Atomic-Resolution Simulations Predict a Transition State for Vesicle Fusion Defined by Contact of a Few Lipid Tails

Membrane fusion is essential to both cellular vesicle trafficking and infection by enveloped viruses. While the fusion protein assemblies that catalyze fusion are readily identifiable, the specific activities of the proteins involved and nature of the membrane changes they induce remain unknown. Here, we use many atomic-resolution simulations of vesicle fusion to examine the molecular mechanisms for fusion in detail. We employ committor analysis for these million-atom vesicle fusion simulations to identify a transition state for fusion stalk formation. In our simulations, this transition state occurs when the bulk properties of each lipid bilayer remain in a lamellar state but a few hydrophobic tails bulge into the hydrophilic interface layer and make contact to nucleate a stalk. Additional simulations of influenza fusion peptides in lipid bilayers show that the peptides promote similar local protrusion of lipid tails. Comparing these two sets of simulations, we obtain a common set of structural changes between the transition state for stalk formation and the local environment of peptides known to catalyze fusion. Our results thus suggest that the specific molecular properties of individual lipids are highly important to vesicle fusion and yield an explicit structural model that could help explain the mechanism of catalysis by fusion proteins

Embryonic Stem Cells: New Possible Therapy for Degenerative Diseases That Affect Elderly People

The capacity of embryonic stem (ES) cells for virtually unlimited self renewal and differentiation has opened up the prospect of widespread applications in biomedical research and regenerative medicine. The use of these cells would overcome the problems of donor tissue shortage and implant rejection, if the cells are made immunocompatible with the recipient. Since the derivation in 1998 of human ES cell lines from preimplantation embryos, considerable research is centered on their biology, on how differentiation can be encouraged toward particular cell lineages, and also on the means to enrich and purify derivative cell types. In addition, ES cells may be used as an in vitro system not only to study cell differentiation but also to evaluate the effects of new drugs and the identification of genes as potential therapeutic targets. This review will summarize what is known about animal and human ES cells with particular emphasis on their application in four animal models of human diseases. Present studies of mouse ES cell transplantation reveal encouraging results but also technical barriers that have to be overcome before clinical trials can be considered

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Transition from Hospital to Community Care: The Experience of Cancer Patients

Purpose: This study examines care transition experiences of cancer patients and assesses barriers to effective transitions.Methods: Participants were adult Hebrew, Arabic, or Russian speaking oncology patients and health care providers from hospital and community settings. Qualitative (n=77) and quantitative (n=422) methods such as focus groups, interviews and self-administered questionnaires were used. Qualitative analysis showed that patients faced difficulties navigating a complex and fragmented healthcare system.Results: Mechanisms to overcome barriers included informal routes such as personal relationships, coordinating roles by nurse coordinators and the patients' general practitioners (GPs). The most significant variable was GPs involvement, which affected transition process quality as rated on the CTM (p<0.001). Our findings point to the important interpersonal role of oncology nurses to coordinate and facilitate the care transition process.Conclusion: Interventions targeted towards supporting the care transition process should emphasize ongoing counseling throughout a patient’s care, during and after hospitalization.-----------------------------------------Cite this article as:  Admi H, Muller E, Shadmi E. Transition from Hospital to Community Care: The Experience of Cancer Patients. Int J Cancer Ther Oncol 2015; 3(4):34011.[This abstract was presented at the BIT’s 8th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.

Transition from Hospital to Community Care: The Experience of Cancer Patients

Purpose: This study examines care transition experiences of cancer patients and assesses barriers to effective transitions.Methods: Participants were adult Hebrew, Arabic, or Russian speaking oncology patients and health care providers from hospital and community settings. Qualitative (n=77) and quantitative (n=422) methods such as focus groups, interviews and self-administered questionnaires were used. Qualitative analysis showed that patients faced difficulties navigating a complex and fragmented healthcare system.Results: Mechanisms to overcome barriers included informal routes such as personal relationships, coordinating roles by nurse coordinators and the patients' general practitioners (GPs). The most significant variable was GPs involvement, which affected transition process quality as rated on the CTM (p&lt;0.001). Our findings point to the important interpersonal role of oncology nurses to coordinate and facilitate the care transition process.Conclusion: Interventions targeted towards supporting the care transition process should emphasize ongoing counseling throughout a patient’s care, during and after hospitalization.-----------------------------------------Cite this article as:  Admi H, Muller E, Shadmi E. Transition from Hospital to Community Care: The Experience of Cancer Patients. Int J Cancer Ther Oncol 2015; 3(4):34011.[This abstract was presented at the BIT’s 8th Annual World Cancer Congress, which was held from May 15-17, 2015 in Beijing, China.]</p

MIMOSA2: a metabolic network-based tool for inferring mechanism-supported relationships in microbiome-metabolome data.

MotivationRecent technological developments have facilitated an expansion of microbiome-metabolome studies, in which samples are assayed using both genomic and metabolomic technologies to characterize the abundances of microbial taxa and metabolites. A common goal of these studies is to identify microbial species or genes that contribute to differences in metabolite levels across samples. Previous work indicated that integrating these datasets with reference knowledge on microbial metabolic capacities may enable more precise and confident inference of microbe-metabolite links.ResultsWe present MIMOSA2, an R package and web application for model-based integrative analysis of microbiome-metabolome datasets. MIMOSA2 uses genomic and metabolic reference databases to construct a community metabolic model based on microbiome data and uses this model to predict differences in metabolite levels across samples. These predictions are compared with metabolomics data to identify putative microbiome-governed metabolites and taxonomic contributors to metabolite variation. MIMOSA2 supports various input data types and customization with user-defined metabolic pathways. We establish MIMOSA2's ability to identify ground truth microbial mechanisms in simulation datasets, compare its results with experimentally inferred mechanisms in honeybee microbiota, and demonstrate its application in two human studies of inflammatory bowel disease. Overall, MIMOSA2 combines reference databases, a validated statistical framework, and a user-friendly interface to facilitate modeling and evaluating relationships between members of the microbiota and their metabolic products.Availability and implementationMIMOSA2 is implemented in R under the GNU General Public License v3.0 and is freely available as a web server at http://elbo-spice.cs.tau.ac.il/shiny/MIMOSA2shiny/ and as an R package from http://www.borensteinlab.com/software_MIMOSA2.html.Supplementary informationSupplementary data are available at Bioinformatics online