Loss of p53 promotes RhoA–ROCK-dependent cell migration and invasion in 3D matrices

In addition to its role in controlling cell cycle progression, the tumor suppressor protein p53 can also affect other cellular functions such as cell migration. In this study, we show that p53 deficiency in mouse embryonic fibroblasts cultured in three-dimensional matrices induces a switch from an elongated spindle morphology to a markedly spherical and flexible one associated with highly dynamic membrane blebs. These rounded, motile cells exhibit amoeboid-like movement and have considerably increased invasive properties. The morphological transition requires the RhoA–ROCK (Rho-associated coil-containing protein kinase) pathway and is prevented by RhoE. A similar p53-mediated transition is observed in melanoma A375P cancer cells. Our data suggest that genetic alterations of p53 in tumors are sufficient to promote motility and invasion, thereby contributing to metastasis

Autoavaliação de estudantes universitários sobre seu desempenho acadêmico durante a pandemia da COVID-19

Objetivo: Analisar como os estudantes universitários autoavaliam o seu desempenho acadêmico durante a pandemia da COVID-19 em uma universidade pública do sul do Brasil. Método: estudo transversal realizado por meio de um questionário online respondido por 527 estudantes em julho e agosto de 2020. Realizou-se análise estatística descritiva e o teste qui-quadrado para avaliar associações. Resultados: Entre os participantes,49,5% referiram um desempenho acadêmico insuficiente,24,1% suficiente,19,40% bom,5,90% muito bom e 1,10% excelente. Verificou-se que houve associação entre as variáveis curso (p=0,034), forma de ingresso na instituição (p=0,016) e atividade de trabalho (p=0,010) e o desempenho acadêmico durante a pandemia de COVID-19. Conclusão: O desempenho acadêmico durante a suspensão das aulas presenciais está sendo insuficiente para muitos estudantes. The occupational therapy students who entered in the university through the system of quotas and work in addition to studying had a worse academic performance during the COVID-19 pandemic. Palavras-chave: Infecções por coronavírus. Pandemias. Desempenho acadêmico. Capacitação de recursos humanos em saúde

Antibacterial potential of commercial and wild lactic acid bacteria strains isolated from ovine and caprine raw milk against Mycoplasma agalactiae

© 2023 Toquet, Bataller, Gomis, Sánchez, Toledo-Perona, De la Fe, Corrales and Gómez-Martín. This is an open-access article distributed under the terms of the Creative Commons CC-BY license, http://creativecommons.org/licenses/by /4.0/ This document is the Published version of a Published Work that appeared in final form in Frontiers in Veterinary Science. To access the final edited and published work see https://doi.org/10.3389/fvets.2023.1197701Introduction: The complexity of fighting contagious agalactia (CA) has raised the necessity of alternative antimicrobial therapies, such as probiotics. Lactic acid bacteria (LAB) are present in the mammary gland of small ruminants and their antimicrobial effect have been previously described against species like Mycoplasma bovis but never against Mycoplasma agalactiae (Ma). This in vitro study aims to evaluate the antimicrobial activity against Ma of ovine and caprine LAB strains and a human commercial probiotic (L2) of Lactobacillus spp. Methods: A total of 63 possible LAB strains were isolated from nine ovine and caprine farms in Spain, three isolates (33B, 248D, and 120B) from the 63 strains were selected, based on their capacity to grow in a specific medium in vitro, for an in vitro experiment to assess their antimicrobial activity against Ma in Ultra High Temperature (UHT) processed goat milk (GM). A women commercial vaginal probiotic was also included in the study. The inoculum of L2 was prepared at a concentration of 3.24 × 108  CFU/mL and the average concentration of the inoculum of the wild LAB varied from 7.9 × 107 to 8.4 × 108  CFU/mL. Results: The commercial probiotic L2 significantly reduced the concentration of Ma to 0.000 log CFU/mL (p < 0.001), strain 33B reduced it from 7.185 to 1.279 log CFU/mL (p < 0.001), and 120B from 6.825 to 6.466 log CFU/mL (p < 0.05). Strain 248D presented a bacteriostatic effect in GM. Moreover, the three wild strains and the commercial probiotic produced a significative reduction of the pH (p < 0.001). Discussion: This is the first in vivo report of the antimicrobial potential of LAB strains against Ma and its interaction. Our results support possible future alternative strategies to antibiotic therapy, previously not contemplated, to fight CA in small ruminants. Further studies are necessary to elucidate the action mechanisms through which these LAB are able to inhibit Ma and to assess the safety of using these strains in possible in vivo studies

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

TCL, une nouvelle GTPase de la famille Rho impliquée dans le trafic cellulaire

MONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Modeling and optimal control formulation for manual wheelchair locomotion: The influence of mass and slope on performance

A framework to generate predictive simulations is proposed to investigate the influence of system's mass on manual wheelchair locomotion. The approach is based on a model of wheelchair propulsion dynamics and an optimal control formulation. In this study, predictive simulations of steady-state wheelchair locomotion are generated for different combinations of model mass and uphill slope inclination angle. The results show that the influence of system's mass is negligible in level surfaces in steady-state, a finding which agrees with experimental observations in the literature. On the other hand, the results show that the influence of mass on slopes is critical, with large increases in propulsion effort with system's mass, even for slight inclination angles. This shows the importance of reducing wheelchair mass for improving locomotion performance, particularly in overcoming obstacles and ramps. Decreasing the wheelchair's mass may not be sufficient. Therefore, and on the light of these findings, we propose the reduction of system's apparent mass through the implementation of an impedance control scheme in power-assisted wheelchairs.CNP

The gene for a new brain specific RhoA exchange factor maps to the highly unstable chromosomal region 1p36.2–1p36.3.

International audienc

Analysis of cell migration and its regulation by Rho GTPases and p53 in a three-dimensional environment.

International audienceCell migration plays a key role both in physiological conditions, such as tissue repair or embryonic development, and in pathological processes, including tumor metastasis. Understanding the mechanisms that allow cancer cells to invade tissues during metastasis requires studying their ability to migrate. While spectacular, the movements observed in cells growing on two-dimensional supports are likely only to represent a deformation of the physiological migratory behavior. In contrast, the analysis of cell migration on a support, which resembles the three-dimensional (3D) extracellular matrix, provides a more pertinent model of physiological relevance. This chapter provides protocols to assay the ability of cells to migrate or to invade a 3D matrix and to analyze their phenotypes. The invasion assay allows the quantification of tumor cell invasiveness, and the 3D migration assay permits the visual observation of the movements and morphology of migrating cells. This chapter also describes a method to examine the localization of different markers during 3D migration. Because Rho GTPases are clearly involved in migration and invasion, a protocol is supplied to evaluate their activation during cell migration. These techniques are especially suitable to elucidate the type of motility in a 3D matrix, particularly to discriminate between two different modes of migration adopted by cancer cells: blebbing versus elongation. Indeed, the way a cell moves may have important consequences for its invasiveness, as, for example, cancer cells adopt a rounded blebbing movement when deficient in p53

Modulation of Yorkie activity by alternative splicing is required for developmental stability

The mechanisms that contribute to developmental stability are barely known. Here we show that alternative splicing of yorkie ( yki ) is required for developmental stability in Drosophila . Yki encodes the effector of the Hippo pathway that has a central role in controlling organ growth and regeneration. We identify the splicing factor B52 as necessary for inclusion of yki alternative exon 3 that encodes one of the two WW domains of Yki protein. B52 depletion favors expression of Yki1 isoform carrying a single WW domain, and reduces growth in part through modulation of yki alternative splicing. Compared to the canonical Yki2 isoform containing two WW domains, Yki1 isoform has reduced transcriptional and growth-promoting activities, decreased binding to PPxY-containing partners, and lacks the ability to bridge two proteins containing PPxY motifs. Yet, Yki1 and Yki2 interact similarly with transcription factors and can thus compete in vivo . Strikingly, flies deprived from Yki1 isoform exhibit increased fluctuating wing asymmetry, a signal of increased developmental noise. Our results identify yki alternative splicing as a new level of control of the Hippo pathway and provide the first experimental evidence that alternative splicing participates in developmental robustness

The GTP/GDP Cycling of Rho GTPase TCL Is an Essential Regulator of the Early Endocytic Pathway

Rho GTPases are key regulators of actin dynamics. We report that the Rho GTPase TCL, which is closely related to Cdc42 and TC10, localizes to the plasma membrane and the early/sorting endosomes in HeLa cells, suggesting a role in the early endocytic pathway. Receptor-dependent internalization of transferrin (Tf) is unaffected by suppression of endogenous TCL by small interfering RNA treatment. However, Tf accumulates in Rab5-positive uncoated endocytic vesicles and fails to reach the early endosome antigen-1–positive early endosomal compartments and the pericentriolar recycling endosomes. Moreover, Tf release upon TCL knockdown is significantly slower. Conversely, in the presence of dominant active TCL, internalized Tf accumulates in early endosome antigen-1–positive early/sorting endosomes and not in perinuclear recycling endosomes. Tf recycles directly from the early/sorting endosomes and it is normally released by the cells. The same phenotype is generated by replacing the C terminus of dominant active Cdc42 and TC10 with that of TCL, indicating that all three proteins share downstream effector proteins. Thus, TCL is essential for clathrin-dependent endocytosed receptors to enter the early/sorting endosomes. Furthermore, the active GTPase favors direct recycling from early/sorting endosomes without accumulating in the perinuclear recycling endosomes