Shan X. Wang

Abstract

Genetically encoded methods for protein conjugation are of high importance as biological tools. Here we describe the development of a new class of dyes for genetically encoded tagging that add new capabilities for protein reporting and detection via HaloTag methodology. Oligodeoxyfluorosides (ODFs) are short DNA-like oligomers in which the natural nucleic acid bases are replaced by interacting fluorescent chromophores, yielding a broad range of emission colors using a single excitation wavelength. We describe the development of an alkyl halide dehalogenase-compatible chloroalkane linker phosphoramidite derivative that enables the rapid automated synthesis of many possible dyes for protein conjugation. Experiments to test the enzymatic self-conjugation of nine different DNA-like dyes to proteins with HaloTag domains in vitro were performed, and the data confirmed the rapid and efficient covalent labeling of the proteins. Notably, a number of the ODF dyes were found to increase in brightness or change color upon protein conjugation. Tests in mammalian cellular settings revealed that the dyes are functional in multiple cellular contexts, both on the cell surface and within the cytoplasm, allowing protein localization to be imaged in live cells by epifluorescence and laser confocal microscopy.

View details for DOI 10.1021/ja4004393

View details for PubMedID 23590213

Abstract

To investigate the potential association between glaucoma prevalence and supplemental intake, as well as serum levels of vitamins A, C and E.This cross-sectional study included 2912 participants in the 2005-2006 National Health and Nutrition Examination Survey, age ?40 years, who self-reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements during the preceding 30-day period. Participants also underwent serum measurements of vitamins A, C, and E (both alpha- and gamma-tocopherol). Information on the primary outcome measure, presence or absence of glaucoma, as well as demographic information, comorbidities and health-related behaviors, was assessed via interview.Multivariate odds ratios for self-reported glaucoma, comparing the highest quartile of consumption to no consumption, and adjusted for potential confounding variables were 0.48 (95% confidence interval (CI) 0.13-1.82) for vitamin A, 0.47 (95% CI 0.23-0.97) for vitamin C, and 2.59 (95% CI 0.89-7.56) for vitamin E. Adjusted odds ratios for self-reported glaucoma comparing the highest vs lowest quintiles of vitamin serum levels were 1.44 (95% CI 0.79-2.62) for vitamin A, 0.94 (95% CI 0.42-2.11) for vitamin C, 1.40 (95% CI 0.70-2.81) for alpha-tocopherol, and 0.64 (95% CI 0.24-1.70) for gamma-tocopherol.Neither supplementary consumption with nor serum levels of vitamins A and E were found to be associated with glaucoma prevalence. While low- and high-dose supplementary consumption of vitamin C was found to be associated with decreased odds of glaucoma, serum levels of vitamin C did not correlate with glaucoma prevalence.

View details for DOI 10.1038/eye.2013.10

View details for Web of Science ID 000317594000005

View details for PubMedID 23429409

Abstract

Size is among the most important traits of any organism, yet the factors that control its evolution remain poorly understood. In this study, we investigate controls on the evolution of organismal size using a newly compiled database of nearly 25,000 foraminiferan species and subspecies spanning the past 400 million years. We find a transition in the pattern of foraminiferan size evolution from correlation with atmospheric pO2 during the Paleozoic (400-250 million years ago) to long-term stasis during the post-Paleozoic (250 million years ago to present). Thus, a dramatic shift in the evolutionary mode coincides with the most severe biotic catastrophe of the Phanerozoic (543 million years ago to present). Paleozoic tracking of pO2 was confined to Order Fusulinida, whereas Paleozoic lagenides, miliolids, and textulariids were best described by the stasis model. Stasis continued to best describe miliolids and textulariids during post-Paleozoic time, whereas random walk was the best supported mode for the other diverse orders. The shift in evolutionary dynamics thus appears to have resulted primarily from the selective elimination of fusulinids at the end of the Permian Period. These findings illustrate the potential for mass extinction to alter macroevolutionary dynamics for hundreds of millions of years.

View details for DOI 10.1111/j.1558-5646.2012.01807.x

View details for Web of Science ID 000315894800018

View details for PubMedID 23461330

Abstract

We aim to study radiation induced white matter injury in a pre-clinical model using Diffusion tensor MR imaging (DTI). Nineteen 12-week old Sprague-Dawley rats were irradiated to the right hemisphere using a linear accelerator. The dose distribution map was coregistered to the DTI map to generate the actual radiation dose to each white matter tract. Rats underwent longitudinal DTI scans at five time points from 4 to 48 weeks post-radiation with histological evaluations. Fractional anisotropy (FA) of the external capsule, fornix, cerebral peduncle, anterior commissure, optic tract and optic nerve was evaluated. Radiation dose was highest at the ipsilateral external capsule and fornix (29.4 ± 1.3 and 29.8 ± 1.1 Gy, respectively). Optic nerve received 50 % dose to the external capsule and other white matter tracts received 80 % dose. Significantly lower FA was firstly found in the ipsilateral external capsule at 4 weeks post-radiation and in the ipsilateral fornix at 40 weeks post-radiation compared to the contralateral side. Significantly lower FA was found in contralateral optic nerve compared to ipsilateral optic nerve at 48 weeks post-radiation despite ipsilateral optic nerves receiving higher radiation dose than contralateral optic nerve (p = 0.021). No differences were found in other white matter regions until 48 weeks. Histology indicated demyelination, axonal degeneration and coagulative necrosis in all injured white matter. DTI can serve as a promising tool for assessment of radiation induced white matter injury and regional radiosensitivity of white matter tracts.

View details for DOI 10.1007/s11060-012-1031-0

View details for Web of Science ID 000315487900002

View details for PubMedID 23334608

Abstract

Lung cancer incidence is associated with markers of lower socioeconomic status (SES) in whites, blacks, and Asians but with markers of higher SES in Hispanics. The magnitude and etiology of this positive gradient in Hispanics remain undefined. We examined non-small-cell lung cancer (NSCLC) incidence and ever-smoking rates among California Hispanics according to measures of SES.We computed neighborhood (n)SES-specific incidence rates by sex and race or ethnicity for 74,179 NSCLC cases in the California Cancer Registry, 1998-2002. Associations between nSES and NSCLC incidence were examined, using incidence rate ratios and linear trend tests, and stratified by age, stage, and histology. Ever-smoking rates among Hispanics were obtained from California Health Interview Survey 2001 data, and odds ratios for ever-smoking were calculated for measures of SES and acculturation.Compared with the lowest nSES quintile, the NSCLC incidence in the highest quintile was 1.86 and 1.18 times higher for Hispanic women and men, respectively. The positive nSES gradients remained significant for all ages, stages, and nonsquamous histologies in women, and only for older age, local or regional stages, and adenocarcinoma histology in men. Ever-smoking rates were associated with English-speaking households and U.S.-born status for Hispanic women and low education and U.S.-born status for Hispanic men.For California Hispanics, higher nSES was strongly associated with increased NSCLC incidence in women, but weakly associated in men, and ever-smoking rates were strongly correlated with increased acculturation. This finding may portend an increasing burden of NSCLC in Hispanic women, given future trends in acculturation and SES.

View details for DOI 10.1097/JTO.0b013e31827bd7f5

View details for Web of Science ID 000316205600012

View details for PubMedID 23399956

Abstract

Mammalian FCHSD1 and FCHSD2 are homologous proteins containing an amino-terminal F-BAR domain and two SH3 domains near their carboxyl-termini. We report here that FCHSD1 and FCHSD2 are expressed in mouse cochlear sensory hair cells. FCHSD1 mainly localizes to the cuticular plate, whereas FCHSD2 mainly localizes along the stereocilia in a punctuate pattern. Nervous Wreck (Nwk), the Drosophila ortholog of FCHSD1 and FCHSD2, has been shown to bind Wsp and play an important role in F-actin assembly. We show that, like its Drosophila counterpart, FCHSD2 interacts with WASP and N-WASP, the mammalian orthologs of Drosophila Wsp, and stimulates F-actin assembly in vitro. In contrast, FCHSD1 doesn't bind WASP or N-WASP, and can't stimulate F-actin assembly when tested in vitro. We found, however, that FCHSD1 binds via its F-BAR domain to the SH3 domain of Sorting Nexin 9 (SNX9), a well characterized BAR protein that has been shown to promote WASP-Arp2/3-dependent F-actin polymerization. FCHSD1 greatly enhances SNX9's WASP-Arp2/3-dependent F-actin polymerization activity. In hair cells, SNX9 was detected in the cuticular plate, where it colocalizes with FCHSD1. Our results suggest that FCHSD1 and FCHSD2 could modulate F-actin assembly or maintenance in hair cell stereocilia and cuticular plate.

View details for DOI 10.1371/journal.pone.0056516

View details for Web of Science ID 000315184200089

View details for PubMedID 23437151

View details for DOI 10.1103/PhysRevB.87.054104

View details for Web of Science ID 000314681400001

View details for DOI 10.1093/nar/gks1050

View details for Web of Science ID 000312893300075

Abstract

To investigate the association between myopia and the prevalence of glaucoma.This cross-sectional study included 5277 participants from the 2005 to 2008 National Health and Nutrition Examination Survey, greater than or equal to 40 years old, without history of cataract or refractive surgery, who underwent auto-refraction measurement. The predictor was refractive status; emmetropia (-0.99 to +0.99 diopters [D]), mild myopia (-1.00 to -2.99 D), moderate myopia (-3.00 to -5.99 D), severe myopia (> -6.00 D), and hyperopia (> 1.00 D). The outcomes were self-reported glaucoma, vertical cup-to-disc ratio and visual field defects as found on frequency doubling technology (FDT) testingOdds of self-reported glaucoma were not significantly increased in mild (odds ratio [OR] 0.90, confidence interval [CI] 0.56-1.45), moderate (OR 1.40, CI 0.62-3.16), or severe (OR 0.26, CI 0.08-0.80) myopes compared with emmetropes. Odds of vertical cup-to-disc ratio greater than or equal to 0.7 were not significantly increased in mild (OR 0.84, CI 0.31-2.25), moderate (OR 0.37, CI 0.04-3.57), or severe (OR 0.85, CI 0.09-8.42) myopes compared with emmetropes. Odds of any visual field defects were significantly increased in mild (OR 2.02, CI 1.28-3.19), moderate (OR 3.09, CI 1.42-6.72), and severe (OR 14.43, CI 5.13-40.61) myopes compared with emmetropes. The ?(2) test indicated a significant difference (P = 0.001) in the distribution of subjects with each category of visual field status across subjects with each refractive status; the proportion of subjects with worse visual field defects increased with worsening myopia severity.The association between myopia and visual field defects may represent an increased risk of glaucoma among myopes, and the lack of association with self-reported glaucoma may suggest a need for greater glaucoma surveillance in this population.

View details for DOI 10.1167/iovs.12-11158

View details for Web of Science ID 000314338400109

View details for PubMedID 23299483

Abstract

Poor cell survival severely limits the beneficial effects of stem cell therapy for peripheral arterial disease (PAD). This study was designed to investigate the role of mammalian target of rapamycin (mTOR) in the survival and therapeutic function of transplanted murine adipose-derived stromal cells (mADSCs) in a murine PAD model. mADSCs (1.0 × 10(7)) were isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein-positive transgenic mice, intramuscularly implanted into the hind limb of C57BL/6 mice after femoral artery ligation/excision, and monitored using noninvasive bioluminescence imaging (BLI). Although engrafted mADSCs produced antiapoptotic/proangiogenic effects in vivo by modulating the inflammatory and angiogenic cytokine response involving the mTOR pathway, longitudinal BLI revealed progressive death of post-transplant mADSCs within ~4 weeks in the ischemic hind limb. Selectively targeting mTOR complex-1 (mTORC1) using low-dose rapamycin treatment with mADSCs attenuated proinflammatory cytokines (interleukin [IL]-1? and tumor necrosis factor-alpha [TNF-?]) expression and neutrophil/macrophage infiltration, which overtly promoted mADSCs viability and antiapoptotic/proangiogenic efficacy in vivo. However, targeting dual mTORC1/mTORC2 using PP242 or high-dose rapamycin caused IL-1?/TNF-? upregulation and anti-inflammatory IL-10, IL-6, and vascular endothelial growth factor/vascular endothelial growth factor receptor 2 downregulation, undermining the survival and antiapoptotic/proangiogenic action of mADSCs in vivo. Furthermore, low-dose rapamycin abrogated TNF-? secretion by mADSCs and rescued the cells from hypoxia/reoxygenation-induced death in vitro, while PP242 or high-dose rapamycin exerted proinflammatory effects and promoted cell death. In conclusion, mTORC1 and mTORC2 may differentially regulate inflammation and affect transplanted mADSCs' functional survival in ischemic hind limb. These findings uncover that mTOR may evolve into a promising candidate for mechanism-driven approaches to facilitate the translation of cell-based PAD therapy.

View details for DOI 10.1002/stem.1265

View details for Web of Science ID 000312561000020

View details for PubMedID 23081858

Abstract

Pierre Robin sequence (PR) and Treacher Collins syndrome (TC) are congenital disorders associated with multiple craniofacial abnormalities. The mandibular malformations linked with these maladies are closely associated with the form and function of the temporalis muscle. Despite these associations, a paucity of research has been directed at quantifying how these malformations affect the tissues of the temporal region. In this paper, we seek to quantify differences in the temporalis muscle and the temporal fat pad using a novel CT-derived analytic program to examine craniofacial morphomic indices within these patient groups in comparison to normal age-matched controls. We posit that the temporalis muscle and temporal fat pad, like other derivatives of the first branchial arch, are hypoplastic in patients with TC and PR compared to age-matched controls.High-throughput image analysis was used to reconstruct the 3-dimensional (3D) anatomy and quantify morphomic measures of the temporalis muscle and temporal fat pad in children with PR, TC, and age-matched controls. These steps were completed in a semi-automated method using algorithms programmed in MATLAB v13.0. The 3D reconstructions were analyzed in 3 children with PR (6 temporal regions), 3 children with TC (6 temporal regions), and a control group of 19 children (38 temporal regions). We also quantified the same measurements in a localized "core" sample in the area of greatest thickness, providing a more consistent sample of the tissue position. Relationships between the temporal muscle and fat pad values and craniofacial abnormality type were assessed using Wilcoxon nonparametric test using exact distribution, with a P value of less than 0.05 being deemed significant.The mean age of our patients was 6.0 years in PR and 4.5 years in TC cohorts. We were able to establish an automated methodology to quantify the temporalis muscle and temporal fat pad based on CT characteristics. Localized temporalis volume and localized temporalis area were significantly smaller in children with PR than in the control group. Total temporalis fat volume and localized temporalis area were significantly less in children with TC than in the control group. When compared to each other, the PR group had small morphomic values compared to TC group.There are significant morphomic differences in the temporalis muscle and the temporal fat pad in children with either PR or TC when compared to age-matched control group which can be measured from pre-existing CT scans. Specifically, both of these test groups show decreases in the morphomic measures of the temporalis region. The quantification of these changes corroborates and objectifies the clinical findings associated with these congenital deformities while simultaneously allowing for preoperative planning. Furthermore, this finding confirms that the hypoplasia seen in these patient populations is not only hypoplasia of the mandible but also of the surrounding functional matrix, which includes the temporalis muscle and temporal fat pad.

View details for DOI 10.1097/SCS.0b013e3182646411

View details for Web of Science ID 000314853300079

View details for PubMedID 23348276

View details for DOI 10.1016/j.proci.2012.06.108

View details for Web of Science ID 000313125400050

Abstract

Haploidentical stem cell transplantation (SCT) has been generally performed using a T cell depleted (TCD) graft; however, a high rate of nonrelapse mortality (NRM) has been reported, particularly in adult patients. We hypothesized that using a T cell replete (TCR) graft followed by effective posttransplantation immunosuppressive therapy would reduce NRM and improve outcomes. We analyzed 65 consecutive adult patients with hematologic malignancies who received TCR (N = 32) or TCD (N = 33) haploidentical transplants. All patients received a preparative regimen consisting of melphalan, fludarabine, and thiotepa. The TCR group received posttransplantation treatment with cyclophosphamide (Cy), tacrolimus (Tac), and mycophenolate mofetil (MMF). Patients with TCD received antithymocyte globulin followed by infusion of CD34+ selected cells with no posttransplantation immunosuppression. The majority of patients in each group had active disease at the time of transplantation. Outcomes are reported for the TCR and TCD recipients, respectively. Engraftment was achieved in 94% versus 81% (P = NS). NRM at 1 year was 16% versus 42% (P = .02). Actuarial overall survival (OS) and progression-free survival (PFS) rates at 1 year posttransplantation were 64% versus 30% (P = .02) and 50% versus 21% (P = .02). The cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was 20% versus 11% (P = .20), and chronic GVHD (cGVHD) 7% versus 18% (P = .03). Improved reconstitution of T cell subsets and a lower rate of infection were observed in the TCR group. These results indicate that a TCR graft followed by effective control of GVHD posttransplantation may lower NRM and improve survival after haploidentical SCT.

View details for DOI 10.1016/j.bbmt.2012.07.003

View details for Web of Science ID 000311593900010

View details for PubMedID 22796535

Abstract

Colorectal cancer is one of the most common malignant tumors worldwide. Loss of imprinting (LOI) of the insulin-like growth factor 2 (IGF2) gene is an epigenetic abnormality observed in human colorectal neoplasms. Our aim was to investigate the feasibility of using the IGF2 imprinting system for targeted gene therapy of colorectal cancer.We constructed a novel oncolytic adenovirus, Ad315-E1A, and a replication-deficient recombinant adenovirus, Ad315-EGFP, driven by the IGF2 imprinting system by inserting the H19 promoter, CCCTC binding factor, enhancer, human adenovirus early region 1A (E1A) and enhanced green fluorescent protein (EGFP) reporter gene into a pDC-315 shuttle plasmid. Cell lines with IGF2 LOI (HCT-8 and HT-29), which were infected with Ad315-EGFP, produced EGFP. However, no EGFP was produced in cell lines with maintenance of imprinting (HCT116 and GES-1). We found that Ad315-E1A significantly decreased cell viability and induced apoptosis only in LOI cell lines in vitro. In addition, mice bearing HCT-8-xenografted tumors, which received intratumoral administration of the oncolytic adenovirus, showed significantly reduced tumor growth and enhanced survival.Our recombinant oncolytic virus targeting the IGF2 LOI system inhibits LOI cell growth in vitro and in vivo, and provides a novel approach for targeted gene therapy.

View details for DOI 10.1186/1476-4598-11-86

View details for Web of Science ID 000314051700001

View details for PubMedID 23171475

Abstract

DNA damage and repair are hallmarks of cellular responses to ionizing radiation. We hypothesized that monitoring the expression of DNA repair-associated genes would enhance the detection of individuals exposed to radiation versus other forms of physiological stress. We employed the human blood ex vivo radiation model to investigate the expression responses of DNA repair genes in repeated blood samples from healthy, non-smoking men and women exposed to 2 Gy of X-rays in the context of inflammation stress mimicked by the bacterial endotoxin lipopolysaccharide (LPS). Radiation exposure significantly modulated the transcript expression of 12 genes of 40 tested (2.2E-06

View details for DOI 10.1371/journal.pone.0048619

View details for Web of Science ID 000311935800084

View details for PubMedID 23144912

Abstract

We report a magneto-nanosensor biochip for fungal detection. The chip is made of arrays of giant magnetoresistive (GMR) spin-valve sensors, and is able to detect protein biomarkers at low concentrations in solutions. As a demonstration, a standard curve for fungal pathogen Asp f 1 was obtained by measuring signals from various concentrations of Asp f 1 spiked in PBS solutions, indicating a detection limit of ~100 pg/ml. Five positive and negative Asp f 1 solution samples were discriminated correctly in blind experiments. Our data suggest that the magneto-nanosensor biochips are very promising as sensitive diagnostic devices for fungal pathogens. Given the generality of the detection scheme used in the magneto-nanosensor, we anticipate that the platform will be very useful for the detection of many types of biomarkers.

View details for DOI 10.1109/TMAG.2012.2195163

View details for Web of Science ID 000310194400137

View details for PubMedID 23494403

View details for DOI 10.1116/1.4759260

View details for Web of Science ID 000311458500002

Abstract

Advanced sensing and measurement techniques are key technologies to realize a smart grid. The giant magnetoresistance (GMR) effect has revolutionized the fields of data storage and magnetic measurement. In this work, a design of a GMR current sensor based on a commercial analog GMR chip for applications in a smart grid is presented and discussed. Static, dynamic and thermal properties of the sensor were characterized. The characterizations showed that in the operation range from 0 to ±5 A, the sensor had a sensitivity of 28 mV·A(-1), linearity of 99.97%, maximum deviation of 2.717%, frequency response of ?1.5 dB at 10 kHz current measurement, and maximum change of the amplitude response of 0.0335%·°C(-1) with thermal compensation. In the distributed real-time measurement and monitoring of a smart grid system, the GMR current sensor shows excellent performance and is cost effective, making it suitable for applications such as steady-state and transient-state monitoring. With the advantages of having a high sensitivity, high linearity, small volume, low cost, and simple structure, the GMR current sensor is promising for the measurement and monitoring of smart grids.

View details for DOI 10.3390/s121115520

View details for Web of Science ID 000311429500064

View details for PubMedID 23202221

Abstract

There is evidence across several species for genetic control of phenotypic variation of complex traits, such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using ?170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of ?0.5?kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI, possibly mediated by DNA methylation. Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.

View details for DOI 10.1038/nature11401

View details for Web of Science ID 000309733300051

View details for PubMedID 22982992

Abstract

This study aims to evaluate (64)Cu-DOTA-rituximab (PETRIT) in a preclinical transgenic mouse model expressing human CD20 for potential clinical translation.(64)Cu was chelated to DOTA-rituximab. Multiple radiolabeling, quality assurance, and imaging experiments were performed. The human CD20 antigen was expressed in B cells of transgenic mice (CD20TM). The mice groups studied were: (a) control (nude mice, n?=?3) that received 7.4 MBq/dose, (b) with pre-dose (CD20TM, n?=?6) received 2 mg/kg pre-dose of cold rituximab prior to PETRIT of 7.4 MBq/dose, and (c) without pre-dose (CD20TM, n?=?6) PETRIT alone received 7.4 MBq/dose. Small animal PET was used to image mice at various time points (0, 1, 2, 4, 24, 48, and 72 h). The OLINDA/EXM software was used to determine the human equivalent dose for individual organs.PETRIT was obtained with a specific activity of 545?±?38.91 MBq/nmole, radiochemical purity >95%, and immunoreactivity >75%. At 24 h, spleenic uptake of PETRIT%ID/g (mean?±?STD) with and without pre-dose was 1.76?±?0.43% and 16.5?±?0.45%, respectively (P value?=?0.01). Liver uptake with and without pre-dose was 0.41?±?0.51% and 0.52?±?0.17% (P value?=?0.86), respectively. The human equivalents of highest dose organs with and without pre-dose are osteogenic cells at 30.8?±?0.4 ?Sv/MBq and the spleen at 99?±?4 ?Sv/MBq, respectively.PET imaging with PETRIT in huCD20 transgenic mice provided human dosimetry data for eventual applications in non-Hodgkins lymphoma patients.

View details for DOI 10.1007/s11307-011-0537-8

View details for Web of Science ID 000308819300011

View details for PubMedID 22231277

View details for DOI 10.5061/dryad.3rp1p

View details for Web of Science ID 000309197500008

View details for DOI 10.1002/aenm.201200022

View details for Web of Science ID 000309595900014

View details for DOI 10.1016/j.jct.2012.04.028

View details for Web of Science ID 000305346100019

View details for DOI 10.1103/PhysRevB.86.094407

View details for Web of Science ID 000308392400002

Abstract

To investigate the prevalence of and risk factors for depression among participants with glaucoma and the predictive value of glaucoma for depression.Cross-sectional study.This study included 6760 participants in the National Health and Nutrition Examination Survey (NHANES) between 2005 and 2008, aged ?40 years, who reported a presence or absence of glaucoma. Demographic and disease-related information was obtained by interview. Self-reported measures of vision were ascertained via items from the Visual Function Questionnaire (VFQ-25). Participants underwent visual acuity examination, fundus photography, and visual field testing with screening frequency-doubling technology (FDT N-30-5). The main outcome was presence of depression, as determined by a score ?10 on the Patient Health Questionnaire-9 (PHQ-9).Prevalence of depression among participants with and without glaucoma was 10.9% (SEM 2.2%) and 6.9% (SEM 0.62%), respectively. While the presence of glaucoma was significantly associated with depression after adjustment for demographic factors (OR 1.80, 95% CI 1.16-2.79), this association was not significant after adjustment for self-reported general health condition (OR 1.35, 95% CI 0.822-2.23). Among participants with glaucoma, objective measures of glaucoma severity were not significant predictors for depression. However, several self-reported measures of visual function were significantly associated with depression.Glaucoma is a significant predictor of depression after adjustment for demographic factors and multiple comorbidities, but not after adjustment for self-reported general health condition. Among participants with glaucoma, self-reported measures of vision were significant risk factors for depression, whereas objective measures of vision were not.

View details for DOI 10.1016/j.ajo.2012.03.039

View details for Web of Science ID 000308115600005

View details for PubMedID 22789562

Abstract

Oncogenes, which are essential for tumor initiation, development, and maintenance, are valuable targets for cancer therapy. However, it remains a challenge to effectively inhibit oncogene activity by targeting their downstream pathways without causing significant toxicity to normal tissues. Here we show that deletion of mir-181a-1/b-1 expression inhibits the development of Notch1 oncogene-induced T cell acute lymphoblastic leukemia (T-ALL). mir-181a-1/b-1 controls the strength and threshold of Notch activity in tumorigenesis in part by dampening multiple negative feedback regulators downstream of NOTCH and pre-T cell receptor (TCR) signaling pathways. Importantly, although Notch oncogenes utilize normal thymic progenitor cell genetic programs for tumor transformation, comparative analyses of mir-181a-1/b-1 function in normal thymocyte and tumor development demonstrate that mir-181a-1/b-1 can be specifically targeted to inhibit tumor development with little toxicity to normal development. Finally, we demonstrate that mir-181a-1/b-1, but not mir-181a-2b-2 and mir-181-c/d, controls the development of normal thymic T cells and leukemia cells. Together, these results illustrate that NOTCH oncogene activity in tumor development can be selectively inhibited by targeting the molecular networks controlled by mir-181a-1/b-1.

View details for DOI 10.1371/journal.pgen.1002855

View details for Web of Science ID 000308529300016

View details for PubMedID 22916024

Abstract

Early detection and targeted therapy are two major challenges in the battle against cancer. Novel imaging contrast agents and targeting approaches are greatly needed to improve the sensitivity and specificity of cancer theranostic agents. Here, we implemented a novel approach using a magnetic micromesh and biocompatible fluorescent magnetic nanoparticles (FMN) to magnetically enhance cancer targeting in living subjects. This approach enables magnetic targeting of systemically administered individual FMN, containing a single 8 nm superparamagnetic iron oxide core. Using a human glioblastoma mouse model, we show that nanoparticles can be magnetically retained in both the tumor neovasculature and surrounding tumor tissues. Magnetic accumulation of nanoparticles within the neovasculature was observable by fluorescence intravital microscopy in real time. Finally, we demonstrate that such magnetically enhanced cancer targeting augments the biological functions of molecules linked to the nanoparticle surface.

View details for DOI 10.1021/nn301670a

View details for Web of Science ID 000307988900039

View details for PubMedID 22857784

Abstract

DNA damage as a result of environmental stress is recognized by sensor proteins that trigger repair mechanisms, or, if repair is unsuccessful, initiate apoptosis. Defects in DNA damage-induced apoptosis promote genomic instability and tumourigenesis. The protein ataxia-telangiectasia mutated (ATM) is activated by DNA double-strand breaks and regulates apoptosis via p53. Here we show that FOXO3 interacts with the ATM-Chk2-p53 complex, augments phosphorylation of the complex and induces the formation of nuclear foci in cells on DNA damage. FOXO3 is essential for DNA damage-induced apoptosis and conversely FOXO3 requires ATM, Chk2 and phosphorylated p53 isoforms to trigger apoptosis as a result of DNA damage. Under these conditions FOXO3 may also have a role in regulating chromatin retention of phosphorylated p53. These results suggest an essential link between FOXO3 and the ATM-Chk2-p53-mediated apoptotic programme following DNA damage.

View details for DOI 10.1038/ncomms2008

View details for Web of Science ID 000308801100016

View details for PubMedID 22893124

View details for DOI 10.2138/am.2012.4001

View details for Web of Science ID 000307415100018

View details for DOI 10.1167/iovs.12-10433

View details for Web of Science ID 000307096400073

Abstract

Heterotopic ossification (HO), or the abnormal development of bone tissue in soft-tissue locations, can be physically debilitating and clinically devastating. For unclear reasons, HO is highly associated with burn injury. The objective of this review is to summarize 1) cells that are responsible for HO, 2) in vitro and in vivo models of HO and how they have contributed to our current knowledge of the disease process, 3) the effects of the adipose compartment on HO, 4) the effects of inflammation on HO, and 5) the effects of mesenchymal stem cells (MSCs) on HO. Preclinical models of HO suggest several possible mechanisms for the development of this pathologic process, including progenitor cell differentiation and paracrine modulation of local inflammatory responses. Further studies are needed to elucidate the molecular mechanisms driving HO so that targeted therapies can be developed. Current literature supports a role for MSCs in modulating heterotopic bone formation, and direct manipulation of MSCs might one day be used to prevent and treat HO.

View details for DOI 10.1097/BCR.0b013e31825af547

View details for Web of Science ID 000306275000013

View details for PubMedID 22683987

Abstract

Gut microbial induction of host immune maturation exemplifies host-microbe mutualism. We colonized germ-free (GF) mice with mouse microbiota (MMb) or human microbiota (HMb) to determine whether small intestinal immune maturation depends on a coevolved host-specific microbiota. Gut bacterial numbers and phylum abundance were similar in MMb and HMb mice, but bacterial species differed, especially the Firmicutes. HMb mouse intestines had low levels of CD4(+) and CD8(+) T cells, few proliferating T cells, few dendritic cells, and low antimicrobial peptide expression--all characteristics of GF mice. Rat microbiota also failed to fully expand intestinal T cell numbers in mice. Colonizing GF or HMb mice with mouse-segmented filamentous bacteria (SFB) partially restored T cell numbers, suggesting that SFB and other MMb organisms are required for full immune maturation in mice. Importantly, MMb conferred better protection against Salmonella infection than HMb. A host-specific microbiota appears to be critical for a healthy immune system.

View details for DOI 10.1016/j.cell.2012.04.037

View details for Web of Science ID 000305753800022

View details for PubMedID 22726443

View details for DOI 10.1029/2011JB008808

View details for Web of Science ID 000305156700003

Abstract

Both LMO2 (LIM domain only 2) mRNA and protein expression in diffuse large B-cell lymphoma (DLBCL) have been associated with superior survival. However, a role for germline genetic variation in LMO2 has not been previously reported. Immunohistochemistry (IHC) for LMO2 was conducted on tumor tissue from diagnostic biopsies, and 20 tag single nucleotide polymorphisms (SNPs) from LMO2 were genotyped from germline DNA. LMO2 IHC positivity was associated with superior survival (hazard ratio [HR] = 0.55; 95% confidence interval [CI] 0.31-0.97). Four LMO2 SNPs (rs10836127, rs941940, rs750781, rs1885524) were associated with survival after adjusting for LMO2 IHC and clinical factors (p < 0.05), and one of these SNPs (rs941940) was also associated with IHC positivity (p = 0.02). Compared to a model with clinical factors only (c-statistic = 0.676), adding the four SNPs (c-statistic = 0.751) or LMO2 IHC (c-statistic = 0.691) increased the predictive ability of the model, while inclusion of all three factors (c-statistic = 0.754) did not meaningfully add predictive ability above a model with clinical factors and the four SNPs. In conclusion, germline genetic variation in LMO2 was associated with DLBCL prognosis and provided slightly stronger predictive ability relative to LMO2 IHC status.

View details for DOI 10.3109/10428194.2011.638717

View details for Web of Science ID 000304311500016

View details for PubMedID 22066713

Abstract

Recently, hybrid Si/organic solar cells have been studied for low-cost Si photovoltaic devices because the Schottky junction between the Si and organic material can be formed by solution processes at a low temperature. In this study, we demonstrate a hybrid solar cell composed of Si nanocones and conductive polymer. The optimal nanocone structure with an aspect ratio (height/diameter of a nanocone) less than two allowed for conformal polymer surface coverage via spin-coating while also providing both excellent antireflection and light trapping properties. The uniform heterojunction over the nanocones with enhanced light absorption resulted in a power conversion efficiency above 11%. Based on our simulation study, the optimal nanocone structures for a 10 ?m thick Si solar cell can achieve a short-circuit current density, up to 39.1 mA/cm(2), which is very close to the theoretical limit. With very thin material and inexpensive processing, hybrid Si nanocone/polymer solar cells are promising as an economically viable alternative energy solution.

View details for DOI 10.1021/nl300713x

View details for Web of Science ID 000305106400054

View details for PubMedID 22545674

Abstract

Ghrelin is a well-characterized hormone that has protective effects on endothelial cells. Elevated HCY (homocysteine) can be a cardiovascular risk factor, but it is not known whether ghrelin can inhibit HCY-induced dysfunction and inflammatory response in rat CMECs (cardiac microvascular endothelial cells). We found that HCY treatment for 24 h inhibited proliferation and NO (nitric oxide) secretion, but with increased cell apoptosis and secretion of cytokines in CMECs. In contrast, ghrelin pretreatment significantly improved proliferation and NO secretion, and inhibited cell apoptosis and secretion of cytokines in HCY-induced CMECs. In addition, Western blot assay showed that NF-?B (nuclear factor ?B) and cleaved-caspase 3 expression were elevated, and PCNA (proliferating cell nuclear antigen) and eNOS (endothelial nitric oxide synthase) expression were decreased after treatment with HCY, which was significantly reversed by pretreatment with ghrelin. The data suggest that ghrelin inhibits HCY-induced CMEC dysfunction and inflammatory response, probably mediated by inhibition of NF-?B activation.

View details for DOI 10.1042/CBI20110235

View details for Web of Science ID 000305113500002

View details for PubMedID 22339616

Abstract

We report a general scheme to systematically construct two classes of structural families of superhard sp(3) carbon allotropes of cold-compressed graphite through the topological analysis of odd 5+7 or even 4+8 membered carbon rings stemmed from the stacking of zigzag and armchair chains. Our results show that the previously proposed M, bct-C(4), W and Z allotropes belong to our currently proposed families and that depending on the topological arrangement of the native carbon rings numerous other members are found that can help us understand the structural phase transformation of cold-compressed graphite and carbon nanotubes (CNTs). In particular, we predict the existence of two simple allotropes, R and P carbon, which match well the experimental x-ray diffraction patterns of cold-compressed graphite and CNTs, respectively, display a transparent wide-gap insulator ground state and possess a large Vickers hardness comparable to diamond.

View details for DOI 10.1103/PhysRevLett.108.135501

View details for Web of Science ID 000302019600007

View details for PubMedID 22540712

Abstract

The regulation of cell shape is a common challenge faced by organisms across all biological kingdoms. In nearly all bacteria, cell shape is determined by the architecture of the peptidoglycan cell wall, a macromolecule consisting of glycan strands crosslinked by peptides. In addition to shape, cell growth must also maintain the wall structural integrity to prevent lysis due to large turgor pressures. Robustness can be accomplished by establishing a globally ordered cell-wall network, although how a bacterium generates and maintains peptidoglycan order on the micron scale using nanometer-sized proteins remains a mystery. Here, we demonstrate that left-handed chirality of the MreB cytoskeleton in the rod-shaped bacterium Escherichia coli gives rise to a global, right-handed chiral ordering of the cell wall. Local, MreB-guided insertion of material into the peptidoglycan network naturally orders the glycan strands and causes cells to twist left-handedly during elongational growth. Through comparison with the right-handed twisting of Bacillus subtilis cells, our work supports a common mechanism linking helical insertion and chiral cell-wall ordering in rod-shaped bacteria. These physical principles of cell growth link the molecular structure of the bacterial cytoskeleton, mechanisms of wall synthesis, and the coordination of cell-wall architecture.

View details for DOI 10.1073/pnas.1117132109

View details for Web of Science ID 000301117700005

View details for PubMedID 22343529

View details for DOI 10.1088/2041-8205/745/2/L17

View details for Web of Science ID 000300228800002

Abstract

To investigate the relationship between supplementary consumption of the oxidants calcium and iron and the prevalence of glaucoma.This cross-sectional study included 3833 participants in the National Health and Nutrition Examination Survey (NHANES) for 2007 and 2008, ? 40 years of age, who reported a presence or absence of glaucoma. Participants were interviewed regarding the use of dietary supplements and antacids during the preceding 30-day period. Data pertaining to the supplementary intake of calcium and iron was aggregated and divided into quintiles. Information regarding the presence or absence of glaucoma and demographics, comorbidities, and health-related behavior was obtained via interview.Participants who consumed ? 800 mg/d of supplementary calcium or ? 18 mg/d of supplementary iron had significantly higher odds of having been diagnosed with glaucoma than did those who had not consumed supplementary calcium or iron, after adjustment for potential confounders (odds ratio [OR] 2.44, 95% confidence interval [CI] 1.25-4.76 for calcium; OR 3.80, 95% CI 1.79-8.06 for iron). Concurrent consumption of both calcium and iron above these levels was associated with still greater odds of having been diagnosed with glaucoma (OR 7.24, 95% CI 2.42-21.62). A clear dose-response relationship between quintiles of supplementary calcium or iron intake and glaucoma prevalence was not found.These results suggest that there may be a threshold intake of iron and calcium above which there is an increased risk of development of glaucoma. Prospective longitudinal studies are needed, to assess whether oxidant intake is a risk factor for development and progression of glaucoma.

View details for DOI 10.1167/iovs.11-9038

View details for Web of Science ID 000302788600024

View details for PubMedID 22247455

Abstract

We report the fluorogenic detection of the product of base excision repair (an abasic site) in a specific sequence of duplex DNA. This is achieved by DNA-templated chemistry, employing triple helix-forming probes that contain unnatural nucleobases designed to selectively recognize the site of a missing base. Light-up signals of up to 36-fold were documented, and probes could be used to monitor enzymatic removal of a damaged base.

View details for DOI 10.1039/c2cc34060g

View details for Web of Science ID 000306573800008

View details for PubMedID 22782065

View details for DOI 10.1063/1.3672835

View details for Web of Science ID 000299127200058

View details for DOI 10.1002/anie.201108135

View details for Web of Science ID 000299946400036

View details for PubMedID 22241823

Abstract

Dye-ing to live: Spectral limitations of common organic dyes make it difficult or impossible to visualize and follow multiple biological components in rapidly moving systems. The development of a multispectral set of improved DNA-scaffolded fluorophores is described. Their use in multicolor cellular imaging (see scheme) and in tracking of biological motions on the subsecond timescale is demonstrated.

View details for DOI 10.1002/anie.201201928

View details for Web of Science ID 000306314300020

View details for PubMedID 22684777

Abstract

Despite differences in the crystal structures of ice and nucleosides, antifreeze polypeptides (AFPs) have been demonstrated to inhibit nucleation of 5-methyluridine, cytidine, and inosine and modify the crystal growth of the nucleosides efficiently. The molecular recognition repertoire of AFPs has been expanded to non-ice-like crystalline solids.

View details for DOI 10.1039/c2cc36264c

View details for Web of Science ID 000310459400019

View details for PubMedID 23089878

View details for DOI 10.1093/nar/gkr1028

View details for Web of Science ID 000298601300084

View details for DOI 10.1140/epjc/s10052-011-1795-y

View details for Web of Science ID 000297706700015

Abstract

Antifreeze proteins (AFPs) found in many organisms can noncolligatively lower the freezing point of water without altering the melting point. The difference between the depressed freezing point and the melting point, termed thermal hysteresis (TH), is usually a measure of the antifreeze activity of AFPs. Certain low molecular mass molecules and proteins can further enhance the antifreeze activity of AFPs. Interaction between an enhancer and arginine is known to play an important role in enhancing the antifreeze activity of an AFP from the beetle Dendroides canadensis (DAFP-1). Here, we examined the enhancement effects of several prevalent phosphate-containing coenzymes on the antifreeze activity of DAFP-1. ?-Nicotinamide adenine dinucleotide (reduced) (NADH) is identified as the most efficient enhancer of DAFP-1, which increases the antifreeze activity of DAFP-1 by around 10 times. Examination of the enhancement abilities of a series of NADH analogs and various molecular fragments of NADH reveals that the modifications of nicotinamide generate a series of highly efficient enhancers, though none as effective as NADH itself, and the whole molecular structure of NADH is necessary for its highly efficient enhancement effect. We also demonstrated a 1:1 binding between DAFP-1 and NADH. The binding was characterized by high-performance liquid chromatography (HPLC) using the gel filtration method of Hummel and Dreyer. The data analysis suggests binding between DAFP-1 and NADH with a dissociation constant in the micromolar range. Interactions between DAFP-1 and NADH are discussed along with molecular mechanisms of enhancer action.

View details for DOI 10.1002/jmr.1151

View details for Web of Science ID 000298599500014

View details for PubMedID 22038809

Abstract

Bacterial cells possess multiple cytoskeletal proteins involved in a wide range of cellular processes. These cytoskeletal proteins are dynamic, but the driving forces and cellular functions of these dynamics remain poorly understood. Eukaryotic cytoskeletal dynamics are often driven by motor proteins, but in bacteria no motors that drive cytoskeletal motion have been identified to date. Here, we quantitatively study the dynamics of the Escherichia coli actin homolog MreB, which is essential for the maintenance of rod-like cell shape in bacteria. We find that MreB rotates around the long axis of the cell in a persistent manner. Whereas previous studies have suggested that MreB dynamics are driven by its own polymerization, we show that MreB rotation does not depend on its own polymerization but rather requires the assembly of the peptidoglycan cell wall. The cell-wall synthesis machinery thus either constitutes a novel type of extracellular motor that exerts force on cytoplasmic MreB, or is indirectly required for an as-yet-unidentified motor. Biophysical simulations suggest that one function of MreB rotation is to ensure a uniform distribution of new peptidoglycan insertion sites, a necessary condition to maintain rod shape during growth. These findings both broaden the view of cytoskeletal motors and deepen our understanding of the physical basis of bacterial morphogenesis.

View details for DOI 10.1073/pnas.1108999108

View details for Web of Science ID 000295030000036

View details for PubMedID 21903929

Abstract

To lend clarity to inconsistent prior findings of an inverse association between ultraviolet radiation (UVR) exposure and risk of lymphoid malignancies, we examined the association of prospectively ascertained residential ambient UVR exposure with risk of non-Hodgkin lymphomas (NHLs), multiple myeloma (MM), and classical Hodgkin lymphoma in the California Teachers Study cohort. Among 121 216 eligible women, 629 were diagnosed with NHL, 119 with MM, and 38 with Hodgkin lymphoma between 1995-1996 and 2007. Cox proportional hazards regression was used to estimate incidence rate ratios (RRs) with 95% confidence intervals (CIs). Residential UVR levels within a 20-km radius were associated with reduced risk of overall NHL (RR for highest vs lowest statewide quartile of minimum UVR [? 5100 vs < 4915 W-h/m(2)], 0.58; 95% CI, 0.42-0.80), especially diffuse large B-cell lymphoma (RR, 0.36; 95% CI, 0.17-0.78) and chronic lymphocytic leukemia/small lymphocytic lymphoma (RR, 0.46; 95% CI, 0.21-1.01), and MM (RR for maximum UVR, 0.57; 95% CI, 0.36-0.90). These associations were not modified by skin sensitivity to sunlight, race/ethnicity, body mass index, or neighborhood socioeconomic status. Dietary vitamin D also was not associated with risk of lymphoid malignancies. These results support a protective effect of routine residential UVR exposure against lymphomagenesis through mechanisms possibly independent of vitamin D.

View details for DOI 10.1182/blood-2011-02-336065

View details for Web of Science ID 000293787300026

View details for PubMedID 21622649

Abstract

Si nano-well arrays, with precisely controlled undercut Si sidewall profiles and flat bottomed pockets, enable uniform nanoscale pattern transfer from resists to metal deposits without degradation of the initial lithographic resolution, as verified by the formation of arrays of Au nano-dots with 10 nm diameter. An additional functionality of the Si nano-wells as local nano-reactors, where the patterned material is enclosed in a Si pocket during high temperature reaction, is demonstrated by thermally inducing a phase transformation of the as-deposited A1 phase of FePt nano-dots to the high coercivity, chemically ordered L1(0) phase.

View details for DOI 10.1088/0957-4484/22/30/305304

View details for Web of Science ID 000292455300006

View details for PubMedID 21709347

Abstract

The cellular response to double-strand breaks (DSBs) in DNA is a complex signalling network, mobilized by the nuclear protein kinase ataxia-telangiectasia mutated (ATM), which phosphorylates many factors in the various branches of this network. A main question is how ATM regulates DSB repair. Here, we identify the DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) as an ATM target. PNKP phosphorylates 5'-OH and dephosphorylates 3'-phosphate DNA ends that are formed at DSB termini caused by DNA-damaging agents, thereby regenerating legitimate ends for further processing. We establish that the ATM phosphorylation targets on human PNKP-Ser 114 and Ser 126-are crucial for cellular survival following DSB induction and for effective DSB repair, being essential for damage-induced enhancement of the activity of PNKP and its proper accumulation at the sites of DNA damage. These findings show a direct functional link between ATM and the DSB-repair machinery.

View details for DOI 10.1038/embor.2011.96

View details for Web of Science ID 000292325700023

View details for PubMedID 21637298

View details for DOI 10.1007/s11207-011-9791-9

View details for Web of Science ID 000293143100007

Abstract

The strong light-matter interaction within a semiconductor high-Q microcavity has been used to produce half-matter/half-light quasiparticles, exciton-polaritons. The exciton-polaritons have very small effective mass and controllable energy-momentum dispersion relation. These unique properties of polaritons provide the possibility to investigate the fundamental physics including solid-state cavity quantum electrodynamics, and dynamical Bose-Einstein condensates (BECs). Thus far the polariton BEC has been demonstrated using optical excitation. However, from a practical viewpoint, the current injection polariton devices operating at room temperature would be most desirable. Here we report the first realization of a current injection microcavity GaN exciton-polariton light emitting diode (LED) operating under room temperature. The exciton-polariton emission from the LED at photon energy 3.02 eV under strong coupling condition is confirmed through temperature-dependent and angle-resolved electroluminescence spectra.

View details for DOI 10.1021/nl2011164

View details for Web of Science ID 000292849400039

View details for PubMedID 21675759

Abstract

Versatile Brønsted-Evans-Polanyi (BEP) relations are found from density functional theory for a wide range of transition metal oxides including rutiles and perovskites. For oxides, the relation depends on the type of oxide, the active site, and the dissociating molecule. The slope of the BEP relation is strongly coupled to the adsorbate geometry in the transition state. If it is final state-like the dissociative chemisorption energy can be considered as a descriptor for the dissociation. If it is initial state-like, on the other hand, the dissociative chemisorption energy is not suitable as descriptor for the dissociation. Dissociation of molecules with strong intramolecular bonds belong to the former and molecules with weak intramolecular bonds to the latter group. We show, for the prototype system La-perovskites, that there is a "cyclic" behavior in the transition state characteristics upon change of the active transition metal of the oxide.

View details for DOI 10.1063/1.3602323

View details for Web of Science ID 000292331900043

View details for PubMedID 21721645

Abstract

Malignancies of the lymphoid cells, including non-Hodgkin lymphomas (NHL), HL, and multiple myeloma, occur at much lower rates in Asians than other racial/ethnic groups in the United States. It remains unclear whether these deficits are explained by genetic or environmental factors. To better understand environmental contributions, we examined incidence patterns of lymphoid malignancies among populations characterized by ethnicity, birthplace, and residential neighborhood socioeconomic status (SES) and ethnic enclave status.We obtained data about all Asian patients diagnosed with lymphoid malignancies between 1988 and 2004 from the California Cancer Registry and neighborhood characteristics from U.S. Census data.Although incidence rates of most lymphoid malignancies were lower among Asian than white populations, only follicular lymphoma (FL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), and nodular sclerosis (NS) HL rates were statistically significantly lower among foreign-born than U.S.-born Asians with incidence rate ratios ranging from 0.34 to 0.87. Rates of CLL/SLL and NS HL were also lower among Asian women living in ethnic enclaves or lower SES neighborhoods than those living elsewhere.These observations support strong roles of environmental factors in the causation of FL, CLL/SLL, and NS HL.Studying specific lymphoid malignancies in U.S. Asians may provide valuable insight toward understanding their environmental causes.

View details for DOI 10.1158/1055-9965.EPI-11-0038

View details for Web of Science ID 000291308600003

View details for PubMedID 21493873

Abstract

Human embryonic stem cells (hESC) are self-renewing and pluripotent cells that hold great promise. Our objective was to compare the effect of three different embryo culture methods for derivation of human embryonic stem cells from discarded embryos. A prospective and randomized trial was conducted using 381 discarded human embryos at days 2-3 postfertilization in Beijing Obstetrics and Gynecology Hospital IVF center. After removal of the zona pellucida, discarded human embryos were cultured by three different methods as multiple embryo aggregates, single embryo, and blastomeres. Outgrowth of embryos and hESC derivation were observed. The outgrowth rate of embryos cultured as multiple embryo aggregates was higher than that of those cultured as single embryos or blastomeres (p < 0.05). Three propagating hESC lines were derived from poor quality day 2-3 postfertilization nonblastocyst embryos cultured as multiple embryo aggregates. Derived hESC lines expressed hESC-specific markers of pluripotency and had normal diploid karyotype. The cells were able to form derivatives of all three germ layers in vivo as teratomas. Our results demonstrate that culturing these discarded embryos as multiple embryo aggregates was more profitable for outgrowth and derivation of ESC line than culturing these as single embryo or blastomeres.

View details for DOI 10.1089/cell.2010.0092

View details for Web of Science ID 000291205400005

View details for PubMedID 21453052

Abstract

Gravity Probe B, launched 20 April 2004, is a space experiment testing two fundamental predictions of Einstein's theory of general relativity (GR), the geodetic and frame-dragging effects, by means of cryogenic gyroscopes in Earth orbit. Data collection started 28 August 2004 and ended 14 August 2005. Analysis of the data from all four gyroscopes results in a geodetic drift rate of -6601.8±18.3??mas/yr and a frame-dragging drift rate of -37.2±7.2??mas/yr, to be compared with the GR predictions of -6606.1??mas/yr and -39.2??mas/yr, respectively ("mas" is milliarcsecond; 1??mas=4.848×10(-9)??rad).

View details for DOI 10.1103/PhysRevLett.106.221101

View details for Web of Science ID 000291093600003

View details for PubMedID 21702590

View details for DOI 10.1088/1367-2630/13/5/053033

View details for Web of Science ID 000292002100003

View details for DOI 10.1116/1.3574390

View details for Web of Science ID 000291111300036

View details for DOI 10.2110/palo.2011.S03

View details for Web of Science ID 000292342800001

View details for DOI 10.1016/j.molcel.2011.03.009

View details for Web of Science ID 000289500500015

Abstract

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined)? = 0.64, P(combined)? = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted) ?= 0.70, P(adjusted)? =? 4 × 10(-12); rs10484561:OR(adjusted) ?= 1.64, P(adjusted) ?= 5 × 10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined) ?= 1.36, P(combined)? =? 1.4 × 10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

View details for DOI 10.1371/journal.pgen.1001378

View details for Web of Science ID 000289977000026

View details for PubMedID 21533074

View details for DOI 10.1063/1.3559475

View details for Web of Science ID 000289952100198

Abstract

The cellular response to DNA double-strand breaks (DSBs) is mobilized by the protein kinase ATM, which phosphorylates key players in the DNA damage response (DDR) network. A major question is how ATM controls DSB repair. Optimal repair requires chromatin relaxation at damaged sites. Chromatin reorganization is coupled to dynamic alterations in histone posttranslational modifications. Here, we show that in human cells, DSBs induce monoubiquitylation of histone H2B, a modification that is associated in undamaged cells with transcription elongation. We find that this process relies on recruitment to DSB sites and ATM-dependent phosphorylation of the responsible E3 ubiquitin ligase: the RNF20-RNF40 heterodimer. H2B monoubiquitylation is required for timely recruitment of players in the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair-and optimal repair via both pathways. Our data and previous data suggest a two-stage model for chromatin decondensation that facilitates DSB repair.

View details for DOI 10.1016/j.molcel.2011.02.015

View details for Web of Science ID 000288150700006

View details for PubMedID 21362549

View details for DOI 10.1109/TCPMT.2010.2100711

View details for Web of Science ID 000292780700004

Abstract

Most current approaches to multiantigen fluorescent imaging require overlaying of multiple images taken with separate filter sets as a result of differing dye excitation requirements. This requirement for false-color composite imaging prevents the user from visualizing multiple species in real time and disallows imaging of rapidly moving specimens. To address this limitation, here we investigate the use of oligodeoxyfluoroside (ODF) fluorophores as labels for antibodies. ODFs are short DNA-like oligomers with fluorophores replacing the DNA bases and can be assembled in many colors with excitation at a single wavelength. A DNA synthesizer was used to construct several short ODFs carrying a terminal alkyne group and having emission maxima of 410-670 nm. We developed a new approach to antibody conjugation, using Huisgen-Sharpless cycloaddition, which was used to react the alkynes on ODFs with azide groups added to secondary antibodies. Multiple ODF-tagged secondary antibodies were then used to mark primary antibodies. The set of antibodies was tested for spectral characteristics in labeling tubulin in HeLa cells and revealed a wide spectrum of colors, ranging from violet-blue to red with excitation through a single filter (340-380 nm). Selected sets of the differently labeled secondary antibodies were then used to simultaneously mark four antigens in fixed cells, using a single image and filter set. We also imaged different surface tumor markers on two live cell lines. Experiments showed that all colors could be visualized simultaneously by eye under the microscope, yielding multicolor images of multiple cellular antigens in real time.

View details for DOI 10.1073/pnas.1017349108

View details for Web of Science ID 000287844400014

View details for PubMedID 21321224

View details for DOI 10.1007/s10562-010-0477-y

View details for Web of Science ID 000287506800002

Abstract

We examined whether dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or specific foods rich in these compounds is associated with reduced risk of B-cell non-Hodgkin lymphoma (NHL), multiple myeloma (MM), or Hodgkin lymphoma (HL) in a large, prospective cohort of women.Between 1995-1996 and 31 December 2007, among 110,215 eligible members of the California Teachers Study cohort, 536 women developed incident B-cell NHL, 104 developed MM, and 34 developed HL. Cox proportional hazards regression, with age as the time scale, was used to estimate adjusted rate ratios (RRs) with 95% confidence intervals (CIs) for risk of lymphoid malignancies.Weak inverse associations with risk of diffuse large B-cell lymphoma were observed for isothiocyanates (RR for ?12.1 vs. <2.7 mcM/day = 0.67, 95% CI: 0.43-1.05) and an antioxidant index measuring hydroxyl radical absorbance capacity (RR for ?2.2 vs. <0.9 ?M Trolox equiv/g/day = 0.68, 95% CI: 0.42-1.10; p (trend) = 0.08). Risk of other NHL subtypes, overall B-cell NHL, MM, or HL was not generally associated with dietary intake of isoflavones, lignans, isothiocyanates, antioxidants, or major food sources of these compounds.Isoflavones, lignans, isothiocyanates, and antioxidant compounds are not associated with risk of most B-cell malignancies, but some phytocompounds may decrease the risk of selected subtypes.

View details for DOI 10.1007/s10552-010-9692-5

View details for Web of Science ID 000286465000009

View details for PubMedID 21107674

View details for DOI 10.1016/j.asr.2010.08.001

View details for Web of Science ID 000287422000014

View details for DOI 10.1109/JMEMS.2010.2093560

View details for Web of Science ID 000286934900012

Abstract

Variations in target volume delineation represent a significant hurdle in clinical trials involving conformal radiotherapy. We sought to determine the effect of a consensus guideline-based visual atlas on contouring the target volumes.A representative case was contoured (Scan 1) by 14 physician observers and a reference expert with and without target volume delineation instructions derived from a proposed rectal cancer clinical trial involving conformal radiotherapy. The gross tumor volume (GTV), and two clinical target volumes (CTVA, including the internal iliac, presacral, and perirectal nodes, and CTVB, which included the external iliac nodes) were contoured. The observers were randomly assigned to receipt (Group A) or nonreceipt (Group B) of a consensus guideline and atlas for anorectal cancers and then instructed to recontour the same case/images (Scan 2). Observer variation was analyzed volumetrically using the conformation number (CN, where CN = 1 equals total agreement).Of 14 evaluable contour sets (1 expert and 7 Group A and 6 Group B observers), greater agreement was found for the GTV (mean CN, 0.75) than for the CTVs (mean CN, 0.46-0.65). Atlas exposure for Group A led to significantly increased interobserver agreement for CTVA (mean initial CN, 0.68, after atlas use, 0.76; p = .03) and increased agreement with the expert reference (initial mean CN, 0.58; after atlas use, 0.69; p = .02). For the GTV and CTVB, neither the interobserver nor the expert agreement was altered after atlas exposure.Consensus guideline atlas implementation resulted in a detectable difference in interobserver agreement and a greater approximation of expert volumes for the CTVA but not for the GTV or CTVB in the specified case. Visual atlas inclusion should be considered as a feature in future clinical trials incorporating conformal RT.

View details for DOI 10.1016/j.ijrobp.2009.11.012

View details for Web of Science ID 000286451000023

View details for PubMedID 20400244

Abstract

Polyfluorophores built on a DNA scaffold (ODFs) were synthesized and tested for fluorescence responses to the volatiles from M. tuberculosis, E. coli and P. putida in closed Petri dishes. Two sensors in a pattern-based response could distinguish the bacterial strains accurately, suggesting the use of ODFs in rapid identification of infectious agents.

View details for DOI 10.1039/c1cc14871k

View details for Web of Science ID 000295696300011

View details for PubMedID 21935547

Abstract

Herein we report a parallel solid-phase synthesis of 1,3,5-triazine based nucleoside analogues by a three-step substitution, starting from 2,4,6-trichloro-1,3,5-triazine. A library of 80 galactosyl-1,3,5-triazine compounds was prepared in high purity without extensive reaction conditions or tedious purification, suggesting the generality of this method.

View details for DOI 10.1039/c1ob05733b

View details for Web of Science ID 000295889900009

View details for PubMedID 21863155

Abstract

We analyse the transition state energies for 249 hydrogenation/dehydrogenation reactions of atoms and simple molecules over close-packed and stepped surfaces and nanoparticles of transition metals using Density Functional Theory. Linear energy scaling relations are observed for the transition state structures leading to transition state scaling relations for all the investigated reactions. With a suitable choice of reference systems the transition state scaling relations form a universality class that can be approximated with one single linear relation describing the entire range of reactions over all types of surfaces and nanoclusters.

View details for DOI 10.1039/c1cp20547a

View details for Web of Science ID 000297071400029

View details for PubMedID 21996683

Abstract

The high concentration of molecular oxygen in Earth's atmosphere is arguably the most conspicuous and geologically important signature of life. Earth's early atmosphere lacked oxygen; accumulation began after the evolution of oxygenic photosynthesis in cyanobacteria around 3.0-2.5 billion years ago (Gya). Concentrations of oxygen have since varied, first reaching near-modern values ~600 million years ago (Mya). These fluctuations have been hypothesized to constrain many biological patterns, among them the evolution of body size. Here, we review the state of knowledge relating oxygen availability to body size. Laboratory studies increasingly illuminate the mechanisms by which organisms can adapt physiologically to the variation in oxygen availability, but the extent to which these findings can be extrapolated to evolutionary timescales remains poorly understood. Experiments confirm that animal size is limited by experimental hypoxia, but show that plant vegetative growth is enhanced due to reduced photorespiration at lower O(2):CO(2). Field studies of size distributions across extant higher taxa and individual species in the modern provide qualitative support for a correlation between animal and protist size and oxygen availability, but few allow prediction of maximum or mean size from oxygen concentrations in unstudied regions. There is qualitative support for a link between oxygen availability and body size from the fossil record of protists and animals, but there have been few quantitative analyses confirming or refuting this impression. As oxygen transport limits the thickness or volume-to-surface area ratio-rather than mass or volume-predictions of maximum possible size cannot be constructed simply from metabolic rate and oxygen availability. Thus, it remains difficult to confirm that the largest representatives of fossil or living taxa are limited by oxygen transport rather than other factors. Despite the challenges of integrating findings from experiments on model organisms, comparative observations across living species, and fossil specimens spanning millions to billions of years, numerous tractable avenues of research could greatly improve quantitative constraints on the role of oxygen in the macroevolutionary history of organismal size.

View details for DOI 10.1007/s11120-010-9593-1

View details for Web of Science ID 000286199300004

View details for PubMedID 20821265

Abstract

Several previous studies found inverse associations between alcohol consumption and risk of non-Hodgkin lymphoma (NHL) and multiple myeloma. However, most studies were retrospective, and few distinguished former drinkers or infrequent drinkers from consistent nondrinkers. Therefore, the authors investigated whether history of alcohol drinking affected risks of NHL and multiple myeloma among 102,721 eligible women in the California Teachers Study, a prospective cohort study in which 496 women were diagnosed with B-cell NHL and 101 were diagnosed with multiple myeloma between 1995-1996 and December 31, 2007. Incidence rate ratios and 95% confidence intervals were estimated using Cox proportional hazards regression. Risk of all types of B-cell NHL combined or multiple myeloma was not associated with self-reported past consumption of alcohol, beer, wine, or liquor at ages 18-22 years, at ages 30-35 years, or during the year before baseline. NHL subtypes were inconsistently associated with alcohol intake. However, women who were former alcohol drinkers at baseline were at elevated risk of overall B-cell NHL (rate ratio = 1.46, 95% confidence interval: 1.08, 1.97) and follicular lymphoma (rate ratio = 1.81, 95% confidence interval: 1.00, 3.28). The higher risk among former drinkers emphasizes the importance of classifying both current and past alcohol consumption and suggests that factors related to quitting drinking, rather than alcohol itself, may increase B-cell NHL risk.

View details for DOI 10.1093/aje/kwq309

View details for Web of Science ID 000285193200008

View details for PubMedID 20952595

View details for DOI 10.1140/epjc/s10052-010-1508-y

View details for Web of Science ID 000285208000023

Abstract

Cationic nanoparticles of biodegradable polymers such as poly (lactide) (PLA) have been shown to be promising carrier systems for DNA and siRNA delivery. However, the parameters which influence the transfection efficiency have not been investigated in details. In this work, four groups of cationic PLA-based nanoparticles were synthesized by the nanoprecipitation method and solvent evaporation method with polyethyleneimine (PEI) and chitosan as two types of surface coating materials. Cationic poly (D,L-lactide-co-glycolide) (PLGA)-PEI, PLGA-chitosan and methoxy poly (ethylene glycol)-poly (lactide) (mPEG)-PLA/PEI, mPEG-PLA-chitosan nanoparticles were characterized in terms of size and size distribution by laser scattering, surface charge by zeta potential measurement, and surface chemistry by X-ray electron spectroscopy (XPS). The four type pg nanoparticles were compared for their interaction with siRNA and nanoparticles mediated siRNA transfection efficiency with a hepatitis B model, where the inhibition effects of the double strand RNA (dsRNA) mediated by the four types of nanoparticles were evaluated by measuring the HBsAg expression level. The highest inhibition effect of HBsAg (the surface antigen of the hepatitis B Virus (HBV), which indicates current hepatitis B infection) expression was achieved by the mPEG-PLA-PEI nanoparticles mediated siRNA transfection. The results demonstrated that the siRNA delivery follows a size and surface charge dependant manner.

View details for DOI 10.1016/j.ijpharm.2010.08.026

View details for Web of Science ID 000283829900025

View details for PubMedID 20801205

Abstract

The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research.

View details for DOI 10.1038/nature09534

View details for Web of Science ID 000283548600039

View details for PubMedID 20981092

View details for DOI 10.1103/PhysRevB.82.144428

View details for Web of Science ID 000283117100008

Abstract

A search for new heavy particles manifested as resonances in two-jet final states is presented. The data were produced in 7 TeV proton-proton collisions by the LHC and correspond to an integrated luminosity of 315??nb?¹ collected by the ATLAS detector. No resonances were observed. Upper limits were set on the product of cross section and signal acceptance for excited-quark (q*) production as a function of q* mass. These exclude at the 95% C.L. the q* mass interval 0.30

View details for DOI 10.1103/PhysRevLett.105.161801

View details for Web of Science ID 000282753000004

View details for PubMedID 21230962

View details for Web of Science ID 000283763000008

View details for DOI 10.1038/nbt.1665

View details for Web of Science ID 000285268700003

View details for DOI 10.1103/PhysRevB.82.104115

View details for Web of Science ID 000282007200002

Abstract

To identify susceptibility loci for non-Hodgkin lymphoma subtypes, we conducted a three-stage genome-wide association study. We identified two variants associated with follicular lymphoma at 6p21.32 (rs10484561, combined P = 1.12 x 10(-29) and rs7755224, combined P = 2.00 x 10(-19); r(2) = 1.0), supporting the idea that major histocompatibility complex genetic variation influences follicular lymphoma susceptibility. We also found confirmatory evidence of a previously reported association between chronic lymphocytic leukemia/small lymphocytic lymphoma and rs735665 (combined P = 4.24 x 10(-9)).

View details for DOI 10.1038/ng.626

View details for Web of Science ID 000280524000008

View details for PubMedID 20639881

Abstract

Loss of imprinting (LOI) of the insulin-like growth factor 2 gene (IGF2) is one of the most common epigenetic abnormalities seen in human neoplasms. LOI may be associated with the lack of Zinc-finger DNA binding protein CTCF-mediated enhancer insulation, presumably due to the gain of methylation on the maternal allele of the differentially methylated domain (DMD) of the imprinting control region. This results in an interaction between the IGF2 promoters and enhancers; and IGF2 is produced from both alleles. In this study we investigated the feasibility of a novel anti-cancer adenovirus (AdDC312-DT-A) driven by H19 enhancer DMD-H19 promoter complex. Cell lines with IGF2 LOI (HCT-8, HT-29 and H-522) that were infected with AdDC312-EGFP produced the EGFP protein. However, in cells in which imprinting was maintained (MOI) (MCF-7 and GES-1), no EGFP protein was produced. The AdDC312-DT-A significantly decreased cell viability and induced apoptosis only in LOI cells in vitro, and suppressed tumour development in HCT-8 xenografts in nude mice. In conclusion, the toxin gene therapy proves effective in inhibiting LOI cell growth in vitro and in vivo and provides a novel option for targeted gene therapy based on loss of IGF2 imprinting.

View details for Web of Science ID 000281005600012

View details for PubMedID 20592487

Abstract

Gene expression data from microarrays are being applied to predict preclinical and clinical endpoints, but the reliability of these predictions has not been established. In the MAQC-II project, 36 independent teams analyzed six microarray data sets to generate predictive models for classifying a sample with respect to one of 13 endpoints indicative of lung or liver toxicity in rodents, or of breast cancer, multiple myeloma or neuroblastoma in humans. In total, >30,000 models were built using many combinations of analytical methods. The teams generated predictive models without knowing the biological meaning of some of the endpoints and, to mimic clinical reality, tested the models on data that had not been used for training. We found that model performance depended largely on the endpoint and team proficiency and that different approaches generated models of similar performance. The conclusions and recommendations from MAQC-II should be useful for regulatory agencies, study committees and independent investigators that evaluate methods for global gene expression analysis.

View details for DOI 10.1038/nbt.1665

View details for Web of Science ID 000280757500023

View details for PubMedID 20676074

Abstract

We hypothesized that subjects with obsessive-compulsive disorder (OCD) who received extended-release fluvoxamine (fluvoxamine ER) in a 12-week placebo-controlled trial would exhibit improvements in psychosocial domains of health-related quality of life (HRQOL) and that additional improvements would occur after a 40-week open-label extension trial. We also hypothesized that greater OCD symptom improvement in the first 12 weeks of treatment would be associated with greater HRQOL improvement after 52 weeks of treatment.In the 12-week placebo-controlled trial, subjects were randomized to receive placebo or 100 mg/d of fluvoxamine ER and then titrated in weekly 50 mg increments to a final dose of 100 to 300 mg/d. All subjects enrolled in the 40-week extension trial followed a similar titration, during which they were maintained on their highest well-tolerated dose.After 12 weeks of treatment, fluvoxamine ER subjects experienced significantly greater decreases than placebo subjects in Yale-Brown Obsessive-Compulsive Scale scores (P = .001). Both the active drug and placebo groups exhibited significant improvements in psychosocial domains of HRQOL; further improvement occurred after 40 weeks of open-label treatment with active drug. The greater the improvement in OCD severity at 12 weeks, the greater the improvement at 52 weeks in the psychosocial domains (Social Functioning r = -0.39, P = .027; Emotional Problems r = -0.37, P = .037; Mental Health r = -0.49, P = .004).Improvement in Yale-Brown Obsessive-Compulsive Scale severity scores during treatment with fluvoxamine ER was associated with improvements in psychosocial aspects of HRQOL that increased over an extended period of treatment.

View details for DOI 10.1016/j.comppsych.2009.10.001

View details for Web of Science ID 000279303500008

View details for PubMedID 20579510

Abstract

The scallop is an economically important sea food prized for its large and delicious adductor muscle. Studying the molecular basis of scallop muscle growth is important for both scallop breeding and our understanding of muscle mass regulation in bivalve. Myostatin (MSTN) is a conserved negative regulator of muscle growth and development. Here we report the MSTN gene from Zhikong scallop (Chlamys farreri Jones et Preston 1904). The C. farreri MSTN consists of 11651 nucleotides encoding 457 amino acids. The gene has a 3-exon/2-intron structure that is conserved with vertebrate homologs. The exons are 586, 380 and 408 bp in length, respectively, and separated by introns of 5086 and 1518 bp. The protein sequence contains characteristic conserved residues including a cleavage motif of proteolysis (RXXR) and nine cysteines. Three transcription initiation sites were found at 62, 146, and 296 bp upstream of the translation start codon ATG. In silico analysis of the promoter region identified a TATA-box and several muscle-specific regulatory elements including COMP, MEF2s, MTBFs and E-boxes. Minisatellite DNA was found in intron 1. By fluorescence in situ hybridization (FISH), the gene was mapped to the long arm of a pair of middle subtelocentric chromosome. Quantitative analysis of MSTN transcripts in embryos/larvae indicated high expression level in gastrulae and limited expression at other stages. In adult scallops, MSTN is predominantly expressed in striated muscle, with different expression levels in other tissues. Our data provide valuable genomic and expression information which will aid the further study on scallop MSTN function and MSTN evolution.

View details for Web of Science ID 000285433600005

View details for PubMedID 21041979

View details for DOI 10.1109/TMAG.2010.2044982

View details for Web of Science ID 000278037800288

View details for DOI 10.1016/j.physletb.2010.03.064

View details for Web of Science ID 000286150500001

View details for DOI 10.1016/j.jala.2009.10.008

View details for Web of Science ID 000285163500004

Abstract

Rapid and multiplexed measurement is vital in the detection of food-borne pathogens. While highly specific and sensitive, traditional immunochemical assays such as enzyme-linked immunosorbent assays (ELISAs) often require expensive read-out equipment (e.g. fluorescent labels) and lack the capability of multiplex detection. By combining the superior specificity of immunoassays with the sensitivity and simplicity of magnetic detection, we have developed a novel multiplex magnetic nanotag-based detection platform for mycotoxins that functions on a sub-picomolar concentration level. Unlike fluorescent labels, magnetic nanotags (MNTs) can be detected with inexpensive giant magnetoresistive (GMR) sensors such as spin-valve sensors. In the system presented here, each spin-valve sensor has an active area of 90 microm x 90 microm, arranged in an 8 x 8 array. Sample is added to the antibody-immobilized sensor array prior to the addition of the biotinylated detection antibody. The sensor response is recorded in real time upon the addition of streptavidin-linked MNTs on the chip. Here we demonstrate the simultaneous detection of multiple mycotoxins (aflatoxins B(1), zearalenone and HT-2) and show that a detection limit of 50 pg/mL can be achieved.

View details for DOI 10.1016/j.bios.2009.11.028

View details for Web of Science ID 000275978700013

View details for PubMedID 20047828

Abstract

Cervical cancer incidence was evaluated by histologic type, age at diagnosis, and disease stage for 6 Asian ethnic groups residing in the United States.Incidence rates were estimated for cervical squamous cell carcinoma (SCC) and adenocarcinoma by age and stage for 6 Asian ethnic groups-Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, and Vietnamese-in 5 US cancer registry areas during 1996 through 2004. For comparison, rates among non-Hispanic whites, non-Hispanic blacks, and Hispanics were also calculated.During 1996 through 2004, Vietnamese women had the highest (18.9 per 100,000) and Asian Indian/Pakistani women had the lowest (4.5) incidence of cervical cancer; this pattern was consistent by histologic type. Vietnamese women also had the highest incidence for localized (7.3) and regional (5.7) SCC and for localized (2.4) adenocarcinoma. Contrary to the plateau of SCC incidence apparent among white women by age 45 years, SCC rates continued to rise with age among Chinese, Filipina, Korean, and Vietnamese women.There exists large variation in invasive cervical cancer incidence patterns among Asian ethnic groups in the United States and in comparison with rates for blacks, Hispanics, and whites. Early detection and prevention strategies for cervical cancer among Asians require targeted strategies by ethnic group.

View details for DOI 10.1002/cncr.24843

View details for Web of Science ID 000274315800024

View details for PubMedID 20029972

View details for DOI 10.1063/1.3285163

View details for Web of Science ID 000274319500073

View details for DOI 10.1088/1742-6596/200/12/122001

View details for Web of Science ID 000291321303100

View details for DOI 10.1016/j.sedgeo.2009.07.004

View details for Web of Science ID 000272431100004

Abstract

The effect of loss-of-function of Attractin (Atrn) on the male mouse reproduction system was examined in the study. The weights and pathological changes of testes and epididymes were compared between Atrn mutant (Atrn(mg-3J)) mice and wild-type mice (C3HeB/FeJ) at different months of age. The number and motility of sperms were measured in the mutant and control mice. Furthermore, the testicular lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH) in these animals were detected. The fertility potential of the sperms was observed in vivo and in vitro. The results showed that the testes of 3-month-old Atrn (mg-3J) mice experienced no significantly different pathological changes from the control mice at the same month of age but the SDH activity was substantially reduced. In the 5-month-old mutant mice, as compared with the control mice, mild vacuolation was found in the testes, the density and motility of sperms were decreased in the epididymes, the sperm fertility was impaired and the testicular enzyme activity was reduced. It is concluded that the age-related Atrn gene progressively loses its function and can cause testis vacuolation and impaired sperm function, which may be responsible for the impairment of male reproductive ability.

View details for DOI 10.1007/s11596-009-0616-0

View details for Web of Science ID 000273129100016

View details for PubMedID 20037821

View details for DOI 10.1109/TADVP.2009.2019845

View details for Web of Science ID 000271435900010

Abstract

Spatial patterning of proteins is a valuable technique for many biological applications and is the prevailing tool for defining microenvironments for cells in culture, a required procedure in developmental biology and tissue engineering research. However, it is still challenging to achieve protein patterns that closely mimic native microenvironments, such as gradient protein distributions with desirable mechanical properties. By combining projection dynamic mask lithography and protein engineering with non-canonical photosensitive amino acids, we demonstrate a simple, scalable strategy to fabricate any user-defined 2D or 3D stable gradient pattern with complex geometries from an artificial extracellular matrix (aECM) protein. We show that the elastic modulus and chemical nature of the gradient profile are biocompatible and allow useful applications in cell biological research.

View details for DOI 10.1007/s10544-009-9329-1

View details for Web of Science ID 000270679400019

View details for PubMedID 19495986

Abstract

We present a device concept based on controlled micromagnetic configurations in a corner-shaped permalloy nanostructure terminated with two circular disks, specifically designed for the capture and detection of a small number of magnetic beads in suspension. A transverse head-to-head domain wall (TDW) placed at the corner of the structure plays the role of an attracting pole for magnetic beads. The TDW is annihilated in the terminating disks by applying an appropriate magnetic field, whose value is affected by the presence of beads chemically bound to the surface. In the case where the beads are not chemically bound to the surface, the annihilation of the TDW causes their release into the suspension. The variation of the voltage drop across the corner, due to the anisotropic magnetoresistance (AMR) while sweeping the magnetic field, is used to detect the presence of a chemically bound bead. The device response has been characterized by using both synthetic antiferromagnetic nanoparticles (disks of 70 nm diameter and 20 nm height) and magnetic nanobeads, for different thicknesses of the protective capping layer. We demonstrate the detection down to a single nanoparticle, therefore the device holds the potential for the localization and detection of small numbers of molecules immobilized on the particle's functionalized surface.

View details for DOI 10.1088/0957-4484/20/38/385501

View details for Web of Science ID 000269356900009

View details for PubMedID 19713593

Abstract

To determine if magnetotactic bacteria can target tumors in mice and provide positive contrast for visualization using magnetic resonance imaging.The ability of the magnetotactic bacterium, Magnetospirillum magneticum AMB-1 (referred to from here as AMB-1), to confer positive magnetic resonance imaging contrast was determined in vitro and in vivo. For the latter studies, AMB-1 were injected either i.t. or i.v. Bacterial growth conditions were manipulated to produce small (approximately 25-nm diameter) magnetite particles, which were observed using transmission electron microscopy. Tumor targeting was confirmed using 64Cu-labeled bacteria and positron emission tomography and by determination of viable cell counts recovered from different organs and the tumor.We show that AMB-1 bacteria with small magnetite particles generate T1-weighted positive contrast, enhancing in vivo visualization by magnetic resonance imaging. Following i.v. injection of 64Cu-labeled AMB-1, positron emission tomography imaging revealed increasing colonization of tumors and decreasing infection of organs after 4 hours. Viable cell counts showed that, by day 6, the bacteria had colonized tumors but were cleared completely from other organs. Magnetic resonance imaging showed a 1.22-fold (P = 0.003) increased positive contrast in tumors on day 2 and a 1.39-fold increase (P = 0.0007) on day 6.Magnetotactic bacteria can produce positive magnetic resonance imaging contrast and colonize mouse tumor xenografts, providing a potential tool for improved magnetic resonance imaging visualization in preclinical and translational studies to track cancer.

View details for DOI 10.1158/1078-0432.CCR-08-3206

View details for Web of Science ID 000269024900019

View details for PubMedID 19671860

Abstract

The X-ray crystal structures of the methylcobalamin (MeCbl) analogues ethylcobalamin (EtCbl) and butylcobalamin (BuCbl) are reported. The X-ray crystal structures of EtCbl and BuCbl were obtained with some of the lowest crystallographic residuals ever achieved for cobalamins (R = 0.0468 and 0.0438, respectively). The Co-C bond distances for EtCbl and BuCbl are 2.023(2) and 2.028(4) A, whereas the Co-alpha-5,6-dimethylbenzimidazole (Co-N3B) bond distances were 2.232(1) and 2.244(1) A, respectively. Although EtCbl and BuCbl displayed a longer Co-N3B bond than that observed in the naturally occurring methylcobalamin, the orientation of the alpha-5,6-dimethylbenzimidazole moiety with respect to the corrin ring did not vary substantially among the structures. The lengthening of both Co-C and Co-N3B bonds in EtCbl and BuCbl can be attributed to the "inverse" trans influence exerted by the sigma-donating alkyl groups, typically observed in alkylcobalamins. Analysis of the molecular surface maps showed that the alkyl ligands in EtCbl and BuCbl are directed toward the hydrophobic side of the corrin ring. The corrin fold angles in EtCbl and BuCbl were determined to be 14.7 degrees and 13.1 degrees, respectively. A rough correlation exists between the corrin fold angle and the length of the Co-N3B bond, and both alkylcobalamins follow the same trend.

View details for DOI 10.1021/ic900590p

View details for Web of Science ID 000268137900042

View details for PubMedID 19545130

View details for DOI 10.1007/s12541-009-0045-9

View details for Web of Science ID 000268009600006

Abstract

Antifreeze proteins (AFPs) noncolligatively depress the nonequilibrium freezing point of a solution and produce a difference between the melting and freezing points termed thermal hysteresis (TH). Some low-molecular-mass solutes can affect the TH values. The TH enhancement effects of selected polyhydroxy compounds including polyols and carbohydrates on an AFP from the beetle Dendroides canadensis were systematically investigated using differential scanning calorimetry (DSC). The number of hydroxyl groups dominates the molar enhancement effectiveness of polyhydroxy compounds having one to five hydroxyl groups. However, the above rule does not apply for polyhydroxy compounds having more than five hydroxyl groups. The most efficient polyhydroxy enhancer identified is trehalose. In a combination of enhancers the strongest enhancer plays the major role in determining the TH enhancement. Mechanistic insights into identification of highly efficient AFP enhancers are discussed.

View details for DOI 10.1016/j.bbapap.2008.10.011

View details for Web of Science ID 000262952600022

View details for PubMedID 19038370

View details for DOI 10.1063/1.3063124

View details for Web of Science ID 000262357800053

View details for DOI 10.1393/ncr/i2009-10049-y

View details for Web of Science ID 000273677400001

Abstract

Ethnicity and culture represent important factors in shaping psychopathology as well as pharmacotherapeutic responses in psychiatric patients. A large body of literature, accumulated over the past several decades, demonstrates that these factors not only determine the metabolism and disposition of medications (pharmacokinetics), but also their interactions with therapeutic targets (pharmacodynamics). This article focuses on the impact of such variations on the diagnosis and treatment of depression and anxiety disorders between East and West. Genes controlling the expression of drug metabolizing enzymes as well as the function of the brain are highly polymorphic, and the patterns and distribution of these polymorphisms are typically divergent across ethnic groups. To the extent that these genetic patterns determine drug response, ethnic variations in these genetic dispositions will lead to differential responses in clinical settings. In addition, the expression of these genes is significantly influenced by environmental factors including diet as well as exposure to other natural products. Superimposed on these biological influences, culturally determined beliefs and behavioral patterns also profoundly influence patients' expectations of treatment response, adherence, and interactions with clinicians. In addition to pharmacotherapeutic responses, emerging data also indicate that significant ethnic variations exist in genetic polymorphisms and neurobiologic correlates (biomarkers) that may be associated with the vulnerability to psychiatric disorders. These considerations argue for the importance of examining biological variations across ethnic groups, especially in the clinical context, in terms of the assessment and treatment of psychiatric patients, and in our understanding of psychiatric phenomenology and nosology.

View details for DOI 10.1111/j.1755-5949.2009.00093.x

View details for Web of Science ID 000268790700010

View details for PubMedID 19691548

Abstract

A major challenge in molecular biology is interrogating the human transcriptome on a genome wide scale when only a limited amount of biological sample is available for analysis. Current methodologies using microarray technologies for simultaneously monitoring mRNA transcription levels require nanogram amounts of total RNA. To overcome the sample size limitation of current technologies, we have developed a method to probe the global gene expression in biological samples as small as 150 cells, or the equivalent of approximately 300 pg total RNA. The new method employs microfluidic devices for the purification of total RNA from mammalian cells and ultra-sensitive whole transcriptome amplification techniques. We verified that the RNA integrity is preserved through the isolation process, accomplished highly reproducible whole transcriptome analysis, and established high correlation between repeated isolations of 150 cells and the same cell culture sample. We validated the technology by demonstrating that the combined microfluidic and amplification protocol is capable of identifying biological pathways perturbed by stimulation, which are consistent with the information recognized in bulk-isolated samples.

View details for DOI 10.1039/b814329c

View details for Web of Science ID 000266978200011

View details for PubMedID 20023796

Abstract

Precisely regulated signal transduction pathways are crucial for the regulation of developmental events and prevention of tumorigenesis. Both the Transforming Growth Factor beta (TGFbeta)/Bone morphogenetic protein (BMP) and Wnt/Wingless (Wg) pathways play essential roles in organismal patterning and growth, and their deregulation can lead to cancers. We describe a mechanism of interaction between Drosophila Wg and BMP signaling in which Wg target gene expression is antagonized by BMP signaling. In vivo, high levels of both an activated BMP receptor and the BMP effector Mad can inhibit the expression of Wg target genes. Conversely, loss of mad can induce Wg target gene expression. In addition, we find that ectopic expression in vivo of the Wg transcription factor dTcf is able to suppress the inhibitory effect caused by ectopic Mad. In vitro binding studies revealed competition for dTcf binding between Mad and the Wnt effector beta-catenin/Armadillo (Arm). Our in vivo genetic analyses and target gene studies support a mechanism consistent with the in vitro binding and competition studies, namely that BMP pathway components can repress Wg target gene expression by influencing the binding of Arm and dTcf.

View details for DOI 10.1371/journal.pone.0003893

View details for Web of Science ID 000265455200008

View details for PubMedID 19065265

Abstract

To establish baseline data for lymphoid neoplasm incidence by subtype for six Asian-American ethnic groups.Incident rates were estimated by age and sex for six Asian ethnic groups--Asian Indian/Pakistani, Chinese, Filipino, Japanese, Korean, Vietnamese--in five United States cancer registry areas during 1996-2004. For comparison, rates for non-Hispanic Whites were also estimated.During 1996-2004, Filipinos had the highest (24.0) and Koreans had the lowest incidence (12.7) of total lymphoid neoplasms. By subtype, Vietnamese and Filipinos had the highest incidence for diffuse large B-cell lymphoma (DLBCL) (8.0 and 7.2); Japanese had the highest incidence of follicular lymphoma (2.3). Although a general male predominance of lymphoid neoplasms was observed, this pattern varied by lymphoid neoplasm subtype. Whites generally had higher rates than all Asian ethnic groups for all lymphoid neoplasms and most lymphoma subtypes, although the magnitude of the difference varied by both ethnicity and lymphoma subtype.The observed variations in incidence patterns among Asian ethnic groups in the United States suggest that it may be fruitful to pursue studies that compare Asian populations for postulated environmental and genetic risk factors.

View details for DOI 10.1007/s10552-008-9184-z

View details for Web of Science ID 000260766300017

View details for PubMedID 18543071

Abstract

Antifreeze proteins (AFPs) lower the noncolligative freezing point of water in the presence of ice below the ice melting point. The temperature difference between the melting point and the noncolligative freezing point is termed thermal hysteresis (TH). The magnitude of the TH depends on the specific activity and the concentration of AFP, and the concentration of enhancers in the solution. Known enhancers are certain low molecular mass molecules and proteins. Here, we investigated a series of polycarboxylates that enhance the TH activity of an AFP from the beetle Dendroides canadensis (DAFP) using differential scanning calorimetry (DSC). Triethylenetetramine-N,N,N',N'',N''',N'''-hexaacetate, the most efficient enhancer identified in this work, can increase the TH of DAFP by nearly 1.5 fold over than that of the published best enhancer, citrate. The Zn(2+) coordinated carboxylate results in loss of the enhancement ability of the carboxylate on antifreeze activity. There is not an additional increase in TH when a weaker enhancer is added to a stronger enhancer solution. These observations suggest that the more carboxylate groups per enhancer molecule the better the efficiency of the enhancer and that the freedom of motion of these molecules is necessary for them to serve as enhancers for AFP. The hydroxyl groups in the enhancer molecules can also positively affect their TH enhancement efficiency, though not as strongly as carboxylate groups. Mechanisms are discussed.

View details for DOI 10.1016/j.bbapap.2008.06.003

View details for Web of Science ID 000261673300007

View details for PubMedID 18620083

View details for DOI 10.1209/0295-5075/84/27009

View details for Web of Science ID 000263598500034

Abstract

This paper investigates the structural characteristics of templated synthetic anti-ferromagnetic (SAF) magnetic nanoparticles fabricated on two different release layers. When copper was used as the latter, the layered structure of the SAFs was found to be disrupted with wavy multi-layers due to the formation of copper grains from the release layer. By introducing oxygen into the copper release layer before the deposition of the film, the topography of the oxidized copper grains was effectively controlled. This led to the fabrication of SAF nanoparticles with flat multi-layers.

View details for DOI 10.1016/j.ultramic.2008.03.012

View details for Web of Science ID 000260518200014

View details for PubMedID 18672328

Abstract

We demonstrate a direct correlation between the domain structure of multiferroic BiFeO3 thin films and exchange bias of Co 0.9Fe 0.1/BiFeO3 heterostructures. Two distinct types of interactions - an enhancement of the coercive field ( exchange enhancement) and an enhancement of the coercive field combined with large shifts of the hysteresis loop ( exchange bias) - have been observed in these heterostructures, which depend directly on the type and crystallography of the nanoscale ( approximately 2 nm) domain walls in the BiFeO3 film. We show that the magnitude of the exchange bias interaction scales with the length of 109 degrees ferroelectric domain walls in the BiFeO 3 thin films which have been probed via piezoresponse force microscopy and X-ray magnetic circular dichroism.

View details for DOI 10.1021/nl801391m

View details for Web of Science ID 000257504500046

View details for PubMedID 18547121

View details for DOI 10.1109/TMAG.2008.920962

View details for Web of Science ID 000257238200001

View details for Web of Science ID 000258212400002

Abstract

Multiferroics are of interest for memory and logic device applications, as the coupling between ferroelectric and magnetic properties enables the dynamic interaction between these order parameters. Here, we report an approach to control and switch local ferromagnetism with an electric field using multiferroics. We use two types of electromagnetic coupling phenomenon that are manifested in heterostructures consisting of a ferromagnet in intimate contact with the multiferroic BiFeO(3). The first is an internal, magnetoelectric coupling between antiferromagnetism and ferroelectricity in the BiFeO(3) film that leads to electric-field control of the antiferromagnetic order. The second is based on exchange interactions at the interface between a ferromagnet (Co(0.9)Fe(0.1)) and the antiferromagnet. We have discovered a one-to-one mapping of the ferroelectric and ferromagnetic domains, mediated by the colinear coupling between the magnetization in the ferromagnet and the projection of the antiferromagnetic order in the multiferroic. Our preliminary experiments reveal the possibility to locally control ferromagnetism with an electric field.

View details for DOI 10.1038/nmat2184

View details for Web of Science ID 000256110200022

View details for PubMedID 18438412

View details for DOI 10.1002/adma.200703077

View details for Web of Science ID 000255694200015

View details for DOI 10.1166/jno.2008.003

View details for Web of Science ID 000255548200005

View details for DOI 10.2747/0020-6814.50.2.121

View details for Web of Science ID 000252256300002

View details for DOI 10.1063/1.2831716

View details for Web of Science ID 000252284200029

View details for DOI 10.1080/14786430802585133

View details for Web of Science ID 000261804200002

Abstract

The purpose of this study was to synthesize biocompatible polyvinylpyrrolidone (PVP)-coated iron oxide (PVP-IO) nanoparticles and to evaluate their efficacy as a magnetic resonance imaging (MRI) contrast agent. The PVP-IO nanoparticles were synthesized by a thermal decomposition method and characterized by x-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic light scattering (DLS), and a superconducting quantum interface device (SQUID). The core size of the particles is about 8-10 nm and the overall size is around 20-30 nm. The measured r(2) (reciprocal of T(2) relaxation time) and r2? (reciprocal of T2? relaxation time) are 141.2 and 338.1 (s mM)(-1), respectively. The particles are highly soluble and stable in various buffers and in serum. The macrophage uptake of PVP-IO is comparable to that of Feridex as measured by a Prussian blue iron stain and phantom study. The signal intensity of a rabbit liver was effectively reduced after intravenous administration of PVP-IO. Therefore PVP-IO nanoparticles are potentially useful for T(2)-weighted MR imaging.

View details for PubMedID 21394237

View details for DOI 10.1529/biophysj.107.120709

View details for Web of Science ID 000251615800001

View details for DOI 10.1142/S0218271807011528

View details for Web of Science ID 000207564700007

View details for Web of Science ID 000250965400066

Abstract

We examined genetic diversity and population structure in the American landmass using 678 autosomal microsatellite markers genotyped in 422 individuals representing 24 Native American populations sampled from North, Central, and South America. These data were analyzed jointly with similar data available in 54 other indigenous populations worldwide, including an additional five Native American groups. The Native American populations have lower genetic diversity and greater differentiation than populations from other continental regions. We observe gradients both of decreasing genetic diversity as a function of geographic distance from the Bering Strait and of decreasing genetic similarity to Siberians--signals of the southward dispersal of human populations from the northwestern tip of the Americas. We also observe evidence of: (1) a higher level of diversity and lower level of population structure in western South America compared to eastern South America, (2) a relative lack of differentiation between Mesoamerican and Andean populations, (3) a scenario in which coastal routes were easier for migrating peoples to traverse in comparison with inland routes, and (4) a partial agreement on a local scale between genetic similarity and the linguistic classification of populations. These findings offer new insights into the process of population dispersal and differentiation during the peopling of the Americas.

View details for DOI 10.1371/journal.pgen.0030185

View details for Web of Science ID 000251310200002

View details for PubMedID 18039031

Abstract

Breast cancer, especially estrogen receptor (ER)-negative breast cancer, remains hard to treat despite major advances in surgery and adjuvant therapies. The deletion of ER has been consistently associated with tumor progression, recurrence, metastasis and poor prognosis. Among other differences in biological features, ER-negative breast cancers express high levels of interleukin-8 (IL-8), whereas their ER-positive counterparts do not. IL-8 is a multi-functional cytokine with many important biological functions in tumor formation and development. We aimed to study the role(s) of IL-8 in ER-negative breast cancer progression by using RNA interference to specifically knockdown IL-8 expression in ER-negative breast cancer cell lines MDA-MB-231 and MDA-MB-468. In vitro, suppression of IL-8 led to significant reductions in cell invasion (p<0.001), but had no effects on cell proliferation or cell cycle. In vivo, suppression of IL-8 significantly reduced the microvessel density (p<0.05), and markedly reduced neutrophil infiltration into the tumors (p<0.05). In contrast to in vitro observations, suppression of IL-8 promoted tumor growth in nude mice (p<0.05). Our results imply that the complex roles of IL-8 in the regulation of ER-negative breast cancer progression may in part be related to its potent chemotactic effects on neutrophils, which in turn mediates many of the biological functions of IL-8.

View details for DOI 10.1002/ijc.22930

View details for Web of Science ID 000249718100009

View details for PubMedID 17621625

View details for DOI 10.1063/1.2801695

View details for Web of Science ID 000250468200064

Abstract

Hypermethylation of CpG islands is a common epigenetic alteration associated with cancer. Global patterns of hypermethylation are tumor-type specific and nonrandom. The biological significance and the underlying mechanisms of tumor-specific aberrant promoter methylation remain unclear, but some evidence suggests that this specificity involves differential sequence susceptibilities, the targeting of DNA methylation activity to specific promoter sequences, or the selection of rare DNA methylation events during disease progression. Using restriction landmark genomic scanning on samples derived from tissue culture and in vivo models of T cell lymphomas, we found that MYC overexpression gave rise to a specific signature of CpG island hypermethylation. This signature reflected gene transcription profiles and was detected only in advanced stages of disease. The further inactivation of the Pten, p53, and E2f2 tumor suppressors in MYC-induced lymphomas resulted in distinct and diagnostic CpG island methylation signatures. Our data suggest that tumor-specific DNA methylation in lymphomas arises as a result of the selection of rare DNA methylation events during the course of tumor development. This selection appears to be driven by the genetic configuration of tumor cells, providing experimental evidence for a causal role of DNA hypermethylation in tumor progression and an explanation for the tremendous epigenetic heterogeneity observed in the evolution of human cancers. The ability to predict genome-wide epigenetic silencing based on relatively few genetic alterations will allow for a more complete classification of tumors and understanding of tumor cell biology.

View details for DOI 10.1371/journal.pgen.0030167

View details for Web of Science ID 000249767800018

View details for PubMedID 17907813

Abstract

The analysis of short tandem repeats (STRs) plays an important role in forensic science, human identification, genetic mapping, and disease diagnostics. Traditional STR analysis utilizes gel- or column-based approaches to analyze DNA repeats. Individual STR alleles are separated and distinguished according to fragment length; thus the assay is generally hampered by its low multiplex capacity. However, use of DNA microarray would employ a simple hybridization and detection for field forensics and biology. Here we demonstrate a rapid, highly sensitive method for STR analysis that utilizes DNA microarray technology. We describe two adaptations to accomplish this: the use of competitive hybridization to remove unpaired ssDNA from an array and the use of neural network classification to automate the analysis. The competitive displacement technique mimics the branch migration process that occurs during DNA recombination. Our technique will facilitate the rapid deduction of identity, length, and number of repeats for the multiple STRs in an unknown DNA sample.

View details for DOI 10.1073/pnas.0700921104

View details for Web of Science ID 000245737500012

View details for PubMedID 17389407

Abstract

We describe a novel method for rapidly identifying and distinguishing between different DNA sequences using short tandem repeat (STR) analysis and DNA microarrays. The method can be used to deduce identity, length, and number of STRs of the target molecule. We refer to this technique as the "variable-length probe array" method for STR profiling (VLPA). The method involves hybridization of the unknown STR target sequence to a DNA microarray displaying complementary probes that vary in length to cover the range of possible STRs. A post-hybridization enzymatic digestion of the DNA hybrids is then used to selectively remove labeled single-stranded regions of DNA from the microarray surface. The number of repeats in the unknown target is then deduced based on the pattern of target DNA that remains hybridized to the array. This DNA profiling technique is useful for performing forensic analysis to uniquely identify individual humans or other species.

View details for Web of Science ID 000231660300013

View details for PubMedID 16225215

View details for DOI 10.1109/TMAG.2004.835096

View details for Web of Science ID 000223446700276