Endocytosis of the non-catalytic ADAM23: Recycling and long half-life properties

A Disintegrin And Metalloprotease 23 (ADAM23) is a member of the ADAMs family of transmembrane proteins, mostly expressed in nervous system, and involved in traffic and stabilization of Kv1-potassium channels, synaptic transmission, neurite outgrowth, neuronal morphology and cell adhesion. Also, ADAM23 has been linked to human pathological conditions, such as epilepsy, cancer metastasis and cardiomyopathy. ADAM23 functionality depends on the molecule presence at the cell surface and along the secretory pathway, as expected for a cell surface receptor. Because endocytosis is an important functional regulatory mechanism of plasma membrane receptors and no information is available about the traffic or turnover of non-catalytic ADAMs, we investigated ADAM23 internalization, recycling and half-life properties. Here, we show that ADAM23 undergoes constitutive internalization from the plasma membrane, a process that depends on lipid raft integrity, and is redistributed to intracellular vesicles, especially early and recycling endosomes. Furthermore, we observed that ADAM23 is recycled from intracellular compartments back to the plasma membrane and thus has longer half-life and higher cell surface stability compared with other ADAMs. Our findings suggest that regulation of ADAM23 endocytosis/stability could be exploited therapeutically in diseases in which ADAM23 is directly involved, such as epilepsy, cancer progression and cardiac hypertrophy.     

Replication and partitioning of the apicoplast genome of Toxoplasma gondii is linked to the cell cycle and requires DNA polymerase and gyrase

Apicomplexans are the causative agents of numerous important infectious diseases including malaria and toxoplasmosis. Most of them harbour a chloroplast-like organelle called the apicoplast that is essential for the parasites’ metabolism and survival. While most apicoplast proteins are nuclear encoded, the organelle also maintains its own genome, a 35 kb circle. In this study we used Toxoplasma gondii to identify and characterise essential proteins involved in apicoplast genome replication and to understand how apicoplast genome segregation unfolds over time. We demonstrated that the DNA replication enzymes Prex, DNA gyrase and DNA single stranded binding protein localise to the apicoplast. We show in knockdown experiments that apicoplast DNA Gyrase A and B, and Prex are required for apicoplast genome replication and growth of the parasite. Analysis of apicoplast genome replication by structured illumination microscopy in T. gondii tachyzoites showed that apicoplast nucleoid division and segregation initiate at the beginning of S phase and conclude during mitosis. Thus, the replication and division of the apicoplast nucleoid is highly coordinated with nuclear genome replication and mitosis. Our observations highlight essential components of apicoplast genome maintenance and shed light on the timing of this process in the context of the overall parasite cell cycle.     

Observations of coastal aggregations of the broadnose sevengill shark (Notorynchus cepedianus) in Chilean waters

The presence of four sharks was documented in coastal waters of Antofagasta (Chile) using an unmanned aerial video camera. Fishers took advantage of this aggregation to catch and sold three adult broadnose sevengill sharks Notorynchus cepedianus. Species identity was determined by using the cox1 gene. One additional video was later recorded 3000 km south of Antofagasta, and shows a large female interacting with a salmon farming facility. Shallow water records of N. cepedianus were previously undocumented in Chilean waters, yet historically have provided an opportunistic event to fishers in Chile.     

Diet and trophic position of two mackerel species in the archipelago of Madeira,Portugal

The Atlantic chub mackerel Scomber colias and the blue jack mackerel Trachurus picturatus are two abundant species in the Macaronesia region which includes the archipelago of Madeira, Portugal. Both are key species in the trophic web, being important prey for several local top predators, such as seabirds and marine mammals. Nonetheless, little is known about their feeding ecology in oceanic environments. In this study, the authors describe the seasonal variation in the diet of S. colias and T. picturatus in the oceanic region of Madeira throughout a year. Visual inspection of stomach contents revealed that S. colias fed on a broader range of prey groups than T. picturatus, but for both species, zooplankton (particularly calanoid copepods) and fish were the most important food items. The diet of S. colias included a higher proportion of fish, namely Atlantic saury Scomberesox saurus and S. colias, than that of T. picturatus, that included mostly the longspine snipefish Macroramphosus scolopax. T. picturatus consumed a higher proportion of decapods and other copepods. Seasonal variation was found in the diet of both species, with zooplanktonic species being more important in colder months (February to April) for S. colias and during warm months (May to October) for T. picturatus. Their diet in other seasons was dominated by fish. Although they consume similar prey, carbon and nitrogen stable isotope analysis of muscle of S. colias and T. picturatus showed little overlap in their diets, and T. picturatus showed higher δ¹⁵N and a narrower isotopic niche.     

Differences between species in seed bank and vegetation helps to hold functional diversity in a floodable Neotropical savanna

种子库和植被物种之间的差异有助于保持新热带稀树草原的功能多样性 本研究的目的是量化种子库和建立的植被对物种组成、功能组成和多样性的贡献,并讨论这些差异对冲积平原植物群落更新和稳定性的影响。我们在巴西潘塔纳尔湿地的一个周期性洪水泛滥的稀树大草原上,在旱季和雨季对分布在5个地点的25个地块(10 m × 1 m)的1.5 m高度的地面覆盖植被和种子库进行了采样。采用出苗法对土壤种子库进行了评价。研究结果表明,种子库物种具有赋予群落更新的特征,而植被则具有稳定性特征。种子库的功能丰富度高于植被,而功能均匀度则低于植被。由于种子库和植被的植物特征不同,使得具有不同功能稳定性和更新特性的物种得以共存,这将有助于维持植物的功能多样性。这可能会让植物种群在应对干旱、火灾和洪水等不同的环境选择时更具有弹性。     

Potent Anti-Candida Fraction Isolated from Capsicum chinense Fruits Contains an Antimicrobial Peptide That is Similar to Plant Defensin and is Able to Inhibit the Activity of Different α-Amylase Enzymes

Antimicrobial peptides (AMPs) are molecules present in several life forms, possess broad-spectrum of inhibitory activity against pathogenic microorganisms, and are a promising alternative to combat the multidrug resistant pathogens. The aim of this work was to identify and characterize AMPs from Capsicum chinense fruits and to evaluate their inhibitory activities against yeasts of the genus Candida and α-amylases. Initially, after protein extraction from fruits, the extract was submitted to anion exchange chromatography resulting two fractions. Fraction D1 was further fractionated by molecular exclusion chromatography, and three fractions were obtained. These fractions showed low molecular mass peptides, and in fraction F3, only two protein bands of approximately 6.5 kDa were observed. Through mass spectrometry, we identified that the lowest molecular mass protein band of fraction F3 showed similarity with AMPs from plant defensin family. We named this peptide CcDef3 (Capsicum chinense defensin 3). The antifungal activity of these fractions was analyzed against yeasts of the genus Candida. At 200 μg/mL, fraction F1 inhibited the growth of C. tropicalis by 26%, fraction F2 inhibited 35% of the growth of C. buinensis, and fraction F3 inhibited all tested yeasts, exhibiting greater inhibition activity on the growth of the yeast C. albicans (86%) followed by C. buinensis (69%) and C. tropicalis (21%). Fractions F1 and F2 promoted membrane permeabilization of all tested yeasts and increased the endogenous induction of reactive oxygen species (ROS) in C. buinensis and C. tropicalis, respectively. We also observed that fraction F3 at a concentration of 50 µg/mL inhibited the α-amylase activities of Tenebrio molitor larvae by 96% and human salivary by 100%. Thus, our results show that fraction F3, which contains CcDef3, is a very promising protein fraction because it has antifungal potential and is able to inhibit the activity of different α-amylase enzymes.

     

Bacillus Toyonensis BCT-7112T Spores as Parenteral Adjuvant of BoHV-5 Vaccine in a Murine Model

Probiotics and Antimicrobial Proteins - Bacterial spores of the genus Bacillus are being evaluated as adjuvant molecules capable of improving the immune response to vaccines. In this study, we...     

Cardamonin Presents in Vivo Activity against Schistosoma mansoni and Inhibits Potato Apyrase

Schistosomiasis, a neglected tropical disease caused by Schistosoma species, harms over 250 million people in several countries. The treatment is achieved with only one drug, praziquantel. Cardamonin, a natural chalcone with in vitro schistosomicidal activity, has not been in vivo evaluated against Schistosoma. In this work, we evaluated the in vivo schistosomicidal activities of cardamonin against Schistosoma mansoni worms and conducted enzymatic apyrase inhibition assay, as well as molecular docking analysis of cardamonin against potato apyrase, S. mansoni NTPDase 1 and S. mansoni NTPDase 2. In a mouse model of schistosomiasis, the oral treatment with cardamonin (400 mg/kg) showed efficacy against S. mansoni, decreasing the total worm load in 46.8 % and reducing in 54.5 % the number of eggs in mice. Cardamonin achieved a significant inhibition of the apyrase activity and the three-dimensional structure of the potato apyrase, obtained by homology modeling, showed that cardamonin may interact mainly through hydrogen bonds. Molecular docking studies corroborate with the action of cardamonin in binding and inhibiting both potato apyrase and S. mansoni NTPDases.     

Synthetic Aurones: New Features for Schistosoma mansoni Therapy

In this work, two synthetic aurones revealed moderate schistosomicidal potential in in vitro and in vivo assays. Aurones ( 1 ) and ( 2 ) promoted changes in tegument integrity and motor activity, leading to death of adult Schistosoma mansoni worms in in vitro assays. When administered orally (two doses of 50 mg/kg) in experimentally infected animals, synthetic aurones ( 1 ) and ( 2 ) promoted reductions of 56.20 % and 57.61 % of the parasite load and stimulated the displacement towards the liver of the remaining adult worms. The oogram analysis revealed that the treatment with both aurones interferes with the egg development kinetics in the intestinal tissue. Seeking an action target for compounds ( 1 ) and ( 2 ), the connection with NTPDases enzymes, recognized as important therapeutic targets for S. mansoni, was evaluated. Molecular docking studies have shown promising results. The dataset reveals the anthelmintic character of these compounds, which can be used in the development of new therapies for schistosomiasis.     

Phytochemical profile and antioxidant activity of extracts of the peruvian peppertree Schinus areira L. from Chile

The Andean tree Schinus areira L. has multiple traditional uses, from the treatment of bronchitis and rheumatic diseases to menstrual cycle regulation and wound healing. With reported hypotensive, analgesic, antitumoral and anti-inflammatory properties, it acts predominantly against diseases related to oxidative stress. This study focuses on the antioxidant activity and phytochemical profile of the extracts of Schinus areira L.Serial extraction of the fruits was performed both by maceration and by Soxhlet. Total phenols and flavonoids were measured using the Folin-Ciocalteu method and AlCl₃, respectively. In vitro antioxidant activity was determined by FRAP and DPPH.Results were similar for both extraction methods. Primary metabolites detected included carbohydrates, proteins and amino acids; secondary metabolites included tannins, flavonoids, saponins, steroids and triterpenes. Antioxidant activity was confirmed for ethyl acetate, methanolic and aqueous extracts. The methanolic extract had both the highest polyphenol content (>195 mg GAE/ g dry weight) and the highest antioxidant activity [EC₅₀ > 476 μg/mL; >273 mg AA/g dry weight (DPPH); >301 mg AA/ g dry weight (FRAP)]. The extract does not produce macrophage cytotoxicity in RAW 264.7, which is indicated by an average cytotoxicity of 2% over 24 h.Our study serves as a starting point for future research on the pharmacological properties of Schinus areira L.