Influence of monolayer, spheroid, and tumor growth conditions on chromosome 3 gene expression in tumorigenic epithelial ovarian cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Expression microarray analyses of epithelial ovarian cancer (EOC) cell lines may be exploited to elucidate genetic and epigenetic events important in this disease. A possible variable is the influence of growth conditions on discerning candidates. The present study examined the influence of growth conditions on the expression of chromosome 3 genes in the tumorigenic EOC cell lines, OV-90, TOV-21G and TOV-112D using Affymetrix GeneChip^®HG-U133A expression microarray analysis.</p> <p>Methods</p> <p>Chromosome 3 gene expression profiles (n = 1147 probe sets, representing 735 genes) were extracted from U133A expression microarray analyses of the EOC cell lines OV-90, TOV-21G and TOV-112D that were grown as monolayers, spheroids or nude mouse xenografts and monolayers derived from these tumors. Hierarchical cluster analysis was performed to compare chromosome 3 transcriptome patterns of each growth condition. Differentially expressed genes were identified and characterized by two-way comparative analyses of fold-differences in gene expression between monolayer cultures and each of the other growth conditions, and between the maximum and minimum values of expression of all growth conditions for each EOC cell line.</p> <p>Results</p> <p>An overall high degree of similarity (> 90%) in gene expression was observed when expression values of alternative growth conditions were compared within each EOC cell line group. Two-way comparative analysis of each EOC cell line grown in an alternative condition relative to the monolayer culture showed that overall less than 15% of probe sets exhibited at least a 3-fold difference in expression profile. Less than 23% of probe sets exhibited greater than 3-fold differences in gene expression in comparisons of the maximum and minimum value of expression of all growth conditions within each EOC cell line group. The majority of these differences were less than 5-fold. There were 17 genes in common which were differentially expressed in all EOC cell lines. However, the patterns of expression of these genes were not necessarily the same for each growth condition when one cell line was compared with another.</p> <p>Conclusion</p> <p>The various alternative <it>in vivo </it>and <it>in vitro </it>growth conditions of tumorigenic EOC cell lines appeared to modestly influence the global chromosome 3 transcriptome supporting the notion that the <it>in vitro </it>cell line models are a viable option for testing gene candidates.</p

Temporal Dynamics of Host Molecular Responses Differentiate Symptomatic and Asymptomatic Influenza A Infection

Exposure to influenza viruses is necessary, but not sufficient, for healthy human hosts to develop symptomatic illness. The host response is an important determinant of disease progression. In order to delineate host molecular responses that differentiate symptomatic and asymptomatic Influenza A infection, we inoculated 17 healthy adults with live influenza (H3N2/Wisconsin) and examined changes in host peripheral blood gene expression at 16 timepoints over 132 hours. Here we present distinct transcriptional dynamics of host responses unique to asymptomatic and symptomatic infections. We show that symptomatic hosts invoke, simultaneously, multiple pattern recognition receptors-mediated antiviral and inflammatory responses that may relate to virus-induced oxidative stress. In contrast, asymptomatic subjects tightly regulate these responses and exhibit elevated expression of genes that function in antioxidant responses and cell-mediated responses. We reveal an ab initio molecular signature that strongly correlates to symptomatic clinical disease and biomarkers whose expression patterns best discriminate early from late phases of infection. Our results establish a temporal pattern of host molecular responses that differentiates symptomatic from asymptomatic infections and reveals an asymptomatic host-unique non-passive response signature, suggesting novel putative molecular targets for both prognostic assessment and ameliorative therapeutic intervention in seasonal and pandemic influenza

The architecture and effect of participation: a systematic review of community participation for communicable disease control and elimination. Implications for malaria elimination

Community engagement and participation has played a critical role in successful disease control and elimination campaigns in many countries. Despite this, its benefits for malaria control and elimination are yet to be fully realized. This may be due to a limited understanding of the influences on participation in developing countries as well as inadequate investment in infrastructure and resources to support sustainable community participation. This paper reports the findings of an atypical systematic review of 60 years of literature in order to arrive at a more comprehensive awareness of the constructs of participation for communicable disease control and elimination and provide guidance for the current malaria elimination campaign.Evidence derived from quantitative research was considered both independently and collectively with qualitative research papers and case reports. All papers included in the review were systematically coded using a pre-determined qualitative coding matrix that identified influences on community participation at the individual, household, community and government/civil society levels. Colour coding was also carried out to reflect the key primary health care period in which community participation programmes originated. These processes allowed exhaustive content analysis and synthesis of data in an attempt to realize conceptual development beyond that able to be achieved by individual empirical studies or case reports.Of the 60 papers meeting the selection criteria, only four studies attempted to determine the effect of community participation on disease transmission. Due to inherent differences in their design, interventions and outcome measures, results could not be compared. However, these studies showed statistically significant reductions in disease incidence or prevalence using various forms of community participation. The use of locally selected volunteers provided with adequate training, supervision and resources are common and important elements of the success of the interventions in these studies. In addition, qualitative synthesis of all 60 papers elucidates the complex architecture of community participation for communicable disease control and elimination which is presented herein.The current global malaria elimination campaign calls for a health systems strengthening approach to provide an enabling environment for programmes in developing countries. In order to realize the benefits of this approach it is vital to provide adequate investment in the 'people' component of health systems and understand the multi-level factors that influence their participation. The challenges of strengthening this component of health systems are discussed, as is the importance of ensuring that current global malaria elimination efforts do not derail renewed momentum towards the comprehensive primary health care approach. It is recommended that the application of the results of this systematic review be considered for other diseases of poverty in order to harmonize efforts at building 'competent communities' for communicable disease control and optimising health system effectiveness

Dynamics of early juvenile winter flounder predation risk on a North West Atlantic estuarine nursery ground

In an effort to determine the characteristics of estuarine habitats suitable for early juvenile winter flounder Pseudopleuronectes americanus survivorship, we examined piscivorous fish distributions and diets, and flounder predation risk along estuarine gradients in the Navesink River/Sandy Hook Bay estuarine system, New Jersey, USA. Demersal fish, striped searobin Prionotus evolans and summer flounder Paralichthys dentatus, were more important predators of winter flounder than pelagic fish (Pomatomus saltatrix, Cynoscion regalis, Morone saxatilis) based on diet analysis of 4 yr of gill (1998 and 1999) and trammel net (2001 and 2002) fish collections. From April through June newly settled winter flounder \u3c20 mm standard length (SL) were eaten by striped searobin that were common in habitats with salinities ≥ 20‰. Fish \u3e20 mm standard length (SL) were consumed by summer flounder in shallow habitats in June and July. In May and June tethering experiments, Age-0 winter flounder predation risk was high in habitats with salinities \u3e19‰ and temperatures \u3e20°C. In 3 yr, salinities were \u3c20‰ in the upstream reach of estuary which probably served as a predator refuge for settling flounder. During 2002, however, historically low freshwater discharge associated with a spring drought produced high salinities ≥20‰ in upstream habitats where searobins ate large numbers of settling winter flounder and predation risk was high. These results suggest that the volume of estuarine habitat suitable for early juvenile flounder survivorship is determined, in part, by predator and prey responses to spatially dynamic physico-chemical gradients. Because gradient dynamics are controlled by climate forcing, climate variation may cause nursery habitat volumes to contract or expand resulting in variation in the local production of Age-0 recruits

Shallow water predation risk for a juvenile flatfish (winter flounder; Pseudopleuronectes americanus, Walbaum) in a northwest Atlantic estuary

Many small fish, including several juvenile Atlantic flatfish, are most abundant in shallow areas presumable because these habitats enhance survivorship and/or growth. In this study, we investigated size-dependent depth distributions and the role of shallow habitats as predator refuges for age-0 winter flounder (Pseudopleuronectes americanus) in a northwest Atlantic estuarine nursery. Analysis of trawl surveys performed during the larval settlement period throughout the Navesink River and Sandy Hook Bay, New Jersey, showed that as fish increased in size, depth of occurrence gradually decreased, so that individuals \u3e35 mm standard length (SL) were concentrated in habitats ∼1 m deep. Tethering in structurally simple and adjacent shallow and deep habitats showed that predation risk for flounder (30–50 mm SL) was low in shallow water (\u3c1 m) and increased rapidly with depth. Summer flounder (Paralychthys dentatus), which were more abundant in trammel nets in deep habitats and included winter flounder in their diets, appeared to be important consumers of tethered fish. Our results indicate that following larval settlement, winter flounder emigrate from or suffer high mortality in deeper water to become concentrated in shallow habitats that can serve as predator refuges even when they lack complex physical structures. These results highlight the potential for functional habitat loss when natural and/or anthropogenic factors make shallow habitats unavailable to young fish

Uncertainty quantification of density and stratification estimates with implications for predicting ocean dynamics

We present a statistical method for reconstructing continuous background density profiles that embeds incomplete measurements and a physically intuitive density stratification model within a Bayesian hierarchal framework. A double hyperbolic tangent function is used as a parametric density stratification model that captures various pycnocline structures in the upper ocean and offers insight into several density profile characteristics (e.g., pycnocline depth). The posterior distribution is used to quantify uncertainty and is estimated using recent advances in Markov chain Monte Carlo sampling. Temporally evolving posterior distributions of density profile characteristics, isopycnal heights, and nonlinear ocean process models for internal gravity waves are presented as examples of how uncertainty propagates through models dependent on the density stratification. The results show 0.95 posterior interval widths that ranged from 2.5% to 4% of the expected values for the linear internal wave phase speed and 15%–40% for the nonlinear internal wave steepening parameter. The data, collected over a year from a through-the-column mooring, and code, implemented in the software package Stan, accompany the article