Rapid progesterone actions on thymulin-secreting epithelial cells cultured from rat thymus

Many soluble factors of neural, endocrine, paracrine and autocrine origin are present in the thymus and modulate its function. Long-term effects of sex steroids have! been documented for thymocytes and cells of the thymic microenvironment. In this report we examine rapid actions of progesterone upon aspects of epithelial cell physiology. Progesterone (0.1-10 mu M) was applied to cultured thymulin-secreting thymic epithelial cells (TS-TEC) and changes in transmembrane potential, transmembrane current, intracellular calcium levels and thymulin secretion were assessed. Rapid changes in electrophysiology and intracellular calcium provide evidence for a membrane-bound progesterone receptor in these cells, in addition to classical cytoplasmic receptors. Application of progesterone to TS-TEC caused electrophysiological changes in 56% of cells (n = 40), activating an inward current (-24 +/- 9 pA at 1 mu M, n = 7, p < 0.02) and dose-dependent depolarization (7.1 +/- 1.8 mV at 1 mu M, n = 19, p < 0.01). Intracellular calcium levels, monitored by the ratiometric fluorescent calcium indicator fura-2, increased within seconds of progesterone (1 mu M) application. Progesterone(1 mu M) increased thymulin levels in supernatant, as measured by ELISA, above the levels in the preapplication period (142 +/- 16% of the preapplication period, n = 3, p < 0.02). This effect was reduced in the presence of cobalt chloride which blocks voltage-dependent calcium channels. In addition, TS-IEC in culture were immunoreactive to antibody AG7. This antibody was raised to a membrane-bound antigen involved in calcium influx subsequent to progesterone binding in sperm. thus we suggest that progesterone acts upon many aspects of TS-TEC physiology through both cytoplasmic and membrane-bound receptors

Newly discovered Ebola virus associated with hemorrhagic fever outbreak in Uganda

In this report we describe a newly discovered ebolavirus species which caused a large hemorrhagic fever outbreak in western Uganda. The virus is genetically distinct, differing by more than 30% at the genome level from all other known ebolavirus species. The unique nature of this virus created challenges for traditional filovirus molecular based diagnostic assays and genome sequencing approaches. Instead, we quickly determined over 70% of the virus genome using a recently developed random-primed pyrosequencing approach that allowed the rapid development of a molecular detection assay that was deployed in the disease outbreak response. This draft sequence allowed easy completion of the whole genome sequence using a traditional primer walking approach and prompt confirmation that this virus represented a new ebolavirus species. Current efforts to design effective diagnostics, antivirals and vaccines will need to take into account the distinct nature of this important new member of the filovirus family

Is health research undertaken where the burden of disease is greatest? Observational study of geographical inequalities in recruitment to research in England 2013–2018

Background: Research is fundamental to high-quality care, but concerns have been raised about whether health research is conducted in the populations most affected by high disease prevalence. Geographical distribution of research activity is important for many reasons. Recruitment is a major barrier to research delivery, and undertaking recruitment in areas of high prevalence could be more efficient. Regional variability exists in risk factors and outcomes, so research done in healthier populations may not generalise. Much applied health research evaluates interventions, and their impact may vary by context (including geography). Finally, fairness dictates that publically funded research should be accessible to all, so that benefits of participating can be fairly distributed. We explored whether recruitment of patients to health research is aligned with disease prevalence in England. Methods: We measured disease prevalence using the Quality and Outcomes Framework in England (total long-term conditions, mental health and diabetes). We measured research activity using data from the NIHR Clinical Research Network. We presented descriptive data on geographical variation in recruitment rates. We explored associations between the recruitment rate and disease prevalence rate. We calculated the share of patient recruitment that would need to be redistributed to align recruitment with prevalence. We assessed whether associations between recruitment rate and disease prevalence varied between conditions, and over time. Results: There was significant geographical variation in recruitment rates. When areas were ranked by disease prevalence, recruitment was not aligned with prevalence, with disproportionately low recruitment in areas with higher prevalence of total long-term and mental health conditions. At the level of 15 local networks, analyses suggested that around 12% of current recruitment activity would need to be redistributed to align with disease prevalence. Overall, alignment showed little change over time, but there was variation in the trends over time in individual conditions. Conclusions: Geographical variations in recruitment do not reflect the suitability of the population for research. Indicators should be developed to assess the fit between research and need, and to allow assessment of interventions among funders, researchers and patients to encourage closer alignment between research activity and burden

Different paths to the modern state in Europe: the interaction between domestic political economy and interstate competition

Theoretical work on state formation and capacity has focused mostly on early modern Europe and on the experience of western European states during this period. While a number of European states monopolized domestic tax collection and achieved gains in state capacity during the early modern era, for others revenues stagnated or even declined, and these variations motivated alternative hypotheses for determinants of fiscal and state capacity. In this study we test the basic hypotheses in the existing literature making use of the large date set we have compiled for all of the leading states across the continent. We find strong empirical support for two prevailing threads in the literature, arguing respectively that interstate wars and changes in economic structure towards an urbanized economy had positive fiscal impact. Regarding the main point of contention in the theoretical literature, whether it was representative or authoritarian political regimes that facilitated the gains in fiscal capacity, we do not find conclusive evidence that one performed better than the other. Instead, the empirical evidence we have gathered lends supports to the hypothesis that when under pressure of war, the fiscal performance of representative regimes was better in the more urbanized-commercial economies and the fiscal performance of authoritarian regimes was better in rural-agrarian economie

Sharing Space: The Presence of Other Bodies Extends the Space Judged as Near

Background: As social animals we share the space with other people. It is known that perceived extension of the peripersonal space (the reaching space) is affected by the implicit representation of our own and other's action potentialities. Our issue concerns whether the co-presence of a body in the scene influences our extrapersonal space (beyond reaching distance) categorization. Methodology/Principal Findings: We investigated, through 3D virtual scenes of a realistic environment, whether egocentric spatial categorization can be influenced by the presence of another human body (Exp. 1) and whether the effect is due to her action potentialities or simply to her human-like morphology (Exp. 2). Subjects were asked to judge the location ("Near" or "Far") of a target object located at different distances from their egocentric perspective. In Exp. 1, the judgment was given either in presence of a virtual avatar (Self-with-Other), or a non-corporeal object (Self-with-Object) or nothing (Self). In Exp. 2, the Self condition was replaced by a Self-with-Dummy condition, in which an inanimate body (a wooden dummy) was present. Mean Judgment Transition Thresholds (JTTs) were calculated for each subject in each experimental condition. Self-with-Other condition induced a significant extension of the space judged as "Near" as compared to both the Selfwith- Object condition and the Self condition. Such extension was observed also in Exp. 2 in the Self-with-Dummy condition. Results suggest that the presence of others impacts on our perception of extrapersonal space. This effect holds also when the other is a human-like wooden dummy, suggesting that structural and morphological shapes resembling human bodies are sufficient conditions for the effect to occur. Conclusions: The observed extension of the portion of space judged as near could represent a wider portion of "accessible" space, thus an advantage in the struggle to survive in presence of other potential competing individuals

U.S. Billion-ton Update: Biomass Supply for a Bioenergy and Bioproducts Industry

The Report, Biomass as Feedstock for a Bioenergy and Bioproducts Industry: The Technical Feasibility of a Billion-Ton Annual Supply (generally referred to as the Billion-Ton Study or 2005 BTS), was an estimate of “potential” biomass within the contiguous United States based on numerous assumptions about current and future inventory and production capacity, availability, and technology. In the 2005 BTS, a strategic analysis was undertaken to determine if U.S. agriculture and forest resources have the capability to potentially produce at least one billion dry tons of biomass annually, in a sustainable manner—enough to displace approximately 30% of the country’s present petroleum consumption. To ensure reasonable confidence in the study results, an effort was made to use relatively conservative assumptions. However, for both agriculture and forestry, the resource potential was not restricted by price. That is, all identified biomass was potentially available, even though some potential feedstock would more than likely be too expensive to actually be economically available. In addition to updating the 2005 study, this report attempts to address a number of its shortcoming

Concordant Gene Expression in Leukemia Cells and Normal Leukocytes Is Associated with Germline cis-SNPs

The degree to which gene expression covaries between different primary tissues within an individual is not well defined. We hypothesized that expression that is concordant across tissues is more likely influenced by genetic variability than gene expression which is discordant between tissues. We quantified expression of 11,873 genes in paired samples of primary leukemia cells and normal leukocytes from 92 patients with acute lymphoblastic leukemia (ALL). Genetic variation at >500,000 single nucleotide polymorphisms (SNPs) was also assessed. The expression of only 176/11,783 (1.5%) genes was correlated (p<0.008, FDR = 25%) in the two tissue types, but expression of a high proportion (20 of these 176 genes) was significantly related to cis-SNP genotypes (adjusted p<0.05). In an independent set of 134 patients with ALL, 14 of these 20 genes were validated as having expression related to cis-SNPs, as were 9 of 20 genes in a second validation set of HapMap cell lines. Genes whose expression was concordant among tissue types were more likely to be associated with germline cis-SNPs than genes with discordant expression in these tissues; genes affected were involved in housekeeping functions (GSTM2, GAPDH and NCOR1) and purine metabolism

A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL)1–3, but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia

Sustainable drainage system site assessment method using urban ecosystem services

The United Kingdom's recently updated approach to sustainable drainage enhanced biodiversity and amenity objectives by incorporating the ecosystem approach and the ecosystem services concept. However, cost-effective and reliable methods to appraise the biodiversity and amenity values of potential sustainable drainage system (SuDS)sites and their surrounding areas are still lacking, as is a method to enable designers to distinguish and link the amenity and biodiversity benefits that SuDS schemes can offer. In this paper, therefore, the authors propose two ecosystem services- and disservices-based methods (i.e. vegetation structure cover-abundance examination and cultural ecosystem services and disservices variables appraisal) to aid SuDS designers to distinguish and link amenity and biodiversity benefits, and allow initial site assessments to be performed in a cost-effective and reliable fashion. Forty-nine representative sites within Greater Manchester were selected to test the two methods. Amenity and biodiversity were successfully assessed and habitat for species, carbon sequestration, recreation and education ecosystem services scores were produced,which will support SuDS retrofit design decision-making. Large vegetated SuDS sites with permanent aquatic features were found to be most capable of enhancing biodiversity- and amenity-related ecosystem services. Habitat for species and recreation ecosystem services were also found to be positively linked to each other. Finally, waste bins on site were found to help reduce dog faeces and litter coverage. Overall, the findings presented here enable future SuDS retrofit designs to be more wildlife friendly and socially inclusive