Immunohistochemical Investigation of Tracks Left by the Migration of Fibroblasts on Titanium Surfaces

Fibronectin, a major attachment protein, has been thought to be involved in pathway guidance, a process in which cells migrate along specific pathways within a tissue during development. Fibroblasts exhibit the phenomenon of contact guidance, the tendency of cells to be guided in their direction of migration by the shape of the substratum. The purpose of our study was to test the hypothesis that fibronectin tracks are deposited by fibroblasts moving on smooth and grooved titanium surfaces. The study was carried out on human gingival fibroblasts which were plated onto both smooth and grooved titanium substrata using medium containing either serum or fibronectin-depleted serum. The migratory paths of the cells were determined by time-lapse photography using reflected-light differential-interference- contrast optics. Anti-fibronectin antibody, 1 nm gold particle conjugated secondary antibody, and silver enhancement techniques were applied to the cultured cells, and the specimens observed in a scanning electron microscope using backscattered detection. By correlating the paths of the cells with the location of the fibronectin- containing material, it could be demonstrated that cells left behind fibronectin tracks on both smooth and grooved titanium surfaces. Fibronectin tracks appeared to be deposited more abundantly by fibroblasts cultured in medium with 5 % serum depleted in fibronectin than in complete, i.e., non-depleted, 5 % serum. On the grooved titanium substratum, the tracks were found on the ridges as well as on the floors and walls of the grooves. The fibronectin tracks are aligned with the grooves so that they would be expected to reinforce the contact guidance produced by the substratum

The Role of Implant Surface Geometry on Mineralization In Vivo and In Vitro; A Transmission and Scanning Electron Microscopic Study

The purpose of th.is study was to examine the effect of substratum surface topography on bone formation in vivo and in vitro. Precise control over substratum topography was achieved using micromachining, a technique developed from the fabrication of microelectronic components. In the in vivo studies, titanium-coated epoxy replicas of micromachined surfaces were implanted subcutaneously in the parietal area of rats. After 6 weeks, bone-like tissue was found adjacent to some micromachined surfaces. Detailed observation of this tissue with the transmission electron microscope revealed osteoblast/osteocyte-like cells and a fully or partially mineralized collagenous matrix. Mineralized matrix and collagen bundles were found contacting the titanium coating without any intervening material. Mineralized tissue was not found adjacent to smooth surfaces. In vitro, enzymatically released osteogenic cells from calvarial bone produced large ( ~ 10 μm) and small ( ~ 0.5-3 μm) mineralized globules on the micromachined surfaces, whereas only small mineralized globules formed on the smooth control surfaces after 4 weeks of culture. The mineralized nature of the globules was confirmed by energy dispersive X-ray analysis. In a second osteogenic culture system, micromachined or smooth control surfaces were placed on calvarial explants. After 4 weeks, partially mineralized globules ( ~ 5 μm) were noted interspersed between cells and extracellular matrix on the micromachined surfaces but not on the smooth surfaces. This study suggests that the surface topography of an implant influences bone formation in vivo and in vitro and that micromachined surfaces of the dimensions used in these experiments promote mineralized tissue formation

Perceptions of Mask Use During the COVID-19 Pandemic

The CDC recommends covering of the face and nose during the COVID-19 pandemic as a primary mitigation strategy for viral transmission. Masks minimize the number of viral particles emitted by the wearer; mask use serves to reduce the effects on population transmission. Mask wearing behaviors have been shown to vary across different groups like gender identity, however, differences between people with and without lung disease have yet to be explored. Goal: Examine perceptions, attitudes, and behaviors related to mask use during the COVID-19 pandemic of those with and without lung disease nationally.https://scholarworks.uvm.edu/comphp_gallery/1307/thumbnail.jp

Somewhere in Europe (1947): locating Hungary within a shifting geopolitical landscape

Somewhere in Europe/Valahol Európában (Radványi, 1947) was one of the first films made in Hungary after 1945. Financed by the Hungarian Communist Party (MKP), it loudly proclaimed a broad European pertinence in an effort to privilege the universal narrative of childhoods disrupted by the war over narrowly national political concerns. The film’s story of a gang of half-starved children battling for survival in a bombed-out Central European landscape places it squarely within a transnational post-war film-making tradition. Similarities with both Italian neorealism and Soviet socialist realist cinema indicate a shared European experience of the war, but is also attributable to the international training and experience of the film’s personnel. The director Radványi had worked in the Italian industry, while the scriptwriter was the well-known film theorist Béla Balázs, who had worked in Weimar Germany and Soviet Russia. This article argues that in spite of its ostensible commitment to a communist and humanist ideology, the film gives an insight into the Hungarian national obsession with territorial integrity. Hungary’s participation in World War II on the side of the Axis, and its position as a defeated nation under Allied occupation, are seen to complicate the film text. This article contends that in spite its transnational flavour, the film’s focus on lost children wandering a borderless Europe suggests a preoccupation with the country’s uncertain position within a shifting geopolitical landscape. In turn, the film’s official reading by Nemeskürty shows an eagerness to accept the film’s representation of Hungary as a blameless victim of the war, and gives evidence of a need to insert a (false) break between the country’s wartime past as a member of the Axis, and the country’s 1968 present as a member of the Communist world order

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations