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Spatiotemporal Evolution of the Primary Glioblastoma Genome
Kim, J.,Lee, I.H.,Cho, H.,Park, C.K.,Jung, Y.S.,Kim, Y.,Nam, S.,Kim, B.,Johnson, Mark D.,Kong, D.S.,Seol, H.,Lee, J.I.,Joo, K.,Yoon, Y.,Park, W.Y.,Lee, J.,Park, Peter J.,Nam, D.H. Cell Press 2015 CANCER CELL Vol. No.
Tumor recurrence following treatment is the major cause of mortality for glioblastoma multiforme (GBM) patients. Thus, insights on the evolutionary process at recurrence are critical for improved patient care. Here, we describe our genomic analyses of the initial and recurrent tumor specimens from each of 38 GBM patients. A substantial divergence in the landscape of driver alterations was associated with distant appearance of a recurrent tumor from the initial tumor, suggesting that the genomic profile of the initial tumor can mislead targeted therapies for the distally recurred tumor. In addition, in contrast to IDH1-mutated gliomas, IDH1-wild-type primary GBMs rarely developed hypermutation following temozolomide (TMZ) treatment, indicating low risk for TMZ-induced hypermutation for these tumors under the standard regimen.
Park, Chan H.,Kimler, Bruce F.,Yi, Seong Yoon,Park, Se Hoon,Kim, Kihyun,Jung, Chul Won,Kim, Sun Hee,Lee, Eun Ryung,Rha, Miyong,Kim, Seonwoo,Park, Mary H.,Lee, Sook J.,Park, Hye K.,Lee, Mark H.,Yoon, S Blackwell Publishing Ltd 2009 European journal of haematology Vol.83 No.2
<P>Abstract</P><P>Purpose: </P><P><SMALL>L</SMALL>-ascorbic acid (LAA) modifies the <I>in vitro</I> growth of leukemic cells from ∼50% of patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). To test the hypothesis that depletion of LAA, alternating with supplementation to prevent scurvy, would provide therapeutic benefit, a single-arm pilot trial was conducted (ClinicalTrials.gov identifier: NCT00329498).</P><P>Experimental results: </P><P>During depletion phase, patients with refractory AML or MDS were placed on a diet deficient in LAA; during supplementation phase, patients received daily intravenous administration of LAA. An <I>in vitro</I> assay was performed pretherapy for LAA sensitivity of leukemic cells from individual patients.</P><P>Results: </P><P>Of 18 patients enrolled, eight of 16 evaluable patients demonstrated a clinical response. Responses were obtained during depletion (four patients) as well as during supplementation (five patients) but at a pharmacologic plasma level achievable only with intravenous administration. Of nine patients for whom the <I>in vitro</I> assay indicated their leukemic cells were sensitive to LAA, seven exhibited a clinical response; compared with none of six patients who were insensitive to LAA.</P><P>Conclusions: </P><P>The clinical benefit, along with a conspicuous absence of significant adverse events, suggests that further testing of LAA depletion alternating with pharmacologic dose intravenous supplementation in patients with these and other malignancies is warranted.</P>
Brown, Daren W,Lee, Seung-Ho,Kim, Lee-Han,Ryu, Jae-Gee,Lee, Soohyung,Seo, Yunhee,Kim, Young Ho,Busman, Mark,Yun, Sung-Hwan,Proctor, Robert H,Lee, Theresa APS Press 2015 Molecular plant-microbe interactions Vol.28 No.3
<P>In fungi, genes involved in biosynthesis of a secondary metabolite (SM) are often located adjacent to one another in the genome and are coordinately regulated. These SM biosynthetic gene clusters typically encode enzymes, one or more transcription factors, and a transport protein. Fusaric acid is a polyketide-derived SM produced by multiple species of the fungal genus Fusarium. This SM is of concern because it is toxic to animals and, therefore, is considered a mycotoxin and may contribute to plant pathogenesis. Preliminary descriptions of the fusaric acid (FA) biosynthetic gene (FUB) cluster have been reported in two Fusarium species, the maize pathogen F. verticillioides and the rice pathogen F. fujikuroi. The cluster consisted of five genes and did not include a transcription factor or transporter gene. Here, analysis of the FUB region in F. verticillioides, F. fujikuroi, and F. oxysporum, a plant pathogen with multiple hosts, indicates the FUB cluster consists of at least 12 genes (FUB1 to FUB12). Deletion analysis confirmed that nine FUB genes, including two Zn(II)2Cys6 transcription factor genes, are required for production of wild-type levels of FA. Comparisons of FUB cluster homologs across multiple Fusarium isolates and species revealed insertion of non-FUB genes at one or two locations in some homologs. Although the ability to produce FA contributed to the phytotoxicity of F. oxysporum culture extracts, lack of production did not affect virulence of F. oxysporum on cactus or F. verticillioides on maize seedlings. These findings provide new insights into the genetic and biochemical processes required for FA production.</P>
A baseline drift detrending technique for fast scan cyclic voltammetry
DeWaele, Mark,Oh, Yoonbae,Park, Cheonho,Kang, Yu Min,Shin, Hojin,Blaha, Charles D.,Bennet, Kevin E.,Kim, In Young,Lee, Kendall H.,Jang, Dong Pyo The Royal Society of Chemistry 2017 The Analyst Vol.142 No.22
<P>Fast scan cyclic voltammetry (FSCV) has been commonly used to measure extracellular neurotransmitter concentrations in the brain. Due to the unstable nature of the background currents inherent in FSCV measurements, analysis of FSCV data is limited to very short amounts of time using traditional background subtraction. In this paper, we propose the use of a zero-phase high pass filter (HPF) as the means to remove the background drift. Instead of the traditional method of low pass filtering across voltammograms to increase the signal to noise ratio, a HPF with a low cutoff frequency was applied to the temporal dataset at each voltage point to remove the background drift. As a result, the HPF utilizing cutoff frequencies between 0.001 Hz and 0.01 Hz could be effectively used to a set of FSCV data for removing the drifting patterns while preserving the temporal kinetics of the phasic dopamine response recorded <I>in vivo</I>. In addition, compared to a drift removal method using principal component analysis, this was found to be significantly more effective in reducing the drift (unpaired <I>t</I>-test <I>p</I> < 0.0001, <I>t</I> = 10.88) when applied to data collected from Tris buffer over 24 hours although a drift removal method using principal component analysis also showed the effective background drift reduction. The HPF was also applied to 5 hours of FSCV <I>in vivo</I> data. Electrically evoked dopamine peaks, observed in the nucleus accumbens, were clearly visible even without background subtraction. This technique provides a new, simple, and yet robust, approach to analyse FSCV data with an unstable background.</P>
A Tetra(Ethylene Glycol) Derivative of Benzothiazole Aniline Enhances Ras-Mediated Spinogenesis
Megill, Andrea,Lee, Taehee,DiBattista, Amanda Marie,Song, Jung Min,Spitzer, Matthew H.,Rubinshtein, Mark,Habib, Lila K.,Capule, Christina C.,Mayer, Michael,Turner, R. Scott,Kirkwood, Alfredo,Yang, Jer Society for Neuroscience 2013 The Journal of neuroscience Vol.33 No.22
<P>The tetra(ethylene glycol) derivative of benzothiazole aniline, BTA-EG<SUB>4</SUB>, is a novel amyloid-binding small molecule that can penetrate the blood–brain barrier and protect cells from Aβ-induced toxicity. However, the effects of Aβ-targeting molecules on other cellular processes, including those that modulate synaptic plasticity, remain unknown. We report here that BTA-EG<SUB>4</SUB> decreases Aβ levels, alters cell surface expression of amyloid precursor protein (APP), and improves memory in wild-type mice. Interestingly, the BTA-EG<SUB>4</SUB>-mediated behavioral improvement is not correlated with LTP, but with increased spinogenesis. The higher dendritic spine density reflects an increase in the number of functional synapses as determined by increased miniature EPSC (mEPSC) frequency without changes in presynaptic parameters or postsynaptic mEPSC amplitude. Additionally, BTA-EG<SUB>4</SUB> requires APP to regulate dendritic spine density through a Ras signaling-dependent mechanism. Thus, BTA-EG<SUB>4</SUB> may provide broad therapeutic benefits for improving neuronal and cognitive function, and may have implications in neurodegenerative disease therapy.</P>
You, Sung H.,Jang, Sung Ho,Kim, Yun-Hee,Hallett, Mark,Ahn, Sang Ho,Kwon, Yong-Hyun,Kim, Joong Hwi,Lee, Mi Young Ovid Technologies Wolters Kluwer -American Heart A 2005 Stroke Vol.36 No.6
<P>BACKGROUND AND PURPOSE: Virtual reality (VR) is a new promising computer-assisted technology to promote motor recovery in stroke patients. VR-induced neuroplasticity supporting locomotor recovery is not known. We investigated the effects of VR intervention on cortical reorganization and associated locomotor recovery in stroke patients. METHODS: Ten chronic stroke patients were assigned randomly to either the control group or the VR group. VR was designed to provide interactive real-life practice environments in which practice parameters can be individualized to optimize motor relearning. Laterality index (LI) in the regions of interests (ROIs) and locomotor recovery were measured before and after VR using functional MRI (fMRI) and standardized locomotor tests, respectively. The t test and nonparametric test were performed to compare the mean differences at P<0.05. RESULTS: There was a significant difference in the interval change in the LI score for the primary sensorimotor cortex (SMC) between the groups (P<0.05), indicating that VR practice produced a greater increase in LI for the control group. However, the interval changes in the other ROIs were not significantly different (P>0.05). Motor function was significantly improved after VR (P<0.05). CONCLUSIONS: Our novel findings suggest that VR could induce cortical reorganization from aberrant ipsilateral to contralateral SMC activation. This enhanced cortical reorganization might play an important role in recovery of locomotor function in patients with chronic stroke. This is the first fMRI study in the literature that provides evidence for neuroplasticity and associated locomotor recovery after VR.</P>
IL10 and TNF variants and risk of non-Hodgkin lymphoma among three Asian populations
Hosgood III, H. Dean,Au, Wing-Yan,Kim, Hee Nam,Liu, Jie,Hu, Wei,Tse, Jovic,Song, Bao,Wong, Kit-fai,Lee, Je-Jung,Chanock, Stephen J.,Siu, L. P.,Purdue, Mark P.,Shin, Min-ho,Yu, Jinming,Liang, Raymond,K Springer-Verlag 2013 International journal of hematology Vol.97 No.6
<P>Genetic variation in immune-related genes, such as IL10 and TNF, have been associated with the development of non-Hodgkin lymphoma (NHL) in Caucasian populations. To test the hypothesis that IL10 and TNF polymorphisms may be associated with NHL risk in Asian populations, we genotyped 20 single nucleotide polymorphisms (SNPs) within the IL10 and TNF/LTA loci in three independent case-control studies (2635 cases and 4234 controls). IL10 rs1800871, rs1800872, and rs1800896 were genotyped in all three studies, while 5 of the remaining SNPs were genotyped in two studies, and 12 in a single study. IL10 rs1800896 was associated with B cell lymphoma [per-allele odds ratio (OR)?=?1.25, 95?% confidence interval (CI)?1.08-1.45; p trend?=?0.003], specifically diffuse large B cell lymphoma (DLBCL) (per-allele OR?=?1.29, 95?% CI?1.08-1.53; p trend?=?0.004), as well as T cell lymphoma (per-allele OR?=?1.44, 95?% CI?1.13-1.82; p trend?=?0.003). TNF rs1800629, which was genotyped in only two of our studies, was also associated with B cell lymphoma (per-allele OR?=?0.77, 95?% CI?0.64-0.91; p trend?=?0.003), specifically DLBCL (per-allele OR?=?0.69, 95?% CI?0.55-0.86; p trend?=?0.001). Our findings suggest that genetic variation in IL10 and TNF may also play a role in lymphomagenesis in Asian populations.</P>