CD1a expression in psoriatic skin following treatment with propylthiouracil, an antithyroid thioureylene

BACKGROUND: The antithyroid thioureylenes, propylthiouracil (PTU) and methimazole (MMI), are effective in the treatment of patients with plaque psoriasis. The mechanism of action of the drugs in psoriasis is unknown. Since the drugs reduce circulating IL-12 levels in patients with Graves' hyperthyroidism, the effect of propylthiouracil on CD1a expression in psoriatic lesions was examined in biopsy samples of patients with plaque psoriasis. CD1a is a marker of differentiated skin antigen presenting cells (APC, Langerhans cells). Langerhans cells and skin monocyte/macrophages are the source of IL-12, a key cytokine involved in the events that lead to formation of the psoriatic plaque. METHODS: Biopsy specimens were obtained from six patients with plaque psoriasis who were treated with 300 mg propylthiouracil (PTU) daily for three months. Clinical response to PTU as assessed by PASI scores, histological changes after treatment, and CD1a expression in lesional skin before and after treatment were studied. RESULTS: Despite significant improvement in clinical and histological parameters the expression of CD1a staining cells in the epidermis did not decline with propylthiouracil treatment. CONCLUSIONS: It appears that the beneficial effect of propylthiouracil in psoriasis is mediated by mechanisms other than by depletion of skin antigen-presenting cells

Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis

Background Ultrasound (US) has largely replaced contrast venography as the definitive diagnostic test for deep vein thrombosis (DVT). We aimed to derive a definitive estimate of the diagnostic accuracy of US for clinically suspected DVT and identify study-level factors that might predict accuracy. Methods We undertook a systematic review, meta-analysis and meta-regression of diagnostic cohort studies that compared US to contrast venography in patients with suspected DVT. We searched Medline, EMBASE, CINAHL, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Controlled Trials Register, Database of Reviews of Effectiveness, the ACP Journal Club, and citation lists (1966 to April 2004). Random effects meta-analysis was used to derive pooled estimates of sensitivity and specificity. Random effects meta-regression was used to identify study-level covariates that predicted diagnostic performance. Results We identified 100 cohorts comparing US to venography in patients with suspected DVT. Overall sensitivity for proximal DVT (95% confidence interval) was 94.2% (93.2 to 95.0), for distal DVT was 63.5% (59.8 to 67.0), and specificity was 93.8% (93.1 to 94.4). Duplex US had pooled sensitivity of 96.5% (95.1 to 97.6) for proximal DVT, 71.2% (64.6 to 77.2) for distal DVT and specificity of 94.0% (92.8 to 95.1). Triplex US had pooled sensitivity of 96.4% (94.4 to 97.1%) for proximal DVT, 75.2% (67.7 to 81.6) for distal DVT and specificity of 94.3% (92.5 to 95.8). Compression US alone had pooled sensitivity of 93.8 % (92.0 to 95.3%) for proximal DVT, 56.8% (49.0 to 66.4) for distal DVT and specificity of 97.8% (97.0 to 98.4). Sensitivity was higher in more recently published studies and in cohorts with higher prevalence of DVT and more proximal DVT, and was lower in cohorts that reported interpretation by a radiologist. Specificity was higher in cohorts that excluded patients with previous DVT. No studies were identified that compared repeat US to venography in all patients. Repeat US appears to have a positive yield of 1.3%, with 89% of these being confirmed by venography. Conclusion Combined colour-doppler US techniques have optimal sensitivity, while compression US has optimal specificity for DVT. However, all estimates are subject to substantial unexplained heterogeneity. The role of repeat scanning is very uncertain and based upon limited data

Mapping an atlas of tissue-specific drosophila melanogaster metabolomes by high resolution mass spectrometry

Metabolomics can provide exciting insights into organismal function, but most work on simple models has focussed on the whole organism metabolome, so missing the contributions of individual tissues. Comprehensive metabolite profiles for ten tissues from adult Drosophila melanogaster were obtained here by two chromatographic methods, a hydrophilic interaction (HILIC) method for polar metabolites and a lipid profiling method also based on HILIC, in combination with an Orbitrap Exactive instrument. Two hundred and forty two polar metabolites were putatively identified in the various tissues, and 251 lipids were observed in positive ion mode and 61 in negative ion mode. Although many metabolites were detected in all tissues, every tissue showed characteristically abundant metabolites which could be rationalised against specific tissue functions. For example, the cuticle contained high levels of glutathione, reflecting a role in oxidative defence; the alimentary canal (like vertebrate gut) had high levels of acylcarnitines for fatty acid metabolism, and the head contained high levels of ether lipids. The male accessory gland uniquely contained decarboxylated S-adenosylmethionine. These data thus both provide valuable insights into tissue function, and a reference baseline, compatible with the FlyAtlas.org transcriptomic resource, for further metabolomic analysis of this important model organism, for example in the modelling of human inborn errors of metabolism, aging or metabolic imbalances such as diabetes

Savanna turning into forest: concerted vegetation change at the ecotone between the Amazon and “Cerrado” biomes

In the “Cerrado”–Amazon ecotone in central Brazil, recent studies suggest some encroachment of forest into savanna, but how, where, and why this might be occurring is unclear. To better understand this phenomenon, we assessed changes in the structure and dynamics of tree species in three vegetation types at the “Cerrado”–Amazon ecotone that are potentially susceptible to encroachment: open “cerrado” (OC), typical “cerrado” (TC) and dense woodland (DW). We estimated changes in density, basal area and aboveground biomass of trees with diameter ≥ 10 cm over four inventories carried out between 2008 and 2015 and classified the species according to their preferred habitat (savanna, generalist, or forest). There was an increase in all structural parameters assessed in all vegetation types, with recruitment and gains in basal area and biomass greater than mortality and losses. Thus, there were net gains between the first and final inventories in density (OC: 3.4–22.9%; TC: 1.8–12.6%; DW: 0.2–8.3%), in basal area (OC: 8.3–18.2%; TC: 2–12.7%; DW: 2.3–8.9%), and in biomass (OC: 10.6–16.4%; TC: 1–12%; DW: 5.2–18.7%). Furthermore, all vegetation types also experienced net gains in forest and generalist species relative to savanna species. A decline in recruitment of savanna species was a likely consequence of vegetation encroachment and environmental changes. Our results indicate, for the first time based on quantitative and standardized multi-site temporal data, that concerted structural changes caused by vegetation encroachment are occurring at the ecotone between the two largest biomes in Brazil

Climate and crown damage drive tree mortality in southern Amazonian edge forests

This is the final version. Available on open access from Wiley via the DOI in this recordData availability statement: The data are available as a data package on ForestPlots.net: https://doi.org/10.5521/forestplots.net/2022_1 (Reis et al., 2022). The tree-level data used in Figure 5 are available on request from ForestPlot.net: https://www.forestplots.net/en/join-forestplots/working-with-dataTree death is a key process for our understanding of how forests are and will respond to global change. The extensive forests across the southern Amazonia edge—the driest, warmest and most fragmented of the Amazon regions—provide a window onto what the future of large parts of Amazonia may look like. Understanding tree mortality and its drivers here is essential to anticipate the process across other parts of the basin. Using 10 years of data from a widespread network of long-term forest plots, we assessed how trees die (standing, broken or uprooted) and used generalised mixed-effect models to explore the contribution of plot-, species- and tree-level factors to the likelihood of tree death. Most trees died from stem breakage (54%); a smaller proportion died standing (41%), while very few were uprooted (5%). The mortality rate for standing dead trees was greatest in forests subject to the most intense dry seasons. While trees with the crown more exposed to light were more prone to death from mechanical damage, trees less exposed were more susceptible to death from drought. At the species level, mortality rates were lowest for those species with the greatest wood density. At the individual tree level, physical damage to the crown via branch breakage was the strongest predictor of tree death. Synthesis. Wind- and water deficit-driven disturbances are the main causes of tree death in southern Amazonia edge which is concerning considering the predicted increase in seasonality for Amazonia, especially at the edge. Tree mortality here is greater than any in other Amazonian region, thus any increase in mortality here may represent a tipping point for these forests

Drought generates large, long-term changes in tree and liana regeneration in a monodominant Amazon forest

The long-term dynamics of regeneration in tropical forests dominated by single tree species remains largely undocumented, yet is key to understanding the mechanisms by which one species can gain dominance and resist environmental change. We report here on the long-term regeneration dynamics in a monodominant stand of Brosimum rubescens Taub. (Moraceae) at the southern border of the Amazon forest. Here the climate has warmed and dried since the mid-1990′s. Twenty-one years of tree and liana regeneration were evaluated in four censuses in 30 plots by assessing species abundance, dominance, and diversity in all regeneration classes up to 5 cm diameter. The density of B. rubescens seedlings declined markedly, from 85% in 1997 to 29% in 2018 after the most intense El Niño-driven drought. While the fraction contributed by other tree species changed little, the relative density of liana seedlings increased from just 1 to 54% and three-quarters of liana species underwent a ten-fold or greater increase in abundance. The regeneration community experienced a high rate of species turnover, with changes in the overall richness and species diversity determined principally by lianas, not trees. Long-term maintenance of monodominance in this tropical forest is threatened by a sharp decline in the regeneration of the monodominant species and the increase in liana density, suggesting that monodominance will prove to be a transitory condition. The close association of these rapid changes with drying indicates that monodominant B. rubescens forests are impacted by drought-driven changes in regeneration, and therefore are particularly sensitive to climatic change

Hunting and Shooting:The Ambiguities of ‘Country Sports’

An introduction to sports shooting as an aspect of animal abuse and the criminal, social and environmental harms - direct, indirect and collateral - associated with the field sports shooting industry

A proteogenomic update to Yersinia: enhancing genome annotation

<p>Abstract</p> <p>Background</p> <p>Modern biomedical research depends on a complete and accurate proteome. With the widespread adoption of new sequencing technologies, genome sequences are generated at a near exponential rate, diminishing the time and effort that can be invested in genome annotation. The resulting gene set contains numerous errors in even the most basic form of annotation: the primary structure of the proteins.</p> <p>Results</p> <p>The application of experimental proteomics data to genome annotation, called proteogenomics, can quickly and efficiently discover misannotations, yielding a more accurate and complete genome annotation. We present a comprehensive proteogenomic analysis of the plague bacterium, <it>Yersinia pestis KIM</it>. We discover non-annotated genes, correct protein boundaries, remove spuriously annotated ORFs, and make major advances towards accurate identification of signal peptides. Finally, we apply our data to 21 other <it>Yersinia </it>genomes, correcting and enhancing their annotations.</p> <p>Conclusions</p> <p>In total, 141 gene models were altered and have been updated in RefSeq and Genbank, which can be accessed seamlessly through any NCBI tool (e.g. blast) or downloaded directly. Along with the improved gene models we discover new, more accurate means of identifying signal peptides in proteomics data.</p