64 research outputs found
Old beacon of hope when nothing else works
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Variação da distribuição espacial das comunidades meiobentónicas dos sedimentos subtidais, sujeitos a diferentes níveis de pressão antropogénica: estuários do Mira e Mondego
Esta apresentação oral Analisa o padrão de distribuição espacial das comunidades subtidais de meiofauna ao longo dos gradientes estuarinos, nomeadamente ao longo dos gradientes de salinidade. Concluindo quea composição trófica das comunidades de nemátodes parecem permitir distinguir o efeito do stress natural do stress antropogénico na variabilidade das comunidades meiobentónicas
Examination of change factor methodologies for climate change impact assessment
Citation: Anandhi, A., Frei, A., Pierson, D. C., Schneiderman, E. M., Zion, M. S., Lounsbury, D., and Matonse, A. H. ( 2011), Examination of change factor methodologies for climate change impact assessment, Water Resour. Res., 47, W03501, doi:10.1029/2010WR009104.A variety of methods are available to estimate values of meteorological variables at future times and at spatial scales that are appropriate for local climate change impact assessment. One commonly used method is Change Factor Methodology (CFM), sometimes referred to as delta change factor methodology. Although more sophisticated methods exist, CFM is still widely applicable and used in impact analysis studies. While there are a number of different ways by which change factors (CFs) can be calculated and used to estimate future climate scenarios, there are no clear guidelines available in the literature to decide which methodologies are most suitable for different applications. In this study several categories of CFM (additive versus multiplicative and single versus multiple) for a number of climate variables are compared and contrasted. The study employs several theoretical case studies, as well as a real example from Cannonsville watershed, which supplies water to New York City, USA. Results show that in cases when the frequency distribution of Global Climate Model (GCM) baseline climate is close to the frequency distribution of observed climate, or when the frequency distribution of GCM future climate is close to the frequency distribution of GCM baseline climate, additive and multiplicative single CFMs provide comparable results. Two options to guide the choice of CFM are suggested. The first option is a detailed methodological analysis for choosing the most appropriate CFM. The second option is a default method for use under circumstances in which a detailed methodological analysis is too cumbersome
Membrane structure and interactions of a short Lycotoxin I anaiogue
Lycotoxin I and Lycotoxin II are natural anti-microbial peptides, that were identified in the venom of the Wolf Spider Lycosa carolinensis. These peptides were found to be potent growth inhibitors for bacteria (Escherichia coli) and yeast (Candida glabrata) at micromolar concentrations. Recently, shortened analogues of Lycol and LycoII have been reported to have decreased haemolytic effects. A shorter Lyco-I analogue studied, Lycol 1-15 (H-IWLTALKFLGKHAAK-NH2), was active only above 10 pm, but was also the least haemolytic. On the basis of these findings, we became interested in obtaining a deeper insight into the membrane activity of LycoI 1-15, as this peptide may represent the first major step for the future development of selective, i.e. non-haemolytic, Lycotoxin-based antibiotics. The interaction of this peptide with liposomes of different composition was studied by microcalorimetry [differential scanning calorimetry (DSC) and isothermal titration calorimetry (ITC)l and CD. The results obtained from the calorimetric and spectroscopic techniques were jointly discussed in an attempt to further understand the interaction of this peptide with model membranes. Copyright (c) 2007 European Peptide Society and John Wiley & Sons, Ltd
Conserving pattern and process in the Southern Ocean: designing a Marine Protected Area for the Prince Edward Islands
South Africa is currently proclaiming a Marine Protected Area (MPA) in the Exclusive Economic Zone (EEZ) of its sub-Antarctic Prince Edward Islands. The objectives of the MPA are to: 1) contribute to a national and global representative system of MPAs, 2) serve as a scientific reference point to inform future management, 3) contribute to the recovery of the Patagonian toothfish (Dissostichus eleginoides), and 4) reduce the bird bycatch of the toothfish fishery, particularly of albatrosses and petrels. This study employs systematic conservation planning methods to delineate a MPA within the EEZ that will conserve biodiversity patterns and processes within sensible management boundaries, while minimizing conflict with the legal toothfish fishery. After collating all available distributional data on species, benthic habitats and ecosystem processes, we used C-Plan software to delineate a MPA with three management zones: four IUCN Category Ia reserves (13% of EEZ); two Conservation Zones (21% of EEZ); and three Category IV reserves (remainder of EEZ). Compromises between conservation target achievement and the area required by the MPA are apparent in the final reserve design. The proposed MPA boundaries are expected to change over time as new data become available and as impacts of climate change become more evident
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Loss of Kat2A Enhances Transcriptional Noise and Depletes Acute Myeloid Leukemia Stem-Like Cells
Acute Myeloid Leukemia (AML) is an aggressive hematological malignancy with abnormal progenitor self-renewal and defective myelo-monocytic differentiation. Its pathogenesis comprises subversion of transcriptional regulation, through mutation and by hijacking normal chromatin regulation. Kat2a is a histone acetyltransferase central to promoter activity that we recently associated with stability of pluripotency networks, and identified as a genetic vulnerability in AML. Through combined chromatin profiling and single-cell transcriptomics, we demonstrate that Kat2a contributes to leukemia propagation through homogeneity of transcriptional programs and preservation of leukemia stem-like cells. Kat2a loss reduces transcriptional bursting frequency in a subset of gene promoters, generating enhanced variability of transcript levels but minimal effects on mean gene expression. Destabilization of target programs shifts cellular equilibrium out of self-renewal towards differentiation. We propose that control of transcriptional variability is central to leukemia stem-like cell propagation, and establish a paradigm exploitable in different tumors and at distinct stages of cancer evolution.This work was funded by a Kay Kendall Leukaemia Fund Intermediate Fellowship (KKL888) and by a Leuka John Goldman Fellowship for Future Science (2017) to C.P.. S.P. is funded through a Cambridge-DBT Lectureship; R.K. was funded by an Isaac Newton Trust (INT) Research Grant and a Wellcome Trust ISSF/INT/University of Cambridge Joint Research Grant to C.P.; S.G. is funded by a Lady Tata Memorial Trust PhD Studentship, a Trinity Henry Barlow Trust Scholarship, and the Cambridge Trust; K.Z. received funding from
AIRC (Italian Association for Cancer Research) and is the current recipient of a European Commission Horizon 2020 Marie Sklodowska Curie Post-Doctoral Fellowship
The thromboxane receptor antagonist NTP42 promotes beneficial adaptation and preserves cardiac function in experimental models of right heart overload
Background: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary artery pressure leading to right ventricular (RV) failure. While current PAH therapies improve patient outlook, they show limited benefit in attenuating RV dysfunction. Recent investigations demonstrated that the thromboxane (TX) A2 receptor (TP) antagonist NTP42 attenuates experimental PAH across key hemodynamic parameters in the lungs and heart. This study aimed to validate the efficacy of NTP42:KVA4, a novel oral formulation of NTP42 in clinical development, in preclinical models of PAH while also, critically, investigating its direct effects on RV dysfunction. Methods: The effects of NTP42:KVA4 were evaluated in the monocrotaline (MCT) and pulmonary artery banding (PAB) models of PAH and RV dysfunction, respectively, and when compared with leading standard-of-care (SOC) PAH drugs. In addition, the expression of the TP, the target for NTP42, was investigated in cardiac tissue from several other related disease models, and from subjects with PAH and dilated cardiomyopathy (DCM). Results: In the MCT-PAH model, NTP42:KVA4 alleviated disease-induced changes in cardiopulmonary hemodynamics, pulmonary vascular remodeling, inflammation, and fibrosis, to a similar or greater extent than the PAH SOCs tested. In the PAB model, NTP42:KVA4 improved RV geometries and contractility, normalized RV stiffness, and significantly increased RV ejection fraction. In both models, NTP42:KVA4 promoted beneficial RV adaptation, decreasing cellular hypertrophy, and increasing vascularization. Notably, elevated expression of the TP target was observed both in RV tissue from these and related disease models, and in clinical RV specimens of PAH and DCM. Conclusion: This study shows that, through antagonism of TP signaling, NTP42:KVA4 attenuates experimental PAH pathophysiology, not only alleviating pulmonary pathologies but also reducing RV remodeling, promoting beneficial hypertrophy, and improving cardiac function. The findings suggest a direct cardioprotective effect for NTP42:KVA4, and its potential to be a disease-modifying therapy in PAH and other cardiac conditions
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