24 research outputs found

    Cooperation between Apoptotic and Viable Metacyclics Enhances the Pathogenesis of Leishmaniasis

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    Mimicking mammalian apoptotic cells by exposing phosphatidylserine (PS) is a strategy used by virus and parasitic protozoa to escape host protective inflammatory responses. With Leishmania amazonensis (La), apoptotic mimicry is a prerogative of the intramacrophagic amastigote form of the parasite and is modulated by the host. Now we show that differently from what happens with amastigotes, promastigotes exposing PS are non-viable, non-infective cells, undergoing apoptotic death. As part of the normal metacyclogenic process occurring in axenic cultures and in the gut of sand fly vectors, a sub-population of metacyclic promastigotes exposes PS. Apoptotic death of the purified PS-positive (PSPOS) sub-population was confirmed by TUNEL staining and DNA laddering. Transmission electron microscopy revealed morphological alterations in PSPOS metacyclics such as DNA condensation, cytoplasm degradation and mitochondrion and kinetoplast destruction, both in in vitro cultures and in sand fly guts. TUNELPOS promastigotes were detected only in the anterior midgut to foregut boundary of infected sand flies. Interestingly, caspase inhibitors modulated parasite death and PS exposure, when added to parasite cultures in a specific time window. Efficient in vitro macrophage infections and in vivo lesions only occur when PSPOS and PS-negative (PSNEG) parasites were simultaneously added to the cell culture or inoculated in the mammalian host. The viable PSNEG promastigote was the infective form, as shown by following the fate of fluorescently labeled parasites, while the PSPOS apoptotic sub-population inhibited host macrophage inflammatory response. PS exposure and macrophage inhibition by a subpopulation of promastigotes is a different mechanism than the one previously described with amastigotes, where the entire population exposes PS. Both mechanisms co-exist and play a role in the transmission and development of the disease in case of infection by La. Since both processes confer selective advantages to the infective microorganism they justify the occurrence of apoptotic features in a unicellular pathogen

    Omics-based molecular techniques in oral pathology centred cancer: Prospect and challenges in Africa

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    : The completion of the human genome project and the accomplished milestones in the human proteome project; as well as the progress made so far in computational bioinformatics and “big data” processing have contributed immensely to individualized/personalized medicine in the developed world.At the dawn of precision medicine, various omics-based therapies and bioengineering can now be applied accurately for the diagnosis, prognosis, treatment, and risk stratifcation of cancer in a manner that was hitherto not thought possible. The widespread introduction of genomics and other omics-based approaches into the postgraduate training curriculum of diverse medical and dental specialties, including pathology has improved the profciency of practitioners in the use of novel molecular signatures in patient management. In addition, intricate details about disease disparity among diferent human populations are beginning to emerge. This would facilitate the use of tailor-made novel theranostic methods based on emerging molecular evidences

    Diversity and Evolution of Frog Visual Opsins: Spectral Tuning and Adaptation to Distinct Light Environments

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    \ua9 The Author(s) 2024. Published by Oxford University Press on behalf of Society for Molecular Biology and Evolution. Visual systems adapt to different light environments through several avenues including optical changes to the eye and neurological changes in how light signals are processed and interpreted. Spectral sensitivity can evolve via changes to visual pigments housed in the retinal photoreceptors through gene duplication and loss, differential and coexpression, and sequence evolution. Frogs provide an excellent, yet understudied, system for visual evolution research due to their diversity of ecologies (including biphasic aquatic-terrestrial life cycles) that we hypothesize imposed different selective pressures leading to adaptive evolution of the visual system, notably the opsins that encode the protein component of the visual pigments responsible for the first step in visual perception. Here, we analyze the diversity and evolution of visual opsin genes from 93 new eye transcriptomes plus published data for a combined dataset spanning 122 frog species and 34 families. We find that most species express the four visual opsins previously identified in frogs but show evidence for gene loss in two lineages. Further, we present evidence of positive selection in three opsins and shifts in selective pressures associated with differences in habitat and life history, but not activity pattern. We identify substantial novel variation in the visual opsins and, using microspectrophotometry, find highly variable spectral sensitivities, expanding known ranges for all frog visual pigments. Mutations at spectral-tuning sites only partially account for this variation, suggesting that frogs have used tuning pathways that are unique among vertebrates. These results support the hypothesis of adaptive evolution in photoreceptor physiology across the frog tree of life in response to varying environmental and ecological factors and further our growing understanding of vertebrate visual evolution

    Risk assessment and incidence of falls in adult hospitalized patients

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    Objectives: assess the risk of falls in adult hospitalized patients and verify the incidence of the event in this environment. Method: cohort study, with approval by the Research Ethics Committee, which monitored 831 patients hospitalized at a university hospital. The Morse Fall Scale (MFS) was used to assess the risk and patients with high risk (≥45 points) were considered exposed to falls. Results: the mean MFS score was 39.4 (±19.4) points. Between the first and the final assessment, the score increased by 4.6%. The first assessment score presented a strong and positive correlation with the final assessment score (r=0.810; p=0.000). Conclusion: the higher the risk score for falls when the patient is admitted, the higher the score at the end of the hospitalization period and vice-versa. The incidence rate corresponded to 1.68% with a higher percentage of patients classified at high risk of falls.Objetivos: avaliar o risco para quedas de pacientes adultos hospitalizados e verificar a incidência do evento nesse ambiente. Método: estudo de coorte, aprovado por Comitê de Ética em Pesquisa, que acompanhou 831 pacientes internados em um hospital universitário. Utilizou-se a Morse Fall Scale (MFS) para avaliar o risco e considerou-se exposto às quedas o paciente com risco elevado (≥45 pontos). Resultados: a média da pontuação da MFS foi de 39,4 (±19,4) pontos. Entre a primeira e a última avaliação, existiu um aumento de 4,6% na pontuação. O escore da primeira avaliação apresentou uma correlação positiva forte com o da última avaliação (r=0,810; p=0,000). Conclusão: quanto maior a pontuação de risco para quedas na admissão do paciente, maior ao final do período de internação e vice-versa. A taxa de incidência foi de 1,68% com maior percentual de pacientes classificados com risco elevado para quedas.Objetivos: evaluar el riesgo para caídas de pacientes hospitalizados y verificar la incidencia del evento en ese ambiente. Método: estudio de cohorte, aprobado por Comité de Ética en Investigación, que siguió 831 pacientes internados en un hospital universitario. Se utilizó la Morse Fall Scale (MFS) para evaluar el riesgo y se consideró como expuesto a las caídas el paciente con riesgo elevado (≥45 puntos). Resultados: la puntuación media de la MFS fue de 39,4 (±19,4) puntos. Entre la primera y la última evaluación, la puntuación aumentó en 4,6%. La puntuación de la primera evaluación mostró correlación positiva fuerte con la de la última evaluación (r=0,810; p=0,000). Conclusión: cuanto mayor la puntuación de riesgo para caídas en el momento de la admisión del paciente, mayor al final del período de internación y vice-versa. La tasa de incidencia fue 1,68% con mayor porcentaje de pacientes clasificados con riesgo elevado para caídas
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