Malarial hemozoin: From target to tool

Malaria is an extremely devastating disease that continues to affect millions of people each year. A distinctive attribute of malaria infected red blood cells is the presence of malarial pigment or so-called hemozoin. Hemozoin is a biocrystal synthesized by Plasmodium and other blood-feeding parasites to avoid the toxicity of free heme derived from the digestion of hemoglobin during invasion of the erythrocytes.Malaria is an extremely devastating disease that continues to affect millions of people each year. A distinctive attribute of malaria infected red blood cells is the presence of malarial pigment or so-called hemozoin. Hemozoin is a biocrystal synthesized by Plasmodium and other blood-feeding parasites to avoid the toxicity of free heme derived from the digestion of hemoglobin during invasion of the erythrocytes.Centro de Biología Celulary Molecularde Enfermedades, Instituto de Investigaciones Científicas y Servicios de AltaTecnología, Ciudad del Saber, Panama b Department ofBiotechnology, Acharya Nagarjuna University, Guntur 522510, A.P., India c Electricaland Computer Engineering, Clarkson University, Postdam, NY 13699-5720, US

Antiplasmodial activity of Cocos nucifera leaves in Plasmodium berghei-infected mice

Plasmodium falciparum (P. falciparum) malaria presents serious public health problems worldwide. The parasite s resistance to antimalarial drugs has proven to be a significant hurdle in the search for effective treatments against the disease. For this reason, the study of natural products to find new antimalarials remains a crucial step in the fight against malaria. In this study, we aimed to study the in vivo performance of the decoction of C. nucifera leaves in P. berghei-infected mice. We analyzed the effectiveness of different routes of administration and the acute toxicity of the extract. Additionally, we determined the suppressive, curative and prophylactic activity of the extract. The results showed that the decoction of leaves of C. nucifera is most effective when administered intramuscularly to mice in comparison to intraperitoneal, subcutaneous and intragastric methods. We also found that organ signs of acute toxicity appear at 2000 mg/kg/day as evidenced by necropsy examination. Additionally, we found that the prophylactic effect of the extract is of 48% inhibition, however, there is no curative effect. Finally, in a 4-day suppressive assay, we found that the extract can inhibit the growth of the parasite by up to 54% at sub-toxic doses when administered intramuscularly.Plasmodium falciparum (P. falciparum) malaria presents serious public health problems worldwide. The parasite s resistance to antimalarial drugs has proven to be a significant hurdle in the search for effective treatments against the disease. For this reason, the study of natural products to find new antimalarials remains a crucial step in the fight against malaria. In this study, we aimed to study the in vivo performance of the decoction of C. nucifera leaves in P. berghei-infected mice. We analyzed the effectiveness of different routes of administration and the acute toxicity of the extract. Additionally, we determined the suppressive, curative and prophylactic activity of the extract. The results showed that the decoction of leaves of C. nucifera is most effective when administered intramuscularly to mice in comparison to intraperitoneal, subcutaneous and intragastric methods. We also found that organ signs of acute toxicity appear at 2000 mg/kg/day as evidenced by necropsy examination. Additionally, we found that the prophylactic effect of the extract is of 48% inhibition, however, there is no curative effect. Finally, in a 4-day suppressive assay, we found that the extract can inhibit the growth of the parasite by up to 54% at sub-toxic doses when administered intramuscularly

Multi-Omics and Genome Editing Studies on Plant Cell Walls to Improve Biomass Quality

Biomass is one of the most important sources of renewable energy and plays an important role in reducing our reliance on fossil fuels. Efficient biomass production is essential to obtain large amounts of sustainable energy with minimal environmental cost. However, the biochemical and molecular processes behind the synthesis of the main components of biomass are still not fully understood. This review provides a comprehensive summary of the most relevant studies on cell wall biosynthesis and degradation mechanisms, focusing on the lignocellulosic component, in which the conversion process to fermentable sugars is expensive, due to its recalcitrant nature. A focus is placed on multi-omics research involving genomics, transcriptomics, proteomics, metabolomics, and phenomics, since multi-omics approaches offer a unique opportunity to investigate the biological pathways underlying the genotype traits characterizing cell wall energy crops. Furthermore, our study highlights the advances in genome editing approaches and proposes the modification of the genes that are involved in the complex cell wall structure as a feasible solution to an efficient biomass production. Several key points for future research activities based on these emerging technologies are also discussed, focusing on the combination of multi-omics and gene editing approaches, which offer potential for improved biomass valorization and the development of tangible bioproducts

Magnetic Reversal Time in Open Long Range Systems

Topological phase space disconnection has been recently found to be a general phenomenon in isolated anisotropic spin systems. It sets a general framework to understand the emergence of ferromagnetism in finite magnetic systems starting from microscopic models without phenomenological on-site barriers. Here we study its relevance for finite systems with long range interacting potential in contact with a thermal bath. We show that, even in this case, the induced magnetic reversal time is exponentially large in the number of spins, thus determining {\it stable} (to any experimental observation time) ferromagnetic behavior. Moreover, the explicit temperature dependence of the magnetic reversal time obtained from the microcanonical results, is found to be in good agreement with numerical simulations. Also, a simple and suggestive expression, indicating the Topological Energy Threshold at which the disconnection occurs, as a real energy barrier for many body systems, is obtained analytically for low temperature

Biochemical and molecular changes in peach fruit exposed to cold stress conditions

: Storage or transportation temperature is very important for preserving the quality of fruit. However, low temperature in sensitive fruit such as peach can induce loss of quality. Fruit exposed to a specific range of temperatures and for a longer period can show chilling injury (CI) symptoms. The susceptibility to CI at low temperature varies among cultivars and genetic backgrounds. Along with agronomic management, appropriate postharvest management can limit quality losses. The importance of correct temperature management during postharvest handling has been widely demonstrated. Nowadays, due to long-distance markets and complex logistics that require multiple actors, the management of storage/transportation conditions is crucial for the quality of products reaching the consumer.Peach fruit exposed to low temperatures activate a suite of physiological, metabolomic, and molecular changes that attempt to counteract the negative effects of chilling stress. In this review an overview of the factors involved, and plant responses is presented and critically discussed. Physiological disorders associated with CI generally only appear after the storage/transportation, hence early detection methods are needed to monitor quality and detect internal changes which will lead to CI development. CI detection tools are assessed: they need to be easy to use, and preferably non-destructive to avoid loss of products

Respuesta

Lo estimulante de ambos comentarios es que nos invitan a ir más allá de los propósitos que nos habíamos fijado. Originalmente nos interesaba problematizar la correspondencia entre impulsos localizadores o globalizadores y posiciones de poder, para proponer que al menos en ciertos escenarios transnacionalizados la disputa política por la fijación de sentidos distingue a las partes enfrentadas no tanto por determinaciones supuestamente divergentes a globalizar (posición hcgcmónica) o localizar (posición subalterna), sino más bien poruña disputa centrada en qué y cómo globalizar y/o localizar. Obviamente, tal disputa no está al margen de que la dinámica de poder que entrama esos escenarios signe diferencialmente la suerte de lo que en concreto se globalice o localice.Respuesta sobre los comentarios realizados respecto del artículo de Briones, Claudia ...[et. al.]: “Desinflando el globo: otras caras de la globalización”. Relaciones de la Sociedad Argentina de Antropología, XXI, 1996, pp. 119-136.Sociedad Argentina de Antropologí

Respuesta

Lo estimulante de ambos comentarios es que nos invitan a ir más allá de los propósitos que nos habíamos fijado. Originalmente nos interesaba problematizar la correspondencia entre impulsos localizadores o globalizadores y posiciones de poder, para proponer que al menos en ciertos escenarios transnacionalizados la disputa política por la fijación de sentidos distingue a las partes enfrentadas no tanto por determinaciones supuestamente divergentes a globalizar (posición hcgcmónica) o localizar (posición subalterna), sino más bien poruña disputa centrada en qué y cómo globalizar y/o localizar. Obviamente, tal disputa no está al margen de que la dinámica de poder que entrama esos escenarios signe diferencialmente la suerte de lo que en concreto se globalice o localice.Respuesta sobre los comentarios realizados respecto del artículo de Briones, Claudia ...[et. al.]: “Desinflando el globo: otras caras de la globalización”. Relaciones de la Sociedad Argentina de Antropología, XXI, 1996, pp. 119-136.Sociedad Argentina de Antropologí

Effects of β2-receptor stimulation by indacaterol in chronic heart failure treated with selective or non-selective β-blockers: a randomized trial

Alveolar \u3b22-receptor blockade worsens lung diffusion in heart failure (HF). This effect could be mitigated by stimulating alveolar \u3b22-receptors. We investigated the safety and the effects of indacaterol on lung diffusion, lung mechanics, sleep respiratory behavior, cardiac rhythm, welfare, and exercise performance in HF patients treated with a selective (bisoprolol) or a non-selective (carvedilol) \u3b2-blocker. Study procedures were performed before and after indacaterol and placebo treatments according to a cross-over, randomized, double-blind protocol in forty-four patients (27 on bisoprolol and 17 on carvedilol). No differences between indacaterol and placebo were observed in the whole population except for a significantly higher VE/VCO2 slope and lower maximal PETCO2 during exercise with indacaterol, entirely due to the difference in the bisoprolol group (VE/VCO2 31.8\u2009\ub1\u20095.9 vs. 28.5\u2009\ub1\u20095.6, p\u2009<\u20090.0001 and maximal PETCO2 36.7\u2009\ub1\u20095.5 vs. 37.7\u2009\ub1\u20095.8\u2009mmHg, p\u2009<\u20090.02 with indacaterol and placebo, respectively). In carvedilol, indacaterol was associated with a higher peak heart rate (119\u2009\ub1\u200934 vs. 113\u2009\ub1\u200930 bpm, with indacaterol and placebo) and a lower prevalence of hypopnea during sleep (3.8 [0.0;6.3] vs. 5.8 [2.9;10.5] events/hour, with indacaterol and placebo). Inhaled indacaterol is well tolerated in HF patients, it does not influence lung diffusion, and, in bisoprolol, it increases ventilation response to exercise

Marine cyanobacteria-derived serotonin receptor 2C active fraction induces psychoactive behavioral effects in mice

Context—Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. Objective—To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects. Materials and methods—Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests.Context—Marine cyanobacteria offer a robust resource for natural products drug discovery due to the secondary metabolites they produce. Objective—To identify novel cyanobacterial compounds that exhibit CNS psychoactive effects. Materials and methods—Cyanobacteria were collected from Las Perlas Archipelago, Panama and subjected to dichloromethane/methanol extraction and fractionation by column chromatography before being screened for affinity against a panel of CNS targets. A 50:50 ethyl acetate:methanol fraction of one cyanobacterial extract (2064H) was subjected to HPLC and the major peak was isolated (2064H3). At a dose of 20 μg per animal, 2064H and 2064H3 were tested in mice using behavioral assays that included the forced swim, open field, and formalin tests