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11.
Justin R. Prigge James A. Wiley Emily A. Talago Elise M. Young Laura L. Johns Jean A. Kundert Katherine M. Sonsteng William P. Halford Mario R. Capecchi Edward E. Schmidt 《Mammalian genome》2013,24(9-10):389-399
Cre-responsive dual-fluorescent alleles allow in situ marking of cell lineages or genetically modified cells. Here we report a dual-fluorescent allele, ROSA nT-nG , which directs nuclear accumulation of tdTomato in Cre-naïve lineages. Cre converts the allele to ROSA nG , which drives nuclear EGFP accumulation. Conditions were established for analyzing marked nuclei by flow cytometry on the basis of red–green fluorescence and ploidy, with a particular focus on liver nuclei. Hydrodynamic delivery of a Cre-expression plasmid was used to time-stamp arbitrary hepatocytes for lineage tracing. The distinct green fluorescence of nuclei from Cre-exposed lineages facilitated analyses of ploidy transitions within clones. To assess developmental transitions in liver nuclei, ROSA nT-nG was combined with the hepatocyte-specific AlbCre transgene, facilitating discrimination between hepatocyte and nonhepatocyte nuclei. Nuclei extracted from postnatal day 2 (P2) livers were 41 % green and 59 % red and reached a stable level of 84 % green by P22. Until P20, green nuclei were >98 % diploid (2N); at P40 they were ~56 % 2N, 43 % 4N, and <1 % 8N; and by P70 they reached a stable distribution of ~46 % 2N, 45 % 4N, and 9 % 8N. In conclusion, ROSA nT-nG will facilitate in vivo and ex vivo studies on liver and will likely be valuable for studies on tissues like muscle, kidney, or brain in which cells are refractory to whole-cell flow cytometry, or like trophectoderm derivatives or cancers in which cells undergo ploidy transitions. 相似文献
12.
Students who work during the school year face the potential of sleep deprivation and its effects, since they have to juggle between school and work responsibilities along with social life. This may leave them with less time left for sleep than their nonworking counterparts. Chronotype is a factor that may exert an influence on the sleep of student workers. Also, light and social zeitgebers may have an impact on the sleep-related problems of this population. This study aimed to document sleep, light exposure patterns, social rhythms, and work-related fatigue of student workers aged 19-21 yrs and explore possible associations with chronotype. A total of 88 student workers (mean ± SD: 20.18 ± .44 yrs of age; 36 males/52 females) wore an actigraph (Actiwatch-L; Mini-Mitter/Respironics,Bend, OR) and filled out the Social Rhythm Metric for two consecutive weeks during the school year. Also, they completed the Morningness-Eveningness Questionnaire (MEQ), Epworth Sleepiness Scale (ESS), Pittsburgh Sleep Quality Index (PSQI), and Occupational Fatigue Exhaustion/Recovery Scale (OFER). Repeated and one-way analyses of variance (ANOVAs), Pearson's chi-square tests, and correlation coefficients were used for statistical comparisons. Subjects slept an average of 06:28 h/night. Actigraphic sleep parameters, such as sleep duration, sleep efficiency, wake after sleep onset, and sleep latency, did not differ between chronotypes. Results also show that evening types (n = 17) presented lower subjective sleep quality than intermediate types (n = 58) and morning types (n = 13). Moreover, evening types reported higher levels of chronic work-related fatigue, exhibited less regular social rhythms, and were exposed to lower levels of light during their waking hours (between 2 and 11 h after wake time) as compared to intermediate types and morning types. In addition, exposure to light intensities between 100 and 500 lux was lower in evening types than in intermediate types and morning types. However, bright light exposure (≥ 1000 lux) did not differ between chronotypes. In conclusion, results suggest that student workers may constitute a high-risk population for sleep deprivation. Evening types seemed to cope less well with sleep deprivation, reporting poorer sleep quality and higher levels of work-related fatigue than intermediate types and morning types. The higher chronic work-related fatigue of evening types may be linked to their attenuated level of light exposure and weaker social zeitgebers. These results add credence to the hypothesis that eveningness entails a higher risk of health-impairing behaviors. 相似文献
13.
Kenmogne M Prost E Harakat D Jacquier MJ Frédérich M Sondengam LB Zèches M Waffo-Téguo P 《Phytochemistry》2006,67(5):433-438
Five labdane diterpenoids, (3-5), zambesiacolactone A (7) and zambesiacolactone B (8), were isolated from the seeds of Aframomum zambesiacum (Baker) K. Schum., along with five known labdanes and a linear sesquiterpene, nerolidol. Their structures were elucidated by spectroscopic analysis. Their antiplasmodial activity was evaluated in vitro against Plasmodium falciparum. Compound 3 was the most active with an IC(50) value of 4.97 microM. 相似文献
14.
Dana M. Blumenthal Julie A. Kray William Ortmans Lewis H. Ziska Elise Pendall 《Global Change Biology》2016,22(9):3026-3038
Elevated CO2 and warming may alter terrestrial ecosystems by promoting invasive plants with strong community and ecosystem impacts. Invasive plant responses to elevated CO2 and warming are difficult to predict, however, because of the many mechanisms involved, including modification of phenology, physiology, and cycling of nitrogen and water. Understanding the relative and interactive importance of these processes requires multifactor experiments under realistic field conditions. Here, we test how free‐air CO2 enrichment (to 600 ppmv) and infrared warming (+1.5 °C day/3 °C night) influence a functionally and phenologically distinct invasive plant in semi‐arid mixed‐grass prairie. Bromus tectorum (cheatgrass), a fast‐growing Eurasian winter annual grass, increases fire frequency and reduces biological diversity across millions of hectares in western North America. Across 2 years, we found that warming more than tripled B. tectorum biomass and seed production, due to a combination of increased recruitment and increased growth. These results were observed with and without competition from native species, under wet and dry conditions (corresponding with tenfold differences in B. tectorum biomass), and despite the fact that warming reduced soil water. In contrast, elevated CO2 had little effect on B. tectorum invasion or soil water, while reducing soil and plant nitrogen (N). We conclude that (1) warming may expand B. tectorum's phenological niche, allowing it to more successfully colonize the extensive, invasion‐resistant northern mixed‐grass prairie, and (2) in ecosystems where elevated CO2 decreases N availability, CO2 may have limited effects on B. tectorum and other nitrophilic invasive species. 相似文献
15.
Mycobacteria are able to enter into a state of non-replication or dormancy, which may result in their chronic persistence in soil, aquatic environments, and permissive hosts. Stresses such as nutrient deprivation and hypoxia provide environmental cues to enter a persistent state; however, a clear definition of the mechanism that mycobacteria employ to achieve this remains elusive. While the concept of sporulation in mycobacteria is not novel, it continues to spark controversy and challenges our perceptions of a non-replication. We investigated the potential role of sporulation in one-year old broth cultures of Mycobacterium subsp. paratuberculosis (MAP). We show that dormant cultures of MAP contain a mix of vegetative cells and a previously unknown morphotype resembling a spore. These spore-like structures can be enriched for using sporulating media. Furthermore, purified MAP spore forms survive exposure to heat, lysozyme and proteinase K. Heat-treated spores are positive for MAP 16SrRNA and IS900. MAP spores display enhanced infectivity as well as maintain acid-fast characteristics upon germination in a well-established bovine macrophage model. This is the first study to demonstrate a new MAP morphotype possessing spore-like qualities. Data suggest that sporulation may be a viable mechanism by which MAP accomplishes persistence in the host and/or environment. Thus, our current understanding of mycobacterial persistence, pathogenesis, epidemiology and rational drug and vaccine design may need to be reevaluated. 相似文献
16.
Diane Frankel Valérie Delecourt Karim Harhouri Annachiara De Sandre‐Giovannoli Nicolas Lévy Elise Kaspi Patrice Roll 《Aging cell》2018,17(4)
Hereditary and sporadic laminopathies are caused by mutations in genes encoding lamins, their partners, or the metalloprotease ZMPSTE24/FACE1. Depending on the clinical phenotype, they are classified as tissue‐specific or systemic diseases. The latter mostly manifest with several accelerated aging features, as in Hutchinson–Gilford progeria syndrome (HGPS) and other progeroid syndromes. MicroRNAs are small noncoding RNAs described as powerful regulators of gene expression, mainly by degrading target mRNAs or by inhibiting their translation. In recent years, the role of these small RNAs has become an object of study in laminopathies using in vitro or in vivo murine models as well as cells/tissues of patients. To date, few miRNAs have been reported to exert protective effects in laminopathies, including miR‐9, which prevents progerin accumulation in HGPS neurons. The recent literature has described the potential implication of several other miRNAs in the pathophysiology of laminopathies, mostly by exerting deleterious effects. This review provides an overview of the current knowledge of the functional relevance and molecular insights of miRNAs in laminopathies. Furthermore, we discuss how these discoveries could help to better understand these diseases at the molecular level and could pave the way toward identifying new potential therapeutic targets and strategies based on miRNA modulation. 相似文献
17.
Said El?Shamieh Marion Neuillé Angélique Terray Elise Orhan Christel Condroyer Vanessa Démontant Christelle Michiels Aline Antonio Fiona Boyard Marie-Elise Lancelot Mélanie Letexier Jean-Paul Saraiva Thierry Léveillard Saddek Mohand-Sa?d Olivier Goureau José-Alain Sahel Christina Zeitz Isabelle Audo 《American journal of human genetics》2014,94(4):625-633
18.
Mita Das Marjan Boerma Jessica R. Goree Elise G. Lavoie Michel Fausther Igor B. Gubrij Amanda K. Pangle Larry G. Johnson Jonathan A. Dranoff 《PloS one》2014,9(4)
Rationale
Lack of an experimental model of portopulmonary hypertension (POPH) has been a major obstacle in understanding of pathophysiological mechanisms underlying the disease.Objective
We investigated the effects of CCl4-mediated cirrhosis on the pulmonary vasculature, as an initial step towards an improved understanding of POPH.Methods And Results
Male C57BL/6 mice received intraperitoneal injection of either sterile olive oil or CCl4 3 times/week for 12 weeks. Cirrhosis and portal hypertension were confirmed by evidence of bridging fibrosis and nodule formation in CCl4-treated liver determined by trichrome/picrosirius red staining and an increase in spleen weight/body weight ratio, respectively. Staining for the oxidative stress marker, 4-hydroxynonenal (4-HNE), was strong in the liver but was absent in the lung, suggesting that CCl4 did not directly induce oxidative injury in the lung. Pulmonary acceleration time (PAT) and the ratio of PAT/pulmonary ejection time (PET) measured by echocardiography were significantly decreased in cirrhotic mice. Increase in right ventricle (RV) weight/body weight as well as in the weight ratio of RV/(left ventricle + septum) further demonstrated the presence of pathological changes in the pulmonary circulation in these mice. Histological examination revealed that lungs of cirrhotic mice have excessive accumulation of perivascular collagen and thickening of the media of the pulmonary artery.Conclusion
Collectively, our data demonstrate that chronic CCl4 treatment induces pathological changes in pulmonary circulation in cirrhotic mice. We propose that this murine cirrhotic model provides an exceptional tool for future studies of the molecular mechanisms mediating pulmonary vascular diseases associated with cirrhosis and for evaluation of novel therapeutic interventions. 相似文献19.
Jeannine Günther Angela Kill Mike Oliver Becker Harald Heidecke Judith Rademacher Elise Siegert Mislav Radi? Gerd-Rüdiger Burmester Duska Dragun Gabriela Riemekasten 《Arthritis research & therapy》2014,16(2):R65
Introduction
Agonistic autoantibodies (Aabs) against the angiotensin II receptor type 1 (AT1R) and the endothelin receptor type A (ETAR) have been identified in patients with systemic sclerosis (SSc). In our present study, we examined the expression of the AT1R and the ETAR in human immune cells and the pathological effects mediated through these receptors by their corresponding Aabs.Methods
Protein expression of AT1R and ETAR on peripheral blood mononuclear cells (PBMCs) from healthy individuals and SSc patients was analyzed using flow cytometry, and mRNA expression of both receptors in PBMCs from healthy donors was examined by real-time PCR. In addition, PBMCs from healthy donors were stimulated in vitro with affinity-purified immunoglobulin G (IgG) fractions from SSc patients positive for AT1R and ETAR Aabs, as well as with IgG from healthy donors serving as controls. Alterations in cell surface marker expression, cytokine secretion and chemotactic motility were analyzed using flow cytometry, enzyme-linked immunosorbent assays and chemotaxis assays, respectively. The results were correlated with the characteristics and clinical findings of the IgG donors.Results
Both AT1R and ETAR were expressed on PBMCs in humans. Protein expression of both receptors was decreased in SSc patients compared with that of healthy donors and declined during the course of disease. IgG fractions of SSc patients positive for AT1R and ETAR Aabs induced T-cell migration in an Aab level–dependent manner. Moreover, IgG of SSc patients stimulated PBMCs to produce more interleukin 8 (IL-8) and chemokine (C-C motif) ligand 18 (CCL18) than did the IgG of healthy donors. All effects were significantly reduced by selective AT1R and ETAR antagonists. Statistical analysis revealed an association of SSc-IgG induced high IL-8 concentrations with an early disease stage and of high CCL18 concentrations with lung fibrosis onset and vascular complications in the respective IgG donors.Conclusion
In our present study, we could demonstrate the expression of both AT1R and ETAR on human peripheral T cells, B cells and monocytes. The decreased receptor expression in SSc patients, the inflammatory and profibrotic effects upon Aab stimulation of PBMCs in vitro and the associations with clinical findings suggest a role for Aab-induced activation of immune cells mediated by the AT1R and the ETAR in the pathogenesis or even the onset of the disease. 相似文献20.
de Boer M. Karin; Koolmees Elise M.; Vrieling Engel G.; Breeman Anneke M.; van Rijssel Marion 《Journal of plankton research》2005,27(1):47-60
The harmful bloom alga Fibrocapsa japonica has a worldwide distributionin temperate regions and is occasionally responsible for massmortality of fish. Little is known about requirements for optimalgrowth and survival of this species, especially about temperatureconstraints that define natural distribution. Therefore, westudied thermal traits in three Fibrocapsa strains from differentclimate regions. All strains were eurythermal and viable between4 and 32°C, explaining their presence in temperate regions.Some differences in temperature response among the strains wereobserved, not only for growth rate but also for biovolume andnet production. The implication of the observed responses wasevaluated by translating growth performance of strains in thelaboratory to potential performance in the natural habitats.Only the Japanese strain seemed to be well adapted to its environment,while the New Zealand strain exhibited growth and survival overa much broader temperature range, despite the small temperaturefluctuations in its habitat. Interestingly, the German WaddenSea strain encounters lethal temperatures in winter and musthave a resting stage, able to survive temperatures <4°C,to explain its occurrence in this region. However, in general,the responses of the three F. japonica strains in culture werein good agreement with the observed seasonal occurrence in thefield. 相似文献