Whole blood microarray analysis of pigs showing extreme phenotypes after a porcine reproductive and respiratory syndrome virus infection

Citation: Schroyen, M., Steibel, J. P., Koltes, J. E., Choi, I., Raney, N. E., Eisley, C., . . . Tuggle, C. K. (2015). Whole blood microarray analysis of pigs showing extreme phenotypes after a porcine reproductive and respiratory syndrome virus infection. Bmc Genomics, 16(1). doi:10.1186/s12864-015-1741-8Background: The presence of variability in the response of pigs to Porcine Reproductive and Respiratory Syndrome virus (PRRSv) infection, and recent demonstration of significant genetic control of such responses, leads us to believe that selection towards more disease resistant pigs could be a valid strategy to reduce its economic impact on the swine industry. To find underlying molecular differences in PRRS susceptible versus more resistant pigs, 100 animals with extremely different growth rates and viremia levels after PRRSv infection were selected from a total of 600 infected pigs. A microarray experiment was conducted on whole blood RNA samples taken at 0, 4 and 7 days post infection (dpi) from these pigs. From these data, we examined associations of gene expression with weight gain and viral load phenotypes. The single nucleotide polymorphism (SNP) marker WUR10000125 (WUR) on the porcine 60 K SNP chip was shown to be associated with viral load and weight gain after PRRSv infection, and so the effect of the WUR10000125 (WUR) genotype on expression in whole blood was also examined. Results: Limited information was obtained through linear modeling of blood gene differential expression (DE) that contrasted pigs with extreme phenotypes, for growth or viral load or between animals with different WUR genotype. However, using network-based approaches, molecular pathway differences between extreme phenotypic classes could be identified. Several gene clusters of interest were found when Weighted Gene Co-expression Network Analysis (WGCNA) was applied to 4dpi contrasted with 0dpi data. The expression pattern of one such cluster of genes correlated with weight gain and WUR genotype, contained numerous immune response genes such as cytokines, chemokines, interferon type I stimulated genes, apoptotic genes and genes regulating complement activation. In addition, Partial Correlation and Information Theory (PCIT) identified differentially hubbed (DH) genes between the phenotypically divergent groups. GO enrichment revealed that the target genes of these DH genes are enriched in adaptive immune pathways. Conclusion: There are molecular differences in blood RNA patterns between pigs with extreme phenotypes or with a different WUR genotype in early responses to PRRSv infection, though they can be quite subtle and more difficult to discover with conventional DE expression analyses. Co-expression analyses such as WGCNA and PCIT can be used to reveal network differences between such extreme response groups. © 2015 Schroyen et al

Nitrogen enrichment alters mycorrhizal allocation at five mesic to semiarid grasslands.

Abstract. Arbuscular mycorrhizal (AM) fungi are integral components of grasslands because most plants are associated with interconnected networks of AM hyphae. Mycorrhizae generally facilitate plant uptake of nutrients from the soil. However, mycorrhizal associations are known to vary in their mutualistic function, and there is currently no metric that links AM functioning with fungal colonization of roots. Mycorrhizal structures differ in their physiological and ecological functioning, so changes in AM allocation to intraradical (inside roots) and extraradical (in soil) structures may signal shifts in mycorrhizal function. We hypothesize that the functional equilibrium model applies to AM fungi and that fertilization should reduce allocation to arbuscules, coils, and extraradical hyphae, the fungal structures that are directly involved in nutrient acquisition and transfer to plants. This study compared AM responses to experimental N enrichment at five grasslands distributed across North America. Samples were collected from replicated N-enriched (and some P-enriched) and control plots throughout the growing season for three years. Intraradical AM structures were measured in over 1400 root samples, extraradical hyphal density was measured in over 590 soil samples, and spore biovolume was analyzed in over 400 soil samples. There were significant site ϫ N interactions for spore biovolume, extraradical hyphae, intraradical hyphae, and vesicles. Nitrogen enrichment strongly decreased AM structures at Cedar Creek, the site with the lowest soil N:P, and it increased AM structures at Konza Prairie, the site with the highest soil N:P. As predicted by the functional equilibrium model, in soils with sufficient P, relative allocation to arbuscules, coils, and extraradical hyphae was generally reduced by N enrichment. Allocation to spores and hyphae was most sensitive to fertilization. At the mesic sites, this response was associated with a shift in the relative abundance of Gigasporaceae within AM fungal communities. This study demonstrates that N enrichment impacts mycorrhizal allocation across a wide range of grassland ecosystems. Such changes are important because they suggest an alteration in mycorrhizal functioning that, in turn, may impact plant community composition and ecosystem function

Symptom Experience and Quality of Life of Women Following Breast Cancer Treatment

Background: Few studies have examined the correlates of breast cancer-related symptoms that persist posttreatment and determined the relationship between symptoms and quality of life (QOL). Methods: A population-based sample of women in the United States with stage 0–II breast cancer (n = 1372) completed a survey including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and the Breast Cancer-Specific Quality of Life Questionnaire. Described are the presence and frequency of 13 symptom scales and their associations with 10 QOL dimensions. Results: All study participants had completed primary treatment (surgery and radiation and/or chemotherapy, if applicable). Mean time from initial surgical treatment to completion of the questionnaire was 7.2 months (range 0.5–14.9 months). Mean number of symptoms reported was 6.8, with the 5 most common symptom scales being systemic therapy side effects (87.7%), fatigue (81.7%), breast symptoms (72.1%), sleep disturbance (57.1%), and arm symptoms (55.6%). Younger age and poorer health status at diagnosis were associated with worse symptoms. Fatigue had the greatest impact on QOL, with significant differences between those with high and low fatigue across 7 QOL dimensions. Sociodemographic, prior health status, clinical, and treatment/diagnostic factors explained only 9%–27% of the variance in QOL outcomes. Adding symptom experience increased the variance explained to 18%–60%. Conclusions: More attention to the reduction and management of disease and treatment-related symptoms could improve QOL among women with breast cancer.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63179/1/jwh.2006.0255.pd

Effect of elevated CO2 on peanut performance in a semi-arid production region

With the intensification and frequency of heat waves and periods of water deficit stress, along with rising atmospheric carbon dioxide [CO2], understanding the seasonal leaf-gas-exchange responses to combined abiotic factors will be important in predicting crop performance in semi-arid production systems. In peanut (Arachis hypogaea L.), the availability of developmental stage physiological data on the response to repeated water deficit stress periods in an elevated [CO2] (EC) environment is limited and necessary to improve crop model predictions. Here, we investigated the effects of season-long EC (650 µmol CO2 m−2 s−1) on the physiology and productivity of peanut in a semi-arid environment. This study was conducted over two-growing seasons using field-based growth chambers to maintain EC conditions, and impose water-stress at three critical developmental stages. Our results showed that relative to ambient [CO2] (AC), long-term EC during water-stress episodes, increased leaf-level light-saturated CO2 assimilation (Asat), transpiration efficiency (TE), vegetative biomass, and pod yield by 58%, 73%, 58%, and 39%, respectively. Although leaf nitrogen content was reduced by 16%, there was 41% increase in maximum Rubisco carboxylation efficiency in EC, indicating that there was minimal photosynthetic down-regulation. Furthermore, long-term EC modified the short-term physiological response (Asat) to rapid changes in [CO2] during the water-stress episodes, generating a much greater change in EC (54%) compared to AC (10%). Additionally, long-term EC generated a 23% greater Asat compared to the short-term EC during the water-stress episodes. These findings indicate high levels of physiological adjustment in EC, which may increase drought resilience. We concluded that EC may reduce the negative impacts of repeated water-stress events at critical developmental stages on rain-fed peanut in semi-arid regions. These results can inform current models to improve the projections of peanut response to future climates

Bodyweight Perceptions among Texas Women: The Effects of Religion, Race/Ethnicity, and Citizenship Status

Despite previous work exploring linkages between religious participation and health, little research has looked at the role of religion in affecting bodyweight perceptions. Using the theoretical model developed by Levin et al. (Sociol Q 36(1):157–173, 1995) on the multidimensionality of religious participation, we develop several hypotheses and test them by using data from the 2004 Survey of Texas Adults. We estimate multinomial logistic regression models to determine the relative risk of women perceiving themselves as overweight. Results indicate that religious attendance lowers risk of women perceiving themselves as very overweight. Citizenship status was an important factor for Latinas, with noncitizens being less likely to see themselves as overweight. We also test interaction effects between religion and race. Religious attendance and prayer have a moderating effect among Latina non-citizens so that among these women, attendance and prayer intensify perceptions of feeling less overweight when compared to their white counterparts. Among African American women, the effect of increased church attendance leads to perceptions of being overweight. Prayer is also a correlate of overweight perceptions but only among African American women. We close with a discussion that highlights key implications from our findings, note study limitations, and several promising avenues for future research

Protocol for a four parallel-arm, single-blind, cluster-randomised trial to assess the effectiveness of three types of dual active ingredient treated nets compared to pyrethroid-only long-lasting insecticidal nets to prevent malaria transmitted by pyrethroid insecticide-resistant vector mosquitoes in Tanzania.

INTRODUCTION: The massive scale-up of long-lasting insecticidal nets (LLINs) has led to major reductions in malaria burden in many sub-Saharan African countries. This progress is threatened by widespread insecticide resistance among malaria vectors. This cluster-randomised controlled trial (c-RCT) compares three of the most promising dual active ingredients LLINs (dual-AI LLINs), which incorporate mixtures of insecticides or insecticide synergists to standard LLINs in an area of pyrethroid insecticide resistance. METHODS: A four-arm, single-blinded, c-RCT will evaluate the effectiveness of three types of dual-AI LLINs (1) Royal Guard, combining two insecticides, pyriproxyfen and the pyrethroid alpha-cypermethrin; (2) Interceptor G2, combining chlorfenapyr and alpha-cypermethrin; (3) Olyset Plus, an LLIN combining a synergist, piperonyl butoxide and the pyrethroid permethrin, compared with; (4) Interceptor LN, a standard LLIN containing the pyrethroid alpha-cypermethrin as the sole AI. The primary outcomes are malaria infection prevalence in children aged 6 months-14 years and entomological inoculation rate (EIR), as a standard measure of malaria transmission at 24 months postintervention and cost-effectiveness. ETHICS AND DISSEMINATION: Ethical approval was received from the institutional review boards of the Tanzanian National Institute for Medical Research, Kilimanjaro Christian Medical University College, London School of Hygiene and Tropical Medicine, and University of Ottawa. Study findings will be actively disseminated via reports and presentations to stakeholders, local community leaders, and relevant national and international policy makers as well as through conferences, and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT03554616

Will a lack of fabric durability be their downfall? Impact of textile durability on the efficacy of three types of dual-active-ingredient long-lasting insecticidal nets: a secondary analysis on malaria prevalence and incidence from a cluster-randomized trial in north-west Tanzania.

BACKGROUND: The Dual-Active Ingredient long-lasting insecticidal nets (Dual-AI LLIN) have been developed to counteract the reduced efficacy of pyrethroid (PY)-only nets due to widespread pyrethroid insecticide resistance in malaria vector mosquitoes. They constitute half of the nets distributed in sub-Saharan Africa between 2022 and 2024. However, their effectiveness once they develop holes is unclear, particularly in pyrethroid-resistant settings. This study evaluates the textile integrity of three dual- AI LLINs compared to standard PY LLN, over 3 years of use in a community in Tanzania and the associated impact on malaria prevalence and incidence. METHODS: A secondary analysis of data from a randomized controlled trial (RCT) in North-western Tanzania was conducted to evaluate the effectiveness of α-cypermethrin only; pyriproxyfen and α-cypermethrin (PPF-PY); chlorfenapyr and α-cypermethrin (chlorfenapyr-PY); and the synergist piperonyl butoxide and permethrin (PBO-PY) LLINs on malaria infection prevalence and case incidence. The association between the net textile condition and 1/malaria prevalence over 3 years of use between 2019 and 2022, and 2/malaria case incidence in a cohort of children over 2 years of follow-up was assessed between 2019 and 2021. RESULTS: There was no significant association between damaged (OR 0.98, 95% CI 0.71-1.37, p-value  = 0.655) and too-torn (OR 1.07, 95% CI 0.77-1.47, p-value = 0.694) compared to intact nets on malaria prevalence for all net types. However, there were reduced rates of malaria case incidence in children sleeping under a net in good condition compared to too-torn nets (incidence rate ratio (IRR) 0.76 [95% CI 0.63-0.92], p = 0.005). Malaria incidence was also consistently lower in too-torn PBO-PY LLIN (IRR = 0.37 [95% CI 0.19-0.72], p = 0.003) and chlorfenapyr-PY LLIN (IRR = 0.45 [95% CI 0.33-0.97], p = 0.053) compared to an intact PY-only LLIN during the first year of follow up. In year 2, the incidence was only significantly lower in intact chlorfenapyr-PY LLIN (IRR = 0.49 [95% CI 0.29-0.81], p = 0.006) compared to intact PY LLIN. CONCLUSION: The study confirmed that sleeping under a chlorfenapyr-PY LLIN or PBO-PY LLIN offered superior protection to pyrethroid-only nets even when torn. Preventing the development of holes is essential as they impact the level of protection offered against malaria infection. TRIAL REGISTRATION: ClinicalTrials.gov, number (NCT03554616)

The Effectiveness of Non-pyrethroid Insecticide-treated Durable Wall Lining to Control Malaria in Rural Tanzania: Study Protocol for a Two-armed Cluster Randomized Trial.

Despite considerable reductions in malaria achieved by scaling-up long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS), maintaining sustained community protection remains operationally challenging. Increasing insecticide resistance also threatens to jeopardize the future of both strategies. Non-pyrethroid insecticide-treated wall lining (ITWL) may represent an alternate or complementary control method and a potential tool to manage insecticide resistance. To date no study has demonstrated whether ITWL can reduce malaria transmission nor provide additional protection beyond the current best practice of universal coverage (UC) of LLINs and prompt case management. A two-arm cluster randomized controlled trial will be conducted in rural Tanzania to assess whether non-pyrethroid ITWL and UC of LLINs provide added protection against malaria infection in children, compared to UC of LLINs alone. Stratified randomization based on malaria prevalence will be used to select 22 village clusters per arm. All 44 clusters will receive LLINs and half will also have ITWL installed on interior house walls. Study children, aged 6 months to 11 years old, will be enrolled from each cluster and followed monthly to estimate cumulative incidence of malaria parasitaemia (primary endpoint), time to first malaria episode and prevalence of anaemia before and after intervention. Entomological inoculation rate will be estimated using indoor CDC light traps and outdoor tent traps followed by detection of Anopheles gambiae species, sporozoite infection, insecticide resistance and blood meal source. ITWL bioefficacy and durability will be monitored using WHO cone bioassays and household surveys, respectively. Social and cultural factors influencing community and household ITWL acceptability will be explored through focus-group discussions and in-depth interviews. Cost-effectiveness, compared between study arms, will be estimated per malaria case averted. This protocol describes the large-scale evaluation of a novel vector control product, designed to overcome some of the known limitations of existing methods. If ITWL is proven to be effective and durable under field conditions, it may warrant consideration for programmatic implementation, particularly in areas with long transmission seasons and where pyrethroid-resistant vectors predominate. Trial findings will provide crucial information for policy makers in Tanzania and other malaria-endemic countries to guide resource allocations for future control efforts

An increasing role of pyrethroid-resistant Anopheles funestus in malaria transmission in the Lake Zone, Tanzania.

Anopheles funestus is playing an increasing role in malaria transmission in parts of sub-Saharan Africa, where An. gambiae s.s. has been effectively controlled by long-lasting insecticidal nets. We investigated vector population bionomics, insecticide resistance and malaria transmission dynamics in 86 study clusters in North-West Tanzania. An. funestus s.l. represented 94.5% (4740/5016) of all vectors and was responsible for the majority of malaria transmission (96.5%), with a sporozoite rate of 3.4% and average monthly entomological inoculation rate (EIR) of 4.57 per house. Micro-geographical heterogeneity in species composition, abundance and transmission was observed across the study district in relation to key ecological differences between northern and southern clusters, with significantly higher densities, proportions and EIR of An. funestus s.l. collected from the South. An. gambiae s.l. (5.5%) density, principally An. arabiensis (81.1%) and An. gambiae s.s. (18.9%), was much lower and closely correlated with seasonal rainfall. Both An. funestus s.l. and An. gambiae s.l. were similarly resistant to alpha-cypermethrin and permethrin. Overexpression of CYP9K1, CYP6P3, CYP6P4 and CYP6M2 and high L1014S-kdr mutation frequency were detected in An. gambiae s.s. populations. Study findings highlight the urgent need for novel vector control tools to tackle persistent malaria transmission in the Lake Region of Tanzania

Randomised controlled trial of school-based humanistic counselling for emotional distress in young people: Feasibility study and preliminary indications of efficacy

The purpose of this study was to test the feasibility of a randomised controlled trial comparing six weeks of humanistic school-based counselling versus waiting list in the reduction of emotional distress in young people, and to obtain initial indications of efficacy. Following a screening procedure, young people (13 - 15 years old) who experienced emotional distress were randomised to either humanistic counselling or waiting list in this multi-site study. Outcomes were assessed using a range of self-report mental health measures, with the emotional symptoms subscale of the Strengths and Difficulties Questionnaire (SDQ) acting as the primary outcome indicator. Recruitment procedures were successful, with 32 young people consenting to participate in the trial and 27 completing endpoint measures. Trial procedures were acceptable to all involved in the research. No significant differences were found between the counselling and waiting list groups in reductions in levels of emotional symptoms (Hedges' g = 0.03), but clients allocated to counselling showed significantly greater improvement in prosocial behaviour (g = 0.89) with an average effect size (g) across the nine outcome measures of 0.25. Participants with higher levels of depressive symptoms showed significantly greater change. This study suggested that a randomised controlled trial of counselling in schools is acceptable and feasible, although initial indications of efficacy are mixed