Assessing present and future suitability of European cities to the Asian Tiger mosquito, a vector of dengue and Zika

The Asian Tiger mosquito (Aedes albopictus) is already established in many countries of Europe and cities are particularly vulnerable to the spread of vector-borne diseases. We evaluated the suitability of 62 large urban areas in Europe to the establishment of this mosquito, based on the level of agreement between published predictions of its potential distribution. We classified levels of suitability and uncertainty according to the number of matching models at a 25 km cell size and retrieved the predominant class within the boundaries of each urban area. We analysed 7 independent predictions for current conditions and 5 for future conditions (2050-2080), as well as changes in classes between the two timeframes. Currently, 60% of the cities are suitable to the mosquito, 8% are unsuitable and 32% show high uncertainty. In the future, 87% will be suitable and none will be unsuitable, including cities in the British Isles and Scandinavia, which will have to adapt their public health policies.publishe

Gut immune dysfunction through impaired innate pattern recognition receptor expression and gut microbiota dysbiosis in chronic SIV infection.

HIV targets the gut mucosa early in infection, causing immune and epithelial barrier dysfunction and disease progression. However, gut mucosal sensing and innate immune signaling through mucosal pattern recognition receptors (PRRs) during HIV infection and disease progression are not well defined. Using the simian immunodeficiency virus (SIV)-infected rhesus macaque model of AIDS, we found a robust increase in PRRs and inflammatory cytokine gene expression during the acute SIV infection in both peripheral blood and gut mucosa, coinciding with viral replication. PRR expression remained elevated in peripheral blood following the transition to chronic SIV infection. In contrast, massive dampening of PRR expression was detected in the gut mucosa, despite the presence of detectable viral loads. Exceptionally, expression of Toll-like receptor 4 (TLR4) and TLR8 was downmodulated and diverged from expression patterns for most other TLRs in the gut. Decreased mucosal PRR expression was associated with increased abundance of several pathogenic bacterial taxa, including Pasteurellaceae members, Aggregatibacter and Actinobacillus, and Mycoplasmataceae family. Early antiretroviral therapy led to viral suppression but only partial maintenance of gut PRRs and cytokine gene expression. In summary, SIV infection dampens mucosal innate immunity through PRR dysregulation and may promote immune activation, gut microbiota changes, and ineffective viral clearance

Heat flow parameters affecting dendrite spacings during unsteady-state solidification of Sn-Pb and Al-Cu alloys

Solidification thermal parameters and dendrite arm spacings have been measured in hypoeutectic Sn-Pb and Al-Cu alloys solidified under unsteady-state heat flow conditions. It was observed that both primary and secondary spacings decreased with increased solute content for Sn-Pb alloys. For Al-Cu alloys, the primary spacing was found to be independent of composition, and secondary spacings decrease as the solute content is increased. The predictive theoretical models for primary spacings existing in the literature did not generate the experimental observations concerning the Sn-Pb and Al-Cu alloys examined in the present study. The theoretical Bouchard-Kirkaldy's (BK's) equation relating secondary spacings with tip growth rate has generated adequately the experimental results for both metallic systems. The insertion of analytical expressions for tip growth rate and cooling rate into the predictive model, or into the resulting experimental equations in order to establish empirical formulas permitting primary and secondary dendritic spacings to be determined as functions of unsteady-state solidification parameters such as melt superheat, type of mold, and transient metal/mold heat-transfer coefficient is proposed.34A4995100

Dose-dependent effects of Allopurinol on human foreskin fibroblast cell and human umbilical vein endothelial cell under hypoxia

Allopurinol, an inhibitor of xanthine oxidase, has been used in clinical trials of patients with cardiovascular and chronic kidney disease. These are two pathologies with extensive links to hypoxia and activation of the transcription factor hypoxia inducible factor (HIF) family. Here we analysed the effects of allopurinol treatment in two different cellular models, and their response to hypoxia. We explored the dose-dependent effect of allopurinol on Human Foreskin Fibroblasts (HFF) and Human Umbilical Vein Endothelial Cells (HUVEC) under hypoxia and normoxia. Under normoxia and hypoxia, high dose allopurinol reduced the accumulation of HIF-1α protein in HFF and HUVEC cells. Allopurinol had only marginal effects on HIF-1α mRNA level in both cellular systems. Interestingly, allopurinol effects over the HIF system were independent of prolyl-hydroxylase activity. Finally, allopurinol treatment reduced angiogenesis traits in HUVEC cells in an in vitro model. Taken together these results indicate that high doses of allopurinol inhibits the HIF system and pro-angiogenic traits in cells

Comparativo de personajes de la historia de la enfermería brasileña

Este artículo es una reflexión sobre la historia de los profesionales que se destacaron en la enfermería. Para ello, la búsqueda se llevó a cabo en algunos personajes que hicieron mucho para la enfermería y la salud en el país. El análisis de las historias de estas enfermeras puesto de manifiesto en hechos común como: la ruptura de paradigmas relacionado con el matrimonio, la formación en instituciones de renombre, la ocupación en puestos de gran importancia, la participación en asociaciones profesionales expresiva, a si como una relación con la formación de calidad. A través de sus biografías, se puede ver que a pesar del contexto político de la época han favorecido la formación de esas enfermeras, mucho esfuerzo y dedicación fueron necesarios para esas trayectorias de éxito, que cooperaron en la consolidación de la enfermería brasileña.This article presents a reflection about the story of outstanding nursing professionals. For this purpose, a survey was conducted among some people who contributed a lot to nursing and health in Brazil. The analysis of these nurses' stories unveiled facts in common: breaking of paradigms relating to marriage, education at renowned institutions, holding of very important jobs, significant membership in professional associations, and quality education. The bios of these nurses reveal that, while the political scenario then existing contributed to their education, unswerving dedication and diligence, were the key for their successful careers and helped consolidate nursing in Brazil.Este artigo trata de uma reflexão sobre a história de profissionais que se destacaram na Enfermagem. Para isso, foi realizada uma pesquisa sobre algumas personagens que muito realizaram pela Enfermagem e pela saúde no país. A análise das histórias dessas enfermeiras revelou fatos em comum, como: o rompimento de paradigmas relacionados ao casamento; a formação em instituições renomadas; a ocupação em cargos de grande importância; a participação expressiva em entidades de classe, assim como uma relação com a formação de qualidade. Através de suas biografias, percebe-se que, apesar de o contexto político da época ter favorecido na formação dessas enfermeiras, muito esforço e dedicação foram necessários para essas trajetórias de sucesso, que colaboraram para a consolidação da Enfermagem brasileira.UNIFESPUNIFESPSciEL

The Significance of the ProtDeform Score for Structure Prediction and Alignment

Background: When a researcher uses a program to align two proteins and gets a score, one of her main concerns is how often the program gives a similar score to pairs that are or are not in the same fold. This issue was analysed in detail recently for the program TM-align with its associated TM-score. It was shown that because the TM-score is length independent, it allows a P-value and a hit probability to be defined depending only on the score. Also, it was found that the TM-scores of gapless alignments closely follow an Extreme Value Distribution (EVD). The program ProtDeform for structural protein alignment was developed recently and is characterised by the ability to propose different transformations of different protein regions. Our goal is to analyse its associated score to allow a researcher to have objective reasons to prefer one aligner over another, and carry out a better interpretation of the output. Results: The study on the ProtDeform score reveals that it is length independent in a wider score range than TM-scores and that PD-scores of gapless (random) alignments also approximately follow an EVD. On the CASP8 predictions, PD-scores and TM-scores, with respect to native structures, are highly correlated (0.95), and show that around a fifth of the predictions have a quality as low as 99.5 % of the random scores. Using the Gold Standard benchmark, ProtDeform has lower probabilities of error than TM-align both at a similar speed. The analysis is extended to homology discrimination showing that, again, ProtDeform offers higher hit probabilities than TM-align. Finally, we suggest using three different P-value

Sialic Acid Glycobiology Unveils Trypanosoma cruzi Trypomastigote Membrane Physiology.

Trypanosoma cruzi, the flagellate protozoan agent of Chagas disease or American trypanosomiasis, is unable to synthesize sialic acids de novo. Mucins and trans-sialidase (TS) are substrate and enzyme, respectively, of the glycobiological system that scavenges sialic acid from the host in a crucial interplay for T. cruzi life cycle. The acquisition of the sialyl residue allows the parasite to avoid lysis by serum factors and to interact with the host cell. A major drawback to studying the sialylation kinetics and turnover of the trypomastigote glycoconjugates is the difficulty to identify and follow the recently acquired sialyl residues. To tackle this issue, we followed an unnatural sugar approach as bioorthogonal chemical reporters, where the use of azidosialyl residues allowed identifying the acquired sugar. Advanced microscopy techniques, together with biochemical methods, were used to study the trypomastigote membrane from its glycobiological perspective. Main sialyl acceptors were identified as mucins by biochemical procedures and protein markers. Together with determining their shedding and turnover rates, we also report that several membrane proteins, including TS and its substrates, both glycosylphosphatidylinositol-anchored proteins, are separately distributed on parasite surface and contained in different and highly stable membrane microdomains. Notably, labeling for α(1,3)Galactosyl residues only partially colocalize with sialylated mucins, indicating that two species of glycosylated mucins do exist, which are segregated at the parasite surface. Moreover, sialylated mucins were included in lipid-raft-domains, whereas TS molecules are not. The location of the surface-anchored TS resulted too far off as to be capable to sialylate mucins, a role played by the shed TS instead. Phosphatidylinositol-phospholipase-C activity is actually not present in trypomastigotes. Therefore, shedding of TS occurs via microvesicles instead of as a fully soluble form

Ruthenium complex containing 1,3-thiazolidine-2-thione inhibits hepatic cancer stem cells by suppressing Akt/mTOR signalling and leading to apoptotic and autophagic cell death

\ua9 2024 The AuthorsHepatic cancer is one of the main causes of cancer-related death worldwide. Cancer stem cells (CSCs) are a unique subset of cancer cells that promote tumour growth, maintenance, and therapeutic resistance, leading to recurrence. In the present work, the ability of a ruthenium complex containing 1,3-thiazolidine-2-thione (RCT), with the chemical formula [Ru(tzdt)(bipy)(dppb)]PF6, to inhibit hepatic CSCs was explored in human hepatocellular carcinoma HepG2 cells. RCT exhibited potent cytotoxicity to solid and haematological cancer cell lines and reduced the clonogenic potential, CD133+ and CD44high cell percentages and tumour spheroid growth of HepG2 cells. RCT also inhibited cell motility, as observed in the wound healing assay and transwell cell migration assay. RCT reduced the levels of Akt1, phospho-Akt (Ser473), phospho-Akt (Thr308), phospho-mTOR (Ser2448), and phospho-S6 (Ser235/Ser236) in HepG2 cells, indicating that interfering with Akt/mTOR signalling is a mechanism of action of RCT. The levels of active caspase-3 and cleaved PARP (Asp214) were increased in RCT-treated HepG2 cells, indicating the induction of apoptotic cell death. In addition, RCT modulated the autophagy markers LC3B and p62/SQSTM1 in HepG2 cells and increased mitophagy in a mt-Keima-transfected mouse embryonic fibroblast (MEF) cell model, and RCT-induced cytotoxicity was partially prevented by autophagy inhibitors. Furthermore, mutant Atg5-/- MEFs and PentaKO HeLa cells (human cervical adenocarcinoma with five autophagy receptor knockouts) were less sensitive to RCT cytotoxicity than their parental cell lines, indicating that RCT induces autophagy-mediated cell death. Taken together, these data indicate that RCT is a novel potential anti-liver cancer drug with a suppressive effect on CSCs