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Biology subjects

Almeida, L. G.

Publications and source records attributed to Almeida, L. G..

5 recordsLinked to original sources

Identification of a sub-population of synovial mesenchymal stem cells with enhanced treatment efficacy in a rat model of Osteoarthritis

Osteoarthritis (OA) is a painful and debilitating disease which has no cure and there are no treatments which can predictably stop/reverse its progression. Treating this disease is particularly difficult since the articular cartilage lacks intrinsic repair capacity even though mesenchymal stem cells (MSCs) are present in the joint environment and have robust chondrogenic potential. We have previously shown that there is heterogeneity of MSC sub-types within the human synovium, yet it remains unclear if any of these MSC types can regenerate cartilage and/or impact OA disease progression. Therefore, we have undertaken this study focusing on clonally derived MSC populations derived from the synovium of normal and OA patients to characterize if any MSC populations can positively impact OA disease trajectory in a rat model of OA. MSCs were clonally isolated by indexed flow cytometry, expanded in culture and then characterized for differentiation capacity and by quantitative proteomics. MSC clones were then transplanted into a xenograft rat OA model and treatment effect was determined by histology and immunofluorescence outcomes. We identified heterogeneity in putative MSCs derived from within and between patient groups (normal vs. OA) and the ability of these cells to effect repair in a rat OA model. However, these different sub-types of MSCs could not be distinguished by traditional cell surface markers showing the need for a better understanding of these populations at the single cell level. Using an unbiased proteomics approach, CD47 was identified a novel marker of human MSCs. Using the same rat model of OA, CD47Hi expressing cells were found to have robust treatment efficacy and directly contributed to the formation of new articular cartilage tissue. Characterizing MSCs is essential to understand which sub-types are appropriate for further clinical investigation. If OA patients still have functional MSCs in their synovium, then it is possible these cells can be exploited for cartilage regeneration / OA treatment strategies.

cell biology↗

Comparative genomics of pesticide-degrading Enterococcus symbionts of Spodoptera frugiperda (Lepidoptera: Noctuidae) leads to the identification of two new species and the reappraisal of insect-associated Enterococcus species

Enterococcus species have been described as core members of the microbial community of Spodoptera frugiperda (Lepidoptera:Noctuidae) and have been reported in previous studies as insecticide degrading agents. Phenotypic assays and comparative genomics analyses of several pesticide-degrading Enterococcus isolated from the larval gut of S. frugiperda led to the identification of Enterococcus entomosocium n. sp. and Enterococcus spodopteracolus n. sp. Their identities as new species were confirmed by whole genome alignment using the cut-offs of 95-96% for the average nucleotide identity (ANI) and 70% for the digital DNA:DNA hybridization (dDDH) values. The systematic positioning of these new species within the genus Enterococcus was resolved using genome-based analysis, placing Enterococcus casseliflavus as the sister group of E. entomosocium n. sp., and Enterococcus mundtii of E. spodopteracolus n. sp. Comparative genomic analyses of several isolates of E. entomosocium n. sp. and E. spodopteracolus n. sp. led to a better assessment of the interactions established in the symbiotic association with S. frugiperda, and the discovery of misidentified new species of Enterococcus associated with insects. Our analyses also indicated the potential of E. entomosocium n. sp. And E. spodopteracolus n. sp. to metabolize different pesticides arises from molecular mechanisms that result in the rapid evolution of new phenotypes in response to environmental stressors; in this case, the pesticides their host insect is exposed to.

microbiology↗

SARS-CoV-2 infection of circulating immune cells is not responsible for virus dissemination in severe COVID-19 patients

In late 2019 a novel coronavirus (SARS-CoV-2) emerged, and has since caused a global pandemic. Understanding the pathogenesis of COVID-19 disease is necessary to inform development of therapeutics, and management of infected patients. Using scRNAseq of blood drawn from SARS-CoV-2 patients, we asked whether SARS-CoV-2 may exploit immune cells as a Trojan Horse to disseminate and access multiple organ systems. Our data suggests that circulating cells are not actively infected with SARS-CoV-2, and do not appear to be a source of viral dissemination.

immunology↗

Anthropometric and functional profiles of elite athletes from different categories at ABADA Capoeira World Championship

This study aimed to characterize the anthropometric and functional profiles of 50 male elite competitors at the 2017 Capoeira World Championship organized by ABADA Capoeira School in the city of Rio de Janeiro. The competitors were divided into different weight categories: lightweight (VIOLA, [&le;]76.9 kg; n = 15), intermediate weight (MEDIO, 77.0-85.9 kg; n = 25), and heavyweight (GUNGA, [&ge;]86.0 kg; n = 10). Two evaluation batteries were performed: 1) anthropometry and somatotype determination and 2) functional performance on push-up, sit-up, and sit-and-reach tests; quadrant jump test (QJT); squat jump (SJ); and countermovement jump (CMJ). Results reveal that the mesomorphic component of the somatotype differed between the GUNGA subgroup and other groups (F[2,47] = 7.617; p = 0.001), while ectomorphy differed between the VIOLA and GUNGA subgroups (F[2,47] = 3.899; p = 0.027). The \"endo-mesomorph\" classification predominated in the three investigated categories. For functional performance, there was a difference in QJT between the VIOLA and GUNGA subgroups (F[2,47] = 4.299; p = 0.019). The endomorphism had a negative correlation (p < 0.01) with the performance in the sit-up (r = -0.51), push -up (r = -0.39), SJ (r = -0.45), and CMJ (r = -0.49). We concluded that at the international level, male elite competitors show predominance in the mesomorphic component of the somatotype. Furthermore, the endomorphic component correlated inversely with functional performance in trunk and upper limb resistance tests and lower limb explosive strength tests. These results can help coaches in targeting specific training programs for Capoeira athletes who aim for a high competitive level.

physiology↗

Continuous rearrangement of the postsynaptic gephyrin scaffolding domain: a super-resolution quantified and energetic approach

Synaptic function and plasticity requires a delicate balance between overall structural stability and the continuous rearrangement of the components that make up the presynaptic active zone and the postsynaptic density (PSD). Photoactivated localization microscopy (PALM) has provided a detailed view of the nanoscopic structure and organization of some of these synaptic elements. Still lacking, are tools to address the morphing and stability of such complexes at super-resolution. We describe an approach to quantify morphological changes and energetic states of multimolecular assemblies over time. With this method, we studied the scaffold protein gephyrin, which forms postsynaptic clusters that play a key role in the stabilization of receptors at inhibitory synapses. Postsynaptic gephyrin clusters exhibit an internal microstructure composed of nanodomains. We found, that within the PSD, gephyrin molecules continuously undergo spatial reorganization. This dynamic behavior depends on neuronal activity and cytoskeleton integrity. The proposed approach also allowed access to the effective energy responsible for the tenacity of the PSD despite molecular instability.\n\nSignificant statementSuper-resolution microscopy has become an important tool for the study of biological systems, allowing detailed, nano-scale structural reconstruction, single molecule tracking, particle counting, and interaction studies. However, quantification tools that take full advantage of the information provided by this technology are still lacking. We describe a novel quantification method to obtain information related to the size, directionality, dynamics, and stability of clustered structures from super-resolution microscopy. With this method, we studied the stability of gephyrin clusters, the main inhibitory scaffold protein. We found that gephyrin molecules continuously undergo reorganization based on neuronal activity and changes in the cytoskeleton.

biophysics↗