Lane Medical Library

Serum Urate and Incidence of Kidney Disease Among Veterans with Gout.

J Rheumatol. 2013 May 15;

Authors: Krishnan E, Akhras KS, Sharma H, Marynchenko M, Wu E, Tawk RH, Liu J, Shi L

Abstract
OBJECTIVE: To study the association between serum urate level (sUA) and the risk of incident kidney disease among US veterans with gouty arthritis. METHODS: From 2002 through 2011 adult male patients with gout who were free of kidney disease were identified in the data from the Veterans Administration VISN 16 database and were followed until incidence of kidney disease, death, or the last available observation. Accumulated hazard curves for time to kidney disease were estimated for patients with average sUA levels > 7 mg/dl (high) versus ≤ 7 mg/dl (low) based on Kaplan-Meier analyses; and statistical comparison was conducted using a log-rank test. A Cox proportional hazard model with time-varying covariates was used to estimate the unadjusted and adjusted hazard ratios for kidney disease. RESULTS: Eligible patients (n = 2116) were mostly white (53%), with average age 62.6 years, mean body mass index 31.2 kg/m2, and high baseline prevalence of hypertension (93%), hyperlipidemia (67%), and diabetes (20%). Mean followup time was 6.5 years. The estimated rates of all incident kidney disease in the overall low versus high sUA groups were 2% versus 4% at Year 1, 3% versus 6% at Year 2, and 5% versus 9% at Year 3, respectively (p < 0.0001). After adjustment, high sUA continued to predict a significantly higher risk of kidney disease development (HR 1.43, 95% CI 1.20-1.70). CONCLUSION: Male veterans with gout and sUA levels > 7 mg/dl had an increased incidence of kidney disease.

PMID: 23678154 [PubMed - as supplied by publisher]

Golimumab in Patients with Active Rheumatoid Arthritis Despite Methotrexate Therapy: Results Through 2 Years of the GO-FORWARD Study Extension.

J Rheumatol. 2013 May 15;

Authors: Keystone EC, Genovese MC, Hall S, Miranda PC, Bae SC, Palmer W, Wu Z, Xu S, Hsia EC

Abstract
OBJECTIVE: To assess the longterm efficacy and safety of golimumab in patients with active rheumatoid arthritis (RA) despite methotrexate (MTX) therapy. METHODS: We randomized 444 RA patients with inadequate response to MTX (3:3:2:2) to placebo + MTX (Group 1), golimumab 100 mg + placebo (Group 2), golimumab 50 mg + MTX (Group 3), or golimumab 100 mg + MTX (Group 4). Subcutaneous golimumab/placebo was injected every 4 weeks. Patients could escape early (Group 1 added golimumab 50 mg, Group 2 added MTX, Group 3 increased golimumab to 100 mg, Group 4 continued 100 mg) based on Week 16 swollen and tender joint counts. From Week 24, Group 1 patients received golimumab 50 mg + MTX. After the Week 52 database lock, patients in the longterm extension received golimumab 50-100 mg ± MTX. Coprimary endpoints [Week 14 American College of Rheumatology (ACR)20, Week 24 Health Assessment Questionnaire Disability Index (HAQ-DI)] and Week 52 findings have been published; 2-year findings (observed data by randomized group, no imputation) are presented. RESULTS: Of 444 randomized patients, 392 continued from Week 52 (Group 1: n = 116, Group 2: n = 116, Group 3: n = 84, Group 4: n = 76). Clinical improvement was maintained through Week 104; ~75% and 72% of patients randomized to golimumab 50 mg + MTX and 100 mg + MTX achieved ACR20 response, respectively. The majority [88% (105/120)] of golimumab + MTX-treated patients with Week 24 HAQ-DI improvement ≥ 0.25 maintained improved physical function through Week 104. Group 1 patients with delayed golimumab treatment exhibited more Week 104 radiographic progression (mean change score = 1.15) than golimumab + MTX-randomized patients (0.52). Incidences of serious infections were 2.24, 4.77, 5.78/100 patient-years of followup for golimumab 50 mg + MTX, 100 mg + placebo, and 100 mg + MTX, respectively. CONCLUSION: Clinical improvement was maintained and no new safety signals were identified with 2 years of golimumab + MTX. Golimumab efficacy and safety, including serious infections, will continue to be monitored through 5 years (Clinical Trial No. NCT00264550).

PMID: 23678153 [PubMed - as supplied by publisher]

Shh/Boc signaling is required for sustained generation of ipsilateral projecting ganglion cells in the mouse retina.

J Neurosci. 2013 May 15;33(20):8596-607

Authors: Sánchez-Arrones L, Nieto-Lopez F, Sánchez-Camacho C, Carreres MI, Herrera E, Okada A, Bovolenta P

Abstract
Sonic Hedgehog (Shh) signaling is an important determinant of vertebrate retinal ganglion cell (RGC) development. In mice, there are two major RGC populations: (1) the Islet2-expressing contralateral projecting (c)RGCs, which both produce and respond to Shh; and (2) the Zic2-expressing ipsilateral projecting RGCs (iRGCs), which lack Shh expression. In contrast to cRGCs, iRGCs, which are generated in the ventrotemporal crescent (VTC) of the retina, specifically express Boc, a cell adhesion molecule that acts as a high-affinity receptor for Shh. In Boc(-/-) mutant mice, the ipsilateral projection is significantly decreased. Here, we demonstrate that this phenotype results, at least in part, from the misspecification of a proportion of iRGCs. In Boc(-/-) VTC, the number of Zic2-positive RGCs is reduced, whereas more Islet2/Shh-positive RGCs are observed, a phenotype also detected in Zic2 and Foxd1 null embryos. Consistent with this observation, organization of retinal projections at the dorsal lateral geniculate nucleus is altered in Boc(-/-) mice. Analyses of the molecular and cellular consequences of introducing Shh into the developing VTC and Zic2 and Boc into the central retina indicate that Boc expression alone is insufficient to fully activate the ipsilateral program and that Zic2 regulates Shh expression. Taking these data together, we propose that expression of Boc in cells from the VTC is required to sustain Zic2 expression, likely by regulating the levels of Shh signaling from the nearby cRGCs. Zic2, in turn, directly or indirectly, counteracts Shh and Islet2 expression in the VTC and activates the ipsilateral program.

PMID: 23678105 [PubMed - in process]

Physiological plasticity of cardiorespiratory function in a eurythermal marine teleost, the longjaw mudsucker, Gillichthys mirabilis.

J Exp Biol. 2013 Jun 1;216(Pt 11):2111-21

Authors: Jayasundara N, Somero GN

Abstract
An insufficient supply of oxygen under thermal stress is thought to define thermal optima and tolerance limits in teleost fish. When under thermal stress, cardiac function plays a crucial role in sustaining adequate oxygen supply for respiring tissues. Thus, adaptive phenotypic plasticity of cardiac performance may be critical for modifying thermal limits during temperature acclimation. Here we investigated effects of temperature acclimation on oxygen consumption, cardiac function and blood oxygen carrying capacity of a eurythermal goby fish, Gillichthys mirabilis, acclimated to 9, 19 and 26°C for 4 weeks. Acclimation did not alter resting metabolic rates or heart rates; no compensation of rates was observed at acclimation temperatures. However, under an acute heat ramp, warm-acclimated fish exhibited greater heat tolerance (CTmax=33.3, 37.1 and 38.9°C for 9°C-, 19°C- and 26°C-acclimated fish, respectively) and higher cardiac arrhythmia temperatures compared with 9°C-acclimated fish. Heart rates measured under an acute heat stress every week during 28 days of acclimation suggested that both maximum heart rates and temperature at onset of maximum heart rates changed over time with acclimation. Hemoglobin levels increased with acclimation temperature, from 35 g l(-1) in 9°C-acclimated fish to 60-80 g l(-1) in 19°C- and 26°C-acclimated fish. Oxygen consumption rates during recovery from acute heat stress showed post-stress elevation in 26°C-acclimated fish. These data, coupled with elevated resting metabolic rates and heart rates at warm temperatures, suggest a high energetic cost associated with warm acclimation in G. mirabilis. Furthermore, acclimatory capacity appears to be optimized at 19°C, a temperature shown by behavioral studies to be close to the species' preferred temperature.

PMID: 23678101 [PubMed - in process]

Canonical and Noncanonical Wnt Proteins Program Dendritic Cell Responses for Tolerance.

J Immunol. 2013 May 15;

Authors: Oderup C, Lajevic M, Butcher EC

Abstract
Ag-presenting dendritic cells (DCs) interpret environmental signals to orchestrate local and systemic immune responses. They govern the balance between tolerance and inflammation at epithelial surfaces, where the immune system must provide robust pathogen responses while maintaining tolerance to commensal flora and food Ags. The Wnt family of secreted proteins, which control epithelial and hematopoietic development and homeostasis, is emerging as an important regulator of inflammation. In this study, we show that canonical and noncanonical Wnts directly stimulate murine DC production of anti-inflammatory cytokines. Wnt3A triggers canonical β-catenin signaling and preferentially induces DC TGF-β and VEGF production, whereas Wnt5A induces IL-10 through alternative pathways. The Wnts also alter DC responses to microbe- or pathogen-associated molecular patterns, inhibiting proinflammatory cytokine induction in response to TLR ligands and promoting DC generation of Foxp3(+) regulatory T cells. Moreover, although both Wnts suppress proinflammatory responses to bacterial endotoxin and to TLR1/2, TLR7, and TLR9 ligands, Wnt5A, but not Wnt3A, inhibits IL-6 production in response to the viral mimic, polyinosinic:polycytidylic acid. Thus, Wnt family members directly and differentially regulate DC functions, an ability that may contribute to the balance between tolerance and inflammation at epithelial sites of exposure to microbes and environmental Ags.

PMID: 23677472 [PubMed - as supplied by publisher]

The rewards of restraint in the collective regulation of foraging by harvester ant colonies.

Nature. 2013 May 15;

Authors: Gordon DM

Abstract
Collective behaviour, arising from local interactions, allows groups to respond to changing conditions. Long-term studies have shown that the traits of individual mammals and birds are associated with their reproductive success, but little is known about the evolutionary ecology of collective behaviour in natural populations. An ant colony operates without central control, regulating its activity through a network of local interactions. This work shows that variation among harvester ant (Pogonomyrmex barbatus) colonies in collective response to changing conditions is related to variation in colony lifetime reproductive success in the production of offspring colonies. Desiccation costs are high for harvester ants foraging in the desert. More successful colonies tend to forage less when conditions are dry, and show relatively stable foraging activity when conditions are more humid. Restraint from foraging does not compromise a colony's long-term survival; colonies that fail to forage at all on many days survive as long, over the colony's 20-30-year lifespan, as those that forage more regularly. Sensitivity to conditions in which to reduce foraging activity may be transmissible from parent to offspring colony. These results indicate that natural selection is shaping the collective behaviour that regulates foraging activity, and that the selection pressure, related to climate, may grow stronger if the current drought in their habitat persists.

PMID: 23676676 [PubMed - as supplied by publisher]

Variation and genetic control of protein abundance in humans.

Nature. 2013 May 15;

Authors: Wu L, Candille SI, Choi Y, Xie D, Jiang L, Li-Pook-Than J, Tang H, Snyder M

Abstract
Gene expression differs among individuals and populations and is thought to be a major determinant of phenotypic variation. Although variation and genetic loci responsible for RNA expression levels have been analysed extensively in human populations, our knowledge is limited regarding the differences in human protein abundance and the genetic basis for this difference. Variation in messenger RNA expression is not a perfect surrogate for protein expression because the latter is influenced by an array of post-transcriptional regulatory mechanisms, and, empirically, the correlation between protein and mRNA levels is generally modest. Here we used isobaric tag-based quantitative mass spectrometry to determine relative protein levels of 5,953 genes in lymphoblastoid cell lines from 95 diverse individuals genotyped in the HapMap Project. We found that protein levels are heritable molecular phenotypes that exhibit considerable variation between individuals, populations and sexes. Levels of specific sets of proteins involved in the same biological process covary among individuals, indicating that these processes are tightly regulated at the protein level. We identified cis-pQTLs (protein quantitative trait loci), including variants not detected by previous transcriptome studies. This study demonstrates the feasibility of high-throughput human proteome quantification that, when integrated with DNA variation and transcriptome information, adds a new dimension to the characterization of gene expression regulation.

PMID: 23676674 [PubMed - as supplied by publisher]

Commentary to "A Transatlantic Difference in Aesthetic Surgery Training"

Ann Plast Surg. 2013 May 13;

Authors: Momeni A, Sstark GB

PMID: 23676523 [PubMed - as supplied by publisher]

Test-retest and interrater reliability of the functional movement screen.

J Athl Train. 2013 May-Jun;48(3):331-6

Authors: Shultz R, Anderson SC, Matheson GO, Marcello B, Besier T

Abstract
Context: The Functional Movement Screen (FMS) is a popular test to evaluate the degree of painful, dysfunctional, and asymmetric movement patterns. Despite great interest in the FMS, test-retest reliability data have not been published. Objective: To assess the test-retest and interrater reliability of the FMS and to compare the scoring by 1 rater during a live session and the same session on video. Design: Cross-sectional study. Setting: Human performance laboratory in the sports medicine center. Patients or Other Participants: A total of 21 female (age = 19.6 ± 1.5 years, height = 1.7 ± 0.1 m, mass = 64.4 ± 5.1 kg) and 18 male (age = 19.7 ± 1.0 years, height = 1.9 ± 0.1 m, mass = 80.1 ± 9.9 kg) National Collegiate Athletic Association Division IA varsity athletes volunteered. Intervention(s): Each athlete was tested and retested 1 week later by the same rater who also scored the athlete's first session from a video recording. Five other raters scored the video from the first session. Main Outcome Measure(s): The Krippendorff α (K α) was used to assess the interrater reliability, whereas intraclass correlation coefficients (ICCs) were used to assess the test-retest reliability and reliability of live-versus-video scoring. Results: Good reliability was found for the test-retest (ICC = 0.6), and excellent reliability was found for the live-versus-video sessions (ICC = 0.92). Poor reliability was found for the interrater reliability (K α = .38). Conclusions: The good test-retest and high live-versus-video session reliability show that the FMS is a usable tool within 1 rater. However, the low interrater K α values suggest that the FMS within the limits of generalization should not be used indiscriminately to detect deficiencies that place the athlete at greater risk for injury. The FMS interrater reliability may be improved with better training for the rater.

PMID: 23675792 [PubMed - in process]

Geriatric dermatology: Part II. Risk factors and cutaneous signs of elder mistreatment for the dermatologist.

J Am Acad Dermatol. 2013 Apr;68(4):533.e1-10; quiz 543-4

Authors: Chang AL, Wong JW, Endo JO, Norman RA

Abstract
Cutaneous signs may be the most visible hint of elder mistreatment. Dermatologists are in a unique position to recognize and report physical abuse and neglect in the older patient population. In this review, we describe the scope and impact, risk factors, cutaneous signs, and appropriate responses to suspected elder mistreatment. There is a critical need for additional evidence to inform clinical practice in the field of elder abuse and neglect. Recognition and reporting of suspected elder mistreatment by the dermatologist can be life-saving for the older patient.

PMID: 23522422 [PubMed - indexed for MEDLINE]

MicroRNAs: regulators of neuronal fate.

Curr Opin Cell Biol. 2013 Apr;25(2):215-21

Authors: Sun AX, Crabtree GR, Yoo AS

Abstract
Mammalian neural development has been traditionally studied in the context of evolutionarily conserved signaling pathways and neurogenic transcription factors. Recent studies suggest that microRNAs, a group of highly conserved noncoding regulatory small RNAs also play essential roles in neural development and neuronal function. A part of their action in the developing nervous system is to regulate subunit compositions of BAF complexes (ATP-dependent chromatin remodeling complexes), which appear to have dedicated functions during neural development. Intriguingly, ectopic expression of a set of brain-enriched microRNAs, miR-9/9* and miR-124 that promote the assembly of neuron-specific BAF complexes, converts the nonneuronal fate of human dermal fibroblasts towards postmitotic neurons, thereby revealing a previously unappreciated instructive role of these microRNAs. In addition to these global effects, accumulating evidence indicates that many microRNAs could also function locally, such as at the growth cone or at synapses modulating synaptic activity and neuronal connectivity. Here we discuss some of the recent findings about microRNAs' activity in regulating various developmental stages of neurons.

PMID: 23374323 [PubMed - indexed for MEDLINE]

All's well that ends well: alternative polyadenylation and its implications for stem cell biology.

Curr Opin Cell Biol. 2013 Apr;25(2):222-32

Authors: Mueller AA, Cheung TH, Rando TA

Abstract
Stem cell quiescence, activation, and differentiation are governed by a complex network of molecular pathways. There has been a growing recognition that posttranscriptional modifications, such as alternative polyadenylation (APA) of transcripts, play an important role in regulating gene expression and function. Recent analyses of stem cell populations have suggested that APA controls stem cell fate and behavior. Here, we review recent developments that have shaped our understanding of the control of stem cell behavior by APA and we highlight promising areas for future investigation.

PMID: 23357469 [PubMed - indexed for MEDLINE]

Pitfalls of drug development: lessons learned from trials of denufosol in cystic fibrosis.

J Pediatr. 2013 Apr;162(4):676-80

Authors: Moss RB

PMID: 23290508 [PubMed - indexed for MEDLINE]

Usefulness of the addition of beta-2-microglobulin, cystatin C and C-reactive protein to an established risk factors model to improve mortality risk prediction in patients undergoing coronary angiography.

Am J Cardiol. 2013 Mar 15;111(6):851-6

Authors: Nead KT, Zhou MJ, Caceres RD, Sharp SJ, Wehner MR, Olin JW, Cooke JP, Leeper NJ

Abstract
Evidence-based therapies are available to reduce the risk for death from cardiovascular disease, yet many patients go untreated. Novel methods are needed to identify those at highest risk for cardiovascular death. In this study, the biomarkers β2-microglobulin, cystatin C, and C-reactive protein were measured at baseline in a cohort of participants who underwent coronary angiography. Adjusted Cox proportional-hazards models were used to determine whether the biomarkers predicted all-cause and cardiovascular mortality. Additionally, improvements in risk reclassification and discrimination were evaluated by calculating the net reclassification improvement, C-index, and integrated discrimination improvement with the addition of the biomarkers to a baseline model of risk factors for cardiovascular disease and death. During a median follow-up period of 5.6 years, there were 78 deaths among 470 participants. All biomarkers independently predicted future all-cause and cardiovascular mortality. A significant improvement in risk reclassification was observed for all-cause (net reclassification improvement 35.8%, p = 0.004) and cardiovascular (net reclassification improvement 61.9%, p = 0.008) mortality compared to the baseline risk factors model. Additionally, there was significantly increased risk discrimination with C-indexes of 0.777 (change in C-index 0.057, 95% confidence interval 0.016 to 0.097) and 0.826 (change in C-index 0.071, 95% confidence interval 0.010 to 0.133) for all-cause and cardiovascular mortality, respectively. Improvements in risk discrimination were further supported using the integrated discrimination improvement index. In conclusion, this study provides evidence that β2-microglobulin, cystatin C, and C-reactive protein predict mortality and improve risk reclassification and discrimination for a high-risk cohort of patients who undergo coronary angiography.

PMID: 23290308 [PubMed - indexed for MEDLINE]

Cytotopic localization by long noncoding RNAs.

Curr Opin Cell Biol. 2013 Apr;25(2):195-9

Authors: Batista PJ, Chang HY

Abstract
Cells are highly organized structures. In addition to membrane delimited organelles, proteins and RNAs can organize themselves into specific domains. Some examples include stress granules and subnuclear bodies. This level of organization is essential for the correct execution of multiple processes in the cell, ranging from cell signaling to assembly of structures such as the ribosomes. Here we will review evidence that noncoding RNAs play a critical role in the establishment and regulation of these domains. The unique abilities of RNA to mark the genome in a gene-specific and condition-specific manner and to serve as tethers nominate them as ideal molecular address codes.

PMID: 23279909 [PubMed - indexed for MEDLINE]

Relation of B-type natriuretic peptide level in heart failure to sudden cardiac death in patients with and without QT interval prolongation.

Am J Cardiol. 2013 Mar 15;111(6):886-90

Authors: Vrtovec B, Knezevic I, Poglajen G, Sebestjen M, Okrajsek R, Haddad F

Abstract
Increased levels of B-type natriuretic peptide (BNP) are associated with prolongation of the action potential in ventricular myocardium. We investigated the relation of a BNP increase, QT interval, and sudden cardiac death (SCD) in the presence of heart failure (HF). We enrolled 398 patients with HF, New York Heart Association class III or IV, and left ventricular ejection fraction <40%. At baseline and after 3 months, we measured BNP and the QT interval. A BNP increase was defined as a change in BNP of ≥+10%. The QTc interval was calculated using the Bazett formula. QTc interval prolongation was defined as a change in QTc of ≥+10%. The patients were followed up for 1 year. During a 3-month period, BNP increased significantly in 53% of the patients (group 1) and did not in 47% (group 2). During the same period, the QTc interval was more prolonged in group 1 (+44 ± 12 ms) than in group 2 (+7 ± 6 ms; p = 0.01). During 1 year of follow-up, 20 patients died suddenly (SCD), 16 from pump failure. Although the SCD rates did not differ between the 2 groups (5.7% in group 1 vs 4.2% in group 2, p = 0.53), they were significantly greater in the patients in group 1 with QTc interval prolongation ≥+10% (13.8%, p <0.001). The Kaplan-Meier-derived SCD-free survival rates were 2.9 times greater in patients without QTc interval prolongation than in those with prolonged QTc (p <0.001). QTc interval prolongation was an independent correlate of SCD (p = 0.006), but BNP increase was not (p = 0.32). In conclusion, a BNP increase in patients with HF was associated with an increased risk of SCD only in patients with QTc interval prolongation.

PMID: 23273526 [PubMed - indexed for MEDLINE]

Barriers to faculty pedagogical change: lack of training, time, incentives, and...tensions with professional identity?

CBE Life Sci Educ. 2012;11(4):339-46

Authors: Brownell SE, Tanner KD

PMID: 23222828 [PubMed - indexed for MEDLINE]

Aflibercept in lung cancer.

Expert Opin Biol Ther. 2013 Jan;13(1):115-20

Authors: Neal JW, Wakelee HA

Abstract
INTRODUCTION: Angiogenesis, the recruitment and growth of blood vessels, is a process central to the growth of solid tumors. One of the key mediators of angiogenesis is the vascular endothelial growth factor (VEGF) family of ligands. An antibody to VEGF-A, bevacizumab, has demonstrated a survival benefit in conjunction with platinum-based doublet chemotherapy in non-small-cell lung cancer (NSCLC). Aflibercept (VEGF Trap) is a recombinant VEGF receptor-antibody protein fusion with higher affinity for VEGF-A than bevacizumab, plus affinity for VEGF-B and placental growth factor (PlGF). AREAS COVERED: This article reviews recent clinical trials investigating the role of aflibercept in the treatment of lung cancer, both published in the literature and those for which preliminary data have been presented at major scientific meetings. EXPERT OPINION: Aflibercept has proven Phase III efficacy in metastatic colorectal cancer, but in lung cancer, large clinical trials have not yielded positive results. There remains hope that identification of biomarkers of response will one day help select patients most likely to benefit from antiangiogenesis therapy.

PMID: 23199019 [PubMed - indexed for MEDLINE]

Sequence-specific crosslinking of electrospun, elastin-like protein preserves bioactivity and native-like mechanics.

Adv Healthc Mater. 2013 Jan;2(1):114-8

Authors: Benitez PL, Sweet JA, Fink H, Chennazhi KP, Nair SV, Enejder A, Heilshorn SC

PMID: 23184558 [PubMed - indexed for MEDLINE]

Evaluation of solution-processable carbon-based electrodes for all-carbon solar cells.

ACS Nano. 2012 Nov 27;6(11):10384-95

Authors: Ramuz MP, Vosgueritchian M, Wei P, Wang C, Gao Y, Wu Y, Chen Y, Bao Z

Abstract
Carbon allotropes possess unique and interesting physical, chemical, and electronic properties that make them attractive for next-generation electronic devices and solar cells. In this report, we describe our efforts into the fabrication of the first reported all-carbon solar cell in which all components (the anode, active layer, and cathode) are carbon based. First, we evaluate the active layer, on standard electrodes, which is composed of a bilayer of polymer sorted semiconducting single-walled carbon nanotubes and C(60). This carbon-based active layer with a standard indium tin oxide anode and metallic cathode has a maximum power conversion efficiency of 0.46% under AM1.5 Sun illumination. Next, we describe our efforts in replacing the electrodes with carbon-based electrodes, to demonstrate the first all-carbon solar cell, and discuss the remaining challenges associated with this process.

PMID: 23113673 [PubMed - indexed for MEDLINE]

Gold nanorods for ovarian cancer detection with photoacoustic imaging and resection guidance via Raman imaging in living mice.

ACS Nano. 2012 Nov 27;6(11):10366-77

Authors: Jokerst JV, Cole AJ, Van de Sompel D, Gambhir SS

Abstract
Improved imaging approaches are needed for ovarian cancer screening, diagnosis, staging, and resection guidance. Here, we propose a combined photoacoustic (PA)/Raman approach using gold nanorods (GNRs) as a passively targeted molecular imaging agent. GNRs with three different aspect ratios were studied. Those with an aspect ratio of 3.5 were selected for their highest ex vivo and in vivo PA signal and used to image subcutaneous xenografts of the 2008, HEY, and SKOV3 ovarian cancer cell lines in living mice. Maximum PA signal was observed within 3 h for all three lines tested and increased signal persisted for at least two days postadministration. There was a linear relationship (R(2) = 0.95) between the PA signal and the concentration of injected molecular imaging agent with a calculated limit of detection of 0.40 nM GNRs in the 2008 cell line. The same molecular imaging agent could be used for clear visualization of the margin between tumor and normal tissue and tumor debulking via surface-enhanced Raman spectroscopy (SERS) imaging. Finally, we validated the imaging findings with biodistribution data and elemental analysis. To the best of our knowledge, this is the first report of in vivo imaging of ovarian cancer tumors with a photoacoustic and Raman imaging agent.

PMID: 23101432 [PubMed - indexed for MEDLINE]

Measuring grief and depression in seriously ill outpatients using the Palliative Grief Depression Scale.

J Palliat Med. 2012 Dec;15(12):1350-5

Authors: Periyakoil VS, Kraemer HC, Noda A

PMID: 23066859 [PubMed - indexed for MEDLINE]

Atomic force and super-resolution microscopy support a role for LapA as a cell-surface biofilm adhesin of Pseudomonas fluorescens.

Res Microbiol. 2012 Nov-Dec;163(9-10):685-91

Authors: Ivanov IE, Boyd CD, Newell PD, Schwartz ME, Turnbull L, Johnson MS, Whitchurch CB, O'Toole GA, Camesano TA

Abstract
Pseudomonas fluorescence Pf0-1 requires the large repeat protein LapA for stable surface attachment. This study presents direct evidence that LapA is a cell-surface-localized adhesin. Atomic force microscopy (AFM) revealed a significant 2-fold reduction in adhesion force for mutants lacking the LapA protein on the cell surface compared to the wild-type strain. Deletion of lapG, a gene encoding a periplasmic cysteine protease that functions to release LapA from the cell surface, resulted in a 2-fold increase in the force of adhesion. Three-dimensional structured illumination microscopy (3D-SIM) revealed the presence of the LapA protein on the cell surface, consistent with its role as an adhesin. The protein is only visualized in the cytoplasm for a mutant of the ABC transporter responsible for translocating LapA to the cell surface. Together, these data highlight the power of combining the use of AFM and 3D-SIM with genetic studies to demonstrate that LapA, a member of a large group of RTX-like repeat proteins, is a cell-surface adhesin.

PMID: 23064158 [PubMed - indexed for MEDLINE]

The influence of climate change on global crop productivity.

Plant Physiol. 2012 Dec;160(4):1686-97

Authors: Lobell DB, Gourdji SM

PMID: 23054565 [PubMed - indexed for MEDLINE]

Molecular junctions of self-assembled monolayers with conducting polymer contacts.

ACS Nano. 2012 Nov 27;6(11):9920-31

Authors: Neuhausen AB, Hosseini A, Sulpizio JA, Chidsey CE, Goldhaber-Gordon D

Abstract
We present a method to fabricate individually addressable junctions of self-assembled monolayers (SAMs) that builds on previous studies which have shown that soft conductive polymer top contacts virtually eliminate shorts through the SAMs. We demonstrate devices with nanoscale lateral dimensions, representing an order of magnitude reduction in device area, with high yield and relatively low device-to-device variation, improving several features of previous soft contact devices. The devices are formed in pores in an inorganic dielectric layer with features defined by e-beam lithography and dry etching. We replace the aqueous PEDOT:PSS conductive polymer used in prior devices with Aedotron P, a low-viscosity, amphiphilic polymer, allowing incorporation of self-assembled monolayers with either hydrophobic or hydrophilic termination with the same junction geometry and materials. We demonstrate the adaptability of this new design by presenting transport measurements on SAMs composed of alkanethiols with methyl, thiol, carboxyl, and azide terminations. We establish that the observed room-temperature tunnel barrier is primarily a function of monolayer thickness, independent of the terminal group's hydrophilicity. Finally, we investigate the temperature dependence of transport and show that the low-temperature behavior is based on the energy distribution of sites from which carriers can tunnel between the polymer and gold contacts, as described by a model of variable-range hopping transport in a disordered conductor.

PMID: 23035989 [PubMed - indexed for MEDLINE]

Life form and life history explain variation in population processes in a grassland community invaded by exotic plants and mammals.

PLoS One. 2012;7(8):e42906

Authors: Nelis LC

Abstract
The existence of general characteristics of plant invasiveness is still debated. One reason we may not have found these characteristics is because we do not yet understand how processes underlying population dynamics contribute to community composition in invaded communities. Here I modify Ricker stock-recruitment models to parameterize processes important to community dynamics in an invaded grassland community: immigration, maximum intrinsic growth rate, self-regulation, and limitation by other species. I then used the parameterized models in a multi-species stochastic simulation to determine how processes affected long-term community dynamics. By parameterizing the models using the frequency of the 18 most common species in the grassland, I determined that life history and life form are stronger predictors of underlying processes than is native status. Immigration maintains exotic annual grasses and the dominant native perennial grass in the community. Growth rate maintains other perennial species. While the model mirrors the frequency of native species well, exotic species have lower observed than parameterized frequencies, suggesting that they are not reaching their potential frequency. These results, combined with results from past research, suggest that disturbance may be key to maintaining exotic species in the community. Here I showed that a continuous modified Ricker model fit discrete grassland frequency data well. This allowed me to model the dominant species in the community simultaneously and gain insight into the processes that determine community composition.

PMID: 22916178 [PubMed - indexed for MEDLINE]

Fast and accurate read alignment for resequencing.

Bioinformatics. 2012 Sep 15;28(18):2366-73

Authors: Mu JC, Jiang H, Kiani A, Mohiyuddin M, Bani Asadi N, Wong WH

Abstract
MOTIVATION: Next-generation sequence analysis has become an important task both in laboratory and clinical settings. A key stage in the majority sequence analysis workflows, such as resequencing, is the alignment of genomic reads to a reference genome. The accurate alignment of reads with large indels is a computationally challenging task for researchers.
RESULTS: We introduce SeqAlto as a new algorithm for read alignment. For reads longer than or equal to 100 bp, SeqAlto is up to 10 × faster than existing algorithms, while retaining high accuracy and the ability to align reads with large (up to 50 bp) indels. This improvement in efficiency is particularly important in the analysis of future sequencing data where the number of reads approaches many billions. Furthermore, SeqAlto uses less than 8 GB of memory to align against the human genome. SeqAlto is benchmarked against several existing tools with both real and simulated data.
AVAILABILITY: Linux and Mac OS X binaries free for academic use are available at http://www.stanford.edu/group/wonglab/seqalto
CONTACT: whwong@stanford.edu.

PMID: 22811546 [PubMed - indexed for MEDLINE]

CytoSPADE: high-performance analysis and visualization of high-dimensional cytometry data.

Bioinformatics. 2012 Sep 15;28(18):2400-1

Authors: Linderman MD, Bjornson Z, Simonds EF, Qiu P, Bruggner RV, Sheode K, Meng TH, Plevritis SK, Nolan GP

Abstract
MOTIVATION: Recent advances in flow cytometry enable simultaneous single-cell measurement of 30+ surface and intracellular proteins. CytoSPADE is a high-performance implementation of an interface for the Spanning-tree Progression Analysis of Density-normalized Events algorithm for tree-based analysis and visualization of this high-dimensional cytometry data. AVAILABILITY: Source code and binaries are freely available at http://cytospade.org and via Bioconductor version 2.10 onwards for Linux, OSX and Windows. CytoSPADE is implemented in R, C++ and Java. CONTACT: michael.linderman@mssm.edu SUPPLEMENTARY INFORMATION: Additional documentation available at http://cytospade.org.

PMID: 22782546 [PubMed - indexed for MEDLINE]