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Ali Zarrinpar

Bio: Ali Zarrinpar is an academic researcher from University of Florida. The author has contributed to research in topics: Liver transplantation & Transplantation. The author has an hindex of 27, co-authored 84 publications receiving 3260 citations. Previous affiliations of Ali Zarrinpar include National University of Singapore & University of California, Los Angeles.


Papers
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Journal ArticleDOI
TL;DR: This STKE Review describes one class of protein interaction domains: the proline-binding domains, which serve two main functions: to serve as assembly points in signaling complexes and to serve a regulatory role in controlling protein activity.
Abstract: One particularly abundant group of modular recognition domains consists of those that bind proline-rich motifs. Such modules, including the SH3, WW, and EVH1 domains, play a critical role in the assembly and regulation of many intracellular signaling complexes. These domains use strikingly similar molecular mechanisms of proline recognition. We discuss some of the potential biological advantages conferred by proline recognition, which may explain its widespread use in signaling.

370 citations

Journal ArticleDOI
14 Feb 2003-Science
TL;DR: It is found that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions could functionally replace native kinase recruitment interactions, indicating that simple tethering is largely sufficient for scaffold-mediated signaling.
Abstract: How scaffold proteins control information flow in signaling pathways is poorly understood: Do they simply tether components, or do they precisely orient and activate them? We found that the yeast mitogen-activated protein (MAP) kinase scaffold Ste5 is tolerant to major stereochemical perturbations; heterologous protein interactions could functionally replace native kinase recruitment interactions, indicating that simple tethering is largely sufficient for scaffold-mediated signaling. Moreover, by engineering a scaffold that tethers a unique kinase set, we could create a synthetic MAP kinase pathway with non-natural input-output properties. These findings demonstrate that scaffolds are highly flexible organizing factors that can facilitate pathway evolution and engineering.

362 citations

Journal ArticleDOI
11 Dec 2003-Nature
TL;DR: It is shown that an isolated peptide ligand from the yeast protein Pbs2 recognizes its biological partner, the SH3 domain from Sho1, with near-absolute specificity, suggesting that system-wide negative selection is a subtle but powerful evolutionary mechanism to optimize specificity within an interaction network composed of overlapping recognition elements.
Abstract: Most proteins that participate in cellular signalling networks contain modular protein-interaction domains. Multiple versions of such domains are present within a given organism1: the yeast proteome, for example, contains 27 different Src homology 3 (SH3) domains2. This raises the potential problem of cross-reaction. It is generally thought that isolated domain–ligand pairs lack sufficient information to encode biologically unique interactions, and that specificity is instead encoded by the context in which the interaction pairs are presented3,4. Here we show that an isolated peptide ligand from the yeast protein Pbs2 recognizes its biological partner, the SH3 domain from Sho1, with near-absolute specificity—no other SH3 domain present in the yeast genome cross-reacts with the Pbs2 peptide, in vivo or in vitro. Such high specificity, however, is not observed in a set of non-yeast SH3 domains, and Pbs2 motif variants that cross-react with other SH3 domains confer a fitness defect, indicating that the Pbs2 motif might have been optimized to minimize interaction with competing domains specifically found in yeast. System-wide negative selection is a subtle but powerful evolutionary mechanism to optimize specificity within an interaction network composed of overlapping recognition elements.

280 citations

Journal ArticleDOI
TL;DR: The most recent developments in diagnosis and management of acetaminophen-induced ALF are outlined, including auxiliary, artificial, and bioartificial support systems.
Abstract: As the most common cause of acute liver failure (ALF) in the USA and UK, acetaminophen-induced hepatotoxicity remains a significant public health concern and common indication for emergent liver transplantation. This problem is largely attributable to acetaminophen combination products frequently prescribed by physicians and other healthcare professionals, with unintentional and chronic overdose accounting for over 50 % of cases of acetaminophen-related ALF. Treatment with N-acetylcysteine can effectively reduce progression to ALF if given early after an acute overdose; however, liver transplantation is the only routinely used life-saving therapy once ALF has developed. With the rapid course of acetaminophen-related ALF and limited supply of donor livers, early and accurate diagnosis of patients that will require transplantation for survival is crucial. Efforts in developing novel treatments for acetaminophen-induced ALF are directed toward bridging patients to recovery. These include auxiliary, artificial, and bioartificial support systems. This review outlines the most recent developments in diagnosis and management of acetaminophen-induced ALF.

231 citations

Journal ArticleDOI
TL;DR: Analysis of incidence, outcomes, and utilization of health care resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH) reports the largest single institution experience of LT for NASH.
Abstract: OBJECTIVE: To analyze incidence, outcomes, and utilization of health care resources in liver transplantation (LT) for nonalcoholic steatohepatitis (NASH). SUMMARY OF BACKGROUND DATA: With the epidemic of obesity and metabolic syndrome in nearly 33% of the US population, NASH is projected to become the leading indication for LT in the next several years. Data on predictors of outcome and utilization of health care resources after LT in NASH is limited. METHODS: We conducted an analysis from our prospective database of 144 adult NASH patients who underwent LT between December 1993 and August 2011. Outcomes and resource utilization were compared with other common indications for LT. Independent predictors of graft and patient survival were identified. RESULTS: The average Model for End-Stage Liver Disease score was 33. The frequency of NASH as the primary indication for LT increased from 3% in 2002 to 19% in 2011 to become the second most common indication for LT at our center behind hepatitis C. NASH patients had significantly longer operative times (402 vs 322 minutes; P < 0.001), operative blood loss (18 vs 14 packed red blood cell units; P = 0.001), and posttransplant length of stay (35 vs 29 days; P = 0.032), but 1-, 3-, and 5-year graft (81%, 71%, 63%) and patient (84%, 75%, 70%) survival were comparable with other diagnoses. Age greater than 55 years, pretransplant intubation, dialysis, hospitalization, presence of hepatocellular carcinoma on explant, donor age greater than 55 years, and cold ischemia time greater than 550 minutes were significant independent predictors of survival for all patients, whereas body mass index greater than 35 was a predictor in NASH patients only. CONCLUSIONS: We report the largest single institution experience of LT for NASH. Over a 10-year period, the frequency of LT for NASH has increased 5-fold. Although outcomes are comparable with LT for other indications, health care resources are stressed significantly by this new and increasing group of transplant candidates.

221 citations


Cited by
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Journal ArticleDOI
TL;DR: The following Clinical Practice Guidelines will give up-to-date advice for the clinical management of patients with hepatocellular carcinoma, as well as providing an in-depth review of all the relevant data leading to the conclusions herein.

7,851 citations

Journal ArticleDOI
TL;DR: In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.

2,061 citations

Journal ArticleDOI
14 Aug 2003-Nature
TL;DR: An astonishing variety of natural photonic structures exists: a species of Brittlestar uses photonic elements composed of calcite to collect light, Morpho butterflies use multiple layers of cuticle and air to produce their striking blue colour and some insects use arrays of elements to reduce reflectivity in their compound eyes.
Abstract: Millions of years before we began to manipulate the flow of light using synthetic structures, biological systems were using nanometre-scale architectures to produce striking optical effects. An astonishing variety of natural photonic structures exists: a species of Brittlestar uses photonic elements composed of calcite to collect light, Morpho butterflies use multiple layers of cuticle and air to produce their striking blue colour and some insects use arrays of elements, known as nipple arrays, to reduce reflectivity in their compound eyes. Natural photonic structures are providing inspiration for technological applications.

1,698 citations

Journal ArticleDOI
18 Apr 2003-Science
TL;DR: The sequencing of complete genomes provides a list that includes the proteins responsible for cellular regulation, but this does not immediately reveal what these proteins do, nor how they are assembled into the molecular machines and functional networks that control cellular behavior.
Abstract: The sequencing of complete genomes provides a list that includes the proteins responsible for cellular regulation. However, this does not immediately reveal what these proteins do, nor how they are assembled into the molecular machines and functional networks that control cellular behavior. The regulation of many different cellular processes requires the use of protein interaction domains to direct the association of polypeptides with one another and with phospholipids, small molecules, or nucleic acids. The modular nature of these domains, and the flexibility of their binding properties, have likely facilitated the evolution of cellular pathways. Conversely, aberrant interactions can induce abnormal cellular behavior and disease. The fundamental properties of protein interaction domains are discussed in this review and in detailed reviews on individual domains at Science's STKE at http://www.sciencemag.org/cgi/content/full/300/5618/445/DC1.

1,489 citations