Updating known distribution models for forecasting climate change impact on endangered species

To plan endangered species conservation and to design adequate management programmes, it is necessary to predict their distributional response to climate change, especially under the current situation of rapid change. However, these predictions are customarily done by relating de novo the distribution of the species with climatic conditions with no regard of previously available knowledge about the factors affecting the species distribution. We propose to take advantage of known species distribution models, but proceeding to update them with the variables yielded by climatic models before projecting them to the future. To exemplify our proposal, the availability of suitable habitat across Spain for the endangered Bonelli’s Eagle (Aquila fasciata) was modelled by updating a pre-existing model based on current climate and topography to a combination of different general circulation models and Special Report on Emissions Scenarios. Our results suggested that the main threat for this endangered species would not be climate change, since all forecasting models show that its distribution will be maintained and increased in mainland Spain for all the XXI century. We remark on the importance of linking conservation biology with distribution modelling by updating existing models, frequently available for endangered species, considering all the known factors conditioning the species’ distribution, instead of building new models that are based on climate change variables only.Ministerio de Ciencia e Innovación and FEDER (project CGL2009-11316/BOS

Nitroheterocyclic drugs cure experimental <i>Trypanosoma cruzi</i> infections more effectively in the chronic stage than in the acute stage

The insect-transmitted protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, and infects 5-8 million people in Latin America. Chagas disease is characterised by an acute phase, which is partially resolved by the immune system, but then develops as a chronic life-long infection. There is a consensus that the front-line drugs benznidazole and nifurtimox are more effective against the acute stage in both clinical and experimental settings. However, confirmative studies have been restricted by difficulties in demonstrating sterile parasitological cure. Here, we describe a systematic study of nitroheterocyclic drug efficacy using highly sensitive bioluminescence imaging of murine infections. Unexpectedly, we find both drugs are more effective at curing chronic infections, judged by treatment duration and therapeutic dose. This was not associated with factors that differentially influence plasma drug concentrations in the two disease stages. We also observed that fexinidazole and fexinidazole sulfone are more effective than benznidazole and nifurtimox as curative treatments, particularly for acute stage infections, most likely as a result of the higher and more prolonged exposure of the sulfone derivative. If these findings are translatable to human patients, they will have important implications for treatment strategies

Sediment geochemistry of streams draining abandoned lead / zinc mines in central Wales: the Afon Twymyn

Purpose Despite the decline of metal mining in the UK during the early 20th century, a substantial legacy of heavy metal contamination persists in river channel and floodplain sediments. Poor sediment quality is likely to impede the achievement of ’good’ chemical and ecological status for surface waters under the European Union Water Framework Directive. This paper examines the environmental legacy of the Dylife lead/zinc mine in the central Wales mining district. Leachable heavy metal concentrations in the bed sediments of the Afon Twymyn are established and the geochemical partitioning, potential mobility and bioavailability of sediment-associated heavy metals are established. Materials and methods Sediment samples were collected from the river bed and dry-sieved into two size fractions (<63 μm and 64–2,000 μm). The fractionated samples were then subjected to a sequential extraction procedure to isolate heavy metals (Pb, Zn, Cu, Cd, Fe, Mn) in three different geochemical phases. Sediment samples were then analysed for heavy metals using ICP-AES. Results and discussion The bed sediment of the Afon Twymyn is grossly polluted with heavy metals. Within the vicinity of the former mine, Pb concentrations are up to 100 times greater than levels reported to have deleterious impacts on aquatic ecology. Most heavy metals exist in the most mobile easily exchangeable and carbonate-bound geochemical phases, potentially posing serious threats to ecological integrity and constituting a significant, secondary, diffuse source of pollution. Metal concentrations decrease sharply downstream of the former mine, although there is a gradual increase in the proportion of readily extractable Zn and Cd. Conclusions Implementation of sediment quality guidelines is important in order to achieve the aims of the Water Framework Directive. Assessments of sediment quality should include measurements of background metal concentrations, river water physico-chemistry and, most importantly, metal mobility and potential bioavailability. Uniformity of sediment guidelines throughout Europe and flexibility of targets with regard to the most heavily contaminated mine sites are recommended

Drug Resistance in Eukaryotic Microorganisms

Eukaryotic microbial pathogens are major contributors to illness and death globally. Although much of their impact can be controlled by drug therapy as with prokaryotic microorganisms, the emergence of drug resistance has threatened these treatment efforts. Here, we discuss the challenges posed by eukaryotic microbial pathogens and how these are similar to, or differ from, the challenges of prokaryotic antibiotic resistance. The therapies used for several major eukaryotic microorganisms are then detailed, and the mechanisms that they have evolved to overcome these therapies are described. The rapid emergence of resistance and the restricted pipeline of new drug therapies pose considerable risks to global health and are particularly acute in the developing world. Nonetheless, we detail how the integration of new technology, biological understanding, epidemiology and evolutionary analysis can help sustain existing therapies, anticipate the emergence of resistance or optimize the deployment of new therapies

Food allergy, airborne allergies, and allergic sensitisation among adolescents living in two disparate socioeconomic regions in Ecuador: A cross-sectional study

Background Allergic diseases are under-investigated and overlooked health conditions in developing countries. We measured the prevalence of food allergy (FA), airborne allergic disease, and allergic sensitisation among adolescents living in 2 socio-demographically disparate regions in Ecuador. We investigated which risk factors are associated with these conditions. Methods A cross-sectional study involved 1338 students (mean age: 13 ± 0.9 years old) living in Cuenca (n = 876) and Santa Isabel (n = 462). History of allergic symptoms (noted by parents or doctor) to food, house dust mites (HDM), pollen, and pets were recorded. Sociodemographic characteristics, environmental exposures, and parental history of allergic disorders data were collected. Sensitisation to 19 food and 20 aeroallergens was measured by skin-prick testing (SPT). FA and airborne allergic diseases (to HDM, pollen, cat, or dog) were defined as a report of allergic symptoms noted by doctor, together with a positive SPT (wheal size ≥3 mm). Logistic regression models were used to identify environmental and parental factors associated with allergic conditions. Results FA was prevalent among 0.4% (95% CI 0.2%–0.9%), and food sensitisation among 19.1% of the adolescents. Shrimp was the most frequent food linked with FA and food sensitisation. Risk factors associated with FA could not be evaluated due to the low prevalence. Food sensitisation was higher among adolescents exposed to family smoking (OR 1.63, 95% CI 1.14–2.34, p = 0.008) and those with parental history of allergic disorders (OR 1.68, 95% CI 1.13–2.49, p = 0.01), but less common among adolescents owning dogs (OR 0.59, 95% CI 0.41–0.84, p = 0.003). Airborne allergic diseases were prevalent amongst 12.0% of the adolescents (95% CI: 10.4–13.9, n = 1321), with HDM as the primary allergen (11.2%). Airborne allergic diseases were less common among adolescents with more siblings (OR 0.79, 95% CI 0.65–0.96, p = 0.02) and those who lived with farm animals in the first year of life (OR 0.47, 95% CI 0.23–0.95, p = 0.04), but, most common among adolescents with a smoking family (OR 1.67, 95% CI 1.04–2.70, p = 0.03) and with a parental history of allergic disorders (OR self-perceived: 2.62, 95% CI 1.46–4.71, p = 0.001; OR diagnosed by a doctor: 4.07, 95% CI 2.44–6.80, p < 0.001). Conclusions FA and airborne allergies are less prevalent in Ecuador than in developed regions; there is a great dissociation between the prevalence of allergic disease and allergic sensitisation. Shrimp and HDM were the most prevalent allergens. Risk factors identified in this study to be related to allergic diseases should be considered by physicians, health practitioners, and epidemiologists in Ecuador

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S

Cyclooxygenase-2 and prostaglandin E<inf>2</inf> signaling through prostaglandin receptor EP- 2 favor the development of myocarditis during acute trypanosoma cruzi infection

Inflammation plays an important role in the pathophysiology of Chagas disease, caused by Trypanosoma cruzi. Prostanoids are regulators of homeostasis and inflammation and are produced mainly by myeloid cells, being cyclooxygenases, COX-1 and COX-2, the key enzymes in their biosynthesis from arachidonic acid (AA). Here, we have investigated the expression of enzymes involved in AA metabolism during T. cruzi infection. Our results show an increase in the expression of several of these enzymes in acute T. cruzi infected heart. Interestingly, COX-2 was expressed by CD68+ myeloid heart-infiltrating cells. In addition, infiltrating myeloid CD11b+Ly6G- cells purified from infected heart tissue express COX-2 and produce prostaglandin E2 (PGE2) ex vivo. T. cruzi infections in COX-2 or PGE2- dependent prostaglandin receptor EP-2 deficient mice indicate that both, COX-2 and EP-2 signaling contribute significantly to the heart leukocyte infiltration and to the release of chemokines and inflammatory cytokines in the heart of T. cruzi infected mice. In conclusion, COX-2 plays a detrimental role in acute Chagas disease myocarditis and points to COX-2 as a potential target for immune intervention.This work was supported by (NG) grants from “Fondo de Investigaciones Sanitarias” (PS09/00538 and PI12/00289); “Universidad Autónoma de Madrid” and “Comunidad de Madrid” (CC08-UAM/SAL-4440/08); by (MF) grants from “Ministerio de Ciencia e Innovación” (SAF2010-17833); “Red de Investigación de Centros de Enfermedades Tropicales” (RICET RD12/0018/0004); European Union (HEALTH-FE-2008-22303, ChagasEpiNet); AECID Cooperation with Argentine (A/025417/09 and A/031735/10), Comunidad de Madrid (S-2010/BMD- 2332) and “Fundación Ramón Areces”. NAG was recipient of a ISCIII Ph.D. fellowship financed by the Spanish “Ministerio de Sanidad”. CCM and HC were recipients of contracts from SAF2010-17833 and PI060388, respectively.Peer Reviewe

p53 Interacts with RNA Polymerase II through Its Core Domain and Impairs Pol II Processivity In Vivo

The tumor suppressor p53 principally functions as a gene-specific transcription factor. p53 triggers a variety of anti-proliferative programs by activating or repressing the transcription of effector genes in response to genotoxic stress. To date, much effort has been placed on understanding p53's ability to affect transcription in the context of its DNA-binding activity. How p53 regulates transcriptional output independent of DNA binding is less well understood. Here we provide evidence that human p53 can physically interact with the large subunit of RNA polymerase II (Pol II) both in in vitro interaction assays and in whole cell extracts, and that this interaction is mediated (at least in part) through p53's core DNA-binding domain and the Ser5-phosphorylated CTD of Pol II. Ectopic expression of p53, combined with mutations in transcription elongation factors or exposure to drugs that inhibit Pol II elongation, elicit sickness or lethality in yeast cells. These phenotypes are suppressed by oncogenic point mutations within p53's core domain. The growth phenotypes raise the possibility that p53 impairs Pol II elongation. Consistent with this, a p53-dependent increase in Pol II density is seen at constitutively expressed genes without a concomitant increase in transcript accumulation. Additionally, p53-expressing yeast strains exhibit reduced transcriptional processivity at an episomal reporter gene; this inhibitory activity is abolished by a core domain point mutation. Our results suggest a novel mechanism by which p53 can regulate gene transcription, and a new biological function for its core domain that is susceptible to inactivation by oncogenic point mutations

Impact of COVID-19 pandemic on asthma symptoms and management: A prospective analysis of asthmatic children in Ecuador

Background Asthma affects up to 33% of children in Latin American settings. The ongoing COVID-19 pandemic has had a significant impact on access to and use of health services. We aimed to evaluate the impact of the COVID-19 lockdown on asthma exacerbations, medical facility visits, and use of asthma medications in children. Methods We used data from a prospective cohort of 213 children aged 5–17 years in 3 Ecuadorian cities and analysed the impact of the COVID-19 lockdown on asthma. Outcomes (asthma exacerbations, emergency room [ER] visits, planned and unplanned outpatient visits, and use of inhaled corticosteroids and Beta-2 agonists) were analysed using repeated Poisson counts (ie, number of events per participant before and during the COVID-19 lockdown). Results During compared to before lockdown: a) the number of asthma exacerbations remained constant (IRR, 0.87; 95% CI: 0.72–1.05; p = 0.152); b) outpatient visits (IRR 0.26, 95% CI 0.14–0.47, p < 0.001) declined 74% while ER visits declined 89% (IRR 0.11, 95% CI 0.04–0.32, p < 0.001); and c) there was no change in inhaled corticosteroids use (IRR 1.03, 95% CI 0.90–1.16, P = 0.699) while Beta-2 agonist use increased (IRR 1.32, 95% CI 1.10–1.58, P = 0.003). Conclusions In a cohort of Ecuadorian children with asthma, health services attendance decreased dramatically after COVID-19 lockdown, but asthma exacerbations and use of inhaled corticosteroids were unchanged. Future analyses will address the question of the effect of SARS-CoV-2 infection on asthma exacerbations and control in this paediatric population