UCI Authors in PubMed
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Dana CE,Glauber KM,Chan TA,Bridge DM,Steele RE Department of Biological Chemistry, University of California Irvine, Irvine, California, United States of America. |
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Incorporation of a Horizontally Transferred Gene into an Operon during Cnidarian Evolution. PLoS One. 2012;7(2):e31643 Genome sequencing has revealed examples of horizontally transferred genes, but we still know little about how such genes are incorporated into their host genomes. We have previously reported the identification of a gene (flp) that appears to have entered the Hydra genome through horizontal transfer. Here we provide additional evidence in support of our original hypothesis that the transfer was from a unicellular organism, and we show that the transfer occurred in an ancestor of two medusozoan cnidarian species. In addition we show that the gene is part of a bicistronic operon in the Hydra genome. These findings identify a new animal phylum in which trans-spliced leader addition has led to the formation of operons, and define the requirements for evolution of an operon in Hydra. The identification of operons in Hydra also provides a tool that can be exploited in the construction of transgenic Hydra strains. PMID: 22328943 |
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Lee JA,Zierler BK,Zierler RE Program in Nursing Science, University of California Irvine, Irvine, California. |
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The Risk Factors and Clinical Outcomes of Upper Extremity Deep Vein Thrombosis. Vasc Endovascular Surg. 2012 Feb 9;: The prevalence of upper extremity deep vein thrombosis (UEDVT) has shown a dramatic increase with the use of central venous catheters (CVCs) for patient care. The objective of this study was to identify risk factors and clinical outcomes in patients diagnosed with UEDVT at an academic medical center over a 1-year period. Medical records of 373 consecutive patients who underwent upper extremity venous duplex ultrasound (VDU) examination were retrospectively reviewed. A quarter of the patients screened by VDU (94 of 373) had acute UEDVT; 63% presented with arm swelling or arm pain; 48% had cancer; and 93% had indwelling CVCs. Cancer patients with CVCs were more likely to develop UEDVT (48%). Of the 94 UEDVTs, 16% had concurrent lower extremity DVT. The incidence of objectively confirmed pulmonary embolism (PE) was 9% (8 of 94 patients), and the 1-month mortality rate was 6.4%. The majority of patients (80%) with UEDVT received anticoagulation therapy and 20% were not treated. The most common risk factors for UEDVT were indwelling CVCs and a diagnosis of cancer. The incidence rate of PE and mortality rate from UEDVT were not insignificant at 9% and 6%, respectively. There were no institutional screening protocols for patients at risk of UEDVT associated with CVCs. Future research should focus on risk assessment and management protocols for patients at risk of UEDVT. In addition, a comparison of clinical outcomes associated with the type, size, and duration of catheter placement should be conducted in patients at risk of or diagnosed with UEDVT. PMID: 22328450 |
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Patel PM,Kern MJ 1Division of Cardiology, University of California, Irvine, Orange, California. pranavp@uci.edu. |
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Moving renal embolic protection forward. Catheter Cardiovasc Interv. 2012 Feb 15;79(3):437-8 PMID: 22328234 |
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Hinde E,Cardarelli F,Digman MA,Gratton E Laboratory for Fluorescence Dynamics, Department of Biomedical Engineering, University of California, Irvine, California. |
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Changes in Chromatin Compaction During the Cell Cycle Revealed by Micrometer-Scale Measurement of Molecular Flow in the Nucleus. Biophys J. 2012 Feb 8;102(3):691-7 We present a quantitative fluctuation-based assay to measure the degree of local chromatin compaction and investigate how chromatin density regulates the diffusive path adopted by an inert protein in dividing cells. The assay uses CHO-K1 cells coexpressing untagged enhanced green fluorescent protein (EGFP) and histone H2B tagged mCherry. We measure at the single-cell level the EGFP localization and molecular flow patterns characteristic of each stage of chromatin compaction from mitosis through interphase by means of pair-correlation analysis. We find that the naturally occurring changes in chromatin organization impart a regulation on the spatial distribution and temporal dynamics of EGFP within the nucleus. Combined with the analysis of Ca(2+) intracellular homeostasis during cell division, EGFP flow regulation can be interpreted as the result of controlled changes in chromatin compaction. For the first time, to our knowledge, we were able to probe chromatin compaction on the micrometer scale, where the regulation of molecular diffusion may become relevant for many cellular processes. PMID: 22325293 |
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Imeraj L,Antrop I,Roeyers H,Swanson J,Deschepper E,Bal S,Deboutte D Child and Adolescent Psychiatry Research Unit, Department of Psychiatry and Medical Psychology, Ghent University Hospital, Ghent Department of Experimental-Clinical and Health Psychology, Ghent University, Ghent, Belgium Child Developmental Centre, University of California, Irvine, CA Centre for Children and Families, Florida International University, Miami, FL, USA Biostatistics Unit, Ghent University, Ghent Collaborate Antwerp Psychiatry Research, Antwerp University, Antwerp University Centre Child and Adolescent Psychiatry, Antwerp, Belgium. |
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Time-of-day effects in arousal: disrupted diurnal cortisol profiles in children with ADHD. J Child Psychol Psychiatry. 2012 Feb 10;: Background: Fluctuations in attention-deficit hyperactivity disorder (ADHD) symptoms related to regulatory deficits in arousal states are themselves characterized by circadian rhythms. Although cortisol is an important circadian arousal-related marker, studies focusing on across-the-day cortisol variations in ADHD are scarce. There is no study with multiple measurements to take into account interday and intraday variability. Methods: Salivary cortisol was sampled five times a day (awakening, 30 min after awakening, noon, 4 p.m., 8 p.m.) across five consecutive days in 33 children with ADHD (22 with and 11 without oppositional defiant disorder; ODD) and 33 class- and sex-matched controls (aged 6-12). The cortisol awakening response (increase from awakening to 30 min after awakening) and the diurnal cortisol profile (across-the-day variations) were compared for ADHD with ODD (ADHD + ODD) and without ODD (ADHD) subgroups and the control group. Results: The cortisol awakening response was not significantly different between groups. However, longitudinal analyses to evaluate cortisol profiles across the day revealed a significant Group - Time effect (p < .001). More specifically, compared to each other, the ADHD subgroup showed a flatter slope with relative morning hypo-arousal and evening hyperarousal, whereas the ADHD + ODD subgroup showed a steeper slope with relative morning hyperarousal and evening hypo-arousal (p < .001). Conclusions: Findings support time-related arousal disruptions in children with ADHD associated with the presence or absence of ODD comorbidity. We recommend research on cortisol in larger samples for a better understanding of arousal mechanisms involved in ADHD not only with and without ODD but also with other comorbidities which may have implications for timing of arousal-based treatments. PMID: 22324289 |
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Weng RR,Foster CE,Hsieh LL,Patel PR Department of Pharmacy Practice, Division of Renal and Pancreas Transplantation, University of California Irvine Medical Center, 333 City Boulevard West, Orange, CA 92868, USA. rweng@uci.edu |
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Oral ulcers associated with mycophenolate mofetil use in a renal transplant recipient. Am J Health Syst Pharm. 2011 Apr 1;68(7):585-8 A case study of mycophenolate mofetil-induced oral ulcers in a renal transplant patient is reported. PMID: 21411799 |
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Carpenter PM,Chen WP,Mendez A,McLaren CE,Su MY Department of Pathology and Laboratory Medicine, University of California, Irvine Medical Center, 101 The City Dr., Orange, CA 92868, USA. pmcarpen@uci.edu |
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Angiogenesis in the progression of breast ductal proliferations. Int J Surg Pathol. 2011 Jun;19(3):335-41 Angiogenesis, the formation of blood vessels, is necessary for a tumor to grow, but when angiogenesis first appears in the progression of breast ductal carcinomas is unknown. To determine when this occurs, the authors examined microvessel density (MVD) by CD31 and CD105 immunostaining in normal ducts, 32 cases of usual hyperplasia, 19 cases of atypical hyperplasia, and 29 cases of ductal carcinoma in situ (DCIS). Simple hyperplasia had a 22-fold greater MVD than normal ducts (P < .0001). An increase during the progression of ductal changes was highly significant (P < .0001). To determine a possible mechanism, immunohistochemistry for vascular endothelial growth factor (VEGF) was evaluated. VEGF staining intensity of ductal epithelium increased during the progression from normal to hyperplastic to DCIS. This study shows that the first significant increase in angiogenesis occurs very early in the evolution of ductal proliferations as ductal cells become hyperplastic. PMID: 19403546 |
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Fortier MA,Wahi A,Maurer EL,Tan ET,Sender LS,Kain ZN *Department of Anesthesiology and Perioperative Care, Chao Family Comprehensive Cancer Center, University of California-Irvine,Department of Pediatric Psychology, Department of Pediatrics, CHOC Children's Hospital, CHOC Children's Cancer Institute, Orange, CA. |
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Attitudes Regarding Analgesic Use and Pain Expression in Parents of Children With Cancer. J Pediatr Hematol Oncol. 2012 Feb 8;: BACKGROUND:: Children with cancer often experience significant levels of pain and their pain is generally undermanaged. Management of care to patients with cancer has shifted from the hospital to the home, and as such parents are charged with managing children's pain. However, parents may have misconceptions of analgesic use, which can lead to undertreatment of pain in children. The purpose of this study is to examine attitudes toward pain medication and perceptions of pain expression among parents of children undergoing cancer treatment. PROCEDURE:: Parents of children who were undergoing cancer treatment at a hospital were recruited to take part in a survey study. A total of 187 parents completed a survey examining their attitudes toward medication and perceptions of pain expression in children. RESULTS:: Many parents reported concerns regarding analgesic use to treat their children's pain and misconceptions about how children can express pain. Regression analyses noted that parental perceptions of pain expression were related to children's experience of chronic or recurring pain and the 2 dimensions of child temperament: emotionality and sociability. CONCLUSIONS:: Many parents of children with cancer have misconceptions regarding issues of pain management; these misconceptions can potentially lead to undertreatment of pain in children. These misconceptions are associated with aspects of children's temperament. PMID: 22322939 |
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Kao HW,Tsai FY,Hasso AN Department of Radiological Sciences, University of California at Irvine Medical Center, 101 City Dr. South, Orange, Irvine, CA, 92868, USA. |
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Predicting stroke evolution: comparison of susceptibility-weighted MR imaging with MR perfusion. Eur Radiol. 2012 Feb 10;: OBJECTIVES: To investigate the ability of susceptibility-weighted imaging (SWI) to predict stroke evolution in comparison with perfusion-weighted imaging (PWI). METHODS: In a retrospective analysis of 15 patients with non-lacunar ischaemic stroke studied no later than 24 h after symptom onset, we used the Alberta Stroke Program Early CT Score (ASPECTS) to compare lesions on initial diffusion-weighted images (DWI), SWI, PWI and follow-up studies obtained at least 5 days after symptom onset. The National Institutes of Health Stroke Scale scores at entry and stroke risk factors were documented. The clinical-DWI, SWI-DWI and PWI-DWI mismatches were calculated. RESULTS: SWI-DWI and mean transit time (MTT)-DWI mismatches were significantly associated with higher incidence of infarct growth (P = 0.007 and 0.028) and had similar ability to predict stroke evolution (P = 1.0). ASPECTS values on initial DWI, SWI and PWI were significantly correlated with those on follow-up studies (P ≤ 0.026) but not associated with infarct growth. The SWI ASPECTS values were best correlated with MTT ones (ρ = 0.8, P < 0.001). CONCLUSIONS: SWI is an alternative to PWI to assess penumbra and predict stroke evolution. Further prospective studies are needed to evaluate the role of SWI in guiding thrombolytic therapy. Key Points • SWI can provide perfusion information comparable to MTT • SWI-DWI mismatch can indicate ischaemic penumbra • SWI-DWI mismatch can be a predictor for stroke evolution. PMID: 22322311 |
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Soyfoo M,Konno A,Bolaky N,Oak J,Fruman D,Nicaise C,Takiguchi M,Delporte C Laboratory of Biological Chemistry and Nutrition, Université Libre de Bruxelles, Brussels Department of Rheumatology, Erasme University Hospital, Brussels, Belgium Laboratory of Anatomy, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan Department of Molecular Biology and Biochemistry, Institute for Immunology, University of California, Irvine, CA, USA Laboratory of Histology, Neuroanatomy and Neuropathology, Université Libre de Bruxelles, Brussels, Belgium Laboratory of Veterinary Internal Medicine, Department of Veterinary Clinical Sciences, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan. |
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Link between inflammation and aquaporin-5 distribution in submandibular gland in sjögren's syndrome? Oral Dis. 2012 Jan 16;: Oral Diseases (2012) doi: 10.1111/j.1601-0825.2012.01909.x Objective: To determine whether a link exists between inflammation and aquaporin-5 distribution in submandibular glands from three animal models for Sjögren's syndrome: IQI/JIC, r1"T/r2n and non-obese diabetic mice. Methods: Mice of different ages were used. Inflammatory infiltrates were quantified using the focus score. Acinar aquaporin-5 subcellular distribution was determined by immunohistochemistry and quantified using labelling indices. Results: Minor inflammatory infiltrates were present in r1f/r2n mice. Massive inflammatory infiltrates and acinar destruction were observed in 24-week-old non-obese diabetic mice, 10-and 13-month-old IQI/JIC mice and some r1"T/r2n mice. Aquaporin-5 immunoreactivity was primarily apical in submandibular glands from 8- and 24-week-old Balb/C mice, 8-week-old non-obese diabetic mice, 2-, 4- and 7-month-old IQI/JIC mice and r1f/r2n mice. In contrast, decreased apical aquaporin-5 labelling index with concomitant increased apical-basolateral, apical-cytoplasmic and/or apical-basolateral-cytoplasmic aquaporin-5 labelling indices was observed in 24-week-old non-obese diabetic, 10- and 13-month-old IQI/JIC and r1"T/r2n mice with a focus score ≥ 1. Conclusions: Altered aquaporin-5 distribution in submandibular acinar cells from IQI/JIC, non-obese diabetic and r1"T/r2n mice with a focus score ≥ 1 appears to be concomitant to the presence of inflammatory infiltrates and acinar destruction. PMID: 22320885 |
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Afrane YA,Githeko AK,Yan G Climate and Human Health Research Unit, Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya. School of Health Sciences, Bondo University, Bondo, Kenya. Program in Public Health, College of Health Sciences, University of California Irvine, Irvine, California. |
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The ecology of Anopheles mosquitoes under climate change: case studies from the effects of deforestation in East African highlands. Ann N Y Acad Sci. 2012 Feb 9;: Climate change is expected to lead to latitudinal and altitudinal temperature increases. High-elevation regions such as the highlands of Africa and those that have temperate climate are most likely to be affected. The highlands of Africa generally exhibit low ambient temperatures. This restricts the distribution of Anopheles mosquitoes, the vectors of malaria, filariasis, and O'nyong'nyong fever. The development and survival of larval and adult mosquitoes are temperature dependent, as are mosquito biting frequency and pathogen development rate. Given that various Anopheles species are adapted to different climatic conditions, changes in climate could lead to changes in species composition in an area that may change the dynamics of mosquito-borne disease transmission. It is important to consider the effect of climate change on rainfall, which is critical to the formation and persistence of mosquito breeding sites. In addition, environmental changes such as deforestation could increase local temperatures in the highlands; this could enhance the vectorial capacity of the Anopheles. These experimental data will be invaluable in facilitating the understanding of the impact of climate change on Anopheles. PMID: 22320421 |
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Avery MC,Nitz DA,Chiba AA,Krichmar JL Department of Cognitive Sciences, University of California, Irvine CA, USA. |
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Simulation of cholinergic and noradrenergic modulation of behavior in uncertain environments. Front Comput Neurosci. 2012;6:5 Attention is a complex neurobiological process that involves rapidly and flexibly balancing sensory input and goal-directed predictions in response to environmental changes. The cholinergic and noradrenergic systems, which have been proposed to respond to expected and unexpected environmental uncertainty, respectively, play an important role in attention by differentially modulating activity in a multitude of cortical targets. Here we develop a model of an attention task that involves expected and unexpected uncertainty. The cholinergic and noradrenergic systems track this uncertainty and, in turn, influence cortical processing in five different, experimentally verified ways: (1) nicotinic enhancement of thalamocortical input, (2) muscarinic regulation of corticocortical feedback, (3) noradrenergic mediation of a network reset, (4) locus coeruleus (LC) activation of the basal forebrain (BF), and (5) cholinergic and noradrenergic balance between sensory input and frontal cortex predictions. Our results shed light on how the noradrenergic and cholinergic systems interact with each other and a distributed set of neural areas, and how this could lead to behavioral adaptation in the face of uncertainty. PMID: 22319488 |
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Ikrar T,Shi Y,Velasquez T,Goulding M,Xu X Department of Anatomy and Neurobiology, School of Medicine, University of California, Irvine CA, USA. |
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Cell-type specific regulation of cortical excitability through the allatostatin receptor system. Front Neural Circuits. 2012;6:2 Recent technical advances enable the regulation of neuronal circuit activity with high spatial and temporal resolution through genetic delivery of molecular activation or inactivation systems.Among them, the allatostatin receptor (AlstR)/ligand system has been developed for selective and quickly reversible silencing of mammalian neurons. However, targeted AlstR-mediated inactivation of specific neuronal types, particularly diverse types of inhibitory interneurons, remains to be established. In the present study, we achieved Cre-directed expression of AlstRs to excitatory and inhibitory cell-types in the cortex, and found that the AlstR-mediated inactivation was specific and robust at single-cell and neuronal population levels. Bath application of the allatostatin peptide markedly reduced spiking activity of AlstR-expressing excitatory and inhibitory neurons in response to intrasomatic current injections and laser photostimulation via glutamate uncaging, but control neurons without AlstR expression were not affected. As for the cortical network activity, the peptide application constrained photostimulation-evoked excitatory activity propagation detected by fast voltage-sensitive dye (VSD) imaging of the slices expressing AlstRs selectively in excitatory neurons, while it augmented excitatory activity in those slices with inhibitory neurons expressing AlstRs. In addition, AlstR-mediated inactivation effectively suppressed pharmacologically induced seizure activity in the slices targeting AlstRs to excitatory neurons. Taken together, our work demonstrated that the genetic delivery of AlstRs can be used for regulation of cortical excitability in a cell-type specific manner, and suggested that the AlstR system can be potentially used for fast seizure control. PMID: 22319474 |
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Díaz-Castillo C,Xia XQ,Ranz JM Department of Ecology and Evolutionary Biology, University of California Irvine, Irvine, California, United States of America. |
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Evaluation of the role of functional constraints on the integrity of an ultraconserved region in the genus Drosophila. PLoS Genet. 2012 Feb;8(2):e1002475 Why gene order is conserved over long evolutionary timespans remains elusive. A common interpretation is that gene order conservation might reflect the existence of functional constraints that are important for organismal performance. Alteration of the integrity of genomic regions, and therefore of those constraints, would result in detrimental effects. This notion seems especially plausible in those genomes that can easily accommodate gene reshuffling via chromosomal inversions since genomic regions free of constraints are likely to have been disrupted in one or more lineages. Nevertheless, no empirical test has been performed to this notion. Here, we disrupt one of the largest conserved genomic regions of the Drosophila genome by chromosome engineering and examine the phenotypic consequences derived from such disruption. The targeted region exhibits multiple patterns of functional enrichment suggestive of the presence of constraints. The carriers of the disrupted collinear block show no defects in their viability, fertility, and parameters of general homeostasis, although their odorant perception is altered. This change in odorant perception does not correlate with modifications of the level of expression and sex bias of the genes within the genomic region disrupted. Our results indicate that even in highly rearranged genomes, like those of Diptera, unusually high levels of gene order conservation cannot be systematically attributed to functional constraints, which raises the possibility that other mechanisms can be in place and therefore the underpinnings of the maintenance of gene organization might be more diverse than previously thought. PMID: 22319453 |
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Raivio T,Avbelj M,McCabe MJ,Romero CJ,Dwyer AA,Tommiska J,Sykiotis GP,Gregory LC,Diaczok D,Tziaferi V,Elting MW,Padidela R,Plummer L,Martin C,Feng B,Zhang C,Zhou QY,Chen H,Mohammadi M,Quinton R,Sidis Y,Radovick S,Dattani MT,Pitteloud N Children's Hospital (T.R., J.T.), Helsinki University Central Hospital, Institute of Biomedicine/Physiology, University of Helsinki, 00290 Helsinki, Finland; University Children's Hospital (M.A.), University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia; Developmental Endocrinology Research Group Clinical and Molecular Genetics Unit (M.J.M., L.C.G., V.T., M.T.D.), University College London-Institute of Child Health, London EC1V 9EL, United Kingdom; Division of Pediatric Endocrinology (C.J.R., D.D., S.R.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205; Endocrinology, Diabetes, and Metabolism Service of the Centre Hospitalier Universitaire Vaudois and University of Lausanne (A.A.D., Y.S., N.P.), 1011 Lausanne, Switzerland; Department of Internal Medicine, Division of Endocrinology, and Department of Pharmacology (G.P.S.), University of Patras Medical School, 26500 Patras, Greece; Department of Clinical Genetics and Human Genetics (M.W.E.), VU Medical Centre, 1081 HL Amsterdam, Netherlands; Department of Paediatric Endocrinology (R.P.), Royal Manchester Children's Hospital, Manchester M13 9WL, United Kingdom; Harvard Reproductive Endocrine Sciences Center and the Reproductive Endocrine Unit of the Department of Medicine (L.P., C.M., B.F.), Massachusetts General Hospital, Boston, Massachusetts 02114; Department of Pharmacology (C.Z., Q.-Y.Z.), University of California, Irvine, Irvine, California 92697; Department of Pharmacology, (H.C., M.M.), New York Uniersity School of Medicine, New York, New York; and Institute for Genetic Medicine (R.Q.), Newcastle University, and Department of Endocrinology, Newcastle upon Tyne Hospitals, Newcastle upon Tyne NE1 7RU, United Kingdom. |
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Genetic Overlap in Kallmann Syndrome, Combined Pituitary Hormone Deficiency, and Septo-Optic Dysplasia. J Clin Endocrinol Metab. 2012 Feb 8;: Context:Kallmann syndrome (KS), combined pituitary hormone deficiency (CPHD), and septo-optic dysplasia (SOD) all result from development defects of the anterior midline in the human forebrain.Objective:The objective of the study was to investigate whether KS, CPHD, and SOD have shared genetic origins.Design and Participants:A total of 103 patients with either CPHD (n = 35) or SOD (n = 68) were investigated for mutations in genes implicated in the etiology of KS (FGFR1, FGF8, PROKR2, PROK2, and KAL1). Consequences of identified FGFR1, FGF8, and PROKR2 mutations were investigated in vitro.Results:Three patients with SOD had heterozygous mutations in FGFR1; these were either shown to alter receptor signaling (p.S450F, p.P483S) or predicted to affect splicing (c.336C>T, p.T112T). One patient had a synonymous change in FGF8 (c.216G>A, p.T72T) that was shown to affect splicing and ligand signaling activity. Four patients with CPHD/SOD were found to harbor heterozygous rare loss-of-function variants in PROKR2 (p.R85G, p.R85H, p.R268C).Conclusions:Mutations in FGFR1/FGF8/PROKR2 contributed to 7.8% of our patients with CPHD/SOD. These data suggest a significant genetic overlap between conditions affecting the development of anterior midline in the human forebrain. PMID: 22319038 |
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Wong ND,Dede J,Chow VH,Wong KS,Franklin SS Heart Disease Prevention Program, Division of Cardiology, University of California, Irvine, California, USA. |
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Global Cardiovascular Risk Associated With Hypertension and Extent of Treatment and Control According to Risk Group. Am J Hypertens. 2012 Feb 9;: BackgroundHypertension (HTN) confers increased cardiovascular disease (CVD) risk; however, the variation in risk and how treatment and control rates may differ according to extent of risk needs clarification. We examined CVD risk distribution and treatment and control patterns according to risk group.MethodsWe estimated 10-year Framingham global risk in 1,509 US persons aged ≥30 years from the National Health and Nutrition Examination Survey (NHANES) 2005-2006 with HTN and the proportion of subjects in low (<10%), intermediate (10-20%), and high (>20%) risk groups, or with pre-existing CVD, or who otherwise had high cardiometabolic risk according to European Society of Hypertension (ESH) criteria (diabetes (DM), metabolic syndrome (MetS), stage 3 HTN, or 3 additional CVD risk factors). We also examined HTN treatment and control rates by risk group.ResultsFrom Framingham risk assessment, 24% of subjects were low risk, 21% intermediate risk, 23% high risk, and 32% had CVD. An additional 39% of low and 51% of intermediate risk subjects were at high or very high risk based on European criteria, for a total of 80% classified high risk or with CVD by either criterion. Treatment rates across Framingham risk groups ranged from 58 to 75%. HTN control rates were over 80% for lower risk persons, but under 50% for higher risk subjects.ConclusionsThere is a wide variation in CVD risk in persons with HTN with control rates still suboptimal in higher risk subjects. Future guidelines should consider risk stratification combining shorter and longer-term risk assessment to best identify those who have the greatest CVD risk.American Journal of Hypertension 2012; doi:10.1038/ajh.2012.2. PMID: 22318511 |
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Freitas S,Hatosy S,Fuhrman JA,Huse SM,Mark Welch DB,Sogin ML,Martiny AC Department of Earth System Science, University of California, Irvine, CA, USA. |
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Global distribution and diversity of marine Verrucomicrobia. ISME J. 2012 Feb 9;: Verrucomicrobia is a bacterial phylum that is commonly detected in soil, but little is known about the distribution and diversity of this phylum in the marine environment. To address this, we analyzed the marine microbial community composition in 506 samples from the International Census of Marine Microbes as well as 11 coastal samples taken from the California Current. These samples from both the water column and sediments covered a wide range of environmental conditions. Verrucomicrobia were present in 98% of the analyzed samples, and thus appeared nearly ubiquitous in the ocean. Based on the occurrence of amplified 16S ribosomal RNA sequences, Verrucomicrobia constituted on average 2% of the water column and 1.4% of the sediment bacterial communities. The diversity of Verrucomicrobia displayed a biogeography at multiple taxonomic levels and thus, specific lineages appeared to have clear habitat preference. We found that subdivision 1 and 4 generally dominated marine bacterial communities, whereas subdivision 2 was more frequent in low salinity waters. Within the subdivisions, Verrucomicrobia community composition were significantly different in the water column compared with sediment as well as within the water column along gradients of salinity, temperature, nitrate, depth and overall water column depth. Although we still know little about the ecophysiology of Verrucomicrobia lineages, the ubiquity of this phylum suggests that it may be important for the biogeochemical cycle of carbon in the ocean. PMID: 22318305 |
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Kalantari-Dehaghi M,Chun S,Chentoufi A,Pablo J,Liang L,Dasgupta G,Molina DM,Jasinskas A,Nakajima-Sasaki R,Felgner J,Hermanson G,Benmohamed L,Felgner PL,Davies DH Division of Infectious Diseases, School of Medicine, University of California, Irvine, Irvine CA 92697. |
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Discovery of potential diagnostic and vaccine antigens in herpes simplex virus-1 and -2 by proteome-wide antibody profiling. J Virol. 2012 Feb 8;: Routine serodiagnosis of HSV infections is currently performed using recombinant glycoprotein G (gG) antigens from HSV-1 and HSV-2. This is a single antigen test and has only one diagnostic application. Relatively little is known about HSV antigenicity at the proteome-wide level, and the full potential of mining the antibody repertoire to identify antigens with other useful diagnostic properties and candidate vaccine antigens is yet to be realized. To this end we produced HSV-1 and -2 proteome microarrays in E. coli and probed them against a panel of sera from patients serotyped using commercial gG-1 and gG-2 ELISAs. We identified many reactive antigens in both HSV- 1 and -2, some of which were type-specific (i.e, recognized by HSV-1 or HSV-2 positive donors only) and others non-specific or cross-reactive (i.e., recognized by both HSV-1 and HSV-2 positive donors). Both membrane and non-membrane virion proteins were antigenic, although type-specific antigens were enriched for membrane proteins despite being expressed in E. coli. PMID: 22318154 |
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Dasgupta G,Chentoufi AA,Kalantari M,Falatoonzadeh P,Chun S,Lim CH,Felgner PL,Davies DH,Benmohamed L Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697. |
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Immunodominant "Asymptomatic" Herpes Simplex Virus Type 1 and Type 2 Protein Antigens Identified by Probing Whole ORFome Microarrays By Serum Antibodies From Seropositive Asymptomatic Versus Symptomatic Individuals. J Virol. 2012 Feb 8;: Herpes simplex virus type 1 and type 2 (HSV-1 & HSV-2) are medically significant pathogens. The development of an effective herpes vaccine remains a global public health priority. HSV-1 & HSV-2 immunodominant "asymptomatic" antigens (ID-A-Ags), that are strongly recognized by B- and T-cells from seropositive healthy asymptomatic individuals, may be critical to be included in an effective immunotherapeutic herpes vaccine. In contrast, immunodominant "symptomatic" Ags (ID-S-Ag), may exacerbate herpetic disease, and therefore must be excluded from any herpes vaccine. In the present study, proteome microarrays of 88 HSV-1 and 84 HSV-2 open reading frames (ORFomes) were constructed and probed with sera from 32 HSV-1, 6 HSV-2, 5 HSV-1/HSV-2 seropositive individuals, and 47 seronegative healthy individuals (negative controls). The proteins detected in both HSV-1 and HSV-2 proteome microarrays were further classified according to their recognition by sera from HSV-seropositive clinically defined symptomatic (n = 10) and asymptomatic (n =10) individuals. We found that: (i) serum antibodies recognized an average of 6 ORFs per seropositive individual; (ii) the antibody responses to herpes antigens were diverse among HSV-1 and HSV-2 seropositive individuals; (iii) a panel of twenty-one and thirty ID-Ags were identified from HSV-1 and HSV-2 ORFome as highly and frequently recognized by serum antibodies from seropositive individuals; (iv) interestingly, four HSV-1 and HSV-2 cross-reactive "asymptomatic" ID-A-Ags, US4, US11, UL30, and UL42, were strongly and frequently recognized by sera from 10 of 10 asymptomatic patients, but not by sera from 10 of 10 symptomatic patients (p < 0.001). In contrast, sera from symptomatic patients preferentially recognized US10 "symptomatic" ID-S-Ag (p < 0.001). We have identified previously unreported immunodominant herpes antigens, among which 4 "asymptomatic" ID-A-Ags and one "symptomatic" ID-S-Ags. These newly identified ID-A-Ags could lead to developing an efficient "asymptomatic" vaccine against ocular, oro-facial and genital herpes. PMID: 22318137 |
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Ou SH Department of Medicine, Division of Hematology Oncology, Chao Family Comprehensive Cancer Center, University of California Irvine Medical Center, 101 City Drive, Building 56, Orange, CA 92868, USA. ignatius.ou@uci.edu. |
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Crizotinib: a drug that crystallizes a unique molecular subset of non-small-cell lung cancer. Expert Rev Anticancer Ther. 2012 Feb;12(2):151-62 Crizotinib (Pfizer, CA, USA) is an oral small-molecule RTK inhibitor that targets ALK and MET, and potentially other RTKs. Crizotinib was approved by the US FDA on 26 August 2011 for the treatment of ALK-rearranged non-small-cell lung cancer (NSCLC), as detected by ALK break-apart FISH assay. This conditional approval was based on response rates of 50-61% from 255 ALK-rearranged NSCLC patients enrolled in two ongoing single-arm crizotinib trials. Side effects of crizotinib mostly consist of grade 1-2 gastrointestinal events (nausea, vomiting, diarrhea and constipation), grade 1-2 edema and fatigue, grade 1 visual disorders, rare cases of elevated liver enzymes and pneumonitis (1.6%). Confirmatory trials comparing crizotinib to standard chemotherapy in upfront (ClinicalTrials.gov identifier: NCT01154140) and salvage (ClinicalTrials.gov identifier: NCT00932451) treatment settings of ALK-rearranged NSCLC are ongoing. It took an unprecedented rapid 4 years from the publication of the discovery of ALK-rearranged NSCLC in August 2007 to the conditional approval of crizotinib in August 2011. PMID: 22316363 |
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Cannon JS,Olson AC,Overman LE,Solomon NS Department of Chemistry, 1102 Natural Sciences II, University of California , Irvine, California 92697-2025, United States. |
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Palladium(II)-Catalyzed Enantioselective Synthesis of 2-Vinyl Oxygen Heterocycles. J Org Chem. 2012 Feb 8;: 2-Vinylchromanes (1), 2-vinyl-1,4-benzodioxanes (2), and 2,3-dihydro-2-vinyl-2H-1,4-benzoxazines (3) can be prepared in high yields (90-98%) and excellent enantiomeric purities (87-98% ee) by [COP-OAc](2)-catalyzed cyclization of phenolic (E)-allylic trichloroacetimidate precursors. Deuterium-labeling and computational experiments are consistent with these cyclization reactions taking place by an anti-oxypalladation/syn-deoxypalladation mechanism. 2-Vinylchromanes can also be prepared in good yields and high enantiomeric purities from analogous (E)-allylic acetate precursors, which constitutes the first report that acetate is a competent leaving group in COP-catalyzed enantioselective S(N)2' substitution reactions. PMID: 22316285 |
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Jimenez RM,Rampášek L,Brejová B,Vinař T,Lupták A Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA. |
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Discovery of RNA Motifs Using a Computational Pipeline that Allows Insertions in Paired Regions and Filtering of Candidate Sequences. Methods Mol Biol. 2012;848:145-58 The enormous impact of noncoding RNAs on biology and biotechnology has motivated the development of systematic approaches to their discovery and characterization. Here we present a methodology for reliable detection of genomic ribozymes that centers on pipelined structure-based searches, utilizing two versatile algorithms for structure prediction. RNArobo is a prototype structure-based search package that enables a single search to return all sequences matching a designated motif descriptor, taking into account the possibility of single nucleotide insertions within base-paired regions. These outputs are then filtered through a structure prediction algorithm based on free energy minimization in order to maximize the proportion of catalytically active RNA motifs. This pipeline provides a fast approach to uncovering new catalytic RNAs with known secondary structures and verifying their activity in vitro. PMID: 22315068 |
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Jimenez RM,Lupták A Department of Pharmaceutical Sciences, University of California, Irvine, CA, USA. |
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Structure-based search and in vitro analysis of self-cleaving ribozymes. Methods Mol Biol. 2012;848:131-43 Detecting functional RNAs is increasingly accomplished through structure-based searches for patterns of conserved secondary structure. With large amounts of new sequencing data becoming available, there is a greater demand for efficient methods of identifying new RNAs. Here we present a method of identifying self-cleaving ribozymes and characterizing the in vitro activity. PMID: 22315067 |
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Chikawa T,Sakai T,Bhatia NN,Miyagi R,Sairyo K,Goda Y,Nakamura M,Nakano S,Shimakawa T,Minato A *Department of Orthopedic Surgery, Tokushima Municipal Hospital †Department of Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan ‡Department of Orthopedic Surgery, University of California, Irvine, CA §Department of Orthopedic Surgery, University of Teikyo Mizonokuchi Hospital, Kawasaki, Japan. |
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Clinical Outcomes of Spinal Surgery in Patients Treated With Hemodialysis. J Spinal Disord Tech. 2012 Feb 6;: STUDY DESIGN:: Retrospective study. OBJECTIVE:: The purpose of this study is to review clinical outcomes, including survival rate, and to discuss the potential benefit of surgical treatments for spinal disorders in patients treated with long-term hemodialysis (HD). SUMMARY OF BACKGROUND DATA:: Long-term HD is known to possibly cause destructive spondyloarthropathy (DSA) with spinal canal stenosis. There have been few reports, however, regarding clinical outcomes and patient survival rates after spinal surgeries in this population. METHODS:: We retrospectively reviewed 33 chronic HD patients who underwent 21 cervical and 13 lumbar spinal surgeries. According to the radiologic findings, we divided them into the non-DSA and the DSA groups. In general, only decompression was performed for the non-DSA patients, whereas spinal fusion was added for the DSA patients. We analyzed the following data, respectively: male-female ratio, age, operative time, estimated blood loss, duration of HD, follow-up duration, preoperative and postoperative Japanese Orthopaedic Association score, improvement ratio of the Japanese Orthopaedic Association score, amyloid deposition characteristics, and survival rate. RESULTS:: All patients improved neurologically and functionally after surgery. There were significant differences in the operative time between the DSA and the non-DSA groups in patients with cervical spinal lesions, whereas in patients with lumbar spinal lesions, there were significant differences in sex, operative time, and estimated blood loss. Amyloid deposition was found signficantly more commonly in DSA than in non-DSA patients and was associated with a longer duration of HD. Nine patients died within 49 months of the surgery because of HD-related complications, but there was no surgery-related morbidity. Kaplan-Meier analysis showed a trend toward decreased survival rate in non-DSA patients more than 40 months after the index surgery. CONCLUSIONS:: Even in patients treated with long-term HD, spinal surgeries reliably obtain neurological and functional improvement if surgeons judge the preoperative inclusion criteria correctly. However, if surgeries are necessary for these patients, surgeons should consider the patients' comorbidity-related survival rate after the spinal surgeries. PMID: 22314519 |
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Siddiqi N,Kern MJ,Patel PM Division of Cardiology, Department of Medicine, University of California, Irvine, Orange, California. |
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Asymmetric focal pericardial thickening causing physiologically significant constrictive pericarditis. Catheter Cardiovasc Interv. 2012 Feb 6;: A 34-year-old woman presented with refractory ascites and edema. Echocardiography revealed normal left ventricular function with a restrictive diastolic filling pattern. Tissue Doppler velocities of the mitral annulus were normal. Cardiac magnetic resonance imaging (MRI) revealed a focal region of pericardial thickening anterior to the right ventricle and normal thickness pericardium in the other segments. However, abnormal delayed enhancement MRI (consistent with inflammation) was present in both the thickened and the normal pericardial segments. Invasive hemodynamics confirmed constrictive physiology and the patient underwent successful pericardiectomy. This case highlights the utility of multimodality imaging in the diagnosis of constrictive pericarditis and the underappreciated fact that the pericardium need not be globally thickened to cause hemodynamically significant constrictive physiology.© 2012 Wiley Periodicals, Inc. PMID: 22311855 |
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