Control of globin gene expression by Kruppel-like factors

Kruppel-like factors (KLFs) are a family of seventeen proteins designated KLF1 to KLF17. KLFs are transcriptional factors that bind GC-rich sequences such as CACCC elements. The DNA binds to KLFs via three carboxyl-terminal Cys-2/His-2 zinc fingers. KLFs control cell differentiation and embryonic development. They are also implicated in a number of cellular functions such as erythropoiesis, proliferation and tissue development. This review will focus primarily on KLFs that are involved in haemoglobin control. These include KLF1, KLF2, KLF3, KLF8 and KLF10. The connection between human KLF1 and elevated foetal haemoglobin was first identified in a study done by Borg et al (2010) on a large Maltese family with Hereditary Persistence of Foetal Haemoglobin (HPFH) where a nonsense mutation in the Erythroid Kruppel-Like Factor 1 gene (KLF1) was identified as the main cause of HPFH. KLF2 is a positive regulator of mouse and human embryonic beta-globin genes and it overlaps with KLF1 in embryonic erythropoiesis. KLF3 and KLF8 expression is driven by KLF1 while together KLF3 and KLF8 participate in the silencing of embyronic globin expression during development. KLF10 expression was also shown to be associated with high foetal haemoglobin levels in beta-thalassaemia patients undergoing hydroxyurea treatment.peer-reviewe

Differential expression of the sphingolipid pathway is associated with sensitivity to the PP2A activator FTY720 in colorectal cancer cell lines

Protein phosphatase 2A (PP2A) is a ubiquitously expressed intracellular serine/threonine phosphatase. Deregulation of PP2A is a common event associated with adenocarcinomas of the colon and rectum. We have previously shown that breast cancer cell lines are sensitive to the PP2A activator FTY720, and that sensitivity is predicted by high Aurora kinase A (AURKA) mRNA expression. In this study, we hypothesized that high relative AURKA expression could predict sensitivity to FTY720-induced apoptosis in colorectal cancer (CRC). The CRC cell lines NCI H716, COLO320DM, DLD-1, SW480, and HT-29 show a high relative AURKA expression as compared to LS411N, T84, HCT116, SW48, and LOVO. Following viability assays, LS411N, T84, HCT116, and SW480 were shown to be sensitive to FTY720, whereas DLD-1 and HT-29 were non-sensitive. Hence, AURKA mRNA expression does not predict sensitivity to FTY720 in CRC cell lines. Differentially expressed genes (DEGs) were obtained by comparing the sensitive CRC cell lines (LS411N and HCT116) against the non-sensitive (HT-29 and DLD-1). We found that 253 genes were significantly altered in expression, and upregulation of CERS4, PPP2R2C, GNAZ, PRKCG, BCL2, MAPK12, and MAPK11 suggests the involvement of the sphingolipid signaling pathway, known to be activated by phosphorylated-FTY720. In conclusion, although AURKA expression did not predict sensitivity to FTY720, it is evident that specific CRC cell lines are sensitive to 5 µM FTY720, potentially because of the differential expression of genes involved in the sphingolipid pathway.peer-reviewe

The role of temperature in shaping Culex acharistus mosquitoes life history traits in its southern limit of distribution (Patagonia-Argentina)

There is substantial evidence showing that temperature have a great impact on insects behavior, phenology and life histories. Because of mosquito global importance as disease vectors, in temperate regions where climatic conditions could be only borderline suitable for mosquito development, there is a growing interest in understanding the effect of temperature shifts on vital statistics to more accurately define how such changes could impact distribution and abundance patterns, as well as disease transmission cycles. We determined the role of ambient temperature under fluctuating conditions in shaping Culex acharistus (Diptera: Culicidae) life history traits, and estimated its development threshold and physiological time, in its southern limit of distribution in the Argentine Patagonia region. Four horizontal life tables were conducted under natural fluctuating temperature range in Esquel city (42°S – 71°W; 563 m a.s.l.), during spring-summer (17°C), summer (15.4°C), summer-autumn (12.7°C) and autumn-winter (5.6°C) seasons. Larvae, pupae and adult traits were recorded. The mean duration of the experiments varied between 28 to ≅100 days for spring-summer and autumn-winter seasons. Only during the cold season experiment pupae experienced the most severe temperatures and freeze-thaw cycles, and failed to reach adult stage. We found that larva and pupa development time, adult emergence time and longevity significantly increased with decreasing temperatures, while larval survival was greatest at an intermediate temperature and decreased toward low and high values. Also, protandry was observed and males emerge 2 days before females across seasons. Temperature development threshold and physiological time estimated for larva + pupa were 5.98°C and 211.24°C-days. Our study contributes to a growing body of knowledge by examining the effect of seasonal changes in temperature on mosquito life history traits. Results obtained here can be applied as useful parameters in the development of population dynamic models, improving current mosquito control strategies in cold-temperate regions.Fil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Miserendino, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Almiron, Walter Ricardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

Diagnosis of beta thalassaemia trait

Haemoglobin (Hb) is chemically best considered as a duplex of globin heterodimers. The main adult haemoglobin (HbA) is composed of two alpha (α) and two beta (β) chains assembled in two αβ dimers (α1β1 and α2β2), while foetal haemoglobin (HbF) is composed of two alpha-gamma (αγ) dimers. Their main function is to transport oxygen from the lungs to tissues, but it also specifically interacts with three other gases, carbon dioxide, carbon monoxide and nitric oxide. [excerpt]peer-reviewe

Determination of potential habitat suitability for the European Otter (Lutra lutra) in geographical sectors of metropolitan France

Après une longue période de régression (de 1930 à 1990), la Loutre d’Europe est aujourd’hui en phase de recolonisation en France. Afin de favoriser sa reconquête, un des objectifs du plan national d’action en faveur de ce mustélidé est de déterminer et localiser les habitats potentiellement favorables à cette espèce. Pour cela, pour chaque sous-secteur hydrographique, nous avons renseigné des facteurs indispensables à la présence de la Loutre : disponibilité et qualité du milieu aquatique et des zones humides, disponibilité de la ressource alimentaire, dérangement humain et caractéristiques générales de l’écosystème (type d’occupation du sol, relief) afin de pouvoir créer un modèle Maxent. D’après ce modèle, 30 % des sous-secteurs de France métropolitaine sont peu favorables à la Loutre, 68 % sont assez favorables à l’implantation de cette espèce et 2 % peuvent être considérés comme très favorables à l’installation de la Loutre d’Europe.After a long period of decline, the European Otter is now in the process of recolonizing the French territory. In order to facilitate its expansion, one of the objectives of the National Action Plan is to define and locate the habitat suitability for this mustelid in France. For each river sub-sector we gathered all available information about the factors (availability and quality of aquatic habitat, availability of food resources, human disturbances and general characteristics of the ecosystem) essential to the presence of the otter in order to create a Maxent model. According to this model, 30 % of the sub-sectors in metropolitan France are unlikely to offer favourable habitats for the Otter, 68 % should contain favourable habitats and 2 % could be considered as very favourable for the settling of European otters

Mosquito (Diptera: Culicidae) larval ecology in natural habitats in the cold temperate Patagonia region of Argentina

Knowledge of immature habitats is an important focus for investigations of mosquito community ecology, and may improve our understanding of how environmental variables increase risk of mosquito-borne diseases by influencing the distributions and abundances of species. In Patagonia region, where climatic and ecological factors could be only borderline suitable for mosquito development, relatively little is known about larval ecology. The present study focuses on associations of environmental conditions in natural aquatic habitats with abundances of mosquito species that have colonized such habitats in Patagonia. We described the mosquito community composition within 26 natural temporary pools, and assessed the general relationships between environmental variables (pH, water temperature, conductivity, salinity, dissolved oxygen, aquatic plant cover and main nutrients) and larval abundances using redundancy analysis (RDA). Additionally, we compiled monthly climate data and vegetation indices for each larval habitat, and estimated the probability of presence for two of the most abundant species, describing through generalized linear models (GLM) the environmental, climatic and landscape variables-probability of occurrence relationships. Seven species belonging to the genera Culex and Aedes were identified, with Culex apicinus, Cx. acharistus and Aedes albifasciatus being the most abundant. Mean larval densities were low (6.8 ± 2.8 larvae/dip), and the highestspecies richness and larval densities were recorded in northern and central areas. Aedes albifasciatus, a species of sanitary importance, was widely distributed, being the only one collected south of the 45th parallel of S latitude. RDA indicated that aquatic conductivity, pH, water depth, dissolved oxygen, ammonia and soluble reactive phosphorous accounted for the main part of the variation in the species composition. According to GLMs, wind speed was thevariable that best described the presence of Ae. albifasciatus, and the probability of finding this species was positively associated with high wind speed values. On the other hand, the EVI vegetation index was the only variable included in the Cx. apicinus model, whereby there was a great probability of presence in arid areas with lower EVI values. Our results enhance our knowledge of larval habitat ecology under the extreme environmental conditions of Patagonia and will guide future efforts to understand how multiple effects can affect mosquito ecology and public health at higher latitudes.Fil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Manzo, Luz Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Epele, Luis Beltran. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Laurito, Magdalena. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; ArgentinaFil: Claverie, Alfredo Ñancuche. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Ludueña Almeida, Francisco. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; ArgentinaFil: Miserendino, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagóica. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Esquel. Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Almiron, Walter Ricardo. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Centro de Investigaciones Entomológicas de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones Biológicas y Tecnológicas. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas, Físicas y Naturales. Instituto de Investigaciones Biológicas y Tecnológicas; Argentin

CIP2A expression is upregulated in triple-negative breast cancer

Introduction: Expression of cancerous inhibitor of protein phosphatase 2A (CIP2A) has been correlated with the clinical aggression and progression of breast cancer. CIP2A inhibits protein phosphatase 2A promoting proliferation and survival. This study aims to compare the transcript and protein expression in triple negative breast cancer (TNBC) and determine the signifìcance of CIP2A localisation using formalin fìxed paraffin embedded (FFPE) breast cancer tissue. Breast cancers with increased CIP2A are potential candidates for novel PP2A activation therapy.peer-reviewe

Structural variability of the macrophytes community as a function of a pluviometric gradient in the province of Chubut

Los mallines son humedales patagónicos con suelos en permanente anegación, en los cuales se pueden generar lagunas con una vasta biodiversidad. En estos ecosistemas, las plantas acuáticas (i.e. macrófitas) se desarrollan y presentan hábitos de vida para adaptarse a las condiciones de humedad, siendo capaces de regular las condiciones fisicoquímicas del agua. Una característica distintiva de la Patagonia es la disminución pluvial en un gradiente oeste-este que genera tres biozonas: bosque, ecotono y estepa. Estas biozonas fueron caracterizadas en base a vegetación terrestre, pero aún no se ha evaluado si los ensambles de macrófitas se corresponden con ellas. El objetivo de este estudio es comparar los atributos de la comunidad de macrófitas acuáticas y de las plantas terrestres asociadas a humedales presentes en las tres biozonas. Durante el verano 2013-2014 se muestrearon 20 lagunas someras de la provincia de Chubut, se analizaron las características físicas y químicas del agua y se registró la riqueza taxonómica de macrófitas. Las macrófitas fueron clasificadas según su origen y hábito, y se calculó su diversidad. Se identificaron 62 taxones, la mayoría pertenecientes a las familias Cyperaceae, Poaceae y Ranunculaceae. Las lagunas esteparias se diferenciaron de las de ecotono y de bosque por poseer pH alcalino y valores elevados de conductividad y de fósforo reactivo soluble (PRS). Los valores altos de PRS favorecieron la abundancia de macrófitas y macroalgas. Sin embargo, las concentraciones elevadas de fósforo total y de clorofila a fitoplanctónica indicaron que tres lagunas estarían eutrofizadas. Las macroalgas fueron más abundantes en los sitios con mayor estado trófico y la cobertura de macrófitas emergentes aumentó en esos sitios. Dado que las lagunas estudiadas funcionarían como reservorios de diversidad de macrófitas acuáticas, conocer la relación comunidad biológica-ambiente sería útil para generar planes tendientes a conservar la biodiversidad de los mallines patagónicos.Mallines are Patagonian wetlands characterized by permanent waterlogging on its soils, sustaining small shallow lakes that hosts a vast biodiversity. In these ecosystems, aquatic plants (i.e. macrophytes) develop different life forms adapted to humid conditions, allowing them to regulate the physical and chemical conditions of the mallín. A distinctive characteristic of Patagonia is the exponential west-east decrease in rainfall, which generates three biozones: forest, ecotone and steppe. These biozones have been typified using landform plants, but whether macrophytes assemblages are related to each biozone or not has not been evaluated yet. The aim of this work is to compare the atributes of the macrophyte and wetlands landform plants community in each biozone. During the 2013-2014 austral Summer, 20 shallow lakes were sampled in the west province of Chubut, assessing macrophyte richness and physical and chemical water variables. Macrophytes were classified according to their life forms, origin, and its diversity was calculated. A total of 62 taxa were determined, most of them corresponding to the Cyperaceae, Poaceae and Ranunculaceae families. The steppe exhibited alkaline pH values, and higher conductivity and soluble reactive phosphorus (SRP) than the ecotone and the forest. High SRP values favored the abundance of macrophytes and macroalgae. However, three sites were eutrophic, exhibiting high chlorophyll a and total phosphorus values. Those sites showed higher abundances of macroalgae and emerging macrophytes. The sampled shallow lakes would act as reservoirs of macrophyte diversity at both local and regional scales. Thus, understanding the relationships among macrophytes and environmental variables could be useful for the mallines biodiversity conservation plans.Fil: Claverie, Alfredo Ñancuche. Universidad Nacional de Tierra del Fuego. Instituto de Ciencias Polares, Recursos Naturales y Ambiente; ArgentinaFil: Epele, Luis Beltran. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Kutschker, Adriana Mabel. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Grech, Marta Gladys. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: Manzo, Luz Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; ArgentinaFil: Miserendino, Maria Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Patagonia Norte. Centro de Investigación Esquel de Montaña y Estepa Patagónica. Universidad Nacional de la Patagonia "San Juan Bosco". Centro de Investigación Esquel de Montaña y Estepa Patagónica; Argentina. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentin

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The challenge of setting restoration targets for macroalgal forests under climate changes

Este artículo contiene 10 páginas, 5 figuras, 1 tabla.The process of site selection and spatial planning has received scarce attention in the scientific literature dealing with marine restoration, suggesting the need to better address how spatial planning tools could guide restoration interventions. In this study, for the first time, the consequences of adopting different restoration targets and criteria on spatial restoration prioritization have been assessed at a regional scale, including the consideration of climate changes. We applied the decision-support tool Marxan, widely used in systematic conservation planning on Mediterranean macroalgal forests. The loss of this habitat has been largely documented, with limited evidences of natural recovery. Spatial priorities were identified under six planning scenarios, considering three main restoration targets to reflect the objectives of the EU Biodiversity Strategy for 2030. Results show that the number of suitable sites for restoration is very limited at basin scale, and targets are only achieved when the recovery of 10% of regressing and extinct macroalgal forests is planned. Increasing targets translates into including unsuitable areas for restoration in Marxan solutions, amplifying the risk of ineffective interventions. Our analysis supports macroalgal forests restoration and provides guiding principles and criteria to strengthen the effectiveness of restoration actions across habitats. The constraints in finding suitable areas for restoration are discussed, and recommendations to guide planning to support future restoration interventions are also included.This study was funded by the EASME–EMFF (Sustainable Blue Economy) Project AFRIMED (http://afrimed-project.eu/, grant agreement N. 789059), supported by the European Community.Peer reviewe