Podosomes and Invadopodia: Related structures with Common Protein Components that May Promote Breast Cancer Cellular Invasion

A rate-limiting step in breast cancer progression is acquisition of the invasive phenotype, which can precede metastasis. Expression of cell-surface proteases at the leading edge of a migrating cell provides cells with a mechanism to cross tissue barriers. A newly appreciated mechanism that may be relevant for breast cancer cell invasion is the formation of invadopodia, well-defined structures that project from the ventral membrane and promote degradation of the extracellular matrix, allowing the cell to cross a tissue barrier. Recently, there has been some controversy and discussion as to whether invadopodia, which are associated with carcinoma cells, are related to a similar structure called podosomes, which are associated with normal cells. Invadopodia and podosomes share many common characteristics, including a similar size, shape, subcellular localization and an ability to promote invasion. These two structures also share many common protein components, which we outline herein. It has been speculated that podosomes may be precursors to invadopodia and by extension both structures may be relevant to cancer cell invasion. Here, we compare and contrast the protein components of invadopodia and podosomes and discuss a potential role for these proteins and the evidence that supports a role for invadopodia and podosomes in breast cancer invasion

Urelumab alone or in combination with rituximab in patients with relapsed or refractory B-cell lymphoma

Altres ajuts: This study was supported by Bristol-Myers Squibb, Princeton, NJ.Urelumab, a fully human, non-ligand binding, CD137 agonist IgG4 monoclonal antibody, enhances T-cell and natural killer-cell antitumor activity in preclinical models, and may enhance cytotoxic activity of rituximab. Here we report results in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and other B-cell lymphomas, in phase 1 studies evaluating urelumab alone (NCT01471210) or combined with rituximab (NCT01775631). Sixty patients received urelumab (0.3 mg/kg IV Q3W, 8 mg IV Q3W, or 8 mg IV Q6W); 46 received urelumab (0.1 mg/kg, 0.3 mg/kg, or 8 mg IV Q3W) plus rituximab 375 mg/m 2 IV QW. The maximum tolerated dose (MTD) of urelumab was determined to be 0.1 mg/kg or 8 mg Q3W after a single event of potential drug-induced liver injury occurred with urelumab 0.3 mg/kg. Treatment-related AEs were reported in 52% (urelumab: grade 3/4, 15%) and 72% (urelumab + rituximab: grade 3/4, 28%); three led to discontinuation (grade 3 increased AST, grade 4 acute hepatitis [urelumab]; one death from sepsis syndrome [urelumab plus rituximab]). Objective response rates/disease control rates were 6%/19% (DLBCL, n = 31), 12%/35% (FL, n = 17), and 17%/42% (other B-cell lymphomas, n = 12) with urelumab and 10%/24% (DLBCL, n = 29) and 35%/71% (FL, n = 17) with urelumab plus rituximab. Durable remissions in heavily pretreated patients were achieved; however, many were observed at doses exceeding the MTD. These data show that urelumab alone or in combination with rituximab demonstrated manageable safety in B-cell lymphoma, but the combination did not enhance clinical activity relative to rituximab alone or other current standard of care

An Examination of the Discriminant Validity of the Strain-Free Negative Affectivity Scale

This study reports evidence supporting the discriminant validity of the Strain-Free Negative Affectivity (SFNA) scale (Fortunato & Stone-Romero, 1999). Stressor-strain correlations controlling for neuroticism and negative emotional reactivity (NER), both considered markers of negative affectivity (NA), were examined using partial correlation and latent variable procedures. Support was found for the authors\u27 hypothesis that correlations between self-reports of work-related stressors and physiological and psychological strain would be attenuated to a much greater degree when neuroticism was controlled than. when NER was controlled. Thus the SFNA is a viable measure of NA, especially for research examining stresser-strain relations

Greening Your Laneways pilot VR project, City of Melbourne

VR experience created with the City of Melbourne to explore new technologies. The work featured the creation of an interaction virtual reality experience and a 360 degree video for Google Carboard

Examination of the Coordinate Effects of Pseudomonas aeruginosa ExoS on Rac1

Exoenzyme S (ExoS) is a bifunctional toxin directly translocated into eukaryotic cells by the Pseudomonas aeruginosa type III secretory (TTS) process. The amino-terminal GTPase-activating (GAP) activity and the carboxy-terminal ADP-ribosyltransferase (ADPRT) activity of ExoS have been found to target but exert opposite effects on the same low-molecular-weight G protein, Rac1. ExoS ADP-ribosylation of Rac1 is cell line dependent. In HT-29 human epithelial cells, where Rac1 is ADP-ribosylated by TTS-ExoS, Rac1 was activated and relocalized to the membrane fraction. Arg66 and Arg68 within the GTPase-binding region of Rac1 were identified as preferred sites of ExoS ADP-ribosylation. The modification of these residues by ExoS would be predicted to interfere with Rac1 inactivation and explain the increase in active Rac1 caused by ExoS ADPRT activity. Using ExoS-GAP and ADPRT mutants to examine the coordinate effects of the two domains on Rac1 function, limited effects of ExoS-GAP on Rac1 inactivation were evident in HT-29 cells. In J774A.1 macrophages, where Rac1 was not ADP-ribosylated, ExoS caused a decrease in the levels of active Rac1, and this decrease was linked to ExoS-GAP. Using immunofluorescence staining of Rac1 to understand the cellular basis for the targeting of ExoS ADPRT activity to Rac1, an inverse relationship was observed between Rac1 plasma membrane localization and Rac1 ADP-ribosylation. The results obtained from these studies have allowed the development of a model to explain the differential targeting and coordinate effects of ExoS GAP and ADPRT activity on Rac1 within the host cell

Virtual forest

The Virtual Forest is an interactive, screen-based experience commissioned by Dementia Australia. First created several years ago, Virtual Forest was completely recreated and rebuilt by Deakin, including integration with new hardware, software, and new CG assets. The experience is simple to use, and allows people (with dementia or their family members) to move their arms and, in doing so (through the tracking of their movement) influence activity on the screen. This includes ducks and fish swimming, seasons changing, the flight patterns of butterflies and dragonflies and a range of other activity. By rebuilding and recreating the Virtual Forest, Deakin is now able to work with Dementia Australia to create more experiences

Motion capture, animation, previsualization and virtual production for The Unknown Patient (VR interactive short film)

DML inventions applied to an industry application, in the creation of this creative product. The Unknown Patient is a Virtual Reality, interactive short film that was selected for premiere at the highly prestigious Venice Film Festival