Effect of oxamniquine on cell adhesion to Schistosoma mansoni larvae in the peritoneal cavity of naive mice

The treatment of naive mice with high closes of oxamniquine, 1 hour before the intraperitoneal inoculation of Schistosoma mansoni cercariae, induces a delay in the transformation process resulting in a longer host cell adhesion.

Analysing the innovation process in the EU Integrated Programme, ISAFRUIT

ISAFRUIT is an integrated European Union Project focussed on increasing fruit consumption as a means to improve human health, through evaluating the fruit chain and addressing bottlenecks therein.The innovations which are being developed throughout the ISAFRUIT Project have been analysed to determine both the success factors and the obstacles in reaching the commercialisation stage. Only 9.58% of the deliverables planned within the Project were focussed on developing technological innovations.There is evidence, however, of successes in the development of new innovations arising from the ISAFRUIT Project, with several other potential innovations in the pipeline. Of the technologies identified, 67% are still at the “invention stage”; that is, the stage prior to bridging the so-called “valley of death”, the stage between an invention and an innovation. Those which are considered to have moved over the “valley of death” either had industry partners included in the Project, or had consulted with industry to ensure that the technology was relevant, or met a recognised industry need. Many of the technologies which made less progress did not have the same interactions with industry. A number of other issues were identified which prevented further progress towards innovation. The need for scientists to publish scientific papers, both for their career pathways and to increase their chances of future funding, was identified as one issue, although the filing of patents is now becoming more accepted and recognised. The patenting system is considered complex by many scientists and is not well-understood. Finally, agreements between partners on the sharing of intellectual property rights can cause a delay in the innovation process.

Functional complementation of a yeast knockout strain by Schistosoma mansoni Rho1 GTPase in the presence of caffeine, an agent that affects mutants defective in the protein kinase C signal transduction pathway

In a previous study, the Schistosoma mansoni Rho1 protein was able to complement Rho1 null mutant Saccharomyces cerevisiae cells at restrictive temperatures and under osmotic stress (low calcium concentration) better than the human homologue (RhoA). It is known that under osmotic stress, the S. cerevisiae Rho1 triggers two distinct pathways: activation of the membrane 1,3-beta-glucan synthase enzymatic complex and activation of the protein kinase C1 signal transduction pathway, promoting the transcription of response genes. In the present work the SmRho1 protein and its mutants smrho1E97P, smrho1L101T, and smrho1E97P, L101T were used to try to clarify the basis for the differential complementation of Rho1 knockout yeast strain by the human and S. mansoni genes. Experiments of functional complementation in the presence of caffeine and in the presence of the osmotic regulator sorbitol were conducted. SmRho1 and its mutants showed a differential complementation of the yeast cells in the presence of caffeine, since smrho1E97P and smrho1E97P, L101T mutants showed a delay in the growth when compared to the yeast complemented with the wild type SmRho1. However, in the presence of sorbitol and caffeine the wild type SmRho1 and mutants showed a similar complementation phenotype, as they allowed yeast growth in all caffeine concentrations tested.

Invasive candidiasis as a cause of sepsis in the critically ill patient.

Invasive fungal infections are an increasingly frequent etiology of sepsis in critically ill patients causing substantial morbidity and mortality. Candida species are by far the predominant agent of fungal sepsis accounting for 10% to 15% of health-care associated infections, about 5% of all cases of severe sepsis and septic shock and are the fourth most common bloodstream isolates in the United States. One-third of all episodes of candidemia occur in the intensive care setting. Early diagnosis of invasive candidiasis is critical in order to initiate antifungal agents promptly. Delay in the administration of appropriate therapy increases mortality. Unfortunately, risk factors, clinical and radiological manifestations are quite unspecific and conventional culture methods are suboptimal. Non-culture based methods (such as mannan, anti-mannan, β-d-glucan, and polymerase chain reaction) have emerged but remain investigational or require additional testing in the ICU setting. Few prophylactic or pre-emptive studies have been performed in critically ill patients. They tended to be underpowered and their clinical usefulness remains to be established under most circumstances. The antifungal armamentarium has expanded considerably with the advent of lipid formulations of amphotericin B, the newest triazoles and the echinocandins. Clinical trials have shown that the triazoles and echinocandins are efficacious and well tolerated antifungal therapies. Clinical practice guidelines for the management of invasive candidiasis have been published by the European Society for Clinical Microbiology and Infectious Diseases and the Infectious Diseases Society of North America.

Delayed Cyclic Activity Development on Early Amplitude-Integrated EEG in the Preterm Infant with Brain Lesions.

Background: Maturation of amplitude-integrated electroencephalogram (aEEG) activity is influenced by both gestational age (GA) and postmenstrual age. It is not fully known how this process is influenced by cerebral lesions. Objective: To compare early aEEG developmental changes between preterm newborns with different degrees of cerebral lesions on cranial ultrasound (cUS). Methods: Prospective cohort study on preterm newborns with GA <32.0 weeks, undergoing continuous aEEG recording during the first 84 h after birth. aEEG characteristics were qualitatively and quantitatively evaluated using pre-established criteria. Based on cUS findings three groups were formed: normal (n = 78), mild (n = 20), and severe cerebral lesions (n = 6). Linear mixed models for repeated measures were used to analyze aEEG maturational trajectories. Results: 104 newborns with a mean GA (range) 29.5 (24.4-31.7) weeks, and birth weight 1,220 (580-2,020) g were recruited. Newborns with severe brain lesions started with similar aEEG scores and tendentially lower aEEG amplitudes than newborns without brain lesions, and showed a slower development of the cyclic activity (p < 0.001), but a more rapid increase of the maximum and minimum aEEG amplitudes (p = 0.002 and p = 0.04). Conclusions: Preterm infants with severe cerebral lesions manifest a maturational delay in the aEEG cyclic activity already early after birth, but show a catch-up of aEEG amplitudes to that of newborns without cerebral lesions. Changes in the maturational aEEG pattern may be a marker of severe neurological lesions in the preterm infant.

Intravitreous injection of PLGA microspheres encapsulating GDNF promotes the survival of photoreceptors in the rd1/rd1 mouse.

PURPOSE: To evaluate the potential delay of the retinal degeneration in rd1/rd1 mice using recombinant human glial cell line-derived neurotrophic factor (rhGDNF) encapsulated in poly(D,L-lactide-co-glycolide) (PLGA) microspheres. METHODS: rhGDNF-loaded PLGA microspheres were prepared using a water in oil in water (w/o/w) emulsion solvent extraction-evaporation process. In vitro, the rhGDNF release profile was assessed using radiolabeled factor. In vivo, rhGDNF microspheres, blank microspheres, or microspheres loaded with inactivated rhGDNF were injected into the vitreous of rd1/rd1 mice at postnatal day 11 (PN11). The extent of retinal degeneration was examined at PN28 using rhodopsin immunohistochemistry on whole flat-mount retinas, outer nuclear layer (ONL) cell counting on histology sections, and electroretinogram tracings. Immunohistochemical reactions for glial fibrillary acidic protein (GFAP), F4/80, and rhodopsin were performed on cryosections. RESULTS: Significant delay of rod photoreceptors degeneration was observed in mice receiving the rhGDNF-loaded microspheres compared to either untreated mice or to mice receiving blank or inactivated rhGDNF microspheres. The degeneration delay in the eyes receiving the rhGDNF microspheres was illustrated by the increased rhodopsin positive signals, the preservation of significantly higher number of cell nuclei within the ONL, and significant b-wave increase. A reduction of the subretinal glial proliferation was also observed in these treated eyes. No significant intraocular inflammatory reaction was observed after the intravitreous injection of the various microspheres. CONCLUSIONS: A single intravitreous injection of rhGDNF-loaded microspheres slows the retinal degeneration processes in rd1/rd1 mice. The use of injectable, biodegradable polymeric systems in the vitreous enables the efficient delivery of therapeutic proteins for the treatment of retinal diseases.

Induction of chagasic-like arrhythmias in the isolated beating hearts of healthy rats perfused with Trypanosoma cruzi-conditioned medium

Chagas' myocardiopathy, caused by the intracellular protozoan Trypanosoma cruzi, is characterized by microvascular alterations, heart failure and arrhythmias. Ischemia and arrythmogenesis have been attributed to proteins shed by the parasite, although this has not been fully demonstrated. The aim of the present investigation was to study the effect of substances shed by T. cruzi on ischemia/reperfusion-induced arrhythmias. We performed a triple ischemia-reperfusion (I/R) protocol whereby the isolated beating rat hearts were perfused with either Vero-control or Vero T. cruzi-infected conditioned medium during the different stages of ischemia and subsequently reperfused with Tyrode's solution. ECG and heart rate were recorded during the entire experiment. We observed that triple I/R-induced bradycardia was associated with the generation of auricular-ventricular blockade during ischemia and non-sustained nodal and ventricular tachycardia during reperfusion. Interestingly, perfusion with Vero-infected medium produced a delay in the reperfusion-induced recovery of heart rate, increased the frequency of tachycardic events and induced ventricular fibrillation. These results suggest that the presence of parasite-shed substances in conditioned media enhances the arrhythmogenic effects that occur during the I/R protocol.

A possible role for chemokine signalling through CXCR4 as a downstream effector of retinoic acid signalling in the regenerating tail and spinal cord of Notophthalmus viridescens

The newt, Notopthalmus viridescens is one of the few tet rapod vertebrates capable of extensive regeneration of the central nervous system, however, the factors involved in this process are still unknown. Chemokine signalling through the receptor CXCR4, has been found to be involved in the development of the central nervous system of mammals and more recently in epimorphic fin regeneration in zebrafish. We have hypothesized that the CXCR4 signalling pathway is involved in spinal cord and tail regeneration in the adul t newt , possibly as a downstream target of retinoic acid signalling. We found that CXCR4 mRNA expression was observed in the brain, spinal cord, heart, gut, liver and regenerating tail blastemas. CXCR4 expression increased over the f i rst 12 days of tail regeneration and returned to basal expression levels at day 21 of regeneration. Inhibition of CXCR4 wi th AMD3100, a specific receptor antagonist, led to a decrease in CXCR4 mRNA in the regenerating tail 14 days post amputation. Histological analysis suggests a delay in the early stages of tail and spinal cord regeneration. Spinal cord explants t reated wi th CXCL12, the ligand to CXCR4, displayed enhanced neurite outgrowth in vitro. Explants t reated wi th AMD3100 abolished any retinoic acid enhanced neurite outgrowth effects suggesting a link between these signalling pathways.

Roll of the rhythmic component in the proactive control of a human hand

In terms of evolution, the strategy of catching prey would have been an important part of survival in a constantly changing environment. A prediction mechanism would have developed to compensate for any delay in the sensory-motor system. In a previous study, “proactive control” was found, in which the motion of the hands preceded the virtual moving target. These results implied that the positive phase shift of the hand motion represents the proactive nature of the visual-motor control system, which attempts to minimize the brief error in the hand motion when the target changes position unexpectedly. In our study, a visual target moves in circle (13 cm diameter) on a computer screen, and each subject is asked to keep track of the target’s motion by the motion of a cursor. As the frequency of the target increases, a rhythmic component was found in the velocity of the cursor in spite of the fact that the velocity of the target was constant. The generation of a rhythmic component cannot be explained simply as a feedback mechanism for the phase shifts of the target and cursor in a sensory-motor system. Therefore, it implies that the rhythmic component was generated to predict the velocity of the target, which is a feed-forward mechanism in the sensory-motor system. Here, we discuss the generation of the rhythmic component and its roll in the feed-forward mechanism.

Excitation and decay of solar-wind driven flows in the magnetosphere-ionosphere system

Basic concepts of the form of high-latitude ionospheric flows and their excitation and decay are discussed in the light of recent high time-resolution measurements made by ground-based radars. It is first pointed out that it is in principle impossible to adequately parameterize these flows by any single quantity derived from concurrent interplanetary conditions. Rather, even at its simplest, the flow must be considered to consist of two basic time-dependent components. The first is the flow driven by magnetopause coupling processes alone, principally by dayside reconnection. These flows may indeed be reasonably parameterized in terms of concurrent near-Earth interplanetary conditions, principally by the interplanetary magnetic field (IMF) vector. The second is the flow driven by tail reconnection alone. As a first approximation these flows may also be parameterized in terms of interplanetary conditions, principally the north-south component of the IMF, but with a delay in the flow response of around 30-60 min relative to the IMF. A delay in the tail response of this order must be present due to the finite speed of information propagation in the system, and we show how "growth" and "decay" of the field and flow configuration then follow as natural consequences. To discuss the excitation and decay of the two reconnection-driven components of the flow we introduce that concept of a flow-free equilibrium configuration for a magnetosphere which contains a given (arbitrary) amount of open flux. Reconnection events act either to create or destroy open flux, thus causing departures of the system from the equilibrium configuration. Flow is then excited which moves the system back towards equilibrium with the changed amount of open flux. We estimate that the overall time scale associated with the excitation and decay of the flow is about 15 min. The response of the system to both impulsive (flux transfer event) and continuous reconnection is discussed in these terms.

Further considerations of cosmic ray modulation of infra-red radiation in the atmosphere

Understanding effects of ionisation in the lower atmosphere is a new interdisciplinary area, crossing the traditionally distinct scientific boundaries between astro-particle and atmospheric physics and also requiring understanding of both heliospheric and magnetospheric influences on cosmic rays. Following the paper of Erlykin et al. (2014) we develop further the interpretation of our observed changes in long-wave (LW) radiation, Aplin and Lockwood (2013) by taking account of both cosmic ray ionisation yields and atmospheric radiative transfer. To demonstrate this, we show that the thermal structure of the whole atmosphere needs to be considered along with the vertical profile of ionisation. Allowing for, in particular, ionisation by all components of a cosmic ray shower and not just by the muons, reveals that the effect we have detected is certainly not inconsistent with laboratory observations of the LW absorption cross section. The analysis presented here, although very different from that of Erlykin et al., does come to the same conclusion that the events detected by AL were not caused by individual cosmic ray primaries – not because it is impossible on energetic grounds, but because events of the required energy are too infrequent for the 12 h_1 rate at which they were seen by the AL experiment. The present paper numerically models the effect of three different scenario changes to the primary GCR spectrum which all reproduce the required magnitude of the effect observed by AL. However, they cannot solely explain the observed delay in the peak effect which, if confirmed, would appear to open up a whole new and interesting area in the study of water oligomers and their effects on LW radiation. We argue that a technical artefact in the AL experiment is highly unlikely and that our initial observations merit both a wide-ranging follow-up experiment and more rigorous, self-consistent, three-dimensional radiative transfer modelling

Effects of tissucol™ and epsilon aminocaproic acid in the healing process following dental extraction in dehydrated rats

A histological study was conducted of the alveolar bone healing process following tooth extraction of dehydrated rats after the implantation of fibrin adhesive (TISSUCOL™) associated to previous irrigation of the wound with a 5% epsilon aminocaproic acid solution (EACA). Seventy two rats were used, divided into three groups receiving different treatments after the surgical procedure. In group I, the gingival mucosa was sutured after extraction of the right upper incisor. In groups II and III, chronic dehydration was produced by water deprivation for 9 days (3 days in the preoperative period and 6 days in the postoperative period). In the animals of Group II, after tooth extraction, the gingival mucosa was sutured in the same way as performed in group I. In group III, after extraction, the dental socket was irrigated with 5% EACA, followed by implantation of the fibrin adhesive (TISSUCOL™). The mucosa was sutured in the same way as performed in the other groups. At 3, 7, 15 and 21 postoperative days, the animals were sacrificed in number of 6 for each group. Specimens containing the dental socket were removed and fixed in 10% formalin and decalcified in an equal part formic acid and sodium citrate solution. After routine processing, the specimens were embedded in paraffin for microtomy. We obtained 6 μm semi-serial slices that were stained with hematoxylin and eosin for histological evaluation. The results showed that the water deprivation in the pre- and postoperative periods caused a delay in the alveolar bone healing process. The use of the fibrin adhesive (TISSUCOL™) produced an improvement in the fibrinolytic picture caused by dehydration.

An assessment of the economic impact of climate change on the tourism sector in the Bahamas

The Bahamas is at great risk and vulnerability given its geographical features as a low-lying, sea encircled country. If projected sea level rise is reached by 2050, between 10-12% of territory will be lost, especially in coastal zones where the main tourism assets are located. Vulnerability could also be manifested if flight carbon emission taxes are established in the main source markets, representing an economic threat to the tourism sector for the islands. The impact of climate change on main tourism demand variables will cause some losses to the country‟s income and government revenues. This would be acting conjointly with some local threats to tourism assets and trends in future global tourism demand. The second and no less important threat is tropical cyclones, which may be associated with raising sea level. Estimations posited the amount of losses in excess of 2400 million US$ for the four decades under examination. It is to be pointed out that there is still a lack of comparatively accurate data collection and analysis on this subject, a point deserving more attention in order to deepen the understanding of, and to extract better lessons from these extreme events. In the same period, total estimated impacts of progressive climate change are between 17 and 19 billions of B$ with estimated discount rates applied. The Bahamas is a Small Island Developing State with low growth on GHG emissions (second in Latin America), as well as a relative short capacity to lower emissions in the future. The country has a relative delay in the application of renewable energy systems, a solution that, provided documented studies on-site, might turn out to be fundamental in the country‟s efforts to establish mitigation related policies. The Bahamas currently has institutions and organizations that deal with climate change-related issues and an important number of measures and courses of action have been set up by the government. Nevertheless, more coordination among them is needed and should include international institutions. This coordination is essential even for the first steps, i.e. to conduct studies with a bottom-up approach in order to draw more accurate programs on adaptation and mitigation. It is fundamental for tourism to keep track of potential losses in tourist attractions (and to act accordingly), related to correspondent losses in biodiversity, water resources and coastal erosion. Also, actions to fight climate change impacts might improve the islands security standards, quality of living and protect cultural and heritage assets. These elements may definitely shape the future of the country‟s competitiveness as a tourism destination. It is possible and necessary to decide about the options with good cost-benefit ratio and reasonable payback periods, notwithstanding that cost-benefit analysis requires more refined and accurate data to provide precise and locally adapted options.

The importance of feeding in the larval development of the ghost shrimp Callichirus major (Decapoda: Callianassidae)

O presente estudo investigou se o callianassid Callichirus major apresenta um comportamento lecitotrófico durante o desenvolvimento larval. Dois experimentos foram realizados. No primeiro experimento, larvas foram submetidas a um período inicial de alimentação, enquanto no segundo elas foram submetidas a um período inicial de inanição. No experimento 1, 80% das larvas de C. major mudaram com sucesso para o estágio de juvenil no tratamento com larvas alimentadas diariamente. Nos tratamentos com larvas alimentadas por 1, 2 e 3 dias, houve uma mortalidade total antes de alcançarem o estágio de megalopa. No experimento 2, as larvas zoés mostraram mais resistência quando submetidas a um período inicial de inanição. Nos tratamentos nos quais as larvas estiveram em inanição por 1, 2 e 3 dias, as taxas de sobrevivência foram100%, 60% e 90%, respectivamente. Porém atrasos na duração do desenvolvimento dos estágios de zoés foram observados. Houve mortalidade total para as larvas cultivadas no tratamento com ausência constante de alimento. Os resultados sugerem não existir um comportamento lecitotrófico nas zoés de C. major.

Roles of p38 mitogen-activated protein kinase pathway in the regulation of SOX9 activity and chondrogenesis

Sox9 is a master transcription factor in chondrocyte differentiation. Several lines of evidence suggest that the p38 mitogen-activated protein kinase (MAPK) pathway is involved in chondrocyte differentiation. In the present study, we examined the roles of p38 in the regulation of SOX9 activity and chondrogenesis. ^ COS7 cells were transfected with a SOX9 expression vector and 4x48-p89, a luciferase construction harboring four tandem copies of a SOX9-dependent 48-bp enhancer in Col2a1. Coexpression of MKK6EE, a constitutively active mutant of MKK6, a MAPKK that specifically activates p38, further increased the activity of the SOX9-dependent 48-bp enhancer about 5-fold, and SOX9 protein levels were not increased under these conditions. This increase in enhancer activity was not observed in a mutant enhancer construct harboring mutations that abolish SOX9 binding. These data strongly suggested that activation of the p38 pathway results in increased activity of SOX9. In addition, the increase of the activity of the SOX9-dependent 48-bp enhancer by MKK6EE was also observed in primary chondrocytes, and this increase was abolished by coexpression of a p38 phosphatase, MKP5, and p38 specific inhibitors. Furthermore, treatment of primary chondrocytes with p38 inhibitors decreased the expression of Col2a1, a downstream target of Sox9, without affecting Sox9 RNA levels, further supporting the hypothesis that p38 plays a role in regulating Sox9 activity in chondrocytes. ^ To further study the role of the p38 MAPK pathway in chondrogenesis, we generated transgenic mice that express MKK6EE in chondrocytes under the control of the Col2a1 promoter/intron regulatory sequences. These mice showed a dwarf phenotype characterized by reduced chondrocyte proliferation and a delay in the formation of primary and secondary ossification centers. Histological analysis using in situ hybridization showed reduced expression of Indian hedgehog, PTH/PTHrP receptor, cyclin D1 and increased expression of p21. In addition, consistent with the notion that Sox9 activity was increased in these mice, transgenic mice that express MKK6EE in chondrocytes showed phenotypes similar to those of mice that overexpress SOX9 in chondrocytes. Therefore, our study provides in vivo evidence for the role of p38 in chondrocyte differentiation and suggests that Sox9 is a downstream target of the p38 MAPK pathway. ^