An attempt to determine variability of RNA/DNA ratios during Dicentrarchus labrax larval development

RNA and DNA content of seabass (Dicentrarchus labra.x) larvae were determined from day 10 to day 60 after hatching in an aquaculture facility. Our results show a two-phase modulation of the RNA/DNA ratio throughout seabass larvae development. From day 10 after hatching there is an increase in the RNA/DNA ratio reaching maximal values at day 30 of age. Then, the RNA/DNA ratio decreased reaching minimal values at day 60 after hatching. These results are consistent with a high rate of protein synthesis during the first 30 days of seabass development compared with the rest of the developmental period studied. The results are compared with that of otolith growth carried out for the same species larvaeAPROXIMACIÓ A LA DETERMINACIÓ DE LA VARIABILITAT DE LA RELACIÓ DNA/RNA DURANT EL DESENVOLUPAMENT LARVAL DEL LLOBARRO Dicentrarchus labrax. S'ha determinat el contingut de DNA (àcid desoxiribonucleic) i de RNA (àcid ribonucleic) en larves de llobarro (Dicentrarchus labrax) d'edats compreses entre 10 i 60 dies de vida, procedents d'una planta de cultiu. Els resultats obtinguts mostren dues fases diferenciades de desenvolupament d'aquestes larves, basades en la relaci6 RNA/DNA avaluada. S'observa un augment de la proporci6 de RNNDNA des del dia 10 fins el dia 30 de vida, per a decréixer a continuació, trobant els valors mínims en les larves de 60 dies de vidaPublicado

Amphoteric polyamidoamines in the treatment of malaria

The present invention relates to the use of amphoteric polyamidoamines with MW of 10-100 kDa as antimalarial agents or carriers of antimalarial drugs and to formulations thereof

Self-recognition and Ca2+-dependent carbohydrate–carbohydrate cell adhesion provide clues to the Cambrian explosion

Author Posting. © The Authors, 2009. This is the author's version of the work. It is posted here by permission of Oxford University Press for personal use, not for redistribution. The definitive version was published in Molecular Biology and Evolution 26 (2009): 2551-2561, doi:10.1093/molbev/msp170.The Cambrian explosion of life was a relatively short period ca. 540 million years ago that marked a generalized acceleration in the evolution of most animal phyla, but the trigger of this key biological event remains elusive. Sponges are the oldest extant Precambrian metazoan phylum and thus a valid model to study factors that could have unleashed the rise of multicellular animals. One such factor is the advent of self/non-self recognition systems, which would be evolutionarily beneficial to organisms to prevent germ cell parasitism or the introduction of deleterious mutations resulting from fusion with genetically different individuals. However, the molecules responsible for allorecognition probably evolved gradually before the Cambrian period, and some other (external) factor remains to be identified as the missing triggering event. Sponge cells associate through calcium-dependent, multivalent carbohydrate-carbohydrate interactions of the g200 glycan found on extracellular proteoglycans. Single molecule force spectroscopy analysis of g200-g200 binding indicates that calcium affects the lifetime (+Ca/-Ca: 680 s/3 s) and bond reaction length (+Ca/-Ca: 3.47 Å/2.27 Å). Calculation of mean g200 dissociation times in low and high calcium within the theoretical framework of a cooperative binding model indicates the non-linear and divergent characteristics leading to either disaggregated cells or stable multicellular assemblies, respectively. This fundamental phenomenon can explain a switch from weak to strong adhesion between primitive metazoan cells caused by the well documented rise in ocean calcium levels at the end of Precambrian time. We propose that stronger cell adhesion allowed the integrity of genetically uniform animals composed only of “self” cells, facilitating genetic constitutions to remain within the metazoan individual and be passed down inheritance lines. The Cambrian explosion might have been triggered by the coincidence in time of primitive animals endowed with self/non-self recognition, and of a surge in sea water calcium that increased the binding forces between their calcium-dependent cell adhesion molecules.D.A. and A.K. acknowledge financial support from the Collaborative Research Center SFB 613 from the Deutsche Forschungsgemeinschaft (DFG), and X.F.-B. acknowledges financial support from grants BIO2002-00128, BIO2005-01591, and CSD2006-00012 from the Ministerio de Ciencia y Tecnología, Spain, which included Fondo Europeo de Desarrollo Regional funds, and from grant 2005SGR-00037 from the Generalitat de Catalunya, Spain

Loading of beclomethasone in liposomes and hyalurosomes improved with mucin as effective approach to counteract the oxidative stress generated by cigarette smoke extract

In this work beclomethasone dipropionate was loaded into liposomes and hyalurosomes modified with mucin to improve the ability of the payload to counteract the oxidative stress and involved damages caused by cigarette smoke in the airway. The vesicles were prepared by dispersing all components in the appropriate vehicle and sonicating them, thus avoiding the use of organic solvents. Unilamellar and bilamellar vesicles small in size (~117 nm), homogeneously dispersed (polydispersity index lower than 0.22) and negatively charged (~−11 mV), were obtained. Moreover, these vesicle dispersions were stable for five months at room temperature (~25◦C). In vitro studies performed using the Next Generation Impactor confirmed the suitability of the formulations to be nebulized as they were capable of reaching the last stages of the impactor that mimic the deeper airways, thus improving the deposition of beclomethasone in the target site. Further, biocompatibility studies performed by using 16HBE bronchial epithelial cells confirmed the high biocompatibility and safety of all the vesicles. Among the tested formulations, only mucin-hyalurosomes were capable of effectively counteracting the production of reactive oxygen species (ROS) induced by cigarette smoke extract, suggesting that this formulation may represent a promising tool to reduce the damaging effects of cigarette smoke in the lung tissues, thus reducing the pathogenesis of cigarette smoke-associated diseases such as chronic obstructive pulmonary disease, emphysema, and cancer

New 4-(N-cinnamoylbutyl)aminoacridines as potential multi-stage antiplasmodial leads

A novel family of 4-aminoacridine derivatives was obtained by linking this heteroaromatic core to different trans-cinnamic acids. The 4-(N-cinnamoylbutyl)aminoacridines obtained exhibited in vitro activity in the low- or sub-micromolar range against (i) hepatic stages of Plasmodium berghei, (ii) erythrocytic forms of Plasmodium falciparum, and (iii) early and mature gametocytes of Plasmodium falciparum. The most active compound, having a meta-fluorocinnamoyl group linked to the acridine core, was 20- and 120-fold more potent, respectively, against the hepatic and gametocyte stages of Plasmodium infection than the reference drug, primaquine. Moreover, no cytotoxicity towards mammalian and red blood cells at the concentrations tested was observed for any of the compounds under investigation. These novel conjugates represent promising leads for the development of new multi-target antiplasmodials.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved

The ESCRT-III machinery participates in the production of extracellular vesicles and protein export during Plasmodium falciparum infection

Malaria is a disease caused by Plasmodium parasites that is still a leading cause of death in many low-income countries, and for which currently available therapeutic strategies are not succeeding in its control, let alone eradication. An interesting feature observed after Plasmodium invasion is the increase of extracellular vesicles (EVs) generated by parasitized red blood cells (pRBCs), which lack a vesicular trafficking that would explain EV production. Here, by combining different approaches, we demonstrated the participation of the endosomal sorting complex required for transport (ESCRT) machinery from Plasmodium falciparum in the production of EVs in pRBCs. Moreover, we were able to detect ESCRT-III proteins adjacent to the membrane of the host and in EVs purified from a pRBC culture, which shows the export of these proteins and their participation in EV production. Finally, the disruption of an ESCRT-III associated gene, Pfvps60, led to a significant reduction in the amount of EVs. Altogether, these results confirm ESCRT-III participation in EV production and provide novel information on the P. falciparum protein export mechanisms, which can be used for the development of new therapeutic strategies against malaria, based on the disruption of EV formation and trafficking

Pathobiology and transmission of highly and low pathogenic avian influenza viruses in European quail (Coturnix c. coturnix)

European quail (Coturnix c. coturnix) may share with Japanese quail (Coturnix c. japonica) its potential as an intermediate host and reservoir of avian influenza viruses (AIV). To elucidate this question, European quail were experimentally challenged with two highly pathogenic AIV (HPAIV) (H7N1/HP and H5N1/HP) and one low pathogenic AIV (LPAIV) (H7N2/LP). Contact animals were also used to assess the viral transmission among birds. Severe neurological signs and mortality rates of 67% (H7N1/HP) and 92% (H5N1/HP) were observed. Although histopathological findings were present in both HPAIV-infected groups, H5N1/HP-quail displayed a broader viral antigen distribution and extent of microscopic lesions. Neither clinical nor pathological involvement was observed in LPAIV-infected quail. Consistent long-term viral shedding and effective transmission to naive quail was demonstrated for the three studied AIV. Drinking water arose as a possible transmission route and feathers as a potential origin of HPAIV dissemination. The present study demonstrates that European quail may play a major role in AI epidemiology, highlighting the need to further understand its putative role as an intermediate host for avian/mammalian reassortant viruses

Ecological Factors Driving Avian Influenza Virus Dynamics in Spanish Wetland Ecosystems

Studies exploring the ecological interactions between avian influenza viruses (AIV), natural hosts and the environment are scarce. Most work has focused on viral survival and transmission under laboratory conditions and through mathematical modelling. However, more integrated studies performed under field conditions are required to validate these results. In this study, we combined information on bird community, environmental factors and viral epidemiology to assess the contribution of biotic and abiotic factors in the occurrence of low pathogenic AIV in Spanish wetlands. For that purpose, seven locations in five different wetlands were studied during two years (2007-2009), including seven sampling visits by location. In each survey, fresh faeces (n = 4578) of wild birds and water samples were collected for viral detection. Also, the vegetation structure, water physical properties of wetlands, climatic conditions and wild bird community composition were determined. An overall AIV prevalence of 1.7%±0.4 was detected in faecal samples with important fluctuations among seasons and locations. Twenty-six AIV were isolated from the 78 RRT-PCR positive samples and eight different haemagglutinines and five neuraminidases were identified, being the combination H3N8 the most frequent. Variation partitioning procedures identified the combination of space and time variables as the most important pure factor - independently to other factors - explaining the variation in AIV prevalence (36.8%), followed by meteorological factor (21.5%) and wild bird community composition/vegetation structure (21.1%). These results contribute to the understanding of AIV ecological drivers in Spanish ecosystems and provide useful guidelines for AIV risk assessment identifying potential hotspots of AIV activity

Copolimeri ad innesto PLGA-g-PVP per la veicolazione e il rilascio controllato di farmaci antimalariali

I copolimeri PLGA-g-PVP, aventi una catena di PLGA centrale ad alto peso molecolare e segmenti laterali oligomerici di PVP sono state recentemente sintetizzati tramite un processo sintetico a singolo step. La reazione consiste in una polimerizzazione a trasferimento di catena del N-vinilpirrolidone (N-VP) a partire da PLGA fuso, in presenza di un iniziatore radicalico quale \ue8 l\u2019AIBN (azobisisobutirronitrile). Diverse percentuali di PVP sono state innestati sulla catena principale, in modo da variare l\u2019idrofilia del copolimero. Lo scopo di questo lavoro \ue8 stato quello di formulare tali copolimeri PLGA-g-PVP in presenza di farmaci idrofobici, quali l\u2019artemisinina e la curcumina, sotto forma di nanocapsule da utilizzare come sospensioni antimalariche

Avaluació de l’estat fisiològic del conill (Oryctolagus cuniculus) per mitjà de biomarcadors bioquímics

[cat] El conill europeu (Oryctolagus cuniculus) és una de les espècies de vertebrats més importants dels ecosistemes Mediterranis. L'arribada de malalties virals, com la mixomatosi, han donat lloc a disminucions importants de les poblacions de conills salvatges. La determinació de biomarcadors de l’estat pro-oxidant / anti-oxidant permeten avaluar l’existència d’algun factor ambiental o infecciós que indueixi una situació d’estrès a l’animal. L’objectiu del present estudi va ser avaluar biomarcadors d’estrès a conills obtinguts en diferents modes de captura i en conills afectats per mixomatosi. Els resultats obtinguts no evidencien cap tipus de diferència en les activitats plasmàtiques dels enzims antioxidants, de l’activitat mieloperoxidasa ni dels nivells de malondialdehid en funció de la diferent modalitat de captura: ca eivissenc, fura o grup estabulat. La producció d’espècies reactives per part de les cèl·lules immunitàries tampoc no es veu modificada. Per contra, les activitats dels enzims catalasa, glutatió peroxidasa i glutatió reductasa són significativament més baixes a fetge en animals afectats de mixomatosi respecte als animals sans, mentre que els nivells de malondialdehid són significativament més elevats als animals malalts. En conclusió, el fet que no s’hagin observat diferències derivades del procés de captura ni respecte al grup control, demostra que els conills capturats gaudien d’un bon estat de salut. Els conills afectats per mixomatosi presenten a nivell hepàtic una disminució general de les defenses antioxidants i un augment del dany oxidatiu, cosa que posa de manifest la gravetat de la patologia.[eng] The European rabbit (Oryctolagus cuniculus) is one of the most important vertebrate species in Mediterranean ecosystems. In the last 60 years, the arrival of viral diseases, such as myxomatosis, has led to significant diminution of the populations of wild rabbits. The determination of biomarkers of the pro-oxidant / anti-oxidant status allows the evaluation of the existence of an environmental or infectious factor that induces a situation of stress to the animal and the ability to respond and adapt to this situation. The aim of the present study was to evaluate stress biomarkers from rabbits obtained in different capture modes and rabbits affected by myxomatosis. The results obtained do not show any difference in the plasma activities of antioxidant enzymes, myeloperoxidase activity or malondialdehyde levels depending on the different way of capturing rabbits: Ibizan dogs, ferrets or the confined group. The production of reactive species by immune cells is also unchanged. In contrast, the activities of catalase enzymes, glutathione peroxidase and glutathione reductase are significantly lower in liver in animals affected by myxomatosis compared to healthy animals, while levels of malondialdehyde are significantly higher in diseased animals. In conclusion, the fact that no differences derived from the capture process or the control group have been observed demonstrates that the captured rabbits are in a good state of health. Rabbits affected by myxomatosis have a general decrease in antioxidant defences and an increase in oxidative damage, evidencing the seriousness of the pathology