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Find video protocols related to scientific articles indexed in Pubmed.
Real-time in vivo cancer diagnosis using raman spectroscopy.
J Biophotonics
PUBLISHED: 07-03-2015
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Raman spectroscopy has becoming a practical tool for rapid in vivo tissue diagnosis. This paper provides an overview on the latest development of real-time in vivo Raman systems for cancer detection. Instrumentation, data handling, as well as oncology applications of Raman techniques were covered. Optic fiber probes designs for Raman spectroscopy were discussed. Spectral data pre-processing, feature extraction, and classification between normal/benign and malignant tissues were surveyed. Applications of Raman techniques for clinical diagnosis for different types of cancers, including skin cancer, lung cancer, stomach cancer, oesophageal cancer, colorectal cancer, cervical cancer, and breast cancer, were summarized. Schematic of a real-time Raman spectrometer for skin cancer detection. Without correction, the image captured on CCD camera for a straight entrance slit has a curvature. By arranging the optic fiber array in reverse orientation, the curvature could be effectively corrected.
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Efficient Generation of Marker-Free Transgenic Rice Plants Using an Improved Transposon-Mediated Transgene Reintegration Strategy.
Plant Physiol.
PUBLISHED: 11-04-2014
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Marker-free transgenic plants can be developed through transposon-mediated transgene reintegration, which allows intact transgene insertion with defined boundaries and requires only a few primary transformants. In this study, we improved the selection strategy and validated that the maize Ac/Ds transposable element can be routinely used to generate marker-free transgenic plants. A Ds-based gene of interest (GOI) was linked to green fluorescent protein (GFP) in T-DNA, and a GFP-aided counter-selection against T-DNA was used together with PCR-based positive selection for the GOI to screen marker-free progeny. To test the efficacy of this strategy, we cloned the Bacillus thuringiensis (Bt) ð-endotoxin gene into the Ds elements and transformed transposon vectors into rice cultivars via Agrobacterium. PCR assays of the transposon empty donor site exhibited transposition in somatic cells in 60.5% to 100% of the rice transformants. Marker-free (T-DNA-free) transgenic rice plants derived from unlinked germinal transposition were obtained from the T1 generation of 26.1% of the primary transformants. Individual marker-free transgenic rice lines were subjected to TAIL-PCR to determine Ds(Bt) reintegration positions, RT-PCR and ELISA to detect Bt expression levels, and bioassays to confirm resistance against the striped stem borer Chilo suppressalis (Walker). Overall, we efficiently generated marker-free transgenic plants with optimized transgene insertion and expression. The transposon-mediated marker-free platform established in this study can be used in rice and possibly in other important crops.
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Efficient model selection for mixtures of probabilistic PCA via hierarchical BIC.
IEEE Trans Cybern
PUBLISHED: 09-16-2014
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This paper concerns model selection for mixtures of probabilistic principal component analyzers (MPCA). The well known Bayesian information criterion (BIC) is frequently used for this purpose. However, it is found that BIC penalizes each analyzer implausibly using the whole sample size. In this paper, we present a new criterion for MPCA called hierarchical BIC in which each analyzer is penalized using its own effective sample size only. Theoretically, hierarchical BIC is a large sample approximation of variational Bayesian lower bound and BIC is a further approximation of hierarchical BIC. To learn hierarchical-BIC-based MPCA, we propose two efficient algorithms: two-stage and one-stage variants. The two-stage algorithm integrates model selection with respect to the subspace dimensions into parameter estimation, and the one-stage variant further integrates the selection of the number of mixture components into a single algorithm. Experiments on a number of synthetic and real-world data sets show that: 1) hierarchical BIC is more accurate than BIC and several related competitors and 2) the two proposed algorithms are not only effective but also much more efficient than the classical two-stage procedure commonly used for BIC.
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Two-Stage Regularized Linear Discriminant Analysis for 2-D Data.
IEEE Trans Neural Netw Learn Syst
PUBLISHED: 09-10-2014
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Fisher linear discriminant analysis (LDA) involves within-class and between-class covariance matrices. For 2-D data such as images, regularized LDA (RLDA) can improve LDA due to the regularized eigenvalues of the estimated within-class matrix. However, it fails to consider the eigenvectors and the estimated between-class matrix. To improve these two matrices simultaneously, we propose in this paper a new two-stage method for 2-D data, namely a bidirectional LDA (BLDA) in the first stage and the RLDA in the second stage, where both BLDA and RLDA are based on the Fisher criterion that tackles correlation. BLDA performs the LDA under special separable covariance constraints that incorporate the row and column correlations inherent in 2-D data. The main novelty is that we propose a simple but effective statistical test to determine the subspace dimensionality in the first stage. As a result, the first stage reduces the dimensionality substantially while keeping the significant discriminant information in the data. This enables the second stage to perform RLDA in a much lower dimensional subspace, and thus improves the two estimated matrices simultaneously. Experiments on a number of 2-D synthetic and real-world data sets show that BLDA +RLDA outperforms several closely related competitors.
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The study of vacuolar-type ATPases by single particle electron microscopy.
Biochem. Cell Biol.
PUBLISHED: 09-03-2014
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Nature's molecular machines often work through the concerted action of many different protein subunits, which can give rise to large structures with complex activities. Vacuolar-type ATPases (V-ATPases) are membrane-embedded protein assemblies with a unique rotary catalytic mechanism. The dynamic nature and instability of V-ATPases make structural and functional studies of these enzymes challenging. Electron microscopy (EM) techniques, especially single particle electron cryomicroscopy (cryo-EM) and negative-stain EM, have provided extensive insight into the structure and function of these protein complexes. This minireview outlines what has been learned about V-ATPases using electron microscopy, highlights current challenges for their structural study, and discusses what cryo-EM will allow us to learn about these fascinating enzymes in the future.
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A meta-analysis of genotypes and haplotypes of methylenetetrahydrofolate reductase gene polymorphisms in breast cancer.
Mol. Biol. Rep.
PUBLISHED: 06-11-2014
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The association between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and breast cancer risk has been extensively explored, but their results are conflicting rather than conclusive. To derive a more precise estimation, we carried out not only an updated meta-analysis but also a combined analysis based on all the available studies estimating the association between MTHFR C677T and/or A1298C and breast cancer risk. With respect to C677T polymorphism, the results suggested that 677T allele was associated with significantly elevated breast cancer risk in overall analysis (T vs. C: OR 1.073, 95 % CI 1.028-1.120; TT vs. CC: OR 1.177, 95 % CI 1.072-1.293; TT vs. CC + CT: OR 1.175, 95 % CI 1.073-1.288); Stratifying by ethnicity, significantly increased risk was only found in East Asians (T vs. C: OR 1.150, 95 % CI 1.039-1.273; TT vs. CC: OR 1.441, 95 % CI 1.145-1.814; TT vs. CC + CT: OR 1.413, 95 % CI 1.148-1.739); When stratified by menopausal status, statistically significant association was found for postmenopausal women (CT + TT vs. CC: OR 1.092, 95 % CI 1.011-1.179). In regard to A1298C polymorphism, no significant associations were found between the polymorphism and breast cancer risk. With respect to MTHFR haplotypes, significantly elevated breast cancer risk was associated with 677T-1298C for overall result (OR 1.498, 95 % CI 1.143-1.962) and for Caucasians (OR 2.088, 95 % CI 1.277-3.416) when compared with 677C-1298A; Haplotype 677C-1298C might provide higher protection than 677C-1298A in East Asians (OR 0.840, 95 % CI 0.742-0.949). The combined genotypes for C677T and A1298C produced a significant OR for the 677TT/1298AC relative to 677CC/1298AA in overall population (OR 2.047, 95 % CI 1.275-3.288); When stratified by ethnicity, significant ORs were only found for East Asians (677CC/1298CC vs. 677CC/1298AA: OR 0.686, 95 % CI 0.478-0.985; 677TT/1298AC vs. 677CC/1298AA: OR 2.181, 95 % CI 1.179-4.035). The findings suggest that the MTHFR C677T polymorphism but not A1298C, and some variants on their combined genotypes or haplotypes may be involved with the development of breast cancer.
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Nonoccupational physical activity and risk of ovarian cancer: a meta-analysis.
Tumour Biol.
PUBLISHED: 06-08-2014
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Previous studies concerning the association between nonoccupational physical activity (PA) and risk of ovarian cancer yielded mixed results. We investigated the association by performing a meta-analysis. Relevant studies were identified by searching PubMed and EMBASE to June 2014. We calculated the summary relative risks (RRs) and 95 % confidence intervals (CIs) using random-effects models. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Nine cohort studies and ten case-control studies involving 730,703 participants and 9,459 cases of ovarian cancer were selected for meta-analysis. The analyses showed that individuals who participated in any amount of nonoccupational PA had a RR of 0.92 (95 % CI?=?0.84-1.00) for risk of ovarian cancer. Those who participated in high or moderate nonoccupational PA had a RR of ovarian cancer risk of 0.89 (95 % CI?=?0.79-1.01) and 0.91 (95 % CI?=?0.85-0.99), respectively. Stratifying by study design and cancer subtype (borderline and invasive tumors), inverse association was only found in case-control studies. A linear but not significant dose-response relationship was found between nonoccupational PA and ovarian cancer risk. In conclusion, a weak inverse association exists between nonoccupational PA and the risk of ovarian cancer. Regarding the significant heterogeneity among included studies, confirmation in further prospective cohort studies with more accurate assessment of PA level is essential.
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[Extraction and identification of exosomes from drug-resistant breast cancer cells and their potential role in cell-to-cell drug-resistance transfer].
Zhonghua Zhong Liu Za Zhi
PUBLISHED: 05-03-2014
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To explore whether docetaxel-resistant cells (MCF-7/Doc) and doxorubicin-resistant cells (MCF-7/ADM) can secrete Exosomes and their potential role in cell-cell drug-resistance transfer.
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Clinical Raman measurements under special ambient lighting illumination.
J Biomed Opt
PUBLISHED: 02-28-2014
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One challenge in facing the application of biomedical Raman spectroscopy is that the Raman signal is acquired in a dark operation room. It is inconvenient for both the operator and the patient because it is difficult for the operator to accurately and precisely locate the target in the dark environment, and the patient feels uncomfortable in such a setting. In this note, we propose a method to implement biomedical Raman measurement with an illumination source, by multiple filtering of the illumination and the collection optics. Experimental results are demonstrated on skin Raman measurement under 785-nm excitation.
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Induction of B7-H1 expression by human cytomegalovirus in extravillous cytotrophoblast cells and role of MAPK pathway.
Pak J Med Sci
PUBLISHED: 02-25-2014
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This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in extravillous cytotrophoblast cell line HPT-8 and possible underlying mechanism.
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Controlled synthesis of phase-pure InAs nanowires on Si(111) by diminishing the diameter to 10 nm.
Nano Lett.
PUBLISHED: 02-18-2014
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Here we report the growth of phase-pure InAs nanowires on Si (111) substrates by molecular-beam epitaxy using Ag catalysts. A conventional one-step catalyst annealing process is found to give rise to InAs nanowires with diameters ranging from 4.5 to 81 nm due to the varying sizes of the Ag droplets, which reveal strong diameter dependence of the crystal structure. In contrast, a novel two-step catalyst annealing procedure yields vertical growth of highly uniform InAs nanowires ?10 nm in diameter. Significantly, these ultrathin nanowires exhibit a perfect wurtzite crystal structure, free of stacking faults and twin defects. Using these high-quality ultrathin InAs nanowires as the channel material of metal-oxide-semiconductor field-effect transistor, we have obtained a high ION/IOFF ratio of ?10(6), which shows great potential for application in future nanodevices with low power dissipation.
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Association between physical activity and mortality in breast cancer: a meta-analysis of cohort studies.
Eur. J. Epidemiol.
PUBLISHED: 01-31-2014
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Previous studies concerning the association between physical activity (PA) and mortality in breast cancer yielded mixed results. We investigated the association by performing a meta-analysis of all available studies. Relevant studies were identified by searching PubMed and EMBASE to January 2014. We calculated the summary relative risk (RR) and 95 % confidence intervals (CIs) using random-effects models. The dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Sixteen cohort studies involving 42,602 patients of breast cancer were selected for meta-analysis. The analyses showed that patients who participated in any amount of PA before diagnosis had a RR of 0.82 (95 % CI 0.74-0.91) for breast cancer-specific mortality (vs. low PA). Those who participated in high PA and moderate PA before diagnosis had a RR of breast cancer-specific mortality of 0.81 (95 % CI 0.72-0.90) and 0.83 (95 % CI 0.73-0.94), respectively. Similar inverse associations of prediagnosis PA were found for all-cause mortality. Postdiagnosis PA on breast cancer-specific and all-cause mortality also showed the same results. Stratifying by body mass index (<25 vs. ?25) or menopausal status, all the subgroups experienced benefits with PA, with a stronger mortality reduction among overweight women than normal weight women and among postmenopausal women than premenopausal women. A linear and significant dose-response association was only found for breast cancer-specific or all-cause mortality and prediagnosis PA (P for nonlinearity = 0.07 and 0.10, respectively). In conclusion, both prediagnosis and postdiagnosis PA were associated with reduced breast cancer-specific mortality and all-cause mortality.
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Tea consumption and leukemia risk: a meta-analysis.
Tumour Biol.
PUBLISHED: 01-22-2014
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Epidemiologic findings concerning the association between tea consumption and leukemia risk yielded mixed results. We aimed to investigate the association by performing a meta-analysis of all available studies. One cohort studies and six case-control studies with 1,019 cases were identified using PubMed, Web of Science, and EMBASE. We computed summary relative risks (RRs) and 95 % confidence intervals (CIs) using random effect model applied to the relative risk associated with ever, moderate, or highest drinkers vs. non/lowest drinkers. Subgroup analyses were performed based on country (China and USA). Compared with non/lowest drinkers, the combined RR for ever drinkers was 0.76 (95 % CI=0.65-0.89). In subgroup analyses, significant inverse associations were found for both China and USA studies. The summary RR was 0.57 (95 % CI=0.41-0.78) for highest drinkers. Same results were only found in China studies. No significant associations were found for moderate drinkers in overall analysis or in subgroup analyses. There was some evidence of publication bias. In conclusion, this meta-analysis suggests a significant inverse association of high tea consumption and leukemia risk. Results should be interpreted cautiously given the potential publication bias.
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Near infrared radiation rescues mitochondrial dysfunction in cortical neurons after oxygen-glucose deprivation.
Metab Brain Dis
PUBLISHED: 01-10-2014
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Near infrared radiation (NIR) is known to penetrate and affect biological systems in multiple ways. Recently, a series of experimental studies suggested that low intensity NIR may protect neuronal cells against a wide range of insults that mimic diseases such as stroke, brain trauma and neurodegeneration. However, the potential molecular mechanisms of neuroprotection with NIR remain poorly defined. In this study, we tested the hypothesis that low intensity NIR may attenuate hypoxia/ischemia-induced mitochondrial dysfunction in neurons. Primary cortical mouse neuronal cultures were subjected to 4 h oxygen-glucose deprivation followed by reoxygenation for 2 h, neurons were then treated with a 2 min exposure to 810-nm NIR. Mitochondrial function markers including MTT reduction and mitochondria membrane potential were measured at 2 h after treatment. Neurotoxicity was quantified 20 h later. Our results showed that 4 h oxygen-glucose deprivation plus 20 h reoxygenation caused 33.8?±?3.4 % of neuron death, while NIR exposure significantly reduced neuronal death to 23.6?±?2.9 %. MTT reduction rate was reduced to 75.9?±?2.7 % by oxygen-glucose deprivation compared to normoxic controls, but NIR exposure significantly rescued MTT reduction to 87.6?±?4.5 %. Furthermore, after oxygen-glucose deprivation, mitochondria membrane potential was reduced to 48.9?±?4.39 % of normoxic control, while NIR exposure significantly ameliorated this reduction to 89.6?±?13.9 % of normoxic control. Finally, NIR significantly rescued OGD-induced ATP production decline at 20 min after NIR. These findings suggest that low intensity NIR can protect neurons against oxygen-glucose deprivation by rescuing mitochondrial function and restoring neuronal energetics.
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Subtotal splenectomy for splenomegaly in cirrhotic patients.
Int J Clin Exp Pathol
PUBLISHED: 01-01-2014
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In recent years, the spleen has become to be recognized as the "control center" of the immune-metabolic-endocrine network. However, It is controversial that splenomegaly due to portal hypertension is treated by subtotal splenectomy. The aim of this study was to evaluate the distribution of fibrous tissue, morphology of cells as well as splenic size, hemodynamics, hematological and immunological indexes in the residual spleen after subtotal splenectomy. This information may help finding the basis for the operation of subtotal splenectomy.
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Radial scars and subsequent breast cancer risk: a meta-analysis.
PLoS ONE
PUBLISHED: 01-01-2014
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The relationship between radial scars and breast cancer is unclear, as the results of different studies are inconsistent. We aim to solve the controversy and assess the breast cancer risk of radial scars.
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Formylpeptide receptors mediate rapid neutrophil mobilization to accelerate wound healing.
PLoS ONE
PUBLISHED: 01-01-2014
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Wound healing is a multi-phased pathophysiological process requiring chemoattractant receptor-dependent accumulation of myeloid cells in the lesion. Two G protein-coupled formylpeptide receptors Fpr1 and Fpr2 mediate rapid neutrophil infiltration in the liver of Listeria-infected mice by sensing pathogen-derived chemotactic ligands. These receptors also recognize host-derived chemotactic peptides in inflammation and injury. Here we report the capacity of Fprs to promote the healing of sterile skin wound in mice by initiating neutrophil infiltration. We found that in normal miceneutrophils rapidly infiltrated the dermis in the wound before the production of neutrophil-specific chemokines by the injured tissue. In contrast, rapid neutrophil infiltration was markedly reduced with delayed wound closure in mice deficient in both Fprs. In addition, we detected Fpr ligand activity that chemoattracted neutrophils into the wound tissue. Our study thus demonstrates that Fprs are critical for normal healing of the sterile skin wound by mediating the first wave of neutrophil infiltration.
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Effects of Tissue Plasminogen Activator and Annexin A2 Combination Therapy on Long-Term Neurological Outcomes of Rat Focal Embolic Stroke.
Stroke
PUBLISHED: 12-24-2013
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Tissue-type plasminogen activator (tPA) in combination with recombinant annexin A2 (rA2) is known to reduce acute brain damage after focal ischemia. Here, we ask whether tPA-plus-rA2 combination therapy can lead to sustained long-term neurological improvements as well.
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Quantifying the backscattering of second harmonic generation in tissues with confocal multiphoton microscopy.
J Biomed Opt
PUBLISHED: 05-04-2013
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The backward second harmonic generation (SHG) in mouse tissues is studied with a confocal multiphoton microscopy system. The total backward collected SHG (B-SHG) consists of the backward generated SHG and the backward-scattered forward-generated SHG (BS-SHG), which can be modeled by a Gaussian and a uniform distribution, respectively, at the confocal pinhole plane. By varying the pinhole size with a series of collection fibers, the proportion of the BS-SHG to the B-SHG and the proportion of BS-SHG to the forward generated SHG can be obtained. The approach is first validated by Monte Carlo simulation. It is then applied to two types of mouse tissues: mouse tail tendon and Achilles tendon. It is found that the BS-SHG contributes less to the B-SHG for the tail tendon than Achilles tendon with thicknesses of ~300 ?m. With the thickness of the Achilles tendon tissue increased to 1000 ?m but the focal plane kept at the same depth, as high as ~10% of the total forward SHG is backscattered and collected. The results indicate that BS-SHG may not be the major source of B-SHG in the tail tendon, but it may be the major source in the Achilles tendon. These methods and results provide a noninvasive method and supporting information for investigating the generation mechanism of SHG and help with optimizing backward SHG microscopy and spectroscopy measurements.
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Generation of high quality chromatin immunoprecipitation DNA template for high-throughput sequencing (ChIP-seq).
J Vis Exp
PUBLISHED: 05-01-2013
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ChIP-sequencing (ChIP-seq) methods directly offer whole-genome coverage, where combining chromatin immunoprecipitation (ChIP) and massively parallel sequencing can be utilized to identify the repertoire of mammalian DNA sequences bound by transcription factors in vivo. "Next-generation" genome sequencing technologies provide 1-2 orders of magnitude increase in the amount of sequence that can be cost-effectively generated over older technologies thus allowing for ChIP-seq methods to directly provide whole-genome coverage for effective profiling of mammalian protein-DNA interactions. For successful ChIP-seq approaches, one must generate high quality ChIP DNA template to obtain the best sequencing outcomes. The description is based around experience with the protein product of the gene most strongly implicated in the pathogenesis of type 2 diabetes, namely the transcription factor transcription factor 7-like 2 (TCF7L2). This factor has also been implicated in various cancers. Outlined is how to generate high quality ChIP DNA template derived from the colorectal carcinoma cell line, HCT116, in order to build a high-resolution map through sequencing to determine the genes bound by TCF7L2, giving further insight in to its key role in the pathogenesis of complex traits.
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MiR-222 and miR-29a contribute to the drug-resistance of breast cancer cells.
Gene
PUBLISHED: 04-24-2013
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Adriamycin (Adr) and docetaxel (Doc) are two chemotherapeutic agents commonly used in the treatment of breast cancer. However, patients with breast cancer who are treated by the drugs often develop resistance to them and some other drugs. Recently studies have shown that microRNAs (miRNAs, miRs) play an important role in drug-resistance. In present study, miRNA expression profiles of MCF-7/S and its two resistant variant MCF-7/Adr and MCF-7/Doc cells were analyzed using microarray and the results were confirmed by real-time quantitative polymerase chain reaction. Here, 183 differentially expressed miRNAs were identified in the two resistant sublines compared to MCF-7/S. Then, five up-regulated miRNAs (miR-100, miR-29a, miR-196a, miR-222 and miR-30a) in both MCF-7/Adr and MCF-7/Doc were selected to explore their roles in acquisition of drug-resistance using transfection experiment. The results showed that miR-222 and miR-29a mimics and inhibitors had partially changed the drug-resistance of breast cancer cells, which was also confirmed by apoptosis assay. Western blot results suggested that miR-222 and -29a could regulate the expression of PTEN, maybe through which the two miRNAs conferred Adr and Doc resistance in MCF-7 cells. Finally, pathway mapping tools were employed to further analyze signaling pathways affected by the two miRNAs. In summary, this study demonstrates that altered miRNA expression pattern is involved in acquiring resistance to Adr and Doc in breast cancer MCF-7 cells, and that there are some miRNAs who displayed consistent up- or down-regulated expression changes in the two resistant sublines. The most importance is that we identify two miRNAs (miR-222 and miR-29a) involved in drug-resistance, at least in part via targeting PTEN.
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Methionine synthase A2756G polymorphism and breast cancer risk: an up-to-date meta-analysis.
Gene
PUBLISHED: 04-04-2013
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The methionine synthase (MTR) gene polymorphism A2756G has been linked to the risk of developing breast cancer, but the available results were inconsistent and underpowered. To derive a more precise estimation of the association between A2756G and breast cancer risk, an updated meta-analysis of 16 available studies with 9866 cases and 11,702 controls estimating the association between MTR A2756G and breast cancer risk was conducted. The quality of these studies was generally good except 2 studies with a lowest score 4 according to the Newcastle-Ottawa Scale (NOS). The results suggested that there is no significant association between A2756G and breast cancer risk in overall results. In the stratified analysis by ethnicity, source of controls (population or hospital-based), Hardy-Weinberg equilibrium (HWE) in controls, sample size (?1000 and <1000 subjects), and menopausal status, the 2756G allele was associated with a decreased risk in Caucasians, PB (population-based) subgroup, and large studies. But the associations disappeared after removing the studies not in HWE. On the contrary, an increased risk was found in small studies. In conclusion, the findings suggest that MTR A2756G polymorphism is not associated with altered susceptibility to breast cancer, while the observed decreased risk in Caucasians, PB subgroup, and large studies and increased risk in small studies may be due to selection bias or other unknown factors.
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All zinc-blende GaAs/(Ga,Mn)As core-shell nanowires with ferromagnetic ordering.
Nano Lett.
PUBLISHED: 03-26-2013
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Combining self-catalyzed vapor-liquid-solid growth of GaAs nanowires and low-temperature molecular-beam epitaxy of (Ga,Mn)As, we successfully synthesized all zinc-blende (ZB) GaAs/(Ga,Mn)As core-shell nanowires on Si(111) substrates. The ZB GaAs nanowire cores are first fabricated at high temperature by utilizing the Ga droplets as the catalyst and controlling the triple phase line nucleation, then the (Ga,Mn)As shells are epitaxially grown on the side facets of the GaAs core at low temperature. The growth window for the pure phase GaAs/(Ga,Mn)As core-shell nanowires is found to be very narrow. Both high-resolution transmission electron microscopy and scanning electron microscopy observations confirm that all-ZB GaAs/(Ga,Mn)As core-shell nanowires with smooth side surface are obtained when the Mn concentration is not more than 2% and the growth temperature is 245 °C or below. Magnetic measurements with different applied field directions provide strong evidence for ferromagnetic ordering in the all-ZB GaAs/(Ga,Mn)As nanowires. The hybrid nanowires offer an attractive platform to explore spin transport and device concepts in fully epitaxial all-semiconductor nanospintronic structures.
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The missense variation landscape of FTO, MC4R, and TMEM18 in obese children of African Ancestry.
Obesity (Silver Spring)
PUBLISHED: 03-19-2013
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Common variation at the loci harboring fat mass and obesity (FTO), melanocortin receptor 4 (MC4R), and transmembrane protein 18 (TMEM18) is consistently reported as being statistically most strongly associated with obesity. Investigations if these loci also harbor rarer missense variants that confer substantially higher risk of common childhood obesity in African American (AA) children were conducted.
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Monte Carlo simulation of in vivo Raman spectral Measurements of human skin with a multi-layered tissue optical model.
J Biophotonics
PUBLISHED: 03-18-2013
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Raman photon generation inside human skin and escaping to skin surface were modeled in an eight-layered skin optical model. Intrinsic Raman spectra of different skin layers were determined by microscopy measurements of excised skin tissue sections. Monte Carlo simulation was used to study the excitation light distribution and intrinsic Raman signal distortion caused by tissue reabsorption and scattering during in vivo measurements. The simulation results demonstrated how different skin layers contributed to the observed in vivo Raman spectrum. Using the strongest Raman peak at 1445 cm(-1) as an example, the simulation suggested that the integrated contributions of the stratum corneum layer is 1.3%, the epidermis layer 28%, the dermis layer 70%, and the subcutaneous fat layer 1.1%. Reasonably good matching between the calculated spectrum and the measured in vivo Raman spectra was achieved, thus demonstrated great utility of our modeling method and approaches for help understanding the clinical measurements. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
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Calibrating the measurement of wavelength-dependent second harmonic generation from biological tissues with a BaB?O? crystal.
J Biomed Opt
PUBLISHED: 02-12-2013
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Although second harmonic generation (SHG) imaging has emerged as a powerful tool for imaging biological tissues with submicron resolution, the excitation wavelength dependence of SHG intensity in biological tissues is an optical property that is not fully understood so far. We first calibrate system factors which may potentially affect the accuracy of the wavelength-dependent SHG measurement. Then our calibration is validated by measuring the wavelength dependence of SHG signal from a BaB?O? crystal under different focusing conditions and comparing with the theoretical calculations. The good agreement between the experimental results and theoretical calculations demonstrates that we have established a reliable method to validate wavelength-dependent SHG measurement over a broad wavelength range. We also investigate the wavelength dependence of a 10-?m thick mouse tendon tissue in both forward and backward directions. It is found that SHG of mouse tendon tissue decreases monotonically for excitation from 750 to 950 nm.
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Imaging directed photothermolysis through two-photon absorption demonstrated on mouse skin - a potential novel tool for highly targeted skin treatment.
J Biophotonics
PUBLISHED: 01-25-2013
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One-photon absorption based traditional laser treatment may not necessarily be selective at the microscopic level, thus could result in un-intended tissue damage. Our objective is to test whether two-photon absorption (TPA) could provide highly targeted tissue alteration of specific region of interest without damaging surrounding tissues. TPA based laser treatments (785 nm, 140 fs pulse width, 90 MHz) were performed on ex vivo mouse skin using different average power levels and irradiation times. Reflectance confocal microscopy (RCM) and combined second-harmonic-generation (SHG) and two-photon fluorescence (TPF) imaging channels were used to image before, during, and after each laser treatment. The skin was fixed, sectioned and H & E stained after each experiment for histological assessment of tissue alterations and for comparison with the non-invasive imaging assessments. Localized destruction of dermal fibers was observed without discernible epidermal damage on both RCM and SHG + TPF images for all the experiments. RCM and SHG + TPF images correlated well with conventional histological examination. This work demonstrated that TPA-based light treatment provides highly localized intradermal tissue alteration. With further studies on optimizing laser treatment parameters, this two-photon absorption photothermolysis method could potentially be applied in clinical dermatology. (© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim).
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Polybrominated diphenyl ethers in birds from Chongming Island, Yangtze estuary, China: insight into migratory behavior.
Chemosphere
PUBLISHED: 01-16-2013
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Sum-PBDEs concentrations in shorebirds and Anatidae ducks muscles from Chongming Dongtan National Nature Reserve ranged from 21-324 to 14-159ngg(-1) lw, respectively. PBDEs were detected in muscles of all the studied species. Compared with flyways around the world, migratory waterbirds on the East Asian-Australasian flyway exhibited lower PBDEs burdens than those reported on Black Sea-Mediterranean flyway in Europe and Pacific, Atlantic, Mississippi flyway in North America. Residential Eurasian tree sparrow samples indicated few PBDE products were used in Chongming Island developed in the idea of world famous eco-island. There was no significant difference in PBDEs concentrations between shorebirds and ducks. However, PBDEs composition varied between them. BDE 209 (29-44%) contributed to sum-PBDEs more than BDE 47 (17-19%) in muscles of ducks, while BDE 47 was the predominant congener in shorebirds contributing 32-48%. Stable nitrogen and carbon isotopes and stomach content analysis indicated shorebirds and ducks had the same dietary composition, but showed different preference to bivalves, gastropods and crustaceans for shorebirds and aquatic plant material for ducks. Migratory species had inherent migratory routes and thus had exposure to PBDEs during their stay in breeding grounds, stopover sites and wintering grounds with high use of different commercial PBDE mixtures. Higher percentage of BDE 209 in ducks than shorebirds suggested that breeding ranges and wintering grounds of ducks comprise wetlands in inland and coastal China and Korea where decaBDEs pollution was serious in Asian-Pacific region. Our findings reveal the influence of migratory behavior on PBDEs distribution in migratory waterbirds.
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TMaCS: a hybrid template matching and classification system for partially-automated particle selection.
J. Struct. Biol.
PUBLISHED: 01-16-2013
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Selection of particle images from electron micrographs presents a bottleneck in determining the structures of macromolecular assemblies by single particle electron cryomicroscopy (cryo-EM). The problem is particularly important when an experimentalist wants to improve the resolution of a 3D map by increasing by tens or hundreds of thousands of images the size of the dataset used for calculating the map. Although several existing methods for automatic particle image selection work well for large protein complexes that produce high-contrast images, it is well known in the cryo-EM community that small complexes that give low-contrast images are often refractory to existing automated particle image selection schemes. Here we develop a method for partially-automated particle image selection when an initial 3D map of the protein under investigation is already available. Candidate particle images are selected from micrographs by template matching with template images derived from projections of the existing 3D map. The candidate particle images are then used to train a support vector machine, which classifies the candidates as particle images or non-particle images. In a final step in the analysis, the selected particle images are subjected to projection matching against the initial 3D map, with the correlation coefficient between the particle image and the best matching map projection used to assess the reliability of the particle image. We show that this approach is able to rapidly select particle images from micrographs of a rotary ATPase, a type of membrane protein complex involved in many aspects of biology.
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Maize grain concentrations and above-ground shoot acquisition of micronutrients as affected by intercropping with turnip, faba bean, chickpea, and soybean.
Sci China Life Sci
PUBLISHED: 01-15-2013
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Most research on micronutrients in maize has focused on maize grown as a monocrop. The aim of this study was to determine the effects of intercropping on the concentrations of micronutrients in maize grain and their acquisition via the shoot. We conducted field experiments to investigate the effects of intercropping with turnip (Brassica campestris L.), faba bean (Vicia faba L.), chickpea (Cicer arietinum L.), and soybean (Glycine max L.) on the iron (Fe), manganese (Mn), copper (Cu) and zinc (Zn) concentrations in the grain and their acquisition via the above-ground shoots of maize (Zea mays L.). Compared with monocropped maize grain, the grain of maize intercropped with legumes showed lower concentrations of Fe, Mn, Cu, and Zn and lower values of their corresponding harvest indexes. The micronutrient concentrations and harvest indexes in grain of maize intercropped with turnip were the same as those in monocropped maize grain. Intercropping stimulated the above-ground maize shoot acquisition of Fe, Mn, Cu and Zn, when averaged over different phosphorus (P) application rates. To our knowledge, this is the first report on the effects of intercropping on micronutrient concentrations in maize grain and on micronutrients acquisition via maize shoots (straw+grain). The maize grain Fe and Cu concentrations, but not Mn and Zn concentrations, were negatively correlated with maize grain yields. The concentrations of Fe, Mn, Cu, and Zn in maize grain were positively correlated with their corresponding harvest indexes. The decreased Fe, Mn, Cu, and Zn concentrations in grain of maize intercropped with legumes were attributed to reduced translocation of Fe, Mn, Cu, and Zn from vegetative tissues to grains. This may also be related to the delayed senescence of maize plants intercropped with legumes. We conclude that turnip/maize intercropping is beneficial to obtain high maize grain yield without decreased concentrations of Fe, Mn, Cu, and Zn in the grain. Further research is required to clarify the mechanisms underlying the changes in micronutrient concentrations in grain of intercropped maize.
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A handheld electromagnetically actuated fiber optic raster scanner for reflectance confocal imaging of biological tissues.
IEEE Trans Biomed Eng
PUBLISHED: 01-08-2013
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We present a hand-held device aimed for reflectance-mode confocal imaging of biological tissues. The device consists of a light carrying optical fiber and a miniaturized raster scanner located at the distal end of the fiber. It is fabricated by mounting a polarization maintaining optical fiber on a cantilever beam that is attached to another beam such that their bending axes are perpendicular to each other. Fiber scanner is driven by electromagnetic forces and enables large fiber deflections with low driving currents. Optical resolutions of the system are 1.55 and 8.45 ?m in the lateral and axial directions, respectively. Functionality of the system is demonstrated by obtaining confocal images of a fly wing and a human colon tissue sample.
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Full range characterization of the Raman spectra of organs in a murine model.
Opt Express
PUBLISHED: 11-24-2011
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Raman spectroscopy is a minimally-invasive optical technique with great potential for in vivo cancer detection and disease diagnosis. However, there is no systematic study of the Raman spectra from different organs to date. We measured and characterized the Raman spectra eighteen naïve mouse organs in a broad frequency range of 700 to 3100 cm?¹. The peaks of generic proteins and lipids appeared in Raman spectra of all organs. Some organs like bone, teeth, brain and lung had unique Raman peaks. The autofluorescence was strong in liver, spleen, heart, and kidney. These results suggest that organ specific Raman probe design and specific data processing strategies are required in order to get the most useful information.
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Paclitaxel induced B7-H1 expression in cancer cells via the MAPK pathway.
J Chemother
PUBLISHED: 10-19-2011
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In this study, we investigated the mechanisms by which the chemotherapeutic agent paclitaxel (PTX) induced the expression of B7-H1 immunosuppressive molecules in the human colorectal adenocarcinoma cell line SW480 and the hepatocellular carcinoma cell line HepG2. We found ptX induced B7-H1 protein expression in SW480 and HepG2 cells as demonstrated by immunofluorescence and flow cytometry and mRNA expression by using real-time quantitative polymerase chain reaction (PCR). Moreover, PTX treatment induced Erk½ phosphorylation in both cell lines. PTX-increased B7-H1 mRNA expression was significantly blocked by MEK inhibitor U0126. However, the protein expression caused by PTX was only partially blocked by U0126. Our results suggest that PTX upregulated B7-H1 expression in cultured SW480 and HepG2 cells via both transcriptional and post-transcriptional mechanisms. This may help us better understand PTX-related tumor immune evasion.
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Advances in whole genome sequencing technology.
Curr Pharm Biotechnol
PUBLISHED: 09-03-2011
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Sanger sequencing revolutionized the field of genetics by becoming the standard approach to appraise a given region of the genome at base-level resolution. However, the relatively recent need to sequence entire genomes has driven innovative developments within the market-place to allow for sequencing technology to be faster, cheaper and more accurate. In this review, we will cover these recent developments from both a technical and cost perspective. Firstly, we will place sequencing in a historical context by describing how it first came to the attention of the scientific community. Next, we will address the current high-throughput technologies generally available, including Roches 454, Illuminas Genome Analyzer, Applied BioSystems SOLiD, Complete Genomics, Helios, Pacific Biosciences and IonTorrent. These next-generation technologies also allow for applications related to target region deep sequencing, epigenetics(ChIP-seq), transcriptome sequencing (RNA-seq), megagenomics. Thus, these technologies offer unprecedented opportunities to increase our understanding of the functions and dynamics of the human genome in the near future.
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Vertical optical sectioning using a magnetically driven confocal microscanner aimed for in vivo clinical imaging.
Opt Express
PUBLISHED: 09-02-2011
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This paper presents a confocal microscanner for direct vertical optical sectioning of biological samples. Confocal imaging is performed by transverse (X-axis) and axial (Z-axis) scanning of a focused laser beam using an optical fiber and a microlens respectively. The actuators are fabricated by laser micromachining techniques and are driven by electromagnetic forces. Optical and mechanical performance of the system is predicted by simulation software packages and characterized by experimental measurements. The scanner has lateral resolution of 3.87 µm and axial resolution of 10.68 µm with a field of view of 145 µm in X and 190 µm in Z directions. Confocal imaging of a polymer layer deposited on a silicon wafer and onion epidermal cells is demonstrated.
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In vivo video rate multiphoton microscopy imaging of human skin.
Opt Lett
PUBLISHED: 08-03-2011
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We present a multiphoton microscopy instrument specially designed for in vivo dermatological use that is capable of imaging human skin at 27 frames per second with 256 pixels × 256 pixels resolution without the use of exogenous contrast agents. Imaging at fast frame rates is critical to reducing image blurring due to patient motion and to providing practically short clinical measurement times. Second harmonic generation and two-photon fluorescence images and videos acquired at optimized wavelengths are presented showing cellular and tissue structures from the skin surface down to the reticular dermis.
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Role of BMI-associated loci identified in GWAS meta-analyses in the context of common childhood obesity in European Americans.
Obesity (Silver Spring)
PUBLISHED: 07-21-2011
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Obesity is a serious health concern for children and adolescents, particularly in Western societies, where its incidence is now considered to have reached epidemic proportions. A number of genetic determinants of adult BMI have already been established through genome wide association studies (GWAS), most recently from the GIANT meta-analysis of such datasets combined. In this current study of European Americans, we examined the 32 loci detected in that GIANT study in the context of common childhood obesity within a cohort of 1,097 cases (defined as BMI ?95th percentile), together with 2,760 lean controls (defined as BMI <50th percentile), aged between 2 and 18 years old. Nine of these single-nucleotide polymorphims (SNPs) yielded at least nominal evidence for association with common childhood obesity, namely at the FTO, TMEM18, NRXN3, MC4R, SEC16B, GNPDA2, TNNI3K, QPCTL, and BDNF loci. However, overall 28 of the 32 loci showed directionally consistent effects to that of the adult BMI meta-analysis. We conclude that among the 32 loci that have been reported to associate with adult BMI in the largest meta-analysis of BMI to date, at least nine also contribute to the determination of common obesity in childhood in European Americans, as demonstrated by their associations in our pediatric cohort.
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Enhancing the Curie temperature of ferromagnetic semiconductor (Ga,Mn)As to 200 K via nanostructure engineering.
Nano Lett.
PUBLISHED: 06-27-2011
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We demonstrate by magneto-transport measurements that a Curie temperature as high as 200 K can be obtained in nanostructures of (Ga,Mn)As. Heavily Mn-doped (Ga,Mn)As films were patterned into nanowires and then subject to low-temperature annealing. Resistance and Hall effect measurements demonstrated a consistent increase of T(C) with decreasing wire width down to about 300 nm. This observation is attributed primarily to the increase of the free surface in the narrower wires, which allows the Mn interstitials to diffuse out at the sidewalls, thus enhancing the efficiency of annealing. These results may provide useful information on optimal structures for (Ga,Mn)As-based nanospintronic devices operational at relatively high temperatures.
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Monte Carlo simulation of near infrared autofluorescence measurements of in vivo skin.
J. Photochem. Photobiol. B, Biol.
PUBLISHED: 04-13-2011
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The autofluorescence properties of normal human skin in the near-infrared (NIR) spectral range were studied using Monte Carlo simulation. The light-tissue interactions including scattering, absorption and anisotropy propagation of the regenerated autofluorescence photons in the skin tissue were taken into account in the theoretical modeling. Skin was represented as a turbid seven-layered medium. To facilitate the simulation, ex vivo NIR autofluorescence spectra and images from different skin layers were measured from frozen skin vertical sections to define the intrinsic fluorescence properties. Monte Carlo simulation was then used to study how the intrinsic fluorescence spectra were distorted by the tissue reabsorption and scattering during in vivo measurements. We found that the reconstructed model skin spectra were in good agreement with the measured in vivo skin spectra from the same anatomical site as the ex vivo tissue sections, demonstrating the usefulness of this modeling. We also found that difference exists over the melanin fluorescent wavelength range (880-910 nm) between the simulated spectrum and the measured in vivo skin spectrum from a different anatomical site. This difference suggests that melanin contents may affect in vivo skin autofluorescence properties, which deserves further investigation.
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Genetics of childhood obesity.
J Obes
PUBLISHED: 04-06-2011
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Obesity is a major health problem and an immense economic burden on the health care systems both in the United States and the rest of the world. The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. Genome-wide association studies (GWAS) have revealed strongly associated genomic variants associated with most common disorders; indeed there is general consensus on these findings from generally positive replication outcomes by independent groups. To date, there have been only a few GWAS-related reports for childhood obesity specifically, with studies primarily uncovering loci in the adult setting instead. It is clear that a number of loci previously reported from GWAS analyses of adult BMI and/or obesity also play a role in childhood obesity.
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Strain-induced high ferromagnetic transition temperature of MnAs epilayer grown on GaAs (110).
Nanoscale Res Lett
PUBLISHED: 02-09-2011
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MnAs films are grown on GaAs surfaces by molecular beam epitaxy. Specular and grazing incidence X-ray diffractions are used to study the influence of different strain states of MnAs/GaAs (110) and MnAs/GaAs (001) on the first-order magnetostructural phase transition. It comes out that the first-order magnetostructural phase transition temperature Tt, at which the remnant magnetization becomes zero, is strongly affected by the strain constraint from different oriented GaAs substrates. Our results show an elevated Tt of 350 K for MnAs films grown on GaAs (110) surface, which is attributed to the effect of strain constraint from different directions.PACS: 68.35.Rh, 61.50.Ks, 81.15.Hi, 07.85.Qe.
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BMD-associated variation at the Osterix locus is correlated with childhood obesity in females.
Obesity (Silver Spring)
PUBLISHED: 01-06-2011
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Recent genome wide association studies (GWAS) have revealed a number of genetic variants robustly associated with bone mineral density (BMD) and/or osteoporosis. Evidence from epidemiological and clinical studies has shown an association between BMD and BMI, presumably as a consequence of bone loading. We investigated the 23 previously published BMD GWAS-derived loci in the context of childhood obesity by leveraging our existing genome-wide genotyped European American cohort of 1106 obese children (BMI ? 95th percentile) and 5997 controls (BMI < 95th percentile). Evidence of association was only observed at one locus, namely Osterix (SP7), with the G allele of rs2016266 being significantly over-represented among childhood obesity cases (P = 2.85 × 10(-3)). When restricting these analyses to each gender, we observed strong association between rs2016266 and childhood obesity in females (477 cases and 2867 controls; P = 3.56 × 10(-4)), which survived adjustment for all tests applied. However, no evidence of association was observed among males. Interestingly, Osterix is the only GWAS locus uncovered to date that has also been previously implicated in the determination of BMD in childhood. In conclusion, these findings indicate that a well established variant at the Osterix locus associated with increased BMD is also associated with childhood obesity primarily in females.
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Single-wall carbon nanotubes assisted photothermal cancer therapy: animal study with a murine model of squamous cell carcinoma.
Lasers Surg Med
PUBLISHED: 10-16-2010
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There has been a dramatic increase in photothermal therapy as a minimally invasive treatment modality for cancer treatment due to the development of novel nanomaterials as the light absorption agents. Single-wall carbon nanotubes (SWNTs) with strong optical absorption in the broad visible and near IR offer unique advantages for photothermal cancer therapy. A broad range of wavelengths can be used for the treatment with SWNTs, whereas conventional photothermal therapeutic agent is designed to absorb light only near one selected wavelength. The objective of this study is to validate the hypothesis that intratumoral injected SWNTs can absorb 785 nm near IR laser light and generate significant local hyperthermia to destroy tumors.
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A genome-wide study reveals copy number variants exclusive to childhood obesity cases.
Am. J. Hum. Genet.
PUBLISHED: 07-12-2010
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The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Genomic copy number variations (CNVs) have been strongly implicated in subjects with extreme obesity and coexisting developmental delay. To complement these previous studies, we addressed CNVs in common childhood obesity by examining children with a BMI in the upper 5(th) percentile but excluding any subject greater than three standard deviations from the mean in order to reduce severe cases in the cohort. We performed a whole-genome CNV survey of our cohort of 1080 defined European American (EA) childhood obesity cases and 2500 lean controls (< 50(th) percentile BMI) who were genotyped with 550,000 SNP markers. Positive findings were evaluated in an independent African American (AA) cohort of 1479 childhood obesity cases and 1575 lean controls. We identified 17 CNV loci that were unique to at least three EA cases and were both previously unreported in the public domain and validated via quantitative PCR. Eight of these loci (47.1%) also replicated exclusively in AA cases (six deletions and two duplications). Replicated deletion loci consisted of EDIL3, S1PR5, FOXP2, TBCA, ABCB5, and ZPLD1, whereas replicated duplication loci consisted of KIF2B and ARL15. We also observed evidence for a deletion at the EPHA6-UNQ6114 locus when the AA cohort was investigated as a discovery set. Although these variants may be individually rare, our results indicate that CNVs contribute to the genetic susceptibility of common childhood obesity in subjects of both European and African ancestry.
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Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits.
Int Orthop
PUBLISHED: 06-04-2010
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To assess the potential efficacy of mechano growth factor (MGF) for bone injury, we firstly investigated the effects of growth factors, including MGF, its E peptide (a short 24-amino acid C-terminal peptide, MGF-Ct24E), and insulin-like growth factor 1(IGF-1) on MC3T3-E1 osteoblast-like cell proliferation. MGF-Ct24E had the highest pro-proliferation activity among three growth factors, which was 1.4 times greater than that of IGF-1. Moreover, MGF-Ct24E promoted cell proliferation by inducing cell cycle arrest in the S and G(2)/M phase of the cell cycle, but also mainly by the activation of the MAPK-Erk1/2 pathway. In vivo, a 5-mm segmental bone defect in the radius of 27 rabbits was treated with MGF-Ct24E by two doses (28.5 and 57 ?g /kg body weight) vs. non-growth factor injection for five consecutive days postoperatively. The cumulative rate of radiographically healed defects and histological scores of bone defect-healing revealed a statistical difference between high-dose treatment and non treatment (p?
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Variants in ADCY5 and near CCNL1 are associated with fetal growth and birth weight.
Nat. Genet.
PUBLISHED: 03-17-2010
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To identify genetic variants associated with birth weight, we meta-analyzed six genome-wide association (GWA) studies (n = 10,623 Europeans from pregnancy/birth cohorts) and followed up two lead signals in 13 replication studies (n = 27,591). rs900400 near LEKR1 and CCNL1 (P = 2 x 10(-35)) and rs9883204 in ADCY5 (P = 7 x 10(-15)) were robustly associated with birth weight. Correlated SNPs in ADCY5 were recently implicated in regulation of glucose levels and susceptibility to type 2 diabetes, providing evidence that the well-described association between lower birth weight and subsequent type 2 diabetes has a genetic component, distinct from the proposed role of programming by maternal nutrition. Using data from both SNPs, we found that the 9% of Europeans carrying four birth weight-lowering alleles were, on average, 113 g (95% CI 89-137 g) lighter at birth than the 24% with zero or one alleles (P(trend) = 7 x 10(-30)). The impact on birth weight is similar to that of a mother smoking 4-5 cigarettes per day in the third trimester of pregnancy.
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Genotype and tissue-specific effects on alternative splicing of the transcription factor 7-like 2 gene in humans.
J. Clin. Endocrinol. Metab.
PUBLISHED: 01-22-2010
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Context: Noncoding single-nucleotide polymorphisms (SNPs) within the TCF7L2 gene are confirmed risk factors for type 2 diabetes, but the mechanism by which they increase risk is unknown. Objective: We hypothesized that associated SNPs alter TCF7L2 splicing and that splice forms have altered biological roles. Design: Splice forms and 5 and 3 untranslated regions were characterized in sc adipose, muscle, liver, HepG2 cells, pancreas, and islet. Isoform-specific transcript levels were quantified in sc adipose. Alternative splice forms were characterized in HepG2 liver cells under glucose and insulin conditions and in SGBS cells with differentiation. Major isoforms were characterized by transfection. Setting: The study was conducted at an ambulatory general clinical research center. Patients: Patients included 78 healthy, nondiabetic study subjects characterized for insulin sensitivity and secretion. Results: We identified 32 alternatively spliced transcripts and multiple-length 3 untranslated region transcripts in adipose, muscle, islet, and pancreas. Alternative exons 3a, 12, 13, and 13a were observed in all tissues, whereas exon 13b was islet specific. Transcripts retaining exons 13 and 13a but not total TCF7L2 transcripts were significantly correlated with both obesity measures (P < 0.01) and rs7903146 genotype (P < 0.026) in sc adipose. Insulin (5-10 nm) suppressed all TCF7L2 isoforms in SGBS cells but suppressed exon 13a-containing isoforms most significantly (P < 0.001). The isoform distribution differed throughout SGBS cell differentiation. Isoforms with predicted early stop codons yielded stable proteins of the predicted size, bound beta-catenin, and targeted correctly to the nucleus. Conclusions: Intronic TCF7L2 variants may regulate alternative transcript isoforms, which in turn may have distinct physiologic roles.
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The role of height-associated loci identified in genome wide association studies in the determination of pediatric stature.
BMC Med. Genet.
PUBLISHED: 01-20-2010
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Human height is considered highly heritable and correlated with certain disorders, such as type 2 diabetes and cancer. Despite environmental influences, genetic factors are known to play an important role in stature determination. A number of genetic determinants of adult height have already been established through genome wide association studies.
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Examination of all type 2 diabetes GWAS loci reveals HHEX-IDE as a locus influencing pediatric BMI.
Diabetes
PUBLISHED: 11-23-2009
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A number of studies have found that BMI in early life influences the risk of developing type 2 diabetes later in life. Our goal was to investigate if any type 2 diabetes variants uncovered through genome-wide association studies (GWAS) impact BMI in childhood.
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Spectroscopic characterization and microscopic imaging of extracted and in situ cutaneous collagen and elastic tissue components under two-photon excitation.
Skin Res Technol
PUBLISHED: 10-17-2009
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Understanding the two-photon excitation spectral characteristics and microscopic morphology of cutaneous collagen and elastic tissue components is important for applying multiphoton microscopy (MPM) in basic skin biology research and for clinical diagnosis.
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Examination of type 2 diabetes loci implicates CDKAL1 as a birth weight gene.
Diabetes
PUBLISHED: 07-10-2009
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A number of studies have found that reduced birth weight is associated with type 2 diabetes later in life; however, the underlying mechanism for this correlation remains unresolved. Recently, association has been demonstrated between low birth weight and single nucleotide polymorphisms (SNPs) at the CDKAL1 and HHEX-IDE loci, regions that were previously implicated in the pathogenesis of type 2 diabetes. In order to investigate whether type 2 diabetes risk-conferring alleles associate with low birth weight in our Caucasian childhood cohort, we examined the effects of 20 such loci on this trait.
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The quantitative research of composite immune indicator for crustacean.
Fish Shellfish Immunol.
PUBLISHED: 07-09-2009
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Through analyzing the immunity indicators in recent crustacean research, two defects are pointed in comprehensive immunity evaluation, 1) the integrant indicators cannot comprehensively reflect the change of immunity, and 2) the conclusions that obtained from different indicators of immunity level cannot be compared objectively and scientifically. Basing on that, the paper firstly indicated that the immunity system could be regarded as a composite indicator. Secondly, the paper gave the specific definition of the composite immunity indicator (CII), and discussed the methods of calculation, especially provided two calculation methods of the weights, that is, the Analytic Hierarchy Process (AHP) and the Principal Component Analysis (PCA). Finally, examples were given to clarify the specific steps to compute the composite immunity indicator. The computing results gave the quantitative evaluation, which were in concordance with the existing conclusions.
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The role of obesity-associated loci identified in genome-wide association studies in the determination of pediatric BMI.
Obesity (Silver Spring)
PUBLISHED: 05-28-2009
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The prevalence of obesity in children and adults in the United States has increased dramatically over the past decade. Besides environmental factors, genetic factors are known to play an important role in the pathogenesis of obesity. A number of genetic determinants of adult BMI have already been established through genome-wide association (GWA) studies. In this study, we examined 25 single-nucleotide polymorphisms (SNPs) corresponding to 13 previously reported genomic loci in 6,078 children with measures of BMI. Fifteen of these SNPs yielded at least nominally significant association to BMI, representing nine different loci including INSIG2, FTO, MC4R, TMEM18, GNPDA2, NEGR1, BDNF, KCTD15, and 1q25. Other loci revealed no evidence for association, namely at MTCH2, SH2B1, 12q13, and 3q27. For the 15 associated variants, the genotype score explained 1.12% of the total variation for BMI z-score. We conclude that among 13 loci that have been reported to associate with adult BMI, at least nine also contribute to the determination of BMI in childhood as demonstrated by their associations in our pediatric cohort.
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Mitogen-activated protein kinase hog1 in the entomopathogenic fungus Beauveria bassiana regulates environmental stress responses and virulence to insects.
Appl. Environ. Microbiol.
PUBLISHED: 04-10-2009
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Beauveria bassiana is an economically important insect-pathogenic fungus which is widely used as a biocontrol agent to control a variety of insect pests. However, its insecticide efficacy in the field is often influenced by adverse environmental factors. Thus, understanding the genetic regulatory processes involved in the response to environmental stress would facilitate engineering and production of a more efficient biocontrol agent. Here, a mitogen-activated protein kinase (MAPK)-encoding gene, Bbhog1, was isolated from B. bassiana and shown to encode a functional homolog of yeast HIGH-OSMOLARITY GLYCEROL 1 (HOG1). A Bbhog1 null mutation was generated in B. bassiana by targeted gene replacement, and the resulting mutants were more sensitive to hyperosmotic stress, high temperature, and oxidative stress than the wild-type controls. These results demonstrate the conserved function of HOG1 MAPKs in the regulation of abiotic stress responses. Interestingly, DeltaBbhog1 mutants exhibited greatly reduced pathogenicity, most likely due to a decrease in spore viability, a reduced ability to attach to insect cuticle, and a reduction in appressorium formation. The transcript levels of two hydrophobin-encoding genes, hyd1 and hyd2, were dramatically decreased in a DeltaBbhog1 mutant, suggesting that Bbhog1 may regulate the expression of the gene associated with hydrophobicity or adherence.
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HACE1: A novel repressor of RAR transcriptional activity.
J. Cell. Biochem.
PUBLISHED: 04-08-2009
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The diverse biological actions of retinoic acid (RA) are mediated by RA receptors (RARs) and retinoid X receptors (RXRs). While the coregulatory proteins that interact with the ligand-dependent AF-2 in the E region are well studied, the ligand-independent N-terminal AF-1 domain-interacting partners and their influence(s) on the function of RARs are poorly understood. HECT domain and Ankyrin repeat containing E3 ubiquitin-protein ligase (HACE1) was isolated as a RARbeta(3) AB region interacting protein. HACE1 interacts with RARbeta(3) both in in vitro GST pull-down and in cell-based coprecipitation assays. The interaction sites map to the N terminus of RARbeta(3) and the C terminus of HACE1. HACE1 functionally represses the transcriptional activity of RARalpha(1), RARbeta isoforms 1, 2, and 3, but not RARgamma(1) in luciferase reporter assays. In addition, HACE1 represses the endogenous RAR-regulated genes CRABP II, RIG1 and RARbeta(2), but not RAI3 in CAOV3 cells. Mutation of the putative catalytic cysteine (C876 of LF HACE1), which is indispensable for its E3 ubiquitin ligase activity, does not alter the repressive effect of HACE1 on the transcriptional activity of RARbeta(3). On the other hand, HACE1 inhibits the RA dependent degradation of RARbeta(3). It is possible that the repression of RAR-regulated transcription by HACE1 is due to its ability to inhibit the RA-dependent degradation of RARs.
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Endometrioid carcinoma of the fallopian tube resembling an adnexal tumor of probable wolffian origin: a case of report and review of the literature.
Pathol. Res. Pract.
PUBLISHED: 02-26-2009
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Endometrioid carcinoma is a common tumor of the female genital tract, mainly affecting the uterus corpus and ovary. In the fallopian tube, endometrioid carcinoma is relatively uncommon. The female adnexal tumor of probable wolffian origin (FATWO), although occasionally seen elsewhere, is most typically encountered in the broad ligament. Endometrioid carcinoma of the fallopian tube resembling FATWO is a rare type of endometrioid carcinoma, and only 20 cases have been reported to date. Here, we report a case of endometrioid carcinoma of the fallopian tube resembling FATWO and review the literature. A 67-year-old woman presented with a history of prolapse for about one month outside the vulva. Physical examination and pelvic ultrasonography of the patient revealed a streak mass covering the left ovary. A total hysterectomy and a bilateral salpingo-oophorectomy were performed. The tumor was confined to the tube and strongly resembled FATWO. Immunohistochemically, the tumor cells were positive for AE1/AE3, epithelial membrane antigen (EMA), and p16, but negative for CD10, inhibin-alpha, calretinin, vimentin, myogenin, and desmin, CD99,CgA, and Syn. We review the previously published cases of endometrioid carcinomas of the fallopian tube resembling FATWO, and discuss the principal differential diagnosis of the tumor in the fallopian tube.
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Anti-viral effects of urosolic acid on guinea pig cytomegalovirus in vitro.
J. Huazhong Univ. Sci. Technol. Med. Sci.
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This study examined the anti-viral effect of ursolic acid on guinea pig cytomegalovirus (GPCMV) and explored the steps of viral replication targeted by ursolic acid. Cytopathic effect assay and MTT method were employed to determine the 50% cellular cytotoxicity (CC(50)), 50% effective concentration (EC(50)) and therapeutic index (TI) with GPCMV. To investigate the specific anti-viral effect of ursolic acid at different temperatures and time points, two other medicines, ganciclovir and Jinyebaidu (JYBD), serving as controls, were studied for comparison. Our results showed that the CC50 of ganciclovir, JYBD and ursolic acid were 333.8, 3015.6, 86.7 ?g/mL, respectively; EC(50) of ganciclovir, JYBD and ursolic acid was 48.1, 325.5 and 6.8 ?g/mL, respectively; TI of ganciclovir, JYBD and ursolic acid was 7, 9, 13, respectively. Similar with ganciclovir, ursolic acid could inhibit the viral synthesis, but did not affect the viral adsorption onto and penetration into cells. We are led to conclude that the anti-cytomegalovirus effect of ursolic acid is significantly stronger than ganciclovir or JYBD, and the cytotoxic effect of ursolic acid lies in its ability to inhibit viral synthesis.
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Pre-mir-27a rs895819 polymorphism and cancer risk: a meta-analysis.
Mol. Biol. Rep.
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Aberrant expression of miRNAs plays critical roles in cancer development. Single nucleotide polymorphism (SNP) in miRNA precursors may affect miRNA expression levels. An important SNP in the pre-mir-27a with a A to G change (rs895819) was identified. Several original studies have explored the role of this SNP in cancer risk, but the results of these studies remain conflicting rather than conclusive. Therefore, we performed a meta-analysis of the published studies to derive a more precise estimation of the association between pre-mir-27a rs895819 polymorphism and cancer risk. In this meta-analysis, a total of 6 case-control studies (including 3,255 cases and 4,181 controls) were analyzed. The results of the overall meta-analysis did not suggest any associations between pre-mir-27a rs895819 polymorphism and cancer susceptibility. However, an decreased risk was observed in the subgroup of breast cancer patients (G vs A: OR = 0.90, 95 % CI = 0.83 ~ 0.97; P heterogeneity = 0.75) or in the subgroup of Caucasian race (G vs A: OR = 0.90, 95 % CI = 0.83 ~ 0.97, P heterogeneity = 0.78, I (2) = 0; AG vs AA: OR = 0.84, 95 % CI = 0.75 ~ 0.94, P heterogeneity = 0.35, I (2) = 3.7 %; GG+AG vs AA: OR = 0.85, 95 % CI = 0.76 ~ 0.94, P heterogeneity = 0.48, I (2) = 0). The findings suggest that pre-mir-27a rs895819 polymorphism may have some relation to breast cancer susceptibility or cancer development in Caucasian.
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New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.
Momoko Horikoshi, Hanieh Yaghootkar, Dennis O Mook-Kanamori, Ulla Sovio, H Rob Taal, Branwen J Hennig, Jonathan P Bradfield, Beate St Pourcain, David M Evans, Pimphen Charoen, Marika Kaakinen, Diana L Cousminer, Terho Lehtimäki, Eskil Kreiner-Møller, Nicole M Warrington, Mariona Bustamante, Bjarke Feenstra, Diane J Berry, Elisabeth Thiering, Thiemo Pfab, Sheila J Barton, Beverley M Shields, Marjan Kerkhof, Elisabeth M van Leeuwen, Anthony J Fulford, Zoltan Kutalik, Jing Hua Zhao, Marcel den Hoed, Anubha Mahajan, Virpi Lindi, Liang-Kee Goh, Jouke-Jan Hottenga, Ying Wu, Olli T Raitakari, Marie N Harder, Aline Meirhaeghe, Ioanna Ntalla, Rany M Salem, Karen A Jameson, Kaixin Zhou, Dorota M Monies, Vasiliki Lagou, Mirna Kirin, Jani Heikkinen, Linda S Adair, Fowzan S Alkuraya, Ali Al-Odaib, Philippe Amouyel, Ehm Astrid Andersson, Amanda J Bennett, Alexandra I F Blakemore, Jessica L Buxton, Jean Dallongeville, Shikta Das, Eco J C de Geus, Xavier Estivill, Claudia Flexeder, Philippe Froguel, Frank Geller, Keith M Godfrey, Frederic Gottrand, Christopher J Groves, Torben Hansen, Joel N Hirschhorn, Albert Hofman, Mads V Hollegaard, David M Hougaard, Elina Hyppönen, Hazel M Inskip, Aaron Isaacs, Torben Jørgensen, Christina Kanaka-Gantenbein, John P Kemp, Wieland Kiess, Tuomas O Kilpeläinen, Norman Klopp, Bridget A Knight, Christopher W Kuzawa, George McMahon, John P Newnham, Harri Niinikoski, Ben A Oostra, Louise Pedersen, Dirkje S Postma, Susan M Ring, Fernando Rivadeneira, Neil R Robertson, Sylvain Sebert, Olli Simell, Torsten Slowinski, Carla M T Tiesler, Anke Tönjes, Allan Vaag, Jorma S Viikari, Jacqueline M Vink, Nadja Hawwa Vissing, Nicholas J Wareham, Gonneke Willemsen, Daniel R Witte, Haitao Zhang, Jianhua Zhao, , James F Wilson, Michael Stumvoll, Andrew M Prentice, Brian F Meyer, Ewan R Pearson, Colin A G Boreham, Cyrus Cooper, Matthew W Gillman, George V Dedoussis, Luis A Moreno, Oluf Pedersen, Maiju Saarinen, Karen L Mohlke, Dorret I Boomsma, Seang-Mei Saw, Timo A Lakka, Antje Körner, Ruth J F Loos, Ken K Ong, Peter Vollenweider, Cornelia M van Duijn, Gerard H Koppelman, Andrew T Hattersley, John W Holloway, Berthold Hocher, Joachim Heinrich, Chris Power, Mads Melbye, Mònica Guxens, Craig E Pennell, Klaus Bønnelykke, Hans Bisgaard, Johan G Eriksson, Elisabeth Widén, Hakon Hakonarson, André G Uitterlinden, Anneli Pouta, Debbie A Lawlor, George Davey Smith, Timothy M Frayling, Mark I McCarthy, Struan F A Grant, Vincent W V Jaddoe, Marjo-Riitta Järvelin, Nicholas J Timpson, Inga Prokopenko, Rachel M Freathy.
Nat. Genet.
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Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.
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Improving skin Raman spectral quality by fluorescence photobleaching.
Photodiagnosis Photodyn Ther
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Here we present a method for improving Raman spectroscopy signal-to-noise ratio (SNR) based on fluorescence photobleaching. Good SNR is essential to obtain biochemical information about biological tissues. Subtracting high levels of tissue autofluorescence background is a major challenge in extracting weak Raman signals. We found that pre-exposure to laser light significantly reduces tissue autofluorescence, but minimally affects Raman signals, allowing subsequent acquisition of high-SNR Raman spectra. We demonstrated this method with in vivo Raman spectral measurements of human skin. This method will benefit clinical skin Raman measurements of body sites with high autofluorescence background such as the forehead and nose.
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Expression analyses of the genes harbored by the type 2 diabetes and pediatric BMI associated locus on 10q23.
BMC Med. Genet.
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There is evidence that one of the key type 2 diabetes (T2D) loci identified by GWAS exerts its influence early on in life through its impact on pediatric BMI. This locus on 10q23 harbors three genes, encoding hematopoietically expressed homeobox (HHEX), insulin-degrading enzyme (IDE) and kinesin family member 11 (KIF11), respectively.
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Evidence for structural phase transitions induced by the triple phase line shift in self-catalyzed GaAs nanowires.
Nano Lett.
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Self-catalyzed growth of GaAs nanowires are widely ascribed to the vapor-liquid-solid (VLS) mechanism due to the presence of Ga particles at the nanowire tips. Here we report synthesis of self-catalyzed GaAs nanowires by molecular-beam epitaxy covering a large growth parameter space. By carefully controlling the Ga flux and its ratio with the As flux, GaAs nanowires without Ga particles and exhibiting a flat growth front are produced. Using scanning electron microscopy and high-resolution transmission electron microscopy, we compare the growth rate and structure, especially near the growth front, of the nanowires with and without Ga droplets. We find that regardless of whether Ga droplets are present on top, the nanowires have a short wurtzite section following the zinc-blende bulk structure. The nanowires without Ga droplets are terminated by a thin zinc-blende cap, while the nanowires with Ga droplets do not have such a cap. The bulk zinc-blende phase is attributed to the Ga droplet wetting the sidewall during growth, pinning the triple phase line on the sidewall. The zinc-blend/wurtzite/(zinc-blende) phase transitions at the end of growth are fully consistent with the triple phase line shifting up to the growth front due to the progressive consumption of the Ga in the droplet by crystallization with As. The results imply an identical VLS growth mechanism for both types of GaAs NWs, and their intricate structures provide detailed comparison with and specific experimental verification of the recently proposed growth mechanism for self-catalyzed III-V semiconductor nanowires ( Phy. Rev. Lett. 2011 , 106 , 125505 ). Using this mechanism as a guideline, we successfully demonstrated controllable fabrication of two distinct types of axial superlattice GaAs NWs consisting of zinc-blende/defect-section and wurtzite/defect-section units.
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Imaging-guided two-photon excitation-emission-matrix measurements of human skin tissues.
J Biomed Opt
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There are increased interests on using multiphoton imaging and spectroscopy for skin tissue characterization and diagnosis. However, most studies have been done with just a few excitation wavelengths. Our objective is to perform a systematic study of the two-photon fluorescence (TPF) properties of skin fluorophores, normal skin, and diseased skin tissues. A nonlinear excitation-emission-matrix (EEM) spectroscopy system with multiphoton imaging guidance was constructed. A tunable femtosecond laser was used to vary excitation wavelengths from 730 to 920 nm for EEM data acquisition. EEM measurements were performed on excised fresh normal skin tissues, seborrheic keratosis tissue samples, and skin fluorophores including: NADH, FAD, keratin, melanin, collagen, and elastin. We found that in the stratum corneum and upper epidermis of normal skin, the cells have large sizes and the TPF originates from keratin. In the lower epidermis, cells are smaller and TPF is dominated by NADH contributions. In the dermis, TPF is dominated by elastin components. The depth resolved EEM measurements also demonstrated that keratin structure has intruded into the middle sublayers of the epidermal part of the seborrheic keratosis lesion. These results suggest that the imaging guided TPF EEM spectroscopy provides useful information for the development of multiphoton clinical devices for skin disease diagnosis.
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G protein-coupled receptor FPR1 as a pharmacologic target in inflammation and human glioblastoma.
Int. Immunopharmacol.
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Formylpeptide receptor1 (FPR1) is a G protein-coupled receptor (GPCR) originally identified in phagocytic leucocytes and mediates cell chemotaxis and activation in response to bacterial formylated chemotactic peptides. However, FPR1 also participates in a signal relay which regulates the infiltration of phagocytes, in particular neutrophils, to inflammatory sites in response to tissue-derived chemoattractant ligands. In addition to participating in innate immune responses, recently, FPR1 has been shown to be expressed by highly malignant glioblastoma (GBM) cells. Upon activation by an endogenous agonist Annexin 1 (Anx A1) released by necrotic glioma cells, FPR1 transactivates the receptor for epithelial growth factor (EGFR) and consequently to promote glioma cell chemotaxis, invasion, growth and production of angiogenic factors. The observations demonstrate that FPR1, as a multifunctional GPCR with pattern recognition properties, is not only involved in innate immune responses but also in the progression of GBM. Thus, FPR1 is an immunopharmacologic target for development of novel therapies.
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Multifunctional L1(0) -Mn(1.5)Ga films with ultrahigh coercivity, giant perpendicular magnetocrystalline anisotropy and large magnetic energy product.
Adv. Mater. Weinheim
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A new kind of multifunctional L1(0) -Mn(1.5)Ga film is demonstrated for the first time. These MBE-grown epitaxial films exhibit pronounced magnetic properties at room temperature, including ultrahigh perpendicular coercivity up to 42.8 kOe, giant perpendicular magnetic anisotropy with a maximum of 21.7 Merg/cm(3) and large magnetic energy products up to 2.60 MGOe, which allow various applications in ultrahigh density recording, spintronics, and permanent magnets.
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In vivo near-infrared autofluorescence imaging of pigmented skin lesions: methods, technical improvements and preliminary clinical results.
Skin Res Technol
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Fluorescence emission from in vivo cutaneous melanin was recently detected under near-infrared (NIR) excitation by our group. We then built a prototype NIR autofluorescence imaging system to observe and characterize the melanin distribution in human skin. In this article, we reported a new setup of NIR fluorescence imaging system and calibration methods to optimize the system for better clinical feasibility and clearer image.
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Differentiation of HaCaT cell and melanocyte from their malignant counterparts using micro-Raman spectroscopy guided by confocal imaging.
Photodermatol Photoimmunol Photomed
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Skin cancer is the most common type of cancer in humans. Current techniques for identifying normal and neoplastic tissues are either destructive or not sensitive and specific enough. Raman spectroscopy and confocal imaging may obviate many limitations of existing methods by providing noninvasive, high-resolution, and real-time morphological and biochemical analysis of living tissues and cells.
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A genome-wide association meta-analysis identifies new childhood obesity loci.
Nat. Genet.
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Multiple genetic variants have been associated with adult obesity and a few with severe obesity in childhood; however, less progress has been made in establishing genetic influences on common early-onset obesity. We performed a North American, Australian and European collaborative meta-analysis of 14 studies consisting of 5,530 cases (?95th percentile of body mass index (BMI)) and 8,318 controls (<50th percentile of BMI) of European ancestry. Taking forward the eight newly discovered signals yielding association with P < 5 × 10(-6) in nine independent data sets (2,818 cases and 4,083 controls), we observed two loci that yielded genome-wide significant combined P values near OLFM4 at 13q14 (rs9568856; P = 1.82 × 10(-9); odds ratio (OR) = 1.22) and within HOXB5 at 17q21 (rs9299; P = 3.54 × 10(-9); OR = 1.14). Both loci continued to show association when two extreme childhood obesity cohorts were included (2,214 cases and 2,674 controls). These two loci also yielded directionally consistent associations in a previous meta-analysis of adult BMI(1).
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Real-time Raman spectroscopy for in vivo skin cancer diagnosis.
Cancer Res.
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Raman spectroscopy is a noninvasive optical technique capable of measuring vibrational modes of biomolecules within viable tissues. In this study, we evaluated the application of an integrated real-time system of Raman spectroscopy for in vivo skin cancer diagnosis. Benign and malignant skin lesions (n = 518) from 453 patients were measured within 1 second each, including melanomas, basal cell carcinomas, squamous cell carcinomas, actinic keratoses, atypical nevi, melanocytic nevi, blue nevi, and seborrheic keratoses. Lesion classification was made using a principal component with general discriminant analysis and partial least-squares in three distinct discrimination tasks: skin cancers and precancers from benign skin lesions [receiver operating characteristic (ROC) = 0.879]; melanomas from nonmelanoma pigmented lesions (ROC = 0.823); and melanomas from seborrheic keratoses (ROC = 0.898). For sensitivities between 95% and 99%, the specificities ranged between 15% and 54%. Our findings establish that real-time Raman spectroscopy can be used to distinguish malignant from benign skin lesions with good diagnostic accuracy comparable with clinical examination and other optical-based methods.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.