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1.  Adiponectin Enhances Intercellular Adhesion Molecule-1 Expression and Promotes Monocyte Adhesion in Human Synovial Fibroblasts 
PLoS ONE  2014;9(3):e92741.
Adiponectin is a protein hormone secreted predominantly by differentiated adipocytes and is involved in energy homeostasis. Adiponectin expression is significantly high in the synovial fluid of patients with osteoarthritis (OA). Intercellular adhesion molecule-1 (ICAM-1) is an important adhesion molecule that mediates monocyte adhesion and infiltration during OA pathogenesis. Adiponectin-induced expression of ICAM-1 in human OA synovial fibroblasts (OASFs) was examined by using qPCR, flow cytometry and western blotting. The intracellular signaling pathways were investigated by pretreated with inhibitors or transfection with siRNA. The monocyte THP-1 cell line was used for an adhesion assay with OASFs. Stimulation of OASFs with adiponectin induced ICAM-1 expression. Pretreatment with AMP-activated protein kinase (AMPK) inhibitors (AraA and compound C) or transfection with siRNA against AMPKα1 and two AMPK upstream activator- liver kinase B1 (LKB1) and calmodulin-dependent protein kinase II (CaMKII) diminished the adiponectin-induced ICAM-1 expression. Stimulation of OASFs with adiponectin increased phosphorylation of LKB1, CaMKII, AMPK, and c-Jun, resulting in c-Jun binding to AP-1 element of ICAM-1 promoter. In addition, adiponectin-induced activation of the LKB1/CaMKII, AMPK, and AP-1 pathway increased the adhesion of monocytes to the OASF monolayer. Our results suggest that adiponectin increases ICAM-1 expression in human OASFs via the LKB1/CaMKII, AMPK, c-Jun, and AP-1 signaling pathway. Adiponectin-induced ICAM-1 expression promoted the adhesion of monocytes to human OASFs. These findings may provide a better understanding of the pathogenesis of OA and can utilize this knowledge to design a new therapeutic strategy.
PMCID: PMC3965461  PMID: 24667577
2.  PombeX: Robust Cell Segmentation for Fission Yeast Transillumination Images 
PLoS ONE  2013;8(12):e81434.
Schizosaccharomyces pombe shares many genes and proteins with humans and is a good model for chromosome behavior and DNA dynamics, which can be analyzed by visualizing the behavior of fluorescently tagged proteins in vivo. Performing a genome-wide screen for changes in such proteins requires developing methods that automate analysis of a large amount of images, the first step of which requires robust segmentation of the cell. We developed a segmentation system, PombeX, that can segment cells from transmitted illumination images with focus gradient and varying contrast. Corrections for focus gradient are applied to the image to aid in accurate detection of cell membrane and cytoplasm pixels, which is used to generate initial contours for cells. Gradient vector flow snake evolution is used to obtain the final cell contours. Finally, a machine learning-based validation of cell contours removes most incorrect or spurious contours. Quantitative evaluations show overall good segmentation performance on a large set of images, regardless of differences in image quality, lighting condition, focus condition and phenotypic profile. Comparisons with recent related methods for yeast cells show that PombeX outperforms current methods, both in terms of segmentation accuracy and computational speed.
PMCID: PMC3865994  PMID: 24353754
3.  Bis[2-({[2-(methyl­sulfan­yl)phen­yl]imino}­meth­yl)phenolato-κ2 N,O]zinc chloro­form disolvate 
The monomeric title complex, [Zn(C14H12NOS)2]·2CHCl3 or L 2Zn·2CHCl3, where L is the 2-({[2-(methyl­sulfan­yl)phen­yl]imino}­meth­yl)phenolate anion, may be obtained by the reaction of LZnEt with benzyl alcohol or by the reaction of two equivalents of LH with ZnEt2 in tetra­hydro­furan. The Zn atom, located on a twofold axis, is four-coordinated in a distorted tetra­hedral geometry by two O atoms [Zn—O = 1.9472 (19) Å] from the phenolate anions and two imine N atoms [Zn—N = 2.054 (2) Å].
PMCID: PMC3588749  PMID: 23468714
4.  Automatic Morphological Subtyping Reveals New Roles of Caspases in Mitochondrial Dynamics 
PLoS Computational Biology  2011;7(10):e1002212.
Morphological dynamics of mitochondria is associated with key cellular processes related to aging and neuronal degenerative diseases, but the lack of standard quantification of mitochondrial morphology impedes systematic investigation. This paper presents an automated system for the quantification and classification of mitochondrial morphology. We discovered six morphological subtypes of mitochondria for objective quantification of mitochondrial morphology. These six subtypes are small globules, swollen globules, straight tubules, twisted tubules, branched tubules and loops. The subtyping was derived by applying consensus clustering to a huge collection of more than 200 thousand mitochondrial images extracted from 1422 micrographs of Chinese hamster ovary (CHO) cells treated with different drugs, and was validated by evidence of functional similarity reported in the literature. Quantitative statistics of subtype compositions in cells is useful for correlating drug response and mitochondrial dynamics. Combining the quantitative results with our biochemical studies about the effects of squamocin on CHO cells reveals new roles of Caspases in the regulatory mechanisms of mitochondrial dynamics. This system is not only of value to the mitochondrial field, but also applicable to the investigation of other subcellular organelle morphology.
Author Summary
Mitochondria are “cellular power plants” that synthesize adenosine triphosphate (ATP) from degradation of nutrients, providing chemical energy for cellular activities. In addition, mitochondria are involved in a range of other cellular processes, such as signaling, cell differentiation, cell death, cell cycle and cell growth. Dysfunctional mitochondrial dynamics have been linked to several neurodegenerative diseases, and may play a role in the aging process. Previous studies on the correlation between mitochondrial morphological changes and pathological processes involve mostly manual or semi-automated classification and quantification of morphological features, which introduces biases and inconsistency, and are labor intensive. In this work we have developed an automated quantification system for mitochondrial morphology, which is able to extract and distinguish six representative morphological subtypes within cells. Using this system, we have analyzed 1422 cells and extracted more than 200 thousand individual mitochondrion, and calculated morphological statistics for each cell. From the numerical results we were able to derive new biological conclusions about mitochondrial morphological dynamics. With this new system, investigations of mitochondrial morphology can be scaled up and objectively quantified, allowing standardization of morphological distinctions and replicability between experiments. This system will facilitate future research on the relation between subcellular morphology and various physiological processes.
PMCID: PMC3188504  PMID: 21998575
5.  Endoscopic discectomy of L5-S1 disc herniation via an interlaminar approach: Prospective controlled study under local and general anesthesia 
Open discectomy remains the standard method for treatment of lumbar disc herniation, but can traumatize spinal structure and leaves symptomatic epidural scarring in more than 10% of cases. The usual transforaminal approach may be associated with difficulty reaching the epidural space due to anatomical peculiarities at the L5–S1 level. The endoscopic interlaminar approach can provide a direct pathway for decompression of disc herniation at the L5–S1 level. This study aimed to evaluate the clinical results of endoscopic interlaminar lumbar discectomy at the L5–S1 level and compare the technique feasibility, safety, and efficacy under local and general anesthesia (LA and GA, respectively).
One hundred twenty-three patients with L5–S1 disc herniation underwent endoscopic interlaminar lumbar discectomy from October 2006 to June 2009 by two spine surgeons using different anesthesia preferences in two medical centers. Visual analog scale (VAS) scores for back pain and leg pain and Oswestry Disability Index (ODI) sores were recorded preoperatively, and at 3, 6, and 12 months postoperatively. Results were compared to evaluate the technique feasibility, safety, and efficacy under LA and GA.
VAS scores for back pain and leg pain and ODI revealed statistically significant improvement when they were compared with preoperative values. Mean hospital stay was statistically shorter in the LA group. Complications included one case of dural tear with rootlet injury and three cases of recurrence within 1 month who subsequently required open surgery or endoscopic interlaminar lumbar discectomy. There were no medical or infectious complications in either group.
Disc herniation at the L5–S1 level can be adequately treated endoscopically with an interlaminar approach. GA and LA are both effective for this procedure. However, LA is better than GA in our opinion.
PMCID: PMC3130490  PMID: 21748045
General anesthesia; interlaminar approach; local anesthesia; lumbar disc herniation; percutaneous endoscopic discectomy

Results 1-5 (5)