Rationale and practical techniques for mouse models of early vein graft adaptations

Mouse models serve as relatively new yet powerful research tools to study intimal hyperplasia and wall remodeling of vein bypass graft failure. Several model variations have been reported in the past decade. However, the approach demands thoughtful preparation, selected sophisticated equipment, microsurgical technical expertise, advanced tissue processing, and data acquisition. This review compares several described models and aims (building on our personal experiences) to practically aid the investigators who want to utilize mouse models of vein graft failure.Clinical RelevanceSurgical revascularization via vein grafting offers immediate and often dramatic end organ benefit. However, substantial percentages of vein conduits placed develop stenosis or fail, often early. Mechanistic studies of the complex interplay between the biologic and physical forces that drive failure have been hampered by limited quantity and quality of clinical specimens, and the inability of systems such as computer models and cell culture to mimic the clinical circumstance. This review summarizes the power and limitations of mouse vein graft models, and it includes practical experience-based advice for researchers aiming to utilize this tool

Structural and functional protein network analyses predict novel signaling functions for rhodopsin

Proteomic analyses, literature mining, and structural data were combined to generate an extensive signaling network linked to the visual G protein-coupled receptor rhodopsin. Network analysis suggests novel signaling routes to cytoskeleton dynamics and vesicular trafficking

Shaping dots and lines: adding modularity into protein interaction networks using structural information

Determining protein interaction networks and generating models to simulate network changes in time and space are crucial for understanding a biological system and for predicting the effect of mutants found in diseases. In this review we discuss the great potential of using structural information together with computational tools towards reaching this goal: the prediction of new protein interactions, the estimation of affinities and kinetic rate constants between protein complexes, and finally the determination of which interactions are compatible with each other and which interactions are exclusive. The latter one will be important to reorganize large scale networks into functional modular networks. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved

The G protein alpha chaperone and guanine-nucleotide exchange factor RIC-8 regulates cilia morphogenesis in Caenorhabditis elegans sensory neurons.

Heterotrimeric G (αβγ) proteins are canonical transducers of G-protein-coupled receptor (GPCR) signaling and play critical roles in communication between cells and their environment. Many GPCRs and heterotrimeric G proteins localize to primary cilia and modulate cilia morphology via mechanisms that are not well understood. Here, we show that RIC-8, a cytosolic guanine nucleotide exchange factor (GEF) and chaperone for Gα protein subunits, shapes cilia membrane morphology in a subset of Caenorhabditis elegans sensory neurons. Consistent with its role in ciliogenesis, C. elegans RIC-8 localizes to cilia in different sensory neuron types. Using domain mutagenesis, we demonstrate that while the GEF function alone is not sufficient, both the GEF and Gα-interacting chaperone motifs of RIC-8 are required for its role in cilia morphogenesis. We identify ODR-3 as the RIC-8 Gα client and demonstrate that RIC-8 functions in the same genetic pathway with another component of the non-canonical G protein signaling AGS-3 to shape cilia morphology. Notably, despite defects in AWC cilia morphology, ags-3 null mutants exhibit normal chemotaxis toward benzaldehyde unlike odr-3 mutant animals. Collectively, our findings describe a novel function for the evolutionarily conserved protein RIC-8 and non-canonical RIC-8-AGS-3-ODR-3 signaling in cilia morphogenesis and uncouple Gα ODR-3 functions in ciliogenesis and olfaction

The experiences of community health workers when communicating with refugees about COVID-19 vaccines in Syracuse, NY: A qualitative study

Background: Refugees are among the most health-vulnerable members of society. Despite the importance of vaccination to mitigate the risks associated with COVID-19 infection, ensuring adequate access and uptake of the COVID-19 vaccine remains a pressing concern for refugee populations. Research has suggested that community-oriented approaches and open communication with trusted individuals are essential to address this challenge. Vaccine outreach efforts were performed in Syracuse, NY, by Community Health Workers (CHWs) as trusted refugee community members. This study explored CHWs’ experiences during vaccine outreach and perceptions about COVID-19 vaccine hesitancy and acceptance among refugees, including barriers and facilitators to vaccination. Methods: A qualitative study was performed using thematic analysis following six semi-structured interviews with CHWs. Results: Four main themes supported by 16 sub-themes were extracted. CHWs described the (1) diverse beliefs and attitudes of refugees by ethnic group, with most having low vaccine acceptance at first. (2) Barriers included contextual barriers, lack of awareness, misinformation, and withdrawal when forced from vaccine mandates. However, CHWs also identified numerous (3) facilitators to vaccination, including the internal processing and eventual vaccine acceptance, supported by external messaging by CHWs and time. Culturally sensitive intervention strategies occurred through (4) CHW team efforts and their provision of reliable information to refugee clients, with openness and over time. The team efforts of CHWs significantly contributed to refugee acceptance and uptake of the COVID-19 vaccine. Conclusions: This study revealed how the refugee population changed their belief towards the COVID-19 vaccine through trust, time, and reliable information provided by CHWs and describes culturally sensitive strategies for vaccine uptake by refugees. CHWs' reflection on COVID-19 vaccine hesitancy and acceptance among refugees during outreach efforts is an essential perspective when implementing future public health interventions

SAPIN: a framework for the structural analysis of protein interaction networks

Protein interaction networks are widely used to depict the relationships between proteins. These networks often lack the information on physical binary interactions, and they do not inform whether there is incompatibility of structure between binding partners. Here, we introduce SAPIN, a framework dedicated to the structural analysis of protein interaction networks. SAPIN first identifies the protein parts that could be involved in the interaction and provides template structures. Next, SAPIN performs structural superimpositions to identify compatible and mutually exclusive interactions. Finally, the results are displayed using Cytoscape Web