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991.
992.
Miriam A. Mosing Nancy L. Pedersen David Cesarini Magnus Johannesson Patrik K. E. Magnusson Jeanne Nakamura Guy Madison Fredrik Ullén 《PloS one》2012,7(11)
Flow is a psychological state of high but subjectively effortless attention that typically occurs during active performance of challenging tasks and is accompanied by a sense of automaticity, high control, low self-awareness, and enjoyment. Flow proneness is associated with traits and behaviors related to low neuroticism such as emotional stability, conscientiousness, active coping, self-esteem and life satisfaction. Little is known about the genetic architecture of flow proneness, behavioral inhibition and locus of control – traits also associated with neuroticism – and their interrelation. Here, we hypothesized that individuals low in behavioral inhibition and with an internal locus of control would be more likely to experience flow and explored the genetic and environmental architecture of the relationship between the three variables. Behavioral inhibition and locus of control was measured in a large population sample of 3,375 full twin pairs and 4,527 single twins, about 26% of whom also scored the flow proneness questionnaire. Findings revealed significant but relatively low correlations between the three traits and moderate heritability estimates of .41, .45, and .30 for flow proneness, behavioral inhibition, and locus of control, respectively, with some indication of non-additive genetic influences. For behavioral inhibition we found significant sex differences in heritability, with females showing a higher estimate including significant non-additive genetic influences, while in males the entire heritability was due to additive genetic variance. We also found a mainly genetically mediated relationship between the three traits, suggesting that individuals who are genetically predisposed to experience flow, show less behavioral inhibition (less anxious) and feel that they are in control of their own destiny (internal locus of control). We discuss that some of the genes underlying this relationship may include those influencing the function of dopaminergic neural systems. 相似文献
993.
Tjeerd Barf Fredrik Lehmann Kristin Hammer Saba Haile Eva Axen Carmen Medina Jonas Uppenberg Stefan Svensson Lena Rondahl Thomas Lundbäck 《Bioorganic & medicinal chemistry letters》2009,19(6):1745-1748
Small molecule inhibitors of adipocyte fatty-acid binding protein (A-FABP) have gained renewed interest following the recent publication of pharmacologically beneficial effects of such inhibitors. Despite the potential utility of selective A-FABP inhibitors within the fields of metabolic disease, inflammation and atherosclerosis, there are few examples of useful A-FABP inhibitors in the public domain. Herein, we describe the optimization of N-benzyl-tetrahydrocarbazole derivatives through the use of co-crystal structure guided medicinal chemistry efforts. This led to the identification of a potent and selective class of A-FABP inhibitors as illustrated by N-benzyl-hexahydrocyclohepta[b]indole 30. 相似文献
994.
Anna Rydén Elisabeth S?rstadius Klas Bergenheim Alexandru Romanovschi Fredrik Thorén Edward A. Witt Catarina Sternhufvud 《PloS one》2016,11(11)
AimsDiagnoses of Type 1 Diabetes Mellitus (T1DM) in Europe appear to be on the rise. Therefore it is imperative that researchers understand the potential impact that increases in prevalence could have on the affected individuals as well as on society as a whole. Accordingly this study examined the humanistic and economic burden of T1DM in patients relative to those without the condition across a number of health outcomes including health status, work productivity loss, activity impairment, and healthcare resource use.MethodsSurvey data from a large, representative sample of EU adults (The EU National Health and Wellness Survey) were examined.ResultsResults suggest that overall burden is higher for those diagnosed with T1DM than respondents without diabetes and that burden increases as complications associated with T1DM increase.ConclusionsTaken together, these results suggest that treatment strategies for T1DM should balance clinical, humanistic, and economic burden and patients should be educated on the role of complications in disease outcomes. 相似文献
995.
There is persistent commercial interest in the use of growth modified fishes for shortening production cycles and increasing overall food production, but there is concern over the potential impact that transgenic fishes might have if ever released into nature. To explore the ecological consequences of transgenic fish, we performed two experiments in which the early growth and survival of growth-hormone transgenic rainbow trout (Oncorhynchus mykiss) were assessed in naturalized stream mesocosms that either contained predators or were predator-free. We paid special attention to the survival bottleneck that occurs during the early life-history of salmonids, and conducted experiments at two age classes (first-feeding fry and 60 days post-first-feeding) that lie on either side of the bottleneck. In the late summer, the first-feeding transgenic trout could not match the growth potential of their wild-type siblings when reared in a hydrodynamically complex and oligotrophic environment, irrespective of predation pressure. Furthermore, overall survival of transgenic fry was lower than in wild-type (transgenic = 30% without predators, 8% with predators; wild-type = 81% without predators, 31% with predators). In the experiment with 60-day old fry, we explored the effects of the transgene in different genetic backgrounds (wild versus domesticated). We found no difference in overwinter survival but significantly higher growth by transgenic trout, irrespective of genetic background. We conclude that the high mortality of GH-transgenic trout during first-feeding reflects an inability to sustain the basic metabolic requirements necessary for life in complex, stream environments. However, when older, GH-transgenic fish display a competitive advantage over wild-type fry, and show greater growth and equal survival as wild-type. These results demonstrate how developmental age and time of year can influence the response of genotypes to environmental conditions. We therefore urge caution when extrapolating the results of GH-transgenesis risk assessment studies across multiple life-history or developmental stages. 相似文献
996.
Backbone assignments of the 26 kDa neuron-specific ubiquitin carboxyl-terminal hydrolase L1 (UCH-L1)
Fredrik I. Andersson Sophie E. Jackson Shang-Te Danny Hsu 《Biomolecular NMR assignments》2010,4(1):41-43
UCH-L1 is a member of the family of ubiquitin C-terminal hydrolases whose primary role is to hydrolyze small C-terminal adducts of ubiquitin to generate free ubiquitin monomers. Expression of UCH-L1 is highly specific to neurons and point mutations in this enzyme are associated with a hereditary form of Parkinson’s disease. Herein, we present the NMR backbone assignments of human UCH-L1, thus enabling future solution-state NMR spectroscopic studies on the structure and function of this important protein. 相似文献
997.
The stabilisation potential of individual and mixed assemblages of natural bacteria and microalgae 总被引:2,自引:0,他引:2
Lubarsky HV Hubas C Chocholek M Larson F Manz W Paterson DM Gerbersdorf SU 《PloS one》2010,5(11):e13794
It is recognized that microorganisms inhabiting natural sediments significantly mediate the erosive response of the bed ("ecosystem engineers") through the secretion of naturally adhesive organic material (EPS: extracellular polymeric substances). However, little is known about the individual engineering capability of the main biofilm components (heterotrophic bacteria and autotrophic microalgae) in terms of their individual contribution to the EPS pool and their relative functional contribution to substratum stabilisation. This paper investigates the engineering effects on a non-cohesive test bed as the surface was colonised by natural benthic assemblages (prokaryotic, eukaryotic and mixed cultures) of bacteria and microalgae. MagPI (Magnetic Particle Induction) and CSM (Cohesive Strength Meter) respectively determined the adhesive capacity and the cohesive strength of the culture surface. Stabilisation was significantly higher for the bacterial assemblages (up to a factor of 2) than for axenic microalgal assemblages. The EPS concentration and the EPS composition (carbohydrates and proteins) were both important in determining stabilisation. The peak of engineering effect was significantly greater in the mixed assemblage as compared to the bacterial (x 1.2) and axenic diatom (x 1.7) cultures. The possibility of synergistic effects between the bacterial and algal cultures in terms of stability was examined and rejected although the concentration of EPS did show a synergistic elevation in mixed culture. The rapid development and overall stabilisation potential of the various assemblages was impressive (x 7.5 and ×9.5, for MagPI and CSM, respectively, as compared to controls). We confirmed the important role of heterotrophic bacteria in "biostabilisation" and highlighted the interactions between autotrophic and heterotrophic biofilm consortia. This information contributes to the conceptual understanding of the microbial sediment engineering that represents an important ecosystem function and service in aquatic habitats. 相似文献
998.
Biborka Bereczky-Veress Nada Abdelmagid Fredrik Piehl Tomas Bergstr?m Tomas Olsson Birgit Sk?ldenberg Margarita Diez 《PloS one》2010,5(8)
Herpes simplex encephalitis (HSE) is a rare disease with high mortality and significant morbidity among survivors. We have previously shown that susceptibility to HSE was host-strain dependent, as severe, lethal HSE developed after injection of human Herpes simplex type 1 virus (HSV-1) into the whiskers area of DA rats, whereas PVG rats remained completely asymptomatic. In the present study we investigated the early immunokinetics in these strains to address the underlying molecular mechanisms for the observed difference. The virus distribution and the immunological responses were compared in the whiskers area, trigeminal ganglia and brain stem after 12 hours and the first four days following infection using immunohistochemistry and qRT-PCR. A conspicuous immunopathological finding was a strain-dependent difference in the spread of the HSV-1 virus to the trigeminal ganglia, only seen in DA rats already from 12 hpi. In the whiskers area infected perineurial cells were abundant in the susceptible DA strain after 2 dpi, whereas in the resistant PVG rats HSV-1 spread was confined only to the epineurium. In both strains activation of Iba1+/ED1+ phagocytic cells followed the distribution pattern of HSV-1 staining, which was visible already at 12 hours after infection. Notably, in PVG rats higher mRNA expression of Toll-like receptors (Tlr) -2 and -9, together with increased staining for Iba1/ED1 was detected in the whiskers area. In contrast, all other Tlr-pathway markers were expressed at higher levels in the susceptible DA rats. Our data demonstrate the novel observation that genetically encoded properties of the host nerve and perineurial cells, recruitment of phagocyting cells together with the low expression of Tlr2 and -9 in the periphery define the susceptibility to HSV-1 entry into the nervous system. 相似文献
999.
Antonia Kalushkova M?rten Frykn?s Miguel Lemaire Charlotte Fristedt Prasoon Agarwal Maria Eriksson Sarah Deleu Peter Atadja Anders ?sterborg Kenneth Nilsson Karin Vanderkerken Fredrik ?berg Helena Jernberg-Wiklund 《PloS one》2010,5(7)
Multiple myeloma (MM) is a genetically heterogeneous disease, which to date remains fatal. Finding a common mechanism for initiation and progression of MM continues to be challenging. By means of integrative genomics, we identified an underexpressed gene signature in MM patient cells compared to normal counterpart plasma cells. This profile was enriched for previously defined H3K27-tri-methylated genes, targets of the Polycomb group (PcG) proteins in human embryonic fibroblasts. Additionally, the silenced gene signature was more pronounced in ISS stage III MM compared to stage I and II. Using chromatin immunoprecipitation (ChIP) assay on purified CD138+ cells from four MM patients and on two MM cell lines, we found enrichment of H3K27me3 at genes selected from the profile. As the data implied that the Polycomb-targeted gene profile would be highly relevant for pharmacological treatment of MM, we used two compounds to chemically revert the H3K27-tri-methylation mediated gene silencing. The S-adenosylhomocysteine hydrolase inhibitor 3-Deazaneplanocin (DZNep) and the histone deacetylase inhibitor LBH589 (Panobinostat), reactivated the expression of genes repressed by H3K27me3, depleted cells from the PRC2 component EZH2 and induced apoptosis in human MM cell lines. In the immunocompetent 5T33MM in vivo model for MM, treatment with LBH589 resulted in gene upregulation, reduced tumor load and increased overall survival. Taken together, our results reveal a common gene signature in MM, mediated by gene silencing via the Polycomb repressor complex. The importance of the underexpressed gene profile in MM tumor initiation and progression should be subjected to further studies. 相似文献
1000.