH) action by either reducing serum TH or interacting directly with the TH receptor (TR). Individual PCB congeners can activate the TR in vitro when the metabolic enzyme cytochrome P4501A1 (CYP1A1) is induced, suggesting that specific PCB metabolites act as TR agonists. To test this hypothesis in vivo, we compared two combinations of PCB congeners that either activate the TR (PCB 105 and 118) or not (PCB 138 and 153) in the presence or absence of a PCB congener (PCB 126) that induces CYP1A1 in vitro. Aroclor 1254 was used as a positive control, and a group treated with propylthiouracil was included to characterize the effects of low serum TH. We monitored the effects on TH signaling in several peripheral tissues by measuring the mRNA expression of well-known TH-response genes in these tissues. Aroclor 1254 and its component PCB 105/118/126 reduced total T4 to the same extent as that of propylthiouracil but increased the expression of some TH target genes in liver. This effect was strongly correlated with CYP1A1 expression supporting the hypothesis that metabolism is necessary. Effects were gene and tissue specific, indicating that tissue-specific metabolism is an important component of PCB disruption of TH action and that PCB metabolites interact in complex ways with the TR. These are essential mechanisms to consider when evaluating the health risks of contaminant exposures, for both PCB and other polycyclic compounds known to interact with nuclear hormone receptors. PMID:21540284

  14. Highly significant linkage to the SLI1 locus in an expanded sample of individuals affected by specific language impairment.

    Science.gov (United States)

    2004-06-01

    Specific language impairment (SLI) is defined as an unexplained failure to acquire normal language skills despite adequate intelligence and opportunity. We have reported elsewhere a full-genome scan in 98 nuclear families affected by this disorder, with the use of three quantitative traits of language ability (the expressive and receptive tests of the Clinical Evaluation of Language Fundamentals and a test of nonsense word repetition). This screen implicated two quantitative trait loci, one on chromosome 16q (SLI1) and a second on chromosome 19q (SLI2). However, a second independent genome screen performed by another group, with the use of parametric linkage analyses in extended pedigrees, found little evidence for the involvement of either of these regions in SLI. To investigate these loci further, we have collected a second sample, consisting of 86 families (367 individuals, 174 independent sib pairs), all with probands whose language skills are >/=1.5 SD below the mean for their age. Haseman-Elston linkage analysis resulted in a maximum LOD score (MLS) of 2.84 on chromosome 16 and an MLS of 2.31 on chromosome 19, both of which represent significant linkage at the 2% level. Amalgamation of the wave 2 sample with the cohort used for the genome screen generated a total of 184 families (840 individuals, 393 independent sib pairs). Analysis of linkage within this pooled group strengthened the evidence for linkage at SLI1 and yielded a highly significant LOD score (MLS = 7.46, interval empirical Preading-related measures (basic reading [MLS = 1.49], spelling [MLS = 2.67], and reading comprehension [MLS = 1.99] subtests of the Wechsler Objectives Reading Dimensions).

  15. Individualizing Services, Individualizing Responsibility

    DEFF Research Database (Denmark)

    Garsten, Christina; Hollertz, Katarina; Jacobsson, Kerstin

    possibilities for individual voice, autonomy and self-determination in the local delivery of activation policy? What barriers do specific organisational models and practices imply for clients to choose, determine and access tailor-made programmes and services? What policy technologies are at work in governing......-oriented, and the normative demands placed on individuals appear increasingly totalizing, concerning the whole individual rather than the job-related aspects only. The paper is based on 23 in-depth interviews with individual clients as well as individual caseworkers and other professionals engaged in client-related work...

  16. The reconstitution of the thymus in immunosuppressed individuals restores CD4-specific cellular and humoral immune responses

    Science.gov (United States)

    Plana, Montserrat; Garcia, Felipe; Darwich, Laila; Romeu, Joan; López, Anna; Cabrera, Cecilia; Massanella, Marta; Canto, Esther; Ruiz-Hernandez, Raul; Blanco, Julià; Sánchez, Marcelo; Gatell, Josep M; Clotet, Bonaventura; Ruiz, Lidia; Bofill, Margarita

    2011-01-01

    Infection with HIV-1 frequently results in the loss of specific cellular immune responses and an associated lack of antibodies. Recombinant growth hormone (rGH) administration reconstitutes thymic tissue and boosts the levels of peripheral T cells, so rGH therapy may be an effective adjuvant through promoting the recovery of lost cellular and T-cell-dependent humoral immune responses in immunosuppressed individuals. To test this concept, we administered rGH to a clinically defined group of HIV-1-infected subjects with defective cellular and serological immune responses to at least one of three commonly employed vaccines (hepatitis A, hepatitis B or tetanus toxoid). Of the original 278 HIV-1-infected patients entering the trial, only 20 conformed to these immunological criteria and were randomized into three groups: Group A (n = 8) receiving rGH and challenged with the same vaccine to which they were unresponsive and Groups B (n = 5) and C (n = 7) who received either rGH or vaccination alone, respectively. Of the eight subjects in Group A, five recovered CD4 cellular responses to vaccine antigen and four of these produced the corresponding antibodies. In the controls, three of the five in group B recovered cellular responses with two producing antibodies, whereas three of the seven in Group C recovered CD4 responses, with only two producing antibodies. Significantly, whereas seven of ten patients receiving rGH treatment in Group A (six patients) and B (one patient) recovered T-cell responses to HIVp24, only two of six in Group C responded similarly. In conclusion, reconstitution of the thymus in immunosuppressed adults through rGH hormone treatment restored both specific antibody and CD4 T-cell responses. PMID:21501161

  17. Reduced susceptibility of tomato stem to the necrotrophic fungus Botrytis cinerea is associated with a specific adjustment of fructose content in the host sugar pool.

    Science.gov (United States)

    Lecompte, François; Nicot, Philippe C; Ripoll, Julie; Abro, Manzoor A; Raimbault, Astrid K; Lopez-Lauri, Félicie; Bertin, Nadia

    2017-03-01

    Plant soluble sugars, as main components of primary metabolism, are thought to be implicated in defence against pathogenic fungi. However, the function of sucrose and hexoses remains unclear. This study aimed to identify robust patterns in the dynamics of soluble sugars in sink tissues of tomato plants during the course of infection by the necrotrophic fungus Botrytis cinerea . Distinct roles for glucose and fructose in defence against B. cinerea were hypothesized. We examined sugar contents and defence hormonal markers in tomato stem tissues before and after infection by B. cinerea , in a range of abiotic environments created by various nitrogen and water supplies. Limited nitrogen or water supplies increased tomato stem susceptibility to B. cinerea . Glucose and fructose contents of tissues surrounding infection sites evolved differently after inoculation. The fructose content never decreased after inoculation with B. cinerea , while that of glucose showed either positive or negative variation, depending on the abiotic environment. An increase in the relative fructose content (defined as the proportion of fructose in the soluble sugar pool) was observed in the absence of glucose accumulation and was associated with lower susceptibility. A lower expression of the salicylic acid marker PR1a , and a lower repression of a jasmonate marker COI1 were associated with reduced susceptibility. Accordingly, COI1 expression was positively correlated with the relative fructose contents 7 d after infection. Small variations of fructose content among the sugar pool are unlikely to affect intrinsic pathogen growth. Our results highlight distinct use of host glucose and fructose after infection by B. cinerea and suggest strongly that adjustment of the relative fructose content is required for enhanced plant defence.

  18. Interpreting "Personality" Taxonomies: Why Previous Models Cannot Capture Individual-Specific Experiencing, Behaviour, Functioning and Development. Major Taxonomic Tasks Still Lay Ahead.

    Science.gov (United States)

    Uher, Jana

    2015-12-01

    As science seeks to make generalisations, a science of individual peculiarities encounters intricate challenges. This article explores these challenges by applying the Transdisciplinary Philosophy-of-Science Paradigm for Research on Individuals (TPS-Paradigm) and by exploring taxonomic "personality" research as an example. Analyses of researchers' interpretations of the taxonomic "personality" models, constructs and data that have been generated in the field reveal widespread erroneous assumptions about the abilities of previous methodologies to appropriately represent individual-specificity in the targeted phenomena. These assumptions, rooted in everyday thinking, fail to consider that individual-specificity and others' minds cannot be directly perceived, that abstract descriptions cannot serve as causal explanations, that between-individual structures cannot be isomorphic to within-individual structures, and that knowledge of compositional structures cannot explain the process structures of their functioning and development. These erroneous assumptions and serious methodological deficiencies in widely used standardised questionnaires have effectively prevented psychologists from establishing taxonomies that can comprehensively model individual-specificity in most of the kinds of phenomena explored as "personality", especially in experiencing and behaviour and in individuals' functioning and development. Contrary to previous assumptions, it is not universal models but rather different kinds of taxonomic models that are required for each of the different kinds of phenomena, variations and structures that are commonly conceived of as "personality". Consequently, to comprehensively explore individual-specificity, researchers have to apply a portfolio of complementary methodologies and develop different kinds of taxonomies, most of which have yet to be developed. Closing, the article derives some meta-desiderata for future research on individuals' "personality".

  19. HIV-1 Infection Is Associated with Depletion and Functional Impairment ofMycobacterium tuberculosis-Specific CD4 T Cells in Individuals with Latent Tuberculosis Infection.

    Science.gov (United States)

    Day, Cheryl L; Abrahams, Deborah A; Harris, Levelle D; van Rooyen, Michele; Stone, Lynnett; de Kock, Marwou; Hanekom, Willem A

    2017-09-15

    Coinfection with HIV is the single greatest risk factor for reactivation of latent Mycobacterium tuberculosis infection (LTBI) and progression to active tuberculosis disease. HIV-associated dysregulation of adaptive immunity by depletion of CD4 Th cells most likely contributes to loss of immune control of LTBI in HIV-infected individuals, although the precise mechanisms whereby HIV infection impedes successful T cell-mediated control of M. tuberculosis have not been well defined. To further delineate mechanisms whereby HIV impairs protective immunity to M. tuberculosis , we evaluated the frequency, phenotype, and functional capacity of M. tuberculosis -specific CD4 T cells in HIV-infected and HIV-uninfected adults with LTBI. HIV infection was associated with a lower total frequency of cytokine-producing M. tuberculosis -specific CD4 T cells, and preferential depletion of a discrete subset of M. tuberculosis -specific IFN-γ + IL-2 - TNF-α + CD4 T cells. M. tuberculosis -specific CD4 T cells in HIV-infected individuals expressed significantly higher levels of Ki67, compared with HIV-uninfected individuals, thus indicating recent activation and turnover of these cells in vivo. The ex vivo proliferative capacity of M. tuberculosis -specific CD4 T cells was markedly impaired in HIV-infected individuals, compared with HIV-uninfected individuals. Moreover, HIV infection was associated with increased M. tuberculosis Ag-induced CD4 T cell death ex vivo, indicating a possible mechanism contributing to impaired proliferative capacity of M. tuberculosis -specific CD4 T cells in HIV-infected individuals. These data provide new insights into the parameters of M. tuberculosis -specific CD4 T cell immunity that are impaired in HIV-infected individuals with LTBI, which may contribute to their increased risk of developing active tuberculosis disease. Copyright © 2017 by The American Association of Immunologists, Inc.

  20. FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats.

    Science.gov (United States)

    Xu, Jingjing; Wang, Rui; Liu, Yuan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2017-12-01

    Exposure to stressful events induces depressive-like symptoms and increases susceptibility to depression. However, the molecular mechanisms are not fully understood. Studies reported that FK506 binding protein51 (FKBP5), the co-chaperone protein of glucocorticoid receptors (GR), plays a crucial role. Further, miR-124a and miR-18a are involved in the regulation of FKBP5/GR function. However, few studies have referred to effects of early life stress on depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a in the basolateral amygdala (BLA) from adolescence to adulthood. This study aimed to examine the dynamic alternations of depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a expressions in the BLA of chronic unpredictable mild stress (CUMS) rats and dexamethasone administration rats during the adolescent period. Meanwhile, the GR antagonist, RU486, was used as a means of intervention. We found that CUMS and dexamethasone administration in the adolescent period induced permanent depressive-like behaviours and memory impairment, decreased GR expression, and increased FKBP5 and miR-124a expression in the BLA of both adolescent and adult rats. However, increased miR-18a expression in the BLA was found only in adolescent rats. Depressive-like behaviours were positively correlated with the level of miR-124a, whereas GR levels were negatively correlated with those in both adolescent and adult rats. Our results suggested FKBP5/GR and miR-124a in the BLA were associated with susceptibility to depressive disorder in the presence of stressful experiences in early life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The Relationship between Autobiographical Self-Focus and Memory Specificity/Overgenerality: differences between Individuals with and without a Diagnosis of Depression

    Directory of Open Access Journals (Sweden)

    Michael Bender

    2015-12-01

    Full Text Available Research has revealed that clinical depression is related to reduced specificity and/or overgenerality in autobiographical memory. We set out to investigate this relationship by comparing depressed (n = 40 and non-depressed (n = 40 individuals not only in terms of autobiographical memory specificity/generality, but also in terms of narrative structure. Specificity was assessed with the Autobiographical Memory Test (AMT; Williams & Broadbent, 1986 and participants also provided open-ended memories, which were analyzed for autobiographical cognitive complexity (Woike, 1994. Narrative differentiation, as an indicator of self-focus, was negatively related to specificity and positively to overgenerality of particularly negative autobiographical memories - but only in the depressed sample. Relationships were significantly different among non-depressed individuals. Results are discussed in the context of the relation between specificity/overgenerality and self-focus.

  2. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    DEFF Research Database (Denmark)

    Belstrøm, Daniel; Jersie-Christensen, Rosa R; Lyon, David

    2016-01-01

    BACKGROUND: The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with...

  3. Individual Dismissal from the Perspective of the Employer and Specific Regulations if Bankruptcy of the Company in Romania

    OpenAIRE

    Olimpia-Monica Matias

    2015-01-01

    Individual dismissal is individual employment termination as a result of the effective abolition of the position held by the employee, for one or more reasons not related to his person, based on actual cause real and serious under art. 65 Romanian Labour Code. It should be noted that the practice shows that, at present, the reasons are, in fact, the same: economic, technological, organizational. As for checking the validity of the plea raised by the employer, it falls within the jurisdiction ...

  4. Genetic Susceptibility to Atherosclerosis

    Directory of Open Access Journals (Sweden)

    Sanja Kovacic

    2012-01-01

    Full Text Available Atherosclerosis is a complex multifocal arterial disease involving interactions of multiple genetic and environmental factors. Advances in techniques of molecular genetics have revealed that genetic ground significantly influences susceptibility to atherosclerotic vascular diseases. Besides further investigations of monogenetic diseases, candidate genes, genetic polymorphisms, and susceptibility loci associated with atherosclerotic diseases have been identified in recent years, and their number is rapidly increasing. This paper discusses main genetic investigations fields associated with human atherosclerotic vascular diseases. The paper concludes with a discussion of the directions and implications of future genetic research in arteriosclerosis with an emphasis on prospective prediction from an early age of individuals who are predisposed to develop premature atherosclerosis as well as to facilitate the discovery of novel drug targets.

  5. Genetic architecture of intrinsic antibiotic susceptibility.

    Directory of Open Access Journals (Sweden)

    Hany S Girgis

    2009-05-01

    Full Text Available Antibiotic exposure rapidly selects for more resistant bacterial strains, and both a drug's chemical structure and a bacterium's cellular network affect the types of mutations acquired.To better characterize the genetic determinants of antibiotic susceptibility, we exposed a transposon-mutagenized library of Escherichia coli to each of 17 antibiotics that encompass a wide range of drug classes and mechanisms of action. Propagating the library for multiple generations with drug concentrations that moderately inhibited the growth of the isogenic parental strain caused the abundance of strains with even minor fitness advantages or disadvantages to change measurably and reproducibly. Using a microarray-based genetic footprinting strategy, we then determined the quantitative contribution of each gene to E. coli's intrinsic antibiotic susceptibility. We found both loci whose removal increased general antibiotic tolerance as well as pathways whose down-regulation increased tolerance to specific drugs and drug classes. The beneficial mutations identified span multiple pathways, and we identified pairs of mutations that individually provide only minor decreases in antibiotic susceptibility but that combine to provide higher tolerance.Our results illustrate that a wide-range of mutations can modulate the activity of many cellular resistance processes and demonstrate that E. coli has a large mutational target size for increasing antibiotic tolerance. Furthermore, the work suggests that clinical levels of antibiotic resistance might develop through the sequential accumulation of chromosomal mutations of small individual effect.

  6. Susceptible Bodies

    DEFF Research Database (Denmark)

    Grünenberg, Kristina

    2014-01-01

    This article explores a group of complementary alternative medical (CAM) practitioners’ perceptions and cultivation of a specific type of relationship to their clients, which is connected to what they consider a successful treatment process. More specifically, the article explores how what is und...... of new worlds. Methodologically the article draws on practitioner interviews and participant-observation in clinics of acupuncture and reflexology....

  7. Is this your smart phone? : On connecting MAC-addresses to a specific individual using access point data

    OpenAIRE

    Vesterlund, Martin; Wiklund, Viktor

    2015-01-01

    Context. The potential to track individuals become greater and greater in the society today. We want to develop a method that is easy to understand so more people can participate in the discussion about the collection, and storing, of seemingly non-invasive device data and personal integrity. Objectives. In this work we investigate the potential to connect a WiFi enabled device to a known individual by analysing log files. Since we want to keep the method as simple as possible we choose to no...

  8. Magnetic field dependence of the magnetic susceptibility and the specific heat of the doped plasticized polyaniline (PANI-DB3EPSA)0.5.

    Science.gov (United States)

    Djurado, D; Pron, A; Jacquot, J F; Travers, J P; Adriano, C; Vargas, J M; Pagliuso, P G; Rettori, C; Lesseux, G G; Fier, I; Walmsley, L

    2011-05-25

    Specific heat, magnetization and electron spin resonance (ESR) data obtained from a self-standing film of the doped plasticized polyaniline (PANI-DB3EPSA)(0.5) are shown. No long range magnetic order has been observed at zero magnetic field, above 2 K. For a magnetic field of 3.3 kOe applied perpendicular to the plane of the film, a clear signature of an induced ordered state can be seen in the specific heat data and ESR also reveals this antiferromagnetic order. An electronic contribution is detected from ESR, magnetization and specific heat; however, for T ≤ 5 K, the specific heat data show the existence of a gap. Magnetization data also show a low temperature dominant Curie behaviour which cannot be seen from ESR, probably due to a very large linewidth, suggesting short range correlations among spin 1/2 polarons.

  9. Behavioural Flexibility in Individuals with Angelman Syndrome, Down Syndrome, Non-Specific Intellectual Disability and Autism Spectrum Disorder

    Science.gov (United States)

    Didden, R.; Sigafoos, J.; Green, V. A.; Korzilius, H.; Mouws, C.; Lancioni, G. E.; O'Reilly, M. F.; Curfs, L. M. G.

    2008-01-01

    Background: Little is known about behavioural flexibility in children and adults with Angelman syndrome and whether people with this syndrome have more or less problems in being behaviourally flexible as compared with other people. Method: Behavioural flexibility scores were assessed in 129 individuals with Angelman syndrome using 11 items from…

  10. Can food specialization by individual Oystercatchers Haematopus ostralegus be explained by differences in prey specific handling efficiencies?

    NARCIS (Netherlands)

    Wanink, JH; Zwarts, L

    1996-01-01

    Three individually-tested adult Oystercatchers took different proportions of shallow-buried bivalves Mya arenaria and Scrobicularia plana from a mixture on offer in an experimental situation. Two birds, taking mainly or exclusively Scrobicularia, selected the species as predicted by a random search

  11. The Utility of Person-Specific Analyses for Investigating Developmental Processes: An Analytic Primer on Studying the Individual

    Science.gov (United States)

    Gayles, Jochebed G.; Molenaar, Peter C. M.

    2013-01-01

    The fields of psychology and human development are experiencing a resurgence of scientific inquiries about phenomena that unfold at the level of the individual. This article addresses the issues of analyzing intraindividual psychological/developmental phenomena using standard analytical techniques for interindividual variation. When phenomena are…

  12. Aspects of spirituality in medical doctors and their relation to specific views of illness and dealing with their patients' individual situation.

    Science.gov (United States)

    Büssing, Arndt; Hirdes, Almut Tabea; Baumann, Klaus; Hvidt, Niels Christian; Heusser, Peter

    2013-01-01

    We intended to analyse which aspects of spirituality are of relevance for medical doctors in a mostly secular society and how their spiritual/religious attitudes are related to specific views of illness, their dealing with patients' individual situation, and finally physicians' life satisfaction. Data from an anonymous survey enrolling 237 medical doctors from Germany (mean age 45.7 ± 9.6, 58% male, 42% female) indicated that secular forms of spirituality scored highest, while specific religious orientation had the lowest scores. Physicians with a specific specialization in complementary/alternative medicine (CAM) or anthroposophic medicine differed from their conventional counterparts with respect to specific aspects of spirituality; however, the specific views associated with these specialisations were only weakly to moderately correlated with physicians' view on the meaning of illness and how they assume that they would deal with their patients' individual situation. Of interest, the specific aspects of spirituality were negatively correlated with the view of "illness as a meaningless interruption" of life, indicating that physicians with a spiritual attitude would see illness also as a chance for an "individual development" and associated with a "biographical meaning" rather than just a "useless interruption" of life.

  13. Aspects of Spirituality in Medical Doctors and Their Relation to Specific Views of Illness and Dealing with Their Patients' Individual Situation

    Directory of Open Access Journals (Sweden)

    Arndt Büssing

    2013-01-01

    Full Text Available We intended to analyse which aspects of spirituality are of relevance for medical doctors in a mostly secular society and how their spiritual/religious attitudes are related to specific views of illness, their dealing with patients' individual situation, and finally physicians' life satisfaction. Data from an anonymous survey enrolling 237 medical doctors from Germany (mean age 45.7 ± 9.6, 58% male, 42% female indicated that secular forms of spirituality scored highest, while specific religious orientation had the lowest scores. Physicians with a specific specialization in complementary/alternative medicine (CAM or anthroposophic medicine differed from their conventional counterparts with respect to specific aspects of spirituality; however, the specific views associated with these specialisations were only weakly to moderately correlated with physicians' view on the meaning of illness and how they assume that they would deal with their patients' individual situation. Of interest, the specific aspects of spirituality were negatively correlated with the view of “illness as a meaningless interruption” of life, indicating that physicians with a spiritual attitude would see illness also as a chance for an “individual development” and associated with a “biographical meaning” rather than just a “useless interruption” of life.

  14. Captive bottlenose dolphins and killer whales harbor a species-specific skin microbiota that varies among individuals.

    Science.gov (United States)

    Chiarello, M; Villéger, S; Bouvier, C; Auguet, J C; Bouvier, T

    2017-11-10

    Marine animals surfaces host diverse microbial communities, which play major roles for host's health. Most inventories of marine animal surface microbiota have focused on corals and fishes, while cetaceans remain overlooked. The few studies focused on wild cetaceans, making difficult to distinguish intrinsic inter- and/or intraspecific variability in skin microbiota from environmental effects. We used high-throughput sequencing to assess the skin microbiota from 4 body zones of 8 bottlenose dolphins (Tursiops truncatus) and killer whales (Orcinus orca), housed in captivity (Marineland park, France). Overall, cetacean skin microbiota is more diverse than planktonic communities and is dominated by different phylogenetic lineages and functions. In addition, the two cetacean species host different skin microbiotas. Within each species, variability was higher between individuals than between body parts, suggesting a high individuality of cetacean skin microbiota. Overall, the skin microbiota of the assessed cetaceans related more to the humpback whale and fishes' than to microbiotas of terrestrial mammals.

  15. Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls

    Directory of Open Access Journals (Sweden)

    Daniel Belstrøm

    2016-09-01

    Full Text Available Background The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals. Methods Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode. Results We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease. Conclusions Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity.

  16. CTL escape and increased viremia irrespective of HIV-specific CD4+ T-helper responses in two HIV-infected individuals

    NARCIS (Netherlands)

    Geels, Mark J.; Jansen, Christine A.; Baan, Elly; de Cuyper, Iris M.; van Schijndel, Gijs J. M.; Schuitemaker, Hanneke; Goudsmit, Jaap; Pollakis, Georgios; Miedema, Frank; Paxton, William A.; van Baarle, Debbie

    2006-01-01

    We investigated whether development of mutations leads to loss of CD8 T-cell recognition in HIV-1 infection and is possibly linked to alterations in HIV-1-specific CD4(+) T-cell responses in 2 HIV-infected individuals. In patient, H434 full genome sequencing of HIV-1 biological clones at early and

  17. Assessing the specificity of autobiographical memory in individuals at a trait-based vulnerability to bipolar disorder using a sentence completion task.

    Science.gov (United States)

    Dempsey, Robert C; Gooding, Patricia A; Jones, Steven H

    2014-01-01

    Overgeneral autobiographical memory recall has been associated with the diagnosis of bipolar disorder, but the role of overgenerality in the vulnerability to bipolar disorder remains under-researched. While a previous study suggested that high-risk individuals for bipolar disorder recall emotionally negative memories in specific detail, this is in contrast to memory recall patterns noted in bipolar samples. The Autobiographical Memory Test (AMT) used in previous non-clinical studies has also been criticised for not being sensitive to overgenerality due to its repetition of specificity instructions and practice trials. The traditional AMT format may allow some individuals to override their trait-based tendencies to be overgeneral. The current study used a sentence completion task to assess memory specificity in groups of students at a low and high trait-based vulnerability for bipolar disorder. In contrast to previous research, high-risk individuals recalled fewer specific positive memories and greater numbers of overgeneral negative memories than low-risk individuals. These results support the notion that the vulnerability for bipolar disorder might be associated with similar recall biases as demonstrated in bipolar samples, and that the AMT might not be sufficiently sensitive to detect overgenerality in non-clinical groups. The implications of these findings and directions for future research are discussed.

  18. Effects of streamflow diversion on a fish population: combining empirical data and individual-based models in a site-specific evaluation

    Science.gov (United States)

    Bret C. Harvey; Jason L. White; Rodney J. Nakamoto; Steven F. Railsback

    2014-01-01

    Resource managers commonly face the need to evaluate the ecological consequences of specific water diversions of small streams. We addressed this need by conducting 4 years of biophysical monitoring of stream reaches above and below a diversion and applying two individual-based models of salmonid fish that simulated different levels of behavioral complexity. The...

  19. Aspects of spirituality in medical doctors and their relation to specific views of illness and dealing with their patients' individual situation

    DEFF Research Database (Denmark)

    Büssing, Arndt; Hirdes, Almut Tabea; Baumann, Klaus

    2013-01-01

    We intended to analyse which aspects of spirituality are of relevance for medical doctors in a mostly secular society and how their spiritual/religious attitudes are related to specific views of illness, their dealing with patients' individual situation, and finally physicians' life satisfaction....

  20. Identification of ACAT1- and ACAT2-specific inhibitors using a novel, cell-based fluorescence assay: individual ACAT uniqueness

    National Research Council Canada - National Science Library

    Lada, Aaron T; Davis, Matthew; Kent, Carol; Chapman, James; Tomoda, Hiroshi; Omura, Satoshi; Rudel, Lawrence L

    .... In this study, NBD-cholesterol was used to screen for specific inhibitors of ACAT1 and ACAT2. Incubation of AC29 cells, which do not contain ACAT activity, with NBD-cholesterol showed weak fluorescence when the compound was localized in the membrane...

  1. Role of Working Memory in Explaining the Performance of Individuals with Specific Reading Comprehension Difficulties: A Meta-Analysis

    Science.gov (United States)

    Carretti, Barbara; Borella, Erika; Cornoldi, Cesare; De Beni, Rossana

    2009-01-01

    It is well established that working memory is related to reading comprehension ability. However, its role in explaining specific reading comprehension difficulties is still under debate: the issue mainly concerns whether the contribution of working memory is dependent on task modality (verbal tasks being more predictive than visuo-spatial tasks)…

  2. Predicting Homophobic Behavior among Heterosexual Youth: Domain General and Sexual Orientation-Specific Factors at the Individual and Contextual Level

    Science.gov (United States)

    Poteat, V. Paul; DiGiovanni, Craig D.; Scheer, Jillian R.

    2013-01-01

    As a form of bias-based harassment, homophobic behavior remains prominent in schools. Yet, little attention has been given to factors that underlie it, aside from bullying and sexual prejudice. Thus, we examined multiple domain general (empathy, perspective-taking, classroom respect norms) and sexual orientation-specific factors (sexual…

  3. Lexically Specific Knowledge and Individual Differences in Adult Native Speakers' Processing of the English Passive

    Science.gov (United States)

    Street, James A.; Dabrowska, Ewa

    2014-01-01

    This article provides experimental evidence for the role of lexically specific representations in the processing of passive sentences and considerable education-related differences in comprehension of the passive construction. The experiment measured response time and decision accuracy of participants with high and low academic attainment using an…

  4. Microstructural integrity of the superior cerebellar peduncle is associated with an impaired proprioceptive weighting capacity in individuals with non-specific low back pain.

    Directory of Open Access Journals (Sweden)

    Madelon Pijnenburg

    Full Text Available Postural control is a complex sensorimotor task that requires an intact network of white matter connections. The ability to weight proprioceptive signals is crucial for postural control. However, research into central processing of proprioceptive signals for postural control is lacking. This is specifically of interest in individuals with non-specific low back pain (NSLBP, because impairments in postural control have been observed as possible underlying mechanisms of NSLBP. Therefore, the objective was to investigate potential differences in sensorimotor white matter microstructure between individuals with NSLBP and healthy controls, and to determine whether the alterations in individuals with NSLBP are associated with the capacity to weight proprioceptive signals for postural control.The contribution of proprioceptive signals from the ankle and back muscles to postural control was evaluated by local muscle vibration in 18 individuals with NSLBP and 18 healthy controls. Center of pressure displacement in response to muscle vibration was determined during upright standing on a stable and unstable support surface. Diffusion magnetic resonance imaging was applied to examine whether this proprioceptive contribution was associated with sensorimotor white matter microstructure.Individuals with NSLBP showed a trend towards a reduced fractional anisotropy along the left superior cerebellar peduncle compared to healthy controls (p = 0.039. The impaired microstructural integrity of the superior cerebellar peduncle in individuals with NSLBP was significantly correlated with the response to ankle muscle vibration (p<0.003.In individuals with NSLBP, a decreased integrity of the superior cerebellar peduncle was associated with an increased reliance on ankle muscle proprioception, even on unstable support surface, which implies an impaired proprioceptive weighting capacity. Our findings emphasize the importance of the superior cerebellar peduncle in

  5. Specific genes are selectively expressed between cumulus and granulosa cells from individual human pre-ovulatory follicles

    DEFF Research Database (Denmark)

    Grøndahl, M L; Andersen, C Yding; Bogstad, J

    2012-01-01

    During folliculogenesis the granulosa cells differentiate into two cell types: Cumulus cells (CC) and mural granulosa cells (MGC). The objective of the study was to generate and compare the transcriptomes of MGC and CC from the pre-ovulatory follicle to characterize the detailed profile of the tw...... cell populations shortly before ovulation.Twenty-one IVF/ICSI patients undergoing controlled ovarian stimulation (COS) donated CC and MGC from individual follicles containing metaphase-II oocytes. Cells were prepared immediately after recovery and mRNA was isolated for whole......-genome-gene-expression analysis and RT-PCRs. Paired (within the individual follicle) comparisons between the CC and MGC expression profiles were performed and corrected for multiple comparisons.A total of 1562 genes were differentially expressed by >2-fold (p-value8-fold changed and represented specialised cellular functional...... categories such as inflammatory response, extracellular-matrix and cell-cell-communication while the 1406 genes 2-8-fold changed represented functional categories such as proliferation and lipid metabolism. Transcripts not previously linked to the follicle were found to be differentially expressed between CC...

  6. Multifractality in individual honeybee behavior hints at colony-specific social cascades: Reanalysis of radio-frequency identification data from five different colonies

    Science.gov (United States)

    Carver, Nicole S.; Kelty-Stephen, Damian G.

    2017-02-01

    Honeybees (Apis mellifera) exhibit complex coordination and interaction across multiple behaviors such as swarming. This coordination among honeybees in the same colony is remarkably similar to the concept of informational cascades. The multifractal geometry of cascades suggests that multifractal measures of individual honeybee activity might carry signatures of these colony-wide coordinations. The present work reanalyzes time stamps of entrances to and exits from the hive captured by radio-frequency identification (RFID) sensors reading RFID tags on individual bees. Indeed, both multifractal spectrum width for individual bees' inter-reading interval series and differences of those widths from surrogates significantly predicted not just whether the individual bee's hive had a mesh enclosure but also predicted the specific membership of individual bees in one of five colonies. The significant effects of multifractality in matching honeybee activity to type of colony and, further, matching individual honeybees to their exact home colony suggests that multifractality quantifies key features of the colony-wide interactions across many scales. This relevance of multifractality to predicting colony type or colony membership adds additional credence to the cascade metaphor for colony organization. Perhaps, multifractality provides a new tool for exploring the relationship between individual organisms and larger, more complex social behaviors.

  7. Application of Individualized Speed Thresholds to Interpret Position Specific Running Demands in Elite Professional Rugby Union: A GPS Study.

    Directory of Open Access Journals (Sweden)

    Cillian Reardon

    Full Text Available A number of studies have used GPS technology to categorise rugby union locomotive demands. However, the utility of the results of these studies is confounded by small sample sizes, sub-elite player status and the global application of absolute speed thresholds to all player positions. Furthermore, many of these studies have used GPS units with low sampling frequencies. The aim of the present study was to compare and contrast the high speed running (HSR demands of professional rugby union when utilizing micro-technology units sampling at 10 Hz and applying relative or individualised speed zones. The results of this study indicate that application of individualised speed zones results in a significant shift in the interpretation of the HSR demands of both forwards and backs and positional sub-categories therein. When considering the use of an absolute in comparison to an individualised HSR threshold, there was a significant underestimation for forwards of HSR distance (HSRD (absolute = 269 ± 172.02, individualised = 354.72 ± 99.22, p < 0.001, HSR% (absolute = 5.15 ± 3.18, individualised = 7.06 ± 2.48, p < 0.001 and HSR efforts (HSRE (absolute = 18.81 ± 12.25; individualised = 24.78 ± 8.30, p < 0.001. In contrast, there was a significant overestimation of the same HSR metrics for backs with the use of an absolute threshold (HSRD absolute = 697.79 ± 198.11, individualised = 570.02 ± 171.14, p < 0.001; HSR% absolute = 10.85 ± 2.82, individualised = 8.95 ± 2.76, p < 0.001; HSRE absolute = 41.55 ± 11.25; individualised = 34.54 ± 9.24, p < 0.001. This under- or overestimation associated with an absolute speed zone applies to varying degrees across the ten positional sub-categories analyzed and also to individuals within the same positional sub-category. The results of the present study indicated that although use of an individulised HSR threshold improves the interpretation of the HSR demands on a positional basis, inter-individual

  8. Predictive patient-specific dosimetry and individualized dosing of pretargeted radioimmunotherapy in patients with advanced colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schoffelen, Rafke; Woliner-van der Weg, Wietske; Visser, Eric P.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, PO Box 9101, Nijmegen (Netherlands); Goldenberg, David M. [Garden State Cancer Center, Morris Plains, NJ (United States); Immunomedics, Inc., Morris Plains, NJ (United States); IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Sharkey, Robert M.; McBride, William J.; Chang, Chien-Hsing [Immunomedics, Inc., Morris Plains, NJ (United States); Rossi, Edmund A. [IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Graaf, Winette T.A. van der [Radboud University Medical Center, Department of Medical Oncology, Nijmegen (Netherlands)

    2014-08-15

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an {sup 111}In-labeled pretherapy test dose for personalized dosing of {sup 177}Lu-labeled IMP288 following pretargeting with the anti-CEA x anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC). In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after {sup 111}In-IMP288 injection for individualized dosing of PRIT with {sup 177}Lu-IMP288. Different dose schedules were studied, varying the interval between the bsMAb and peptide administration (5 days vs. 1 day), increasing the bsMAb dose (75 mg vs. 150 mg), and lowering the peptide dose (100 μg vs. 25 μg). TF2 and {sup 111}In/{sup 177}Lu-IMP288 clearance was highly variable. A strong correlation was observed between peptide residence times and individual TF2 blood concentrations at the time of peptide injection (Spearman's ρ = 0.94, P < 0.0001). PRIT with 7.4 GBq {sup 177}Lu-IMP288 resulted in low radiation doses to normal tissues (BMD <0.5 Gy, kidney dose <3 Gy). Predicted {sup 177}Lu-IMP288 BMD were in good agreement with the actual measured doses (mean ± SD difference -0.0026 ± 0.028 mGy/MBq). Hematological toxicity was mild in most patients, with only two (10 %) having grade 3-4 thrombocytopenia. A correlation was found between platelet toxicity and BMD (Spearman's ρ = 0.58, P = 0.008). No nonhematological toxicity was observed. These results show that individual high activity doses in PRIT in patients with CEA-expressing CRC could be safely administered by predicting the radiation dose to red marrow and kidneys, based on dosimetric analysis of a test dose of TF2 and {sup 111}In-IMP288. (orig.)

  9. Functionality of Dengue Virus Specific Memory T Cell Responses in Individuals Who Were Hospitalized or Who Had Mild or Subclinical Dengue Infection

    Science.gov (United States)

    Jeewandara, Chandima; Adikari, Thiruni N.; Gomes, Laksiri; Fernando, Samitha; Fernando, R. H.; Perera, M. K. T.; Ariyaratne, Dinuka; Kamaladasa, Achala; Salimi, Maryam; Prathapan, Shamini

    2015-01-01

    Background Although antibody responses to dengue virus (DENV) in naturally infected individuals have been extensively studied, the functionality of DENV specific memory T cell responses in relation to clinical disease severity is incompletely understood. Methodology/Principal findings Using ex vivo IFNγ ELISpot assays, and by determining cytokines produced in ELISpot supernatants, we investigated the functionality of DENV-specific memory T cell responses in a large cohort of individuals from Sri Lanka (n=338), who were naturally infected and were either hospitalized due to dengue or had mild or sub clinical dengue infection. We found that T cells of individuals with both past mild or sub clinical dengue infection and who were hospitalized produced multiple cytokines when stimulated with DENV-NS3 peptides. However, while DENV-NS3 specific T cells of those with mild/sub clinical dengue infection were more likely to produce only granzyme B (p=0.02), those who were hospitalized were more likely to produce both TNFα and IFNγ (p=0.03) or TNFα alone. We have also investigated the usefulness of a novel T cell based assay, which can be used to determine the past infecting DENV serotype. 92.4% of DENV seropositive individuals responded to at least one DENV serotype of this assay and none of the seronegatives responded. Individuals who were seronegative, but had received the Japanese encephalitis vaccine too made no responses, suggesting that the peptides used in this assay did not cross react with the Japanese encephalitis virus. Conclusions/significance The types of cytokines produced by DENV-specific memory T cells appear to influence the outcome of clinical disease severity. The novel T cell based assay, is likely to be useful in determining the past infecting DENV serotype in immune-epidemiological studies and also in dengue vaccine trials. PMID:25875020

  10. Identification of ACAT1- and ACAT2-specific inhibitors using a novel, cell-based fluorescence assay: individual ACAT uniqueness.

    Science.gov (United States)

    Lada, Aaron T; Davis, Matthew; Kent, Carol; Chapman, James; Tomoda, Hiroshi; Omura, Satoshi; Rudel, Lawrence L

    2004-02-01

    Acyl CoA:cholesterol acyltransferase 1 (ACAT1) and ACAT2 are enzymes responsible for the formation of cholesteryl esters in tissues. While both ACAT1 and ACAT2 are present in the liver and intestine, the cells containing either enzyme within these tissues are distinct, suggesting that ACAT1 and ACAT2 have separate functions. In this study, NBD-cholesterol was used to screen for specific inhibitors of ACAT1 and ACAT2. Incubation of AC29 cells, which do not contain ACAT activity, with NBD-cholesterol showed weak fluorescence when the compound was localized in the membrane. When AC29 cells stably transfected with either ACAT1 or ACAT2 were incubated with NBD-cholesterol, the fluorescent signal localized to the nonpolar core of cytoplasmic lipid droplets was strongly fluorescent and was correlated with two independent measures of ACAT activity. Several compounds were found to have greater inhibitory activity toward ACAT1 than ACAT2, and one compound was identified that specifically inhibits ACAT2. The demonstration of selective inhibition of ACAT1 and ACAT2 provides evidence for uniqueness in structure and function of these two enzymes. To the extent that ACAT2 is confined to hepatocytes and enterocytes, the only two cell types that secrete lipoproteins, selective inhibition of ACAT2 may prove to be most beneficial in the reduction of plasma lipoprotein cholesterol concentrations.

  11. Elicitation of Induced Resistance against Pectobacterium carotovorum and Pseudomonas syringae by Specific Individual Compounds Derived from Native Korean Plant Species

    Directory of Open Access Journals (Sweden)

    Choong-Min Ryu

    2013-10-01

    Full Text Available Plants have developed general and specific defense mechanisms for protection against various enemies. Among the general defenses, induced resistance has distinct characteristics, such as broad-spectrum resistance and long-lasting effectiveness. This study evaluated over 500 specific chemical compounds derived from native Korean plant species to determine whether they triggered induced resistance against Pectobacterium carotovorum supsp. carotovorum (Pcc in tobacco (Nicotiana tabacum and Pseudomonas syringae pv. tomato (Pst in Arabidopsis thaliana. To select target compound(s with direct and indirect (volatile effects, a new Petri-dish-based in vitro disease assay system with four compartments was developed. The screening assay showed that capsaicin, fisetin hydrate, jaceosidin, and farnesiferol A reduced the disease severity significantly in tobacco. Of these four compounds, capsaicin and jaceosidin induced resistance against Pcc and Pst, which depended on both salicylic acid (SA and jasmonic acid (JA signaling, using Arabidopsis transgenic and mutant lines, including npr1 and NahG for SA signaling and jar1 for JA signaling. The upregulation of the PR2 and PDF1.2 genes after Pst challenge with capsaicin pre-treatment indicated that SA and JA signaling were primed. These results demonstrate that capsaicin and jaceosidin can be effective triggers of strong induced resistance against both necrotrophic and biotrophic plant pathogens.

  12. A retrospective cohort study on the risk assessment of newly certificated long-term care need of elderly individuals in a community: Basic checklist and specific health checkup.

    Science.gov (United States)

    Katsura, Toshiki; Fujimoto, Megumi; Shizawa, Miho; Hoshino, Akiko; Usui, Kanae; Yokoyama, Eri; Hara, Mayumi

    2017-11-01

    Objective: This study aimed to examine the factors influencing the requirement of a certificate of long-term care using a basic checklist and items listed in the Special Health Checkup. Method: This study included 7,820 individuals living in Uji city, who were selected from among 8,000 elderly individuals who, in 2008, underwent a specific health checkup (hereafter referred to as the 'specific health checkup for the old-old elderly individuals') for those aged 75 years and above. They answered questions from basic checklists at the time, and 180 individuals were excluded as they had already qualified for requiring the certificate of long-term care at the time of the checkup. The follow-up period extended from the day of the specific health checkup for the old-old elderly individuals to March 31, 2013. The data were analyzed using the certificate of needing long-term care as the response variable. The explanatory variables were the basic attributes, items listed in the specific health checkup for the old-old elderly individuals, interview sheets, and basic checklists. Cox proportional hazards regression analysis was conducted. Results: In total, 1,280 elderly individuals qualified for requiring the certificate of needing long-term care. The risk factors for the young-old elderly individuals aged 65 to 74 years were as follows: hepatic dysfunction (hazard ratio {HR}=1.69), the presence of subjective symptoms (HR=1.41), an above-normal abdominal circumference (HR=1.36), old age (HR=1.13), a reduced frequency of going out since the previous year (HR=1.87), the use of support for standing up after being seated on a chair (HR=1.86), no deposit or withdrawals made (HR=1.84), the anxiety of falling down (HR=1.50), an inability to climb stairs without holding a railing or wall (HR=1.49), as well as an increased difficulty in eating tough food items compared with 6 months prior (HR=1.44). The risk factors for the old-old elderly individuals were as follows: a positive

  13. Sex-specific neural activity when resolving cognitive interference in individuals with or without prior internalizing disorders.

    Science.gov (United States)

    Wang, Zhishun; Jacobs, Rachel H; Marsh, Rachel; Horga, Guillermo; Qiao, Jianping; Warner, Virginia; Weissman, Myrna M; Peterson, Bradley S

    2016-03-30

    The processing of cognitive interference is a self-regulatory capacity that is impaired in persons with internalizing disorders. This investigation was to assess sex differences in the neural correlates of cognitive interference in individuals with and without an illness history of an internalizing disorder. We compared functional magnetic resonance imaging blood-oxygenation-level-dependent responses in both males (n=63) and females (n=80) with and without this illness history during performance of the Simon task. Females deactivated superior frontal gyrus, inferior parietal lobe, and posterior cingulate cortex to a greater extent than males. Females with a prior history of internalizing disorder also deactivated these regions more compared to males with that history, and they additionally demonstrated greater activation of right inferior frontal gyrus. These group differences were represented in a significant sex-by-illness interaction in these regions. These deactivated regions compose a task-negative or default mode network, whereas the inferior frontal gyrus usually activates when performing an attention-demanding task and is a key component of a task-positive network. Our findings suggest that a prior history of internalizing disorders disproportionately influences functioning of the default mode network and is associated with an accompanying activation of the task-positive network in females during the resolution of cognitive interference. Copyright © 2016. Published by Elsevier Ireland Ltd.

  14. Functional and immunochemical cross-reactivity of V2-specific monoclonal antibodies from HIV-1-infected individuals

    Energy Technology Data Exchange (ETDEWEB)

    Gorny, Miroslaw K.; Pan, Ruimin; Williams, Constance; Wang, Xiao-Hong; Volsky, Barbara; O; Neal, Timothy; Spurrier, Brett; Sampson, Jared M.; Li, Liuzhe; Seaman, Michael S.; Kong, Xiang-Peng; Zolla-Pazner, Susan (Harvard-Med); (VA); (NYUSM)

    2012-05-18

    The recent analysis of the first successful RV144 vaccine trial revealed that a high titer of plasma anti-V2 antibodies (Abs) correlated with a decreased risk of HIV-1 infection in vaccine recipients. To understand the mechanism of immune correlates, we studied seven anti-V2 monoclonal Abs (mAbs) developed from HIV-1 infected individuals. The V2 mAbs target conserved epitopes, including the binding site for {alpha}4{beta}7 integrin, and are broadly cross-reactive with various gp120 proteins. Preferential usage of the VH1-69 gene by V2 mAbs may depend on selection by the same antigenic structure. Six of seven V2 mAbs weakly neutralized four to eight of the 41 pseudoviruses tested and resistance to neutralization was correlated with longer V2 domains. The data suggest the presence of shared, conserved structural elements in the V2 loop, and these can be used in the design of vaccine immunogens inducing broadly reactive Abs with anti-viral activities.

  15. Risk of Cause-Specific Death in Individuals with Cancer-Modifying Role Diabetes, Statins and Metformin.

    Science.gov (United States)

    Haukka, Jari; Niskanen, Leo; Auvinen, Anssi

    2017-12-15

    Both diabetes mellitus (DM) and cancer are common diseases and they frequently occur in the same patients. We investigated the all-cause and cause-specific mortality dynamics in relation to baseline DM, statin use and metformin use. The study population consisted of 39,900 incident cancer cases from Finland, 19,822 patients were free of DM at the start of follow-up and 20,078 had DM. Mortality from all causes, and cancer, cardiovascular (CVD) and other causes was analysed using Poisson regression model with the following variables: sex, age, DM, statin and metformin usage in baseline, cancer type and stage and calendar period. Statin usage was associated with a reduced cancer-specific mortality with incidence rate ratio (IRR) 0.72 (95% confidence interval 0.69-0.74), IRR for CVD mortality was 0.95 (0.88-1.02) and for other causes 0.64 (0.56-0.74). In a sub-population of DM patients, IRR for metformin in all-cause mortality was 0.74 (0.71-0.78), in cancer mortality 0.75 (0.72-0.79), in CVD mortality 0.75 (0.68-0.83) and other causes 0.68 (0.60-0.78). In conclusion, our register-based study of survival after cancer diagnosis showed that patients with diabetes had substantially poorer outcome in all measures. An association between baseline statin usage and lower all-cause, cancer and cardiovascular mortality was modified by cancer type. The effect of statin use was largest for breast and colorectal cancer. Metformin usage in a subpopulation of oral antidiabetic users was in general associated with lower mortality, but this association was modified by cancer type. The association was strongest for liver, colorectal and breast cancer. © 2017 UICC.

  16. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence.

    Science.gov (United States)

    Liu, Xinyang; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Cai, Xinxia; Wilhelm, Oliver

    2017-01-01

    Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT) Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN), when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account or not. These

  17. Individual Differences in the Speed of Facial Emotion Recognition Show Little Specificity but Are Strongly Related with General Mental Speed: Psychometric, Neural and Genetic Evidence

    Science.gov (United States)

    Liu, Xinyang; Hildebrandt, Andrea; Recio, Guillermo; Sommer, Werner; Cai, Xinxia; Wilhelm, Oliver

    2017-01-01

    Facial identity and facial expression processing are crucial socio-emotional abilities but seem to show only limited psychometric uniqueness when the processing speed is considered in easy tasks. We applied a comprehensive measurement of processing speed and contrasted performance specificity in socio-emotional, social and non-social stimuli from an individual differences perspective. Performance in a multivariate task battery could be best modeled by a general speed factor and a first-order factor capturing some specific variance due to processing emotional facial expressions. We further tested equivalence of the relationships between speed factors and polymorphisms of dopamine and serotonin transporter genes. Results show that the speed factors are not only psychometrically equivalent but invariant in their relation with the Catechol-O-Methyl-Transferase (COMT) Val158Met polymorphism. However, the 5-HTTLPR/rs25531 serotonin polymorphism was related with the first-order factor of emotion perception speed, suggesting a specific genetic correlate of processing emotions. We further investigated the relationship between several components of event-related brain potentials with psychometric abilities, and tested emotion specific individual differences at the neurophysiological level. Results revealed swifter emotion perception abilities to go along with larger amplitudes of the P100 and the Early Posterior Negativity (EPN), when emotion processing was modeled on its own. However, after partialling out the shared variance of emotion perception speed with general processing speed-related abilities, brain-behavior relationships did not remain specific for emotion. Together, the present results suggest that speed abilities are strongly interrelated but show some specificity for emotion processing speed at the psychometric level. At both genetic and neurophysiological levels, emotion specificity depended on whether general cognition is taken into account or not. These

  18. Adolescent Susceptibility to Peer Influence in Sexual Situations

    National Research Council Canada - National Science Library

    Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W; Prinstein, Mitchell J

    2016-01-01

    ...; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes...

  19. Analysis of the Phenotype of Mycobacterium tuberculosis-Specific CD4+ T Cells to Discriminate Latent from Active Tuberculosis in HIV-Uninfected and HIV-Infected Individuals

    Directory of Open Access Journals (Sweden)

    Catherine Riou

    2017-08-01

    Full Text Available Several immune-based assays have been suggested to differentiate latent from active tuberculosis (TB. However, their relative performance as well as their efficacy in HIV-infected persons, a highly at-risk population, remains unclear. In a study of 81 individuals, divided into four groups based on their HIV-1 status and TB disease activity, we compared the differentiation (CD27 and KLRG1, activation (HLA-DR, homing potential (CCR4, CCR6, CXCR3, and CD161 and functional profiles (IFNγ, IL-2, and TNFα of Mycobacterium tuberculosis (Mtb-specific CD4+ T cells using flow cytometry. Active TB disease induced major changes within the Mtb-responding CD4+ T cell population, promoting memory maturation, elevated activation and increased inflammatory potential when compared to individuals with latent TB infection. Moreover, the functional profile of Mtb-specific CD4+ T cells appeared to be inherently related to their degree of differentiation. While these specific cell features were all capable of discriminating latent from active TB, irrespective of HIV status, HLA-DR expression showed the best performance for TB diagnosis [area-under-the-curve (AUC = 0.92, 95% CI: 0.82–1.01, specificity: 82%, sensitivity: 84% for HIV− and AUC = 0.99, 95% CI: 0.98–1.01, specificity: 94%, sensitivity: 93% for HIV+]. In conclusion, these data support the idea that analysis of T cell phenotype can be diagnostically useful in TB.

  20. Motor neurons and glia exhibit specific individualized responses to TDP-43 expression in a Drosophila model of amyotrophic lateral sclerosis

    Directory of Open Access Journals (Sweden)

    Patricia S. Estes

    2013-05-01

    Amyotrophic lateral sclerosis (ALS is a fatal disease characterized by complex neuronal and glial phenotypes. Recently, RNA-based mechanisms have been linked to ALS via RNA-binding proteins such as TDP-43, which has been studied in vivo using models ranging from yeast to rodents. We have developed a Drosophila model of ALS based on TDP-43 that recapitulates several aspects of pathology, including motor neuron loss, locomotor dysfunction and reduced survival. Here we report the phenotypic consequences of expressing wild-type and four different ALS-linked TDP-43 mutations in neurons and glia. We show that TDP-43-driven neurodegeneration phenotypes are dose- and age-dependent. In motor neurons, TDP-43 appears restricted to nuclei, which are significantly misshapen due to mutant but not wild-type protein expression. In glia and in the developing neuroepithelium, TDP-43 associates with cytoplasmic puncta. TDP-43-containing RNA granules are motile in cultured motor neurons, although wild-type and mutant variants exhibit different kinetic properties. At the neuromuscular junction, the expression of TDP-43 in motor neurons versus glia leads to seemingly opposite synaptic phenotypes that, surprisingly, translate into comparable locomotor defects. Finally, we explore sleep as a behavioral readout of TDP-43 expression and find evidence of sleep fragmentation consistent with hyperexcitability, a suggested mechanism in ALS. These findings support the notion that although motor neurons and glia are both involved in ALS pathology, at the cellular level they can exhibit different responses to TDP-43. In addition, our data suggest that individual TDP-43 alleles utilize distinct molecular mechanisms, which will be important for developing therapeutic strategies.

  1. Spinal manipulative therapy-specific changes in pain sensitivity in individuals with low back pain (NCT01168999).

    Science.gov (United States)

    Bialosky, Joel E; George, Steven Z; Horn, Maggie E; Price, Donald D; Staud, Roland; Robinson, Michael E

    2014-02-01

    Spinal manipulative therapy (SMT) is effective for some individuals experiencing low back pain; however, the mechanisms are not established regarding the role of placebo. SMT is associated with changes in pain sensitivity, suggesting related altered central nervous system response or processing of afferent nociceptive input. Placebo is also associated with changes in pain sensitivity, and the efficacy of SMT for changes in pain sensitivity beyond placebo has not been adequately considered. We randomly assigned 110 participants with low back pain to receive SMT, placebo SMT, placebo SMT with the instructional set "The manual therapy technique you will receive has been shown to significantly reduce low back pain in some people," or no intervention. Participants receiving the SMT and placebo SMT received their assigned intervention 6 times over 2 weeks. Pain sensitivity was assessed prior to and immediately following the assigned intervention during the first session. Clinical outcomes were assessed at baseline and following 2 weeks of participation in the study. Immediate attenuation of suprathreshold heat response was greatest following SMT (P = .05, partial η(2) = .07). Group-dependent differences were not observed for changes in pain intensity and disability at 2 weeks. Participant satisfaction was greatest following the enhanced placebo SMT. This study was registered at www.clinicaltrials.gov under the identifier NCT01168999. The results of this study indicate attenuation of pain sensitivity is greater in response to SMT than the expectation of receiving an SMT. These findings suggest a potential mechanism of SMT related to lessening of central sensitization and may indicate a preclinical effect beyond the expectations of receiving SMT. Copyright © 2014 American Pain Society. Published by Elsevier Inc. All rights reserved.

  2. Tree to plot scaling - how individual properties and species specific traits add up to describe a forest

    Science.gov (United States)

    Bohrer, G.; Mirfenderesgi, G.; Matheny, A. M.; Fatichi, S.

    2016-12-01

    Tree-level hydrodynamic observations of sap-flux, water storage and stomatal conductance are becoming available and effective tools to observe forests water relations. These tree-level measurement can now inform us about the dynamics and within plot heterogeneity of hydrological process and provide key information for the development of new mechanistic models that could improve ecosystem and land surface modeling. Upscaling leaf and tree level information to the plot level, at a scale that corresponds with an eddy covariance flux tower's measurement footprint, or a regional and global models' single grid cell is necessary. In an experimental forest plot in Michigan we are testing and evaluating a new approach for upscaling. We found that allometric relationships that link stem diameter and height, stem diameter and active xylem depth, DBH and crown size and crown size with leaf must all be combined to properly scale individual measurements to the whole tree. To further upscale from tree to plot, information about tree size distribution can be obtained from plot census and remote sensing. Because only a small subset of trees in the plot are observed, aggregation of the full species-size distribution into a small number of distinct bins must be conducted. We found that, for scaling hydraulic processes, the current concept of plant functional type is not appropriate. Oaks and Maples in our plot, belonging to the same plant functional type, present opposing hydrodynamic behaviors. We further determined that the classification of hydrodynamic functional types must consider traits at the leaf, stem and root levels. Stomatal regulation by leaves may be isohydric or anisohydric, xylem architectures determine the cavitation and storage discharge curves, described by 4 parameters, and finally, rooting depth and other root properties all combine to classify the hydraulic behavior of trees that compose a forest plot.

  3. Language-Specific Effects on Story and Procedural Narrative tasks between Korean-speaking and English-speaking Individuals with Aphasia

    Directory of Open Access Journals (Sweden)

    Jee Eun Sung

    2015-04-01

    Results suggested that Korean-speaking individuals with aphasia produced more numbers of different verbs, number of verbs per utterance and higher VNRs than English speakers. Both groups generated more words in story. The significant two-way interactions between the language group and task type suggested that there are task-specific effects on linguistic measures across the groups. The study implied that the linguistic characteristics differentially affected language symptoms of aphasia across the different languages and task types.

  4. Young individuals with a more ankle-steered proprioceptive control strategy may develop mild non-specific low back pain.

    Science.gov (United States)

    Claeys, Kurt; Dankaerts, Wim; Janssens, Lotte; Pijnenburg, Madelon; Goossens, Nina; Brumagne, Simon

    2015-04-01

    Altered proprioceptive postural control has been demonstrated in people with non-specific low back pain (LBP). However, the cause-effect relation remains unclear. Therefore, more prospective studies are necessary. Proprioceptive postural control of 104 subjects was evaluated at baseline using a force plate and with application of vibration stimulation on ankle and back muscles. Spinal postural angles were measured with digital photographs. Psychosocial variables and physical activity were registered using questionnaires. Ninety subjects were followed over two years concerning their LBP status, 14 were lost to follow-up. Four distinct groups were determined after two years based on pain and disability scores: never LBP, no LBP at intake with future mild LBP, mild LBP at intake with no further LBP, LBP at intake with further episodes of mild LBP. Risk factors for developing or sustaining LBP were calculated using logistic regression analysis. A more ankle-steered proprioceptive postural control strategy in upright standing increased the risk for developing or having recurrences of mild LBP within two years (Odds: 3.5; 95% CI: 1.1-10.8; p postural sway, altered spinal postural angles, psychosocial and physical activity outcomes were not identified as risk factors for future mild LBP. These findings could contribute to improving the prevention and rehabilitation of LBP. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Probing Coagulation Behavior of Individual Aluminum Species for Removing Corresponding Disinfection Byproduct Precursors: The Role of Specific Ultraviolet Absorbance.

    Directory of Open Access Journals (Sweden)

    He Zhao

    Full Text Available Coagulation behavior of aluminum chloride and polyaluminum chloride (PACl for removing corresponding disinfection byproduct (DBP precursors was discussed in this paper. CHCl3, bromine trihalomethanes (THM-Br, dichloroacetic acid (DCAA and trichloroacetic acid (TCAA formation potential yields were correlated with specific ultraviolet absorbance (SUVA values in different molecular weight (MW fractions of humic substances (HS, respectively. Correlation analyses and principal component analysis were performed to examine the relationships between SUVA and different DBP precursors. To acquire more structural characters of DBP precursors and aluminum speciation, freeze-dried precipitates were analyzed by fourier transform infrared (FTIR and C 1s, Al 2p X-ray photoelectron spectroscopy (XPS. The results indicated that TCAA precursors (no MW limits, DCAA and CHCl3 precursors in low MW fractions (MW30 kDa were preferentially removed by PACl coagulation with preformed Al13 species at pH 5.0. Additionally, for DCAA precursors in high MW fractions (MW>30 kDa with relatively low aromatic content and more carboxylic structures, the greatest removal occurred at pH 6.0 through PACl coagulation with aggregated Al13 species.

  6. Analysis of Individuals from a Dengue-Endemic Region Helps Define the Footprint and Repertoire of Antibodies Targeting Dengue Virus 3 Type-Specific Epitopes

    Directory of Open Access Journals (Sweden)

    Daniela V. Andrade

    2017-09-01

    Full Text Available The four dengue virus serotypes (DENV1 to 4 cause dengue, a major public health problem worldwide. Individuals exposed to primary DENV infections develop serotype-specific neutralizing antibodies, including strongly neutralizing antibodies targeting quaternary epitopes. To date, no studies have measured the levels and kinetics of serum antibodies directed to such epitopes among populations in regions where dengue is endemic. Here, we use a recombinant DENV4 (rDENV4/3-M14 displaying a major DENV3 type-specific quaternary epitope recognized by human monoclonal antibody 5J7 to measure the proportion, magnitude, and kinetics of DENV3 type-specific neutralizing antibody responses targeting this epitope. Primary DENV3 sera from 30 individuals in a dengue hospital-based study in Nicaragua were studied 3, 6, 12, and 18 months post-infection, alongside samples collected annually 1 to 4 years post-primary DENV3 infection from 10 individuals in a cohort study in Nicaragua. We found substantial individual variation in the proportion of DENV3 type-specific neutralizing antibody titers attributed to the 5J7 epitope (range, 0 to 100%, with the mean significantly increasing from 22.6% to 41.4% from 3 to 18 months. We extended the transplanted DENV3 5J7 epitope on the virion (rDENV4/3-M16, resulting in increased recognition in several individuals, helping define the footprint of the epitope. However, 37% and 13% of the subjects still showed little to no recognition of the 5J7 epitope at 3 and 18 months, respectively, indicating that one or more additional DENV3 type-specific epitopes exist. Overall, this study demonstrates how DENV-immune plasma from populations from areas of endemicity, when coupled with structurally guided recombinant viruses, can help characterize the epitope-specific neutralizing antibody response in natural DENV infections, with direct implications for design and evaluation of dengue vaccines.

  7. Gender-specific suicide risk factors: a case-control study of individuals with major depressive disorder.

    Science.gov (United States)

    Dalca, Ioana Mioara; McGirr, Alexander; Renaud, Johanne; Turecki, Gustavo

    2013-12-01

    Available information on risk for suicide completion in females is limited and often extrapolated from studies conducted in males. However, the validity of extending to females risk factors identified among male suicide cases is unclear. In this study, we aimed to investigate clinical and behavioral risk factors for suicide among female depressed patients and compare them to similar factors among male depressed patients. We identified 201 suicide completers (160 male and 41 female) who died during an episode of major depressive disorder (MDD). Cases were compared to 127 living patients with MDD (88 male and 39 female). All subjects were characterized for Axis I and II diagnoses using the Structured Clinical Interview for DSM-IV Axis I Disorders and Structured Clinical Interview for DSM-IV Axis II Personality Disorders according to the DSM-IV, as well as behavioral and temperament dimensions using proxy-based interviews. The primary outcome was measures of impulsive and impulsive-aggressive behaviors. Compared to controls, male, but not female suicide cases had higher levels of impulsive aggression (P suicide cases from controls. However, nonimpulsive aggression and impulsive aggression were correlated constructs in males (r = 0.297; P suicide, such as alcohol and substance dependence, cluster B disorders, and elevated hostility and aggression, were replicated in the pooled-sex analyses, and, though not statistically significant in discriminating between suicide cases and controls by gender, maintained strong group differences. Males and females share many risk factors for suicide in MDD, yet alcohol dependence is much more specific though less sensitive among depressed females. Nonimpulsive aggression is part of a diathesis for suicide in females, which is distinct from the well-characterized impulsive aggression that is consistently reported in a portion of male suicide cases. © Copyright 2013 Physicians Postgraduate Press, Inc.

  8. High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in Individuals Without Previous Cardiovascular Conditions: The CANHEART Study.

    Science.gov (United States)

    Ko, Dennis T; Alter, David A; Guo, Helen; Koh, Maria; Lau, Geoffrey; Austin, Peter C; Booth, Gillian L; Hogg, William; Jackevicius, Cynthia A; Lee, Douglas S; Wijeysundera, Harindra C; Wilkins, John T; Tu, Jack V

    2016-11-08

    The prognostic importance of high-density lipoprotein cholesterol (HDL-C) as a specific risk factor for cardiovascular (CV) disease has been challenged by recent clinical trials and genetic studies. This study sought to reappraise the association of HDL-C level with CV and non-CV mortality using a "big data" approach. An observational cohort study was conducted using the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) dataset, which was created by linking together 17 different individual-level data sources. People were included if they were between 40 and 105 years old on January 1, 2008, living in Ontario, Canada, without previous CV conditions or severe comorbidities, and had an outpatient fasting cholesterol measurement in the year prior to the inception date. The primary outcome was cause-specific mortality. A total of 631,762 individuals were included. The mean age of our cohort was 57.2 years, 55.4% were women, and mean HDL-C level was 55.2 mg/dl. There were 17,952 deaths during a mean follow-up of 4.9 ± 0.4 years. The overall all-cause mortality rate was 8.1 per 1,000 person-years for men and 6.6 per 1,000 person-years for women. Individuals with lower HDL-C levels were more likely to have low incomes, unhealthy lifestyle, higher triglycerides levels, other cardiac risk factors, and medical comorbidities. Individuals with lower HDL-C levels were independently associated with higher risk of CV, cancer, and other mortality compared with individuals in the reference ranges of HDL-C levels. In addition, individuals with higher HDL levels (>70 mg/dl in men, >90 mg/dl in women) had increased hazard of non-CV mortality. Complex associations exist between HDL-C levels and sociodemographic, lifestyle, comorbidity factors, and mortality. HDL-C level is unlikely to represent a CV-specific risk factor given similarities in its associations with non-CV outcomes. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  9. A lack of Wolbachia-specific DNA in samples from apollo butterfly (Parnassius apollo, Lepidoptera: Papilionidae) individuals with deformed or reduced wings.

    Science.gov (United States)

    Łukasiewicz, Kinga; Sanak, Marek; Węgrzyn, Grzegorz

    2016-05-01

    Various insects contain maternally inherited endosymbiotic bacteria which can cause reproductive alterations, modulation of some physiological responses (like immunity, heat shock response, and oxidative stress response), and resistance to viral infections. In butterflies, Wolbachia sp. is the most frequent endosymbiont from this group, occurring in about 30 % of species tested to date. In this report, the presence of Wolbachia-specific DNA has been detected in apollo butterfly (Parnassius apollo). In the isolated population of this insect occurring in Pieniny National Park (Poland), malformed individuals with deformed or reduced wings appear with an exceptionally high frequency. Interestingly, while total DNA isolated from most (about 85 %) normal insects contained Wolbachia-specific sequences detected by PCR, such sequences were absent in a large fraction (70 %) of individuals with deformed wings and in all tested individuals with reduced wings. These results indicate for the first time the correlation between malformation of wings and the absence of Wolbachia sp. in insects. Although the lack of the endosymbiotic bacteria cannot be considered as the sole cause of the deformation or reduction of wings, one might suggest that Wolbachia sp. could play a protective role in the ontogenetic development of apollo butterfly.

  10. Phenotypic and Functional Characterization of Herpes Simplex Virus Glycoprotein B Epitope-Specific Effector and Memory CD8+ T Cells from Symptomatic and Asymptomatic Individuals with Ocular Herpes

    Science.gov (United States)

    Khan, Arif A.; Srivastava, Ruchi; Spencer, Doran; Garg, Sumit; Fremgen, Daniel; Vahed, Hawa; Lopes, Patricia P.; Pham, Thanh T.; Hewett, Charlie; Kuang, Jasmine; Ong, Nicolas; Huang, Lei; Scarfone, Vanessa M.; Nesburn, Anthony B.

    2015-01-01

    ABSTRACT Herpes simplex virus 1 (HSV-1) glycoprotein B (gB)-specific CD8+ T cells protect mice from herpes infection and disease. However, whether and which HSV-1 gB-specific CD8+ T cells play a key role in the “natural” protection seen in HSV-1-seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we have dissected the phenotypes and the functions of HSV-1 gB-specific CD8+ T cells from HLA-A*02:01 positive, HSV-1 seropositive ASYMP and symptomatic (SYMP) individuals (with a history of numerous episodes of recurrent ocular herpes disease). We found the following. (i) Healthy ASYMP individuals maintained a significantly higher proportion of differentiated HSV-1 gB-specific effector memory CD8+ T cells (TEM cells) (CD45RAlow CCR7low CD44high CD62Llow). In contrast, SYMP patients had frequent less-differentiated central memory CD8+ T cells (TCM cells) (CD45RAlow CCR7high CD44low CD62Lhigh). (ii) ASYMP individuals had significantly higher proportions of multifunctional effector CD8+ T cells which responded mainly to gB342–350 and gB561–569 “ASYMP” epitopes, and simultaneously produced IFN-γ, CD107a/b, granzyme B, and perforin. In contrast, effector CD8+ T cells from SYMP individuals were mostly monofunctional and were directed mainly against nonoverlapping gB17–25 and gB183–191 “SYMP” epitopes. (iii) Immunization of an HLA-A*02:01 transgenic mouse model of ocular herpes with “ASYMP” CD8+ TEM cell epitopes, but not with “SYMP” CD8+ TCM cell epitopes, induced a strong CD8+ T cell-dependent protective immunity against ocular herpes infection and disease. Our findings provide insights into the role of HSV-specific CD8+ TEM cells in protection against herpes and should be considered in the development of an effective vaccine. IMPORTANCE A significantly higher proportion of differentiated and multifunctional HSV-1 gB-specific effector memory CD8+ T cells (TEM

  11. Ex-vivo recognition of late-lytic CD8 epitopes specific for Kaposi's sarcoma-associated herpesvirus (KSHV) by HIV/KSHV-coinfected individuals.

    Science.gov (United States)

    Robey, Rebecca C; Mletzko, Salvinia; Bower, Mark; Meys, Rhonda; Boffito, Marta; Nelson, Mark; Bunker, Christopher B; Gotch, Frances M

    2011-06-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), the most common cancer in individuals with untreated HIV/AIDS. Host control of KSHV infection and KS oncogenesis by CD8 T cells remains underexplored. Although KSHV CD8 epitopes have been identified, the responses they elicit are weak and little is known about their relative importance. We sought to make a direct comparison of the recognition of a selection of the best-described known epitopes by a cohort of KSHV-seropositive, HIV-co-infected individuals, in order to assess the relative dominance of these epitopes. We further sought to identify novel epitopes from within a candidate immunogenic protein encoded by KSHV ORF28. MHC binding and denaturation assays identified putative novel A*0201-restricted epitopes from within the late-lytic glycoprotein ORF28. Recognition of these candidate epitopes was tested in a cohort of KSHV-seropositive, HIV-1-seropositive, A*0201-positive individuals by ex vivo ELISPOT, and compared with recognition of nine previously described epitopes. One novel late-lytic epitope from ORF28 was recognized by 7.1% of individuals, and was used for further investigation of KSHV-specific T cells using multimer technology. One known late-lytic epitope from the glycoprotein-encoding K8.1 was recognized by 71.4% of individuals, and represented an immunodominant KSHV epitope, but was too hydrophobic for multimer synthesis. This study identifies two KSHV CD8 epitopes derived from late-lytic antigens that are recognized by KSHV-seropositive, HIV co-infected individuals, and will be useful in future immunological studies into the CD8 response against KSHV in similar patient cohorts.

  12. Identifying a hunter responsible for killing a hunting dog by individual-specific genetic profiling of wild boar DNA transferred to the canine during the accidental shooting.

    Science.gov (United States)

    Schleimer, Anna; Frantz, Alain C; Lang, Johannes; Reinert, Phillipe; Heddergott, Mike

    2016-12-01

    While genetic profiling can be a powerful tool to solve wildlife crime, comparably few examples of individual identification in wildlife forensics are available in the literature. Here, we report a case of an accidental shooting of a hunting dog during a wild boar drive hunt. The market value of trained hunting dogs can reach several thousand euro. No one admitted to killing the dog. Wild boar hairs were found in the dog's wound, suggesting that the bullet first hit a wild boar and then the dog. Since it was known who harvested each boar, we aimed to use individual-specific genetic profiles to link these hairs to a bagged animal and to identify the culprit. We genotyped 19 harvested boar and the unknown hair sample using 13 STRs. In the case of the hair sample, we performed multiple genotyping to ensure the reliability of the genetic profile. We showed that we genotyped sufficient loci to distinguish between separate individuals with certainty. While the three most informative loci were enough to differentiate the 19 reference individuals, we did find a perfect match at all 13 STRs between the hair DNA and one tissue sample. Since our methods were reliable and reproducible, we passed the relevant information on to forestry officials who will use the information we have provided to attempt to find an amicable solution.

  13. High Inter-Individual Diversity of Point Mutations, Insertions, and Deletions in Human Influenza Virus Nucleoprotein-Specific Memory B Cells.

    Directory of Open Access Journals (Sweden)

    Sven Reiche

    Full Text Available The diversity of virus-specific antibodies and of B cells among different individuals is unknown. Using single-cell cloning of antibody genes, we generated recombinant human monoclonal antibodies from influenza nucleoprotein-specific memory B cells in four adult humans with and without preceding influenza vaccination. We examined the diversity of the antibody repertoires and found that NP-specific B cells used numerous immunoglobulin genes. The heavy chains (HCs originated from 26 and the kappa light chains (LCs from 19 different germ line genes. Matching HC and LC chains gave rise to 43 genetically distinct antibodies that bound influenza NP. The median lengths of the CDR3 of the HC, kappa and lambda LC were 14, 9 and 11 amino acids, respectively. We identified changes at 13.6% of the amino acid positions in the V gene of the antibody heavy chain, at 8.4% in the kappa and at 10.6 % in the lambda V gene. We identified somatic insertions or deletions in 8.1% of the variable genes. We also found several small groups of clonal relatives that were highly diversified. Our findings demonstrate broadly diverse memory B cell repertoires for the influenza nucleoprotein. We found extensive variation within individuals with a high number of point mutations, insertions, and deletions, and extensive clonal diversification. Thus, structurally conserved proteins can elicit broadly diverse and highly mutated B-cell responses.

  14. Specific Glial Functions Contribute to Schizophrenia Susceptibility

    NARCIS (Netherlands)

    Goudriaan, A.; de Leeuw, C.A.; Ripke, S.; Hultman, C. M.; Sklar, P.; Sullivan, P.F.; Smit, A.B.; Posthuma, D.; Verheijen, M.H.G.

    2014-01-01

    Schizophrenia is a highly polygenic brain disorder. The main hypothesis for disease etiology in schizophrenia primarily focuses on the role of dysfunctional synaptic transmission. Previous studies have therefore directed their investigations toward the role of neuronal dysfunction. However, recent

  15. Risk markers of all-cause and diagnosis-specific disability pension--a prospective cohort study of individuals sickness absent due to stress-related mental disorders

    DEFF Research Database (Denmark)

    Ishtiak-Ahmed, Kazi; Perski, Aleksander; Mittendorfer-Rutz, Ellenor

    2014-01-01

    BACKGROUND: Stress-related mental disorders rank among the leading causes of sickness absence in several European countries. The aim of this study was to investigate predictors of all-cause and diagnosis-specific disability pension in sickness absentees with stress-related mental disorders. METHODS......: A cohort of 36304 non-retired individuals aged 16-64 years at 31.12.2004 with at-least one sickness absence spell due to stress-related mental disorders (SRMD) initiated in 2005 in Sweden was followed-up with regard to disability pension (2006-2010) by linkage of registers. Uni- and multivariate Hazard...... ratios (HR) with 95% Confidence Intervals, CI, were estimated using Cox regression for several risk markers. RESULTS: During the follow-up period, 2735 individuals (7.5%) were granted a disability pension, predominantly due to mental diagnoses (n = 2004, 73.3%). In the multivariate analyses, female sex...

  16. Leishmania-specific T cells expressing interferon-¿(IFN-¿) and IL-10 upon activation are expanded in individuals cured of visceral leishmaniasis

    DEFF Research Database (Denmark)

    Kemp, K; Kemp, M; Kharazmi, A

    1999-01-01

    Peripheral blood mononuclear cells (PBMC) from patients who have recovered from visceral leishmaniasis often respond to Leishmania antigens in vitro by production of both IL-4, IFN-gamma and IL-10. In order to establish the cellular sources of these cytokines, we activated cells from individuals...... with a history of visceral leishmaniasis with Leishmania antigen for 6 days in culture, and identified cytokine production at the single-cell level by flow cytometry. The cytokines were only found in CD3+ cells and among these mainly within the CD4+ subset. The percentage of cytokine-producing cells was compared...... in Leishmania-activated PBMC cultures from the previous patients and from individuals living in a village where leishmaniasis does not occur. The percentage of IL-10- and IFN-gamma-containing cells was significantly higher in the previous patients than in the controls, indicating that Leishmania-specific T...

  17. Magnetic susceptibilities of minerals

    Science.gov (United States)

    Rosenblum, Sam; Brownfield, I.K.

    2000-01-01

    Magnetic separation of minerals is a topic that is seldom reported in the literature for two reasons. First, separation data generally are byproducts of other projects; and second, this study requires a large amount of patience and is unusually tedious. Indeed, we suspect that most minerals probably are never investigated for this property. These data are timesaving for mineralogists who concentrate mono-mineralic fractions for chemical analysis, age dating, and for other purposes. The data can certainly be used in the ore-beneficiation industries. In some instances, magnetic-susceptibility data may help in mineral identification, where other information is insufficient. In past studies of magnetic separation of minerals, (Gaudin and Spedden, 1943; Tille and Kirkpatrick, 1956; Rosenblum, 1958; Rubinstein and others, 1958; Flinter, 1959; Hess, 1959; Baker, 1962; Meric and Peyre, 1963; Rojas and others, 1965; and Duchesne, 1966), the emphasis has been on the ferromagnetic and paramagnetic ranges of extraction. For readers interested in the history of magnetic separation of minerals, Krumbein and Pettijohn (1938, p. 344-346) indicated nine references back to 1848. The primary purpose of this paper is to report the magnetic-susceptibility data on as many minerals as possible, similar to tables of hardness, specific gravity, refractive indices, and other basic physical properties of minerals. A secondary purpose is to demonstrate that the total and best extraction ranges are influenced by the chemistry of the minerals. The following notes are offered to help avoid problems in separating a desired mineral concentrate from mixtures of mineral grains.

  18. Characterization and quantification of path dependency in landslide susceptibility

    NARCIS (Netherlands)

    Samia, Jalal; Temme, Arnaud; Bregt, Arnold; Wallinga, Jakob; Guzzetti, Fausto; Ardizzone, Francesca; Rossi, Mauro

    2017-01-01

    Landslides cause major environmental damage, economic losses and casualties. Although susceptibility to landsliding is usually considered an exclusively location-specific phenomenon, indications exist that landslide history co-determines susceptibility to future landslides. In this contribution,

  19. Site-Specific One-to-One Click Coupling of Single Proteins to Individual Carbon Nanotubes: A Single-Molecule Approach.

    Science.gov (United States)

    Freeley, Mark; Worthy, Harley L; Ahmed, Rochelle; Bowen, Ben; Watkins, Daniel; Macdonald, J Emyr; Zheng, Ming; Jones, D Dafydd; Palma, Matteo

    2017-12-13

    We report the site-specific coupling of single proteins to individual carbon nanotubes (CNTs) in solution and with single-molecule control. Using an orthogonal Click reaction, Green Fluorescent Protein (GFP) was engineered to contain a genetically encoded azide group and then bound to CNT ends in different configurations: in close proximity or at longer distances from the GFP's functional center. Atomic force microscopy and fluorescence analysis in solution and on surfaces at the single-protein level confirmed the importance of bioengineering optimal protein attachment sites to achieve direct protein-nanotube communication and bridging.

  20. Fine-mapping of the 5p15.33, 6p22.1-p21.31, and 15q25.1 regions identifies functional and histology-specific lung cancer susceptibility loci in African-Americans.

    Science.gov (United States)

    Walsh, Kyle M; Gorlov, Ivan P; Hansen, Helen M; Wu, Xifeng; Spitz, Margaret R; Zhang, Huifeng; Lu, Emily Y; Wenzlaff, Angela S; Sison, Jennette D; Wei, Chongjuan; Lloyd, Stacy M; Chen, Wei; Frazier, Marsha L; Seldin, Michael F; Bierut, Laura J; Bracci, Paige M; Wrensch, Margaret R; Schwartz, Ann G; Wiencke, John K; Amos, Christopher I

    2013-02-01

    Genome-wide association studies of European and East Asian populations have identified lung cancer susceptibility loci on chromosomes 5p15.33, 6p22.1-p21.31, and 15q25.1. We investigated whether these regions contain lung cancer susceptibly loci in African-Americans and refined previous association signals by using the reduced linkage disequilibrium observed in African-Americans. 1,308 African-American cases and 1,241 African-American controls from 3 centers were genotyped for 760 single-nucleotide polymorphisms (SNP) spanning 3 regions, and additional SNP imputation was carried out. Associations between polymorphisms and lung cancer risk were estimated using logistic regression, stratified by tumor histology where appropriate. The strongest associations were observed on 15q25.1 in/near CHRNA5, including a missense substitution [rs16969968: OR, 1.57; 95% confidence interval (CI), 1.25-1.97; P, 1.1 × 10(-4)) and variants in the 5'-UTR. Associations on 6p22.1-p21.31 were histology specific and included a missense variant in BAT2 associated with squamous cell carcinoma (rs2736158: OR, 0.64; 95% CI, 0.48-0.85; P, 1.82 × 10(-3)). Associations on 5p15.33 were detected near TERT, the strongest of which was rs2735940 (OR, 0.82; 95% CI, 0.73-0.93; P, 1.1 × 10(-3)). This association was stronger among cases with adenocarcinoma (OR, 0.75; 95% CI, 0.65-0.86; P, 8.1 × 10(-5)). Polymorphisms in 5p15.33, 6p22.1-p21.31, and 15q25.1 are associated with lung cancer in African-Americans. Variants on 5p15.33 are stronger risk factors for adenocarcinoma and variants on 6p21.33 associated only with squamous cell carcinoma. Results implicate the BAT2, TERT, and CHRNA5 genes in the pathogenesis of specific lung cancer histologies.

  1. SELECTION A METHOD FOR ESTIMATING THE VALUES OF COMMON FACTORS FOR INDIVIDUAL OBJECTS IN THE FACTORIAL ANALYSIS AND THEIR COMPARISON WITH ZERO LOADS ON SOME SPECIFIC FACTORS

    Directory of Open Access Journals (Sweden)

    Viktor B. Turundaevsky

    2015-01-01

    Full Text Available The article considers methods of estimating the values of the common factors for individual observations, make a choice between the three most used methods in practice evaluation of factor values: the regression method, Bartlett method and the method of "ideal settings" Harman. However, these methods cannot be used if the variance of some specific factors equal to zero. A method is proposed for solving the problem in this case. The meaning of the method consists in adding to the original artificially generated variables specific factors, in order to transformed data it was possible to apply the methods of evaluation of factor values. The proposed method is suitable for use in the case of collinearity initial signs that extends the application of factor analysis. More other method considered "ideal settings" Harman. We prove the extreme properties of the method.

  2. Mycobacterium avium and purified protein derivative-specific cytotoxicity mediated by CD4+ lymphocytes from healthy HIV-seropositive and-seronegative individuals

    DEFF Research Database (Denmark)

    Ravn, P; Pedersen, B K

    1996-01-01

    HIV is the greatest single risk factor for the development of tuberculosis. Diseases caused by M. tuberculosis and mycobacteria are the most common opportunistic infections in HIV-infected persons, which may stem from a functional defect of the CD4+ T-cell-mediated killing of macrophages harboring...... with no history of previous or active mycobacterial infection. Antigen-specific killing of macrophages presenting mycobacterial antigens (purified protein derivative or M. avium culture filtrate) was conducted. The phenotype of the killer cells was determined by a fluorescence-activated cell sorter after antigen...... mycobacteria. Our objective was to investigate the M.tuberculosis-and M. avium-specific cytotoxic capacity of T cells from healthy, bacille Calmette-Guérin-vaccinated, HIV-seropositive individuals. Blood mononuclear cells were obtained from 10 healthy HIV-seropositive and 10 healthy seronegative persons...

  3. Mycobacterium avium and purified protein derivative-specific cytotoxicity mediated by CD4+ lymphocytes from healthy HIV-seropositive and-seronegative individuals

    DEFF Research Database (Denmark)

    Ravn, P; Pedersen, B K

    1996-01-01

    HIV is the greatest single risk factor for the development of tuberculosis. Diseases caused by M. tuberculosis and mycobacteria are the most common opportunistic infections in HIV-infected persons, which may stem from a functional defect of the CD4+ T-cell-mediated killing of macrophages harboring...... mycobacteria. Our objective was to investigate the M.tuberculosis-and M. avium-specific cytotoxic capacity of T cells from healthy, bacille Calmette-Guérin-vaccinated, HIV-seropositive individuals. Blood mononuclear cells were obtained from 10 healthy HIV-seropositive and 10 healthy seronegative persons...... with no history of previous or active mycobacterial infection. Antigen-specific killing of macrophages presenting mycobacterial antigens (purified protein derivative or M. avium culture filtrate) was conducted. The phenotype of the killer cells was determined by a fluorescence-activated cell sorter after antigen...

  4. Susceptibility Genes in Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Yoshiyuki Ban

    2005-01-01

    Full Text Available The autoimmune thyroid diseases (AITD are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD and Hashimoto's thyroiditis (HT and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4 and thyroid specific genes (e.g. TSHR, Tg. Most likely, these loci interact and their interactions may influence disease phenotype and severity.

  5. [Age specific and individual psychological factors of post--traumatic stress (PTS) development of children with after-effects of physical damages indicating medical rehabilitation].

    Science.gov (United States)

    Пятакова, Галина В; Лебедева, Екатерина И; Потявина, Валерия В; Церфус, Диана Н

    children and teenagers having received hard physical damages face a difficult life situation which includes events accompanied by feeling of intensive fear and helplessness. Every child's individual psychological features play an important role in coping with negative psychological after-effects of his/her physical trauma. learning PTS manifestations among children and teenagers with hard physical damages indicating medical rehabilitation. patients of the traumatological department of children's surgery clinic took part in the research: 31 preadolescent children and their parents, 45 teengaers and their parents. Physical damages were received by children clinic's patients in accidents and out of negligence. A survey containing clinical and historical method elements, medical documents; semi-structured interviews for identification of signs of children's post-traumatic stress, a survey for parents for identification of children's traumatic experience, colour matrices and J. Raven black-and-white matrices, S. Rosenzweig frustration tolerance methods (children's and adult version) were used as certain research methods. it was shown that intellectual productivity showings and stable ways of emotional reaction can act as individual psychological factos of PTS development. Age specifics of embeddedness of intellectual features and stable ways of emotional reaction to PTS symptoms development among children and teenagers with hard physical damages. the received results can be used as a base for developing specific approaches for psychological support of children and teenagers having the experience of physical damage and difficult medical rehabilitation.

  6. Virulent ¤Blumeria graminis¤ infection induces penetration susceptibility and suppresses race-specific hypersensitive resistance against avirulent attack in ¤Mla1¤-barley

    DEFF Research Database (Denmark)

    Lyngkjær, M.L.; Carver, T.L.W.; Zeyen, R.J.

    2001-01-01

    Leaves of near isogenic barley lines containing the race-specific resistance alleles. Mla1 or mla1 were subjected to double inoculation treatments with virulent and avirulent Blumeria graminis isolates. Attack by the avirulent isolate alone frequently caused hypersensitive death of individual Mla1....... It appears that suppressive factors released during virulent inducer infection prevented the hypersensitive epidermal cell death that normally is induced by the race-specific avirulence elicitor. However, suppression of Mla1 race-specific resistance vas confined to the epidermis. The presence of successful...... avirulent fungus infection of the epidermis often: led to the death of the underlying mesophyll cells, thus generating a novel cellular response phenotype in B. graminis attacked Mla1 barley. (C) 2001 Academic Press....

  7. Plasmid-Encoded RepA Proteins Specifically Autorepress Individual repABC Operons in the Multipartite Rhizobium leguminosarum bv. trifolii Genome.

    Science.gov (United States)

    Żebracki, Kamil; Koper, Piotr; Marczak, Małgorzata; Skorupska, Anna; Mazur, Andrzej

    2015-01-01

    Rhizobia commonly have very complex genomes with a chromosome and several large plasmids that possess genes belonging to the repABC family. RepA and RepB are members of the ParA and ParB families of partitioning proteins, respectively, whereas RepC is crucial for plasmid replication. In the repABC replicons, partitioning and replication functions are transcriptionally linked resulting in complex regulation of rep gene expression. The genome of R. leguminosarum bv. trifolii TA1 (RtTA1) consists of a chromosome and four plasmids (pRleTA1a-d), equipped with functional repABC genes. In this work, the regulation of transcription of the individual repABC cassettes of the four RtTA1 plasmids was studied. The involvement of the RepA and RepB as well as parS-like centromere sites in this process was depicted, demonstrating some dissimilarity in expression of respective rep regions. RtTA1 repABC genes of individual plasmids formed operons, which were negatively regulated by RepA and RepB. Individual RepA were able to bind to DNA without added nucleotides, but in the presence of ADP, bound specifically to their own operator sequences containing imperfect palindromes, and caused operon autorepression, whereas the addition of ATP stimulated non-specific binding of RepA to DNA. The RepA proteins were able to dimerize/oligomerize: in general dimers formed independently of ATP or ADP, although ATP diminished the concentration of oligomers that were produced. By the comprehensive approach focusing on a set of plasmids instead of individual replicons, the work highlighted subtle differences between the organization and regulation of particular rep operons as well as the structures and specificity of RepA proteins, which contribute to the fine-tuned coexistence of several replicons with similar repABC cassettes in the complex bacterial genome.

  8. Pulmonary Immune-Compartment-Specific Interferon Gamma Responses in HIV-Infected Individuals with Active Tuberculosis (TB in an Area of High TB Prevalence

    Directory of Open Access Journals (Sweden)

    S. Buldeo

    2012-01-01

    Full Text Available There is a paucity of data on the pulmonary immune-compartment interferon gamma (IFNγ response to M. tuberculosis, particularly in settings of high tuberculosis (TB prevalence and in HIV-coinfected individuals. This data is necessary to understand the diagnostic potential of commercially available interferon gamma release assays (IGRAs in both the pulmonary immune-compartment and peripheral blood. We used intracellular cytokine staining by flow cytometry to assess the IFNγ response to purified protein derivative (PPD and early secretory antigen 6 (ESAT6 in induced sputa (ISp and blood samples from HIV-infected, smear-negative, TB suspects. We found that individuals with active TB disease produced significantly less IFNγ in response to PPD in their induced sputa samples than individuals with non-active TB (control group. This difference was not reflected in the peripheral blood, even within the CD27− CD4+ memory T lymphocyte population. These findings suggest that progression to active TB disease may be associated with the loss of IFNγ secretion at the site of primary infection. Our findings highlight the importance of studying pulmonary immune-compartment M. tuberculosis specific responses to elucidate IFNγ secretion across the spectrum of TB disease.

  9. Interaction Effect between Handedness and CNTNAP2 Polymorphism (rs7794745 genotype on Voice-specific Frontotemporal Activity in Healthy Individuals: An fMRI Study

    Directory of Open Access Journals (Sweden)

    Michihiko eKoeda

    2015-04-01

    Full Text Available Recent neuroimaging studies have demonstrated that Contactin-associated protein-like2 (CNTNAP2 polymorphisms affect left-hemispheric function of language processing in healthy individuals, but no study has investigated the influence of these polymorphisms on right-hemispheric function involved in human voice perception. Further, although recent reports suggest that determination of handedness is influenced by genetic effect, the interaction effect between handedness and CNTNAP2 polymorphisms for brain activity in human voice perception and language processing has not been revealed. We aimed to investigate the interaction effect of handedness and CNTNAP2 polymorphisms in respect to brain function for human voice perception and language processing in healthy individuals. Brain function of 108 healthy volunteers (74 right-handed and 34 non-right-handed was examined while they were passively listening to reverse sentences (rSEN, identifiable non-vocal sounds (SND, and sentences (SEN. Full factorial design analysis was calculated by using three factors: 1 rs7794745 (A/A or A/T, 2 rs2710102 (G/G or A carrier (A/G and A/A, and 3 voice-specific response (rSEN or SND. The main effect of rs7794745 (A/A or A/T was significantly revealed at the right middle frontal gyrus (MFG and bilateral superior temporal gyrus (STG. This result suggests that rs7794745 genotype affects voice-specific brain function. Furthermore, interaction effect was significantly observed among MFG-STG activations by human voice perception, rs7794745 (A/A or A/T, and handedness. These results suggest that CNTNAP2 polymorphisms could be one of the important factors in the neural development related to vocal communication and language processing in both right-handed and non-right-handed healthy individuals.

  10. Risk markers of all-cause and diagnosis-specific disability pension--a prospective cohort study of individuals sickness absent due to stress-related mental disorders.

    Science.gov (United States)

    Ishtiak-Ahmed, Kazi; Perski, Aleksander; Mittendorfer-Rutz, Ellenor

    2014-08-07

    Stress-related mental disorders rank among the leading causes of sickness absence in several European countries. The aim of this study was to investigate predictors of all-cause and diagnosis-specific disability pension in sickness absentees with stress-related mental disorders. A cohort of 36304 non-retired individuals aged 16-64 years at 31.12.2004 with at-least one sickness absence spell due to stress-related mental disorders (SRMD) initiated in 2005 in Sweden was followed-up with regard to disability pension (2006-2010) by linkage of registers. Uni- and multivariate Hazard ratios (HR) with 95% Confidence Intervals, CI, were estimated using Cox regression for several risk markers. During the follow-up period, 2735 individuals (7.5%) were granted a disability pension, predominantly due to mental diagnoses (n = 2004, 73.3%). In the multivariate analyses, female sex, age exceeding 35 years, low educational level, being born in a country outside EU25 and Northern Europe, residing outside big cities, living alone, having had a long duration of the first spell due to SRMD (>90 days); mental disorders necessitating frequent specialised health care as well as comorbid somatic disorders were found to be predictive of granting disability pension. Some different patterns emerged for risk factors related to diagnosis-specific disability pension and for younger and older individuals. Several predictors could be identified as risk markers for disability pension. The variation in the effect of risk markers with regard to age and diagnosis of disability pension speaks in favour of the importance of a person-centered approach in treatment and rehabilitation.

  11. Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

    Science.gov (United States)

    Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George; Sloan, Derek D; Murry, Jeffrey P

    2017-04-15

    Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently

  12. Multiple HLA Epitopes Contribute to Type 1 Diabetes Susceptibility

    Science.gov (United States)

    Roark, Christina L.; Anderson, Kirsten M.; Simon, Lucas J.; Schuyler, Ronald P.; Aubrey, Michael T.; Freed, Brian M.

    2014-01-01

    Disease susceptibility for type 1 diabetes is strongly associated with the inheritance of specific HLA alleles. However, conventional allele frequency analysis can miss HLA associations because many alleles are rare. In addition, disparate alleles that have similar peptide-binding sites, or shared epitopes, can be missed. To identify the HLA shared epitopes associated with diabetes, we analyzed high-resolution genotyping for class I and class II loci. The HLA epitopes most strongly associated with susceptibility for disease were DQB1 A57, DQA1 V76, DRB1 H13, and DRB1 K71, whereas DPB1 YD9,57, HLA-B C67, and HLA-C YY9,116 were more weakly associated. The HLA epitopes strongly associated with resistance were DQB1 D57, DQA1 Y80, DRB1 R13, and DRB1 A71. A dominant resistance phenotype was observed for individuals bearing a protective HLA epitope, even in the presence of a susceptibility epitope. In addition, an earlier age of disease onset correlated with significantly greater numbers of susceptibility epitopes and fewer resistance epitopes (P epitopes was higher in patients than in control subjects and was not exclusively a result of linkage disequilibrium, suggesting that multiple HLA epitopes may work together to increase the risk of developing diabetes. PMID:24357703

  13. Optimal control in a model of malaria with differential susceptibility

    Science.gov (United States)

    Hincapié, Doracelly; Ospina, Juan

    2014-06-01

    A malaria model with differential susceptibility is analyzed using the optimal control technique. In the model the human population is classified as susceptible, infected and recovered. Susceptibility is assumed dependent on genetic, physiological, or social characteristics that vary between individuals. The model is described by a system of differential equations that relate the human and vector populations, so that the infection is transmitted to humans by vectors, and the infection is transmitted to vectors by humans. The model considered is analyzed using the optimal control method when the control consists in using of insecticide-treated nets and educational campaigns; and the optimality criterion is to minimize the number of infected humans, while keeping the cost as low as is possible. One first goal is to determine the effects of differential susceptibility in the proposed control mechanism; and the second goal is to determine the algebraic form of the basic reproductive number of the model. All computations are performed using computer algebra, specifically Maple. It is claimed that the analytical results obtained are important for the design and implementation of control measures for malaria. It is suggested some future investigations such as the application of the method to other vector-borne diseases such as dengue or yellow fever; and also it is suggested the possible application of free software of computer algebra like Maxima.

  14. Reduced Hepatitis B Virus (HBV)-Specific CD4+ T-Cell Responses in Human Immunodeficiency Virus Type 1-HBV-Coinfected Individuals Receiving HBV-Active Antiretroviral Therapy

    OpenAIRE

    Chang, J. Judy; Wightman, Fiona; Bartholomeusz, Angeline; Ayres, Anna; Kent, Stephen J.; Sasadeusz, Joseph; Sharon R Lewin

    2005-01-01

    Functional hepatitis B virus (HBV)-specific T cells are significantly diminished in individuals chronically infected with HBV compared to individuals with self-limiting HBV infection or those on anti-HBV therapy. In individuals infected with human immunodeficiency virus type 1 (HIV-1), coinfection with HBV is associated with an increased risk of worsening liver function following antiviral therapy and of more rapid HBV disease progression. Total HBV-specific T-cell responses in subjects with ...

  15. The National Trajectory Project of Individuals Found Not Criminally Responsible on Account of Mental Disorder. Part 5: How Essential Are Gender-Specific Forensic Psychiatric Services?

    Science.gov (United States)

    Nicholls, Tonia L; Crocker, Anne G; Seto, Michael C; Wilson, Catherine M; Charette, Yanick; Côté, Gilles

    2015-01-01

    Objective: To state the sociodemographic characteristics, mental health histories, index offence characteristics, and criminal histories of male and female forensic psychiatric patients. Clinicians and researchers advocate that mental health and criminal justice organizations implement gender-specific services; however, few studies have sampled forensic patients to evaluate the extent to which men’s and women’s treatment and management needs are different. Method: Data were collected from Review Board files from May 2000 to April 2005 in the 3 largest Canadian provinces. Using official criminal records, participants were followed for 3 to 8 years, until December 2008. The final sample comprised 1800 individuals: 15.6% were women and 84.4% were men. Results: There were few demographic differences, but women had higher psychosocial functioning than men. Both men and women had extensive mental health histories; women were more likely diagnosed with mood disorders and PDs and men were more likely diagnosed with schizophrenia spectrum disorders and SUDs. The nature of the index offence did not differ by gender, except women were more likely to have perpetrated murders and attempted murders. For offences against a person, women were more likely to offend against offspring and partners and less likely to offend against strangers, compared with men. Women had significantly less extensive criminal histories than men. Conclusions: Not criminally responsible on account of mental disorder–accused women have a distinct psychosocial, clinical, and criminological profile from their male counterparts, which may suggest gender-specific assessment, risk management, and treatment in forensic services could benefit patients. The findings are also consistent with traditional models (Risk-Need-Responsivity) and ultimately demonstrate the importance of individual assessment and client-centred services. PMID:25886689

  16. Clinimetric properties of the Tinetti Mobility Test, Four Square Step Test, Activities-specific Balance Confidence Scale, and spatiotemporal gait measures in individuals with Huntington's disease.

    Science.gov (United States)

    Kloos, Anne D; Fritz, Nora E; Kostyk, Sandra K; Young, Gregory S; Kegelmeyer, Deb A

    2014-09-01

    Individuals with Huntington's disease (HD) experience balance and gait problems that lead to falls. Clinicians currently have very little information about the reliability and validity of outcome measures to determine the efficacy of interventions that aim to reduce balance and gait impairments in HD. This study examined the reliability and concurrent validity of spatiotemporal gait measures, the Tinetti Mobility Test (TMT), Four Square Step Test (FSST), and Activities-specific Balance Confidence (ABC) Scale in individuals with HD. Participants with HD [n = 20; mean age ± SD=50.9 ± 13.7; 7 male] were tested on spatiotemporal gait measures and the TMT, FSST, and ABC Scale before and after a six week period to determine test-retest reliability and minimal detectable change (MDC) values. Linear relationships between gait and clinical measures were estimated using Pearson's correlation coefficients. Spatiotemporal gait measures, the TMT total and the FSST showed good to excellent test-retest reliability (ICC > 0.75). MDC values were 0.30 m/s and 0.17 m/s for velocity in forward and backward walking respectively, four points for the TMT, and 3s for the FSST. The TMT and FSST were highly correlated with most spatiotemporal measures. The ABC Scale demonstrated lower reliability and less concurrent validity than other measures. The high test-retest reliability over a six week period and concurrent validity between the TMT, FSST, and spatiotemporal gait measures suggest that the TMT and FSST may be useful outcome measures for future intervention studies in ambulatory individuals with HD. Copyright © 2014 Elsevier B.V. All rights reserved.

  17. The effects of inbreeding on disease susceptibility: Gyrodactylus turnbulli infection of guppies, Poecilia reticulata.

    Science.gov (United States)

    Smallbone, Willow; van Oosterhout, Cock; Cable, Jo

    2016-08-01

    Inbreeding can threaten population persistence by reducing disease resistance through the accelerated loss of gene diversity (i.e. heterozygosity). Such inbreeding depression can affect many different fitness-related traits, including survival, reproductive success, and parasite susceptibility. Empirically quantifying the effects of inbreeding on parasite resistance is therefore important for ex-situ conservation of vertebrates. The present study evaluates the disease susceptibility of individuals bred under three different breeding regimes (inbred, crossed with full siblings; control, randomly crossed mating; and fully outbred). Specifically, we examined the relationship between inbreeding coefficient (F-coefficient) and susceptibility to Gyrodactylus turnbulli infection in a live bearing vertebrate, the guppy Poecilia reticulata. Host-breeding regime significantly affected the trajectories of parasite population growth on individual fish. Inbred fish showed significantly higher mean parasite intensity than fish from the control and outbred breeding regimes, and in addition, inbred fish were slower in purging their gyrodactylid infections. We discuss the role of inbreeding on the various arms of the immune system, and argue that the increased disease susceptibility of inbred individuals could contribute to the extinction vortex. This is one of the first studies to quantify the effects of inbreeding and breeding regime on disease susceptibility in a captive bred vertebrate of wild origin, and it highlights the risks faced by small (captive-bred) populations when exposed to their native parasites. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Prevalence and correlation of cytokine-specific autoantibodies with epidemiological factors and C-reactive protein in 8,972 healthy individuals

    DEFF Research Database (Denmark)

    von Stemann, Jakob Hjorth; Rigas, Andreas Stribolt; Thørner, Lise Wegner

    2017-01-01

    Natural cytokine-specific autoantibodies (c-aAb) have been measured in healthy and diseased individuals, and have been considered as both endogenous immune-regulators and pathogenic factors. Overall, the etiology and potential pathology of c-aAb are still undefined. To further characterize the sero......-prevalence, predictors and consequences of high c-aAb levels, we performed the largest population-based study of c-aAb to date, using participants and epidemiological data from the Danish Blood Donor Study. Using a validated bead-based multiplex assay we assessed plasma levels of IL-1α, IL-6, IL-10, IFNα and GM......-CSF-specific c-aAb in 8,972 healthy blood donors. Trace levels of at least one of the investigated c-aAb could be measured in 86% of the participants. The presence of high levels of potentially inhibitory c-aAb was generally associated with increasing age and male or female sex, depending on the c...

  19. Immediate effects of Pilates based therapeutic exercise on postural control of young individuals with non-specific low back pain: A randomized controlled trial.

    Science.gov (United States)

    Lopes, Susana; Correia, Christophe; Félix, Gonçalo; Lopes, Mário; Cruz, Ana; Ribeiro, Fernando

    2017-10-01

    Low back pain affects the person's ability to keep balance, especially in challenging conditions. The purpose of this study was to determine the immediate effects of Pilates exercises on postural sway and dynamic balance of young individuals with non-specific low back pain. Controlled laboratory design. Forty-six participants with non-specific low back pain were randomized to a Pilates (n=23, 10 males; age: 21.8±3.2years) and a control group (n=23, 9 males; age: 22.8±3.6years). Postural sway was assessed with a force platform and dynamic balance with the Star Excursion Balance Test, before and after the intervention or rest period. To assess postural sway, participants stood still on an unstable surface set on the force plate for 90s, with eyes closed. The intervention lasted 20min and consisted on four Pilates exercises: single leg stretch (level 1), pelvic press (level 1), swimming (level 1) and kneeling opposite arm and leg reach. At baseline, no differences were found between groups. The Pilates group improved in all the postural sway values (area of CoP: 11.5±3.4 to 9.7±2.7cm2, p=0.002 and CoP velocity: 2.8±0.6 to 2.3±0.5cm/s, pPilates group. Pilates exercises immediately improved postural sway and dynamic balance in young adults with non-specific low back pain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. Experience of parental cancer in childhood is a risk factor for psychological distress during genetic cancer susceptibility testing

    NARCIS (Netherlands)

    van Oostrom, I.; Meijers-Heijboer, H.; Duivenvoorden, H. J.; Brocker-Vriends, A. H. J. T.; van Asperen, C. J.; Sijmons, R. H.; Seynaeve, C.; Van Gool, A. R.; Klijn, J. G. M.; Tibben, A.

    Background: This study explores the effect of age at the time of parental cancer diagnosis or death on psychological distress and cancer risk perception in individuals undergoing genetic testing for a specific cancer susceptibility. Patients and methods: Cancer-related distress, worry and risk

  1. GRAPHICAL USER INTERFACE WITH APPLICATIONS IN SUSCEPTIBLE-INFECTIOUS-SUSCEPTIBLE MODELS.

    Science.gov (United States)

    Ilea, M; Turnea, M; Arotăriţei, D; Rotariu, Mariana; Popescu, Marilena

    2015-01-01

    Practical significance of understanding the dynamics and evolution of infectious diseases increases continuously in contemporary world. The mathematical study of the dynamics of infectious diseases has a long history. By incorporating statistical methods and computer-based simulations in dynamic epidemiological models, it could be possible for modeling methods and theoretical analyses to be more realistic and reliable, allowing a more detailed understanding of the rules governing epidemic spreading. To provide the basis for a disease transmission, the population of a region is often divided into various compartments, and the model governing their relation is called the compartmental model. To present all of the information available, a graphical user interface provides icons and visual indicators. The graphical interface shown in this paper is performed using the MATLAB software ver. 7.6.0. MATLAB software offers a wide range of techniques by which data can be displayed graphically. The process of data viewing involves a series of operations. To achieve it, I had to make three separate files, one for defining the mathematical model and two for the interface itself. Considering a fixed population, it is observed that the number of susceptible individuals diminishes along with an increase in the number of infectious individuals so that in about ten days the number of individuals infected and susceptible, respectively, has the same value. If the epidemic is not controlled, it will continue for an indefinite period of time. By changing the global parameters specific of the SIS model, a more rapid increase of infectious individuals is noted. Using the graphical user interface shown in this paper helps achieving a much easier interaction with the computer, simplifying the structure of complex instructions by using icons and menus, and, in particular, programs and files are much easier to organize. Some numerical simulations have been presented to illustrate theoretical

  2. Susceptibility to malignant hyperthermia

    NARCIS (Netherlands)

    Snoeck, Marcus Matheus Johannes

    2004-01-01

    In this thesis the author studied the diagnostic procedures for susceptibility to malignant hyperthermia (MH), with special emphasis upon refining the biological diagnostic test and improving protocols and guidelines for investigation of MH susceptibility. MH is a pharmacogenetic disease of skeletal

  3. The associations between US state and local social spending, income inequality, and individual all-cause and cause-specific mortality: The National Longitudinal Mortality Study.

    Science.gov (United States)

    Kim, Daniel

    2016-03-01

    To investigate government state and local spending on public goods and income inequality as predictors of the risks of dying. Data on 431,637 adults aged 30-74 and 375,354 adults aged 20-44 in the 48 contiguous US states were used from the National Longitudinal Mortality Study to estimate the impacts of state and local spending and income inequality on individual risks of all-cause and cause-specific mortality for leading causes of death in younger and middle-aged adults and older adults. To reduce bias, models incorporated state fixed effects and instrumental variables. Each additional $250 per capita per year spent on welfare predicted a 3-percentage point (-0.031, 95% CI: -0.059, -0.0027) lower probability of dying from any cause. Each additional $250 per capita spent on welfare and education predicted 1.6-percentage point (-0.016, 95% CI: -0.031, -0.0011) and 0.8-percentage point (-0.008, 95% CI: -0.0156, -0.00024) lower probabilities of dying from coronary heart disease (CHD), respectively. No associations were found for colon cancer or chronic obstructive pulmonary disease; for diabetes, external injury, and suicide, estimates were inverse but modest in magnitude. A 0.1 higher Gini coefficient (higher income inequality) predicted 1-percentage point (0.010, 95% CI: 0.0026, 0.0180) and 0.2-percentage point (0.002, 95% CI: 0.001, 0.002) higher probabilities of dying from CHD and suicide, respectively. Empirical linkages were identified between state-level spending on welfare and education and lower individual risks of dying, particularly from CHD and all causes combined. State-level income inequality predicted higher risks of dying from CHD and suicide. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  4. Adolescent neurobiological susceptibility to social context

    Directory of Open Access Journals (Sweden)

    Roberta A. Schriber

    2016-06-01

    Full Text Available Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment encountered (e.g., high vs. low parental warmth. Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. Ultimately, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes.

  5. Adolescent Neurobiological Susceptibility to Social Context

    Science.gov (United States)

    Schriber, Roberta A.; Guyer, Amanda E.

    2016-01-01

    Adolescence has been characterized as a period of heightened sensitivity to social contexts. However, adolescents vary in how their social contexts affect them. According to neurobiological susceptibility models, endogenous, biological factors confer some individuals, relative to others, with greater susceptibility to environmental influences, whereby more susceptible individuals fare the best or worst of all individuals, depending on the environment they encounter (e.g., high vs. low parental warmth). Until recently, research guided by these theoretical frameworks has not incorporated direct measures of brain structure or function to index this sensitivity. Drawing on prevailing models of adolescent neurodevelopment and a growing number of neuroimaging studies on the interrelations among social contexts, the brain, and developmental outcomes, we review research that supports the idea of adolescent neurobiological susceptibility to social context for understanding why and how adolescents differ in development and well-being. We propose that adolescent development is shaped in part by brain-based individual differences in sensitivity to social contexts – be they positive or negative – such as those created through relationships with parents/caregivers and peers. As such, we recommend that future research measure brain function and structure to operationalize susceptibility factors that moderate the influence of social contexts on developmental outcomes. PMID:26773514

  6. In search of specificity: "not just right experiences" and obsessive-compulsive symptoms in non-clinical and clinical Italian individuals.

    Science.gov (United States)

    Ghisi, Marta; Chiri, Luigi Rocco; Marchetti, Igor; Sanavio, Ezio; Sica, Claudio

    2010-12-01

    The cognitive model of OCD proposes that certain beliefs may contribute to the development and maintenance of this disorder. To date, however, it is not yet clear which beliefs are more relevant for explaining OCD symptomatology; moreover, their causal status is yet to be clearly established. In the effort to identify other constructs and processes related to OCD, the phenomenon labeled "not just right experiences" (NJREs) has received increasing attention. In this study, measures of NJREs (the NJRE-Q-R), OCD symptoms, general distress (i.e., anxiety, and depression), and perfectionism were administered to a large sample of college students and a small sample of OCD and non-OCD patients. The clinical sample also completed a measure of OC beliefs. Results showed that NJREs could be reliably measured through a self-report format in non-clinical and clinical Italian individuals. A specific association between NJREs severity and OCD symptoms was found in the non-clinical sample, after controlling for anxiety, depression, and perfectionism. The NJRE-Q-R Severity scale clearly discriminated OCD patients from patients with other anxiety disorders or depression. Lastly, the NJREs measure differentiated the clinical groups when OC beliefs were controlled, whereas OC beliefs did not discriminate among the groups after NJREs severity was controlled. The concept of NJREs may contribute to improve current psychological and biological model of OCD. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Validation of Individual-Based Markov-Like Stochastic Process Model of Insect Behavior and a “Virtual Farm” Concept for Enhancement of Site-Specific IPM

    Science.gov (United States)

    Lux, Slawomir A.; Wnuk, Andrzej; Vogt, Heidrun; Belien, Tim; Spornberger, Andreas; Studnicki, Marcin

    2016-01-01

    The paper reports application of a Markov-like stochastic process agent-based model and a “virtual farm” concept for enhancement of site-specific Integrated Pest Management. Conceptually, the model represents a “bottom-up ethological” approach and emulates behavior of the “primary IPM actors”—large cohorts of individual insects—within seasonally changing mosaics of spatiotemporally complex faming landscape, under the challenge of the local IPM actions. Algorithms of the proprietary PESTonFARM model were adjusted to reflect behavior and ecology of R. cerasi. Model parametrization was based on compiled published information about R. cerasi and the results of auxiliary on-farm experiments. The experiments were conducted on sweet cherry farms located in Austria, Germany, and Belgium. For each farm, a customized model-module was prepared, reflecting its spatiotemporal features. Historical data about pest monitoring, IPM treatments and fruit infestation were used to specify the model assumptions and calibrate it further. Finally, for each of the farms, virtual IPM experiments were simulated and the model-generated results were compared with the results of the real experiments conducted on the same farms. Implications of the findings for broader applicability of the model and the “virtual farm” approach—were discussed. PMID:27602000

  8. Validation of individual-based Markov-like stochastic process model of insect behaviour and a ‘virtual farm’ concept for enhancement of site-specific IPM

    Directory of Open Access Journals (Sweden)

    Slawomir Antoni Lux

    2016-08-01

    Full Text Available The paper reports application of a Markov-like stochastic process agent-based model and a ‘virtual farm’ concept for enhancement of site-specific Integrated Pest Management. Conceptually, the model represents a ‘bottom-up ethological’ approach and emulates behaviour of the ‘primary IPM actors’ - large cohorts of individual insects - within seasonally changing mosaics of spatiotemporally complex faming landscape, under the challenge of the local IPM actions. Algorithms of the proprietary PESTonFARM model were adjusted to reflect behaviour and ecology of R. cerasi. Model parametrization was based on compiled published information about R. cerasi and the results of auxiliary on-farm experiments. The experiments were conducted on sweet cherry farms located in Austria, Germany and Belgium. For each farm, a customised model-module was prepared, reflecting its spatiotemporal features. Historical data about pest monitoring, IPM treatments and fruit infestation were used to specify the model assumptions and calibrate it further. Finally, for each of the farms, virtual IPM experiments were simulated and the model-generated results were compared with the results of the real experiments conducted on the same farms. Implications of the findings for broader applicability of the model and the ‘virtual farm’ approach - were discussed.

  9. Validation of Individual-Based Markov-Like Stochastic Process Model of Insect Behavior and a "Virtual Farm" Concept for Enhancement of Site-Specific IPM.

    Science.gov (United States)

    Lux, Slawomir A; Wnuk, Andrzej; Vogt, Heidrun; Belien, Tim; Spornberger, Andreas; Studnicki, Marcin

    2016-01-01

    The paper reports application of a Markov-like stochastic process agent-based model and a "virtual farm" concept for enhancement of site-specific Integrated Pest Management. Conceptually, the model represents a "bottom-up ethological" approach and emulates behavior of the "primary IPM actors"-large cohorts of individual insects-within seasonally changing mosaics of spatiotemporally complex faming landscape, under the challenge of the local IPM actions. Algorithms of the proprietary PESTonFARM model were adjusted to reflect behavior and ecology of R. cerasi. Model parametrization was based on compiled published information about R. cerasi and the results of auxiliary on-farm experiments. The experiments were conducted on sweet cherry farms located in Austria, Germany, and Belgium. For each farm, a customized model-module was prepared, reflecting its spatiotemporal features. Historical data about pest monitoring, IPM treatments and fruit infestation were used to specify the model assumptions and calibrate it further. Finally, for each of the farms, virtual IPM experiments were simulated and the model-generated results were compared with the results of the real experiments conducted on the same farms. Implications of the findings for broader applicability of the model and the "virtual farm" approach-were discussed.

  10. Repeatable intra-individual variation in plasma testosterone concentration and its sex-specific link to aggression in a social lizard

    NARCIS (Netherlands)

    While, Geoffrey M.; Isaksson, Caroline; McEvoy, Jo; Sinn, David L.; Komdeur, Jan; Wapstra, Erik; Groothuis, Ton G.G.

    Individual hormone profiles can be important generators of phenotypic variation. Despite this, work on the consequences of hormone profiles has traditionally ignored the large inter-individual variation within natural populations. However, recent research has advocated the need to explicitly

  11. Susceptibility to COPD: differential proteomic profiling after acute smoking.

    Directory of Open Access Journals (Sweden)

    Lorenza Franciosi

    Full Text Available Cigarette smoking is the main risk factor for COPD (Chronic Obstructive Pulmonary Disease, yet only a subset of smokers develops COPD. Family members of patients with severe early-onset COPD have an increased risk to develop COPD and are therefore defined as "susceptible individuals". Here we perform unbiased analyses of proteomic profiles to assess how "susceptible individuals" differ from age-matched "non-susceptible individuals" in response to cigarette smoking. Epithelial lining fluid (ELF was collected at baseline and 24 hours after smoking 3 cigarettes in young individuals susceptible or non-susceptible to develop COPD and older subjects with established COPD. Controls at baseline were older healthy smoking and non-smoking individuals. Five samples per group were pooled and analysed by stable isotope labelling (iTRAQ in duplicate. Six proteins were selected and validated by ELISA or immunohistochemistry. After smoking, 23 proteins increased or decreased in young susceptible individuals, 7 in young non-susceptible individuals, and 13 in COPD in the first experiment; 23 proteins increased or decreased in young susceptible individuals, 32 in young non-susceptible individuals, and 11 in COPD in the second experiment. SerpinB3 and Uteroglobin decreased after acute smoke exposure in young non-susceptible individuals exclusively, whereas Peroxiredoxin I, S100A9, S100A8, ALDH3A1 (Aldehyde dehydrogenase 3A1 decreased both in young susceptible and non-susceptible individuals, changes being significantly different between groups for Uteroglobin with iTRAQ and for Serpin B3 with iTRAQ and ELISA measures. Peroxiredoxin I, SerpinB3 and ALDH3A1 increased in COPD patients after smoking. We conclude that smoking induces a differential protein response in ELF of susceptible and non-susceptible young individuals, which differs from patients with established COPD. This is the first study applying unbiased proteomic profiling to unravel the underlying

  12. FcGammaRIIa polymorphism and anti-malaria specific IgG and IgG subclass responses in populations differing in susceptibility to malaria in Burkina Faso

    DEFF Research Database (Denmark)

    Cherif, Mariama K; Sanou, Guillaume S; Maiga, Boubakar

    2012-01-01

    Fc¿RIIa is known to be polymorphic; and certain variants err associated with differt susceptibilities to malaria. Studies involving the Fulani ethnic group reported an ethnic difference in Fc¿RIIa-R131H genotype frequencies between the Fulani and other sympatric groups. No previous studies have a...

  13. Inter- and intra-individual variation in allele-specific DNA methylation and gene expression in children conceived using assisted reproductive technology.

    Directory of Open Access Journals (Sweden)

    Nahid Turan

    2010-07-01

    Full Text Available Epidemiological studies have reported a higher incidence of rare disorders involving imprinted genes among children conceived using assisted reproductive technology (ART, suggesting that ART procedures may be disruptive to imprinted gene methylation patterns. We examined intra- and inter-individual variation in DNA methylation at the differentially methylated regions (DMRs of the IGF2/H19 and IGF2R loci in a population of children conceived in vitro or in vivo. We found substantial variation in allele-specific methylation at both loci in both groups. Aberrant methylation of the maternal IGF2/H19 DMR was more common in the in vitro group, and the overall variance was also significantly greater in the in vitro group. We estimated the number of trophoblast stem cells in each group based on approximation of the variance of the binomial distribution of IGF2/H19 methylation ratios, as well as the distribution of X chromosome inactivation scores in placenta. Both of these independent measures indicated that placentas of the in vitro group were derived from fewer stem cells than the in vivo conceived group. Both IGF2 and H19 mRNAs were significantly lower in placenta from the in vitro group. Although average birth weight was lower in the in vitro group, we found no correlation between birth weight and IGF2 or IGF2R transcript levels or the ratio of IGF2/IGF2R transcript levels. Our results show that in vitro conception is associated with aberrant methylation patterns at the IGF2/H19 locus. However, very little of the inter- or intra-individual variation in H19 or IGF2 mRNA levels can be explained by differences in maternal DMR DNA methylation, in contrast to the expectations of current transcriptional imprinting models. Extraembryonic tissues of embryos cultured in vitro appear to be derived from fewer trophoblast stem cells. It is possible that this developmental difference has an effect on placental and fetal growth.

  14. CD127 expression, exhaustion status and antigen specific proliferation predict sustained virologic response to IFN in HCV/HIV co-infected individuals.

    Directory of Open Access Journals (Sweden)

    Hassen Kared

    Full Text Available Hepatitis C virus (HCV infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-α therapy with different outcomes including IFN-α non-responders (NR (n = 9 and patients who achieved sustained virologic response (SVR (n = 19. We examined the expression of activation (CD38, HLA-DR, functional (CD127 and exhaustion markers (PD1, Tim-3, CD160 and CD244 on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127+ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-α therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN-based therapies in co-infected individuals.

  15. Influence of specific individual and environmental variables on the relationship between body mass index and health-related quality of life in overweight and obese adolescents.

    Science.gov (United States)

    Kolodziejczyk, Julia K; Gutzmer, Kyle; Wright, Shana M; Arredondo, Elva M; Hill, Linda; Patrick, Kevin; Huang, Jeannie S; Gottschalk, Michael; Norman, Gregory J

    2015-01-01

    Overweight and obese adolescents are at risk for low health-related quality of life (HRQOL). We examined the role of individual- and environmental-level variables on the relationship between body mass index (BMI kg/m(2)) and HRQOL in adolescents. Linear regressions were performed to conduct mediation and moderation analyses on the relationship between BMI and HRQOL in overweight and obese adolescents (N = 205). HRQOL was measured by the Pediatric Quality of Life Inventory. Hypothesized mediators included depression, measured by the Center for Epidemiologic Studies Depression Scale; body image, measured by the gender-specific body dissatisfaction subscale of the Eating Disorder Inventory; and self-esteem, measured by the Rosenberg Self-Esteem Scale. Mediation was assessed using Baron and Kenny's approach and Sobel's test of indirect effects. Anglo-acculturation, measured by the Short Acculturation Scale for Hispanics-Youth, and environmental perception, measured by parent-proxy report of the Neighborhood Environment Walkability Scale, were hypothesized moderators. Body image mediated the relationship between BMI and HRQOL (b = -0.34, SE = 0.17, adj R (2) = 0.19, p = .051), and self-esteem was a partial mediator (b = -0.37, SE = 0.17, adj R (2) = 0.24, p = .027). Sobel's test confirmed these results (p body image and self-esteem, influence the relationship between BMI and HRQOL while environmental factors, such as neighborhood environment and acculturation, do not extends previous research. The finding that body image and self-esteem partially mediate this relationship presents new areas to investigate in interventions that address BMI in youth.

  16. Sex-specific and inter-individual differences in biomarkers of selenium status identified by a calibrated ELISA for selenoprotein P

    Directory of Open Access Journals (Sweden)

    Sandra Hybsier

    2017-04-01

    Full Text Available Selenoprotein P (SELENOP is a liver-derived transporter of selenium (Se in blood, and a meaningful biomarker of Se status. Se is an essential trace element for the biosynthesis of enzymatically-active selenoproteins, protecting the organism from oxidative damage. The usage of uncalibrated assays hinders the comparability of SELENOP concentrations and their pathophysiological interpretation across different clinical studies. On this account, we established a new sandwich SELENOP-ELISA and calibrated against a standard reference material (SRM1950. The ELISA displays a wide working range (11.6–538.4 µg/L, high accuracy (2.9% and good precision (9.3%. To verify whether SELENOP correlates to total Se and to SELENOP-bound Se, serum samples from healthy subjects and age-selected participants from the Berlin Aging Study II were analyzed by SELENOP-ELISA and Se quantification. SELENOP was affinity-purified and its Se content was determined from a subset of samples. There was a high correlation of total Se and SELENOP concentrations in young and elderly men, and in elderly women, but not in young women, indicating a specific sexual dimorphism in these biomarkers of Se status in young subjects. The Se content of isolated SELENOP was independent of sex and age (mean±SD: 5.4±0.5. By using this calibrated SELENOP-ELISA, prior reports on pathological SELENOP concentrations in diabetes and obesity are challenged as the reported values are outside reasonable limits. Biomarkers of Se status in clinical research need to be measured by validated assays in order to avoid erroneous data and incorrect interpretations, especially when analyzing young women. The Se content of circulating SELENOP differs between individuals and may provide some important diagnostic information on Se metabolism and status.

  17. Relationship between high esterase activity and in vitro degradation of /sup 14/C-malathion by organophosphate-resistant and susceptible strains of the Kanzawa spider mite, Tetranychus kanzawai Kishida (Acarina: Tetranychidae), and their inhibition with specific synergists

    Energy Technology Data Exchange (ETDEWEB)

    Kuwahara, M. (National Inst. of Agricultural Sciences, Yatabe, Ibaraki (Japan)); Miyata, T.; Saito, T.; Eto, M.

    1981-08-01

    The relationship between the enzymes which catalyze hydrolysis of ..beta..-naphthyl acetate and degradation of malathion was studied in resistant and susceptible strains of the Kanzawa spider mite, Tetranychus kanzawai Kishida. The homogenate of resistant mites exhibited higher activity in the degradation of malathion in vitro than that of susceptible mites, but such activity was remarkably inhibited by the compound K-1, which also manifested a prominent synergism with malathion to resistant mites. Six esterase bands and three peaks of malathion degradation were resolved by agar-gel electrophoresis. Resistance to malathion was associated with increased esterase activity at E/sub 3/ and E/sub 4/ bands on which the main peak of malathion degradation was detected. The compound K-1 selectively inhibited the esterase and degradation activities. Compounds K-9 and IBP, on the other hand, selectively inhibited E/sub 1/ and E/sub 2/ bands which overlapped with the minor peaks of malanthion degradation.

  18. Association of 677 C>T (rs1801133 and 1298 A>C (rs1801131 polymorphisms in the MTHFR gene and breast cancer susceptibility: a meta-analysis based on 57 individual studies.

    Directory of Open Access Journals (Sweden)

    Kai Li

    Full Text Available OBJECTIVE: The 677 C>T and 1298 A>C polymorphisms of methylenetetrahydrofolate reductase (MTHFR gene have been widely reported and considered to have a significant effect on breast cancer risk, but the results are inconsistent. A meta-analysis based on 57 eligible studies was carried out to clarify the role of MTHFR gene polymorphisms in breast cancer. METHODS AND RESULTS: Eligible articles were identified by searching databases including PubMed, Web of Science, EMBASE, CNKI and CBM for the period up to August 2012. Finally, a total of 57 studies were included in this meta-analysis. Crude ORs with 95% CIs were used to assess the association between the MTHFR polymorphisms and breast cancer risk. The pooled ORs were performed with additive model, dominant model and recessive model, respectively. Subgroup analysis was also performed by ethnicity. The statistical heterogeneity across studies was examined with χ2-based Q-test. A meta-analysis was performed using the Stata 12.0 software. Overall, the 677 C allele was significantly associated with breast cancer risk (OR = 0.942, 95%CI = 0.898 to 0.988 when compared with the 677 T allele in the additive model, and the same results were also revealed under other genetic models. Simultaneously, the 1298 A allele was not associated with the breast cancer susceptibility when compared with the 1298 C allele (OR = 0.993, 95%CI = 0.978 to 1.009. Furthermore, analyses under the dominant, recessive and the allele contrast model yielded similar results. CONCLUSIONS: The results of this meta-analysis suggest that 677 C>T polymorphism in the MTHFR gene may contribute to breast cancer development. However, the 1298 A>C polymorphism is not significantly associated with increased risks of breast cancer.

  19. Association of 677 C>T (rs1801133) and 1298 A>C (rs1801131) Polymorphisms in the MTHFR Gene and Breast Cancer Susceptibility: A Meta-Analysis Based on 57 Individual Studies

    Science.gov (United States)

    Li, Kai; Li, Wusheng; Dong, Xi

    2014-01-01

    Objective The 677 C>T and 1298 A>C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene have been widely reported and considered to have a significant effect on breast cancer risk, but the results are inconsistent. A meta-analysis based on 57 eligible studies was carried out to clarify the role of MTHFR gene polymorphisms in breast cancer. Methods and Results Eligible articles were identified by searching databases including PubMed, Web of Science, EMBASE, CNKI and CBM for the period up to August 2012. Finally, a total of 57 studies were included in this meta-analysis. Crude ORs with 95% CIs were used to assess the association between the MTHFR polymorphisms and breast cancer risk. The pooled ORs were performed with additive model, dominant model and recessive model, respectively. Subgroup analysis was also performed by ethnicity. The statistical heterogeneity across studies was examined with χ2-based Q-test. A meta-analysis was performed using the Stata 12.0 software. Overall, the 677 C allele was significantly associated with breast cancer risk (OR = 0.942, 95%CI = 0.898 to 0.988) when compared with the 677 T allele in the additive model, and the same results were also revealed under other genetic models. Simultaneously, the 1298 A allele was not associated with the breast cancer susceptibility when compared with the 1298 C allele (OR = 0.993, 95%CI = 0.978 to 1.009). Furthermore, analyses under the dominant, recessive and the allele contrast model yielded similar results. Conclusions The results of this meta-analysis suggest that 677 C>T polymorphism in the MTHFR gene may contribute to breast cancer development. However, the 1298 A>C polymorphism is not significantly associated with increased risks of breast cancer. PMID:24945727

  20. Total and cause-specific mortality by elevated transferrin saturation and hemochromatosis genotype in individuals with diabetes - two general population studies

    DEFF Research Database (Denmark)

    Ellervik, Christina; Mandrup-Poulsen, Thomas; Tybjærg-Hansen, Anne

    2013-01-01

    ObjectiveMortality is increased in patients with hereditary hemochromatosis, in individuals from the general population with increased transferrin saturation(TS), and also in patients with diabetes type 1 and increased TS from a highly specialised diabetes clinic. Thus, we have recommended targeted...... and hemochromatosis genotype(HFE) C282Y/C282Y in individuals with diabetes(type 1,N=118;type 2,N=3228;total,N=3346).ResultsThe cumulative survival was reduced in individuals with diabetes with TS≥50% vs....

  1. Environmentally Induced Epigenetic Transgenerational Inheritance of Disease Susceptibility

    Science.gov (United States)

    Nilsson, Eric E.; Skinner, Michael K.

    2014-01-01

    Environmental insults, such as exposure to toxicants or nutritional abnormalities, can lead to epigenetic changes that are in turn related to increased susceptibility to disease. The focus of this review is on the transgenerational inheritance of such epigenetic abnormalities (epimutations), and how it is that these inherited epigenetic abnormalities can lead to increased disease susceptibility, even in the absence of continued environmental insult. Observations of environmental toxicant specificity and exposure specific disease susceptibility are discussed. How epimutations are transmitted across generations and how epigenetic changes in the germline are translated into an increased disease susceptibility in the adult is reviewed in regards to disease etiology. PMID:24657180

  2. Susceptibility to air pollution in elderly males and females

    NARCIS (Netherlands)

    Boezen, H M; Vonk, J.M.; van der Zee, S C; Gerritsen, J; Hoek, G; Brunekreef, B; Schouten, Jan; Postma, D S

    It is important to know which individuals in the general population have increased susceptibility to air pollution. The aim of this study was to identify susceptible subgroups by studying airways hyperresponsiveness (AHR), high total immunoglobulin (Ig)E and sex. Diary data on lower and upper

  3. Diagnostic Value of Direct Antibiotic Susceptibility Test for Faster BacterialSusceptibility Reporting in Bacteremia

    Directory of Open Access Journals (Sweden)

    Rebriarina Hapsari

    2012-12-01

    Methods: Bloods from positive BACTEC bottles which met inclusion and exclusion criteria were put into sterile tubes and centrifuged. The pellets were then used to make 0.5 McFarland bacterial suspensions and directly used for antibiotic susceptibility testing. Interpretations of direct method were compared to standard method to count sensitivity, specificity, sensitive predictive value, resistant predictive value, accuracy, and kappa value. Results: From 58 samples (containing 22 gram negative, 36 gram positive bacteria, there were 309 total antibiotic susceptibility tests. Direct method showed sensitivity, specificity, sensitive predictive value, resistant predictive value, accuracy, and kappa value of 89.3%, 92.9%, 93.8%, 87.8%, 86.4%, and 0.82, respectively. Conclusion: Direct antibiotic susceptibility testing has a good agreement with the standard method so it can aid faster antibiotic susceptibility reporting in bacteraemia (Sains Medika, 4(2:174-181.

  4. Transplantational and specific antitumor immunity in retrospective view: new models based on transgenesis of individual chains of T-cell receptor

    Directory of Open Access Journals (Sweden)

    D. B. Kazanskiy

    2016-01-01

    Full Text Available Findings in experimental oncology in beginning of last century and subsequent achievements of genetics of tissue compatibility resulted in divergence of transplantational immunology and oncoimmunology. However, central achievements of both scientific fields are based on unified phenomenon of interaction between T-cell receptor (TCR and histocompatibility molecules. In this review we describe the history of ideas, achievements and unique experience of the team of the Laboratory of Regulatory Mechanisms in Immunity at Scientific Research Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center for all time of existence. This experience shows that efficiency of immunological defense including immunological surveillance are critically influenced by T-cell receptor repertoire. Transgenesis of individual chains of TCR is one of possible means to manage T-cell repertoire. Functional outcomes of transgenesis may be different due to diverse extent of dependence of α- and β-chains expression on the rules of allelic exclusion. Expression of transgenic β-chains results in the expansion of TCR repertoire diversity. Expression of β-chains is under strong control by allelic exclusion, resulting in formation of repertoire bearing mainly invariant transgenic β-chain pared with different α-chains and overall narrowing of repertoire. Earlier, we cloned genes encoding α- and β-chains of TCR of CD8+ memory cells specific to histocompatibility molecule H-2Kb . After introduction them in zigotes we have obtained transgenic mouse strains, which could be used for modeling of interactions between tumor cells and immune system of recipient. Normally, B10. D2 (R101 mice reject lymphoma EL4 cells in 12–14 days after transplantation, in spite of the fact, that allogeneic difference between B10. D2 (R101 (Kd Id Db mice and lymphoma EL4 (H-2b cells is only in one product of MHC, the H-2Kb molecule. Transgenics carrying β-chains of TCR displayed

  5. Spatially explicit shallow landslide susceptibility mapping over large areas

    Science.gov (United States)

    Bellugi, Dino; Dietrich, William E.; Stock, Jonathan D.; McKean, Jim; Kazian, Brian; Hargrove, Paul

    2011-01-01

    Recent advances in downscaling climate model precipitation predictions now yield spatially explicit patterns of rainfall that could be used to estimate shallow landslide susceptibility over large areas. In California, the United States Geological Survey is exploring community emergency response to the possible effects of a very large simulated storm event and to do so it has generated downscaled precipitation maps for the storm. To predict the corresponding pattern of shallow landslide susceptibility across the state, we have used the model Shalstab (a coupled steady state runoff and infinite slope stability model) which susceptibility spatially explicit estimates of relative potential instability. Such slope stability models that include the effects of subsurface runoff on potentially destabilizing pore pressure evolution require water routing and hence the definition of upslope drainage area to each potential cell. To calculate drainage area efficiently over a large area we developed a parallel framework to scale-up Shalstab and specifically introduce a new efficient parallel drainage area algorithm which produces seamless results. The single seamless shallow landslide susceptibility map for all of California was accomplished in a short run time, and indicates that much larger areas can be efficiently modelled. As landslide maps generally over predict the extent of instability for any given storm. Local empirical data on the fraction of predicted unstable cells that failed for observed rainfall intensity can be used to specify the likely extent of hazard for a given storm. This suggests that campaigns to collect local precipitation data and detailed shallow landslide location maps after major storms could be used to calibrate models and improve their use in hazard assessment for individual storms.

  6. Antimicrobial susceptibility testing for bovine respiratory disease: getting more from diagnostic results.

    Science.gov (United States)

    Lubbers, Brian V; Turnidge, John

    2015-02-01

    Bovine respiratory disease (BRD) is one of the most common diseases of cattle worldwide. Given the significant bacterial component of this disease, antimicrobial agents remain one of the mainstays of therapy. However, the potential welfare and economic impact resulting from the selection of inappropriate antimicrobial therapy for BRD poses significant risks to both animal and animal owner. To determine the 'best' antimicrobial agent for a specific case, the decision-making process needs to incorporate all available evidence, often including the results of bacterial culture and antimicrobial susceptibility testing. While antimicrobial susceptibility testing can be a valuable diagnostic tool, integrating the test results into the clinical decision making process can be a challenging experience. This review details the process by which interpretive criteria for susceptibility tests are developed. Principles for how to best integrate antimicrobial susceptibility testing, both at the individual animal test and aggregate test levels, into the clinical decision making process are discussed. Non-traditional testing methodologies and how they may improve susceptibility testing in the future are also reviewed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Reductions in microfilaridermia by repeated ivermectin treatment are associated with lower Plasmodium-specific Th17 immune responses in Onchocerca volvulus-infected individuals.

    Science.gov (United States)

    Arndts, Kathrin; Klarmann-Schulz, Ute; Batsa, Linda; Debrah, Alexander Y; Epp, Christian; Fimmers, Rolf; Specht, Sabine; Layland, Laura E; Hoerauf, Achim

    2015-03-28

    37 million individuals are currently infected with Onchocerca volvulus (O. volvulus), a parasitic nematode that elicits various dermal manifestations and eye damage in man. Disease control is primarily based on distributing ivermectin in mass drug administration (MDA) programmes which aim at breaking transmission by eliminating microfilariae (MF), the worm's offspring. The majority of infected individuals present generalized onchocerciasis, which is characterized by hyporesponsive immune responses and high parasite burden including MF. Recently, in areas that have been part of MDA programmes, individuals have been identified that present nodules but are amicrofilaridermic (a-MF) and our previous study showed that this group has a distinct immune profile. Expanding on those findings we determined the immune responses of O. volvulus-infected individuals to a Plasmodium-derived antigen MSP-1 (merozoite surface protein-1), which is required by the parasite to enter erythrocytes. Isolated PBMCs from O. volvulus-infected individuals (164 MF(+) and 46 a-MF) and non-infected volunteers from the same region (NEN), were stimulated with MSP-1 and the resulting supernatant screened for the presence of IL-5, IL-13, IFN-γ, TNF-α, IL-6, IL-17A and IL-10. These findings were then further analyzed following regression analysis using the covariates MF, ivermectin (IVM) and region. The latter referred to the Central or Ashanti regions of Ghana, which, at the time sampling, had received 8 or 1 round of MDA respectively. IL-5, IL-13 and IFN-γ responses to MSP-1 were not altered between NEN and O. volvulus-infected individuals nor were any associations revealed in the regression analysis. IL-10, IL-6 and TNF-α MSP-1 responses were, however, significantly elevated in cultures from infected individuals. Interestingly, when compared to a-MF individuals, MSP-induced IL-17A responses were significantly higher in MF(+) patients. Following multivariable regression analysis these IL-10, IL

  8. Genetic susceptibility of periodontitis

    NARCIS (Netherlands)

    Laine, M.L.; Crielaard, W.; Loos, B.G.

    2012-01-01

    In this systematic review, we explore and summarize the peer-reviewed literature on putative genetic risk factors for susceptibility to aggressive and chronic periodontitis. A comprehensive literature search on the PubMed database was performed using the keywords ‘periodontitis’ or ‘periodontal

  9. Fourie susceptible.pmd

    African Journals Online (AJOL)

    Prof. Adipala Ekwamu

    a number of cultivars exhibited field resistance to halo blight and bacterial brown spot, all cultivars were more or less susceptible to .... Cerillos. Alubia. I. 91. 57. Kranskop. Red speckled sugar. II. 97. 63. OPS-RS1. Red speckled sugar. II. 96. 63. OPS-RS2. Red speckled sugar. I. 100. 61. OPS-RS3. Red speckled sugar. II. 97.

  10. HIV-1–Infected Individuals in Antiretroviral Therapy React Specifically With Polyfunctional T-Cell Responses to Gag p24

    DEFF Research Database (Denmark)

    Brandt, Lea; Benfield, Thomas; Kronborg, Gitte

    2013-01-01

    Still no effective HIV-1 prophylactic or therapeutic vaccines are available. However, as the proportion of HIV-1-infected individuals on antiretroviral treatment is increasing, knowledge about the residual immune response is important for the possible development of an HIV-1 vaccine....

  11. Impaired Hepatitis C Virus (HCV)–Specific Interferon-γ Responses in Individuals With HIV Who Acquire HCV Infection: Correlation With CD4+ T-Cell Counts

    Science.gov (United States)

    Flynn, Jacqueline K.; Dore, Gregory J.; Matthews, Gail; Hellard, Margaret; Yeung, Barbara; Rawlinson, William D.; White, Peter A.; Kaldor, John M.; Lloyd, Andrew R.; Ffrench, Rosemary A.

    2012-01-01

    Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4+ T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534). PMID:22949308

  12. Impaired hepatitis C virus (HCV)-specific interferon-γ responses in individuals with HIV who acquire HCV infection: correlation with CD4(+) T-cell counts.

    Science.gov (United States)

    Flynn, Jacqueline K; Dore, Gregory J; Matthews, Gail; Hellard, Margaret; Yeung, Barbara; Rawlinson, William D; White, Peter A; Kaldor, John M; Lloyd, Andrew R; Ffrench, Rosemary A

    2012-11-15

    Studies examining the effect of coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) on the HCV-specific immune response in acute HCV infection are limited. This study directly compared acute HCV-specific T-cell responses and cytokine profiles between 20 HIV/HCV-coinfected and 20 HCV-monoinfected subjects, enrolled in the Australian Trial in Acute Hepatitis C (ATAHC), using HCV peptide enzyme-linked immunospot (ELISPOT) and multiplex in vitro cytokine production assays. HIV/HCV coinfection had a detrimental effect on the HCV-specific cytokine production in acute HCV infection, particularly on HCV-specific interferon γ (IFN-γ) production (magnitude P = .004; breadth P = .046), which correlated with peripheral CD4(+) T-cell counts (ρ = 0.605; P = .005) but not with detectable HIV viremia (ρ = 0.152; P = .534).

  13. Candida and candidaemia. Susceptibility and epidemiology.

    Science.gov (United States)

    Arendrup, Maiken Cavling

    2013-11-01

    In our part of the world invasive fungal infections include invasive yeast infections with Candida as the absolutely dominating pathogen and invasive mould infections with Aspergillus as the main organism. Yeasts are part of our normal micro-flora and invasive infections arise only when barrier leakage or impaired immune function occurs. On the contrary, moulds are ubiquitous in the nature and environment and their conidia inhaled at a daily basis. Hence invasive mould infections typically arise from the airways whereas invasive yeast infections typically enter the bloodstream causing fungaemia. Candida is by far the most common fungal blood stream pathogen; hence this genus has been the main focus of this thesis. As neither the Danish epidemiology nor the susceptibility of fungal pathogens was well described when we initiated our studies we initially wanted to be able to include animal models in our work. Therefore, a comprehensive animal study was undertaken comparing the virulence in a haematogenous mouse model of eight different Candida species including the five most common ones in human infections (C. albicans, C. glabrata, C. krusei, C. parapsilosis and C. tropicalis and in addition three rarer species C. guilliermondii, C. lusitaniae and C. kefyr). We found remarkable differences in the virulence among these species and were able to group the species according to decreasing virulence in three groups I: C. albicans and C. tropicalis, II: C. glabrata, C. lusitaniae and C. kefyr, and III: C. krusei, C. parapsilosis and C. guilliermondii. Apart from being necessary for our subsequent animal experiments exploring in vivo antifungal susceptibility, these findings also helped us understand at least part of the reason for the differences in the epidemiology and the pitfalls associated with the establishment of genus rather than species specific breakpoints. In example, it was less surprising that C. albicans has been the dominant pathogen and associated with a

  14. Epidemiological and antibiotic susceptibility profiles of infectious ...

    African Journals Online (AJOL)

    2011-09-28

    Sep 28, 2011 ... isolation rates among different age groups, educational status, gender, water drank, use of chlorine, toilet use, exposure at home to .... with intermediate susceptibility to ciprofloxacin in the majority of .... Antibiotic and bacterial strain specific distribution of resistance in bacteria isolated from patients attending.

  15. Genetic susceptibility to environmental toxicants

    DEFF Research Database (Denmark)

    2001-01-01

    The toxicological challenges to the chemical industry have in recent years been greatly affected by the rapid innovation and development of analytical, molecular and genetic technologies. ECETOC recognises the importance of developing the technical and intellectual skill bases in academia...... and industrial based laboratories to meet the rapid development of the science base of toxicology. As the technology to determine genetic susceptibility develops, so scientist will be able to describe altered gene expression provoked by chemicals long before they are able to offer valid interpretations...... of their meaning. A potential for inadvertently raising concerns over the effect of chemicals in experimental animals or man, or even the intentional misrepresentation of results to suggest chemicals are “playing” with our genes is enormous. History has shown that some individuals and groups in society are willing...

  16. Principal component analysis of behavioural individual differences suggests that particular aspects of visual working memory may relate to specific aspects of attention.

    Science.gov (United States)

    Machizawa, Maro G; Driver, Jon

    2011-05-01

    The previously separate literatures on visual attention and on visual working memory are converging, with growing interest in how visual attention may relate to visual short-term memory, as exemplified by this special issue. We report exploratory analysis of how individual behavioural differences in separable aspects of attention may relate to particular aspects of visual working memory. Previous work with the Attention Network Test (ANT; Fan, McCandliss, Sommer, Raz, & Posner, 2002) proposed that it can measure three distinct aspects of attention: alerting, spatial orienting, plus executive control of response competition. We implemented the ANT in 50 healthy young adults, who also underwent a behavioural battery of visual working memory (WM) tests. These visual WM tests were all variations on recent paradigms, used here with the aim of measuring potential individual differences in visual WM capacity; WM precision; or WM distractor-filtering. Principal component analysis of the behavioural dataset revealed three main components. Interestingly, each component paired one aspect of ANT scores together with one aspect of WM scores, in terms of the strongest loadings. WM capacity loaded with ANT alerting; WM precision with ANT orienting; and WM filtering with ANT executive control. These results suggest that visual WM may involve separate component processes, and that different aspects of attention relate to different aspects of visual WM, in terms of behavioural individual differences. We discuss the observed pattern in relation to current issues and with respect to possible future work on the potential neural bases of individual differences in the distinct components. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Genetic analysis of the Fourier-transform infrared spectra of bovine milk with emphasis on individual wavelengths related to specific chemical bonds.

    Science.gov (United States)

    Bittante, G; Cecchinato, A

    2013-09-01

    Fourier-transform infrared (FTIR) spectra are used to predict the fat, protein, casein, and lactose contents of milk. These estimates are currently used to predict the individual estimated breeding values of animals. The objective of the present study was to estimate the genetic variation and heritabilities of the milk transmittance spectrum at each individual FTIR wave. Milk was sampled once per cow from a total of 1,064 Italian Brown Swiss cows from 30 herds, sired by 50 artificial insemination sires. The FTIR spectra of all samples were collected within 3 h of sampling from 25 mL of milk. The obtained spectral range comprised wavenumbers 5,000 to 930×cm(-1), corresponding to wavelengths 2.00 to 10.76 μm and frequencies from 149.9 to 27.9 THz, for a total of 1,056 waves. These were acquired using a MilkoScan FT120 FTIR interferometer (Foss Electric A/S, Hillerød, Denmark). Each spectral data point was treated as a single trait and analyzed using an animal model REML method. The results indicated that the transmittance of the bovine milk FTIR spectrum was heritable for most individual waves in the wavenumber interval from 5,000 to 930×cm(-1). Moreover, the transmittance of contiguous FTIR waves was much more highly correlated in terms of the average value and phenotypic variation, compared with genetic variation. In the present study, we characterized 5 regions of the FTIR spectrum that were relevant to the analysis of milk; 2 regions, one in the transition area between the short-wavelength infrared (SWIR) and mid-wavelength infrared (MWIR) divisions of the electromagnetic spectrum (SWIR-MWIR region) and another very short region in the MWIR division (MWIR-2 region), were characterized by very high phenotypic variability in the transmittance of individual milk samples within each wave. This was caused by the absorption peaks of water, which can mask the effects of other important milk components. These regions also showed high genetic variability in

  18. Intra-individual variability in the urine concentrations of inhaled salmeterol in male subjects with reference to doping analysis – impact of urine specific gravity correction

    DEFF Research Database (Denmark)

    Hostrup, Morten; Kalsen, Anders; Hemmersbach, Peter

    2012-01-01

    Since 2010, the World Anti-Doping Agency (WADA) has introduced urinary thresholds for some beta2-agonists. In doping analysis urine samples of beta2-agonists are not corrected for the Urine Specific Gravity (USG) by the WADA laboratories. Several studies have observed high differences in the urine...

  19. Th1 lymphokine production profiles of nickel-specific CD4+T-lymphocyte clones from nickel contact allergic and non-allergic individuals

    NARCIS (Netherlands)

    Kapsenberg, M. L.; Wierenga, E. A.; Stiekema, F. E.; Tiggelman, A. M.; Bos, J. D.

    1992-01-01

    Panels of nickel-specific T-lymphocyte clones (TLC) were prepared from nickel-allergic and non-allergic donors. TLC from both panels showed similar levels of expression of TCR alpha/beta, CD4, CD2, CD25, and CD29 and recognized nickel in association with class II HLA molecules with restriction

  20. The short-term effects of a body awareness program : better self-management of health problems for individuals with chronic a-specific psychosomatic symptoms

    NARCIS (Netherlands)

    Landsman-Dijkstra, Jeanet J. A.; van Wijck, R; Groothoff, JW; Rispens, P

    2004-01-01

    A three-day residential Body Awareness Program (BAP) was developed to teach people with Chronic A-specific Psychosomatic Symptoms (CAPS) to react adequately to disturbances of the balance between a daily workload and the capacity to deal with it. The short-term effects of the program for people with

  1. Marijuana Usage and Hypnotic Susceptibility

    Science.gov (United States)

    Franzini, Louis R.; McDonald, Roy D.

    1973-01-01

    Anonymous self-reported drug usage data and hypnotic susceptibility scores were obtained from 282 college students. Frequent marijuana users (more than 10 times) showed greater susceptibility to hypnosis than nonusers. (Author)

  2. The Emergence of Family-specific Support Constructs: Cross-level Effects of Family-supportive Supervision and Family-Supportive Organization Perceptions on Individual Outcomes.

    Science.gov (United States)

    Hill, Rachel T; Matthews, Russell A; Walsh, Benjamin M

    2016-12-01

    Implicit to the definitions of both family-supportive supervision (FSS) and family-supportive organization perceptions (FSOP) is the argument that these constructs may manifest at a higher (e.g. group or organizational) level. In line with these conceptualizations, grounded in tenants of conservation of resources theory, we argue that FSS and FSOP, as universal resources, are emergent constructs at the organizational level, which have cross-level effects on work-family conflict and turnover intentions. To test our theoretically derived hypotheses, a multilevel model was examined in which FSS and FSOP at the unit level predict individual work-to-family conflict, which in turn predicts turnover intentions. Our hypothesized model was generally supported. Collectively, our results point to FSOP serving as an explanatory mechanism of the effects that mutual perceptions of FSS have on individual experiences of work-to-family conflict and turnover intentions. Lagged (i.e. overtime) cross-level effects of the model were also confirmed in supplementary analyses. Our results extend our theoretical understanding of FSS and FSOP by demonstrating the utility of conceptualizing them as universal resources, opening up a variety of avenues for future research. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  3. Maintenance of Th1 hepatitis C virus (HCV)-specific responses in individuals with acute HCV who achieve sustained virological clearance after treatment.

    Science.gov (United States)

    Flynn, Jacqueline K; Dore, Gregory J; Hellard, Margaret; Yeung, Barbara; Rawlinson, William D; White, Peter A; Kaldor, John M; Lloyd, Andrew R; Ffrench, Rosemary A

    2013-11-01

    T-cell responses against hepatitis C are believed to be critical in achieving both natural and treatment-induced clearance. However, rapid clearance of antigen with early treatment of primary infection may result in reduced or poorly sustained cellular immunity. This study longitudinally examined Th1 and Th2 hepatitis C virus (HCV)-specific cytokine production and T-cell effector function from subjects enrolled in the Australian Trial in Acute Hepatitis C comparing three groups: treatment-induced clearance (sustained virological response [SVR]), treatment non-response, and untreated spontaneous clearance. HCV-specific T-cell responses were characterized by HCV peptide ELISpot, in vitro cytokine production, and T-cell flow cytometry assays. Treated subjects with a sustained virological response (SVR) displayed a better maintenance of HCV-specific Th1 responses compared to treatment non-responders (higher interferon [IFN]-γ and interleukin (IL)-2 magnitude at week 24, broader IFN-γ responses at weeks 24 and 48, P < 0.05) and significantly increased IFN-γ responses between screening and week 48 (magnitude P = 0.026, breadth P = 0.009). Treatment-induced viral clearance was also associated with a trend toward decreased IL-10 responses (screening to week 48, P = 0.070), higher expression of CD45RO (P = 0.042) and CD38 (P = 0.088) on CD4+ T cells, and higher IFN-γR expression (CD56+ IFN-γR+ P = 0.033) compared to treatment non-responders. Untreated subjects with viral clearance also displayed high magnitude and broad HCV-specific IFN-γ and IL-2 responses early in infection; however, IFN-γ responses were not as well maintained compared to treated subjects with a SVR (week 48 magnitude, breadth P = 0.064). Treatment-induced viral clearance of recent HCV infection is associated with maintenance of HCV-specific Th1 responses. © 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

  4. How specific are specific phobias?

    Science.gov (United States)

    Hofmann, S G; Lehman, C L; Barlow, D H

    1997-09-01

    To study the generality of fears among specific phobic individuals and controls, 31 individuals with a DSM-IV diagnosis of specific phobia (natural environmental type: n = 13; blood-injection-injury type: n = 10; and situational type: n = 8) and 33 never mentally ill control subjects participated in an interview and questionnaire study. Based on subjects' fear ratings on the Fear Survey Schedule, subjects were classified as either positive or negative with regard to fear categories that correspond to the five diagnostic subtypes of specific phobia. Phobics showed overall a more generalized form of fear than controls. Furthermore, situational fears were more common among specific phobics who did not meet criteria for specific phobia, situational type, than among controls. These results add to the literature on the functional relationship among different fears and suggest that specific phobias are not as "specific" as is implied by the current diagnostic system.

  5. Age-related and sex-specific differences in proteasome activity in individual Drosophila flies from wild type, longevity-selected and stress resistant strains

    DEFF Research Database (Denmark)

    Hansen, Tina Østergaard; Sarup, Pernille Merete; Loeschcke, Volker

    2012-01-01

    In this study we have measured the caspase-like proteasome activity in individual male and female Drosophila flies by using a non-denaturing lysing technique that consistently extracts total protein. The mean proteasome activity in control C1 females was more than 2 times higher as compared...... with that in C1 males. However, in longevity-selected LS1 flies the proteasome activity was significantly lower compared to C1 flies, but the sex differences were maintained to some extent. Five other stress resistant lines also had significantly reduced proteasome activity in both sexes. During ageing......, there was a progressive decrease in proteasome activity in C1 females, but not in C1 males. This age-related decline in proteasome activity observed in C1 females was not observed in LS1 flies. We conclude that the proteasome activity in control male and female flies is significantly different from each other...

  6. Immune activation and HIV-specific T cell responses are modulated by a cyclooxygenase-2 inhibitor in untreated HIV-infected individuals: An exploratory clinical trial.

    Directory of Open Access Journals (Sweden)

    Christian Prebensen

    Full Text Available Pathologically elevated immune activation and inflammation contribute to HIV disease progression and immunodeficiency, potentially mediated by elevated levels of prostaglandin E2, which suppress HIV-specific T cell responses. We have previously shown that a high dose of the cyclooxygenase-2 inhibitor celecoxib can reduce HIV-associated immune activation and improve IgG responses to T cell-dependent vaccines. In this follow-up study, we included 56 HIV-infected adults, 28 antiretroviral therapy (ART-naïve and 28 on ART with undetectable plasma viremia but CD4 counts below 500 cells/μL. Patients in each of the two study groups were randomized to receive 90 mg qd of the cyclooxygenase-2 inhibitor etoricoxib for six months, two weeks or to a control arm, respectively. T cell activation status, HIV Gag-specific T cell responses and plasma inflammatory markers, tryptophan metabolism and thrombin generation were analyzed at baseline and after four months. In addition, patients received tetanus toxoid, conjugated pneumococcal and seasonal influenza vaccines, to which IgG responses were determined after four weeks. In ART-naïve patients, etoricoxib reduced the density of the activation marker CD38 in multiple CD8+ T cell subsets, improved Gag-specific T cell responses, and reduced in vitro plasma thrombin generation, while no effects were seen on plasma markers of inflammation or tryptophan metabolism. No significant immunological effects of etoricoxib were observed in ART-treated patients. Patients receiving long-term etoricoxib treatment had poorer tetanus toxoid and conjugated pneumococcal vaccine responses than those receiving short-course etoricoxib. Cyclooxygenase-2 inhibitors may attenuate harmful immune activation in HIV-infected patients without access to ART.

  7. Red Cell Genetic Markers in Malarial Susceptibility and Selective Advantage Hypothesis

    Directory of Open Access Journals (Sweden)

    RS Balgir

    2014-02-01

    Full Text Available Malaria is still a serious public health challenge in many parts of the world including India. Human genetic susceptibility to malaria varies from individual to individual depending upon the genetic constitution and from region to region based on geo-ecological and climatic conditions. In the present study, intravenous 334 random blood samples of unrelated adult individuals belonging to Mongoloid ethnic stock were taken after informed consent from the endemic localities of Arunachal Pradesh, Assam and Nagaland to find out the relationship between the abnormal hemoglobin and G6PD enzyme deficiency, and susceptibility to malaria. Abnormal hemoglobin E and G6PD enzyme deficiency seem to interact with malarial parasite in such a way that they probably provide decreased susceptibility or inhibitory effect or increased resistance. Genetic alterations in human genome are maintained in the specific population by natural selection to protect the host against the malarial infection. These findings are consistent with those studies which support the notion of selective genetic advantage hypothesis against the malaria infection.

  8. Differential susceptibility to the environment: an evolutionary--neurodevelopmental theory.

    Science.gov (United States)

    Ellis, Bruce J; Boyce, W Thomas; Belsky, Jay; Bakermans-Kranenburg, Marian J; van Ijzendoorn, Marinus H

    2011-02-01

    Two extant evolutionary models, biological sensitivity to context theory (BSCT) and differential susceptibility theory (DST), converge on the hypothesis that some individuals are more susceptible than others to both negative (risk-promoting) and positive (development-enhancing) environmental conditions. These models contrast with the currently dominant perspective on personal vulnerability and environmental risk: diathesis stress/dual risk. We review challenges to this perspective based on emerging theory and data from the evolutionary, developmental, and health sciences. These challenges signify the need for a paradigm shift in conceptualizing Person x Environment interactions in development. In this context we advance an evolutionary--neurodevelopmental theory, based on DST and BSCT, of the role of neurobiological susceptibility to the environment in regulating environmental effects on adaptation, development, and health. We then outline current thinking about neurogenomic and endophenotypic mechanisms that may underpin neurobiological susceptibility, summarize extant empirical research on differential susceptibility, and evaluate the evolutionary bases and implications of BSCT and DST. Finally, we discuss applied issues including methodological and statistical considerations in conducting differential susceptibility research; issues of ecological, cultural, and racial--ethnic variation in neurobiological susceptibility; and implications of differential susceptibility for designing social programs. We conclude that the differential susceptibility paradigm has far-reaching implications for understanding whether and how much child and adult development responds, for better and for worse, to the gamut of species-typical environmental conditions.

  9. Specific Detection of Naturally Occurring Hepatitis C Virus Mutants with Resistance to Telaprevir and Boceprevir (Protease Inhibitors) among Treatment-Naïve Infected Individuals

    Science.gov (United States)

    Fonseca-Coronado, Salvador; Escobar-Gutiérrez, Alejandro; Ruiz-Tovar, Karina; Cruz-Rivera, Mayra Yolanda; Rivera-Osorio, Pilar; Vazquez-Pichardo, Mauricio; Carpio-Pedroza, Juan Carlos; Ruíz-Pacheco, Juan Alberto; Cazares, Fernando

    2012-01-01

    The use of telaprevir and boceprevir, both protease inhibitors (PI), as part of the specifically targeted antiviral therapy for hepatitis C (STAT-C) has significantly improved sustained virologic response (SVR) rates. However, different clinical studies have also identified several mutations associated with viral resistance to both PIs. In the absence of selective pressure, drug-resistant hepatitis C virus (HCV) mutants are generally present at low frequency, making mutation detection challenging. Here, we describe a mismatch amplification mutation assay (MAMA) PCR method for the specific detection of naturally occurring drug-resistant HCV mutants. MAMA PCR successfully identified the corresponding HCV variants, while conventional methods such as direct sequencing, endpoint limiting dilution (EPLD), and bacterial cloning were not sensitive enough to detect circulating drug-resistant mutants in clinical specimens. Ultradeep pyrosequencing was used to confirm the presence of the corresponding HCV mutants. In treatment-naïve patients, the frequency of all resistant variants was below 1%. Deep amplicon sequencing allowed a detailed analysis of the structure of the viral population among these patients, showing that the evolution of the NS3 is limited to a rather small sequence space. Monitoring of HCV drug resistance before and during treatment is likely to provide important information for management of patients undergoing anti-HCV therapy. PMID:22116161

  10. Examining the predictive utility of an extended theory of planned behaviour model in the context of specific individual safe food-handling.

    Science.gov (United States)

    Mullan, Barbara; Allom, Vanessa; Sainsbury, Kirby; Monds, Lauren A

    2015-07-01

    In order to minimise the occurrence of food-borne illness, it is recommended that individuals perform safe food-handling behaviours, such as cooking food properly, cleaning hands and surfaces before preparing food, keeping food at the correct temperature, and avoiding unsafe foods. Previous research examining the determinants of safe food-handling behaviour has produced mixed results; however, this may be due to the fact that this research examined these behaviours as a totality, rather than considering the determinants of each behaviour separately. As such, the objective for the present study was to examine the predictors of the four aforementioned safe food-handling behaviours by applying an extended theory of planned behaviour to the prediction of each distinct behaviour. Participants were 170 students who completed theory of planned behaviour measures, with the addition of moral norm and habit strength at time 1, and behaviour measures one week later. While the influence of injunctive and descriptive norm and perceived behavioural control differed between behaviours, it appeared that moral norm was an important predictor of intention to engage in each of the four behaviours. Similarly, habit strength was an important predictor of each of the behaviours and moderated the relationship between intention and behaviour for the behaviour of avoiding unsafe food. The implication of these findings is that examining safe food-handling behaviours separately, rather than as a totality, may result in meaningful distinctions between the predictors of these behaviours. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. No serological evidence for Zika virus infection and low specificity for anti-Zika virus ELISA in malaria positive individuals among pregnant women from Madagascar in 2010.

    Science.gov (United States)

    Schwarz, Norbert Georg; Mertens, Eva; Winter, Doris; Maiga-Ascofaré, Oumou; Dekker, Denise; Jansen, Stephanie; Tappe, Dennis; Randriamampionona, Njary; May, Jürgen; Rakotozandrindrainy, Raphael; Schmidt-Chanasit, Jonas

    2017-01-01

    It was previously reported that a malaria infection may interfere with the specificity of a commercial ELISA test against Zika virus (ZIKV). We analyzed 1,216 plasma samples from healthy, pregnant women collected in two sites in Madagascar in 2010 for ZIKV antibodies using a commercial ELISA and for Plasmodium infection by PCR. This screen revealed six putative ZIKV-positive samples by ELISA. These results could not be confirmed by indirect immunofluorescence assays or virus neutralization tests. Four of these six samples were also positive for P. falciparum. We noted that the frequency of malaria positivity was higher in ZIKV-ELISA positive samples (50% and 100% in the two study sites) than ZIKV-negative samples (17% and 10%, respectively), suggesting that malaria may have led to false ZIKV-ELISA positives.

  12. Identification of animal fats via compound specific δ13C values of individual fatty acids: assessments of results for reference fats and lipid extracts of archaeological pottery vessels

    Directory of Open Access Journals (Sweden)

    Richard P. Evershed

    2002-12-01

    Full Text Available The possibility of obtaining molecular information from lipid residues associated with archaeological pottery has dramatically increased the potential for deriving new information on the use of ancient vessels and the commodities processed therein. Motivated by the high proportion of the archaeological potsherds that have been shown to contain animal fats, a new approach invol- ving compound specific stable isotope analysis of remnant fats has been developed to retrieve infor- mation which will allow new insights into animal exploitation, dietary preferences and vessel use amongst prehistoric peoples. The new approach uses the δ13C values of the major saturated fatty acid (C16:0 and C18:0 determined by gas chromatography-combustion-isotope ratio mass spectrometry (GC–C–IRMS to characterise the origins of animal fat recovered from archaeological pottery.

  13. A computational approach to the description of individual immune responses. IgE and IgG-subclass allergen-specific antibodies formed during immunotherapy

    DEFF Research Database (Denmark)

    Søndergaard, I; Poulsen, L K; Osterballe, O

    1991-01-01

    Detailed evaluation of the IgE and IgG-subclass immune response during immunotherapy can now be performed by crossed radio immunoelectrophoresis (CRIE). Some new concepts are introduced facilitating the handling of the vast amount of data obtained by quantitating the immune response. These concepts...... are "distance" between antibody responses and "immune response width". The 20 patients included in this study were pollen-allergic patients who underwent specific immunotherapy in a 3-year prospective study. It was found that the immune response during immunotherapy was restricted to IgG1 and IgG4 antibodies...... and decreased towards six. For the IgG4 antibodies the number of reactions increased towards 15 antigens and decreased towards four. The increase is generally paralleled by an increase in quantitative immune response as well. For some of the antigens a rise in the IgE antibodies is contrasted by a fall...

  14. Seroprevalence and susceptibility to hepatitis A in the European Union and European Economic Area: a systematic review.

    Science.gov (United States)

    Carrillo-Santisteve, Paloma; Tavoschi, Lara; Severi, Ettore; Bonfigli, Sandro; Edelstein, Michael; Byström, Emma; Lopalco, Pierluigi

    2017-10-01

    Most of the European Union (EU) and European Economic Area (EEA) is considered a region of very low hepatitis A virus (HAV) endemicity; however, geographical differences exist. We did a systematic review with the aim of describing seroprevalence and susceptibility in the general population or special groups in the EU and EEA. We searched databases and public health national institutes websites for HAV seroprevalence records published between Jan 1, 1975, and June 30, 2014, with no language restrictions. An updated search was done on Aug 10, 2016. We defined seroprevalence profiles (very low, low, and intermediate) as the proportion of the population with age-specific anti-HAV antibodies at age 15 and 30 years, and susceptibility profiles (low, moderate, high, and very high) as the proportion of susceptible individuals at age 30 and 50 years. We included 228 studies from 28 of 31 EU and EEA countries. For the period 2000-14, 24 countries had a very low seroprevalence profile, compared with five in 1975-89. The susceptibility among adults ranged between low and very high and had a geographical gradient, with three countries in the low susceptibility category. Since 1975, EU and EEA countries have shown decreasing seropositivity; however, considerable regional variability exists. The main limitations of this study are that the studies retrieved for analysis might not be representative of all EU and EEA publications about HAV and might have poor national representativeness. A large proportion of EU and EEA residents are now susceptible to HAV infection. Our Review supports the need to reconsider specific prevention and control measures, to further decrease HAV circulation while providing protection against the infection in the EU and EEA, and could be used to inform susceptible travellers visiting EU and EEA countries with different HAV endemicity levels. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis.

    LENUS (Irish Health Repository)

    Guyot, Nicolas

    2008-11-21

    Elafin is a neutrophil serine protease inhibitor expressed in lung and displaying anti-inflammatory and anti-bacterial properties. Previous studies demonstrated that some innate host defense molecules of the cystic fibrosis (CF) and chronic obstructive pulmonary disease airways are impaired due to increased proteolytic degradation observed during lung inflammation. In light of these findings, we thus focused on the status of elafin in CF lung. We showed in the present study that elafin is cleaved in sputum from individuals with CF. Pseudomonas aeruginosa-positive CF sputum, which was found to contain lower elafin levels and higher neutrophil elastase (NE) activity compared with P. aeruginosa-negative samples, was particularly effective in cleaving recombinant elafin. NE plays a pivotal role in the process as only NE inhibitors are able to inhibit elafin degradation. Further in vitro studies demonstrated that incubation of recombinant elafin with excess of NE leads to the rapid cleavage of the inhibitor. Two cleavage sites were identified at the N-terminal extremity of elafin (Val-5-Lys-6 and Val-9-Ser-10). Interestingly, purified fragments of the inhibitor (Lys-6-Gln-57 and Ser-10-Gln-57) were shown to still be active for inhibiting NE. However, NE in excess was shown to strongly diminish the ability of elafin to bind lipopolysaccharide (LPS) and its capacity to be immobilized by transglutamination. In conclusion, this study provides evidence that elafin is cleaved by its cognate enzyme NE present at excessive concentration in CF sputum and that P. aeruginosa infection promotes this effect. Such cleavage may have repercussions on the innate immune function of elafin.

  16. Alcohol increases hypnotic susceptibility.

    Science.gov (United States)

    Semmens-Wheeler, Rebecca; Dienes, Zoltán; Duka, Theodora

    2013-09-01

    One approach to hypnosis suggests that for hypnotic experience to occur frontal lobe activity must be attenuated. For example, cold control theory posits that a lack of awareness of intentions is responsible for the experience of involuntariness and/or the subjective reality of hypnotic suggestions. The mid-dorso-lateral prefrontal cortex and the ACC are candidate regions for such awareness. Alcohol impairs frontal lobe executive function. This study examined whether alcohol affects hypnotisability. We administered 0.8 mg/kg of alcohol or a placebo to 32 medium susceptible participants. They were subsequently hypnotised and given hypnotic suggestions. All participants believed they had received some alcohol. Participants in the alcohol condition were more susceptible to hypnotic suggestions than participants in the placebo condition. Impaired frontal lobe activity facilitates hypnotic responding, which supports theories postulating that attenuation of executive function facilitates hypnotic response, and contradicts theories postulating that hypnotic response involves enhanced inhibitory, attentional or other executive function. Copyright © 2013. Published by Elsevier Inc.

  17. Structured lifestyle intervention based on a trans-cultural diabetes-specific nutrition algorithm (tDNA) in individuals with type 2 diabetes: a randomized controlled trial

    Science.gov (United States)

    Chee, Winnie S S; Gilcharan Singh, Harvinder Kaur; Hamdy, Osama; Mechanick, Jeffrey I; Lee, Verna K M; Barua, Ankur; Mohd Ali, Siti Zubaidah; Hussein, Zanariah

    2017-01-01

    Objective Trans-cultural diabetes nutrition algorithm (tDNA) was created by international task force and culturally customized for Malaysian population. This study was designed to evaluate its effectiveness versus usual diabetes care in primary care settings. Research design and methods We randomized 230 patients with overweight/obesity, type 2 diabetes, and glycated hemoglobin (A1c) 7%–11% to receive usual care (UC) or UC with tDNA for 6 months. The tDNA intervention consisted of structured low-calorie meal plan, diabetes-specific meal replacements, and increased physical activity. Participants were counseled either through motivational interviewing (tDNA-MI) or conventional counseling (tDNA-CC). The UC group received standard dietary and exercise advice through conventional counseling. All patients were followed for another 6 months after intervention. Results At 6 months, A1c decreased significantly in tDNA-MI (−1.1±0.1%, pdiabetes control and body weight in primary care setting. PMID:29435347

  18. Genetic susceptibility to radiation: which impact on medical practice?

    Energy Technology Data Exchange (ETDEWEB)

    Alapetite, C.; Cosset, J.M. [Institut Curie, Dept. de Radiotherapie, 75 - Paris (France); Bourguignon, M.H.; Masse, R. [Office de Protection contre les Rayonnements Ionisants, 78 - le Vesinet (France)

    2001-07-01

    Recent progress especially in the field of gene identification and expression have raised more attention on genetic susceptibility to cancer possibly enhanced by radiations. Radiation therapists are mostly concerned by this question since hypersensitive patients may suffer from adverse effects in normal tissues following a standard radiation therapy and normally sensitive patients could benefit from higher doses of radiations for a better cure of their malignant tumors. Although only a small percentage of individuals are 'hypersensitive' to radiation effects, all medical specialists using ionising radiations should be aware of these new progress in medical knowledge. The present paper reviews the main pathologies (diseases, syndromes...) known or strongly suspected to be associated with a hypersensitivity to ionizing radiations. Then the main tests capable to detect in advance such pathologies are analyzed and compared. Finally guidelines are provided, especially to the radiation therapists to limit the risk of severe complications (or even deaths) for these specific subset of patients suffering from a genetic disorder with a susceptibility to radiations. (author)

  19. Prediction of susceptibility to the porcine stress syndrome.

    Science.gov (United States)

    Mabry, J W; Christian, L L; Kuhlers, D L; Rasmusen, B A

    1983-01-01

    An experiment designed to compare different predictors of porcine stress syndrome (PSS) was conducted. Animals were exposed to the anesthetic gas, halothane, and their reactions monitored to determine susceptibility or resistance to PSS. Two blood creatine phosphokinase (CPK) traits plus their logs10 were examined as predictors of PSS susceptibility. These were Sigma CPK, Antonik CPK, log Sigma CPK, and log Antonik CPK. The accuracy of these predictors varied from 87 percent to 91 percent in agreement with halothane-determined stress susceptibility. In addition, the relationship of PSS and blood types systems (AO,H) were studied. Two blood types, (+,-/-) and (-,+/+), were consistently stress susceptible while three blood types, (+,a/a), (+,a/c), and (+,c/-), were consistently stress resistant. However, one blood type (+,a/-) contained both stress-susceptible and stress-resistant individuals.

  20. Production of high specific activity (195m) Pt-cisplatinum at South African Nuclear Energy Corporation for Phase 0 clinical trials in healthy individual subjects.

    Science.gov (United States)

    Zeevaart, Jan Rijn; Wagener, Judith; Marjanovic-Painter, Biljana; Sathekge, Mike; Soni, Nischal; Zinn, Christa; Perkins, Gary; Smith, Suzanne V

    2013-01-01

    Platinum agents continue to be the main chemotherapeutic agents used in the first-line and second-line treatments of cancer patients. It is important to fully understand the biological profile of these compounds in order to optimize the dose given to each patient. In a joint project with the Australian Nuclear Science and Technology Organisation and the Nuclear Medicine Department at Steve Biko Academic Hospital, South African Nuclear Energy Corporation synthesized and supplied (195m) Pt-cisplatinum (commonly referred to as cisplatin) for a clinical pilot study on healthy volunteers. Enriched (194) PtCl2 was prepared by digestion of enriched (194) Pt metal (>95%) followed by thermal decomposition over a 3 h period. The (194) PtCl2 was then placed in a quartz ampoule, was irradiated in SAFARI-1 up to 200 h, then decay cooled for a minimum of 34 h prior to synthesis of final product. (195m) Pt(NH3 )2 I2 , formed with the addition of KI and NH4 OH, was converted to the diaqua species [(195m) Pt(NH3 )2 (H2 O)2 ](2+) by reaction with AgNO3 . The conversion to (195m) Pt-cisplatinum was completed by the addition of concentrated HCl. The final product yield was 51.7% ± 5.2% (n = 5). The chemical and radionuclidic purity in each case was >95%. The use of a high flux reactor position affords a higher specific activity product (15.9 ± 2.5 MBq/mg at end of synthesis) than previously found (5 MBq/mg). Volunteers received between 108 and 126 MBq of radioactivity, which is equivalent to 6.8-10.0 mg of carrier cisplatinum. Such high specific activities afforded a significant reduction (~50%) in the chemical dose of a carrier cisplatinum, which represents less than 10% of a typical chemotherapeutic dose given to patients. A good manufacturing practice GMP compliant product was produced and was administered to 10 healthy volunteers as part of an ethically approved Phase 0 clinical trial. The majority of the injected activity 27.5% ± 5.8% was excreted

  1. Individual-specific muscle maximum force estimation using ultrasound for ankle joint torque prediction using an EMG-driven Hill-type model.

    Science.gov (United States)

    de Oliveira, Liliam Fernandes; Menegaldo, Luciano Luporini

    2010-10-19

    EMG-driven models can be used to estimate muscle force in biomechanical systems. Collected and processed EMG readings are used as the input of a dynamic system, which is integrated numerically. This approach requires the definition of a reasonably large set of parameters. Some of these vary widely among subjects, and slight inaccuracies in such parameters can lead to large model output errors. One of these parameters is the maximum voluntary contraction force (F(om)). This paper proposes an approach to find F(om) by estimating muscle physiological cross-sectional area (PCSA) using ultrasound (US), which is multiplied by a realistic value of maximum muscle specific tension. Ultrasound is used to measure muscle thickness, which allows for the determination of muscle volume through regression equations. Soleus, gastrocnemius medialis and gastrocnemius lateralis PCSAs are estimated using published volume proportions among leg muscles, which also requires measurements of muscle fiber length and pennation angle by US. F(om) obtained by this approach and from data widely cited in the literature was used to comparatively test a Hill-type EMG-driven model of the ankle joint. The model uses 3 EMGs (Soleus, gastrocnemius medialis and gastrocnemius lateralis) as inputs with joint torque as the output. The EMG signals were obtained in a series of experiments carried out with 8 adult male subjects, who performed an isometric contraction protocol consisting of 10s step contractions at 20% and 60% of the maximum voluntary contraction level. Isometric torque was simultaneously collected using a dynamometer. A statistically significant reduction in the root mean square error was observed when US-obtained F(om) was used, as compared to F(om) from the literature. Copyright © 2010 Elsevier Ltd. All rights reserved.

  2. Sequence Alignment to Predict Across Species Susceptibility ...

    Science.gov (United States)

    Conservation of a molecular target across species can be used as a line-of-evidence to predict the likelihood of chemical susceptibility. The web-based Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) tool was developed to simplify, streamline, and quantitatively assess protein sequence/structural similarity across taxonomic groups as a means to predict relative intrinsic susceptibility. The intent of the tool is to allow for evaluation of any potential protein target, so it is amenable to variable degrees of protein characterization, depending on available information about the chemical/protein interaction and the molecular target itself. To allow for flexibility in the analysis, a layered strategy was adopted for the tool. The first level of the SeqAPASS analysis compares primary amino acid sequences to a query sequence, calculating a metric for sequence similarity (including detection of candidate orthologs), the second level evaluates sequence similarity within selected domains (e.g., ligand-binding domain, DNA binding domain), and the third level of analysis compares individual amino acid residue positions identified as being of importance for protein conformation and/or ligand binding upon chemical perturbation. Each level of the SeqAPASS analysis provides increasing evidence to apply toward rapid, screening-level assessments of probable cross species susceptibility. Such analyses can support prioritization of chemicals for further ev

  3. Graphene susceptibility in Holstein model

    Energy Technology Data Exchange (ETDEWEB)

    Mousavi, Hamze, E-mail: hamze.mousavi@gmail.co [Department of Physics, Razi University, Kermanshah (Iran, Islamic Republic of); Nano Science and Nano Technology Research Center, Razi University, Kermanshah (Iran, Islamic Republic of)

    2011-06-15

    We study the effects of the electron-phonon interaction on the temperature dependence of the orbital magnetic susceptibility of monolayer graphene. We use the linear response theory and Green's function formalism within the Holstein Hamiltonian model. The results show that the effects of the electron-phonon interaction on the susceptibility of graphene sheet have different behaviors in two temperature regions. In the low temperature region, susceptibility increases when the electron-phonon coupling strength increases. On the other hand, the susceptibility reduces with increasing the electron-phonon coupling strength in the high temperature region. - Highlights: Effect of electron-phonon interaction on the susceptibility of graphene is studied. Linear response theory and Green's function technique in Holstein model are used. Effect of electron-phonon on susceptibility has different behaviors in two temperature regions.

  4. Topological susceptibility from slabs

    Energy Technology Data Exchange (ETDEWEB)

    Bietenholz, Wolfgang [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, A.P. 70-543, Distrito Federal, C.P. 04510 (Mexico); Forcrand, Philippe de [Institute for Theoretical Physics, ETH Zürich,CH-8093 Zürich (Switzerland); CERN, Physics Department, TH Unit, CH-1211 Geneva 23 (Switzerland); Gerber, Urs [Instituto de Ciencias Nucleares, Universidad Nacional Autónoma de México, A.P. 70-543, Distrito Federal, C.P. 04510 (Mexico); Instituto de Física y Matemáticas, Universidad Michoacana de San Nicolás de Hidalgo,Edificio C-3, Apdo. Postal 2-82, Morelia, Michoacán, C.P. 58040 (Mexico)

    2015-12-14

    In quantum field theories with topological sectors, a non-perturbative quantity of interest is the topological susceptibility χ{sub t}. In principle it seems straightforward to measure χ{sub t} by means of Monte Carlo simulations. However, for local update algorithms and fine lattice spacings, this tends to be difficult, since the Monte Carlo history rarely changes the topological sector. Here we test a method to measure χ{sub t} even if data from only one sector are available. It is based on the topological charges in sub-volumes, which we denote as slabs. Assuming a Gaussian distribution of these charges, this method enables the evaluation of χ{sub t}, as we demonstrate with numerical results for non-linear σ-models.

  5. Topological Susceptibility from Slabs

    CERN Document Server

    Bietenholz, Wolfgang; Gerber, Urs

    2015-01-01

    In quantum field theories with topological sectors, a non-perturbative quantity of interest is the topological susceptibility chi_t. In principle it seems straightforward to measure chi_t by means of Monte Carlo simulations. However, for local update algorithms and fine lattice spacings, this tends to be difficult, since the Monte Carlo history rarely changes the topological sector. Here we test a method to measure chi_t even if data from only one sector are available. It is based on the topological charges in sub-volumes, which we denote as slabs. Assuming a Gaussian distribution of these charges, this method enables the evaluation of chi_t, as we demonstrate with numerical results for non-linear sigma-models.

  6. Counselling framework for moderate-penetrance cancer-susceptibility mutations

    OpenAIRE

    Tung, Nadine; Domchek, Susan M.; Stadler, Zsofia; Nathanson, Katherine L.; Couch, Fergus; Garber, Judy E.; Offit, Kenneth; Robson, Mark E.

    2016-01-01

    The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice, particularly in the USA, despite concerns regarding the uncertain clinical validity for some gene variants and the uncertain clinical utility of most multigene panels. So-called ?moderate-penetrance? gene mutations associated with cancer susceptibility are identified in approximately 2?5% of individuals referred for clinical testing; some of these mutations are potentially action...

  7. Combination antimicrobial susceptibility testing for acute exacerbations in chronic infection of Pseudomonas aeruginosa in cystic fibrosis.

    Science.gov (United States)

    Waters, Valerie; Ratjen, Felix

    2017-06-19

    eligible for inclusion in the review. This study prospectively assessed whether the use of multiple combination bactericidal antibiotic testing improved clinical outcomes in participants with acute pulmonary exacerbations of cystic fibrosis who were infected with multiresistant bacteria. A total of 132 participants were randomised in the study. The study investigators provided data specific to the 82 participants who were only infected with Pseudomonas aeruginosa for their primary outcome of time until next pulmonary exacerbation. For participants specifically infected with only Pseudomonas aeruginosa, the hazard ratio of a subsequent exacerbation was 0.82, favouring the control group (95% confidence interval 0.44 to 1.51) (P = 0.52). No further data for any of this review's outcomes specific to participants infected with Pseudomonas aeruginosa were available. The risk of bias for the included study was deemed to be low. The quality of the evidence was moderate for the only outcome providing data solely for individuals with infection due to Pseudomonas aeruginosa. For other outcomes, we were unable to judge the quality of the evidence as no data were available for the relevant subset of participants. The current evidence, limited to one study, shows that there is insufficient evidence to determine effect of choosing antibiotics based on combination antimicrobial susceptibility testing compared to choosing antibiotics based on conventional antimicrobial susceptibility testing in the treatment of acute pulmonary exacerbations in people with cystic fibrosis with chronic Pseudomonas aeruginosa infection. A large international and multicentre study is needed to further investigate this issue.The only study included in the review was published in 2005, and we have not identified any further relevant studies up to March 2017. We therefore do not plan to update this review until new studies are published.

  8. comK Prophage Junction Fragments as Markers for Listeria monocytogenes Genotypes Unique to Individual Meat and Poultry Processing Plants and a Model for Rapid Niche-Specific Adaptation, Biofilm Formation, and Persistence ▿ †

    Science.gov (United States)

    Verghese, Bindhu; Lok, Mei; Wen, Jia; Alessandria, Valentina; Chen, Yi; Kathariou, Sophia; Knabel, Stephen

    2011-01-01

    Different strains of Listeria monocytogenes are well known to persist in individual food processing plants and to contaminate foods for many years; however, the specific genotypic and phenotypic mechanisms responsible for persistence of these unique strains remain largely unknown. Based on sequences in comK prophage junction fragments, different strains of epidemic clones (ECs), which included ECII, ECIII, and ECV, were identified and shown to be specific to individual meat and poultry processing plants. The comK prophage-containing strains showed significantly higher cell densities after incubation at 30°C for 48 h on meat and poultry food-conditioning films than did strains lacking the comK prophage (P Listeria's rapid niche adaptation, biofilm formation, persistence, and subsequent transmission to foods. Also, comK prophage junction fragment sequences may permit accurate tracking of persistent strains back to and within individual food processing operations and thus allow the design of more effective intervention strategies to reduce contamination and enhance food safety. PMID:21441318

  9. comK prophage junction fragments as markers for Listeria monocytogenes genotypes unique to individual meat and poultry processing plants and a model for rapid niche-specific adaptation, biofilm formation, and persistence.

    Science.gov (United States)

    Verghese, Bindhu; Lok, Mei; Wen, Jia; Alessandria, Valentina; Chen, Yi; Kathariou, Sophia; Knabel, Stephen

    2011-05-01

    Different strains of Listeria monocytogenes are well known to persist in individual food processing plants and to contaminate foods for many years; however, the specific genotypic and phenotypic mechanisms responsible for persistence of these unique strains remain largely unknown. Based on sequences in comK prophage junction fragments, different strains of epidemic clones (ECs), which included ECII, ECIII, and ECV, were identified and shown to be specific to individual meat and poultry processing plants. The comK prophage-containing strains showed significantly higher cell densities after incubation at 30°C for 48 h on meat and poultry food-conditioning films than did strains lacking the comK prophage (P Listeria's rapid niche adaptation, biofilm formation, persistence, and subsequent transmission to foods. Also, comK prophage junction fragment sequences may permit accurate tracking of persistent strains back to and within individual food processing operations and thus allow the design of more effective intervention strategies to reduce contamination and enhance food safety.

  10. Evaluation of Psoriasis Genetic Risk Based on Five Susceptibility Markers in a Population from Northern Poland.

    Science.gov (United States)

    Stawczyk-Macieja, Marta; Rębała, Krzysztof; Szczerkowska-Dobosz, Aneta; Wysocka, Joanna; Cybulska, Lidia; Kapińska, Ewa; Haraś, Agnieszka; Miniszewska, Paulina; Nowicki, Roman

    Psoriasis genetic background depends on polygenic and multifactorial mode of inheritance. As in other complex disorders, the estimation of the disease risk based on individual genetic variants is impossible. For this reason, recent investigations have been focused on combinations of known psoriasis susceptibility markers in order to improve the disease risk evaluation. Our aim was to compare psoriasis genetic risk score (GRS) for five susceptibility loci involved in the immunological response (HLA-C, ERAP1, ZAP70) and in the skin barrier function (LCE3, CSTA) between patients with chronic plaque psoriasis (n = 148) and the control group (n = 146). A significantly higher number of predisposing alleles was observed in patients with psoriasis in comparison to healthy individuals (6.1 vs. 5.2, respectively; P = 8.8×10-7). The statistical significance was even more profound when GRS weighted by logarithm odds ratios was evaluated (P = 9.9×10-14). Our results demonstrate the developed panel of five susceptibility loci to be more efficient in predicting psoriasis risk in the Polish population and to possess higher sensitivity and specificity for the disease than any of the markers analyzed separately, including the most informative HLA-C*06 allele.

  11. HIV-1 gp41-specific monoclonal mucosal IgAs derived from highly exposed but IgG-seronegative individuals block HIV-1 epithelial transcytosis and neutralize CD4(+) cell infection: an IgA gene and functional analysis.

    Science.gov (United States)

    Tudor, D; Derrien, M; Diomede, L; Drillet, A-S; Houimel, M; Moog, C; Reynes, J-M; Lopalco, L; Bomsel, M

    2009-09-01

    AIDS is mainly a sexually transmitted disease, and accordingly, mucosal tissues are the primary sites of natural human immunodeficiency virus type-1 (HIV-1) transmission. Mucosal immunoglobulin A (IgA) antibody specific for HIV-1 envelope gp41 subunit is one correlate of protection in individuals who are highly sexually exposed to HIV-1 but remain persistently IgG seronegative (HEPS). Understanding these peculiar IgAs at the gene and functional level is possible only with monoclonal IgAs. We have constructed a mucosal Fab IgA library from HEPS and have characterized a series of HIV-1 IgAs specific for gp41 that, in vitro, are transcytosis-blocking and infection-neutralizing. Characterization of their IgA genes shows that Fab specific for the gp41 membrane-proximal region harbors a long heavy-chain CDR3 loop (CDRH3) similar to the two broadly neutralizing IgG monoclonal antibodies, 2F5 and 4E10. Furthermore, the selected Fab IgA shows extensive somatic mutations that cluster in the CDR regions, indicating that affinity maturation due to an antigen-driven process had occurred in HEPS individuals, presumably upon multiple exposures to HIV. This analysis of HEPS monoclonal IgA gives a unique opportunity to correlate an antibody function (resistance to a pathogen in vivo) with an antibody gene. Such neutralizing monoclonal IgAs could be used in microbicide formulation.

  12. Microwave susceptibility experiments

    Energy Technology Data Exchange (ETDEWEB)

    McConaghy, C.

    1984-05-29

    In certain experimental environments, systems can be affected or damaged by microwave pulses. I have conducted tests at LLNL to understand the phenomenology of microwave susceptibility of system components and subsystem components. To date, my experiments have concentrated on bipolar transistors, similar to what might be used in discrete analog circuits, and on CMOS RAM chips, which might be used in a computer memory system. I observed a decrease in failure energies for both the transistor and the integrated curcuit as I shortened the microwave pulse width. An S band (2.86 GHz) transmit/receive (T/R) tube has also been tested both at S band and at X band (8.16 GHz). The S band pulse had limitations in rise-time from zero power, which had an effect on the amount of power that could be transmitted through the T/R tube, as much as 0.7% of the incident power passed through the tube. All tests were conducted in closed-waveguide or coax test-fixtures, in contrast to the anechoic chambers utilized by other experimenters. I have used both S band and X band Klystron generators. For very high power (greater than 1 MW), I used an additional pulse-compression cavity at S band. Other subsystem components such as an X band mixer and an X band T/R tube will be tested in the future. 8 references.

  13. [Antimicrobial susceptibility cumulative reports].

    Science.gov (United States)

    Canut-Blasco, Andrés; Calvo, Jorge; Rodríguez-Díaz, Juan Carlos; Martínez-Martínez, Luis

    2016-10-01

    Cumulative reports on antimicrobial susceptibility tests data are important for selecting empirical treatments, as an educational tool in programs on antimicrobial use, and for establishing breakpoints defining clinical categories. These reports should be based on data validated by clinical microbiologists using diagnostic samples (not surveillance samples). In order to avoid a bias derived from including several isolates obtained from the same patient, it is recommended that, for a defined period, only the first isolate is counted. A minimal number of isolates per species should be presented: a figure of >=30 isolates is statistically acceptable. The report is usually presented in a table format where, for each cell, information on clinically relevant microorganisms-antimicrobial agents is presented. Depending on particular needs, multiple tables showing data related to patients, samples, services or special pathogens can be prepared. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  14. Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD.

    Science.gov (United States)

    Pouwels, Simon D; Hesse, Laura; Faiz, Alen; Lubbers, Jaap; Bodha, Priya K; Ten Hacken, Nick H T; van Oosterhout, Antoon J M; Nawijn, Martijn C; Heijink, Irene H

    2016-11-01

    Cigarette smoke (CS) exposure is a major risk factor for chronic obstructive pulmonary disease (COPD). We investigated whether CS-induced damage-associated molecular pattern (DAMP) release or DAMP-mediated inflammation contributes to susceptibility for COPD. Samples, including bronchial brushings, were collected from young and old individuals, susceptible and nonsusceptible for the development of COPD, before and after smoking, and used for gene profiling and airway epithelial cell (AEC) culture. AECs were exposed to CS extract (CSE) or specific DAMPs. BALB/cByJ and DBA/2J mice were intranasally exposed to LL-37 and mitochondrial (mt)DAMPs. Functional gene-set enrichment analysis showed that CS significantly increases the airway epithelial gene expression of DAMPs and DAMP receptors in COPD patients. In cultured AECs, we observed that CSE induces necrosis and DAMP release, with specifically higher galectin-3 release from COPD-derived compared with control-derived cells. Galectin-3, LL-37, and mtDAMPs increased CXCL8 secretion in AECs. LL-37 and mtDAMPs induced neutrophilic airway inflammation, exclusively in mice susceptible for CS-induced airway inflammation. Collectively, we show that in airway epithelium from COPD patients, the CS-induced expression of DAMPs and DAMP receptors in vivo and the release of galectin-3 in vitro is exaggerated. Furthermore, our studies indicate that a predisposition to release DAMPs and subsequent induction of inflammation may contribute to the development of COPD. Copyright © 2016 the American Physiological Society.

  15. Genetic heterogeneity in breast cancer susceptibility.

    Science.gov (United States)

    Andersen, T I

    1996-01-01

    Approximately 20% of breast cancer patients have a family history of the disease, and in one-fourth of these cases breast cancer appears to be inherited as an autosomally dominant trait. Five genes and gene regions involved in breast cancer susceptibility have been uncovered. Germ-line mutations in the recently cloned BRCA1 gene at 17q21 is considered to be responsible for the disease in a majority of the breast-ovarian cancer families and in 40-45% of the site-specific breast cancer families, but appears not to be involved in families with both male and female breast cancer cases. The BRCA2 locus at 13q12-q13 appears to be involved in 40-45% of the site-specific breast cancer families, and in most of the families with affected males. The gene located in this region, however, does not seem to confer susceptibility to ovarian cancer. The TP53 gene is involved in breast cancer development in the Li-Fraumeni syndrome and Li-Fraumeni syndrom-like families, whereas germ-line mutations in the androgen receptor (AR) gene is present in a subset of male breast cancers. Furthermore, females who are obligate carriers of ataxia telangiectasia (AT) have a 4-12 times relative risk of developing breast cancer as compared with the general female population, indicating that germ-line mutations in AT also confer susceptibility to breast cancer.

  16. IRGM variants and susceptibility to inflammatory bowel disease in the German population.

    Directory of Open Access Journals (Sweden)

    Jürgen Glas

    Full Text Available BACKGROUND & AIMS: Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD but its impact in ulcerative colitis (UC, its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study. METHODOLOGY/PRINCIPAL FINDINGS: Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin was analyzed for six IRGM single nucleotide polymorphisms (SNPs (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058. In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05-1.65], rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06-1.66] and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01-1.61] with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (p<0.05. Genotype-phenotype analysis revealed no significant associations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes IRGM and ATG16L1 (p<0.05, which, however, did not remain significant after Bonferroni correction. CONCLUSIONS/SIGNIFICANCE: Our results confirm IRGM as susceptibility gene for CD in the German population, supporting a role for the autophagy genes IRGM and ATG16L1 in the pathogenesis of CD.

  17. IRGM variants and susceptibility to inflammatory bowel disease in the German population.

    Science.gov (United States)

    Glas, Jürgen; Seiderer, Julia; Bues, Stephanie; Stallhofer, Johannes; Fries, Christoph; Olszak, Torsten; Tsekeri, Eleni; Wetzke, Martin; Beigel, Florian; Steib, Christian; Friedrich, Matthias; Göke, Burkhard; Diegelmann, Julia; Czamara, Darina; Brand, Stephan

    2013-01-01

    Genome-wide association studies identified the autophagy gene IRGM to be strongly associated with Crohn's disease (CD) but its impact in ulcerative colitis (UC), its phenotypic effects and potential epistatic interactions with other IBD susceptibility genes are less clear which we therefore analyzed in this study. Genomic DNA from 2060 individuals including 817 CD patients, 283 UC patients, and 961 healthy, unrelated controls (all of Caucasian origin) was analyzed for six IRGM single nucleotide polymorphisms (SNPs) (rs13371189, rs10065172 = p.Leu105Leu, rs4958847, rs1000113, rs11747270, rs931058). In all patients, a detailed genotype-phenotype analysis and testing for epistasis with the three major CD susceptibility genes NOD2, IL23R and ATG16L1 were performed. Our analysis revealed an association of the IRGM SNPs rs13371189 (p = 0.02, OR 1.31 [95% CI 1.05-1.65]), rs10065172 = p.Leu105Leu (p = 0.016, OR 1.33 [95% CI 1.06-1.66]) and rs1000113 (p = 0.047, OR 1.27 [95% CI 1.01-1.61]) with CD susceptibility. There was linkage disequilibrium between these three IRGM SNPs. In UC, several IRGM haplotypes were weakly associated with UC susceptibility (p<0.05). Genotype-phenotype analysis revealed no significant associations with a specific IBD phenotype or ileal CD involvement. There was evidence for weak gene-gene-interaction between several SNPs of the autophagy genes IRGM and ATG16L1 (p<0.05), which, however, did not remain significant after Bonferroni correction. Our results confirm IRGM as susceptibility gene for CD in the German population, supporting a role for the autophagy genes IRGM and ATG16L1 in the pathogenesis of CD.

  18. Novel susceptibility loci for Alzheimer's disease.

    Science.gov (United States)

    Reitz, Christiane

    2015-12-01

    Late-onset Alzheimer's disease (AD), a highly prevalent neurodegenerative disorder characterized by progressive deterioration in cognition, function and behavior terminating in incapacity and death, is a clinically and pathologically heterogeneous disease with a substantial heritable component. During the past 5 years, the technological developments in next-generation high-throughput genome technologies have led to the identification of more than 20 novel susceptibility loci for AD, and have implicated specific pathways in the disease, in particular intracellular trafficking/endocytosis, inflammation and immune response and lipid metabolism. These observations have significantly advanced our understanding of underlying pathogenic mechanisms and potential therapeutic targets. This review article summarizes these recent advances in AD genomics and discusses the value of identified susceptibility loci for diagnosis and prognosis of AD.

  19. THE SUSCEPTIBILITY OF MICE TO BACTERIAL ENDOTOXINS

    Science.gov (United States)

    Schaedler, Russell W.; Dubos, Rene J.

    1961-01-01

    Albino mice (Rockefeller NCS strain) raised and maintained free of ordinary bacterial pathogens, as well as of intestinal Escherichia coli and of Proteus bacilli, were found to be highly resistant to the lethal effect of bacterial endotoxins. When newborn mice of this NCS colony were nursed by foster mothers from another colony raised under ordinary conditions (SS colony from which the NCS colony was derived), they acquired the intestinal flora of the latter animals and became susceptible to the lethal effects of endotoxins. NCS adult mice could be rendered susceptible to the lethal effect of endotoxins by vaccination with heat killed Gram-negative bacilli. The susceptibility thus induced exhibited a certain degree of specificity for the bacterial strain used in vaccination. Although untreated NCS mice were resistant to the lethal effect of endotoxins, they proved exquisitively susceptible to the infection-enhancing effect of these materials. For example, 1 µg. or less of endotoxin was found sufficient to help establish a rapidly fatal septicemia with Staphylococcus aureus. Small amounts of endotoxin (1 µg. or less), administered alone, caused a marked but transient loss of weight. Vaccination with heat-killed Gram-negative bacilli or with killed BCG increased the resistance of NCS mice to the infection-enhancing effect of small amounts of endotoxin. This protective effect exhibited a certain degree of specificity for the bacterial strain from which the toxin used in the infection-enhancing test was derived. These various findings can be explained by assuming that the pathological effects of endotoxins involve at least two unrelated mechanisms; (a) a primary toxicity illustrated in this study by the loss of weight and enhancement of infection resulting from the injection of small doses of toxin; (b) an immunological reaction with lethal consequences which became manifest only in animals sensitized to the endotoxin by prior exposure to Gram-negative bacilli. PMID

  20. Does site-specific labelling and individual processing of sextant biopsies improve the accuracy of prostate biopsy in predicting pathological stage in patients with T1c prostate cancer?

    Science.gov (United States)

    Tombal, B; Tajeddine, N; Cosyns, J-P; Feyaerts, A; Opsomer, R; Wese, F X; Van Cangh, P J

    2002-04-01

    To evaluate whether individual labelling and processing of the sextant of origin improves the accuracy of prostate biopsy in predicting the final pathological stage after radical prostatectomy in patients with T1c prostate cancer. The charts of 386 patients treated for prostate cancer by radical prostatectomy between January 1996 and June 1999 were reviewed. In all, 124 patients fulfilled the following inclusion criteria: no abnormality on digital rectal examination (DRE) or transrectal ultrasonography, a prostate specific antigen (PSA) level before biopsy of sextant biopsies, with the cores being submitted in six separate containers individually labelled for the sextant of origin. Within this series of patients with a low tumour burden, the preoperative PSA, biopsy Gleason score and unilateral vs bilateral involvement were not significant predictors of disease extension. The percentage of positive cores and the number and topography of positive sextants were both statistically significant predictors of organ-confined disease. Although these two variables appeared to be statistically equivalent on a first analysis in the overall series, a subgroup of patients was identified who benefited from the complete topographical information, i.e. those 52 (42%) patients with a Gleason score of sextants. These results support the individual labelling of biopsy cores in selected patients with a normal DRE and a moderately elevated PSA, as it helps to better predict the final pathological stage. This substantial benefit outweighs the additional effort by the pathologist.

  1. [Antimicrobial susceptibility in Chile 2012].

    Science.gov (United States)

    Cifuentes-D, Marcela; Silva, Francisco; García, Patricia; Bello, Helia; Briceño, Isabel; Calvo-A, Mario; Labarca, Jaime

    2014-04-01

    Bacteria antimicrobial resistance is an uncontrolled public health problem that progressively increases its magnitude and complexity. The Grupo Colaborativo de Resistencia, formed by a join of experts that represent 39 Chilean health institutions has been concerned with bacteria antimicrobial susceptibility in our country since 2008. In this document we present in vitro bacterial susceptibility accumulated during year 2012 belonging to 28 national health institutions that represent about 36% of hospital discharges in Chile. We consider of major importance to report periodically bacteria susceptibility so to keep the medical community updated to achieve target the empirical antimicrobial therapies and the control measures and prevention of the dissemination of multiresistant strains.

  2. Cognitive distortions and eating pathology: specificity of thought-shape fusion.

    Science.gov (United States)

    Coelho, Jennifer S; Baeyens, Céline; Purdon, Christine; Pitet, Audrey; Bouvard, Martine

    2012-08-01

    Thought-shape fusion (TSF) is a cognitive distortion that has been linked with eating pathology; however, the specificity of this distortion to eating disorders has not yet been examined. The current study set out to investigate the effects of a TSF induction on susceptibility to TSF in three groups of women: individuals with an eating disorder (n = 33), individuals with obsessive-compulsive disorder (OCD; n = 24), and control women with no history of either an eating disorder or obsessive-compulsive disorder (n = 26). Participants were assigned to receive either a TSF induction or a neutral induction, and their cognitive, emotional, and behavioral responses were assessed. As expected, the results demonstrated that individuals with eating disorders were more susceptible to TSF than were women with OCD and control participants, reporting higher state TSF, more negative affect, and more neutralization behavior. The results also supported the specificity of this distortion by demonstrating that individuals with OCD were not particularly susceptible to TSF. In fact, control participants demonstrated an increased susceptibility to TSF relative to women with OCD, as evidenced by their higher levels of trait TSF, and increased self-reported distress/difficulty in imagining a food-related situation. Copyright © 2012 Elsevier Ltd. All rights reserved.

  3. Increased susceptibility of aging gastric mucosa to injury: the mechanisms and clinical implications.

    Science.gov (United States)

    Tarnawski, Andrzej S; Ahluwalia, Amrita; Jones, Michael K

    2014-04-28

    This review updates the current views on aging gastric mucosa and the mechanisms of its increased susceptibility to injury. Experimental and clinical studies indicate that gastric mucosa of aging individuals-"aging gastropathy"-has prominent structural and functional abnormalities vs young gastric mucosa. Some of these abnormalities include a partial atrophy of gastric glands, impaired mucosal defense (reduced bicarbonate and prostaglandin generation, decreased sensory innervation), increased susceptibility to injury by a variety of damaging agents such as ethanol, aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs), impaired healing of injury and reduced therapeutic efficacy of ulcer-healing drugs. Detailed analysis of the above changes indicates that the following events occur in aging gastric mucosa: reduced mucosal blood flow and impaired oxygen delivery cause hypoxia, which leads to activation of the early growth response-1 (egr-1) transcription factor. Activation of egr-1, in turn, upregulates the dual specificity phosphatase, phosphatase and tensin homologue deleted on chromosome ten (PTEN) resulting in activation of pro-apoptotic caspase-3 and caspase-9 and reduced expression of the anti-apoptosis protein, survivin. The imbalance between pro- and anti-apoptosis mediators results in increased apoptosis and increased susceptibility to injury. This paradigm has human relevance since increased expression of PTEN and reduced expression of survivin were demonstrated in gastric mucosa of aging individuals. Other potential mechanisms operating in aging gastric mucosa include reduced telomerase activity, increase in replicative cellular senescence, and reduced expression of vascular endothelial growth factor and importin-α-a nuclear transport protein essential for transport of transcription factors to nucleus. Aging gastropathy is an important and clinically relevant issue because of: (1) an aging world population due to prolonged life span; (2) older

  4. pso.ATION AND ANTIMICROBIAL SUSCEPTIBILITY

    African Journals Online (AJOL)

    isolates vere made using standard methods, Antibiotic susceptibility tests against commonly prescribed ... Acute otitis media is rapid with short .... sensitivity tests. Antimicrobial susceptibility tests: The antimicrobial susceptibility patterns of major Gram positive and negative bacterial isolates obtained from clinical specimens.

  5. Estimation of the Population Susceptibility Against Measles in Slovakia.

    Science.gov (United States)

    Zibolenová, Jana; Chladná, Zuzana; Švihrová, Viera; Baška, Tibor; Waczulíková, Iveta; Hudečková, Henrieta

    2017-03-01

    In Slovakia, thanks to a highly effective vaccination programme, no domestic cases of measles have been reported since 1999. However, there are several outbreaks of measles currently hitting some countries in Europe. Difficulties in reaching the goal of measles elimination make it necessary to monitor the status of the population susceptibility to prevent similar outbreaks in the future. We hypothesize that immunity wanes overtime, which can substantially impact the population susceptibility. This work introduces a model that estimates a proportion of individuals susceptible to measles in the Slovak population in 2015. Our analysis is based on an age-cohort model that incorporates waning immunity, vaccination schedule and changes in demographic structure. The inputs of the model are data on the vaccination coverage, last seroprevalence survey in 2002 and age structure of the population. In a short-term horizon, waning immunity does not affect the estimated proportion of the susceptible population. However, in a long-term horizon, the antibody titers can fall below the level of protection, which would result in a substantial transfer of initially immune individuals to the compartment of the susceptible ones. Incorporating of waning immunity in the cohort model has indicated that the most susceptible cohorts are not-vaccinated youngest children and cohorts born between 1969 and 1986. Applying the model to the current situation shows that people aged 30-45 years and unvaccinated infants represent the most susceptible groups. Model partially replaces missing seroprevalence survey, but, because the parameters of model and phenomenon of waning immunity are not exactly known, we suggest reintroducing the regular national serosurveys in order to empirically determine the level of susceptibility for measles in Slovakia.

  6. Susceptibility of food-borne bacteria to binary combinations of antimicrobials at selected a(w) and pH

    National Research Council Canada - National Science Library

    Santiesteban-López, A; Palou, E; López-Malo, A

    2007-01-01

    .... Antibacterial susceptibilities of Escherichia coli, Listeria innocua, Salmonella Typhimurium and Staphylococcus aureus to individual and binary mixtures of potassium sorbate with a phenolic compound...

  7. Hypnotic susceptibility and dream characteristics.

    Science.gov (United States)

    Zamore, N; Barrett, D

    1989-11-01

    This study examined the relationship of hypnotic susceptibility to a variety of dream characteristics and types of dream content. A Dream Questionnaire was constructed synthesizing Gibson's dream inventory and Hilgard's theoretical conceptions of hypnosis. Employing the Harvard Group Scale of Hypnotic Susceptibility and the Field Inventory for evaluating hypnotic response, several dream dimensions correlated significantly with hypnotizability. For subjects as a whole, the strongest correlates were the frequency of dreams which they believed to be precognitive and out-of-body dreams. Ability to dream on a chosen topic also correlated significantly with hypnotic susceptibility for both genders. For females only, there was a negative correlation of hypnotic susceptibility to flying dreams. Absorption correlated positively with dream recall, ability to dream on a chosen topic, reports of conflict resolution in dreams, creative ideas occurring in dreams, amount of color in dreams, pleasantness of dreams, bizarreness of dreams, flying dreams and precognitive dreams.

  8. Testing abstract behavioral specifications

    NARCIS (Netherlands)

    P.Y.H. Wong; R. Bubel (Richard); F.S. de Boer (Frank); C.P.T. de Gouw (Stijn); M. Gómez-Zamalloa; R Haehnle; K. Meinke; M.A. Sindhu

    2015-01-01

    htmlabstractWe present a range of testing techniques for the Abstract Behavioral Specification (ABS) language and apply them to an industrial case study. ABS is a formal modeling language for highly variable, concurrent, component-based systems. The nature of these systems makes them susceptible to

  9. Ancestral susceptibility to colorectal cancer

    Czech Academy of Sciences Publication Activity Database

    Huhn, S.; Pardini, Barbara; Naccarati, Alessio; Vodička, Pavel (ed.); Hemminki, K.; Försti, A.

    2012-01-01

    Roč. 27, č. 2 (2012), s. 197-204 ISSN 0267-8357 R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286 Grant - others:EU FP7(XE) HEALTH-F4-2007-200767 Institutional research plan: CEZ:AV0Z50390512 Keywords : cancer susceptibility * molecular epidemiology * genetic susceptibility Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.500, year: 2012

  10. Individual Education.

    Science.gov (United States)

    Corsini, Raymond

    1981-01-01

    Paper presented at the 66th Convention of the International Association of Pupil Personnel Workers, October 20, 1980, Baltimore, Maryland, describes individual education based on the principles of Alfred Adler. Defines six advantages of individual education, emphasizing student responsibility, mutual respect, and allowing students to progress at…

  11. Individual Consultations

    OpenAIRE

    Ian Walkinshaw; Todd Milford; Keri Freeman

    2015-01-01

    Responding to calls for research into measurable English language outcomes from individual language support consultations at universities, this study investigated the effect of individual consultations (ICs) on the academic writing skills and lexico-grammatical competence of students who speak English as an additional language (EAL). Attendance by 31 EAL students at ICs was recorded, and samples of their academic writi...

  12. Temperature alters host genotype-specific susceptibility to chytrid infection

    National Research Council Canada - National Science Library

    Gsell, A.S; De Senerpont Domis, L.N; Van Donk, E; Ibelings, B.W

    2013-01-01

    .... We exposed seven genetically different but concurrent strains of the diatom Asterionella formosa to one genotype of its naturally co-occurring chytrid parasite Zygorhizidium planktonicum across five...

  13. Susceptibility to varicella zoster virus infection in health care workers.

    LENUS (Irish Health Repository)

    Gallagher, J

    2012-02-03

    Varicella zoster virus (VZV) is an occupational hazard for a percentage of health care staff. Nine hundred and seventy staff members attending the Occupational Health Department at Cork University Hospital took part in the survey. A latex agglutination assay was used to determine the health care workers immune status to VZV. Of the 970 workers tested, 928 (95.7%) were immune to VZV. The sensitivity, specificity and predictive value of an enquiry regarding a history of chicken-pox was determined on a sample of 206 health care workers. The positive predictive value was 95% (119\\/125) and the negative predictive value was 11% (4\\/35). The sensitivity of the enquiry was 79% (119\\/150), the specificity was 40% (4\\/10), reducing to 61% (119\\/195) and 36% (4\\/11) respectively when individuals with uncertain histories were included in the calculations. The advantages and disadvantages of selective staff screening are discussed. In the authors\\' opinion all health care workers involved in the clinical care of patients should be screened by serology for past VZV infection before taking up duty and those who are susceptible to VZV should be made aware of the risks and health effects associated with VZV if contracted.

  14. The ability of self-rated health to predict mortality among community-dwelling elderly individuals differs according to the specific cause of death: data from the NEDICES Cohort

    Science.gov (United States)

    Fernández-Ruiz, Mario; Guerra-Vales, Juan M.; Trincado, Rocío; Fernández, Rebeca; Medrano, María José; Villarejo, Alberto; Benito-León, Julián; Bermejo-Pareja, Félix

    2013-01-01

    Background The biomedical and psychosocial mechanisms underlying the relationship between self-rated health (SRH) and mortality in elderly individuals remain unclear. Objective To assess the association between different measurements of subjective health (global, age-comparative, and time-comparative SRH) and cause-specific mortality. Methods Neurological Disorders in Central Spain (NEDICES) is a prospective population-based survey of the prevalence and incidence of major age-associated conditions. Data on demographic and health-related variables were collected from 5,278 subjects (≥65 years) at the baseline questionnaire. Thirteen-year mortality and cause of death were obtained from the National Death Registry. Adjusted hazard ratios (aHR) for SRH and all-cause and cause-specific mortality were estimated by Cox proportional hazard models. Results At baseline, 4,958 participants (93.9%) answered the SRH questionnaire. At the end of follow-up 2,468 (49.8%) participants had died (of whom 723 [29.2%] died from cardiovascular diseases, 609 [24.7%] from cancer, and 359 [14.5%] from respiratory diseases). Global SRH predicted independently all-cause mortality (aHR for “poor or very poor” vs. “very good” category: 1.39; 95% confidence interval [CI]: 1.15–1.69). Analysis of cause-specific mortality revealed that global SRH was an independent predictor for death due to respiratory diseases (aHR for “poor or very poor” vs. “very good” category: 2.61; 95% CI: 1.55–4.39), whereas age-comparative SRH exhibited a gradient effect on the risk of death due to stroke. Time-comparative SRH provided small additional predictive value. Conclusions The predictive ability of SRH for mortality largely differs according to the specific cause of death, with the strongest associations found for respiratory disease and stroke mortality. PMID:23615509

  15. Effects of neck-specific exercise with or without a behavioural approach in addition to prescribed physical activity for individuals with chronic whiplash-associated disorders: a prospective randomised study.

    Science.gov (United States)

    Peolsson, Anneli; Landén Ludvigsson, Maria; Overmeer, Thomas; Dedering, Åsa; Bernfort, Lars; Johansson, Gun; Kammerlind, Ann-Sofi; Peterson, Gunnel

    2013-10-30

    Up to 50% of chronic whiplash associated disorders (WAD) patients experience considerable pain and disability and remain on sick-leave. No evidence supports the use of physiotherapy treatment of chronic WAD, although exercise is recommended. Previous randomised controlled studies did not evaluate the value of adding a behavioural therapy intervention to neck-specific exercises, nor did they compare these treatments to prescription of general physical activity. Few exercise studies focus on patients with chronic WAD, and few have looked at patients' ability to return to work and the cost-effectiveness of treatments. Thus, there is a great need to develop successful evidence-based rehabilitation models. The study aim is to investigate whether neck-specific exercise with or without a behavioural approach (facilitated by a single caregiver per patient) improves functioning compared to prescription of general physical activity for individuals with chronic WAD. The study is a prospective, randomised, controlled, multi-centre study with a 2-year follow-up that includes 216 patients with chronic WAD (> 6 months and behavioural approach followed by prescription of physical activity; or (C) prescription of physical activity alone without neck-specific exercises. Treatments will be performed for 3 months. We will examine physical and psychological function, pain intensity, health care consumption, the ability to resume work and economic health benefits. An independent, blinded investigator will perform the measurements at baseline and 3, 6, 12 and 24 months after inclusion. The main study outcome will be improvement in neck-specific disability as measured with the Neck Disability Index. All treatments will be recorded in treatment diaries and medical records. The study findings will help improve the treatment of patients with chronic WAD. ClinicalTrials.gov identifier: NCT01528579.

  16. Local magnetic susceptibility in rare-earth compounds

    CERN Document Server

    Shiozawa, H; Obu, K

    2003-01-01

    The element specific magnetic susceptibilities of some rare-earth compounds are estimated by measuring magnetic circular dichroism at rare-earth M sub 4 sub , sub 5 absorption edges. The temperature dependences of the rare-earth 4f local magnetic susceptibilities in dense Kondo materials, CeNi, CeSn sub 3 and CeRu sub 4 Sb sub 1 sub 2 , are remarkably different from those of the bulk magnetic susceptibilities measured by a conventional magnetometer, although the 4f electron is regarded to mainly hold the magnetic moment in these compounds. In contrast, the rare-earth 4f local magnetic susceptibility of ferromagnetic NdFe sub 4 P sub 1 sub 2 shows almost as similar behavior as the bulk one.

  17. Longitudinal exome-wide association study to identify genetic susceptibility loci for hypertension in a Japanese population.

    Science.gov (United States)

    Yasukochi, Yoshiki; Sakuma, Jun; Takeuchi, Ichiro; Kato, Kimihiko; Oguri, Mitsutoshi; Fujimaki, Tetsuo; Horibe, Hideki; Yamada, Yoshiji

    2017-12-08

    Genome-wide association studies have identified various genetic variants associated with complex disorders. However, these studies have commonly been conducted in a cross-sectional manner. Therefore, we performed a longitudinal exome-wide association study (EWAS) in a Japanese cohort. We aimed to identify genetic variants that confer susceptibility to hypertension using ~244 000 single-nucleotide variants (SNVs) and physiological data from 6026 Japanese individuals who underwent annual health check-ups for several years. After quality control, the association of hypertension with SNVs was tested using a generalized estimating equation model. Finally, our longitudinal EWAS detected seven hypertension-related SNVs that passed strict criteria. Among these variants, six SNVs were densely located at 12q24.1, and an East Asian-specific motif (haplotype) 'CAAAA' comprising five derived alleles was identified. Statistical analyses showed that the prevalence of hypertension in individuals with the East Asian-specific haplotype was significantly lower than that in individuals with the common haplotype 'TGGGT'. Furthermore, individuals with the East Asian haplotype may be less susceptible to the adverse effects of smoking on hypertension. The longitudinal EWAS for the recessive model showed that a novel SNV, rs11917356 of COL6A5, was significantly associated with systolic blood pressure, and the derived allele at the SNV may have spread throughout East Asia in recent evolutionary time.

  18. Self-diagnosis of active head lice infestation by individuals from an impoverished community: high sensitivity and specificity Auto diagnóstico de pediculose por indivíduos de uma comunidade economicamente desfavorecida: alta sensibilidade e especificidade

    Directory of Open Access Journals (Sweden)

    Daniel Pilger

    2008-04-01

    Full Text Available To compare sensitivity, specificity, positive predictive value (PPV and negative predictive value (NPV of self-diagnosis for head lice infestation with visual inspection, we conducted a study in an urban slum in Brazil. Individuals were asked about active head lice infestation (self-diagnosis; we performed visual inspection and thereafter wet combing (gold standard. Of the 175 individuals included, 77 (44% had an active head lice infestation. For self-diagnosis, sensitivity (80.5%, specificity (91.8%, PPV (88.6% and NPV (85.7% were high. Sensitivity of visual inspection was 35.1%. Public health professionals can use self-diagnosis as a diagnostic tool, to estimate accurately prevalence of pediculosis in a community, and to monitor ongoing intervention strategies.Foi conduzido um estudo em uma favela urbana no Brasil com o objetivo de comparar a sensibilidade, especificidade, valor preditivo positivo (VPP e valor preditivo negativo (VPN do auto-diagnóstico de pediculose com a inspeção visual. Dos 175 indivíduos incluídos, 77 (44% apresentavam pediculose. Para o auto-diagnóstico, a sensibilidade (80.5%, a especificidade (91.8%, o VPP (88.6% e o VPN (85.7% foram altos. A sensibilidade da inspeção visual foi 35.1%. Profissionais de saúde podem utilizar o auto-diagnóstico como uma ferramenta diagnóstica para estimar de forma acurada a prevalência de pediculose em uma comunidade, como também para monitorar estratégias de controle da doença.

  19. Cigarette Smoke Induces Immune Responses to Vimentin in both, Arthritis-Susceptible and -Resistant Humanized Mice.

    Directory of Open Access Journals (Sweden)

    Mitali Bidkar

    Full Text Available Rheumatoid arthritis (RA is an autoimmune disease marked by chronic synovial inflammation and both, genetic and environmental factors are involved in its pathogenesis. Human leukocyte antigen (HLA DRB1*0401 is associated with susceptibility to develop RA, while cigarette smoke (CS exposure promotes seropositive disease with increased severity in DRB1*0401+ individuals. Smokers have higher levels of antibodies against citrullinated peptides. In this study, we determined whether the response to a known autoantigen, Vimentin (Vim is shared epitope specific and how CS influences this response using transgenic-mice carrying RA-susceptible,*0401, and -resistant, *0402, genes. Following relatively brief exposure to CS, peptidyl arginine deiminase (PAD enzyme expression was increased in murine lungs. Cigarette smoking led to production of Interferon (IFN-γ with reduced levels of Interleukin (IL-10 by splenocytes of *0401 mice. In contrast, CS augmented Th2 cytokines along with T-regulatory cells in *0402 mice. An increase in levels of antibodies to native and citrullinated Vim was observed in naïve mice of both strains following CS exposure. Our data showed that both arthritis-susceptible and -resistant mice can generate cellular and humoral immunity to Vim; however CS-induced modulation of host immunity is dependent on the interaction with the host HLA genes.

  20. American Society of Clinical Oncology Policy Statement Update: Genetic and Genomic Testing for Cancer Susceptibility.

    Science.gov (United States)

    Robson, Mark E; Bradbury, Angela R; Arun, Banu; Domchek, Susan M; Ford, James M; Hampel, Heather L; Lipkin, Stephen M; Syngal, Sapna; Wollins, Dana S; Lindor, Noralane M

    2015-11-01

    The American Society of Clinical Oncology (ASCO) has long affirmed that the recognition and management of individuals with an inherited susceptibility to cancer are core elements of oncology care. ASCO released its first statement on genetic testing in 1996 and updated that statement in 2003 and 2010 in response to developments in the field. In 2014, the Cancer Prevention and Ethics Committees of ASCO commissioned another update to reflect the impact of advances in this area on oncology practice. In particular, there was an interest in addressing the opportunities and challenges arising from the application of massively parallel sequencing-also known as next-generation sequencing-to cancer susceptibility testing. This technology introduces a new level of complexity into the practice of cancer risk assessment and management, requiring renewed effort on the part of ASCO to ensure that those providing care to patients with cancer receive the necessary education to use this new technology in the most effective, beneficial manner. The purpose of this statement is to explore the challenges of new and emerging technologies in cancer genetics and provide recommendations to ensure their optimal deployment in oncology practice. Specifically, the statement makes recommendations in the following areas: germline implications of somatic mutation profiling, multigene panel testing for cancer susceptibility, quality assurance in genetic testing, education of oncology professionals, and access to cancer genetic services. © 2015 by American Society of Clinical Oncology.

  1. Effect of organ enhancement and habitus on estimation of unenhanced attenuation at contrast-enhanced dual-energy MDCT: concepts for individualized and organ-specific spectral iodine subtraction strategies.

    Science.gov (United States)

    Miller, Chad M; Gupta, Rajan T; Paulson, Erik K; Neville, Amy M; Bashir, Mustafa R; Merkle, Elmar M; Boll, Daniel T

    2011-05-01

    The purpose of this study was to assess whether habitus and organ enhancement influence iodine subtraction and should be incorporated into spectral subtraction algorithms. This study included 171 patients. In the unenhanced phase, MDCT was performed with single-energy acquisition (120 kVp, 250 mAs) and in the parenchymal phase with dual-energy acquisitions (80 kVp, 499 mAs; 140 kVp, 126 mAs). Habitus was determined by measuring trunk diameters and calculating circumference. Iodine subtraction was performed with input parameters individualized to muscle, fat, and blood ratio. Attenuation of the liver, pancreas, spleen, kidneys, and aorta was assessed in truly and virtually unenhanced image series. Pearson analysis was performed to correlate habitus with the input parameters. Analysis of truly unenhanced and virtually unenhanced images was performed with the Student t test; magnitude of variation was evaluated with Bland-Altman plots. Correction strategies were derived from organ-specific regression analysis of scatterplots of truly unenhanced and virtually unenhanced attenuation and implemented in a pixel-by-pixel approach. Analysis of individual organ correction and truly unenhanced attenuation was performed with the Student t test. The correlations between habitus and blood ratio (r = 0.694) and attenuation variation of fat at 80 kVp (r = -0.468) and 140 kV (r = -0.454) were confirmed. Although overall mean attenuation differed by no more than 10 HU between truly and virtually unenhanced scans overall, these differences varied by organ and were large in individual patients. Paired comparisons of truly and virtually unenhanced measurements differed significantly for liver, spleen, pancreas, kidneys, and aortic blood pool (p habitus-based correction strategies were applied (p > 0.38 for all comparisons). Habitus and organ enhancement influence virtually unenhanced imaging and should be incorporated into spectral subtraction algorithms.

  2. Changes in Susceptibility to Oncolytic Vesicular Stomatitis Virus during Progression of Prostate Cancer.

    Science.gov (United States)

    Yu, Nanmeng; Puckett, Shelby; Antinozzi, Peter A; Cramer, Scott D; Lyles, Douglas S

    2015-05-01

    A major challenge to oncolytic virus therapy is that individual cancers vary in their sensitivity to oncolytic viruses, even when these cancers arise from the same tissue type. Variability in response may arise due to differences in the initial genetic lesions leading to cancer development. Alternatively, susceptibility to viral oncolysis may change during cancer progression. These hypotheses were tested using cells from a transgenic mouse model of prostate cancer infected with vesicular stomatitis virus (VSV). Primary cultures from murine cancers derived from prostate-specific Pten deletion contained a mixture of cells that were susceptible and resistant to VSV. Castration-resistant cancers contained a higher percentage of susceptible cells than cancers from noncastrated mice. These results indicate both susceptible and resistant cells can evolve within the same tumor. The role of Pten deletion was further investigated using clonal populations of murine prostate epithelial (MPE) progenitor cells and tumor-derived Pten(-/-) cells. Deletion of Pten in MPE progenitor cells using a lentivirus vector resulted in cells that responded poorly to interferon and were susceptible to VSV infection. In contrast, tumor-derived Pten(-/-) cells expressed higher levels of the antiviral transcription factor STAT1, activated STAT1 in response to VSV, and were resistant to VSV infection. These results suggest that early in tumor development following Pten deletion, cells are primarily sensitive to VSV, but subsequent evolution in tumors leads to development of cells that are resistant to VSV infection. Further evolution in castration-resistant tumors leads to tumors in which cells are primarily sensitive to VSV. There has been a great deal of progress in the development of replication-competent viruses that kill cancer cells (oncolytic viruses). However, a major problem is that individual cancers vary in their sensitivity to oncolytic viruses, even when these cancers arise from the

  3. Mutations in BRCA1, BRCA2 and other breast and ovarian cancer susceptibility genes in Central and South American populations.

    Science.gov (United States)

    Jara, Lilian; Morales, Sebastian; de Mayo, Tomas; Gonzalez-Hormazabal, Patricio; Carrasco, Valentina; Godoy, Raul

    2017-10-06

    Breast cancer (BC) is the most common malignancy among women worldwide. A major advance in the understanding of the genetic etiology of BC was the discovery of BRCA1 and BRCA2 (BRCA1/2) genes, which are considered high-penetrance BC genes. In non-carriers of BRCA1/2 mutations, disease susceptibility may be explained of a small number of mutations in BRCA1/2 and a much higher proportion of mutations in ethnicity-specific moderate- and/or low-penetrance genes. In Central and South American populations, studied have focused on analyzing the distribution and prevalence of BRCA1/2 mutations and other susceptibility genes that are scarce in Latin America as compared to North America, Europe, Australia, and Israel. Thus, the aim of this review is to present the current state of knowledge regarding pathogenic BRCA variants and other BC susceptibility genes. We conducted a comprehensive review of 47 studies from 12 countries in Central and South America published between 2002 and 2017 reporting the prevalence and/or spectrum of mutations and pathogenic variants in BRCA1/2 and other BC susceptibility genes. The studies on BRCA1/2 mutations screened a total of 5956 individuals, and studies on susceptibility genes analyzed a combined sample size of 11,578 individuals. To date, a total of 190 different BRCA1/2 pathogenic mutations in Central and South American populations have been reported in the literature. Pathogenic mutations or variants that increase BC risk have been reported in the following genes or genomic regions: ATM, BARD1, CHECK2, FGFR2, GSTM1, MAP3K1, MTHFR, PALB2, RAD51, TOX3, TP53, XRCC1, and 2q35.

  4. Genetic variation in exon 10 of the BPI gene is associated with Escherichia coli F18 susceptibility in Sutai piglets.

    Science.gov (United States)

    Liu, Lu; Wang, Jing; Zhao, Qiaohui; Zi, Chen; Wu, Zhengchang; Su, Xianmin; Huo, Yongjiu; Zhu, Guoqiang; Wu, Shenglong; Bao, Wenbin

    2013-07-01

    Our aim was to investigate the effect of the porcine bactericidal/permeability-increasing protein (BPI) on the susceptibility to enterotoxigenic Escherichia coli F18 (ETEC F18). Specifically, we wanted to determine whether the HpaII restriction polymorphism in exon 10 of BPI mediates susceptibility to ETEC F18. Thirty verified ETEC F18-resistant and thirty susceptible Sutai (Duroc×Taihu) piglets were identified using the receptor binding assay. Exon 10 of the BPI gene produced the AA, BB, and AB genotypes after HpaII digestion. The genotype distribution among ETEC F18-resistant piglets was significantly different from that among susceptible piglets. Among piglets with the AA genotype, 90% were ETEC F18-resistant; this percentage of resistant piglets was significantly higher than the percentage of resistant piglets with the AB (57.1%) and BB genotypes (17.4%). There was high expression only in the tissues of the duodenum and jejunum, wherein the expression levels in the ETEC F18-resistant group were significantly higher than those in the susceptible group (P<0.05). The average expression levels in individuals with the AA genotype were significantly higher than those in individuals with the AB or BB genotype (P<0.05), while the results of Western blot show the same evidences as real time PCR. These results indicate that the upregulation of porcine BPI gene expression in the small intestines plays a direct role in resistance to ETEC F18 infection. The AA genotype for the HpaII site in exon 10 of the porcine BPI gene was demonstrated to be an anti-ETEC F18 marker and could be used for selective breeding to enhance ETEC F18 resistance. Copyright © 2013 Elsevier B.V. All rights reserved.

  5. Strong ties promote the epidemic prevalence in susceptible-infected-susceptible spreading dynamics

    CERN Document Server

    Cui, Ai-Xiang; Zhou, Tao

    2013-01-01

    Understanding spreading dynamics will benefit society as a whole in better preventing and controlling diseases, as well as facilitating the socially responsible information while depressing destructive rumors. In network-based spreading dynamics, edges with different weights may play far different roles: a friend from afar usually brings novel stories, and an intimate relationship is highly risky for a flu epidemic. In this article, we propose a weighted susceptible-infected-susceptible model on complex networks, where the weight of an edge is defined by the topological proximity of the two associated nodes. Each infected individual is allowed to select limited number of neighbors to contact, and a tunable parameter is introduced to control the preference to contact through high-weight or low-weight edges. Experimental results on six real networks show that the epidemic prevalence can be largely promoted when strong ties are favored in the spreading process. By comparing with two statistical null models respe...

  6. The Accuracy of Mean-Field Approximation for Susceptible-Infected-Susceptible Epidemic Spreading

    CERN Document Server

    Qu, Bo

    2016-01-01

    The epidemic spreading has been studied for years by applying the mean-field approach in both homogeneous case, where each node may get infected by an infected neighbor with the same rate, and heterogeneous case, where the infection rates between different pairs of nodes are different. Researchers have discussed whether the mean-field approaches could accurately describe the epidemic spreading for the homogeneous cases but not for the heterogeneous cases. In this paper, we explore under what conditions the mean-field approach could perform well when the infection rates are heterogeneous. In particular, we employ the Susceptible-Infected-Susceptible (SIS) model and compare the average fraction of infected nodes in the metastable state obtained by the continuous-time simulation and the mean-field approximation. We concentrate on an individual-based mean-field approximation called the N-intertwined Mean Field Approximation (NIMFA), which is an advanced approach considered the underlying network topology. Moreove...

  7. Measles outbreak reveals measles susceptibility among adults in ...

    African Journals Online (AJOL)

    5 Namibia Country Office, Center for Global Health, US Centers for Disease Control and Prevention, Windhoek, Namibia. 6 World Health Organization Field ... The wide age distribution of cases indicated measles-susceptible individuals accumulated over several decades prior to the start of the outbreak. S Afr Med J 2016 ...

  8. A Neurogenetics Approach to Defining Differential Susceptibility to Institutional Care

    Science.gov (United States)

    Brett, Zoe H.; Sheridan, Margaret; Humphreys, Kate; Smyke, Anna; Gleason, Mary Margaret; Fox, Nathan; Zeanah, Charles; Nelson, Charles; Drury, Stacy

    2015-01-01

    An individual's neurodevelopmental and cognitive sequelae to negative early experiences may, in part, be explained by genetic susceptibility. We examined whether extreme differences in the early caregiving environment, defined as exposure to severe psychosocial deprivation associated with institutional care compared to normative rearing,…

  9. An Evolutionary Perspective on Family Studies: Differential Susceptibility to Environmental Influences.

    Science.gov (United States)

    Hartman, Sarah; Belsky, Jay

    2016-12-01

    An evolutionary perspective of human development provides the basis for the differential-susceptibility hypothesis which stipulates that individuals should differ in their susceptibility to environmental influences, with some being more affected than others by both positive and negative developmental experiences and environmental exposures. This paper reviews evidence consistent with this claim while revealing that temperamental and genetic characteristics play a role in distinguishing more and less susceptible individuals. The differential-susceptibility framework under consideration is contrasted to the traditional diathesis-stress view that "vulnerability" traits predispose some to being disproportionately affected by (only) adverse experiences. We raise several issues stimulated by the literature that need to be clarified in further research. Lastly, we suggest that therapy may differ in its effects depending on an individual's susceptibility. © 2015 Family Process Institute.

  10. Adolescent Susceptibility to Peer Influence in Sexual Situations

    Science.gov (United States)

    Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W.; Prinstein, Mitchell J.

    2016-01-01

    Purpose One consistent predictor of adolescents’ engagement in sexual risk behavior is their belief that peers are engaging in similar behavior; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes. The purpose of this project was to identify predictors of susceptibility to peer influence using a novel performance-based measure of sexual risk-taking. Methods Participants were 300 early adolescents (Mage=12.6; 53% female; 44% Caucasian) who completed 1) a pretest assessment of demographics, sexual attitudes, and hypothetical scenarios measuring the likelihood of engaging in sexual risk behavior, and 2) a subsequent experimental procedure that simulated an internet chat room in which youth believed they were communicating with peers regarding these same hypothetical scenarios. In reality, these “peers” were computer-programmed e-confederates. Changes in responses to the sexual scenarios in the private pretest versus during the public chat room provided a performance-based measure of peer influence susceptibility. Results In total, 78% of youth provided more risky responses in the chat room than in pretest. The most robust predictor of this change was gender, with boys significantly more susceptible to peer influence than girls. Significant interactions also were noted, with greater susceptibility among boys with later pubertal development and African American boys. Conclusion Results confirm that not all youth are equally susceptible to peer influence. Consistent with sexual script theory, boys evidence greater susceptibility to social pressure regarding sexual behavior than girls. PMID:26794431

  11. Adolescent Susceptibility to Peer Influence in Sexual Situations.

    Science.gov (United States)

    Widman, Laura; Choukas-Bradley, Sophia; Helms, Sarah W; Prinstein, Mitchell J

    2016-03-01

    One consistent predictor of adolescents' engagement in sexual risk behavior is their belief that peers are engaging in similar behavior; however, not all youth are equally susceptible to these peer influence effects. Understanding individual differences in susceptibility to peer influence is critical to identifying adolescents at risk for negative health outcomes. The purpose of this project was to identify predictors of susceptibility to peer influence using a novel performance-based measure of sexual risk taking. Participants were 300 early adolescents (Mage = 12.6 years; 53% female; 44% Caucasian) who completed (1) a pretest assessment of demographics, sexual attitudes, and hypothetical scenarios measuring the likelihood of engaging in sexual risk behavior and (2) a subsequent experimental procedure that simulated an Internet chat room in which youth believed that they were communicating with peers regarding these same hypothetical scenarios. In reality, these "peers" were computer-programmed e-confederates. Changes in responses to the sexual scenarios in the private pretest versus during the public chat room provided a performance-based measure of peer influence susceptibility. In total, 78% of youth provided more risky responses in the chat room than those in pretest. The most robust predictor of this change was gender, with boys significantly more susceptible to peer influence than girls. Significant interactions also were noted, with greater susceptibility among boys with later pubertal development and African-American boys. Results confirm that not all youth are equally susceptible to peer influence. Consistent with sexual script theory, boys evidence greater susceptibility to social pressure regarding sexual behavior than girls. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

  12. pitting corrosion susceptibility pitting corrosion susceptibility of aisi ...

    African Journals Online (AJOL)

    eobe

    Abstract. The susceptibility of austenitic (AISI 301) stainless steel to pitting corrosion was evaluated in sodium chloride. (NaCl) solutions ... AISI 301 steel suffers from pitting corrosion in all the investigated solutions. AISI 301 steel suffers from ..... [1] Ijeomah, M.N.C. Elements of Corrosion and Protection. Theory, Auto Century ...

  13. Magnetic Susceptability Measurements in Superconductors

    Science.gov (United States)

    Kim, Jason; Mallory, Kendall; Seim, Ryan

    2000-04-01

    A new undergraduate research facility in magnetic susceptability measurements on superconductors is being developed at the University of Northern Colorado. Initial data measurements of the magnetic susceptability of various superconductors will be presented. These measurements were obtained with a liquid helium/nitrogen dewar that was reassembled for use in this project. The cryostat consists of two separate dewars, the first of which contains liquid nitrogen, the second, liquid helium. The liquid nitrogen dewar is used to keep the helium bath from evaporating off too quickly. Data on the evaporation rates of the two liquids will also be presented.

  14. Application of a perialpine landslide susceptibility model in the Alpine region (Slovenia

    Directory of Open Access Journals (Sweden)

    Marko Komac

    2006-06-01

    Full Text Available A very good landslide susceptibility prediction model was developed for the area in the perialpine region in the central western Slovenia. Using multivariate statistics the interactions between spatial factors and landslide distribution were tested, and the importance of individual factor to the landslide susceptibility was defined. On the basis of the statistical results several landslide prediction models were developed using the Analytical Hierarchy Process (AHP method. These models gave very different results, with a prediction error ranging from 6,89 % to 31,8 %. As a final result of the research, weights of different spatial factors from the best models calculated with the AHP method were derived. The results showed that the lithology (31 % variance, the slope inclination (21,2% variance, land cover type (13,7 % variance, the terrain roughness (10,1 % variance, and the terrain curvature (8,6 % variance play an important role in landslide susceptibility in general. Minor roles also play the distance to streams and the distance to structuralelements. These factors weights values were later used as input values in a simple linear weighted landslide susceptibility prediction model for the area in the Alpine region (north-western Slovenia. The fact is that the ideal weight’s value of a factor differs from area to area. Each original weight value used in the new (Alpine model presented only the mean of the new weight’s range/distribution, which was used as an input to the linearmodel. The analysis of the ideal factors weights in the Alpine area