Project description:Impact of aggregate size and clay content on the bacterial community structure in soil microaggregates and macroaggregates of a clay catena
Project description:Chronic lung diseases are marked by excessive inflammation and epithelial remodeling. Reduced Clara cell secretory function and corresponding decreases in the abundance of the major Clara cell secreted protein, CCSP, are characteristically seen in these disease states. We sought to define the impact of Clara cell and CCSP depletion on regulation of the lung inflammatory response. We used chemical and genetic mouse models of Clara cell and CCSP deficiency (CCSP-/-) coupled with P. aeruginosa lipopolysaccharide (LPS) elicited inflammation. Exposure of Clara cell depleted or CCSP-/- mice to LPS resulted in augmented inflammation as assessed by polymorphonuclear leukocyte recruitment to the airspace. Gene expression analysis and pathway modeling of the CCSP-/- inflammatory response implicated increased TNF-alpha signaling. Consistent with this model was the demonstration of significantly elevated TNF-alpha in airway fluid of LPS-stimulated CCSP-/- mice compared to similarly exposed wild type mice. Increased LPS-elicited TNF-alpha production was also observed in cultured lung macrophages from CCSP-/- mice compared to wild type mice. We demonstrate that macrophages from Clara cell depleted and CCSP-/- mice displayed increased TLR4 surface expression. Our results provide evidence that Clara cells can attenuate inflammation through regulation of macrophage behavior and suggest that epithelial remodeling leading to reduced Clara cell secretory function is an important factor that increases the intensity of lung inflammation in chronic lung disease.
Project description:We have previously reported a subpopulation of bone marrow cells (BMC) that express Clara cell secretory protein (CCSP), generally felt to be specific to lung Clara cells. Ablation of lung Clara cells has been reported using a transgenic mouse that expresses thymidine kinase under control of the CCSP promoter. Treatment with ganciclovir results in permanent elimination of CCSP(+) cells, failure of airway regeneration, and death. To determine if transtracheal delivery of wild-type bone marrow CCSP(+) cells is beneficial after ablation of lung CCSP(+) cells, transgenic mice were treated with ganciclovir followed by transtracheal administration of CCSP(+) or CCSP(-) BMC. Compared with mice administered CCSP(-) cells, mice treated with CCSP(+) cells had more donor cells lining the airway epithelium, where they expressed epithelial markers including CCSP. Although donor CCSP(+) cells did not substantially repopulate the airway, their administration resulted in increased host ciliated cells, better preservation of airway epithelium, reduction of inflammatory cells, and an increase in animal survival time. Administration of CCSP(+) BMC is beneficial after permanent ablation of lung Clara cells by increasing bronchial epithelial repair. Therefore, CCSP(+) BMC could be important for treatment of lung diseases where airways re-epithelialization is compromised.
Project description:Administration of human subject research is complex, involving not only the institutional review board but also many other regulatory and compliance entities within a research enterprise. Its efficiency has a direct and substantial impact on the conduct and management of clinical research. In this paper, we report on the Clinical Research Administration (CLARA) platform developed at the University of Arkansas for Medical Sciences. CLARA is a comprehensive web-based system that can streamline research administrative tasks such as submissions, reviews, and approval processes for both investigators and different review committees on a single integrated platform. CLARA not only helps investigators to meet regulatory requirements but also provides tools for managing other clinical research activities including budgeting, contracting, and participant schedule planning.
Project description:BackgroundClara cells are the epithelial progenitor cell of the small airways, a location known to be important in many lung disorders. Although migration of alveolar type II and bronchiolar ciliated epithelial cells has been examined, the migratory response of Clara cells has received little attention.MethodsUsing a modification of existing procedures for Clara cell isolation, we examined mouse Clara cells and a mouse Clara-like cell line (C22) for adhesion to and migration toward matrix substrate gradients, to establish the nature and integrin dependence of migration in Clara cells.ResultsWe observed that Clara cells adhere preferentially to fibronectin (Fn) and type I collagen (Col I) similar to previous reports. Migration of Clara cells can be directed by a fixed gradient of matrix substrates (haptotaxis). Migration of the C22 cell line was similar to the Clara cells so integrin dependence of migration was evaluated with this cell line. As determined by competition with an RGD containing-peptide, migration of C22 cells toward Fn and laminin (Lm) 511 (formerly laminin 10) was significantly RGD integrin dependent, but migration toward Col I was RGD integrin independent, suggesting that Clara cells utilize different receptors for these different matrices.ConclusionThus, Clara cells resemble alveolar type II and bronchiolar ciliated epithelial cells by showing integrin mediated pro-migratory changes to extracellular matrix components that are present in tissues after injury.
Project description:Adolescents are notorious for engaging in risky, reward-motivated behavior, and this behavior occurs most often in response to social reward, typically in the form of peer contexts involving intense positive affect. A combination of greater neural and behavioral sensitivity to peer positive affect may characterize adolescents who are especially likely to engage in risky behaviors. To test this hypothesis, we examined 50 adolescents' reciprocal positive affect and neural response to a personally relevant, ecologically valid pleasant stimulus: positive affect expressed by their best friend during a conversation about past and future rewarding mutual experiences. Participants were typically developing community adolescents (age 14-18?years, 48.6% female), and risky behavior was defined as a factor including domains such as substance use, sexual behavior and suicidality. Adolescents who engaged in more real-life risk-taking behavior exhibited either a combination of high reciprocal positive affect behavior and high response in the left ventrolateral prefrontal cortex-a region associated with impulsive sensation-seeking-or the opposite combination. Behavioral and neural sensitivity to peer influence could combine to contribute to pathways from peer influence to risky behavior, with implications for healthy development.
Project description:Chronic lung diseases are marked by excessive inflammation and epithelial remodeling. Reduced Clara cell secretory function and corresponding decreases in the abundance of the major Clara cell secreted protein, CCSP, are characteristically seen in these disease states. We sought to define the impact of Clara cell and CCSP depletion on regulation of the lung inflammatory response. We used chemical and genetic mouse models of Clara cell and CCSP deficiency (CCSP-/-) coupled with P. aeruginosa lipopolysaccharide (LPS) elicited inflammation. Exposure of Clara cell depleted or CCSP-/- mice to LPS resulted in augmented inflammation as assessed by polymorphonuclear leukocyte recruitment to the airspace. Gene expression analysis and pathway modeling of the CCSP-/- inflammatory response implicated increased TNF-alpha signaling. Consistent with this model was the demonstration of significantly elevated TNF-alpha in airway fluid of LPS-stimulated CCSP-/- mice compared to similarly exposed wild type mice. Increased LPS-elicited TNF-alpha production was also observed in cultured lung macrophages from CCSP-/- mice compared to wild type mice. We demonstrate that macrophages from Clara cell depleted and CCSP-/- mice displayed increased TLR4 surface expression. Our results provide evidence that Clara cells can attenuate inflammation through regulation of macrophage behavior and suggest that epithelial remodeling leading to reduced Clara cell secretory function is an important factor that increases the intensity of lung inflammation in chronic lung disease. 24 samples analyzed (total lung RNA from Mus musculus), 12 wild-type and 12 CCSP knock-out, samples were from control or LPS exposed (1.5, 6, and 12 hours post exposure). N = 3 per group, for a total of 12 per genotype.
Project description:BackgroundMeasuring the seroprevalence of antibodies to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is central to understanding infection risk and fatality rates. We studied Coronavirus Disease 2019 (COVID-19)-antibody seroprevalence in a community sample drawn from Santa Clara County.MethodsOn 3 and 4 April 2020, we tested 3328 county residents for immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to SARS-CoV-2 using a rapid lateral-flow assay (Premier Biotech). Participants were recruited using advertisements that were targeted to reach county residents that matched the county population by gender, race/ethnicity and zip code of residence. We estimate weights to match our sample to the county by zip, age, sex and race/ethnicity. We report the weighted and unweighted prevalence of antibodies to SARS-CoV-2. We adjust for test-performance characteristics by combining data from 18 independent test-kit assessments: 14 for specificity and 4 for sensitivity.ResultsThe raw prevalence of antibodies in our sample was 1.5% [exact binomial 95% confidence interval (CI) 1.1-2.0%]. Test-performance specificity in our data was 99.5% (95% CI 99.2-99.7%) and sensitivity was 82.8% (95% CI 76.0-88.4%). The unweighted prevalence adjusted for test-performance characteristics was 1.2% (95% CI 0.7-1.8%). After weighting for population demographics, the prevalence was 2.8% (95% CI 1.3-4.2%), using bootstrap to estimate confidence bounds. These prevalence point estimates imply that 53 000 [95% CI 26 000 to 82 000 using weighted prevalence; 23 000 (95% CI 14 000-35 000) using unweighted prevalence] people were infected in Santa Clara County by late March-many more than the ∼1200 confirmed cases at the time.ConclusionThe estimated prevalence of SARS-CoV-2 antibodies in Santa Clara County implies that COVID-19 was likely more widespread than indicated by the number of cases in late March, 2020. At the time, low-burden contexts such as Santa Clara County were far from herd-immunity thresholds.