102 research outputs found
Involvement of Girdin in the Determination of Cell Polarity during Cell Migration
Cell migration is a critical cellular process that determines embryonic development and the progression of human diseases. Therefore, cell- or context-specific mechanisms by which multiple promigratory proteins differentially regulate cell migration must be analyzed in detail. Girdin (girders of actin filaments) (also termed GIV, Gα-interacting vesicle associated protein) is an actin-binding protein that regulates migration of various cells such as endothelial cells, smooth muscle cells, neuroblasts, and cancer cells. Here we show that Girdin regulates the establishment of cell polarity, the deregulation of which may result in the disruption of directional cell migration. We found that Girdin interacts with Par-3, a scaffolding protein that is a component of the Par protein complex that has an established role in determining cell polarity. RNA interference-mediated depletion of Girdin leads to impaired polarization of fibroblasts and mammary epithelial cells in a way similar to that observed in Par-3-depleted cells. Accordingly, the expression of Par-3 mutants unable to interact with Girdin abrogates cell polarization in fibroblasts. Further biochemical analysis suggests that Girdin is present in the Par protein complex that includes Par-3, Par-6, and atypical protein kinase C. Considering previous reports showing the role of Girdin in the directional migration of neuroblasts, network formation of endothelial cells, and cancer invasion, these data may provide a specific mechanism by which Girdin regulates cell movement in biological contexts that require directional cell movement
An Electrode Array for Limiting Blood Loss During Liver Resection: Optimization via Mathematical Modeling
Liver resection is the current standard treatment for patients with both primary and metastatic liver cancer. The principal causes of morbidity and mortality after liver resection are related to blood loss (typically between 0.5 and 1 L), especially in cases where transfusion is required. Blood transfusions have been correlated with decreased long-term survival, increased risk of perioperative mortality and complications. The goal of this study was to evaluate different designs of a radiofrequency (RF) electrode array for use during liver resection. The purpose of this electrode array is to coagulate a slice of tissue including large vessels before resecting along that plane, thereby significantly reducing blood loss. Finite Element Method models were created to evaluate monopolar and bipolar power application, needle and blade shaped electrodes, as well as different electrode distances. Electric current density, temperature distribution, and coagulation zone sizes were measured. The best performance was achieved with a design of blade shaped electrodes (5 × 0.1 mm cross section) spaced 1.5 cm apart. The electrodes have power applied in bipolar mode to two adjacent electrodes, then switched sequentially in short intervals between electrode pairs to rapidly heat the tissue slice. This device produces a ~1.5 cm wide coagulation zone, with temperatures over 97 ºC throughout the tissue slice within 3 min, and may facilitate coagulation of large vessels
RACK-1 Acts with Rac GTPase Signaling and UNC-115/abLIM in Caenorhabditis elegans Axon Pathfinding and Cell Migration
Migrating cells and growth cones extend lamellipodial and filopodial protrusions that are required for outgrowth and guidance. The mechanisms of cytoskeletal regulation that underlie cell and growth cone migration are of much interest to developmental biologists. Previous studies have shown that the Arp2/3 complex and UNC-115/abLIM act redundantly to mediate growth cone lamellipodia and filopodia formation and axon pathfinding. While much is known about the regulation of Arp2/3, less is known about regulators of UNC-115/abLIM. Here we show that the Caenorhabditis elegans counterpart of the Receptor for Activated C Kinase (RACK-1) interacts physically with the actin-binding protein UNC-115/abLIM and that RACK-1 is required for axon pathfinding. Genetic interactions indicate that RACK-1 acts cell-autonomously in the UNC-115/abLIM pathway in axon pathfinding and lamellipodia and filopodia formation, downstream of the CED-10/Rac GTPase and in parallel to MIG-2/RhoG. Furthermore, we show that RACK-1 is involved in migration of the gonadal distal tip cells and that the signaling pathways involved in this process might be distinct from those involved in axon pathfinding. In sum, these studies pinpoint RACK-1 as a component of a novel signaling pathway involving Rac GTPases and UNC-115/abLIM and suggest that RACK-1 might be involved in the regulation of the actin cytoskeleton and lamellipodia and filopodia formation in migrating cells and growth cones
G-protein signaling: back to the future
Heterotrimeric G-proteins are intracellular partners of G-protein-coupled receptors (GPCRs). GPCRs act on inactive Gα·GDP/Gβγ heterotrimers to promote GDP release and GTP binding, resulting in liberation of Gα from Gβγ. Gα·GTP and Gβγ target effectors including adenylyl cyclases, phospholipases and ion channels. Signaling is terminated by intrinsic GTPase activity of Gα and heterotrimer reformation — a cycle accelerated by ‘regulators of G-protein signaling’ (RGS proteins). Recent studies have identified several unconventional G-protein signaling pathways that diverge from this standard model. Whereas phospholipase C (PLC) β is activated by Gαq and Gβγ, novel PLC isoforms are regulated by both heterotrimeric and Ras-superfamily G-proteins. An Arabidopsis protein has been discovered containing both GPCR and RGS domains within the same protein. Most surprisingly, a receptor-independent Gα nucleotide cycle that regulates cell division has been delineated in both Caenorhabditis elegans and Drosophila melanogaster. Here, we revisit classical heterotrimeric G-protein signaling and explore these new, non-canonical G-protein signaling pathways
Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes
Transmembrane signalling in eukaryotes: a comparison between higher and lower eukaryotes
Japan Unified Protocol Clinical Trial for Depressive and Anxiety Disorders (JUNP study): study protocol for a randomized controlled trial
Laparoscopic Microwave Coagulo-Necrotic Therapy for Hepatocellular Carcinoma: A Feasible Study of an Alternative Option for Poor-Risk Patients
Semiquantitative analysis of corpus callosum injury using magnetic resonance imaging indicates clinical severity in patients with diffuse axonal injury
Objective: To evaluate the hypothesis that the extent of corpus callosum injury indicates the depth of shearing lesions in the central brain structure and therefore relates to the clinical severity of diffuse axonal injury. Methods: A simple and objective procedure for semiquantitative analysis of magnetic resonance images (MRI)—the maximum signal intensity ratio (MSIR)—was employed prospectively in 21 patients with diffuse axonal injury but without apparent injury to the ventral pons. All were diagnosed using serial combination MRI scans of fluid attenuated inversion recovery (FLAIR) and T2* weighted gradient echo imaging during the initial two weeks after the injury. The signal intensity ratio between the two regions of interest—the corpus callosum and the normal appearing ventral pons—was calculated serially in mid-sagittal and parasagittal FLAIR image sections in each patient. The MSIR during the study period was determined as a semiquantitative index of corpus callosum injury in each patient. The correlations between MSIR and the duration of unconsciousness, Glasgow outcome scale at six months, and the presence of apparent midbrain injury were investigated. Results: The mean (SD) MSIR value was 1.12 (0.18) at 7.4 (3.1) days after the injury (n = 21). MSIR correlated strongly with the duration of unconsciousness (n = 19, R(2) = 0.74, p < 0.0001), and was higher in patients with both an unfavourable GOS outcome (p = 0.020) and apparent midbrain injury (p < 0.001). Conclusions: MSIR, which is a simple and objective procedure for semiquantitative analysis of corpus callosum damage in diffuse axonal injury, correlated with clinical severity. A high MSIR value may indicate the presence of concomitant midbrain injury
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