228 research outputs found
Susceptibility sets and the final outcome of collective ReedâFrost epidemics
This paper is concerned with exact results for the final outcome of stochastic SIR (susceptible â infective â recovered) epidemics among a closed, finite and homogeneously mixing population. The factorial moments of the number of initial susceptibles who ultimately avoid infection by such an epidemic are shown to be intimately related to the concept of a susceptibility set. This connection leads to simple, probabilistically illuminating proofs of exact results concerning the total size and severity of collective ReedâFrost epidemic processes, in terms of Gontcharoff polynomials, first obtained in a series of papers by Claude Lef`evre and Philippe Picard. The proofs extend easily to include general final state random variables defined on SIR epidemics, and also to multitype epidemics
Revisiting the Effect of Acute P. falciparum Malaria on Epstein-Barr Virus: Host Balance in the Setting of Reduced Malaria Endemicity
Burkitt's lymphoma (BL), an EBV-associated tumour, occurs at high incidence in populations where malaria is holoendemic. Previous studies in one such population suggested that acute P.falciparum infection impairs EBV-specific T-cell surveillance, allowing expansion of EBV infected B-cells from which BL derives. We re-examined the situation in the same area, The Gambia, after a reduction in malaria endemicity. Cellular immune responses to EBV were measured in children with uncomplicated malaria before (day 0) and after treatment (day 28), comparing EBV genome loads in blood and EBV-specific CD8+ T-cell numbers (assayed by MHC Class I tetramers and IFNÎł ELISPOTS) with those seen in age- and sex-matched healthy controls. No significant changes were seen in EBV genome loads, percentage of EBV-specific CD8+ T-cells and IFNÎł producing T-cells in acute versus convalescent samples, nor any difference versus controls. Regression assays performed also no longer detected any impairment of EBV-specific T-cell surveillance. Acute uncomplicated malaria infection no longer alters EBV-specific immune responses in children in The Gambia. Given the recent decline in malaria incidence in that country, we hypothesise that gross disturbance of the EBV-host balance may be a specific effect of acute malaria only in children with a history of chronic/recurrent malaria challenge
Selection of suitable reference genes for quantitative real-time polymerase chain reaction in human meningiomas and arachnoidea
<p>Abstract</p> <p>Findings</p> <p>At first 32 housekeeping genes were analyzed in six randomly chosen meningiomas, brain and dura mater using geNorm, NormFinder, Bestkeeper-1 software and the comparative ÎCt method. Reference genes were ranked according to an integration tool for analyzing reference genes expression based on those four algorithms. Eight highest ranked reference genes (CASC3, EIF2B1, IPO8, MRPL19, PGK1, POP4, PPIA, and RPL37A) plus GAPDH and ACTB were then analyzed in 35 meningiomas, arachnoidea, dura mater and normal brain. NormFinder and Bestkeeper-1 identified RPL37A as the most stable expressed gene in meningiomas and their normal control tissue. NormFinder also determined the best combination of genes: RPL37A and EIF2B1. Commonly used reference genes GAPDH and ACTB were considered least stable genes. The critical influence of reference genes on qPCR data analysis is shown for VEGFA transcription patterns.</p> <p>Background</p> <p>In meningiomas quantitative real-time reverse transcription-polymerase chain reaction (qPCR) is most frequently used for accurate determination of gene expression using various reference genes. Although meningiomas are a heterogeneous group of tissue, no data have been reported to validate reference genes for meningiomas and their control tissues.</p> <p>Conclusions</p> <p>RPL37A is the optimal single reference gene for normalization of gene expression in meningiomas and their control tissues, although the use of the combination of RPL37A and EIF2B1 would provide more stable results.</p
Transgenerational Effects of Stress Exposure on Offspring Phenotypes in Apomictic Dandelion
Heritable epigenetic modulation of gene expression is a candidate mechanism to explain parental environmental effects on offspring phenotypes, but current evidence for environment-induced epigenetic changes that persist in offspring generations is scarce. In apomictic dandelions, exposure to various stresses was previously shown to heritably alter DNA methylation patterns. In this study we explore whether these induced changes are accompanied by heritable effects on offspring phenotypes. We observed effects of parental jasmonic acid treatment on offspring specific leaf area and on offspring interaction with a generalist herbivore; and of parental nutrient stress on offspring root-shoot biomass ratio, tissue P-content and leaf morphology. Some of the effects appeared to enhance offspring ability to cope with the same stresses that their parents experienced. Effects differed between apomictic genotypes and were not always consistently observed between different experiments, especially in the case of parental nutrient stress. While this context-dependency of the effects remains to be further clarified, the total set of results provides evidence for the existence of transgenerational effects in apomictic dandelions. Zebularine treatment affected the within-generation response to nutrient stress, pointing at a role of DNA methylation in phenotypic plasticity to nutrient environments. This study shows that stress exposure in apomictic dandelions can cause transgenerational phenotypic effects, in addition to previously demonstrated transgenerational DNA methylation effects
Prognostic implications of negative dobutamine stress echocardiography in African Americans compared to Caucasians
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
Quantifying the relative roles of selective and neutral processes in defining eukaryotic microbial communities
We have a limited understanding of the relative contributions of different processes that regulate microbial communities, which are crucial components of both natural and agricultural ecosystems. The contributions of selective and neutral processes in defining community composition are often confounded in field studies because as one moves through space, environments also change. Managed ecosystems provide an excellent opportunity to control for this and evaluate the relative strength of these processes by minimising differences between comparable niches separated at different geographic scales. We use next-generation sequencing to characterize the variance in fungal communities inhabiting adjacent fruit, soil and bark in comparable vineyards across 1000âkms in New Zealand. By compartmentalizing community variation, we reveal that niche explains at least four times more community variance than geographic location. We go beyond merely demonstrating that different communities are found in both different niches and locations by quantifying the forces that define these patterns. Overall, selection unsurprisingly predominantly shapes these microbial communities, but we show the balance of neutral processes also have a significant role in defining community assemblage in eukaryotic microbes
PI3K/mTOR is a therapeutically targetable genetic dependency in diffuse intrinsic pontine glioma
Diffuse midline glioma (DMG), including tumors diagnosed in the brainstem (diffuse intrinsic pontine glioma; DIPG), are uniformly fatal brain tumors that lack effective treatment. Analysis of CRISPR/Cas9 loss-of-function gene deletion screens identified PIK3CA and MTOR as targetable molecular dependencies across patient derived models of DIPG, highlighting the therapeutic potential of the blood-brain barrierâpenetrant PI3K/Akt/mTOR inhibitor, paxalisib. At the human-equivalent maximum tolerated dose, mice treated with paxalisib experienced systemic glucose feedback and increased insulin levels commensurate with patients using PI3K inhibitors. To exploit genetic dependence and overcome resistance while maintaining compliance and therapeutic benefit, we combined paxalisib with the antihyperglycemic drug metformin. Metformin restored glucose homeostasis and decreased phosphorylation of the insulin receptor in vivo, a common mechanism of PI3K-inhibitor resistance, extending survival of orthotopic models. DIPG models treated with paxalisib increased calcium-activated PKC signaling. The brain penetrant PKC inhibitor enzastaurin, in combination with paxalisib, synergistically extended the survival of multiple orthotopic patient-derived and immunocompetent syngeneic allograft models; benefits potentiated in combination with metformin and standard-of-care radiotherapy. Therapeutic adaptation was assessed using spatial transcriptomics and ATAC-Seq, identifying changes in myelination and tumor immune microenvironment crosstalk. Collectively, this study has identified what we believe to be a clinically relevant DIPG therapeutic combinational strategy
Role of non-nitric oxide non-prostaglandin endothelium-derived relaxing factor(s) in bradykinin vasodilation
Using role-play to improve studentsâ confidence and perceptions of communication in a simulated volcanic crisis
Traditional teaching of volcanic science typically emphasises scientific
principles and tends to omit the key roles, responsibilities, protocols, and
communication needs that accompany volcanic crises. This chapter
provides a foundation in instructional communication, education, and risk
and crisis communication research that identifies the need for authentic
challenges in higher education to challenge learners and provide
opportunities to practice crisis communication in real-time. We present
an authentic, immersive role-play called the Volcanic Hazards Simulation
that is an example of a teaching resource designed to match professional
competencies. The role-play engages students in volcanic crisis concepts
while simultaneously improving their confidence and perceptions of
communicating science. During the role-play, students assume authentic
roles and responsibilities of professionals and communicate through
interdisciplinary team discussions, media releases, and press conferences.
We characterised and measured the studentsâ confidence and perceptions
of volcanic crisis communication using a mixed methods research design
to determine if the role-play was effective at improving these qualities.
Results showed that there was a statistically significant improvement in
both communication confidence and perceptions of science communication.
The exercise was most effective in transforming low-confidence and
low-perception students, with some negative changes measured for our
higher-learners. Additionally, students reported a comprehensive and
diverse set of best practices but focussed primarily on the mechanics of
science communication delivery. This curriculum is a successful example
of how to improve studentsâ communication confidence and perceptions
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