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Alteration by p11 of mGluR5 localization regulates depression-like behaviors
Lee, K-W,Westin, L,Kim, J,Chang, J C,Oh, Y-S,Amreen, B,Gresack, J,Flajolet, M,Kim, D,Aperia, A,Kim, Y,Greengard, P Macmillan Publishers Limited 2015 Molecular psychiatry Vol.20 No.12
Mood disorders and antidepressant therapy involve alterations of monoaminergic and glutamatergic transmission. The protein S100A10 (p11) was identified as a regulator of serotonin receptors, and it has been implicated in the etiology of depression and in mediating the antidepressant actions of selective serotonin reuptake inhibitors. Here we report that p11 can also regulate depression-like behaviors via regulation of a glutamatergic receptor in mice. p11 directly binds to the cytoplasmic tail of metabotropic glutamate receptor 5 (mGluR5). p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell surface availability of the receptor. Whereas p11 overexpression potentiates mGluR5 agonist-induced calcium responses, overexpression of mGluR5 mutant, which does not interact with p11, diminishes the calcium responses in cultured cells. Knockout of mGluR5 or p11 specifically in glutamatergic neurons in mice causes depression-like behaviors. Conversely, knockout of mGluR5 or p11 in GABAergic neurons causes antidepressant-like behaviors. Inhibition of mGluR5 with an antagonist, 2-methyl-6-(phenylethynyl)pyridine (MPEP), induces antidepressant-like behaviors in a p11-dependent manner. Notably, the antidepressant-like action of MPEP is mediated by parvalbumin-positive GABAergic interneurons, resulting in a decrease of inhibitory neuronal firing with a resultant increase of excitatory neuronal firing. These results identify a molecular and cellular basis by which mGluR5 antagonism achieves its antidepressant-like activity.
An active grid for the simulation of atmospheric boundary layers in a wind tunnel
Talamelli, A.,Riparbelli, L.,Westin, J. Techno-Press 2004 Wind and Structures, An International Journal (WAS Vol.7 No.2
A technique for the simulation of atmospheric boundary layers in wind tunnels is developed and tested experimentally. The device consists of a grid made of seven horizontal and vertical evenly distributed bars in which air injection holes are drilled in order to influence the flow in the wind tunnel. The air flow in each bar can be controlled independently. Firstly, the device is used together with a rough carpet, which covers the test section floor, in order to simulate the boundary-layer characteristics over an open rural area. Hot-wire measurements, performed at different positions in the test-section, show the capability of the grid in generating the required boundary layer. An acceptable agreement with statistical values of mean velocity and turbulence profiles has been achieved, together with a good span-wise homogeneity. The results are also compared with those of a passive simulation technique based on the use of spires.
FINITE QUOTIENTS OF SINGULAR ARTIN MONOIDS AND CATEGORIFICATION OF THE DESINGULARIZATION MAP
Helena Jonsson,Volodymyr Mazorchuk,Elin Persson Westin,Shraddha Srivastava,Mateusz Stroinski,Xiaoyu Zhu Korean Mathematical Society 2023 대한수학회지 Vol.60 No.6
We study various aspects of the structure and representation theory of singular Artin monoids. This includes a number of generalizations of the desingularization map and explicit presentations for certain finite quotient monoids of diagrammatic nature. The main result is a categorification of the classical desingularization map for singular Artin monoids associated to finite Weyl groups using BGG category 𝒪.
The influence of surgeon volume on outcomes after pelvic exenteration for a gynecologic cancer
Randa J. Jalloul,Randa J. Jalloul,Mark F. Munsell,Shannon N. Westin,Pedro T. Ramirez,Michael Frumovitz,Pamela T. Soliman 대한부인종양학회 2018 Journal of Gynecologic Oncology Vol.29 No.5
Objective: To determine the effect of surgeon experience on intraoperative, postoperative and long-term outcomes among patients undergoing pelvic exenteration for gynecologic cancer. Methods: This was a retrospective analysis of all women who underwent exenteration for a gynecologic malignancy at MD Anderson Cancer Center, between January 1993 and June 2013. A logistic regression was used to model the relationship between surgeon experience (measured as the number of exenteration cases performed by the surgeon prior to a given exenteration) and operative outcomes and postoperative complications. Cox proportional hazards regression was used to model survival outcomes. Results: A total of 167 exenterations were performed by 19 surgeons for cervix (78, 46.7%), vaginal (43, 25.8%), uterine (24, 14.4%), vulvar (14, 8.4%) and other cancer (8, 4.7%). The most common procedure was total pelvic exenteration (69.4%), incontinent urinary diversion (63.5%) and vertical rectus abdominis musculocutaneous reconstruction (42.5%). Surgical experience was associated with decreased estimated blood loss (p<0.001), intraoperative transfusion (p=0.009) and a shorter length of stay (p=0.03). No difference was noted in the postoperative complication rate (p=0.12–0.95). More surgeon experience was not associated with overall or disease specific survival: OS (hazard ratio [HR]=1.02; 95% confidence interval [CI]=0.97–1.06; p=0.46) and DSS (HR=1.01; 95% CI=0.97–1.04; p=0.66), respectively. Conclusion: Patients undergoing exenteration by more experienced surgeons had improvement in intraoperative factors such as estimated blood loss, transfusion rates and length of stay. No difference was seen in postoperative complication rates, overall or disease specific survival.
Integrative epigenomic and genomic analysis of malignant pheochromocytoma
Sandgren, Johanna,Andersson, Robin,Rada-Iglesias, Alvaro,Enroth, Stefan,Akerstrom, Goran,Dumanski, Jan P.,Komorowski, Jan,Westin, Gunnar,Wadelius, Claes Korean Society for Biochemistry and Molecular Bion 2010 Experimental and molecular medicine Vol.42 No.7
Epigenomic and genomic changes affect gene expression and contribute to tumor development. The histone modifications trimethylated histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) are epigenetic regulators associated to active and silenced genes, respectively and alterations of these modifications have been observed in cancer. Furthermore, genomic aberrations such as DNA copy number changes are common events in tumors. Pheochromocytoma is a rare endocrine tumor of the adrenal gland that mostly occurs sporadic with unknown epigenetic/genetic cause. The majority of cases are benign. Here we aimed to combine the genome-wide profiling of H3K4me3 and H3K27me3, obtained by the ChIP-chip methodology, and DNA copy number data with global gene expression examination in a malignant pheochromocytoma sample. The integrated analysis of the tumor expression levels, in relation to normal adrenal medulla, indicated that either histone modifications or chromosomal alterations, or both, have great impact on the expression of a substantial fraction of the genes in the investigated sample. Candidate tumor suppressor genes identified with decreased expression, a H3K27me3 mark and/or in regions of deletion were for instance TGIF1, DSC3, TNFRSF10B, RASSF2, HOXA9, PTPRE and CDH11. More genes were found with increased expression, a H3K4me3 mark, and/or in regions of gain. Potential oncogenes detected among those were GNAS, INSM1, DOK5, ETV1, RET, NTRK1, IGF2, and the H3K27 trimethylase gene EZH2. Our approach to associate histone methylations and DNA copy number changes to gene expression revealed apparent impact on global gene transcription, and enabled the identification of candidate tumor genes for further exploration.
Yoo, Seung-Schik,Park, Hae-Jeong,Soul, Janet S.,Mamata, Hatsuho,Park, HyunWook,Westin, Carl-Fredrik,Bassan, Haim,Du Plessis, Adre J.,Robertson Jr, Richard L.,Maier, Stephan E.,Ringer, Steven A.,Volpe, J.B. Lippincott 2005 Vol. No.
OBJECTIVE:: The goal of this study was to test the feasibility of visualizing a 3-dimensional structure of cerebral white matter fiber tracts in preterm infants, postconceptional age (PCA) 28 weeks to term, by using volumetric diffusion tensor magnetic resonance imaging (DTI) data. MATERIALS AND METHOD:: We combined tractography algorithms and visualization methods, currently available for adult DTI data, to trace the pixelated principal direction of a diffusion tensor originating from regions-of-interest with high fractional anisotropy. Consequently, white matter fiber bundles from the genu and the splenium of corpus callosum, the corticospinal tracts, the inferior fronto-occipital fasciculi, and optic radiations were visualized. RESULTS:: Our results suggest that major white matter tracts of preterm infant brains, with PCAs ranging from 28 weeks to term (40 weeks old), can be successfully visualized despite the small brain volume and low anisotropy. CONCLUSION:: The feasibility of fiber tractography in preterm neonates with DTI may add a new dimension in detection and characterization of white matter injuries of preterm infants.
Integrative epigenomic and genomic analysis of malignant pheochromocytoma
Johanna Sandgren,Robin Andersson,Alvaro Rada-Iglesias,Stefan Enroth,Jan Komorowski,Claes Wadelius,Göran Åkerström,Jan P. Dumanski,Gunnar Westin 생화학분자생물학회 2010 Experimental and molecular medicine Vol.42 No.7
Epigenomic and genomic changes affect gene expression and contribute to tumor development. The histone modifications trimethylated histone H3 lysine 4 (H3K4me3) and lysine 27 (H3K27me3) are epigenetic regulators associated to active and silenced genes, respectively and alterations of these modifications have been observed in cancer. Furthermore, genomic aberrations such as DNA copy number changes are common events in tumors. Pheochromocytoma is a rare endocrine tumor of the adrenal gland that mostly occurs sporadic with unknown epigenetic/genetic cause. The majority of cases are benign. Here we aimed to combine the genome-wide profiling of H3K4me3 and H3K27me3, obtained by the ChIP-chip methodology,and DNA copy number data with global gene expression examination in a malignant pheochromocytoma sample. The integrated analysis of the tumor expression levels, in relation to normal adrenal medulla,indicated that either histone modifications or chromosomal alterations, or both, have great impact on the expression of a substantial fraction of the genes in the investigated sample. Candidate tumor suppressor genes identified with decreased expression, a H3K27me3 mark and/or in regions of deletion were for instance TGIF1, DSC3, TNFRSF10B, RASSF2, HOXA9,PTPRE and CDH11. More genes were found with increased expression, a H3K4me3 mark, and/or in regions of gain. Potential oncogenes detected among those were GNAS, INSM1, DOK5, ETV1, RET, NTRK1,IGF2, and the H3K27 trimethylase gene EZH2. Our approach to associate histone methylations and DNA copy number changes to gene expression revealed apparent impact on global gene transcription, and enabled the identification of candidate tumor genes for further exploration.