Plasmodium falciparum metacaspase PfMCA-1 triggers a z-VAD-fmk inhibitable protease to promote cell death.

Activation of proteolytic cell death pathways may circumvent drug resistance in deadly protozoan parasites such as Plasmodium falciparum and Leishmania. To this end, it is important to define the cell death pathway(s) in parasites and thus characterize proteases such as metacaspases (MCA), which have been reported to induce cell death in plants and Leishmania parasites. We, therefore, investigated whether the cell death function of MCA is conserved in different protozoan parasite species such as Plasmodium falciparum and Leishmania major, focusing on the substrate specificity and functional role in cell survival as compared to Saccharomyces cerevisae. Our results show that, similarly to Leishmania, Plasmodium MCA exhibits a calcium-dependent, arginine-specific protease activity and its expression in yeast induced growth inhibition as well as an 82% increase in cell death under oxidative stress, a situation encountered by parasites during the host or when exposed to drugs such as artemisins. Furthermore, we show that MCA cell death pathways in both Plasmodium and Leishmania, involve a z-VAD-fmk inhibitable protease. Our data provide evidence that MCA from both Leishmania and Plasmodium falciparum is able to induce cell death in stress conditions, where it specifically activates a downstream enzyme as part of a cell death pathway. This enzymatic activity is also induced by the antimalarial drug chloroquine in erythrocytic stages of Plasmodium falciparum. Interestingly, we found that blocking parasite cell death influences their drug sensitivity, a result which could be used to create therapeutic strategies that by-pass drug resistance mechanisms by acting directly on the innate pathways of protozoan cell death

Effectiveness of Pyriproxyfen and Olyset Duo in Controlling Insecticide Resistant Mosquito Populations in Burkina Faso

The escalation of Long-Lasting Insecticidal Nets (LLINs) mass distribution marked the beginning of a period of malaria decline in sub-Saharan Africa. However, the emergence and spread of insecticide resistance in malaria mosquitoes is a threat to the effectiveness and sustainability of this vector control method. In this context, it is necessary to design and evaluate new compounds and methods that attenuate or even reverse the insecticide resistance trend. Olyset Duo is a novel LLIN that combines the insecticide properties of permethrin and the chemosterilising effect of pyriproxyfen (PPF). The rationale is that resistant mosquitoes that survive the contact with the net would not be able to transfer the resistance genes to the offspring, eventually influencing the resistant phenotype of the mosquito population. In the first part of this study the sterilising and sub-lethal effect of PPF and Olyset Duo was evaluated by a range of bioassays with laboratory and wild mosquito populations. PPF significantly affected the longevity, oogenesis, oviposition and hatching rate of susceptible and resistant mosquitoes, although the effect was partially diminished on the resistant colonies. The possible reasons and implications of PPF performance under controlled conditions are discussed. The second part of this thesis was done within the context of an Olyset Duo Randomised Controlled Trial (RCT) set in Banfora District, Burkina Faso. The RCT had a stepped-wedge design which ensured that Olyset Duo nets gradually replaced Olyset nets in randomly allocated cluster of villages until the Olyset Duo coverage was total. Wild mosquitoes collected in sentinel sites with Olyset Duo showed evident signs of reproductive impairment even after 1 year of deployment. Insecticide resistance strength was monitored during the RCT in several sentinel sites, and time-response data showed an overall reduction of permethrin resistance strength after the distribution of Olyset Duo. This is the most detailed study on the effect of Olyset Duo on key entomological factors of wild mosquito populations. The standardised protocols as well as the dataset obtained are valuable information for ongoing evaluation of Olyset Duo and PPF as a tool for controlling malaria mosquitoes and as a potential alternative for insecticide resistance management

Identification of Aspergillus westerdijkiae and its potential risk of Ochratoxin A synthesis in Cannabis inflorescences

Nowadays, fungal contamination of medical Cannabis inflorescences during postharvest has become an increasingly frequent and worrisome problem for consumers and the industry in general. This is because some of these microorganisms can produce secondary metabolites, such as mycotoxins, which can be toxic to humans. To assess the risk posed by fungal contamination and evaluate the potential for fungal isolates to produce mycotoxins, samples of medicinal Cannabis were tested for the presence of mycotoxin-forming fungi. Inflorescences were isolated on PDA agar at 23 ± 2 °C for ten days, and the microorganisms were identified. The strain with morphological characteristics compatible with the genus Aspergillus spp. was selected as the fungus with the highest risk of forming hazardous mycotoxins. This isolate was characterized conventionally and by molecular identification using primers for the internal transcribed spacer region (ITS) of ribosomal DNA and different coding genes and was identified as Aspergillus westerdijkiae. To determine mycotoxin formation, the genome of A. westerdijkiae was sequenced using the Illumina Novaseq platform in South Korea. The antiSMASH tool was used to search for gene clusters associated with producing secondary metabolites, and genes related to toxins were manually curated. Regions where the cluster of genes directly involved in OTA biosynthesis (otaA, otaB, otaC, otaR and otaD) were found, suggesting a potential risk of synthesis of this toxin

Deep Learning Hamiltonians from Disordered Image Data in Quantum Materials

The capabilities of image probe experiments are rapidly expanding, providing new information about quantum materials on unprecedented length and time scales. Many such materials feature inhomogeneous electronic properties with intricate pattern formation on the observable surface. This rich spatial structure contains information about interactions, dimensionality, and disorder -- a spatial encoding of the Hamiltonian driving the pattern formation. Image recognition techniques from machine learning are an excellent tool for interpreting information encoded in the spatial relationships in such images. Here, we develop a deep learning framework for using the rich information available in these spatial correlations in order to discover the underlying Hamiltonian driving the patterns. We first vet the method on a known case, scanning near-field optical microscopy on a thin film of VO2. We then apply our trained convolutional neural network architecture to new optical microscope images of a different VO2 film as it goes through the metal-insulator transition. We find that a two-dimensional Hamiltonian with both interactions and random field disorder is required to explain the intricate, fractal intertwining of metal and insulator domains during the transition. This detailed knowledge about the underlying Hamiltonian paves the way to using the model to control the pattern formation via, e.g., tailored hysteresis protocols. We also introduce a distribution-based confidence measure on the results of a multi-label classifier, which does not rely on adversarial training. In addition, we propose a new machine learning based criterion for diagnosing a physical system's proximity to criticality

Voltage-Induced Ferromagnetic Resonance in Magnetic Tunnel Junctions

We demonstrate excitation of ferromagnetic resonance in CoFeB/MgO/CoFeB magnetic tunnel junctions (MTJs) by the combined action of voltage-controlled magnetic anisotropy (VCMA) and spin transfer torque (ST). Our measurements reveal that GHz-frequency VCMA torque and ST in low-resistance MTJs have similar magnitudes, and thus that both torques are equally important for understanding high-frequency voltage-driven magnetization dynamics in MTJs. As an example, we show that VCMA can increase the sensitivity of an MTJ-based microwave signal detector to the sensitivity level of semiconductor Schottky diodes.Comment: 5 pages; supplementary material adde

Actitud de los estudiantes de IX y X semestre del Colegio Odontológico Colombiano frente al paciente VIH, 2006-I

Objetivo: Identificar cuál es la actitud de estudiantes de odontologí­a frente al paciente VIH. Materiales y métodos: Se realizó un estudio observacional descriptivo de corte transversal. La muestra fue de 141 estudiantes de las clí­nicas del Colegio Odontológico Colombiano, seleccionados aleatoriamente. La recolección de la información se realizó con una encuesta tipo cuestionario de 19 preguntas. Se evaluaron actitudes del estudiante de odontologí­a frente al paciente VIH positivo, teniendo en cuenta variables como la edad, el semestre, el estado civil, la religión, las actitudes que tení­a el estudiante para la atención de pacientes VIH. Resultados: El género femenino se presentó con mayor proporción en la investigación con un 68.8%. El 64.5% del grupo estudiado pertenecí­a a 9 semestre. Se encontró que el 85.1% de los estudiantes atenderí­an a pacientes VIH+. La condición de bioseguridad fue la más importante para llevar a cabo esta actividad (71.6%), siendo más importante para los estudiantes de 10 semestre. La mayorí­a de los estudiantes manifestó sentir compromiso ético y profesional con porcentajes de 80.2% y 78% respectivamente para la atención de pacientes VIH+, siendo más importante para los estudiantes de 9 semestre (83% y 80% respectivamente). La atención de los pacientes como si fueran todos VIH+ es una práctica que el 84.4% llevan a cabo durante la consulta, situación que es más frecuente en los estudiantes de 10 semestre (86%). Conclusiones: Los estudiantes no presentaron problemas a la hora de atender pacientes VIH positivos; aunque se pudo apreciar que los conocimientos que éstos tienen para atenderlos en muchas ocasiones son insuficientes

Magnetic stray fields in nanoscale magnetic tunnel junctions

The magnetic stray field is an unavoidable consequence of ferromagnetic devices and sensors leading to a natural asymmetry in magnetic properties. Such asymmetry is particularly undesirable for magnetic random access memory applications where the free layer can exhibit bias. Using atomistic dipole-dipole calculations we numerically simulate the stray magnetic field emanating from the magnetic layers of a magnetic memory device with different geometries. We find that edge effects dominate the overall stray magnetic field in patterned devices and that a conventional synthetic antiferromagnet structure is only partially able to compensate the field at the free layer position. A granular reference layer is seen to provide near-field flux closure while additional patterning defects add significant complexity to the stray field in nanoscale devices. Finally we find that the stray field from a nanoscale antiferromagnet is surprisingly non-zero arising from the imperfect cancellation of magnetic sublattices due to edge defects. Our findings provide an outline of the role of different layer structures and defects in the effective stray magnetic field in nanoscale magnetic random access memory devices and atomistic calculations provide a useful tools to study the stray field effects arising from a wide range of defects