ALEXANDRE FERREIRA RAMOS
Projetos de Pesquisa
Unidades Organizacionais
SIN-86, EACH - Docente
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/26 - Laboratório de Pesquisa em Cirurgia Experimental, Hospital das Clínicas, Faculdade de Medicina
4 resultados
Resultados de Busca
Agora exibindo 1 - 4 de 4
conferenceObject A simulation of laser energy absorption by a nanowired surface(2019) VASCONCELOS, Miguel F. S.; RAMOS, Alexandre F.The quest for strategies for performing nuclear fusion induced by laser remains open despite recent experiments demonstrating energy gain. A major challenge of the field is to surmount the plasma shielding which prevents the deposition of larger fractions of the energy of the laser rays into the target. Recently, a petawatt laser and computer simulations were used to show that a nanowired surface enables the trapping of the rays and the formation of a high density plasma. Here we simulate the laser target interaction considering a 0.5 TW laser and compare the energy absorption by both a smoothed and a nanowired target. We show that the nanowires enable a stronger laser-target coupling despite the absence of the trapping of the rays. Our results point out on the necessity of a deeper understanding of the mechanisms underlying the higher absorption of the laser energy by the nanowired surfaces.- Physical implications of so(2,1) symmetry in exact solutions for a self-repressing gene(2019) RAMOS, Alexandre F.; REINITZ, JohnWe chemically characterize the symmetries underlying the exact solutions of a stochastic negatively self-regulating gene. The breaking of symmetry at a low molecular number causes three effects. Two branches of the solution exist, having high and low switching rates, such that the low switching rate branch approaches deterministic behavior and the high switching rate branch exhibits sub-Fano behavior. The average protein number differs from the deterministically expected value. Bimodal probability distributions appear as the protein number becomes a readout of the ON/OFF state of the gene.
- Peri/epicellular protein disulfide isomerase-A1 acts as an upstream organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells(2019) TANAKA, Leonardo Y.; ARAUJO, Thais L. S.; I, Andres Rodriguez; FERRAZ, Mariana S.; PELEGATI, Vitor B.; MORAIS, Mauro C. C.; SANTOS, Aline M. dos; CESAR, Carlos L.; RAMOS, Alexandre F.; ALENCAR, Adriano M.; LAURINDO, Francisco R. M.Although redox processes closely interplay with mechanoresponses to control vascular remodeling, redox pathways coupling mechanostimulation to cellular cytoskeletal organization remain unclear. The peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) supports postinjury vessel remodeling. Using distinct models, we investigated whether pecPDIA1 could work as a redox-dependent organizer of cytoskeletal mechanoresponses. In vascular smooth muscle cells (VSMCs), pecPDIA1 immunoneutralization impaired stress fiber assembly in response to equibiaxial stretch and, under uniaxial stretch, significantly perturbed cell repositioning perpendicularly to stretch orientation. During cyclic stretch, pecPDIA1 supported thiol oxidation of the known mechanosensor beta(1)-integrin and promoted polarized compartmentalization of suifenylated proteins. Using traction force microscopy, we showed that pecPDIA1 organizes intracellular force distribution. The net contractile moment ratio of platelet-derived growth factor-exposed to basal VSMCs decreased from 0.90 +/- 0.09 (IgG-exposed controls) to 0.70 +/- 0.08 after pecPDIA1 neutralization (P < 0.05), together with an enhanced coefficient of variation for distribution of force modules, suggesting increased noise. Moreover, in a single cell model, pecPDIA1 neutralization impaired migration persistence without affecting total distance or velocity, whereas siRNA-mediated total PDIA1 silencing disabled all such variables of VSMC migration. Neither expression nor total activity of the master mechanotransmitter/regulator RhoA was affected by pecPDIA1 neutralization. However, cyclic stretch-induced focal distribution of membrane-bound RhoA was disrupted by pecPDI inhibition, which promoted a nonpolarized pattern of RhoA/caveolin-3 cluster colocalization. Accordingly, FRET biosensors showed that pecPDIA1 supports localized RhoA activity at cell protrusions versus perinuclear regions. Thus. pecPDI acts as a thiol redox-dependent organizer and noise reducer mechanism of cytoskeletal repositioning, oxidant generation, and localized RhoA activation during a variety of VSMC mechanoresponses. NEW & NOTEWORTHY Effects of a peri/epicellular pool of protein disulfide isomerase-A1 (pecPDIA1) during mechanoregulation in vascular smooth muscle cells (VSMCs) were highlighted using approaches such as equibiaxial and uniaxial stretch, random single cell migration, and traction force microscopy. pecPDIA1 regulates organization of the cytoskeleton and minimizes the noise of cell alignment, migration directionality, and persistence. pecPDIA1 mechanisms involve redox control of beta(1)-integrin and localized RhoA activation. pecPDIA1 acts as a novel organizer of mechanoadaptation responses in VSMCs.
- G(D3) ganglioside-enriched extracellular vesicles stimulate melanocyte migration(2019) OTAKE, Andreia Hanada; SAITO, Renata de Freitas; DUARTE, Ana Paula Marques; RAMOS, Alexandre Ferreira; CHAMMAS, RogerMelanomas often accumulate gangliosides, sialic acid-containing glycosphingolipids found in the outer leaflet of plasma membranes, as disialoganglioside G(D3) and its derivatives. Here, we have transfected the G(D3) synthase gene (ST8Sia I) in a normal melanocyte cell line in order to evaluate changes in the biological behavior of non-transformed cells. G(D3) -synthase expressing cells converted G(M3) into G(D3) and accumulated both G(D3) and its acetylated form, 9-O-acetyl-G(D3). Melanocytes were rendered more migratory on laminin-1 surfaces. Cell migration studies using the different transfectants, either treated or not with the glucosylceramide synthase inhibitor D-1-threo-1-phenyl-2-palmitoylamino-3-pyrrolidino-l-propanol (PPPP), allowed us to show that while G(M3) is a negative regulator of melanocyte migration, G(D3) increases it. We showed that gangliosides were shed to the matrix by migrating cells and that GD3 synthase transfected cells shed extracellular vesicles (EVs) enriched in G(D3). EVs enriched in G(D3) stimulated cell migration of G(D3) negative cells, as observed in time lapse microscopy studies. Otherwise, EVs shed by G(M3) (+ve)G(D3)(-ve) cells impaired migration and diminished cell velocity in cells overexpressing G(D3). The balance of antimigratory G(M3) and promigratory G(D3) gangliosides in melanocytes could be altered not only by the overexpression of enzymes such as ST8Sia I, but also by the horizontal transfer of ganglioside enriched extracellular vesicles. This study highlights that extracellular vesicles transfer biological information also through their membrane components, which include a variety of glycosphingolipids remodeled in disease states such as cancer.