Comparative study of gp130 cytokine effects on corticotroph AtT-20 cells - Redundancy or specificity of neuroimmunoendocrine modulators?

Objective: This comparative in vitro study examined the effects of all known gp130 cytokines on murine corticotroph AtT-20 cell function. Methods: Cytokines were tested at equimolar concentrations from 0.078 to 10 nM. Tyrosine phosphorylation of the signal transducer and activator of transcription ( STAT) 3 and STAT1, the STAT-dependent suppressor of cytokine signaling (SOCS)-3 promoter activity, SOCS-3 gene expression, STAT-dependent POMC promoter activity and adrenocorticotropic hormone ( ACTH) secretion were determined. Results: Leukemia inhibitory factor (LIF), human oncostatin M (OSM) and cardiotrophin (CT)-1 (LIFR/gp130 ligands), as well as ciliary neurotrophic factor ( CNTF) and novel neurotrophin1/B-cell stimulating factor-3 (CNTFRalpha/LIFR/gp130 ligands) are potent stimuli of corticotroph cells in vitro. In comparison, interleukin (IL)-6 (IL-6R/gp130 ligand) and IL-11 (IL-11R/gp130 ligand) exhibited only modest direct effects on corticotrophs, while murine OSM (OSMR/gp130 ligand) showed no effect. Conclusion: (i) CNTFR complex ligands are potent stimuli of corticotroph function, comparable to LIFR complex ligands; (ii) IL-6 and IL-11 are relatively weak direct stimuli of corticotroph function; (iii) differential effects of human and murine OSM suggest that LIFR/gp130 (OSMR type I) but not OSMR/gp130 (OSMR type II) are involved in corticotroph signaling. (iv) CT-1 has the hitherto unknown ability to stimulate corticotroph function, and (v) despite redundant immuno-neuroendocrine effects of different gp130 cytokines, corticotroph cells are preferably activated through the LIFR and CNTFR complexes. Copyright (C) 2004 S. Karger AG, Basel

Assessing the reliability of species distribution projections in climate change research

Aim: Forecasting changes in species distribution under future scenarios is one of the most prolific areas of application for species distribution models (SDMs). However, no consensus yet exists on the reliability of such models for drawing conclusions on species’ distribution response to changing climate. In this study, we provide an overview of common modelling practices in the field and assess the reliability of model predictions using a virtual species approach. Location: Global. Methods: We first review papers published between 2015 and 2019. Then, we use a virtual species approach and three commonly applied SDM algorithms (GLM, MaxEnt and random forest) to assess the estimated and actual predictive performance of models parameterized with different modelling settings and violations of modelling assumptions. Results: Most SDM papers relied on single models (65%) and small samples (N < 50, 62%), used presence-only data (85%), binarized models' output (74%) and used a split-sample validation (94%). Our simulation reveals that the split-sample validation tends to be over-optimistic compared to the real performance, whereas spatial block validation provides a more honest estimate, except when datasets are environmentally biased. The binarization of predicted probabilities of presence reduces models’ predictive ability considerably. Sample size is one of the main predictors of the real model accuracy, but has little influence on estimated accuracy. Finally, the inclusion of ecologically irrelevant predictors and the violation of modelling assumptions increases estimated accuracy but decreases real accuracy of model projections, leading to biased estimates of range contraction and expansion. Main conclusions: Our ability to predict future species distribution is low on average, particularly when models’ predictions are binarized. A robust validation by spatially independent samples is required, but does not rule out inflation of model accuracy by assumption violation. Our findings call for caution in the application and interpretation of SDM projections under different climates

Surfactant administration in premature infants with RDS

Background. The significant advancement in the treatment of respiratory distress syndrome can be attributed to prenatal identification of high risk pregnancies, prevention of illness through antenatal care, prenatal administration of glucocorticoids, advancement in respiratory support and surfactant therapy. These measures resulted in the reduction of mortality and morbidity rates in preterm infants. Patients and methods. We analyzed data of 78 preterm babies with respiratory distress syndrome hospitalized in the NICU of the Pediatric Clinic, KCU Sarajevo. All children included in the study were mechanically ventilated and treated with one or more doses of bovine surfactant (Survanta) as rescue therapy. Surfactant was given to children with clinical and radiological signs of RDS, who required FiO2>0,40. We used the standard procedure of giving surfactant therapy to intubated children in sterile conditions, after we confirmed, by X-ray, correct tube placement. Results. We investigated the clinical efficacy of surfactant in relation to time of administration, O2 requirement and necessity of one or more doses of surfactant. We found that early treatment with surfactant replacement- within 6 hours of birth- is more effective, and resulted in a significant reduction of mortality rate (p<0,01). Treatment with multiple doses is more effective in comparison to one dose, although there was not a significant difference (p<0,20) between the treated groups. There is a significant difference (p<0,01) between groups related to O2 requirement. In the group of babies which required 60% or more O2 concentration in inhaled air at the time of surfactant replacement, mortality rate was significantly higher (p<0,01). Conclusion. Our study confirmed the benefits of surfactant therapy in preterm babies with respiratory distress syndrome. We confirmed the advantages of early treatment vs. late treatment, but we could not confirm the obvious advantage of multiple over single doses. So, a reasonable recommendation is to treat the infants as soon as clinical signs of developing respiratory distress appear with an individual dose for each infant

Surfactant administration in premature infants with RDS

Background. The significant advancement in the treatment of respiratory distress syndrome can be attributed to prenatal identification of high risk pregnancies, prevention of illness through antenatal care, prenatal administration of glucocorticoids, advancement in respiratory support and surfactant therapy. These measures resulted in the reduction of mortality and morbidity rates in preterm infants. Patients and methods. We analyzed data of 78 preterm babies with respiratory distress syndrome hospitalized in the NICU of the Pediatric Clinic, KCU Sarajevo. All children included in the study were mechanically ventilated and treated with one or more doses of bovine surfactant (Survanta) as rescue therapy. Surfactant was given to children with clinical and radiological signs of RDS, who required FiO2>0,40. We used the standard procedure of giving surfactant therapy to intubated children in sterile conditions, after we confirmed, by X-ray, correct tube placement. Results. We investigated the clinical efficacy of surfactant in relation to time of administration, O2 requirement and necessity of one or more doses of surfactant. We found that early treatment with surfactant replacement- within 6 hours of birth- is more effective, and resulted in a significant reduction of mortality rate (p<0,01). Treatment with multiple doses is more effective in comparison to one dose, although there was not a significant difference (p<0,20) between the treated groups. There is a significant difference (p<0,01) between groups related to O2 requirement. In the group of babies which required 60% or more O2 concentration in inhaled air at the time of surfactant replacement, mortality rate was significantly higher (p<0,01). Conclusion. Our study confirmed the benefits of surfactant therapy in preterm babies with respiratory distress syndrome. We confirmed the advantages of early treatment vs. late treatment, but we could not confirm the obvious advantage of multiple over single doses. So, a reasonable recommendation is to treat the infants as soon as clinical signs of developing respiratory distress appear with an individual dose for each infant

Surface Display of Small Affinity Proteins on <i>Synechocystis</i> sp Strain PCC 6803 Mediated by Fusion to the Major Type IV Pilin PilA1

Cyanobacteria are gaining interest for their potential as autotrophic cell factories. Development of efficient surface display strategies could improve their suitability for large-scale applications by providing options for designed microbial consortia, cell immobilization, and biomass harvesting. Here, surface display of small affinity proteins was realized by fusing them to the major subunit of the native type IV pili in Synechocystis sp. strain PCC 6803. The display of complementary affinity proteins allowed specific cell-cell binding between Synechocystis and Escherichia coli or Staphylococcus carnosus . Additionally, successful tagging of the putative pilin PilA4 helped determine its localization to the type IV pili. Analogous tagging of the S-layer protein shed light on the regions involved in its secretion and surface anchoring. </jats:p

Applying habitat and population-density models to land-cover time series to inform IUCN Red List assessments

The IUCN (International Union for Conservation of Nature) Red List categories and criteria are the most widely used framework for assessing the relative extinction risk of species. The criteria are based on quantitative thresholds relating to the size, trends, and structure of species’ distributions and populations. However, data on these parameters are sparse and uncertain for many species and unavailable for others, potentially leading to their misclassification or classification as data deficient. We devised an approach that combines data on land-cover change, species-specific habitat preferences, population abundance, and dispersal distance to estimate key parameters (extent of occurrence, maximum area of occupancy, population size and trend, and degree of fragmentation) and hence predict IUCN Red List categories for species. We applied our approach to nonpelagic birds and terrestrial mammals globally (∼15,000 species). The predicted categories were fairly consistent with published IUCN Red List assessments, but more optimistic overall. We predicted 4.2% of species (467 birds and 143 mammals) to be more threatened than currently assessed and 20.2% of data deficient species (10 birds and 114 mammals) to be at risk of extinction. Incorporating the habitat fragmentation subcriterion reduced these predictions 1.5–2.3% and 6.4–14.9% (depending on the quantitative definition of fragmentation) for threatened and data deficient species, respectively, highlighting the need for improved guidance for IUCN Red List assessors on the application of this aspect of the IUCN Red List criteria. Our approach complements traditional methods of estimating parameters for IUCN Red List assessments. Furthermore, it readily provides an early-warning system to identify species potentially warranting changes in their extinction-risk category based on periodic updates of land-cover information. Given our method relies on optimistic assumptions about species distribution and abundance, all species predicted to be more at risk than currently evaluated should be prioritized for reassessment

Large carnivore expansion in Europe is associated with human population density and land cover changes

Aim: The recent recovery of large carnivores in Europe has been explained as resulting from a decrease in human persecution driven by widespread rural land abandonment, paralleled by forest cover increase and the consequent increase in availability of shelter and prey. We investigated whether land cover and human population density changes are related to the relative probability of occurrence of three European large carnivores: the grey wolf (Canis lupus), the Eurasian lynx (Lynx lynx) and the brown bear (Ursus arctos). Location: Europe, west of 64° longitude. Methods: We fitted multi-temporal species distribution models using &gt;50,000 occurrence points with time series of land cover, landscape configuration, protected areas, hunting regulations and human population density covering a 24-year period (1992–2015). Within the temporal window considered, we then predicted changes in habitat suitability for large carnivores throughout Europe. Results: Between 1992 and 2015, the habitat suitability for the three species increased in Eastern Europe, the Balkans, North-West Iberian Peninsula and Northern Scandinavia, but showed mixed trends in Western and Southern Europe. These trends were primarily associated with increases in forest cover and decreases in human population density, and, additionally, with decreases in the cover of mosaics of cropland and natural vegetation. Main conclusions: Recent land cover and human population changes appear to have altered the habitat suitability pattern for large carnivores in Europe, whereas protection level did not play a role. While projected changes largely match the observed recovery of large carnivore populations, we found mismatches with the recent expansion of wolves in Central and Southern Europe, where factors not included in our models may have played a dominant role. This suggests that large carnivores’ co-existence with humans in European landscapes is not limited by habitat availability, but other factors such as favourable human tolerance and policy

Cápsula endoscópica e estudos imagiológicos contrastados: diferentes perspectivas para uma imagem mais completa do intestino delgado

Small bowel evaluation is a challenging task and has been revolutionized by high-quality contrasted sectional imaging (CT enterography - CTE) and magnetic resonance enterography (MRE) as well as by small bowel capsule endoscopy (SBCE).The decision of which technique to employ during the investigation of small bowel diseases is not always simple or straightforward. Moreover, contraindications may preclude the use of these techniques in some patients, and although they are noninvasive procedures, may present with various complications. SBCE plays a crucial role in the investigation of both obscure gastrointestinal bleeding and Crohn's disease, but it is also useful for surveillance of patients with Peutz-Jeghers syndrome, while CTE is very accurate in small bowel tumours and in established Crohn's Disease, and its use in patients presenting with gastrointestinal bleeding is increasing. MRE, an expensive and not widely available technique, is essential for the study of patients with Crohn's Disease, and presents an attractive alternative to SBCE in Peutz-Jeghers syndrome surveillance.These diagnostic modalities are often not competitive but synergistic techniques. Knowing their characteristics, strengths and limitations, indications, contraindications and potential complications, as well as the adaptation to local availability and expertise, is essential to better select which procedures to perform in each patient, both safely and effectively, in order to optimize management and improve patient outcomes.A investigação do intestino delgado, previamente difícil e limitada, sofreu uma revolução com o aparecimento de técnicas imagiológicas contrastadas de elevada qualidade, como a enterografia por tomografia axial computadorizada (enteroTC) e a enterografia por ressonância magnética (enteroRM), assim como pela enteroscopia por cápsula (EC). A decisão na escolha da técnica a utilizar nas diferentes patologias do intestino delgado não é na maioria das vezes simples ou óbvia. Adicionalmente, a presença de contraindicações pode restringir o uso destas técnicas em alguns doentes, e apesar de não serem consideradas técnicas invasivas, não são isentas de riscos e complicações. A EC tem um papel crucial na investigação da hemorragia digestiva de causa obscura e da doença de Crohn, mas tem-se revestido também de utilidade na vigilância de doentes com síndrome de Peutz-Jeghers; a enteroTC revelou uma elevada capacidade diagnóstica para neoplasias do intestino delgado e na doença de Crohn estabelecida, e a sua utilização na hemorragia digestiva de causa obscura tem vindo a expandir. A enteroRM, apesar de dispendiosa e de disponibilidade limitada, tem uma elevada eficácia no estudo da doença de Crohn, e é uma alternativa válida à EC no síndrome de Peutz-Jeghers. Estas técnicas diagnósticas são frequentemente singergísticas e complementares, ao invés de competitivas. O reconhecimento das suas características, das suas capacidades e limitações, assim como das indicações, contraindicações e potenciais complicações, e aliado à adaptação à disponibilidade e competências locais, é essencial na correcta escolha de procedimentos seguros e eficazes para cada doente, de forma a optimizar a abordagem e o prognóstico.(undefined)info:eu-repo/semantics/publishedVersio

Targeting of tumor radioiodine therapy by expression of the sodium iodide symporter under control of the survivin promoter

To test the feasibility of using the survivin promoter to induce specific expression of sodium/iodide symporter (NIS) in cancer cell lines and tumors for targeted use of radionuclide therapy, a recombinant adenovirus, Ad-SUR-NIS, that expressed the NIS gene under control of the survivin promoter was constructed. Ad-SUR-NIS mediating iodide uptake and cytotoxicity was performed in vitro. Scintigraphic, biodistribution and radioiodine therapy studies were performed in vivo. PC-3 (prostate); HepG2 (hepatoma) and A375 (melanoma) cancer cells all exhibited perchlorate-sensitive iodide uptake after infection with Ad-SUR-NIS, ∼50 times higher than that of negative control Ad-CMV-GFP-infected cells. No significant iodide uptake was observed in normal human dental pulp fibroblast (DPF) cells after infection with Ad-SUR-NIS. Clonogenic assays demonstrated that Ad-SUR-NIS-infected cancer cells were selectively killed by exposure to 131I. Ad-SUR-NIS-infected tumors show significant radioiodine accumulation (13.3±2.85% ID per g at 2 h post-injection), and the effective half-life was 3.1 h. Moreover, infection with Ad-SUR-NIS in combination with 131I suppressed tumor growth. These results indicate that expression of NIS under control of the survivin promoter can likely be used to achieve cancer-specific expression of NIS in many types of cancers. In combination with radioiodine therapy, this strategy is a possible method of cancer gene therapy