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51.
Michael CW Chan Renee WY Chan Wendy CL Yu Carol CC Ho WH Chui CK Lo Kit M Yuen Yi Guan John M Nicholls JS Malik Peiris 《Respiratory research》2009,10(1):102
Background
Highly pathogenic avian influenza (HPAI) H5N1 virus is entrenched in poultry in Asia and Africa and continues to infect humans zoonotically causing acute respiratory disease syndrome and death. There is evidence that the virus may sometimes spread beyond respiratory tract to cause disseminated infection. The primary target cell for HPAI H5N1 virus in human lung is the alveolar epithelial cell. Alveolar epithelium and its adjacent lung microvascular endothelium form host barriers to the initiation of infection and dissemination of influenza H5N1 infection in humans. These are polarized cells and the polarity of influenza virus entry and egress as well as the secretion of cytokines and chemokines from the virus infected cells are likely to be central to the pathogenesis of human H5N1 disease.Aim
To study influenza A (H5N1) virus replication and host innate immune responses in polarized primary human alveolar epithelial cells and lung microvascular endothelial cells and its relevance to the pathogenesis of human H5N1 disease.Methods
We use an in vitro model of polarized primary human alveolar epithelial cells and lung microvascular endothelial cells grown in transwell culture inserts to compare infection with influenza A subtype H1N1 and H5N1 viruses via the apical or basolateral surfaces.Results
We demonstrate that both influenza H1N1 and H5N1 viruses efficiently infect alveolar epithelial cells from both apical and basolateral surface of the epithelium but release of newly formed virus is mainly from the apical side of the epithelium. In contrast, influenza H5N1 virus, but not H1N1 virus, efficiently infected polarized microvascular endothelial cells from both apical and basolateral aspects. This provides a mechanistic explanation for how H5N1 virus may infect the lung from systemic circulation. Epidemiological evidence has implicated ingestion of virus-contaminated foods as the source of infection in some instances and our data suggests that viremia, secondary to, for example, gastro-intestinal infection, can potentially lead to infection of the lung. HPAI H5N1 virus was a more potent inducer of cytokines (e.g. IP-10, RANTES, IL-6) in comparison to H1N1 virus in alveolar epithelial cells, and these virus-induced chemokines were secreted onto both the apical and basolateral aspects of the polarized alveolar epithelium.Conclusion
The predilection of viruses for different routes of entry and egress from the infected cell is important in understanding the pathogenesis of influenza H5N1 infection and may help unravel the pathogenesis of human H5N1 disease. 相似文献52.
Qing Lin Ling Song Poon Junling Chen Linan Cheng Basil HoYuen Peter CK Leung 《Reproductive biology and endocrinology : RB&E》2009,7(1):115-8
Background
Obesity has been linked to an increased risk of female infertility. Leptin, an adipocytokine which is elevated during obesity, may influence gonadal function through modulating steroidogenesis in granulosa cells. 相似文献53.
Yassine Amrani Farhat Syed Chris Huang Katherine Li Veronica Liu Deepika Jain Stefan Keslacy Michael W Sims Hasna Baidouri Philip R Cooper Hengjiang Zhao Salman Siddiqui Christopher E Brightling Don Griswold Lily Li Reynold A Panettieri Jr 《Respiratory research》2010,11(1):104
Background
During pregnancy asthma may remain stable, improve or worsen. The factors underlying the deleterious effect of pregnancy on asthma remain unknown. Oxytocin is a neurohypophyseal protein that regulates a number of central and peripheral responses such as uterine contractions and milk ejection. Additional evidence suggests that oxytocin regulates inflammatory processes in other tissues given the ubiquitous expression of the oxytocin receptor. The purpose of this study was to define the role of oxytocin in modulating human airway smooth muscle (HASMCs) function in the presence and absence of IL-13 and TNFα, cytokines known to be important in asthma.Method
Expression of oxytocin receptor in cultured HASMCs was performed by real time PCR and flow cytomery assays. Responses to oxytocin was assessed by fluorimetry to detect calcium signals while isolated tracheal rings and precision cut lung slices (PCLS) were used to measure contractile responses. Finally, ELISA was used to compare oxytocin levels in the bronchoalveloar lavage (BAL) samples from healthy subjects and those with asthma.Results
PCR analysis demonstrates that OXTR is expressed in HASMCs under basal conditions and that both interleukin (IL)-13 and tumor necrosis factor (TNFα) stimulate a time-dependent increase in OXTR expression at 6 and 18 hr. Additionally, oxytocin increases cytosolic calcium levels in fura-2-loaded HASMCs that were enhanced in cells treated for 24 hr with IL-13. Interestingly, TNFα had little effect on oxytocin-induced calcium response despite increasing receptor expression. Using isolated murine tracheal rings and PCLS, oxytocin also promoted force generation and airway narrowing. Further, oxytocin levels are detectable in bronchoalveolar lavage (BAL) fluid derived from healthy subjects as well as from those with asthma.Conclusion
Taken together, we show that cytokines modulate the expression of functional oxytocin receptors in HASMCs suggesting a potential role for inflammation-induced changes in oxytocin receptor signaling in the regulation of airway hyper-responsiveness in asthma. 相似文献54.
Namekawa SH Park PJ Zhang LF Shima JE McCarrey JR Griswold MD Lee JT 《Current biology : CB》2006,16(7):660-667
In mammals, the X and Y chromosomes are subject to meiotic sex chromosome inactivation (MSCI) during prophase I in the male germline, but their status thereafter is currently unclear. An abundance of X-linked spermatogenesis genes has spawned the view that the X must be active . On the other hand, the idea that the imprinted paternal X of the early embryo may be preinactivated by MSCI suggests that silencing may persist longer . To clarify this issue, we establish a comprehensive X-expression profile during mouse spermatogenesis. Here, we discover that the X and Y occupy a novel compartment in the postmeiotic spermatid and adopt a non-Rabl configuration. We demonstrate that this postmeiotic sex chromatin (PMSC) persists throughout spermiogenesis into mature sperm and exhibits epigenetic similarity to the XY body. In the spermatid, 87% of X-linked genes remain suppressed postmeiotically, while autosomes are largely active. We conclude that chromosome-wide X silencing continues from meiosis to the end of spermiogenesis, and we discuss implications for proposed mechanisms of imprinted X-inactivation. 相似文献
55.
Expression of Mirlet7 family microRNAs in response to retinoic acid-induced spermatogonial differentiation in mice 总被引:1,自引:0,他引:1
Spermatogonial differentiation is orchestrated by the precise control of gene expression involving retinoic acid signaling. MicroRNAs have emerged as important regulators of spermatogenesis, and here we show that the Mirlet7 family miRNAs are expressed in mouse spermatogonia and spermatocytes. Retinoic acid significantly leads to the induction of Mirlet7 miRNAs through suppression of Lin28. We further confirmed both in vitro and in vivo that expressions of Mycn, Ccnd1, and Col1a2, which are targets of Mirlet7, were downregulated during spermatogonial differentiation. These results suggest that Mirlet7 family miRNAs play a role in retinoic acid-induced spermatogonial differentiation. 相似文献
56.
Griswold CK 《Journal of theoretical biology》2011,282(1):14-22
Calcium-signals occur in a wide variety of tissue types - from skeletal, smooth and cardiac muscle to pancreatic and brain tissues. Ca2+ signals regulate diverse processes including muscle contraction, hormone secretion, neural communication and gene expression. Together these different tissues and processes form the basis of a multivariate trait. Calcium signals are characterized by Ca2+ transients, which are sharp increases in Ca2+ concentration over a short period of time. In this paper we derive and analyze a model of Ca2+ transients for skeletal muscle, neurons and cardiac tissue based on underlying biophysical principles. Tissue differentiation in our model and in nature comes about by varying the ryanodine receptor (RyR) channel composition of tissues. In vertebrates, there are typically three types of RyR channels (labeled RyR1, RyR2 and RyR3 in mammals and α‐RyR, cardiac-RyR and β‐RyR in birds, amphibians and fish). Different compositions of these three RyR channels generate different Ca2+ transient properties. There are four Ca2+ transient properties that we measure: maximum amplitude, duration, half duration (D50) and integrated concentration. In agreement with experimental work, our results find that the addition of RyR3 amplifies Ca2+ transients in skeletal muscle. An important consequence of shared molecular components between tissue types in a multivariate setting is that the shared components cause individual traits of a multivariate trait to be correlated in function. Here we show how correlations in Ca2+ transient properties between tissues can be predicted using an underlying biophysical model. 相似文献
57.
Shang XZ Ma KY Radewonuk J Li J Song XY Griswold DE Emmell E Li L 《Cellular immunology》2006,241(2):66-74
IgE plays a critical role in the pathogenesis of allergy and asthma. Therefore, suppression of IgE production would provide therapeutic benefits to patients suffering from these diseases. We have reported that the production of IgE is regulated differently in the spleen vs. the draining lymph nodes (LN). IgE isotype switch and IgE producing B cell expansion occur in the draining LN after antigen (Ag) immunization, but do not happen in the spleen. In addition, a population of pre-existing IgE+ cells is observed in the spleen of normal or sham immunized mice, but is not present in the draining LN. To further understand the regulation of IgE production in different lymphoid organs, and the potential inhibitory factors of IgE isotype switch in the spleen, the involvement of IL-21 and IFN-gamma in regulating IgE production was investigated by using the IL-21 and the IFN-gamma deficient mice. We found that in the absence of IL-21 IgE isotype switch and IgE+ cell clonal expansion were dramatically enhanced in the spleen and IgE isotype switch was partially increased in the draining LN. In addition, IgE production of the pre-existing CD19-CD5+B220(low) IgE+ cells in the spleen was also increased in the absence of IL-21 under physiological conditions. In contrast, using the IFN-gamma deficient mice, we did not observe a negative impact of IFN-gamma on either IgE isotype switch or IgE production. Our data suggest that IL-21 appears to be a critical cytokine to keep low IgE levels under physiological and pathological conditions. 相似文献
58.
Erika L. Garcia Charles E. Griswold Lauren A. Esposito 《Journal of Zoological Systematics and Evolutionary Research》2020,58(1):114-126
The eight-eyed haplogyne spider family Plectreuridae Simon, 1893 is one of the oldest of spider families, currently comprising two genera (Kibramoa and Plectreurys), 30 extant species and one subspecies. Plectreuridae have not been rigorously examined since 1958, with only three new species added to Plectreurys. This study revisited a subset of taxa from the genus Kibramoa using a combined morphological and multilocus phylogenetic analysis. Species distribution modeling (SDM) was used to investigate the current and paleo distributional patterns of the genus Kibramoa throughout the biodiverse region of the California Floristic Province (CFP). A reexamination of genitalic morphology reflected cryptic species, yet multilocus Bayesian and maximum likelihood analyses of mitochondrial (COI, 16S) and nuclear (ITS1, 28S) markers consistently suggested several divergent lineages. A time-calibrated phylogeny indicated that the most recent common ancestor of Kibramoa appeared in the Mid-Miocene and continued to diversify throughout the Plio-Pleistocene. Xerophilic Kibramoa, as inferred by SDM, had a much wider distribution during the Mid-Holocene, when climate was at its warmest. This body of work uncovered novel findings regarding the evolution of plectreurids, provided the first phylogeny of the family, and demonstrated similar biogeographic patterns displayed in other CFP taxa. 相似文献
59.
Lisa A. Vrooman Jon M. Oatley Jodi E. Griswold Terry J. Hassold Patricia A. Hunt 《PLoS genetics》2015,11(1)
Bisphenol A (BPA) and other endocrine disrupting chemicals have been reported to induce negative effects on a wide range of physiological processes, including reproduction. In the female, BPA exposure increases meiotic errors, resulting in the production of chromosomally abnormal eggs. Although numerous studies have reported that estrogenic exposures negatively impact spermatogenesis, a direct link between exposures and meiotic errors in males has not been evaluated. To test the effect of estrogenic chemicals on meiotic chromosome dynamics, we exposed male mice to either BPA or to the strong synthetic estrogen, ethinyl estradiol during neonatal development when the first cells initiate meiosis. Although chromosome pairing and synapsis were unperturbed, exposed outbred CD-1 and inbred C3H/HeJ males had significantly reduced levels of crossovers, or meiotic recombination (as defined by the number of MLH1 foci in pachytene cells) by comparison with placebo. Unexpectedly, the effect was not limited to cells exposed at the time of meiotic entry but was evident in all subsequent waves of meiosis. To determine if the meiotic effects induced by estrogen result from changes to the soma or germline of the testis, we transplanted spermatogonial stem cells from exposed males into the testes of unexposed males. Reduced recombination was evident in meiocytes derived from colonies of transplanted cells. Taken together, our results suggest that brief exogenous estrogenic exposure causes subtle changes to the stem cell pool that result in permanent alterations in spermatogenesis (i.e., reduced recombination in descendent meiocytes) in the adult male. 相似文献
60.
Paul Rhoades Terry Griswold Lisette Waits Nilsa A. Bosque-Pérez Christina M. Kennedy Sanford D. Eigenbrode 《Journal of Insect Conservation》2017,21(4):703-714
Reliable and consistent monitoring is essential for bee conservation. Correctly interpreting the influence of habitat characteristics on native bee communities is necessary to develop effective strategies for bee conservation and to support the provision of pollination services to agricultural crops or natural plant communities. Biases imposed by different sampling methods used to monitor bee populations can affect our ability to discern important habitat characteristics, but the extent of this bias is not well understood. We used three common sampling methods (blue vane traps, colored pan traps, and aerial net collection) to assess bee communities in fragments of Palouse Prairie in eastern Washington and northern Idaho. We determined differences in abundance, species richness, proportional representation of different genera, and functional trait characteristics among the three sampling techniques. We also evaluated differences in the relationships between bee species richness and diversity and two key habitat variables known to mediate bee populations: local plant species richness and the amount of suitable bee habitat in the surrounding landscape. Community metrics for bees collected using blue vane traps were correlated with the amount of suitable habitat in the landscape but not with plant species richness. Conversely, community metrics for bees collected using an aerial net were correlated with the local plant species richness but not with the amount of suitable habitat. Our results indicate that effective conservation of insect communities will require a combination of sampling methods to reliably discern the influence of habitat variables at different scales and across taxa with varying functional traits. 相似文献