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81.
Ching‐Cheng Chuang Chung‐Ming Chen Yao‐Sheng Hsieh Tsan‐Chi Liu Chia‐Wei Sun 《Journal of biophotonics》2013,6(3):267-274
The goal of this study is to prove that the light propagation in the head by used the 3‐D optical model from in vivo MRI data set can also provide significant characteristics on the spatial sensitivity of cerebral cortex folding geometry based on Monte Carlo simulation. Thus, we proposed a MRI based approach for 3‐D brain modeling of near‐infrared spectroscopy (NIRS). In the results, the spatial sensitivity profile of the cerebral cortex folding geometry and the arrangement of source‐detector separation have being necessarily considered for applications of functional NIRS. The optimal choice of source‐detector separation is suggested within 3–3.5 cm by the received intensity with different source‐detector separations and the ratio of received light from the gray and white matter layer is greater than 50%. Additionally, this study has demonstrated the capability of NIRS in not only assessing the functional but also detecting the structural change of the brain by taking advantage of the low scattering and absorption coefficients observed in CSF of sagittal view. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
82.
Bharat Thyagarajan Renwei Wang Heather Nelson Helene Barcelo Woon-Puay Koh Jian-Min Yuan 《PloS one》2013,8(6)
Mitochondrial DNA (mtDNA) copy number in peripheral blood is associated with increased risk of several cancers. However, data from prospective studies on mtDNA copy number and breast cancer risk are lacking. We evaluated the association between mtDNA copy number in peripheral blood and breast cancer risk in a nested case-control study of 183 breast cancer cases with pre-diagnostic blood samples and 529 individually matched controls among participants of the Singapore Chinese Health Study. The mtDNA copy number was measured using real time PCR. Conditional logistic regression analyses showed that there was an overall positive association between mtDNA copy number and breast cancer risk (Ptrend = 0.01). The elevated risk for higher mtDNA copy numbers was primarily seen for women with <3 years between blood draw and cancer diagnosis; ORs (95% CIs) for 2nd, 3rd, 4th, and 5th quintile of mtDNA copy number were 1.52 (0.61, 3.82), 2.52 (1.03, 6.12), 3.12 (1.31, 7.43), and 3.06 (1.25, 7.47), respectively, compared with the 1st quintile (Ptrend = 0.004). There was no association between mtDNA copy number and breast cancer risk among women who donated a blood sample ≥3 years before breast cancer diagnosis (Ptrend = 0.41). This study supports a prospective association between increased mtDNA copy number and breast cancer risk that is dependent on the time interval between blood collection and breast cancer diagnosis. Future studies are warranted to confirm these findings and to elucidate the biological role of mtDNA copy number in breast cancer risk. 相似文献
83.
Mindy I. Davis Atsuo T. Sasaki Min Shen Brooke M. Emerling Natasha Thorne Sam Michael Rajan Pragani Matthew Boxer Kazutaka Sumita Koh Takeuchi Douglas S. Auld Zhuyin Li Lewis C. Cantley Anton Simeonov 《PloS one》2013,8(1)
Phosphoinositide kinases regulate diverse cellular functions and are important targets for therapeutic development for diseases, such as diabetes and cancer. Preparation of the lipid substrate is crucial for the development of a robust and miniaturizable lipid kinase assay. Enzymatic assays for phosphoinositide kinases often use lipid substrates prepared from lyophilized lipid preparations by sonication, which result in variability in the liposome size from preparation to preparation. Herein, we report a homogeneous 1536-well luciferase-coupled bioluminescence assay for PI5P4Kα. The substrate preparation is novel and allows the rapid production of a DMSO-containing substrate solution without the need for lengthy liposome preparation protocols, thus enabling the scale-up of this traditionally difficult type of assay. The Z’-factor value was greater than 0.7 for the PI5P4Kα assay, indicating its suitability for high-throughput screening applications. Tyrphostin AG-82 had been identified as an inhibitor of PI5P4Kα by assessing the degree of phospho transfer of γ-32P-ATP to PI5P; its inhibitory activity against PI5P4Kα was confirmed in the present miniaturized assay. From a pilot screen of a library of bioactive compounds, another tyrphostin, I-OMe tyrphostin AG-538 (I-OMe-AG-538), was identified as an ATP-competitive inhibitor of PI5P4Kα with an IC50 of 1 µM, affirming the suitability of the assay for inhibitor discovery campaigns. This homogeneous assay may apply to other lipid kinases and should help in the identification of leads for this class of enzymes by enabling high-throughput screening efforts. 相似文献
84.
Koung Jin Suh June-Won Cheong Inho Kim Hyeoung-Joon Kim Dong-Yeop Shin Youngil Koh Sung-Soo Yoon Yoo Hong Min Jae-Sook Ahn Yeo-Kyeoung Kim Yun-Gyoo Lee Jeong-Ok Lee Soo-Mee Bang Yeung-Chul Mun Chu-Myoung Seong Yong Park Byung-Soo Kim Junshik Hong Jinny Park Jae Hoon Lee Sung-Yong Kim Hong Ghi Lee 《PloS one》2016,11(11)
Chromosomal translocations are rare in myelodysplastic syndrome (MDS) and their impact on overall survival (OS) and response to hypomethylating agents (HMA) is unknown. The prognostic impact of the revised International Prognostic Scoring System (IPSS-R) and for chromosomal translocations was assessed in 751 patients from the Korea MDS Registry. IPSS-R effectively discriminated patients according to leukaemia evolution risk and OS. We identified 40 patients (5.3%) carrying translocations, 30 (75%) of whom also fulfilled complex karyotype criteria. Translocation presence was associated with a shorter OS (median, 12.0 versus 79.7 months, P < 0.01). Multivariate analysis demonstrated that translocations (hazard ratio [HR] 1.64 [1.06–2.63]; P = 0.03) as well as age, sex, IPSS-R, and CK were independent predictors of OS. In the IPSS-R high and very high risk subgroup (n = 260), translocations remained independently associated with OS (HR 1.68 [1.06–2.69], P = 0.03) whereas HMA treatment was not associated with improved survival (median OS, 20.9 versus 21.2 months, P = 0.43). However, translocation carriers exhibited enhanced survival following HMA treatment (median 2.1 versus 12.4 months, P = 0.03). Our data suggest that chromosomal translocation is an independent predictor of adverse outcome and has an additional prognostic value in discriminating patients with MDS having higher risk IPSS-R who could benefit from HMA treatment. 相似文献
85.
Hallucinations and delusions are the most prominent symptoms of schizophrenia and characterized by impaired reality testing. Representation-mediated taste aversion (RMTA) has been proposed as a potential behavioral assessment of reality testing and has been applied to a neurodevelopmental rat model of schizophrenia. However, the theory underlying this approach has not been generalized yet with any demonstration of impaired reality testing in other animal models of schizophrenia, such as genetically-modified mice. We devised a RMTA procedure for mice that combines a Pavlovian association protocol pairing odor conditioned stimulus (CS) with sugar reward unconditioned stimulus (US), and a conditioned taste aversion (CTA) method. In this RMTA paradigm, we compared performances of wild-type (PLCβ1+/+) mice and phospholipase C β1 knock-out (PLCβ1-/-) mice which are known as one of the genetic models for schizophrenia. With a minimal amount of initial odor-sugar associative training, both PLCβ1+/+ and PLCβ1-/- mice were able to form an aversion to the sugar reward when the odor CS predicting sugar was paired with nausea. With an extended initial training, however, only PLCβ1-/- mice could form a RMTA. This persistent RMTA displayed by PLCβ1-/- mice shows their inability to distinguish real sugar from the CS-evoked representation of sugar at a stage in associative learning where wild-type mice normally could differentiate the two. These results demonstrate an impaired reality testing first observed in a genetic mouse model of schizophrenia, and suggest that RMTA paradigm may, with general applicability, allow diverse biological approaches to impaired reality testing. 相似文献
86.
Activation of brain steroidogenesis and neurogenesis during the gonadal differentiation in protandrous black porgy,Acanthopagrus schlegelii 下载免费PDF全文
Chien‐Ju Lin Yi‐Chun Fan‐Chiang Sylvie Dufour Ching‐Fong Chang 《Developmental neurobiology》2016,76(2):121-136
The early brain development, at the time of gonadal differentiation was investigated using a protandrous teleost, black porgy. This natural model of monosex juvenile fish avoids the potential complexity of sexual dimorphism. Brain neurogenesis was evaluated by histological analyses of the diencephalon, at the time of testicular differentiation (in fish between 90 and 150 days after hatching). Increases in the number of both Nissl‐stained total brain cells, and Pcna‐immunostained proliferative brain cells were observed in specific area of the diencephalon, such as ventromedialis thalami and posterior preoptic area, revealing brain cell proliferation. qPCR analyses showed significantly higher expression of the radial glial cell marker blbp and neuron marker bdnf. Strong immunohistochemical staining of Blbp and extended cellular projections were observed. A peak expression of aromatase (cyp19a1b), as well as an increase in estradiol (E2) content were also detected in the early brain. These data demonstrate that during gonadal differentiation, the early brain exhibits increased E2 synthesis, cell proliferation, and neurogenesis. To investigate the role of E2 in early brain, undifferentiated fish were treated with E2 or aromatase inhibitor (AI). E2 treatment upregulated brain cyp19a1b and blbp expression, and enhanced brain cell proliferation. Conversely, AI reduced brain cell proliferation. Castration experiment did not influence the brain gene expression patterns and the brain cell number. Our data clearly support E2 biosynthesis in the early brain, and that brain E2 induces neurogenesis. These peak activity patterns in the early brain occur at the time of gonad differentiation but are independent of the gonads. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 121–136, 2016 相似文献
87.
Julia A. Sabet Lara K. Park Lakshmanan K. Iyer Albert K. Tai Gar Yee Koh Anna C. Pfalzer Laurence D. Parnell Joel B. Mason Zhenhua Liu Alexander J. Byun Jimmy W. Crott 《PloS one》2016,11(3)
Background
The importance of maternal nutrition to offspring health and risk of disease is well established. Emerging evidence suggests paternal diet may affect offspring health as well.Objective
In the current study we sought to determine whether modulating pre-conception paternal B vitamin intake alters intestinal tumor formation in offspring. Additionally, we sought to identify potential mechanisms for the observed weight differential among offspring by profiling hepatic gene expression and lipid content.Methods
Male Apc1638N mice (prone to intestinal tumor formation) were fed diets containing replete (control, CTRL), mildly deficient (DEF), or supplemental (SUPP) quantities of vitamins B2, B6, B12, and folate for 8 weeks before mating with control-fed wild type females. Wild type offspring were euthanized at weaning and hepatic gene expression profiled. Apc1638N offspring were fed a replete diet and euthanized at 28 weeks of age to assess tumor burden.Results
No differences in intestinal tumor incidence or burden were found between male Apc1638N offspring of different paternal diet groups. Although in female Apc1638N offspring there were no differences in tumor incidence or multiplicity, a stepwise increase in tumor volume with increasing paternal B vitamin intake was observed. Interestingly, female offspring of SUPP and DEF fathers had a significantly lower body weight than those of CTRL fed fathers. Moreover, hepatic trigylcerides and cholesterol were elevated 3-fold in adult female offspring of SUPP fathers. Weanling offspring of the same fathers displayed altered expression of several key lipid-metabolism genes. Hundreds of differentially methylated regions were identified in the paternal sperm in response to DEF and SUPP diets. Aside from a few genes including Igf2, there was a striking lack of overlap between these genes differentially methylated in sperm and differentially expressed in offspring.Conclusions
In this animal model, modulation of paternal B vitamin intake prior to mating alters offspring weight gain, lipid metabolism and tumor growth in a sex-specific fashion. These results highlight the need to better define how paternal nutrition affects the health of offspring. 相似文献88.
Chronic kidney disease (CKD) is characterized by a progressive loss of kidney function over a period of months or years. It is estimated that about 7.2 % of adults over the age of 30 have CKD worldwide. Although one of the major risk factors of CKD is family history, the heritability of CKD is not fully understood. It is also known that the diabetic condition is highly influential on the onset of CKD. To understand the genetic bases of CKD that remain unidentified, we performed genetic association analyses for kidney function-related traits such as blood urea nitrogen (BUN) and albumin in subjects stratified by diabetic status. In the discovery stage of the study, we used genome-wide scan data and clinical data in about 8800 subjects from the Korean Association Resource (KARE) project. Health2 study data comprising about 1800 subjects were used for the replication stage. Our two stage association analyses demonstrated that the LOC105374266 locus (rs9820070) showed strong evidence of association with BUN (P = 8.47 × 10?14) in nondiabetic normal subjects (n = ~4300). To extend our knowledge of the genetic determinants influencing kidney function, we also analyzed the association between kidney function-related traits and microRNA related variants. For this analysis, miRNA related SNPs were selected from KARE and Health2 cohort genotype data. Our study suggests the potential relevance of miRNA to the kidney function (miR-518b for BUN; miR-146a and miR-1295a for albumin) in Korean populations. 相似文献
89.
90.
Alfred Chor San Chan Qiu Qiu Siu Wai Choi Stanley Sau Ching Wong Albert Chi Yan Chan Michael G Irwin Chi Wai Cheung 《PloS one》2016,11(2)