UCI Authors in PubMed
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Carrillo JA,Munoz CA Department of Neurology, University of California Irvine, 101 The City Drive South, Shanbrom Hall, Suite 121, Orange, CA 92868, USA. |
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Alternative Chemotherapeutic Agents: Nitrosoureas, Cisplatin, Irinotecan. Neurosurg Clin N Am. 2012 Apr;23(2):297-306 Irinotecan, cisplatin, and nitrosoureas have a long history of use in brain tumors, with demonstrated efficacy in the adjuvant treatment of malignant gliomas. In the era of temozolomide with concurrent radiotherapy given as the standard of care, their use has shifted to treatment at progression or recurrence. Now with the widespread use of bevacizumab in the recurrent setting, irinotecan and other chemotherapies are seeing increased use in combination with bevacizumab and alone in the recurrent setting. The activity of these chemotherapeutic agents in brain tumors will likely ensure a place in the armamentarium of neuro-oncologists for many years. PMID: 22440873 |
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Morgan MJ,Mareschal I,Chubb C,Solomon JA Max Planck Institute for Neurological Research, , 50 Gleueler Strasse, Koeln, Germany, Optometry Department, City University, , London, UK, University of California at Irvine, , Irvine, CA 92697, USA, School of Psychology, University of Sydney, , Sydney, New South Wales 20006, Australia. |
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Perceived pattern regularity computed as a summary statistic: implications for camouflage. Proc Biol Sci. 2012 Mar 21;: Why do the equally spaced dots in figure 1 appear regularly spaced? The answer 'because they are' is naive and ignores the existence of sensory noise, which is known to limit the accuracy of positional localization. Actually, all the dots in figure 1 have been physically perturbed, but in the case of the apparently regular patterns to an extent that is below threshold for reliable detection. Only when retinal pathology causes severe distortions do regular grids appear perturbed. Here, we present evidence that low-level sensory noise does indeed corrupt the encoding of relative spatial position, and limits the accuracy with which observers can detect real distortions. The noise is equivalent to a Gaussian random variable with a standard deviation of approximately 5 per cent of the inter-element spacing. The just-noticeable difference in positional distortion between two patterns is smallest when neither of them is perfectly regular. The computation of variance is statistically inefficient, typically using only five or six of the available dots. PMID: 22438499 |
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Finkbeiner SD,Briscoe AD,Reed RD Department of Ecology and Evolutionary Biology, University of California, , Irvine, CA 92697, USA, Smithsonian Tropical Research Institute, , Panama City 0843-03092, Panama. |
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The benefit of being a social butterfly: communal roosting deters predation. Proc Biol Sci. 2012 Mar 21;: Aposematic passion-vine butterflies from the genus Heliconius form communal roosts on a nightly basis. This behaviour has been hypothesized to be beneficial in terms of information sharing and/or anti-predator defence. To better understand the adaptive value of communal roosting, we tested these two hypotheses in field studies. The information-sharing hypothesis was addressed by examining following behaviour of butterflies departing from natural roosts. We found no evidence of roost mates following one another to resources, thus providing no support for this hypothesis. The anti-predator defence hypothesis was tested using avian-indiscriminable Heliconius erato models placed singly and in aggregations at field sites. A significantly higher number of predation attempts were observed on solitary models versus aggregations of models. This relationship between aggregation size and attack rate suggests that communally roosting butterflies enjoy the benefits of both overall decreased attack frequency as well as a prey dilution effect. Communal roosts probably deter predators through collective aposematism in which aggregations of conspicuous, unpalatable prey communicate a more effective repel signal to predators. On the basis of our results, we propose that predation by birds is a key selective pressure maintaining Heliconius communal roosting behaviour. PMID: 22438492 |
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Wang W,Feng L,Zhang H,Hachy S,Satohisa S,Laurent LC,Parast M,Zheng J,Chen DB Departments of Obstetrics and Gynecology (W.W., L.F., H.Z., S.H., S.S., D.-b.C.), University of California, Irvine, California 92697; Departments of Obstetrics and Gynecology (L.C.L.) and Pathology (M.P.), University of California San Diego, La Jolla, California 92093; and Department of Obstetrics and Gynecology (J.Z.), University of Wisconsin-Madison, Madison, Wisconsin 53715. |
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Preeclampsia Up-Regulates Angiogenesis-Associated MicroRNA (i.e., miR-17, -20a, and -20b) That Target Ephrin-B2 and EPHB4 in Human Placenta. J Clin Endocrinol Metab. 2012 Mar 21;: Context:Placental angiogenesis contributes to the pathogenesis of preeclampsia (PE) that affects 5-8% of all human pregnancies. MicroRNA (miRNA) are a class of noncoding 21- to 25-nucleotide RNA that negatively regulate gene expression posttranscriptionly.Objective:The aim of this study was to test the hypothesis that miRNA are differentially expressed in healthy term and PE placentas and a subclass of angiogenesis-associated miRNA are increased by PE.Design:Total miRNA were extracted from villous placental tissues from healthy term and severe preeclamptic pregnancies. Differential miRNA expression was analyzed by microarray and real-time quantitative PCR. Angiogenesis-associated miRNA were analyzed by target prediction databases. In situ hybridization was used to localize miRNA. Target verification was performed by transfection of miRNA precursors or antagomirs into endothelial and BeWo cells and luciferase reporter assays.Results:Three highly expressed miRNA (miR-17, -20a, and -20b) were found significantly increased in PE compared with healthy term placentas (n = 10 per group). They target on the same group of genes important for angiogenesis. miR-20b was expressed primarily in villous syncytiotrophoblasts in term placenta. Overexpression or inhibition of miR-20b differentially regulated mRNA expression of those genes in endothelial vs. trophoblast cells. Luciferase reporter assay showed that miR-20b targets EPHB4 and ephrin-B2 that have been shown to be critical for early human placental development. Placental ephrin-B2 mRNA was significantly down-regulated in PE compared with normotensive pregnancies.Conclusion:miR-17, miR-20a, and miR-20b are differentially regulated in human placentas by PE. They regulate EPHB4 and ephrin-B2 expression in trophoblast and endothelial cells via the same "seed" sequence, suggesting their roles in early placental development. PMID: 22438230 |
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Nguyen N,Champion JK,Ponce J,Quebbemann B,Patterson E,Pham B,Raum W,Buchwald JN,Segato G,Favretti F Division of GI Surgery, University of California Irvine Medical Center, 333 City Bldg. West, Suite 850, Orange, CA, 92868, USA, ninhn@uci.edu. |
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A Review of Unmet Needs in Obesity Management. Obes Surg. 2012 Mar 22;: The prevalence of obesity continues to escalate in the USA; however, there is no consensus regarding the optimal therapy for obesity. For the vast majority of severely obese patients, conventional medical therapies (i.e., diet, exercise, behavioral counseling) often fail over the long term. Existing pharmacotherapy adjunctive to behavioral therapy has limited effectiveness and an imperfect safety record. In contrast, bariatric surgery has a high degree of weight loss efficacy, yet only a small fraction of the qualifying obese population undergoes these procedures because of the associated perioperative risks and potential late complications. In addition, the role of bariatric surgery is unclear in certain patient populations, such as patients with lower body mass index (BMI, 30-35 kg/m(2)), the high-risk super-super obese patients (BMI > 60), the morbidly obese adolescent, and obese patients requiring weight reduction in preparation for other procedures, such as orthopedic, transplant, or vascular surgeries. In these circumstances, there is a need for an effective but less invasive treatment to bridge the gap between medical and surgical therapy. This review examines current treatment outcomes, identifies prominent areas of unmet clinical needs, and provides an overview of two minimally invasive "temporary procedures for weight loss" that may eventually address some of the unmet needs in obesity management. PMID: 22438220 |
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Amini A,Xiao L,Allen PK,Suzuki A,Hayashi Y,Liao Z,Hofstetter W,Crane C,Komaki R,Bhutani MS,Lee JH,Ajani JA,Welsh J Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; UC Irvine School of Medicine, Irvine, California. |
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Celiac Node Failure Patterns After Definitive Chemoradiation for Esophageal Cancer in the Modern Era. Int J Radiat Oncol Biol Phys. 2012 Mar 19;: PURPOSE: The celiac lymph node axis acts as a gateway for metastatic systemic spread. The need for prophylactic celiac nodal coverage in chemoradiation therapy for esophageal cancer is controversial. Given the improved ability to evaluate lymph node status before treatment via positron emission tomography (PET) and endoscopic ultrasound, we hypothesized that prophylactic celiac node irradiation may not be needed for patients with localized esophageal carcinoma. METHODS AND MATERIALS: We reviewed the radiation treatment volumes for 131 patients who underwent definitive chemoradiation for esophageal cancer. Patients with celiac lymph node involvement at baseline were excluded. Median radiation dose was 50.4 Gy. The location of all celiac node failures was compared with the radiation treatment plan to determine whether the failures occurred within or outside the radiation treatment field. RESULTS: At a median follow-up time of 52.6 months (95% CI 46.1-56.7 months), 6 of 60 patients (10%) without celiac node coverage had celiac nodal failure; in 5 of these patients, the failures represented the first site of recurrence. Of the 71 patients who had celiac coverage, only 5 patients (7%) had celiac region relapse. In multivariate analyses, having a pretreatment-to-post-treatment change in standardized uptake value on PET >52% (odds ratio [OR] 0.198, p = 0.0327) and having failure in the clinical target volume (OR 10.72, p = 0.001) were associated with risk of celiac region relapse. Of those without celiac coverage, the 6 patients that later developed celiac failure had a worse median overall survival time compared with the other 54 patients who did not fail (median overall survival time: 16.5 months vs. 31.5 months, p = 0.041). Acute and late toxicities were similar in both groups. CONCLUSIONS: Although celiac lymph node failures occur in approximately 1 of 10 patients, the lack of effective salvage treatments and subsequent low morbidity may justify prophylactic treatment in distal esophageal cancer patients. PMID: 22436793 |
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Lakon CM,Valente TW Department of Population Health and Disease Prevention, Program in Public Health, University of California, Irvine, CA, USA. |
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Social integration in friendship networks: The synergy of network structure and peer influence in relation to cigarette smoking among high risk adolescents. Soc Sci Med. 2012 Mar 2;: Using data from a study of high risk adolescents in Southern California, U.S.A. (N=851), this study examined synergy between social network measures of social integration and peer influence in relation to past month cigarette smoking. Using Hierarchical Linear Modeling, results indicated that being central in networks was significantly and positively related to past month cigarette smoking, across all study models. In addition, there is modest evidence that the number of reciprocated friendship ties was positively related to past month cigarette smoking. There is also some modest evidence that the relationship between having reciprocated friendships and past month cigarette smoking was moderated by a network peer influence process, smoking with those in youths' best friend networks. Findings indicate that being integrated within a social network context of peer influences favoring drug use relates to more smoking among these high risk youth. PMID: 22436575 |
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White S,Hingorani R,Arora R,Hughes CC,George S,Choi B University of California, Irvine, Biomedical Engineering, 2113 Verano Place, Irvine, California, United States, 92617, 610 733 7519; seanmw@uci.edu. |
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Longitudinal in vivo imaging to assess blood flow and oxygenation in implantable engineered tissues. Tissue Eng Part C Methods. 2012 Mar 21;: The functionality of vascular networks within implanted prevascularized tissues is difficult to assess using traditional analysis techniques such as histology. This is largely due to the inability to visualize hemodynamics in vivo longitudinally. Therefore, we have developed dynamic imaging methods to measure blood flow and hemoglobin oxygen saturation in implanted prevascularized tissues non-invasively and longitudinally. Using laser speckle imaging, multispectral imaging, and intravital microscopy, we demonstrate that fibrin-based tissue implants anastomose with the host (SCID mice) in as short as 20 hours. Anastomosis results in initial perfusion with highly oxygenated blood, and an increase in average hemoglobin oxygenation of 53%. However, shear rates in the preformed vessels were low (20.8 ± 12.8 s-1), and flow did not persist in the vast majority of preformed vessels due to thrombus formation. These findings suggest that designing an appropriate vascular network structure in prevascularized tissues to maintain shear rates above the threshold for thrombosis may be necessary to maintain flow following implantation. We conclude that wide-field and microscopic functional imaging can dynamically assess blood flow and oxygenation in vivo in prevascularized tissues, and can be used to rapidly evaluate and improve prevascularization strategies. PMID: 22435776 |
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Yoshioka H,Burns JE Department of Radiological Sciences, University of California, Irvine, California, USA. hiroshi@uci.edu. |
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Magnetic resonance imaging of triangular fibrocartilage. J Magn Reson Imaging. 2012 Apr;35(4):764-78 Due to their small size and complex structure, diagnosing injury of the proximal wrist ligamentous structures can be challenging. The triangular fibrocartilage complex (TFCC) is an example of one such structure, for which lesions may be missed unless high-resolution magnetic resonance imaging (MRI) obtained via a standard matrix with a small field of view or high-resolution imaging matrix (small spatial scale matrix elements/large matrix size) is utilized. While there have been recent advances in increasing MRI spatial resolution, attempts at improved visualization by isolated increase in the spatial resolution will be ineffective if the signal-to-noise ratio (SNR) of the images obtained is low. Additionally, high contrast resolution is important to facilitate a more precise visualization of these structures and their pathology. Thus, a balance of the three important imaging factor qualifications of high spatial resolution, high SNR, and high contrast resolution must be struck for optimized TFCC and wrist imaging. The goal of this article, then, is to elucidate the theory and techniques of effective high-resolution imaging of the proximal ligamentous structures of the wrist, balancing SNR and high contrast resolution constraints, and focusing on imaging of the TFCC as a prototypical example. J. Magn. Reson. Imaging 2012;35:764-778. © 2011 Wiley Periodicals, Inc. PMID: 22434698 |
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Noam Y,Phan L,McClelland S,Manders EM,Ehrengruber MU,Wadman WJ,Baram TZ,Chen Y Departments of Anatomy/Neurobiology & Pediatrics, University of California-Irvine, Irvine, California 92697-4475, USA; SILS-Center for Neuroscience, University of Amsterdam, 1098XH Amsterdam, The Netherlands. |
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Distinct regional and subcellular localization of the actin-binding protein filamin A in the mature rat brain. J Comp Neurol. 2012 Mar 20;: Filamin A (FLNa) is an actin-binding protein that regulates cell motility, adhesion and elasticity by cross-linking filamentous actin. Additional roles of FLNa include regulation of protein trafficking and surface expression. Whereas the functions of FLNa during brain development are well studied, little is known on its expression, distribution and function in the adult brain. Here, we characterize in detail the neuroanatomical distribution and subcellular localization of FLNa in the mature rat brain, by using two antisera directed against epitopes at either the N'- or the C'-terminus of the protein, further validated by mRNA expression. FLNa was widely and selectively expressed throughout the brain, and the intensity of immunoreactivity was region dependent. The most intensely FLNa-labeled neurons were found in discrete neuronal systems including basal forebrain structures, anterior nuclear group of thalamus, and hypothalamic parvocellular neurons. Pyramidal neurons in neocortex and hippocampus, as well as magnocellular cells in basolateral amygdaloid nucleus were also intensely FLNa-immunoreactive, and strong FLNa labeling was evident in the pontine and medullary raphe nuclei and in sensory and spinal trigeminal nuclei. The subcellular localization of FLNa was evaluated in situ, as well as in primary hippocampal neurons. Punctate expression was found in somata and along the dendritic shaft, but not detected in dendritic spines. These subcellular distribution patterns were recapitulated in hippocampal and neocortical pyramidal neurons in vivo. The characterization of the expression and subcellular localization of FLNa may provide new clues to the functional roles of this cytoskeletal protein in the adult brain. J. Comp. Neurol., 2012. © 2012 Wiley Periodicals, Inc. PMID: 22434607 |
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Mei L,Xue G,Lu ZL,He Q,Zhang M,Xue F,Chen C,Dong Q Department of Psychology and Social Behavior, University of California, Irvine, CA 92697, USA; State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, Beijing 100875, China. |
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Orthographic transparency modulates the functional asymmetry in the fusiform cortex: An artificial language training study. Brain Lang. 2012 Mar 19;: The laterality difference in the occipitotemporal region between Chinese (bilaterality) and alphabetic languages (left laterality) has been attributed to their difference in visual appearance. However, these languages also differ in orthographic transparency. To disentangle the effect of orthographic transparency from visual appearance, we trained subjects to read the same artificial script either as an alphabetic (i.e., transparent orthography) or a logographic (i.e., nontransparent orthography) language. Consistent with our previous results, both types of phonological training enhanced activations in the left fusiform gyrus. More interestingly, the laterality in the fusiform gyrus (especially the posterior region) was modulated by the orthographic transparency of the artificial script (more left-lateralized activation after alphabetic training than after logographic training). These results provide an alternative account (i.e., orthographic transparency) for the laterality difference between Chinese and alphabetic languages, and may have important implications for the role of the fusiform in reading. PMID: 22434043 |
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Phillips SJ University of California, Irvine, CA, USA. |
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APRN consensus model implementation and planning. Nurse Pract. 2012 Jan 19;37(1):22-45 The Annual Legislative Update describes the legislative issues that have the most impact on nurse practitioners and other advanced practice nurses across the country. PMID: 22217662 |
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Sevrioukova IF,Poulos TL Department of Molecular Biology and Biochemistry, University of California, Irvine, California 92697-3900, USA. |
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Structural and mechanistic insights into the interaction of cytochrome P4503A4 with bromoergocryptine, a type I ligand. J Biol Chem. 2012 Jan 27;287(5):3510-7 Cytochrome P4503A4 (CYP3A4), a major human drug-metabolizing enzyme, is responsible for the oxidation and clearance of the majority of administered drugs. One of the CYP3A4 substrates is bromoergocryptine (BEC), a dopamine receptor agonist prescribed for the inhibition of prolactin secretion and treatment of Parkinson disease, type 2 diabetes, and several other pathological conditions. Here we present a 2.15 Å crystal structure of the CYP3A4-BEC complex in which the drug, a type I heme ligand, is bound in a productive mode. The manner of BEC binding is consistent with the in vivo metabolite analysis and identifies the 8' and 9' carbons of the proline ring as the primary sites of oxidation. The crystal structure predicts the importance of Arg(212) and Thr(224) for binding of the tripeptide and lysergic moieties of BEC, respectively, which we confirmed experimentally. Our data support a three-step BEC binding model according to which the drug binds first at a peripheral site without perturbing the heme spectrum and then translocates into the active site cavity, where formation of a hydrogen bond between Thr(224) and the N1 atom of the lysergic moiety is followed by a slower conformational readjustment of the tripeptide group modulated by Arg(212). PMID: 22157006 |
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Wu J,Jiang C,Houston D,Baker D,Delfino R Program in Public Health, University of California, Irvine, USA. junwu@uci.edu |
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Automated time activity classification based on global positioning system (GPS) tracking data. Environ Health. 2011;10:101 Air pollution epidemiological studies are increasingly using global positioning system (GPS) to collect time-location data because they offer continuous tracking, high temporal resolution, and minimum reporting burden for participants. However, substantial uncertainties in the processing and classifying of raw GPS data create challenges for reliably characterizing time activity patterns. We developed and evaluated models to classify people's major time activity patterns from continuous GPS tracking data. PMID: 22082316 |
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Galasko DR,Peskind E,Clark CM,Quinn JF,Ringman JM,Jicha GA,Cotman C,Cottrell B,Montine TJ,Thomas RG,Aisen P, University of California, San Diego (Drs Galasko, Thomas, and Aisen and Ms Cottrell), Mary S. Easton Center for Alzheimer's Disease Research, Department of Neurology, University of California, Los Angeles (Dr Ringman), and Department of Neurobiology, University of California, Irvine (Dr Cotman); Department of Psychiatry, University of Washington, and Seattle VA Medical Center, Seattle (Drs Peskind and Montine); Avid Radiopharmaceuticals, Inc, Philadelphia, Pennsylvania (Dr Clark); Department of Neurology, Oregon Health and Sciences University, Portland (Dr Quinn); and Department of Neurology, University of Kentucky, Lexington (Dr Jicha). |
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Antioxidants for Alzheimer Disease: A Randomized Clinical Trial With Cerebrospinal Fluid Biomarker Measures. Arch Neurol. 2012 Mar 19;: OBJECTIVE: To evaluate whether antioxidant supplements presumed to target specific cellular compartments affected cerebrospinal fluid (CSF) biomarkers. DESIGN: Double-blind, placebo-controlled clinical trial. SETTING: Academic medical centers. PARTICIPANTS: Subjects with mild to moderate Alzheimer disease. Intervention Random assignment to treatment for 16 weeks with 800 IU/d of vitamin E (α-tocopherol) plus 500 mg/d of vitamin C plus 900 mg/d of α-lipoic acid (E/C/ALA); 400 mg of coenzyme Q 3 times/d; or placebo. MAIN OUTCOME MEASURES: Changes from baseline to 16 weeks in CSF biomarkers related to Alzheimer disease and oxidative stress, cognition (Mini-Mental State Examination), and function (Alzheimer's Disease Cooperative Study Activities of Daily Living Scale). RESULTS: Seventy-eight subjects were randomized; 66 provided serial CSF specimens adequate for biochemical analyses. Study drugs were well tolerated, but accelerated decline in Mini-Mental State Examination scores occurred in the E/C/ALA group, a potential safety concern. Changes in CSF Aβ42, tau, and P-tau(181) levels did not differ between the 3 groups. Cerebrospinal fluid F2-isoprostane levels, an oxidative stress biomarker, decreased on average by 19% from baseline to week 16 in the E/C/ALA group but were unchanged in the other groups. CONCLUSIONS: Antioxidants did not influence CSF biomarkers related to amyloid or tau pathology. Lowering of CSF F2-isoprostane levels in the E/C/ALA group suggests reduction of oxidative stress in the brain. However, this treatment raised the caution of faster cognitive decline, which would need careful assessment if longer-term clinical trials are conducted. Trial Registration clinicaltrials.gov Identifier: NCT00117403. PMID: 22431837 |
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Eckel-Mahan KL,Patel VR,Mohney RP,Vignola KS,Baldi P,Sassone-Corsi P Department of Biological Chemistry, Center for Epigenetics and Metabolism and Department of Computer Science, Institute for Genomics and Bioinformatics, University of California, Irvine, CA 92697. |
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Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci U S A. 2012 Mar 19;: The circadian clock governs a large array of physiological functions through the transcriptional control of a significant fraction of the genome. Disruption of the clock leads to metabolic disorders, including obesity and diabetes. As food is a potent zeitgeber (ZT) for peripheral clocks, metabolites are implicated as cellular transducers of circadian time for tissues such as the liver. From a comprehensive dataset of over 500 metabolites identified by mass spectrometry, we reveal the coordinate clock-controlled oscillation of many metabolites, including those within the amino acid and carbohydrate metabolic pathways as well as the lipid, nucleotide, and xenobiotic metabolic pathways. Using computational modeling, we present evidence of synergistic nodes between the circadian transcriptome and specific metabolic pathways. Validation of these nodes reveals that diverse metabolic pathways, including the uracil salvage pathway, oscillate in a circadian fashion and in a CLOCK-dependent manner. This integrated map illustrates the coherence within the circadian metabolome, transcriptome, and proteome and how these are connected through specific nodes that operate in concert to achieve metabolic homeostasis. PMID: 22431615 |
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Alderman MH,Piller LB,Ford CE,Probstfield JL,Oparil S,Cushman WC,Einhorn PT,Franklin SS,Papademetriou V,Ong ST,Eckfeldt JH,Furberg CD,Calhoun DA,Davis BR, Department of Epidemiology and Social Medicine, Albert Einstein College of Medicine, Bronx, NY; Coordinating Center for Clinical Trials, The University of Texas School of Public Health, Houston, TX; Clinical Trials Service Unit, University of Washington, Seattle, WA; Division of Cardiovascular Disease, University of Alabama at Birmingham, Birmingham, AL; Memphis Veterans Affairs Medical Center, Memphis, TN; Division of Cardiovascular Sciences, National Heart, Lung, and Blood Institute, Bethesda, MD; Department of Medicine, University of California, Irvine, CA; Veterans Affairs Medical Center Washington, Washington, DC; Ong Medical Center, Oxon Hill, MD; University of Minnesota Hospital and Clinic, Minneapolis, MN; Wake Forest University School of Medicine, Winston-Salem, NC. |
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Clinical Significance of Incident Hypokalemia and Hyperkalemia in Treated Hypertensive Patients in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial. Hypertension. 2012 Mar 19;: Concerns exist that diuretic-induced changes in serum potassium may have adverse effects in hypertensive patients. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, a large practice-based clinical trial, made it possible to examine consequences of observed changes in potassium during care in conventional practice settings. Normokalemic participants randomized to chlorthalidone (C) versus amlodipine or lisinopril as a first-step drug were stratified by year-1 potassium. Postyear-1 outcomes among hypokalemics (potassium, <3.5 mmol/L) and hyperkalemics (potassium, >5.4 mmol/L) were compared with normokalemics (potassium, 3.5-5.4 mmol/L). Year-1 hypokalemia incidence was 6.8%; incidence in C (12.9%) differed from amlodipine (2.1%; P<0.001) and lisinopril (1.0%; P<0.01). Hyperkalemia incidence (2.0%) was greater in lisinopril (3.6%) than in C (1.2%; P<0.01) or amlodipine (1.9%; P<0.01). Coronary heart disease occurred in 8.1% with hypokalemia, 8.0% with normokalemia, and 11.1% with hyperkalemia. Overall, mortality was higher in hypokalemics than in normokalemics (Cox hazard ratio, 1.21 [95% CI, 1.02-1.44]) with statistically significant (interaction, P<0.01) disparity in hazard ratios for the 3 treatment arms (hazard ratios, C=1.21, amlodipine=1.60, lisinopril=3.82). Hyperkalemia was associated with increased risk of combined cardiovascular disease (hazard ratio, 1.58 [95% CI, 1.15-2.18]) without significant treatment interactions. In conventional practice settings, the uncommon appearance of hyperkalemia was associated with increased cardiovascular disease risk. Hypokalemia was associated with increased mortality; however, the statistically significant heterogeneity in hazard ratios across treatment groups strongly suggests that the observed increase in mortality is unrelated to the specific effects of C. Thus, for most patients, concerns about potassium levels should not influence the clinician's decision about initiating hypertension treatment with low-moderate doses of thiazide diuretics (12.5-25.0 mg of C). PMID: 22431578 |
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Cannon JS,Overman LE Department of Chemistry, University of California, Irvine, Irvine, CA 92697-2025 (USA). |
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Is There No End to the Total Syntheses of Strychnine? Lessons Learned in Strategy and Tactics in Total Synthesis. Angew Chem Int Ed Engl. 2012 Mar 19;: From the 19th century to the present, the complex indole alkaloid strychnine has engaged the chemical community. In this Review, we examine why strychnine has been and remains today an important target for directed synthesis efforts. A selection of the diverse syntheses of strychnine is discussed with the aim of identifying their influence on the evolution of the strategy and tactics of organic synthesis. PMID: 22431197 |
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Chung E,Cannesson M Department of Anesthesiology and Perioperative Care, University of California Irvine, 101 S City Drive, Orange, CA, 92868, USA. |
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Using non invasive dynamic parameters of fluid responsiveness in children: there is still much to learn. J Clin Monit Comput. 2012 Mar 20;: PMID: 22430745 |
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Chandraratna PA,Mohar DS,Sidarous PF,Paila K Division of Cardiology, Long Beach VA Medical Center, UC Irvine School of Medicine, Long Beach, California. |
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Detection of Wall Motion Abnormalities during Ambulatory Echocardiography Using a Novel Ultrasound Transducer. Echocardiography. 2012 Mar 19;: Background: This investigation was designed to determine whether transient wall motion abnormalities due to myocardial ischemia induced by walking could be detected by ambulatory echocardiography. Methods: Two groups were studied. Group 1 consisted of 10 males (mean age 34 years) who had no symptoms of angina. Group 2 consisted of eight selected patients (mean 61 years) with angina and angiographic evidence of coronary artery disease. The 2.5 MHz transducer is spherical in its distal part and mounted in an external housing to permit steering in 360°. The external housing was attached to the chest wall using an adhesive patch. The transducer was placed in the 3rd or 4th intercostal space at the left sternal border to permit imaging of the left ventricle (LV) in its short axis and attached to the chest wall. The transducer was interfaced with an Acuson Cypress echocardiography system which was placed on a mobile cart. To permit portability, the echocardiography system was powered by a capacitor (UPS device). The subjects were asked to walk along the corridor as fast as possible for 10 minutes or until the onset of symptoms while pushing the cart. The short axis of the LV was displayed on a monitor and recorded on optical disks. Results: The heart rate, systolic blood pressure (SBP), and double product of Group 1 at rest were 77 ± 3 beats/min, 119 ± 13 mmHg, and 9,150 ± 868, respectively, and increased to 106 ± 8 beats/min, 129 ± 15 mmHg, and 1,3793 ± 2,176 with walking. The baseline heart rate, SBP, and double product were 71 ± 12 beats/min, 130 ± 14 mmHg, and 8,555 ± 1,928 in Group 2 and increased to 94 ± 14 beats/min, 135 ± 20 mmHg, and 12,480 ± 3,830 with walking. All patients in Group 1 had normal wall motion at rest and during walking. Patients in Group 2 had normal wall motion during rest and new wall motion abnormalities were noted in all subjects during walking (anterior septum and/or anterolateral wall in seven, posterolateral wall in one). The wall motion abnormalities resolved shortly after discontinuation of walking. Conclusion: Ambulatory echocardiography permitted the detection of transient wall motion abnormalities in patients with coronary artery disease (CAD). This technique could be potentially useful in evaluating selected patients for myocardial ischemia. (Echocardiography ****;**:1-4). PMID: 22429086 |
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Wei W,Yuan H,Chen C,Zhou X State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, China Department of Psychology and Social Behavior, University of California, Irvine, USA. |
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Cognitive correlates of performance in advanced mathematics. Br J Educ Psychol. 2012 Mar;82(Pt 1):157-81 Background. Much research has been devoted to understanding cognitive correlates of elementary mathematics performance, but little such research has been done for advanced mathematics (e.g., modern algebra, statistics, and mathematical logic). Aims. To promote mathematical knowledge among college students, it is necessary to understand what factors (including cognitive factors) are important for acquiring advanced mathematics. Samples. We recruited 80 undergraduates from four universities in Beijing. Methods. The current study investigated the associations between students' performance on a test of advanced mathematics and a battery of 17 cognitive tasks on basic numerical processing, complex numerical processing, spatial abilities, language abilities, and general cognitive processing. Results. The results showed that spatial abilities were significantly correlated with performance in advanced mathematics after controlling for other factors. In addition, certain language abilities (i.e., comprehension of words and sentences) also made unique contributions. In contrast, basic numerical processing and computation were generally not correlated with performance in advanced mathematics. Conclusions. Results suggest that spatial abilities and language comprehension, but not basic numerical processing, may play an important role in advanced mathematics. These results are discussed in terms of their theoretical significance and practical implications. PMID: 22429063 |
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Bergfield JP,Barr JD,Stafford CA Departments of Chemistry and Physics, University of California, Irvine, California 92697, USA. |
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Transmission eigenvalue distributions in highly conductive molecular junctions. Beilstein J Nanotechnol. 2012;3:40-51 Background: The transport through a quantum-scale device may be uniquely characterized by its transmission eigenvalues τ(n). Recently, highly conductive single-molecule junctions (SMJ) with multiple transport channels (i.e., several τ(n) > 0) have been formed from benzene molecules between Pt electrodes. Transport through these multichannel SMJs is a probe of both the bonding properties at the lead-molecule interface and of the molecular symmetry.Results: We use a many-body theory that properly describes the complementary wave-particle nature of the electron to investigate transport in an ensemble of Pt-benzene-Pt junctions. We utilize an effective-field theory of interacting π-electrons to accurately model the electrostatic influence of the leads, and we develop an ab initio tunneling model to describe the details of the lead-molecule bonding over an ensemble of junction geometries. We also develop a simple decomposition of transmission eigenchannels into molecular resonances based on the isolated resonance approximation, which helps to illustrate the workings of our many-body theory, and facilitates unambiguous interpretation of transmission spectra.Conclusion: We confirm that Pt-benzene-Pt junctions have two dominant transmission channels, with only a small contribution from a third channel with τ(n) < 1. In addition, we demonstrate that the isolated resonance approximation is extremely accurate and determine that transport occurs predominantly via the HOMO orbital in Pt-benzene-Pt junctions. Finally, we show that the transport occurs in a lead-molecule coupling regime where the charge carriers are both particle-like and wave-like simultaneously, requiring a many-body description. PMID: 22428095 |
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Marshak S,Meynard MM,De Vries YA,Kidane AH,Cohen-Cory S Department of Neurobiology & Behavior, University of California Irvine, Irvine, California, United States of America. |
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Cell-Autonomous Alterations in Dendritic Arbor Morphology and Connectivity Induced by Overexpression of MeCP2 in Xenopus Central Neurons In Vivo. PLoS One. 2012;7(3):e33153 Methyl CpG binding protein-2 (MeCP2) is an essential epigenetic regulator in human brain development. Mutations in the MeCP2 gene have been linked to Rett syndrome, a severe X-linked progressive neurodevelopmental disorder, and one of the most common causes of mental retardation in females. MeCP2 duplication and triplication have also been found to affect brain development, indicating that both loss of function and gain in MeCP2 dosage lead to similar neurological phenotypes. Here, we used the Xenopus laevis visual system as an in vivo model to examine the consequence of increased MeCP2 expression during the morphological maturation of individual central neurons in an otherwise intact brain. Single-cell overexpression of wild-type human MeCP2 was combined with time-lapse confocal microscopy imaging to study dynamic mechanisms by which MeCP2 influences tectal neuron dendritic arborization. Analysis of neurons co-expressing DsRed2 demonstrates that MeCP2 overexpression specifically interfered with dendritic elaboration, decreasing the rates of branch addition and elimination over a 48 hour observation period. Moreover, dynamic analysis of neurons co-expressing wt-hMeCP2 and PSD95-GFP revealed that even though neurons expressing wt-hMeCP2 possessed significantly fewer dendrites and simpler morphologies than control neurons at the same developmental stage, postsynaptic site density in wt-hMeCP2-expressing neurons was similar to controls and increased at a rate higher than controls. Together, our in vivo studies support an early, cell-autonomous role for MeCP2 during the morphological differentiation of neurons and indicate that perturbations in MeCP2 gene dosage result in deficits in dendritic arborization that can be compensated, at least in part, by synaptic connectivity changes. PMID: 22427975 |
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Kwon SY,Chae SW,Wilczynski SP,Arain A,Carpenter PM The Department of Pathology and Laboratory Medicine, the University of California, Irvine CA. |
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Laminin 332 Expression in Breast Carcinoma. Appl Immunohistochem Mol Morphol. 2012 Mar 1;20(2):159-164 Laminin 332 (LN332) is a basally expressed extracellular matrix protein that enhances the migration and invasion of breast carcinoma cells. The goal of this study was to examine LN332 expression breast carcinoma. Triple negative breast carcinomas lack estrogen receptor (ER), progesterone receptor (PR) expression and HER2 positivity. Immunohistochemistry for ER, PR, HER2, and dual silver in situ hybridization for the HER2 gene were used to define the phenotype of 243 breast cancers in biopsies or arrays. Immunohistochemistry for LN332 revealed that 70 % of triple negative carcinomas stained for LN332. Cytokeratin 5/6 (CK5/6), epidermal growth factor receptor (EGFR) and p63 alone stained fewer triple negative breast carcinomas each, but the combination of LN332 and CK 5/6 or EGFR identified 92% of triple negative breast carcinoma.. Of the 163 non- triple negative cases, LN332 was expressed in only 15%. The identification of LN332 in triple negative breast carcinomas is consistent with gene profiling studies showing its expression among breast carcinomas with a basal phenotype. The observation that a pro-invasive protein such as LN332 is expressed in breast cancer suggests another mechanism by which the triple negative phenotype could be aggressive. PMID: 22427740 |
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Díaz-Castillo C,Ranz JM Department of Ecology and Evolutionary Biology, University of California Irvine, CA 92697. |
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Nuclear chromosome dynamics in the Drosophila male germline contribute to the non-random genomic distribution of retrogenes. Mol Biol Evol. 2012 Mar 16;: The origin of RNA-based gene duplicates, i.e. retrogenes, involves the reverse transcription of an mRNA derived from a parental gene to generate a complementary DNA copy, its insertion elsewhere in the genome, and the cooption of regulatory sequences. Drosophila retrogenes are preferentially expressed in testis and a higher than expected number transpose to autosomal locations from the X chromosome. However, the influence of genomic context on the insertion preference of retrogenes remains poorly understood. We find that the distribution of retrogenes in the D. melanogaster genome can be explained by an insertion bias towards chromosome domains containing testis-biased genes that are located at the nuclear periphery in somatic cells, but at inner positions in the male germline. The lower fraction of these chromosome domains accessible in the male germline on the X chromosome as compared to the autosomes also contributes to the scarcity of retrogenes on the X chromosome. PMID: 22427708 |
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