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Skarecky DW
Department of Urology, University of California, Irvine, CA 92697, USA.
Robotic-Assisted Radical Prostatectomy after the First Decade: Surgical Evolution or New Paradigm.
ISRN Urol. 2013;2013:157379
Early studies indicate that robotic-assisted radical prostatectomy (RARP) has promising short-term outcomes; however, RARP is beyond its infancy, and the long-term report cards are now beginning. The important paradigm shift introduced by RARP is the reevaluation of the entire open radical prostatectomy experience in surgical technique by minimizing blood loss and complications, maximizing cancer free outcomes, and a renewed assault in preserving quality of life outcomes by many novel mechanisms. RARP provides a new technical "canvas" for surgical masters to create upon, and in ten years, has reinvigorated a 100-year-old "gold standard" surgery.

PMID: 23691367

Qi X,Vargas E,Larsen L,Knapp W,Hatfield GW,Lathrop R,Sandmeyer S
Department of Biological Chemistry, School of Medicine, University of California Irvine, Irvine, California, United States of America.
Directed DNA Shuffling of Retrovirus and Retrotransposon Integrase Protein Domains.
PLoS One. 2013;8(5):e63957
Chimeric proteins are used to study protein domain functions and to recombine protein domains for novel or optimal functions. We used a library of chimeric integrase proteins to study DNA integration specificity. The library was constructed using a directed shuffling method that we adapted from fusion PCR. This method easily and accurately shuffles multiple DNA gene sequences simultaneously at specific base-pair positions, such as protein domain boundaries. It produced all 27 properly-ordered combinations of the amino-terminal, catalytic core, and carboxyl-terminal domains of the integrase gene from human immunodeficiency virus, prototype foamy virus, and Saccharomyces cerevisiae retrotransposon Ty3. Retrotransposons can display dramatic position-specific integration specificity compared to retroviruses. The yeast retrotransposon Ty3 integrase interacts with RNA polymerase III transcription factors to target integration at the transcription initiation site. In vitro assays of the native and chimeric proteins showed that human immunodeficiency virus integrase was active with heterologous substrates, whereas prototype foamy virus and Ty3 integrases were not. This observation was consistent with a lower substrate specificity for human immunodeficiency virus integrase than for other retrovirus integrases. All eight chimeras containing the Ty3 integrase carboxyl-terminal domain, a candidate targeting domain, failed to target strand transfer in the presence of the targeting protein, suggesting that multiple domains of the Ty3 integrase cooperate in this function.

PMID: 23691126

Vaziri ND,Yuan J,Khazaeli M,Masuda Y,Ichii H,Liu S
Division of Nephrology and Hypertension, University of California, Irvine, Calif., USA.
Oral Activated Charcoal Adsorbent (AST-120) Ameliorates Chronic Kidney Disease-Induced Intestinal Epithelial Barrier Disruption.
Am J Nephrol. 2013 May 15;37(6):518-525
Background: Chronic kidney disease (CKD) impairs intestinal barrier function which by allowing influx of noxious products causes systemic inflammation. We have recently shown that intestinal barrier dysfunction in CKD is due to degradation of epithelial tight junction (TJ) which is, in part, mediated by influx of urea and its conversion to ammonia by microbial urease. We hypothesized that by adsorbing urea and urea-derived ammonia, oral activated charcoal (AST-120) may ameliorate CKD-induced intestinal epithelial barrier disruption and systemic inflammation. Methods: Rats were randomized to the CKD or control groups. The CKD group was fed a chow containing 0.7% adenine for 2 weeks. They were then randomized to receive a chow with or without AST-120 (4 g/kg/day) for 2 weeks. Rats consuming regular diet served as controls. Animals were then euthanized, colons were removed and processed for Western blot and immunohistology, and plasma was used to measure endotoxin and oxidative and inflammatory markers. Results: Compared with the controls, the untreated CKD rats showed elevated plasma endotoxin, IL-6, TNF-α, MCP-1, CINC-3, L-selectin, ICAM-1, and malondialdehyde, and depletions of colonic epithelial TJ proteins, claudin-1, occludin, and ZO1. Administration of AST-120 resulted in partial restoration of the epithelial TJ proteins and reduction in plasma endotoxin and markers of oxidative stress and inflammation. Conclusions : CKD animals exhibited depletion of the key protein constituents of the colonic epithelial TJ which was associated with systemic inflammation, oxidative stress and endotoxemia. Administration of AST-120 attenuated uremia-induced disruption of colonic epithelial TJ and the associated endotoxemia, oxidative stress and inflammation.

PMID: 23689670

Phillips LF
Chemistry Department, University of California at Irvine, USA.
Atmospheric reactions on electrically charged surfaces.
Phys Chem Chem Phys. 2013 May 20;:
It is proposed that tropospheric NO2 at concentrations in the parts-per-billion range can be efficiently converted to HONO in a dust storm, by a process that is initiated by electron capture by NO2 from a negatively-charged dust particle. The electron capture is visualized as a harpoon-type process that does not require the NO2 to be adsorbed on the particle. The resulting electronically excited [NO2(-)]* ion reacts with water to form an HONO molecule plus an OH(-)·(H2O)n cluster ion. It is suggested that analogous processes can occur on other atmospheric aerosol particles with both positive and negative charges, with other molecules of high electron affinity such as SO2, and also, because the earth's surface is effectively the negative plate of a planet-sized capacitor, at the surfaces of terrestrial solids, lakes and oceans.

PMID: 23689618

Allison SD,Lu Y,Weihe C,Goulden ML,Martiny AC,Treseder KK,Martiny JB
Department of Ecology and Evolutionary Biology, University of California, Irvine, California 92697, USA. allisons@uci.edu
Microbial abundance and composition influence litter decomposition response to environmental change.
Ecology. 2013 Mar;94(3):714-25
Rates of ecosystem processes such as decomposition are likely to change as a result of human impacts on the environment. In southern California, climate change and nitrogen (N) deposition in particular may alter biological communities and ecosystem processes. These drivers may affect decomposition directly, through changes in abiotic conditions, and indirectly through changes in plant and decomposer communities. To assess indirect effects on litter decomposition, we reciprocally transplanted microbial communities and plant litter among control and treatment plots (either drought or N addition) in a grassland ecosystem. We hypothesized that drought would reduce decomposition rates through moisture limitation of decomposers and reductions in plant litter quality before and during decomposition. In contrast, we predicted that N deposition would stimulate decomposition by relieving N limitation of decomposers and improving plant litter quality. We also hypothesized that adaptive mechanisms would allow microbes to decompose litter more effectively in their native plot and litter environments. Consistent with our first hypothesis, we found that drought treatment reduced litter mass loss from 20.9% to 15.3% after six months. There was a similar decline in mass loss of litter inoculated with microbes transplanted from the drought treatment, suggesting a legacy effect of drought driven by declines in microbial abundance and possible changes in microbial community composition. Bacterial cell densities were up to 86% lower in drought plots and at least 50% lower on litter derived from the drought treatment, whereas fungal hyphal lengths increased by 13-14% in the drought treatment. Nitrogen effects on decomposition rates and microbial abundances were weaker than drought effects, although N addition significantly altered initial plant litter chemistry and litter chemistry during decomposition. However, we did find support for microbial adaptation to N addition with N-derived microbes facilitating greater mass loss in N plots than in control plots. Our results show that environmental changes can affect rates of ecosystem processes directly through abiotic changes and indirectly through microbial abundances and communities. Therefore models of ecosystem response to global change may need to represent microbial biomass and community composition to make accurate predictions.

PMID: 23687897

Samarasena JB,Nguyen NT,Lee JG
Division of Gastroenterology, University of California-Irvine, Orange, California.
Endoscopic retrograde cholangiopancreatography in patients with roux-en-Y anatomy.
J Interv Gastroenterol. 2012 4;2(2):78-83


PMID: 23687591

Lotfipour S,Cisneros V,Chakravarthy B
University of California Irvine School of Medicine, Department of Emergency Medicine, Irvine, California.
Vital Signs: Fatalities and Binge Drinking Among High School Students: A Critical Issue to Emergency Departments and Trauma Centers.
West J Emerg Med. 2013 May;14(3):271-274
The Centers for Disease Control and Prevention (CDC) has published significant data and trends related to drinking and driving among United States (U.S.) high school students. National data from 1991-2011 shows an overall 54% relative decrease (from 22% to 10.3%) in drinking and driving among U.S. high school students aged ≥ 16 years. In 2011, this still represents approximately 950,000 high school students ages 16-19 years. The decrease in drinking and driving among teens is not fully understood, but is believed to be due to policy developments, enforcement of laws, graduated licenses, and economic impacts. Most significant to emergency physicians is that even with these restrictions, in 2010 approximately 2,700 teens (ages 16-19) were killed in the U.S. and about 282,000 were treated and released from emergency departments for injuries suffered in motor-vehicle accidents. In the same year, 1 in 5 drivers between the ages of 16-19 who were involved in fatal crashes had positive (>0.00%) blood alcohol concentration (BAC). We present findings from the CDC's Morbidity and Mortality Weekly Report with commentary on current recommendations and policies for reducing drinking and driving among adolescents.

PMID: 23687547

Langdorf MI,Lee S,Menchine MD
University of California Irvine, Department of Emergency Medicine, Orange, California.
Financial Implications for Physicians Accepting Higher Level of Care Transfers.
West J Emerg Med. 2013 May;14(3):227-232
Introduction: Higher-level-of-care (HLOC) transfers to tertiary care hospitals are common. While this has been shown profitable for hospitals, the impact on physicians has not been described. Community medical center call panels continue to erode, in part due to the perception that patients needing transfer are underinsured. Surveys show that the problematic specialties to maintain call panels in community hospitals are neurosurgery, otolaryngology, plastic surgery, orthopedics and ophthalmology. This places greater stress on tertiary care hospitals' physicians. The objective of this study is to describe the financial consequences to physicians who care for HLOC transfers across specialties and compare these with all patients from each specialty and specialty-specific national reimbursement benchmarks. Methods: Financial data were obtained for all HLOC transfers to a single tertiary care center from January 2007 through March 2008. Work relative value unit (RVU) and reimbursement were taken from a centralized professional fee billing office. National benchmarks for reimbursement per RVU were calculated from the 2006 Medical Group Management Association (MGMA) Compensation and Production Survey. Results: In this period 570 patients were transferred, 319 (55.9%) through the emergency department (ED). Reimbursement per RVU varied from a high of $74.93 for neurosurgery to $25.91 for family medicine. Reimbursement to emergency medicine (EM) for HLOC patients was 16% above the average reimbursement per RVU for all ED patients ($50.5 vs. $43.7). Similarly, neurosurgery reimbursement per RVU was 22% above the reimbursement per RVU for all patients ($74.93 vs. $61.27). The remainder of specialties was reimbursed less ($25.91 vs $69.60) per RVU for HLOC patients than for all of their patients at this center. All specialties at this site were reimbursed less for each HLOC patient than national average reimbursement for all patients in each specialty. Conclusion: Average professional fee reimbursement for HLOC patients was higher for EM and neurosurgery than for all other patients in these specialties at this site, but lower for the rest of the specialties. Compared to the national benchmarks, this site had an overall lower reimbursement per RVU for all specialties, reflecting a poorer patient mix. At this site HLOC transfers patients are financially advantageous for EM and neurosurgery.

PMID: 23687540

Deleon JC,Scheumann N,Beatty W,Beck JR,Tran JQ,Yau C,Bradley PJ,Gull K,Wickstead B,Morrissette NS
Department of Molecular Biology and Biochemistry, University of California, Irvine, Irvine CA 92697.
A SAS-6-Like Protein Suggests that the Toxoplasma Conoid Complex Evolved from Flagellar Components.
Eukaryot Cell. 2013 May 17;:
SAS-6 is required for centriole biogenesis in diverse eukaryotes. Here, we describe a novel family of SAS-6-like (SAS6L) proteins that share an N-terminal domain with SAS-6, but lack coiled-coil tails. SAS6L proteins are found in a subset of eukaryotes that contain SAS-6, including diverse protozoa and green algae. In the apicomplexan parasite Toxoplasma gondii SAS-6 localizes to the centriole, but SAS6L is found above the conoid, an enigmatic tubulin-containing structure found at the apex of a subset of alveolate organisms. Loss of SAS6L causes reduced fitness in Toxoplasma. The Trypanosoma brucei homolog of SAS6L localizes to the basal plate region, the site in the axoneme where the central pair microtubules are nucleated. When endogenous SAS6L is overexpressed in Toxoplasma tachyzoites or Trypanosoma trypomastigotes, it forms prominent filaments that extend through the cell cytoplasm, indicating that it retains a capacity to form higher-order structures despite lacking a coiled coil domain. We conclude that although SAS6L proteins share a conserved domain with SAS-6, they are a functionally distinct family that pre-dates the last common ancestor of eukaryotes. Moreover, the distinct localization of the SAS6L protein in Trypanosoma and Toxoplasma adds weight to the hypothesis that the conoid complex evolved from flagellar components.

PMID: 23687115

Horvath P,Oliver SR,Ganesan G,Zaldivar FP,Radom-Aizik S,Galassetti PR
From the *Department of Pharmacology, School of Medicine, University of California, Irvine, Irvine, CA; and †Institute for Clinical Translational Science, Department of Pediatrics, University of California, Irvine, Orange, CA.
Fasting Glucose Level Modulates Cell Surface Expression of CD11b and CD66b in Granulocytes and Monocytes of Patients With Type 2 Diabetes.
J Investig Med. 2013 May 16;:
INTRODUCTION: Cardiovascular complications are the leading cause of mortality in type 2 diabetes (T2DM), in which onset and progression of atherosclerosis is linked to chronic inflammation. Activation status of innate immune cells (granulocytes [Gc], monocytes [Mc]), as reflected by increased CD11b, CD66b, and other surface markers, increases their endothelial and cytokines/chemokines release. Whereas this inflammatory activation seems inversely related to poor glycemic control, the effect of acute spontaneous hyperglycemia on innate immune cell activation remains unclear. METHODS: Expression of key markers (CD11b, CD14, CD16, CD62L, and CD66b) was therefore determined by flow cytometry on whole blood of healthy subjects and patients with T2DM with spontaneous fasting euglycemia or hyperglycemia both at baseline and after 30, 90, and 240 minutes of incubation at room temperature. RESULTS: Hyperglycemic patients with T2DM had significantly higher Gc and Mc CD11b and Gc CD66b surface mean fluorescence intensity compared with the euglycemic patients with T2DM whose values were similar to those of the healthy controls. CD16 expression in CD14+CD16+ Mc was elevated in all patients with T2DM, regardless of glycemic levels. CONCLUSION: Our data suggest that whereas the presence of diabetes per se may have a proinflammatory effect, hyperglycemia seems to further acutely exacerbate innate cell inflammatory status and their consequent endothelial adhesion and vascular damage potential.

PMID: 23686079

Mukamel DB,Ladd H,Temkin-Greener H
*Department of Medicine, Health Policy Research Institute, University of California, Irvine, CA †Department of Public Health Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY.
Stability of Cardiopulmonary Resuscitation and Do-Not-Resuscitate Orders Among Long-term Nursing Home Residents.
Med Care. 2013 May 16;:
BACKGROUND:: High-quality care for long-term nursing home residents should include discussions and follow-up on patients' end-of-life care wishes. Yet, recent changes to the Minimum Data Set data collection exclude this information from routine assessment of patients mandated by the Centers for Medicare & Medicaid Services, making the provision of high-quality end-of-life care less likely. We examined the stability of cardiopulmonary resuscitation (CPR) and do-not-resuscitate (DNR) orders to offer guidance to policy and care practice developments. METHODS:: We examined changes in DNR status of a national long-term care nursing home cohort, following them for 5 years after admission. A competing risk model was estimated to identify covariates predicting changes from CPR to DNR status and vice versa. RESULTS:: About half the cohort chose DNR at admission and did not change its status. Of those who entered with CPR status, 40% changed to DNR. The most important factors influencing change were hospitalizations and nursing home transfers, followed by race and ethnicity with black race (relative to white) in particular having the largest effect on change. Other individual and nursing home characteristics influenced the likelihood of changing from CPR to DNR as well. CONCLUSIONS:: Long-term nursing home patients who enter with full-code CPR have a high probability of changing their status to DNR during their stay. High-quality care should offer them the opportunity to revisit their choice periodically, documenting changes in end-of-life choices when they occur, thus ensuring that care will match patients' wishes. As the Minimum Data Set plays a prominent role in patients' care, Centers for Medicare & Medicaid Services should consider reinstating information about advance directive in it.

PMID: 23685402

Gu B,Watanabe K,Sun P,Fallahi M,Dai X
Department of Biological Chemistry, School of Medicine, University of California, Irvine, Irvine, CA 92697, USA.
Chromatin Effector Pygo2 Mediates Wnt-Notch Crosstalk to Suppress Luminal/Alveolar Potential of Mammary Stem and Basal Cells.
Cell Stem Cell. 2013 May 15;:
Epigenetic mechanisms regulating lineage differentiation of mammary stem cells (MaSCs) remain poorly understood. Pygopus 2 (Pygo2) is a histone methylation reader and a context-dependent Wnt/β-catenin coactivator. Here we provide evidence for Pygo2's function in suppressing luminal/alveolar differentiation of MaSC-enriched basal cells. We show that Pygo2-deficient MaSC/basal cells exhibit partial molecular resemblance to luminal cells, such as elevated Notch signaling and reduced mammary repopulating capability upon transplantation. Inhibition of Notch signaling suppresses basal-level and Pygo2-deficiency-induced luminal/alveolar differentiation of MaSC/basal cells, whereas activation of Wnt/β-catenin signaling suppresses luminal/alveolar differentiation and Notch3 expression in a Pygo2-dependent manner. We show that Notch3 is a direct target of Pygo2 and that Pygo2 is required for β-catenin binding and maintenance of a poised/repressed chromatin state at the Notch3 locus in MaSC/basal cells. Together, our data support a model where Pygo2-mediated chromatin regulation connects Wnt signaling and Notch signaling to restrict the luminal/alveolar differentiation competence of MaSC/basal cells.

PMID: 23684539

Wong JM,Lombardo D,Handwerker J,Fisher M
School of Medicine, University of California, Irvine, California.
Cryptogenic Stroke and the Left Atrial Septal Pouch: A Case Report.
J Stroke Cerebrovasc Dis. 2013 May 13;:
The left atrial septal pouch (LASP) is an anatomic variant of the interatrial septum and may be a nidus for thromboembolism. We present the case of a 49 year-old man without known vascular risk factors who experienced bi-hemispheric strokes over the course of 10 days, suggestive of multiple emboli. Transesophageal echocardiography revealed a prominent LASP. We suggest that presence of LASP was a likely cause of stroke in this patient and that further study of a possible association between LASP and ischemic stroke in younger individuals may be warranted.

PMID: 23680685

Houston D,Li W,Wu J
Douglas Houston is with the Department of Planning, Policy, and Design, School of Social Ecology, University of California, Irvine. Wei Li is with the Department of Landscape Architecture and Urban Planning, Texas A&M University, College Station. Jun Wu is with the Program in Public Health and Department of Epidemiology, University of California, Irvine.
Disparities in Exposure to Automobile and Truck Traffic and Vehicle Emissions Near the Los Angeles-Long Beach Port Complex.
Am J Public Health. 2013 May 16;:
Objectives. We assessed how traffic and mobile-source air pollution impacts are distributed across racial/ethnic and socioeconomically diverse groups in port-adjacent communities in southern Los Angeles County, which may experience divergent levels of exposure to port-related heavy-duty diesel truck traffic because of existing residential and land use patterns. Methods. We used spatial regression techniques to assess the association of neighborhood racial/ethnic and socioeconomic composition with residential parcel-level traffic and vehicle-related fine particulate matter exposure after accounting for built environment and land use factors. Results. After controlling for factors associated with traffic generation, we found that a higher percentage of nearby Black and Asian/Pacific Islander residents was associated with higher exposure, a higher percentage of Hispanic residents was associated with higher traffic exposure but lower vehicle particulate matter exposure, and areas with lower socioeconomic status experienced lower exposure. Conclusions. Disparities in traffic and vehicle particulate matter exposure are nuanced depending on the exposure metric used, the distribution of the traffic and emissions, and pollutant dispersal patterns. Future comparative research is needed to assess potential disparities in other transportation and goods movement corridors. (Am J Public Health. Published online ahead of print May 16, 2013: e1-e9. doi:10.2105/AJPH.2012.301120).

PMID: 23678919

Zhang J,Braunstein ML,Andersen GJ
Department of Cognitive Sciences, University of California, Irvine, Irvine, CA 92697-5100, USA.
Changes in angular size and speed affect the judged height of objects moving over a ground surface.
Perception. 2013;42(1):34-44
Kersten et al (1997, Perception 26 171-192) showed that the perceived path of an object moving over a ground surface can be manipulated by changing the path of a shadow. Using a scene similar to Kersten's "ball-in-a-box" scene, we investigated the effect of angular size and angular speed in determining the perceived height of a moving sphere when optical contact (the position at which the object contacted the ground in the image) indicated that the sphere was receding in depth. In four experiments we examined both the effects of changes in size and speed, and the effects of constant levels of size and speed. Increases in angular size or speed during a motion sequence resulted in judgments of increased height above the ground plane. The angular size at the end of the motion sequence was also important in determining judged height, with greater height judged with larger final sizes.

PMID: 23678615

Booher K,Lin DW,Borrego SL,Kaiser P
Department of Biological Chemistry, College of Medicine, University of California Irvine, Irvine, CA USA.
Downregulation of Cdc6 and pre-replication complexes in response to methionine stress in breast cancer cells.
Cell Cycle. 2012 Dec 1;11(23):4414-23
Methionine and homocysteine are metabolites in the transmethylation pathway leading to synthesis of the methyl-donor S-adenosylmethionine (SAM). Most cancer cells stop proliferating during methionine stress conditions, when methionine is replaced in the growth media by its immediate metabolic precursor homocysteine (Met-Hcy+). Non-transformed cells proliferate in Met-Hcy+ media, making the methionine metabolic requirement of cancer cells an attractive target for therapy, yet there is relatively little known about the molecular mechanisms governing the methionine stress response in cancer cells. To study this phenomenon in breast cancer cells, we selected methionine-independent-resistant cell lines derived from MDAMB468 breast cancer cells. Resistant cells grew normally in Met-Hcy+ media, whereas their parental MDAMB468 cells rapidly arrest in the G 1 phase. Remarkably, supplementing Met-Hcy+ growth media with S-adenosylmethionine suppressed the cell proliferation defects, indicating that methionine stress is a consequence of SAM limitation rather than low amino acid concentrations. Accordingly, mTORC1 activity, the primary effector responding to amino acid limitation, remained high. However, we found that levels of the replication factor Cdc6 decreased and pre-replication complexes were destabilized in methionine-stressed MDAMB468 but not resistant cells. Our study characterizes metabolite requirements and cell cycle responses that occur during methionine stress in breast cancer cells and helps explain the metabolic uniqueness of cancer cells.

PMID: 23159852

Dickinson G,Lim KY,Jiang SC
Ecology and Evolutionary Biology, University of California, Irvine, California, USA.
Quantitative microbial risk assessment of pathogenic vibrios in marine recreational waters of southern california.
Appl Environ Microbiol. 2013 Jan;79(1):294-302
This study investigated the occurrence of three types of vibrios in Southern California recreational beach waters during the peak marine bathing season in 2007. Over 160 water samples were concentrated and enriched for the detection of vibrios. Four sets of PCR primers, specific for Vibrio cholerae, V. parahaemolyticus, and V. vulnificus species and the V. parahaemolyticus toxin gene, respectively, were used for the amplification of bacterial genomic DNA. Of 66 samples from Doheny State Beach, CA, 40.1% were positive for V. cholerae and 27.3% were positive for V. parahaemolyticus, and 1 sample (1.5%) was positive for the V. parahaemolyticus toxin gene. Of the 96 samples from Avalon Harbor, CA, 18.7% were positive for V. cholerae, 69.8% were positive for V. parahaemolyticus, and 5.2% were positive for the V. parahaemolyticus toxin gene. The detection of the V. cholerae genetic marker was significantly more frequent at Doheny State Beach, while the detection of the V. parahaemolyticus genetic marker was significantly more frequent at Avalon Harbor. A probability-of-illness model for V. parahaemolyticus was applied to the data. The risk for bathers exposed to recreational waters at two beaches was evaluated through Monte Carlo simulation techniques. The results suggest that the microbial risk from vibrios during beach recreation was below the illness benchmark set by the U.S. EPA. However, the risk varied with location and the type of water recreation activities. Surfers and children were exposed to a higher risk of vibrio diseases. Microbial risk assessment can serve as a useful tool for the management of risk related to opportunistic marine pathogens.

PMID: 23104412

Fox JC,Chiem AT,Rooney KP,Maldonaldo G
UCI School of Medicine, Medical Education Building, 836 Health Sciences Road, Irvine, CA 92697, USA. jfox@uci.edu
Web-based lectures, peer instruction and ultrasound-integrated medical education.
Med Educ. 2012 Nov;46(11):1109-10


PMID: 23078697

Dilbeck CW,Finlayson-Pitts BJ
Department of Chemistry, University of California Irvine, Irvine, CA 92697-2025, USA. bjfinlay@uci.edu.
Hydroxyl radical oxidation of phospholipid-coated NaCl particles.
Phys Chem Chem Phys. 2013 May 15;:
Biological organic compounds mixed with NaCl and other inorganic compounds in sea-salt aerosol particles react in air with oxidants such as ozone and hydroxyl (OH) radicals. Laboratory studies of model systems can provide insight into these reactions. We report here studies of the kinetics and mechanism of oxidation of unsaturated 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) on NaCl by gas phase OH in air at room temperature and 1 atm pressure using diffuse reflection infrared Fourier transform spectrometry (DRIFTS) and matrix-assisted laser desorption/ionization-time-of-flight-mass spectrometry (MALDI-TOF-MS) to identify possible structures of surface-bound reaction products. For comparison, some studies were also carried out on the saturated 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) on NaCl. The calculated concentration of hydroxyl radicals, generated by photolysis of isopropyl nitrite, was (1.6-6.4) × 10(8) radicals cm(-3). Surface-bound aldehydes, ketones, organic nitrates and nitrate ions were identified as products of these reactions and structures of potential products were proposed based on mechanistic considerations combined with the MALDI-TOF-MS and DRIFTS spectra. The loss rate of vinyl hydrogen, [double bond, length as m-dash]C-H, at 3008 cm(-1) was used to obtain a lower limit for the rate constant (k1) for addition of OH to the double bond, k1 > (3 ± 1) × 10(-13) cm(3) molecule(-1) s(-1) (1s), corresponding to a reaction probability of γ(add) > (4 ± 1) × 10(-3) (1s). Assuming that abstraction from -CH2- groups in POPC is the same as for DPPC, the percentage of the reaction that occurs by addition is ∼80%. This is similar to the percent addition predicted using structure-reactivity relationships for gas-phase reactions. Decreasing the amount of POPC relative to NaCl resulted in more nitrate ion formation and less relative loss of POPC, and increasing the OH concentration resulted in a more rapid loss of POPC and faster product formation. These studies suggest that under atmospheric conditions with an OH concentration of 5 × 10(6) radicals cm(-3), the lifetime of POPC with respect to OH is

PMID: 23676928

Han Y,Raghunathan V,Feng RR,Maekawa H,Chung CY,Feng Y,Potma EO,Ge NH
Department of Chemistry, University of California at Irvine, Irvine, California 92697-2025, United States.
Mapping Molecular Orientation with Phase Sensitive Vibrationally Resonant Sum-Frequency Generation Microscopy.
J Phys Chem B. 2013 May 15;:
We demonstrate a phase sensitive, vibrationally resonant sum-frequency generation (PSVR-SFG) microscope that combines high resolution, fast image acquisition speed, chemical selectivity, and phase sensitivity. Using the PSVR-SFG microscope, we generate amplitude and phase images of the second-order susceptibility of collagen I fibers in rat tail tendon tissue on resonance with the methylene vibrations of the protein. We find that the phase of the second-order susceptibility shows dependence on the effective polarity of the fibril bundles, revealing fibrous collagen domains of opposite orientations within the tissue. The presence of collagen microdomains in tendon tissue may have implications for the interpretation of the mechanical properties of the tissue.

PMID: 23675654

Banik M,El-Khoury PZ,Nag A,Rodriguez-Perez A,Guarrottxena N,Bazan GC,Apkarian VA
Department of Chemistry, University of California, Irvine, California 92697, United States.
Surface-enhanced Raman trajectories on a nano-dumbbell: transition from field to charge transfer plasmons as the spheres fuse.
ACS Nano. 2012 Nov 27;6(11):10343-54
By taking advantage of the tensor nature of surface-enhanced Raman scattering (SERS), we track trajectories of the linker molecule and a CO molecule chemisorbed at the hot spot of a nano-dumbbell consisting of dibenzyldithio-linked silver nanospheres. The linear Stark shift of CO serves as an absolute gauge of the local field, while the polyatomic spectra characterize the vector components of the local field. We identify surface-enhanced Raman optical activity due to a transient asperity in the nanojunction in an otherwise uneventful SERS trajectory. During fusion of the spheres, we observe sequential evolution of the enhanced spectra from dipole-coupled Raman to quadrupole- and magnetic dipole-coupled Raman, followed by a transition from line spectra to band spectra, and the full reversal of the sequence. From the spectrum of CO, the sequence can be understood to track the evolution of the junction plasmon resonance from dipolar to quadrupolar to charge transfer as a function of intersphere separation, which evolves at a speed of ∼1 Å/min. The crossover to the conduction limit is marked by the transition of line spectra to Stark-broadened and shifted band spectra. As the junction closes on CO, the local field reaches 1 V/Å, limited to a current of 1 electron per vibrational cycle passing through the molecule, with associated Raman enhancement factor via the charge transfer plasmon resonance of 10(12). The local field identifies that a sharp protrusion is responsible for room-temperature chemisorption of CO on silver. The asymmetric phototunneling junction, Ag-CO-Ag, driven by the frequency-tunable charge transfer plasmon of the dumbbell antenna, combines the design elements of an ideal rectifying photocollector.

PMID: 23092179

Bezaire MJ,Soltesz I
Department of Anatomy and Neurobiology, University of California, Irvine, California, 92697-1280, USA.
Quantitative assessment of CA1 local circuits: Knowledge base for interneuron-pyramidal cell connectivity.
Hippocampus. 2013 May 15;:
In this work, through a detailed literature review, data-mining, and extensive calculations, we provide a current, quantitative estimate of the cellular and synaptic constituents of the CA1 region of the rat hippocampus. Beyond estimating the cell numbers of GABAergic interneuron types, we calculate their convergence onto CA1 pyramidal cells and compare it with the known input synapses on CA1 pyramidal cells. The convergence calculation and comparison are also made for excitatory inputs to CA1 pyramidal cells. In addition, we provide a summary of the excitatory and inhibitory convergence onto interneurons. The quantitative knowledge base assembled and synthesized here forms the basis for data-driven, large-scale computational modeling efforts. Additionally, this work highlights specific instances where the available data are incomplete, which should inspire targeted experimental projects towards a more complete quantification of the CA1 neurons and their connectivity. © 2013 Wiley Periodicals, Inc.

PMID: 23674373

Delfino RJ,Staimer N,Tjoa T,Gillen DL,Schauer JJ,Shafer MM
Department of Epidemiology, School of Medicine, University of California, Irvine, Irvine, California, USA.
Airway inflammation and oxidative potential of air pollutant particles in a pediatric asthma panel.
J Expo Sci Environ Epidemiol. 2013 May 15;:
Airborne particulate matter (PM) components from fossil fuel combustion can induce oxidative stress initiated by reactive oxygen species (ROS). Reported associations between worsening asthma and PM2.5 mass could be related to PM oxidative potential to induce airway oxidative stress and inflammation (hallmarks of asthma pathology). We followed 45 schoolchildren with persistent asthma in their southern California homes daily over 10 days with offline fractional exhaled nitric oxide (FENO), a biomarker of airway inflammation. Ambient exposures included daily average PM2.5, PM2.5 elemental and organic carbon (EC, OC), NO2, O3, and endotoxin. We assessed PM2.5 oxidative potential using both an abiotic and an in vitro bioassay on aqueous extracts of daily particle filters: (1) dithiothreitol (DTT) assay (abiotic), representing chemically produced ROS; and (2) ROS generated intracellularly in a rat alveolar macrophage model using the fluorescent probe 2'7'-dicholorohidroflourescin diacetate. We analyzed relations of FENO to air pollutants in mixed linear regression models. FENO was significantly positively associated with lag 1-day and 2-day averages of traffic-related markers (EC, OC, and NO2), DTT and macrophage ROS, but not PM2.5 mass. DTT associations were nearly twice as strong as other exposures per interquartile range: median FENO increased 8.7-9.9% per 0.43 nmole/min/m(3) DTT. Findings suggest that future research in oxidative stress-related illnesses such as asthma and PM exposure would benefit from assessments of PM oxidative potential and composition.Journal of Exposure Science and Environmental Epidemiology advance online publication, 15 May 2013; doi:10.1038/jes.2013.25.

PMID: 23673461

Lee MD,Vanpaemel W
Department of Cognitive Sciences, University of California Irvine, Irvine CA 92697-5100. mdlee@uci.edu http://faculty.sites.uci.edu/mdlee/publications/
Quantum models of cognition as Orwellian newspeak.
Behav Brain Sci. 2013 Jun;36(3):295-296
Faced with probabilistic relationships between causes and effects, quantum theory assumes that deterministic causes do not exist, and that only incomplete probabilistic expressions of knowledge are possible. As in its application to physics, this fundamental epistemological stance severely limits the ability of quantum theory to provide insight and understanding in human cognition.

PMID: 23673041

Rasool S,Martinez-Coria H,Wu JW,Laferla F,Glabe CG
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA; Department of physiology and Neurosciences NYU Langone Medical Center NY-10016.
Systemic vaccination with anti-oligomeric monoclonal antibodies improves cognitive function by reducing Aβ deposition and tau pathology in 3xTg-AD mice.
J Neurochem. 2013 May 15;:
Alzheimer's disease (AD) is a devastating disorder that is clinically characterized by a comprehensive cognitive decline. Accumulation of the amyloid-beta (Aβ) peptide plays a pivotal role in the pathogenesis of AD. In AD, the conversion of Aβ from a physiological soluble monomeric form into insoluble fibrillar conformation is an important event. The most toxic form of Aβ are oligomers which is the intermediate step during the conversion of monomeric form to fibrillar form. There are at least two types of oligomers: oligomers that are immunologically related to fibrils and those that are not. In transgenic AD animal models, both active and passive anti-Aβ immunotherapies improve cognitive function and clear the parenchymal accumulation of amyloid plaques in the brain. In this report we studied effect of immunotherapy of two sequence-independent non-fibrillar oligomer specific monoclonal antibodies on the cognitive function, amyloid load and tau pathology in 3xTg-AD mice. Anti-oligomeric monoclonal antibodies significantly reduce the amyloid load and improve the cognition. The clearance of amyloid load was significantly correlated with reduced tau hyperphosphorylation and improvement in cognition. These results demonstrate that systemic immunotherapy using oligomer-specific monoclonal antibodies effectively attenuates behavioral and pathological impairments in 3xTg-AD mice. These findings demonstrate the potential of using oligomer specific monoclonal antibodies as a therapeutic approach to prevent and treat Alzheimer's disease. This article is protected by copyright. All rights reserved.

PMID: 23672786



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