Effects of nano-void density, size, and spatial population on thermal conductivity: a case study of GaN crystal

The thermal conductivity of a crystal is sensitive to the presence of surfaces and nanoscale defects. While this opens tremendous opportunities to tailor thermal conductivity, a true "phonon engineering" of nanocrystals for a specific electronic or thermoelectric application can only be achieved when the dependence of thermal conductivity on the defect density, size, and spatial population is understood and quantified. Unfortunately, experimental studies of effects of nanoscale defects are quite challenging. While molecular dynamics simulations are effective in calculating thermal conductivity, the defect density range that can be explored with feasible computing resources is unrealistically high. As a result, previous work has not generated a fully detailed understanding of the dependence of thermal conductivity on nanoscale defects. Using GaN as an example, we have combined physically-motivated analytical model and highly-converged large scale molecular dynamics simulations to study effects of defects on thermal conductivity. An analytical expression for thermal conductivity as a function of void density, size, and population has been derived and corroborated with the model, simulations, and experiments

Haemoglobin interference and increased sensitivity of fluorimetric assays for quantification of low-parasitaemia Plasmodium infected erythrocytes

<p>Abstract</p> <p>Background</p> <p>Improvements on malarial diagnostic methods are currently needed for the correct detection in low-density <it>Plasmodium falciparum </it>infections. Microfluorimetric DNA-based assays have been previously used for evaluation of anti-malarial drug efficacy on <it>Plasmodium </it>infected erythrocytes. Several factors affecting the sensitivity of these methods have been evaluated, and tested for the detection and quantification of the parasite in low parasitaemia conditions.</p> <p>Methods</p> <p>Parasitaemia was assessed by measuring SYBRGreen I^®(SGI) and PicoGreen^®(PG) fluorescence of <it>P. falciparum </it>Dd2 cultures on human red blood cells. Different modifications of standard methods were tested to improve the detection sensitivity. Calculation of IC₅₀for chloroquine was used to validate the method.</p> <p>Results</p> <p>Removal of haemoglobin from infected red-blood cells culture (IRBC) increased considerably the fluorescent signal obtained from both SGI and PG. Detergents used for cell lysis also showed to have an effect on the fluorescent signal. Upon depletion of haemoglobin and detergents the fluorescence emission of SGI and PG increased, respectively, 10- and 60-fold, extending notably the dynamic range of the assay. Under these conditions, a 20-fold higher PG vs. SGI fluorescent signal was observed. The estimated limits of detection and quantification for the PG haemoglobin/detergent-depleted method were 0.2% and 0.7% parasitaemia, respectively, which allow the detection of ~10 parasites per microliter. The method was validated on whole blood-infected samples, displaying similar results as those obtained using IRBC. Removal of white-blood cells prior to the assay allowed to increase the accuracy of the measurement, by reducing the relative uncertainty at the limit of detection from 0.5 to 0.1.</p> <p>Conclusion</p> <p>The use of PG microassays on detergent-free, haemoglobin-depleted samples appears as the best choice both for the detection of <it>Plasmodium </it>in low-density infections and anti-malarial drugs tests.</p

Parasitostatic effect of maslinic acid. II. Survival increase and immune protection in lethal Plasmodium yoelii-infected mice

<p>Abstract</p> <p>Background</p> <p>The anti-malarial activity of maslinic acid (MA), a natural triterpene which has been previously shown to exert a parasitostatic action on <it>Plasmodium falciparum </it>cultures, was analysed <it>in vivo </it>by using the <it>Plasmodium yoelii </it>17XL murine model.</p> <p>Methods</p> <p>ICR mice were infected with <it>P. yoelii </it>and treated with a single dose of MA by a intraperitoneal injection of MA (40 mg kg^-1day^-1) followed by identical dose administration for the following three days. Parasitaemia and accumulation of intraerythrocytic stages was monitored microscopically. To assess protective immunity, cured mice were challenged with the same dose of parasites 40 days after recovery from the primary infection and parasitaemia was further monitored for 30 days. Humoral response was tested by ELISA and visualization of specific anti-<it>P. yoelii </it>antibodies was performed by Western-blotting.</p> <p>Results</p> <p>ICR mice treated with MA increased the survival rate from 20% to 80%, showing an arrest of parasite maturation from day 3 to 7 after infection and leading to synchronization of the intraerythrocytic cycle and accumulation of schizonts by day 6, proving that MA also behaves as a parasitostatic agent <it>in vivo</it>. Mice which survived the primary infection displayed lower rates of parasitic growth, showing a decline of parasitaemia after day 15, and complete clearance at day 20. These mice remained immunoprotected, showing not malaria symptoms or detectable parasitaemia after rechallenge with the same lethal strain. The analysis of specific antibodies against <it>P. yoelii</it>, present in mice which survived the infection, showed a significant increase in the number and intensity of immunoreactive proteins, suggesting that the protected mice may trigger a strong humoral response.</p> <p>Conclusion</p> <p>The survival increase observed in MA-treated mice can be explained considering that the parasitostatic effect exerted by this compound during the first days of infection increases the chances to develop effective innate and/or acquired immune responses. MA may represent a new class of anti-malarial compounds which, as a consequence of its parasitostatic action, favours the development of more effective sterilizing immune responses.</p

Parasitostatic effect of maslinic acid. I. Growth arrest of Plasmodium falciparum intraerythrocytic stages

<p>Abstract</p> <p>Background</p> <p>Natural products have played an important role as leads for the development of new drugs against malaria. Recent studies have shown that maslinic acid (MA), a natural triterpene obtained from olive pomace, which displays multiple biological and antimicrobial activities, also exerts inhibitory effects on the development of some Apicomplexan, including <it>Eimeria, Toxoplasma </it>and <it>Neospora</it>. To ascertain if MA displays anti-malarial activity, the main objective of this study was to asses the effect of MA on <it>Plasmodium falciparum</it>-infected erythrocytes <it>in vitro</it>.</p> <p>Methods</p> <p>Synchronized <it>P. falciparum</it>-infected erythrocyte cultures were incubated under different conditions with MA, and compared to chloroquine and atovaquone treated cultures. The effects on parasite growth were determined by monitoring the parasitaemia and the accumulation of the different infective stages visualized in thin blood smears.</p> <p>Results</p> <p>MA inhibits the growth of <it>P. falciparum </it>Dd2 and 3D7 strains in infected erythrocytes in, dose-dependent manner, leading to the accumulation of immature forms at IC₅₀concentrations, while higher doses produced non-viable parasite cells. MA-treated infected-erythrocyte cultures were compared to those treated with chloroquine or atovaquone, showing significant differences in the pattern of accumulation of parasitic stages. Transient MA treatment at different parasite stages showed that the compound targeted intra-erythrocytic processes from early-ring to schizont stage. These results indicate that MA has a parasitostatic effect, which does not inactivate permanently <it>P. falciparum</it>, as the removal of the compound allowed the infection to continue</p> <p>Conclusions</p> <p>MA displays anti-malarial activity at multiple intraerythrocytic stages of the parasite and, depending on the dose and incubation time, behaves as a plasmodial parasitostatic compound. This novel parasitostatic effect appears to be unrelated to previous mechanisms proposed for current anti-malarial drugs, and may be relevant to uncover new prospective plasmodial targets and opens novel possibilities of therapies associated to host immune response.</p

Human AB0 blood groups: differential membrane protein carbonylation in red cells

Comunicaciones a Congreso

Population proteomics: protein diversity in hake (Merluccius Merluccius) populations

Comunicaciones a congreso

Glutathione peroxidase contributes with heme oxygenase-1 to redox balance in mouse brain during the course of cerebral malaria

Oxidative stress has been attributed both a key pathogenic and rescuing role in cerebral malaria (CM). In a Plasmodium berghei ANKA murine model of CM, host redox signaling and functioning were examined during the course of neurological damage. Host antioxidant defenses were early altered at the transcriptional level indicated by the gradually diminished expression of superoxide dismutase-1 (sod-1), sod-2, sod-3 and catalase genes. During severe disease, this led to the dysfunctional activity of superoxide dismutase and catalase enzymes in damaged brain regions. Vitagene associated markers (heat shock protein 70 and thioredoxin-1) also showed a decaying expression pattern that paralleled reduced expression of the transcription factors Parkinson disease 7, Forkhead box O 3 and X-box binding protein 1 with a role in preserving brain redox status. However, the oxidative stress markers reactive oxygen/nitrogen species were not accumulated in the brains of CM mice and redox proteomics and immunohistochemistry failed to detect quantitative or qualitative differences in protein carbonylation. Thus, the loss of antioxidant capacity was compensated for in all cerebral regions by progressive upregulation of heme oxygenase-1, and in specific regions by early glutathione peroxidase-1 induction. This study shows for the first time a scenario of cooperative glutathione peroxidase and heme oxygenase-1 upregulation to suppress superoxide dismutase, catalase, heat shock protein-70 and thioredoxin-1 downregulation effects in experimental CM, counteracting oxidative damage and maintaining redox equilibrium. Our findings reconcile the apparent inconsistency between the lack of oxidative metabolite build up and reported protective effect of antioxidant therapy against CM.Ministerio de Educación y Ciencia (España)Universidad Complutense de MadridDepto. de Bioquímica y Biología MolecularFac. de FarmaciaTRUEpu

Estandarización de un modelo murino de malaria cerebral en fases clínicas para la evaluación de terapias antimaláricas y de rescate

Cerebral malaria (CM) is included among the more devastating SNC infectious diseases due to its high mortality and severe sequelae in children. Currently, no specific pharmacological treatment for CM or rescue therapy for neurocognitive residual injury are available, and research on this topic has been hampered due to the lack of well-defined experimental models. In the present study we have characterized the CM murine infection phenotypically, evaluating clinical parameters, which allowed establishing a model encompassing four distinct disease stages. This protocol provides the experimental framework to study adjunctive neuroprotective therapies that may prevent and/or eliminate the neurological sequelae in individuals surviving CM.Entre las enfermedades infecciosas más devastadoras del SNC se incluye la MC, debido a la alta mortalidad y las graves secuelas que ocasiona. Actualmente, no existe tratamiento farmacológico específico, ni de rescate de lesiones neurocognitivas residuales, y su desarrollo está limitado por la inexistencia de modelos experimentales bien definidos. En este trabajo se caracterizó fenotípicamente la infección en un modelo murino de MC evaluando parámetros clínicos que permitieron establecer cuatro estadios de la enfermedad. Este protocolo proporciona el marco experimental adecuado para estudiar terapias coadyuvantes neuroprotectoras que puedan prevenir y/o eliminar las secuelas neurológicas presentes en los individuos que sobreviven

Apoptosis-Like Death in Bacteria Induced by HAMLET, a Human Milk Lipid-Protein Complex

Background: Apoptosis is the primary means for eliminating unwanted cells in multicellular organisms in order to preserve tissue homeostasis and function. It is characterized by distinct changes in the morphology of the dying cell that are orchestrated by a series of discrete biochemical events. Although there is evidence of primitive forms of programmed cell death also in prokaryotes, no information is available to suggest that prokaryotic death displays mechanistic similarities to the highly regulated programmed death of eukaryotic cells. In this study we compared the characteristics of tumor and bacterial cell death induced by HAMLET, a human milk complex of alpha-lactalbumin and oleic acid. Methodology/Principal Findings: We show that HAMLET-treated bacteria undergo cell death with mechanistic and morphologic similarities to apoptotic death of tumor cells. In Jurkat cells and Streptococcus pneumoniae death was accompanied by apoptosis-like morphology such as cell shrinkage, DNA condensation, and DNA degradation into high molecular weight fragments of similar sizes, detected by field inverse gel electrophoresis. HAMLET was internalized into tumor cells and associated with mitochondria, causing a rapid depolarization of the mitochondrial membrane and bound to and induced depolarization of the pneumococcal membrane with similar kinetic and magnitude as in mitochondria. Membrane depolarization in both systems required calcium transport, and both tumor cells and bacteria were found to require serine protease activity (but not caspase activity) to execute cell death. Conclusions/Significance: Our results suggest that many of the morphological changes and biochemical responses associated with apoptosis are present in prokaryotes. Identifying the mechanisms of bacterial cell death has the potential to reveal novel targets for future antimicrobial therapy and to further our understanding of core activation mechanisms of cell death in eukaryote cells