Marine sponge as a source of antiangiogenic compounds. The case of aeroplysinin-1

The vast majority of the natural compounds that have been previously described as inhibitors of angiogenesis have been isolated from plants and terrestrial microorganisms, mainly due to their higher availability and because their therapeutic effects had been previously known in folk traditional medicines. However, increasing attention is being paid to the development of marine-derived antiangiogenic agents, probably fuelled by the increase in the number of marine-derived anticancer drugs which are being successfully used for cancer therapy. Marine organisms, adapted to survive in extreme environments by developing chemical means of defence, produce interesting and singular pharmacological lead compounds, derived from the large diversity of marine habitats and environmental conditions. Among the many different types of marine organisms used as a source for drug discovery, sponges represent one of the most promising sources of leads in the research of new cancer drugs. Some angiogenesis inhibitors isolated from marine sponges have been described by us and others. Aeroplysinin-1, a brominated metabolite extracted from the marine sponge Aplysina aerophoba, has been characterized by our group as a potent antiangiogenic compound in vitro and in vivo. Aeroplysinin-1 induces apoptosis in endothelial cells by a mechanism which involves activation of the BH3-only pro-apoptotic protein Bad, cytochrome c release and activation of caspases 2, 3, 8 and 9, what indicates a relevant role of the mitochondria in the apoptogenic activity of this compound. Recent results suggest that aeroplysinin-1 could also be a novel potential anti-inflammatory compound. These results open new ways to the potential pharmacological action of aeroplysinin-1 not only on angiogenesis and cancer, but also on atherosclerosis and inflammation-dependent diseases.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Natural ventilation for the prevention of airborne contagion.

BACKGROUND: Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings. METHODS AND FINDINGS: The study was carried out in eight hospitals in Lima, Peru; five were hospitals of "old-fashioned" design built pre-1950, and three of "modern" design, built 1970-1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open. CONCLUSIONS: Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion

Preliminary results using a P300 brain-computer interface speller: a possible interaction effect between presentation paradigm and set of stimuli

Fernández-Rodríguez Á., Medina-Juliá M.T., Velasco-Álvarez F., Ron-Angevin R. (2019) Preliminary Results Using a P300 Brain-Computer Interface Speller: A Possible Interaction Effect Between Presentation Paradigm and Set of Stimuli. In: Rojas I., Joya G., Catala A. (eds) Advances in Computational Intelligence. IWANN 2019. Lecture Notes in Computer Science, vol 11506. Springer, ChamSeveral proposals to improve the performance controlling a P300-based BCI speller have been studied using the standard row-column presentation (RCP) par-adigm. However, this paradigm could not be suitable for those patients with lack of gaze control. To solve that, the rapid serial visual presentation (RSVP) para-digm, which presents the stimuli located in the same position, has been proposed in previous studies. Thus, the aim of the present work is to assess if a stimuli set of pictures that improves the performance in RCP, could also improve the per-formance in a RSVP paradigm. Six participants have controlled four conditions in a calibration task: letters in RCP, pictures in RCP, letters in RSVP and pictures in RSVP. The results showed that pictures in RCP obtained the best accuracy and information transfer rate. The improvement effect given by pictures was greater in the RCP paradigm than in RSVP. Therefore, the improvements reached under RCP may not be directly transferred to the RSVP.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Histological sub‐classification of cirrhosis using collagen proportionate area in patients with chronic hepatitis C

Collagen proportionate area (CPA, %) is used to quantify liver fibrosis. Here we assessed CPA performance to subclassify cirrhosis. CPA was measured in explanted livers from consecutively transplanted patients for hepatitis C virus‐related cirrhosis. MELD, Child‐Pugh score and decompensating events (ascites, variceal bleeding, non‐obstructive jaundice and encephalopathy) were recorded at the time of liver transplant. Of the 154 patients, 24%, 12%, 35%, 24% and 5% had 0, 1, 2, 3 and 4 previous decompensating events. Patients with decompensation had significantly higher CPA than those without (25.1±8.4 vs. 15.8±5.5, P<0.001). Decompensation was independently associated with CPA, bilirubin and albumin or with CPA and MELD score. CPA did not differ between patients with 1, 2, 3 or 4 decompensating events (22.2±6.3 vs. 26.6±8.9 vs. 24.5±7.7 vs. 24.4±10.9, P=0.242). Overall, CPA correlates with the clinical severity of cirrhosis until the advent of decompensation but not with subsequent decompensating events

Unmasking a new prognostic marker and therapeutic target from the GDNF-RET/PIT1/p14ARF/p53 pathway in acromegaly

Most of acromegaly is caused by a sporadic somatotropinoma and a couple of novel gene mutations responsible for somatotropinoma have recently been reported. To determine the cause of sporadic somatotropinoma in Japanese patients, we analyzed 61 consecutive Japanese patients with somatotropinoma without apparent family history. Comprehensive genetic analysis revealed that 31 patients harbored guanine nucleotide-binding protein, alpha stimulating (GNAS) mutations (50.8%) and three patients harbored aryl hydrocarbon receptor interacting protein (AIP) mutations (4.9%). No patients had G protein-coupled receptor 101 (GPR101) mutations. The patients in this cohort study were categorized into three groups of AIP, GNAS, and others and compared the clinical characteristics. The AIP group exhibited significantly younger age at diagnosis, larger tumor, and higher nadir GH during oral glucose tolerance test. In all patients with AIP mutation, macro- and invasive tumor was detected and repetitive surgery or postoperative medical therapy was needed. One case showed a refractory response to postoperative somatostatin analogue (SSA) but after the addition of cabergoline as combined therapy, serum IGF-I levels were controlled. The other case showed a modest response to SSA and the switching to cabergoline monotherapy was also effective. These data suggest that although resistance to SSA has been reported in patients with AIP mutations, the response to dopamine agonist (DA) may be retained. In conclusion, the cause of sporadic somatotropinoma in Japanese patients was comparable with the previous reports in Caucasians, patients with AIP mutations showed unique clinical characteristics, and DA may be a therapeutic option for patients with AIP mutations

Glycoprotein Ib activation by thrombin stimulates the energy metabolism in human platelets

<div><p>Thrombin-induced platelet activation requires substantial amounts of ATP. However, the specific contribution of each ATP-generating pathway <i>i</i>.<i>e</i>., oxidative phosphorylation (OxPhos) versus glycolysis and the biochemical mechanisms involved in the thrombin-induced activation of energy metabolism remain unclear. Here we report an integral analysis on the role of both energy pathways in human platelets activated by several agonists, and the signal transducing mechanisms associated with such activation. We found that thrombin, Trap-6, arachidonic acid, collagen, A23187, epinephrine and ADP significantly increased glycolytic flux (3–38 times <i>vs</i>. non-activated platelets) whereas ristocetin was ineffective. OxPhos (33 times) and mitochondrial transmembrane potential (88%) were increased only by thrombin. OxPhos was the main source of ATP in thrombin-activated platelets, whereas in platelets activated by any of the other agonists, glycolysis was the principal ATP supplier. In order to establish the biochemical mechanisms involved in the thrombin-induced OxPhos activation in platelets, several signaling pathways associated with mitochondrial activation were analyzed. Wortmannin and LY294002 (PI3K/Akt pathway inhibitors), ristocetin and heparin (GPIb inhibitors) as well as resveratrol, ATP (calcium-release inhibitors) and PP1 (Tyr-phosphorylation inhibitor) prevented the thrombin-induced platelet activation. These results suggest that thrombin activates OxPhos and glycolysis through GPIb-dependent signaling involving PI3K and Akt activation, calcium mobilization and protein phosphorylation.</p></div

In vitro digestibility of O/W emulsions co-ingested with complex meals: Influence of the food matrix

Oil-in-water (O/W) emulsions are promising delivery systems of lipophilic bioactive compounds into meals composed mainly of water. The colloidal stability of β-carotene-loaded O/W emulsion incorporated into whole milk, oatmeal and whole milk-oatmeal meals. Their subsequent gastric emptying rate, lipid digestibility and β-carotene retention during in vitro gastrointestinal digestion were evaluated using a semi-dynamic gastric model followed by a static small intestinal model. The dispersed particles within the meals, lipid droplets, casein micelles as well as protein and β-glucan aggregates, were responsible for the bigger average particle sizes of both O/W-oatmeal and O/W-whole milk-oatmeal (13.07 ± 1.81 and 7.60 ± 1.21 μm, respectively) compared to the O/W emulsions and O/W-whole milk (0.56 ± 0.03 and 0.44 ± 0.04 μm, respectively). Semi-dynamic in vitro gastric digestion of O/W-whole milk showed lipid droplets embedded into an insoluble protein network emptied earlier than the O/W emulsion. Conversely, O/W-oatmeal and O/W-whole milk-oatmeal had delayed lipid emptying, probably because of the gelation of the β-glucan from oats. During the in vitro small intestinal digestion, the rate of the FFA release was linked to the gastric emptying rate. Indeed, both O/W emulsion and O/W-whole milk presented an exponential increase in the FFA release, whereas the O/W-oatmeal and O/W-whole milk-oatmeal followed a stepwise trend. The β-carotene retention during in vitro gastrointestinal digestion depended on the lipid amount at each digestion time moment. Hence, this work provides valuable insight into the behaviour of O/W emulsions incorporated into meals and during their subsequent in vitro gastrointestinal digestion

A global perspective on marine photosynthetic picoeukaryote community structure

A central goal in ecology is to understand the factors affecting the temporal dynamics and spatial distribution of microorganisms and the underlying processes causing differences in community structure and composition. However, little is known in this respect for photosynthetic picoeukaryotes (PPEs), algae that are now recognised as major players in marine CO2 fixation. Here, we analysed dot blot hybridisation and cloning–sequencing data, using the plastid-encoded 16S rRNA gene, from seven research cruises that encompassed all four ocean biomes. We provide insights into global abundance, α- and β-diversity distribution and the environmental factors shaping PPE community structure and composition. At the class level, the most commonly encountered PPEs were Prymnesiophyceae and Chrysophyceae. These taxa displayed complementary distribution patterns, with peak abundances of Prymnesiophyceae and Chrysophyceae in waters of high (25:1) or low (12:1) nitrogen:phosphorus (N:P) ratio, respectively. Significant differences in phylogenetic composition of PPEs were demonstrated for higher taxonomic levels between ocean basins, using Unifrac analyses of clone library sequence data. Differences in composition were generally greater between basins (interbasins) than within a basin (intrabasin). These differences were primarily linked to taxonomic variation in the composition of Prymnesiophyceae and Prasinophyceae whereas Chrysophyceae were phylogenetically similar in all libraries. These data provide better knowledge of PPE community structure across the world ocean and are crucial in assessing their evolution and contribution to CO2 fixation, especially in the context of global climate change

1H, 13C and 15N resonance assignments of the Calmodulin-Munc13-1 peptide complex

Ca2+-Calmodulin binding to the variable N-terminal region of the diacylglycerol/phorbol ester-binding UNC13/Munc13 family of proteins modulates the short-term synaptic plasticity characteristics in neurons. Here, we report the sequential backbone and side chain resonance assignment of the Ca2+-Calmodulin/Munc13-1458–492 peptide complex at pH 6.8 and 35°C (BMRB No. 15470)