UCI Authors in PubMed
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Iwashita T,Nakai Y,Lee JG,Park do H,Muthusamy VR,Chang KJ HH Chao Comprehensive Digestive Disease Center, University of California, Irvine Medical Center, Orange, California 92868, USA. |
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Newly-developed, forward-viewing echoendoscope: a comparative pilot study to the standard echoendoscope in the imaging of abdominal organs and feasibility of endoscopic ultrasound-guided interventions. J Gastroenterol Hepatol. 2012 Feb;27(2):362-7 Multiple diagnostic and therapeutic endoscopic ultrasound (EUS) procedures have been widely performed using a standard oblique-viewing (OV) curvilinear array (CLA) echoendoscope. Recently, a new, forward-viewing (FV) CLA was developed, with the advantages of improved endoscopic viewing and manipulation of devices. However, the FV-CLA echoendoscope has a narrower ultrasound scanning field, and lacks an elevator, which might represent obstacles for clinical use. The aim of this study was to compare the FV-CLA echoendoscope to the OV-CLA echoendoscope for EUS imaging of abdominal organs, and to assess the feasibility of EUS-guided interventions using the FV-CLA echoendoscope. PMID: 21916990 |
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Marro BS,Hosking MP,Lane TE Department of Molecular Biology & Biochemistry, University of California, Irvine 92697-3900. |
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CXCR2 signaling and host defense following coronavirus-induced encephalomyelitis. Future Virol. 2012 Apr;7(4):349-359 Inoculation of the neurotropic JHM strain of mouse hepatitis virus (JHMV) into the central nervous system (CNS) of susceptible strains of mice results in wide-spread replication within glial cells accompanied by infiltration of virus-specific T lymphocytes that control virus through cytokine secretion and cytolytic activity. Virus persists within white matter tracts of surviving mice resulting in demyelination that is amplified by inflammatory T cells and macrophages. In response to infection, numerous cytokines/chemokines are secreted by resident cells of the CNS and inflammatory leukocytes that participate in both host defense and disease. Among these are the ELR-positive chemokines that are able to signal through CXC chemokine receptors including CXCR2. Early following JHMV infection, ELR-positive chemokines contribute to host defense by attracting CXCR2-expressing cells including polymorphonuclear cells to the CNS that aid in host defense through increasing the permeability the blood-brain-barrier (BBB). During chronic disease, CXCR2 signaling on oligodendroglia protects these cells from apoptosis and restricts the severity of demyelination. This review covers aspects related to host defense and disease in response to JHMV infection and highlights the different roles of CXCR2 signaling in these processes. PMID: 22582084 |
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Garg S,Said B,Farid M,Steinert RF Gavin Herbert Eye Institute, Department of Ophthalmology, University of California, Irvine, Irvine, CA. |
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Prevalence of Positive Microbiology Results From Donor Cornea Tissue in Different Methods of Corneal Transplantation. Cornea. 2012 May 10;: PURPOSE:: To evaluate the prevalence of positive microbiology results (culture and/or Gram stain) in donor cornea tissue with newer transplant methods and to assess if the results subsequently correlate with higher incidence of clinical infection. METHODS:: A retrospective review of the microbiology records of 569 consecutive corneal transplants from July 2006 through July 2010 was performed to evaluate positive microbiology results in routine evaluation of cornea donor tissue. RESULTS:: Microbiologic results were available for 544 of 569 transplants. The remaining 25 cases did not have specimens submitted for microbiologic analysis. In cases with results available, 46 (8.5%) positive reports occurred. In 10 of the 46 cases, Gram stain results were positive with subsequent negative cultures. Analysis revealed that the prevalence of positive results was 6 in 137 (4.4%), 14 in 127 (11.0%), and 26 in 271 (9.6%) for femtosecond laser-enabled keratoplasty, Descemet stripping automated endothelial keratoplasty, and conventional penetrating keratoplasty, respectively; 9 femtosecond deep anterior lamellar keratoplasty had no positive results. There was no significant relationship between the types of transplant procedures and the occurrence of positive microbiologic results (P = 0.08). The overall incidence of clinical infection was found to be 0.4% (2 of 569); however, only 1 case (1 of 569 or 0.2%), which was a Candida albicans infection after Descemet stripping automated endothelial keratoplasty, was attributable to the donor. Of 25 cases in which microbiology studies were not performed, none developed a clinical infection. CONCLUSIONS:: Prevalence of positive microbiologic results and subsequent infections do not appear to be increased with the method of donor handling used for newer techniques for keratoplasty. PMID: 22580430 |
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Hanson CA,Fuhrman JA,Horner-Devine MC,Martiny JB Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697 USA. |
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Beyond biogeographic patterns: processes shaping the microbial landscape. Nat Rev Microbiol. 2012 May 14;: Recently, microbiologists have established the existence of biogeographic patterns among a wide range of microorganisms. The focus of the field is now shifting to identifying the mechanisms that shape these patterns. Here, we propose that four processes - selection, drift, dispersal and mutation - create and maintain microbial biogeographic patterns on inseparable ecological and evolutionary scales. We consider how the interplay of these processes affects one biogeographic pattern, the distance-decay relationship, and review evidence from the published literature for the processes driving this pattern in microorganisms. Given the limitations of inferring processes from biogeographic patterns, we suggest that studies should focus on directly testing the underlying processes. PMID: 22580365 |
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Jasion VS,Poulos TL Departments of Molecular Biology and Biochemistry, Chemistry, and Pharmaceutical Sciences, University of California, Irvine, California 92697-3900, United States. |
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Leishmania major peroxidase is a cytochrome c peroxidase. Biochemistry. 2012 Mar 27;51(12):2453-60 Leishmania major peroxidase (LmP) exhibits both ascorbate and cytochrome c peroxidase activities. Our previous results illustrated that LmP has a much higher activity against horse heart cytochrome c than ascorbate, suggesting that cytochrome c may be the biologically important substrate. To elucidate the biological function of LmP, we have recombinantly expressed, purified, and determined the 2.08 Å crystal structure of L. major cytochrome c (LmCytc). Like other types of cytochrome c, LmCytc has an electropositive surface surrounding the exposed heme edge that serves as the site of docking with redox partners. Kinetic assays performed with LmCytc and LmP show that LmCytc is a much better substrate for LmP than horse heart cytochrome c. Furthermore, unlike the well-studied yeast system, the reaction follows classic Michaelis-Menten kinetics and is sensitive to an increasing ionic strength. Using the yeast cocrystal as a control, protein-protein docking was performed using Rosetta to develop a model for the binding of LmP and LmCytc. These results suggest that the biological function of LmP is to act as a cytochrome c peroxidase. PMID: 22372542 |
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Campione S,Steshenko S,Albani M,Capolino F Department of Electrical Engineering and Computer Science, University of California, Irvine, California 92697, USA. |
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Complex modes and effective refractive index in 3D periodic arrays of plasmonic nanospheres. Opt Express. 2011 Dec 19;19(27):26027-43 We characterize the modes with complex wavenumber for both longitudinal and transverse polarization states (with respect to the mode traveling direction) in three dimensional (3D) periodic arrays of plasmonic nanospheres, including metal losses. The Ewald representation of the required dyadic periodic Green's function to represent the field in 3D periodic arrays is derived from the scalar case, which can be analytically continued into the complex wavenumber space. We observe the presence of one longitudinal mode and two transverse modes, one forward and one backward. Despite the presence of two modes for transverse polarization, we notice that the forward one is "dominant" (i.e., it contributes most to the field in the array). Therefore, in case of transverse polarization, we describe the composite material in terms of a homogenized effective refractive index, comparing results from (i) modal analysis, (ii) Maxwell Garnett theory, (iii) Nicolson-Ross-Weir retrieval method from scattering parameters for finite thickness structures (considering different thicknesses, showing consistency of results), and (iv) the fitting of the fields obtained through HFSS simulations. The agreement among the different methods justifies the performed homogenization procedure in case of transverse polarization. PMID: 22274192 |
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Zeng Z,Patel J,Lee SH,McCallum M,Tyagi A,Yan M,Shea KJ Department of Chemistry, University of California, Irvine, Irvine, California 92697, USA. |
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Synthetic polymer nanoparticle-polysaccharide interactions: a systematic study. J Am Chem Soc. 2012 Feb 8;134(5):2681-90 The interaction between synthetic polymer nanoparticles (NPs) and biomacromolecules (e.g., proteins, lipids, and polysaccharides) can profoundly influence the NPs fate and function. Polysaccharides (e.g., heparin/heparin sulfate) are a key component of cell surfaces and the extracelluar matrix and play critical roles in many biological processes. We report a systematic investigation of the interaction between synthetic polymer nanoparticles and polysaccharides by ITC, SPR, and an anticoagulant assay to provide guidelines to engineer nanoparticles for biomedical applications. The interaction between acrylamide nanoparticles (~30 nm) and heparin is mainly enthalpy driven with submicromolar affinity. Hydrogen bonding, ionic interactions, and dehydration of polar groups are identified to be key contributions to the affinity. It has been found that high charge density and cross-linking of the NP can contribute to high affinity. The affinity and binding capacity of heparin can be significantly diminished by an increase in salt concentration while only slightly decreased with an increase of temperature. A striking difference in binding thermodynamics has been observed when the main component of a polymer nanoparticle is changed from acrylamide (enthalpy driven) to N-isopropylacryalmide (entropy driven). This change in thermodynamics leads to different responses of these two types of polymer NPs to salt concentration and temperature. Select synthetic polymer nanoparticles have also been shown to inhibit protein-heparin interactions and thus offer the potential for therapeutic applications. PMID: 22229911 |
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Yang J,Wang J,Gu P,You XJ,Klassen H Department of Ophthalmology, Ophthalmology Research Laboratories, The Gavin Herbert Eye Institute, University of California, Irvine, CA 92697, USA. |
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Feline Neural Progenitor Cells I: Long-Term Expansion under Defined Culture Conditions. Stem Cells Int. 2012;2012:108340 Neural progenitor cells (NPCs) of feline origin (cNPCs) have demonstrated utility in transplantation experiments, yet are difficult to grow in culture beyond the 1 month time frame. Here we use an enriched, serum-free base medium (Ultraculture) and report the successful long-term propagation of these cells. Primary cultures were derived from fetal brain tissue and passaged in DMEM/F12-based or Ultraculture-based proliferation media, both in the presence of EGF + bFGF. Cells in standard DMEM/F12-based medium ceased to proliferate by 1-month, whereas the cells in the Ultraculture-based medium continued to grow for at least 5 months (end of study) with no evidence of senescence. The Ultraculture-based cultures expressed lower levels of progenitor and lineage-associated markers under proliferation conditions but retained multipotency as evidenced by the ability to differentiate into neurons and glia following growth factor removal in the presence of FBS. Importantly, later passage cNPCs did not develop chromosomal aberrations. PMID: 22577394 |
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Buchbinder D,Mertens AC,Zeltzer LK,Leisenring WM,Goodman P,Lown EA,Alderfer MA,Recklitis CJ,Oeffinger KC,Armstrong GT,Hudson MM,Robison LL,Casillas J 1Hematology - Pediatrics, Children's Hospital of Orange County - UC Irvine. |
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Cancer Prevention and Screening Practices of Siblings of Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study. Cancer Epidemiol Biomarkers Prev. 2012 May 10;: OBJECTIVE: To compare the skin and breast/cervical cancer prevention/screening practices of adult siblings of childhood cancer survivors with controls and to identify modifying factors for these practices.METHODS: Cross-sectional, self-report data from 2,588 adult siblings of 5+ year survivors of childhood cancer were analyzed to assess cancer prevention/screening practices. Two age, sex and race/ethnicity-matched samples (n=5,915 and n=37,789) of the Behavioral Risk Factor Surveillance System participants served as the comparison populations. Sociodemographic and cancer-related data were explored as modifying factors for sibling cancer prevention/screening practices through multivariable logistic regression. RESULTS: Compared to controls, siblings were more likely to practice skin cancer prevention behaviors: use of protective clothing (OR 2.85, 95% 2.39-3.39), use of shade (OR 2. 11, 95% 1.88-2.36), use of sunscreen (OR 1.27, 95% 1.14-1.40), and wearing a hat (OR 1.77, 95% 1.58-1.98). No differences were noted for breast/cervical cancer screening including mammography and Pap testing. Having less than a high school education and lack of health insurance were associated with diminished cancer prevention/screening behaviors. Survivor diagnosis, treatment intensity, adverse health, chronic health conditions, and second cancers were not associated with sibling cancer prevention/screening behaviors. CONCLUSIONS: Siblings of cancer survivors report greater skin cancer prevention practices when compared with controls; however, no differences were noted for breast/cervical cancer screening practices. Access to care and lack of education may be associated with decreased cancer prevention/screening behaviors. Interventions are needed to address these barriers. Impact: Research should be directed at understanding the impact of the cancer experience on sibling health behaviors. PMID: 22576363 |
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Liu S,Agalliu D,Yu C,Fisher M UC Irvine Medical Center, 101 The City Drive South, Shanbrom Hall Room 121, Orange, CA 92868. mfisher@uci.edu. |
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The Role of Pericytes in Blood-Brain Barrier Function and Stroke. Curr Pharm Des. 2012 May 11;: Central nervous system pericytes have critical and complex inductive, structural, and regulatory roles interacting with other cell types of the neurovascular unit, especially endothelial cells and astrocytes. Pericyte-endothelial interactions are particularly prominent for blood-brain barrier (BBB) maintenance, with profound effects on basement membrane and endothelial tight junction structure and function. Under experimental conditions of hypoxia-ischemia mimicking stroke, pericytes migrate from their usual microvascular location and influence, directly or indirectly, BBB permeability. The contractile properties of pericytes provide the capacity to regulate capillary blood flow, but this may have detrimental effects on ischemic injury. Stem cell characteristics of pericytes imply an important regenerative role following stroke. Pericytes thus appear to orchestrate multiple critical functions in stroke, involving blood flow, permeability, and repair of the neurovascular unit. PMID: 22574979 |
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Chou CS,Bardwell L,Nie Q,Yi TM Center for Complex Biological Systems, Department of Developmental and Cell Biology, University of California-Irvine, CA 92697, USA. |
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Noise filtering tradeoffs in spatial gradient sensing and cell polarization response. BMC Syst Biol. 2011;5:196 Cells sense chemical spatial gradients and respond by polarizing internal components. This process can be disrupted by gradient noise caused by fluctuations in chemical concentration. PMID: 22166067 |
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Patel PM,Kern MJ Division of Cardiology, Department of Medicine, University of California, Irvine, Orange, California. |
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Mastering transradial techniques: Essential skills for complex endovascular peripheral artery intervention. Catheter Cardiovasc Interv. 2012 May 8;: PMID: 22570315 |
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Sharma A,Patil JA,Gramajo AL,Seigel GM,Kuppermann BD,Kenney CM Department of Ophthalmology, Gavin S. Herbert Eye Institute, University of California, Irvine, CA, USA, . |
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Effects of hydroquinone on retinal and vascular cells in vitro. Indian J Ophthalmol. 2012 May;60(3):189-93 Aim: To explore the molecular pathophysiology that might explain the epidemiologic association between cigarette smoke and age-related macular degeneration (AMD) by examining the effects of hydroquinone (HQ), a toxic compound present in high concentration in cigarette smoke-related tar, on human retinal pigment epithelial cells (ARPE-19), rat retinal neurosensory cells (R-28), and human microvascular endothelial cells (HMVEC). Materials and Methods: ARPE-19, R-28, and HMVEC were treated for 24 h with four different concentrations of HQ (500 μM, 200 μM, 100 μM, 50 μM). Cell viability, caspase-3/7 activation, DNA laddering patterns, and lactate dehydrogenase (LDH) levels were analyzed. Results: At 50 μM HQ, R-28 cells showed a significant decrease in cell viability compared with the dimethyl sulfoxide (DMSO)-treated controls. At the 100-500 μM concentrations, all three cell lines showed significant cell death (P < 0.001). In the ARPE-19, R-28, and HMVEC cultures, the caspase-3/7 activities were not increased at any of the HQ concentration. Conclusion: Our findings suggest that the mechanism of cell death in all three cell lines was through non-apoptotic pathway. In addition, neuroretinal R-28 cells were more sensitive to HQ than the ARPE-19 and HMVEC cultures. PMID: 22569379 |
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Greene MA,Yonova IM,Williams FJ,Jarvo ER Department of Chemistry, University of California , Irvine, California 92697-2025, United States. |
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Traceless Directing Group for Stereospecific Nickel-Catalyzed Alkyl-Alkyl Cross-Coupling Reactions. Org Lett. 2012 May 8;: Stereospecific nickel-catalyzed cross-coupling reactions of benzylic 2-methoxyethyl ethers are reported for the preparation of enantioenriched 1,1-diarylethanes. The 2-methoxyethyl ether serves as a traceless directing group that accelerates cross-coupling. Chelation of magnesium ions is proposed to activate the benzylic C-O bond for oxidative addition. PMID: 22568515 |
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Cerussi AE,Warren R,Hill B,Roblyer D,Leproux A,Durkin AF,O'Sullivan TD,Keene S,Haghany H,Quang T,Mantulin WM,Tromberg BJ Beckman Laser Institute, University of California Irvine, Irvine, California 92617, USA. |
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Tissue phantoms in multicenter clinical trials for diffuse optical technologies. Biomed Opt Express. 2012 May 1;3(5):966-71 Tissue simulating phantoms are an important part of instrumentation validation, standardization/training and clinical translation. Properly used, phantoms form the backbone of sound quality control procedures. We describe the development and testing of a series of optically turbid phantoms used in a multi-center American College of Radiology Imaging Network (ACRIN) clinical trial of Diffuse Optical Spectroscopic Imaging (DOSI). The ACRIN trial is designed to measure the response of breast tumors to neoadjuvant chemotherapy. Phantom measurements are used to determine absolute instrument response functions during each measurement session and assess both long and short-term operator and instrument reliability. PMID: 22567589 |
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Murphy PS,Evans GR Aesthetic and Plastic Surgery Institute, University of California Irvine Medical Center, 200 S. Manchester Avenue, Suite 650, Orange, CA 92868, USA. |
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Advances in wound healing: a review of current wound healing products. Plast Surg Int. 2012;2012:190436 Successful wound care involves optimizing patient local and systemic conditions in conjunction with an ideal wound healing environment. Many different products have been developed to influence this wound environment to provide a pathogen-free, protected, and moist area for healing to occur. Newer products are currently being used to replace or augment various substrates in the wound healing cascade. This review of the current state of the art in wound-healing products looks at the latest applications of silver in microbial prophylaxis and treatment, including issues involving resistance and side effects, the latest uses of negative pressure wound devices, advanced dressings and skin substitutes, biologic wound products including growth factor applications, and hyperbaric oxygen as an adjunct in wound healing. With the abundance of available products, the goal is to find the most appropriate modality or combination of modalities to optimize healing. PMID: 22567251 |
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Klassen H,Kiilgaard JF,Warfvinge K,Samuel MS,Prather RS,Wong F,Petters RM,la Cour M,Young MJ Gavin Herbert Eye Institute, Ophthalmology Research, University of California-Irvine, Irvine, CA 92697-4390, USA. |
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Photoreceptor Differentiation following Transplantation of Allogeneic Retinal Progenitor Cells to the Dystrophic Rhodopsin Pro347Leu Transgenic Pig. Stem Cells Int. 2012;2012:939801 Purpose. Transplantation of stem, progenitor, or precursor cells has resulted in photoreceptor replacement and evidence of functional efficacy in rodent models of retinal degeneration. Ongoing work has been directed toward the replication of these results in a large animal model, namely, the pig. Methods. Retinal progenitor cells were derived from the neural retina of GFP-transgenic pigs and transplanted to the subretinal space of rhodopsin Pro347Leu-transgenic allorecipients, in the early stage of the degeneration and the absence of immune suppression. Results. Results confirm the survival of allogeneic porcine RPCs without immune suppression in the setting of photoreceptor dystrophy. The expression of multiple photoreceptor markers by grafted cells included the rod outer segment-specific marker ROM-1. Further evidence of photoreceptor differentiation included the presence of numerous photoreceptor rosettes within GFP-positive grafts, indicative of the development of cellular polarity and self-assembly into rudiments of outer retinal tissue. Conclusion. Together, these data support the tolerance of RPCs as allografts and demonstrate the high level of rod photoreceptor development that can be obtained from cultured RPCs following transplantation. Strategies for further progress in this area, together with possible functional implications, are discussed. PMID: 22567027 |
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Sigua R,Tripathy S,Anand P,Gross SP Department of Developmental and Cell Biology, School of Biosciences, University of California, Irvine. |
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Isolation and purification of Kinesin from Drosophila embryos. J Vis Exp. 2012;(62): Motor proteins move cargos along microtubules, and transport them to specific sub-cellular locations. Because altered transport is suggested to underlie a variety of neurodegenerative diseases, understanding microtubule based motor transport and its regulation will likely ultimately lead to improved therapeutic approaches. Kinesin-1 is a eukaryotic motor protein which moves in an anterograde (plus-end) direction along microtubules (MTs), powered by ATP hydrolysis. Here we report a detailed purification protocol to isolate active full length kinesin from Drosophila embryos, thus allowing the combination of Drosophila genetics with single-molecule biophysical studies. Starting with approximately 50 laying cups, with approximately 1000 females per cup, we carried out overnight collections. This provided approximately 10 ml of packed embryos. The embryos were bleach dechorionated (yielding approximately 9 grams of embryos), and then homogenized. After disruption, the homogenate was clarified using a low speed spin followed by a high speed centrifugation. The clarified supernatant was treated with GTP and taxol to polymerize MTs. Kinesin was immobilized on polymerized MTs by adding the ATP analog, 5'-adenylyl imidodiphosphate at room temperature. After kinesin binding, microtubules were sedimented via high speed centrifugation through a sucrose cushion. The microtubule pellet was then re-suspended, and this process was repeated. Finally, ATP was added to release the kinesin from the MTs. High speed centrifugation then spun down the MTs, leaving the kinesin in the supernatant. This kinesin was subjected to a centrifugal filtration using a 100 KD cut off filter for further purification, aliquoted, snap frozen in liquid nitrogen, and stored at -80 °C. SDS gel electrophoresis and western blotting was performed using the purified sample. The motor activity of purified samples before and after the final centrifugal filtration step was evaluated using an in vitro single molecule microtubule assay. The kinesin fractions before and after the centrifugal filtration showed processivity as previously reported in literature. Further experiments are underway to evaluate the interaction between kinesin and other transport related proteins. PMID: 22565641 |
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Samarasena JB,Muthusamy VR,Jamal MM 1] Department of Gastroenterology, Long Beach Veterans Affairs Healthcare system, Long Beach, California, USA [2] Division of Gastroenterology, University of California-Irvine, Orange, California, USA. |
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Split-Dosed MiraLAX/Gatorade Is an Effective, Safe, and Tolerable Option for Bowel Preparation in Low-Risk Patients: A Randomized Controlled Study. Am J Gastroenterol. 2012 May 8;: OBJECTIVES:MiraLAX with Gatorade is a low-volume bowel preparation regimen that has been used widely in community practice and is anecdotally better tolerated than Golytely. Despite its widespread use, there are little data on the efficacy and tolerability of this solution and no safety data in the literature. The primary aim of this study was to compare the efficacy, safety, and tolerability of single-dosed and split-dosed regimens of MiraLAX/Gatorade with Golytely for bowel preparation before colonoscopy.METHODS:Adults presenting for outpatient colonoscopy were screened for enrollment into this single-blinded randomized controlled trial. Patients with severe cardiac or renal disease and patients with electrolyte abnormalities were excluded. Subjects were randomized into four groups: 4 l Golytely single-dosed (Go-Si), 4 l Golytely split-dosed (Go-Sp), 238 g MiraLAX in 64 oz of Gatorade single-dosed (Mlax-Si), and MiraLAX/Gatorade split-dosed (Mlax-Sp) groups. Laboratory data including complete blood count, comprehensive metabolic panel, and osmolality were collected before the day of bowel preparation and just before the start of colonoscopy. Subjects completed a survey assessing taste and tolerability of the solution. Colonoscopies were recorded using video recording software and de-identified. Colonoscopy videos were evaluated for efficacy of cleansing by two blinded endoscopists. Two validated bowel preparation scales were used to assess bowel cleansing: the Boston Bowel Preparation Scale (BBPS; 0-9 best) and Ottawa Scale (0-14 worst).RESULTS:A total of 222 patients were evaluated in this study (86.2% male, mean age 59.4). Of these, 57 subjects were randomized to the Go-Si group, 51 to Go-Sp group, 60 to Mlax-Si group, and 54 to Mlax-Sp group. There was no significant difference in age, gender, or timing of colonoscopy between the groups (P>0.05). Mean BBPS scores were: Go-Si=6.07, Go-Sp=8.33, Mlax-Si=6.62, and Mlax-Sp=8.01. Mean Ottawa score for the groups were: Go-Si group=6.77, Go-Sp=4.12, Mlax-Si=6.25, and Mlax-Sp=4.8. Go-Sp resulted in significantly better cleansing than Go-Si (P PMID: 22565162 |
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Rusconi B,Maranhao AC,Fuhrer JP,Krotee P,Choi SH,Grun F,Thireou T,Dimitratos SD,Woods DF,Marinotti O,Walter MF,Eliopoulos E Developmental Biology Center, University of California Irvine, CA 92697, USA. |
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Mapping the Anopheles gambiae Odorant Binding Protein 1 (AgamOBP1) using modeling techniques, site directed mutagenesis, circular dichroism and ligand binding assays. Biochim Biophys Acta. 2012 May 4;: The major malaria vector in Sub-Saharan Africa is the Anopheles gambiae mosquito. This species is a key target of malaria control measures. Mosquitoes find humans primarily through olfaction, yet the molecular mechanisms associated with host-seeking behavior remain largely unknown. To further understand the functionality of A. gambiae odorant binding protein 1 (AgamOBP1), we combined in silico protein structure modeling and site-directed mutagenesis to generate 16 AgamOBP1 protein analogues containing single point mutations of interest. Circular dichroism (CD) and ligand-binding assays provided data necessary to probe the effects of the point mutations on ligand binding and the overall structure of AgamOBP1. Far-UV CD spectra of mutated AgamOBP1 variants displayed both substantial decreases to ordered α-helix structure (up to22%) and increases to disordered α-helix structure(up to 15%) with only minimal changes in random coil (unordered) structure. In mutations Y54A, Y122A and W114Q, aromatic side chain removal from the binding site significantly reduced N-phenyl-1-naphthylamine binding. Several non-aromatic mutations (L15T, L19T, L58T, L58Y, M84Q, M84K, H111A, Y122A and L124T) elicited changes to protein conformation with subsequent effects on ligand binding. This study provides empirical evidence for the in silico predicted functions of specific amino acids in AgamOBP1 folding and ligand binding characteristics. PMID: 22564768 |
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Lioudyno MI,Broccio M,Sokolov Y,Rasool S,Wu J,Alkire MT,Liu V,Kozak JA,Dennison PR,Glabe CG,Lösche M,Hall JE Department of Physiology and Biophysics, University of California Irvine, Irvine, Calfornia, United States of America. |
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Effect of synthetic aβ Peptide oligomers and fluorinated solvents on kv1.3 channel properties and membrane conductance. PLoS One. 2012;7(4):e35090 The impact of synthetic amyloid β (1-42) (Aβ(1-42)) oligomers on biophysical properties of voltage-gated potassium channels Kv 1.3 and lipid bilayer membranes (BLMs) was quantified for protocols using hexafluoroisopropanol (HFIP) or sodium hydroxide (NaOH) as solvents prior to initiating the oligomer formation. Regardless of the solvent used Aβ(1-42) samples contained oligomers that reacted with the conformation-specific antibodies A11 and OC and had similar size distributions as determined by dynamic light scattering. Patch-clamp recordings of the potassium currents showed that synthetic Aβ(1-42) oligomers accelerate the activation and inactivation kinetics of Kv 1.3 current with no significant effect on current amplitude. In contrast to oligomeric samples, freshly prepared, presumably monomeric, Aβ(1-42) solutions had no effect on Kv 1.3 channel properties. Aβ(1-42) oligomers had no effect on the steady-state current (at -80 mV) recorded from Kv 1.3-expressing cells but increased the conductance of artificial BLMs in a dose-dependent fashion. Formation of amyloid channels, however, was not observed due to conditions of the experiments. To exclude the effects of HFIP (used to dissolve lyophilized Aβ(1-42) peptide), and trifluoroacetic acid (TFA) (used during Aβ(1-42) synthesis), we determined concentrations of these fluorinated compounds in the stock Aβ(1-42) solutions by (19)F NMR. After extensive evaporation, the concentration of HFIP in the 100× stock Aβ(1-42) solutions was ∼1.7 μM. The concentration of residual TFA in the 70× stock Aβ(1-42) solutions was ∼20 μM. Even at the stock concentrations neither HFIP nor TFA alone had any effect on potassium currents or BLMs. The Aβ(1-42) oligomers prepared with HFIP as solvent, however, were more potent in the electrophysiological tests, suggesting that fluorinated compounds, such as HFIP or structurally-related inhalational anesthetics, may affect Aβ(1-42) aggregation and potentially enhance ability of oligomers to modulate voltage-gated ion channels and biological membrane properties. PMID: 22563377 |
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Chen PL,Chen CF,Chen Y,Guo XE,Huang CK,Shew JY,Reddick RL,Wallace DC,Lee WH Department of Biological Chemistry, School of Medicine, University of California, Irvine, CA, USA. |
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Mitochondrial genome instability resulting from SUV3 haploinsufficiency leads to tumorigenesis and shortened lifespan. Oncogene. 2012 May 7;: Mitochondrial dysfunction has been a hallmark of cancer. However, whether it has a causative role awaits to be elucidated. Here, using an animal model derived from inactivation of SUV3, a mitochondrial helicase, we demonstrated that mSuv3+/- mice harbored increased mitochondrial DNA (mtDNA) mutations and decreased mtDNA copy numbers, leading to tumor development in various sites and shortened lifespan. These phenotypes were transmitted maternally, indicating the etiological role of the mitochondria. Importantly, reduced SUV3 expression was observed in human breast tumor specimens compared with corresponding normal tissues in two independent cohorts. These results demonstrated for the first time that maintaining mtDNA integrity by SUV3 helicase is critical for cancer suppression.Oncogene advance online publication, 7 May 2012; doi:10.1038/onc.2012.120. PMID: 22562243 |
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Stringari C,Sierra R,Donovan PJ,Gratton E University of California, Irvine, Laboratory of Fluorescence Dynamics, Biomedical Engineering Department, Irvine, California. |
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Label-free separation of human embryonic stem cells and their differentiating progenies by phasor fluorescence lifetime microscopy. J Biomed Opt. 2012 Apr;17(4):046012 We develop a label-free optical technique to image and discriminate undifferentiated human embryonic stem cells (hESCs) from their differentiating progenies in vitro. Using intrinsic cellular fluorophores, we perform fluorescence lifetime microscopy (FLIM) and phasor analysis to obtain hESC metabolic signatures. We identify two optical biomarkers to define the differentiation status of hESCs: Nicotinamide adenine dinucleotide (NADH) and lipid droplet-associated granules (LDAGs). These granules have a unique lifetime signature and could be formed by the interaction of reactive oxygen species and unsaturated metabolic precursor that are known to be abundant in hESC. Changes in the relative concentrations of these two intrinsic biomarkers allow for the discrimination of undifferentiated hESCs from differentiating hESCs. During early hESC differentiation we show that NADH concentrations increase, while the concentration of LDAGs decrease. These results are in agreement with a decrease in oxidative phosphorylation rate. Single-cell phasor FLIM signatures reveal an increased heterogeneity in the metabolic states of differentiating H9 and H1 hESC colonies. This technique is a promising noninvasive tool to monitor hESC metabolism during differentiation, which can have applications in high throughput analysis, drug screening, functional metabolomics and induced pluripotent stem cell generation. PMID: 22559690 |
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Yan H,Lin Y,Barber WC,Unlu MB,Gulsen G Tu and Yuen Center for Functional Onco-Imaging and Department of Radiological Sciences, University of California, Irvine, California 92697, USA. |
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A gantry-based tri-modality system for bioluminescence tomography. Rev Sci Instrum. 2012 Apr;83(4):043708 A gantry-based tri-modality system that combines bioluminescence (BLT), diffuse optical (DOT), and x-ray computed tomography (XCT) into the same setting is presented here. The purpose of this system is to perform bioluminescence tomography using a multi-modality imaging approach. As parts of this hybrid system, XCT and DOT provide anatomical information and background optical property maps. This structural and functional a priori information is used to guide and restrain bioluminescence reconstruction algorithm and ultimately improve the BLT results. The performance of the combined system is evaluated using multi-modality phantoms. In particular, a cylindrical heterogeneous multi-modality phantom that contains regions with higher optical absorption and x-ray attenuation is constructed. We showed that a 1.5 mm diameter bioluminescence inclusion can be localized accurately with the functional a priori information while its source strength can be recovered more accurately using both structural and the functional a priori information. PMID: 22559540 |
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Choi Y,Moody IS,Sims PC,Hunt SR,Corso BL,Seitz DE,Blaszcazk LC,Collins PG,Weiss GA Institute for Surface and Interface Science, University of California, Irvine, California 92697, USA. |
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Single-molecule dynamics of lysozyme processing distinguishes linear and cross-linked peptidoglycan substrates. J Am Chem Soc. 2012 Feb 1;134(4):2032-5 The dynamic processivity of individual T4 lysozyme molecules was monitored in the presence of either linear or cross-linked peptidoglycan substrates. Single-molecule monitoring was accomplished using a novel electronic technique in which lysozyme molecules were tethered to single-walled carbon nanotube field-effect transistors through pyrene linker molecules. The substrate-driven hinge-bending motions of lysozyme induced dynamic electronic signals in the underlying transistor, allowing long-term monitoring of the same molecule without the limitations of optical quenching or bleaching. For both substrates, lysozyme exhibited processive low turnover rates of 20-50 s(-1) and rapid (200-400 s(-1)) nonproductive motions. The latter nonproductive binding events occupied 43% of the enzyme's time in the presence of the cross-linked peptidoglycan but only 7% with the linear substrate. Furthermore, lysozyme catalyzed the hydrolysis of glycosidic bonds to the end of the linear substrate but appeared to sidestep the peptide cross-links to zigzag through the wild-type substrate. PMID: 22239748 |
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