Co-culture of human fibroblasts,smooth muscle and endothelial cells promotes osteopontin induction in hypoxia

Arteriovenous fistulas (AVFs) are the preferred vascular access for haemodialysis of patients suffering from end-stage renal disease, a worldwide public health problem. However, they are prone to a high rate of failure due to neointimal hyperplasia and stenosis. This study aimed to determine if osteopontin (OPN) was induced in hypoxia and if OPN could be responsible for driving AVF failure. Identification of new factors that participate in remodelling of AVFs is a challenge. Three cell lines representing the cells of the three layers of the walls of arteries and veins, fibroblasts, smooth muscle cells and endothelial cells, were tested in mono- and co-culture in vitro for OPN expression and secretion in normoxia compared to hypoxia after silencing the hypoxia-inducible factors (HIF-1α, HIF-2α and HIF-1/2α) with siRNA or after treatment with an inhibitor of NF-kB. None of the cells in mono-culture showed OPN induction in hypoxia, whereas cells in co-culture secreted OPN in hypoxia. The changes in oxygenation that occur during AVF maturation up-regulate secretion of OPN through cell-cell interactions between the different cell layers that form AVF, and in turn, these promote endothelial cell proliferation and could participate in neointimal hyperplasia.     

Metapopulation dynamics and foraging plasticity in a highly vagile seabird,the southern rockhopper penguin

Population connectivity is driven by individual dispersal potential and modulated by natal philopatry. In seabirds, high vagility facilitates dispersal yet philopatry is also common, with foraging area overlap often correlated with population connectivity. We assess the interplay between these processes by studying past and current connectivity and foraging niche overlap among southern rockhopper penguin colonies of the coast of southern South America using genomic and stable isotope analyses. We found two distinct genetic clusters and detected low admixture between northern and southern colonies. Stable isotope analysis indicated niche variability between colonies, with Malvinas/Falklands colonies encompassing the species entire isotopic foraging niche, while the remaining colonies had smaller, nonoverlapping niches. A recently founded colony in continental Patagonia differed in isotopic niche width and position with Malvinas/Falklands colonies, its genetically identified founder population, suggesting the exploitation of novel foraging areas and/or prey items. Additionally, dispersing individuals found dead across the Patagonian shore in an unusual mortality event were also assigned to the northern cluster, suggesting northern individuals reach southern localities, but do not breed in these colonies. Facilitated by variability in foraging strategies, and especially during unfavorable conditions, the number of dispersing individuals may increase and enhance the probability of founding new colonies. Metapopulation demographic dynamics in seabirds should account for interannual variability in dispersal behavior and pay special attention to extreme climatic events, classically related to negative effects on population trends.     

An African bat in Europe,Plecotus gaisleri: Biogeographic and ecological insights from molecular taxonomy and Species Distribution Models

Because of the high risk of going unnoticed, cryptic species represent a major challenge to biodiversity assessments, and this is particularly true for taxa that include many such species, for example, bats. Long‐eared bats from the genus Plecotus comprise numerous cryptic species occurring in the Mediterranean Region and present complex phylogenetic relationships and often unclear distributions, particularly at the edge of their known ranges and on islands. Here, we combine Species Distribution Models (SDMs), field surveys and molecular analyses to shed light on the presence of a cryptic long‐eared bat species from North Africa, Plecotus gaisleri, on the islands of the Sicily Channel, providing strong evidence that this species also occurs in Europe, at least on the islands of the Western Mediterranean Sea that act as a crossroad between the Old Continent and Africa. Species Distribution Models built using African records of P. gaisleri and projected to the Sicily Channel Islands showed that all these islands are potentially suitable for the species. Molecular identification of Plecotus captured on Pantelleria, and recent data from Malta and Gozo, confirmed the species' presence on two of the islands in question. Besides confirming that P. gaisleri occurs on Pantelleria, haplotype network reconstructions highlighted moderate structuring between insular and continental populations of this species. Our results remark the role of Italy as a bat diversity hotspot in the Mediterranean and also highlight the need to include P. gaisleri in European faunal checklists and conservation directives, confirming the usefulness of combining different approaches to explore the presence of cryptic species outside their known ranges—a fundamental step to informing conservation.     

Heme induces significant neutrophil adhesion in vitro via an NFκB and reactive oxygen species-dependent pathway

Molecular and Cellular Biochemistry - Intravascular hemolysis, a major manifestation of sickle cell disease (SCD) and other diseases, incurs the release of hemoglobin and heme from red blood cells,...     

Effects of different branched-chain amino acids supplementation protocols on the inflammatory response of LPS-stimulated RAW 264.7 macrophages

Although branched-chain amino acids (BCAA) are commonly used as a strategy to recover nutritional status of critically ill patients, recent findings on their role as immunonutrients have been associated with unfavorable outcomes, especially in obese patients. The present study aimed to explore the effects of different BCAA supplementation protocols in the inflammatory response of LPS-stimulated RAW 264.7 macrophages. Cell cultures were divided into five groups, with and without BCAA supplementation, (2 mmol/L of each amino acid). Then, cell cultures followed three different treatment protocols, consisting of a pretreatment (PT), an acute treatment (AT), and a chronic treatment (CT) with BCAA and LPS stimulation (1 µg/mL). Cell viability was analyzed by MTT assay, NO production was assessed by the Griess reaction and IL-6, IL-10, TNF-α and PGE2 synthesis, was evaluated by ELISA. BCAA significantly increased cell viability in AT and CT protocols, and NO and IL-10 synthesis in all treatment protocols. IL-6 synthesis was only increased in PT and CT protocols. TNF-α and PGE2 synthesis were not altered in any of the protocols and groups. BCAA supplementation was able to increase both pro and anti-inflammatory mediators synthesis by RAW 264.7 macrophages, which was influenced by the protocol applied. Moreover, these parameters were significantly increased by isoleucine supplementation, highlighting a potential research field for future studies.

     

Recognizing the enemy: do predator cues influence hatching in Neotropical annual killifish?

Annual fish species have evolved complex adaptations to survive in temporary wetlands. The main adaptation of these fish is the ability to produce embryos that survive dry periods. Embryo development of this fish can show variation at multiple levels influenced by many environmental factors, such as photoperiod and temperature. Predator cues are another factor that can influence the embryonic stage. One way in which annual fish could adapt to predators is by using risk-spreading strategies (through bet-hedging). Nonetheless, this strategy depends on the coevolutionary history between predators and preys and on the degree of environmental unpredictability, resulting in different responses across different species. This study investigated the influence of predator cues on the embryonic development and hatching of two Austrolebias species that inhabit ponds that present differences in hydroperiod and the risk of predator presence. The results confirmed a differentiated response between the two annual fish species tested, corroborating the modulation of hatching against the risk of predation by native predatory fish. The authors further showed that development times varied between the two annual fish species, regardless of the presence of predators. They highlight that the variation in embryonic development is strongly affected by different levels of hydroperiod unpredictability faced by the two species. To unravel finer-scale local adaptations in the annual fish embryo development, future studies should focus on a region with greater spatial gradient.     

Dammarane triterpenes targeting α-synuclein: biological activity and evaluation of binding sites by molecular docking

Parkinson''s disease (PD) is a neurodegenerative disorder that affects adult people whose treatment is palliative. Thus, we decided to test three dammarane triterpenes 1, 1a, 1b, and we determined that 1 and 1a inhibit β-aggregation through thioflavine T rather than 1b. Since compound 1 was most active, we determined the interaction between α-synuclein and 1 at 50 µM (Kd) through microscale thermophoresis. Also, we observed differences in height and diameter of aggregates, and α-synuclein remains unfolded in the presence of 1. Also, aggregates treated with 1 do not provoke neurites'' retraction in N2a cells previously induced by retinoic acid. Finally, we studied the potential sites of interaction between 1 with α-synuclein fibrils using molecular modelling. Docking experiments suggest that 1 preferably interact with the site 2 of α-synuclein through hydrogen bonds with residues Y39 and T44.