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961.
In contrast to molecular genetics, in cytogenetic analyses single cells are analyzed individually. This affords an opportunity to detect cells with chromosomal mosaicism. This article provides an overview on problems arising in the detection and interpretation of chromosomal mosaicism in cytogenetic diagnostics. A particular challenge in the diagnostics is to distinguish between clinically relevant genuine mosaicism on the one hand and cultured artifacts, pseudomosaics, age effects, maternal contamination and chimerism on the other. The probability of overlooking mosaicism in cytogenetic routine diagnostics is very high, as on average only 15 of the 1012 cells in the body are examined and usually only a single tissue is analyzed. However, some cytogenetic mosaics are typical for certain syndromes, such as Pallister-Killian syndrome, cat eye syndrome or Ullrich-Turner syndrome and others are characteristic for certain disorders including some hematological malignancies. 相似文献
962.
Maoyin Li Ethan Baughman Mary R. Roth Xianlin Han Ruth Welti Xuemin Wang 《The Plant journal : for cell and molecular biology》2014,77(1):160-172
Plant triacylglycerols (TAGs), or vegetable oils, provide approximately 25% of dietary calories to humans and are becoming an increasingly important source of renewable bioenergy and industrial feedstocks. TAGs are assembled by multiple enzymes in the endoplasmic reticulum from building blocks that include an invariable glycerol backbone and variable fatty acyl chains. It remains a challenge to elucidate the mechanism of synthesis of hundreds of different TAG species in planta. One reason is the lack of an efficient analytical approach quantifying individual molecular species. Here we report a rapid and quantitative TAG profiling approach for Arabidopsis seeds based on electrospray ionization tandem mass spectrometry with direct infusion and multiple neutral loss scans. The levels of 93 TAG molecular species, identified by their acyl components, were determined in Arabidopsis seeds. Quantitative TAG pattern analyses revealed that the TAG assembly machinery preferentially produces TAGs with one elongated fatty acid. The importance of the selectivity in oil synthesis was consistent with an observation that an Arabidopsis mutant overexpressing a patatin‐like phospholipase had enhanced seed oil content with elongated fatty acids. This quantitative TAG profiling approach should facilitate investigations aimed at understanding the biochemical mechanisms of TAG metabolism in plants. 相似文献
963.
964.
Tim Vanuytsel Christophe Vanormelingen Hanne Vanheel Tatsuhiro Masaoka Shadea Salim Rasoel Joran Tóth Els Houben Kristin Verbeke Gert De Hertogh Pieter Vanden Berghe Jan Tack Ricard Farré 《PloS one》2014,9(10)
Background
Impaired intestinal barrier function, low-grade inflammation and altered neuronal control are reported in functional gastrointestinal disorders. However, the sequence of and causal relation between these events is unclear, necessitating a spontaneous animal model. The aim of this study was to describe the natural history of intestinal permeability, mucosal and neuromuscular inflammation and nitrergic motor neuron function during the lifetime of the BioBreeding (BB) rat.Methods
Normoglycemic BB-diabetes prone (DP) and control rats were sacrificed at different ages and jejunum was harvested to characterize intestinal permeability, inflammation and neuromuscular function.Results
Both structural and functional evidence of increased intestinal permeability was found in young BB-DP rats from the age of 50 days. In older animals, starting in the mucosa from 70 days and in half of the animals also in the muscularis propria from 110 days, an inflammatory reaction, characterized by an influx of polymorphonuclear cells and higher myeloperoxidase activity, was observed. Finally, in animals older than 110 days, coinciding with a myenteric ganglionitis, a loss of nitrergic neurons and motor function was demonstrated.Conclusion
In the BB-rat, mucosal inflammatory cell infiltration is preceded by intestinal barrier dysfunction and followed by myenteric ganglionitis and loss of nitrergic function. This sequence supports a primary role for impaired barrier function and provides an insightful model for the pathogenesis of functional gastrointestinal disorders. 相似文献965.
Kristin L. Mercer D. Jason Emry Allison A. Snow Matthew A. Kost Brian A. Pace Helen M. Alexander 《PloS one》2014,9(10)
Understanding the likelihood and extent of introgression of novel alleles in hybrid zones requires comparison of lifetime fitness of parents and hybrid progeny. However, fitness differences among cross types can vary depending on biotic conditions, thereby influencing introgression patterns. Based on past work, we predicted that increased competition would enhance introgression between cultivated and wild sunflower (Helianthus annuus) by reducing fitness advantages of wild plants. To test this prediction, we established a factorial field experiment in Kansas, USA where we monitored the fitness of four cross types (Wild, F1, F2, and BCw hybrids) under different levels of interspecific and intraspecific competition. Intraspecific manipulations consisted both of density of competitors and of frequency of crop-wild hybrids. We recorded emergence of overwintered seeds, survival to reproduction, and numbers of seeds produced per reproductive plant. We also calculated two compound fitness measures: seeds produced per emerged seedling and seeds produced per planted seed. Cross type and intraspecific competition affected emergence and survival to reproduction, respectively. Further, cross type interacted with competitive treatments to influence all other fitness traits. More intense competition treatments, especially related to density of intraspecific competitors, repeatedly reduced the fitness advantage of wild plants when considering seeds produced per reproductive plant and per emerged seedling, and F2 plants often became indistinguishable from the wilds. Wild fitness remained superior when seedling emergence was also considered as part of fitness, but the fitness of F2 hybrids relative to wild plants more than quadrupled with the addition of interspecific competitors and high densities of intraspecific competitors. Meanwhile, contrary to prediction, lower hybrid frequency reduced wild fitness advantage. These results emphasize the importance of taking a full life cycle perspective. Additionally, due to effects of exogenous selection, a given hybrid generation may be especially well-suited to hastening introgression under particular environmental conditions. 相似文献
966.
Tim Lane Thomas Osmand Alexander Marr Starley B. Shade Kristin Dunkle Theodorus Sandfort Helen Struthers Susan Kegeles James A. McIntyre 《PloS one》2014,9(11)
The Mpumalanga Men''s Study (MPMS) is the assessment of the Project Boithato HIV prevention intervention for South African MSM. Boithato aims to increase consistent condom use, regular testing for HIV-negative MSM, and linkage to care for HIV-positive MSM. The MPMS baseline examined HIV prevalence and associated risk behaviors, and testing, care, and treatment behaviors among MSM in Gert Sibande and Ehlanzeni districts in Mpumalanga province, South Africa in order to effectively target intervention activities. We recruited 307 MSM in Gert Sibande and 298 in Ehlanzeni through respondent-driven sampling (RDS) between September 2012-March 2013. RDS-adjusted HIV prevalence estimates are 28.3% (95% CI 21.1%–35.3%) in Gert Sibande, and 13.7% (95% CI 9.1%–19.6%) in Ehlanzeni. Prevalence is significantly higher among MSM over age 25 [57.8% (95% CI 43.1%–72.9%) vs. 17.9% (95% CI 10.6%–23.9%), P<0.001 in Gert Sibande; 34.5% (95%CI 20.5%–56.0%) vs. 9.1% (95% CI 4.6%–13.9%), P<0.001 in Ehlanzeni]. In Gert Sibande, prevalence is higher among self-identified gay and transgender MSM vs. other MSM [39.3% (95%CI, 28.3%–47.9%), P<0.01], inconsistent condom users [38.1% (18.1%–64.2%), P<0.05], those with a current regular male partner [35.0% (27.1%–46.4%), P<0.05], and those with lifetime experience of intimate partner violence with men [40.4%, (95%CI 28.9%–50.9%), P<0.05]. Prevalence of previous HIV testing was 65.8% (95%CI 58.8%–74.0%) in Gert Sibande, and 69.3% (95%CI 61.9%–76.8%) in Ehlanzeni. Regular HIV testing was uncommon [(34.6%, (95%CI 27.9%–41.4%) in Gert Sibande; 31.0% (95%CI 24.9%–37.8%) in Ehlanzeni]. Among HIV-positive participants, few knew their status (28.1% in Gert Sibande and 14.5% in Ehlanzeni), or were appropriately linked to care (18.2% and 11.3%, respectively), or taking antiretroviral therapy (13.6% and 9.6% respectively). MPMS results demonstrate the importance of implementing interventions for MSM to increase consistent condom use, regular HIV testing, and linkage and engagement in care for HIV-infected MSM. 相似文献
967.
Kristin M. Pearson-Fuhrhop Erin C. Dunn Sarah Mortero William J. Devan Guido J. Falcone Phil Lee Avram J. Holmes Marisa O. Hollinshead Joshua L. Roffman Jordan W. Smoller Jonathan Rosand Steven C. Cramer 《PloS one》2014,9(5)
Background
Depression is a common source of human disability for which etiologic insights remain limited. Although abnormalities of monoamine neurotransmission, including dopamine, are theorized to contribute to the pathophysiology of depression, evidence linking dopamine-related genes to depression has been mixed. The current study sought to address this knowledge-gap by examining whether the combined effect of dopamine polymorphisms was associated with depressive symptomatology in both healthy individuals and individuals with depression.Methods
Data were drawn from three independent samples: (1) a discovery sample of healthy adult participants (n = 273); (2) a replication sample of adults with depression (n = 1,267); and (3) a replication sample of healthy adult participants (n = 382). A genetic risk score was created by combining functional polymorphisms from five genes involved in synaptic dopamine availability (COMT and DAT) and dopamine receptor binding (DRD1, DRD2, DRD3).Results
In the discovery sample, the genetic risk score was associated with depressive symptomatology (β = −0.80, p = 0.003), with lower dopamine genetic risk scores (indicating lower dopaminergic neurotransmission) predicting higher levels of depression. This result was replicated with a similar genetic risk score based on imputed genetic data from adults with depression (β = −0.51, p = 0.04). Results were of similar magnitude and in the expected direction in a cohort of healthy adult participants (β = −0.86, p = 0.15).Conclusions
Sequence variation in multiple genes regulating dopamine neurotransmission may influence depressive symptoms, in a manner that appears to be additive. Further studies are required to confirm the role of genetic variation in dopamine metabolism and depression. 相似文献968.
Matthew K. Vendlinski Kristin N. Javaras Carol A. Van Hulle Kathryn Lemery-Chalfant Rose Maier Richard J. Davidson H. Hill Goldsmith 《PloS one》2014,9(7)
Background
Comorbidity among childhood mental health symptoms is common in clinical and community samples and should be accounted for when investigating etiology. We therefore aimed to uncover latent classes of mental health symptoms in middle childhood in a community sample, and to determine the latent genetic and environmental influences on those classes.Methods
The sample comprised representative cohorts of twins. A questionnaire-based assessment of mental health symptoms was used in latent class analyses. Data on 3223 twins (1578 boys and 1645 girls) with a mean age of 7.5 years were analyzed. The sample was predominantly non-Hispanic Caucasian (92.1%).Results
Latent class models delineated groups of children according to symptom profiles–not necessarily clinical groups but groups representing the general population, most with scores in the normative range. The best-fitting models suggested 9 classes for both girls and boys. Eight of the classes were very similar across sexes; these classes ranged from a “Low Symptom” class to a “Moderately Internalizing & Severely Externalizing” class. In addition, a “Moderately Anxious” class was identified for girls but not boys, and a “Severely Impulsive & Inattentive” class was identified for boys but not girls. Sex-combined analyses implicated moderate genetic influences for all classes. Shared environmental influences were moderate for the “Low Symptom” and “Moderately Internalizing & Severely Externalizing” classes, and small to zero for other classes.Conclusions
We conclude that symptom classes are largely similar across sexes in middle childhood. Heritability was moderate for all classes, but shared environment played a greater role for classes in which no one type of symptom predominated. 相似文献969.
Kyoko Yoshida Hongfeng Jiang MiJung Kim Joy Vink Serge Cremers David Paik Ronald Wapner Mala Mahendroo Kristin Myers 《PloS one》2014,9(11)
The changes in the mechanical integrity of the cervix during pregnancy have implications for a successful delivery. Cervical collagens are known to remodel extensively in mice with progressing gestation leading to a soft cervix at term. During this process, mature crosslinked collagens are hypothesized to be replaced with immature less crosslinked collagens to facilitate cervical softening and ripening. To determine the mechanical role of collagen crosslinks during normal mouse cervical remodeling, tensile load-to-break tests were conducted for the following time points: nonpregnant (NP), gestation day (d) 6, 12, 15, 18 and 24 hr postpartum (PP) of the 19-day gestation period. Immature crosslinks (HLNL and DHLNL) and mature crosslinks (DPD and PYD) were measured using ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). There were no significant changes in the total immature crosslink density (HLNL+DHLNL mol per collagen mol) throughout normal mouse gestation (range: 0.31–0.49). Total mature crosslink density (PYD+DPD mol per collagen mol) decreased significantly in early softening from d6 to d15 (d6: 0.17, d12: 0.097, d15: 0.026) and did not decrease with further gestation. The maturity ratio (total mature to total immature crosslinks) significantly decreased in early softening from d6 to d15 (d6: 0.2, d15: 0.074). All of the measured crosslinks correlated significantly with a measure of tissue stiffness and strength, with the exception of the immature crosslink HLNL. This data provides quantitative evidence to support the hypothesis that as mature crosslinked collagens decline, they are replaced by immature collagens to facilitate increased tissue compliance in the early softening period from d6 to d15. 相似文献
970.
Kristen K. McCampbell Kristin N. Springer Rebecca A. Wingert 《Journal of visualized experiments : JoVE》2014,(90)
The zebrafish model has emerged as a relevant system to study kidney development, regeneration and disease. Both the embryonic and adult zebrafish kidneys are composed of functional units known as nephrons, which are highly conserved with other vertebrates, including mammals. Research in zebrafish has recently demonstrated that two distinctive phenomena transpire after adult nephrons incur damage: first, there is robust regeneration within existing nephrons that replaces the destroyed tubule epithelial cells; second, entirely new nephrons are produced from renal progenitors in a process known as neonephrogenesis. In contrast, humans and other mammals seem to have only a limited ability for nephron epithelial regeneration. To date, the mechanisms responsible for these kidney regeneration phenomena remain poorly understood. Since adult zebrafish kidneys undergo both nephron epithelial regeneration and neonephrogenesis, they provide an outstanding experimental paradigm to study these events. Further, there is a wide range of genetic and pharmacological tools available in the zebrafish model that can be used to delineate the cellular and molecular mechanisms that regulate renal regeneration. One essential aspect of such research is the evaluation of nephron structure and function. This protocol describes a set of labeling techniques that can be used to gauge renal composition and test nephron functionality in the adult zebrafish kidney. Thus, these methods are widely applicable to the future phenotypic characterization of adult zebrafish kidney injury paradigms, which include but are not limited to, nephrotoxicant exposure regimes or genetic methods of targeted cell death such as the nitroreductase mediated cell ablation technique. Further, these methods could be used to study genetic perturbations in adult kidney formation and could also be applied to assess renal status during chronic disease modeling. 相似文献