Meditation is associated with increased brain network integration

Publication date: September 2017
Source:NeuroImage, Volume 158
Author(s): Remko van Lutterveld, Edwin van Dellen, Prasanta Pal, Hua Yang, Cornelis Jan Stam, Judson Brewer
IntroductionThis study aims to identify novel quantitative EEG measures associated with mindfulness meditation. As there is some evidence that meditation is associated with higher integration of brain networks, we focused on EEG measures of network integration.MethodsSixteen novice meditators and sixteen experienced meditators participated in the study. Novice meditators performed a basic meditation practice that supported effortless awareness, which is an important quality of experience related to mindfulness practices, while their EEG was recorded. Experienced meditators performed a self-selected meditation practice that supported effortless awareness. Network integration was analyzed with maximum betweenness centrality and leaf fraction (which both correlate positively with network integration) as well as with diameter and average eccentricity (which both correlate negatively with network integration), based on a phase-lag index (PLI) and minimum spanning tree (MST) approach. Differences between groups were assessed using repeated-measures ANOVA for the theta (4–8 Hz), alpha (8–13 Hz) and lower beta (13–20 Hz) frequency bands.ResultsMaximum betweenness centrality was significantly higher in experienced meditators than in novices (P = 0.012) in the alpha band. In the same frequency band, leaf fraction showed a trend toward being significantly higher in experienced meditators than in novices (P = 0.056), while diameter and average eccentricity were significantly lower in experienced meditators than in novices (P = 0.016 and P = 0.028 respectively). No significant differences between groups were observed for the theta and beta frequency bands.ConclusionThese results show that alpha band functional network topology is better integrated in experienced meditators than in novice meditators during meditation. This novel finding provides the rationale to investigate the temporal relation between measures of functional connectivity network integration and meditation quality, for example using neurophenomenology experiments.



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Correction of metal-induced susceptibility artifacts for functional MRI during deep brain stimulation

Publication date: September 2017
Source:NeuroImage, Volume 158
Author(s): Myung-Ho In, Shinho Cho, Yunhong Shu, Hoon-Ki Min, Matt A. Bernstein, Oliver Speck, Kendall H. Lee, Hang Joon Jo
Functional magnetic resonance imaging (fMRI) is an emerging tool for investigating brain activation associated with, or modulated by, deep brain stimulation (DBS). However, DBS-fMRI generally suffers from severe susceptibility to artifacts in regions near the metallic stimulation electrodes, as well as near tissue/air boundaries of the brain. These result in strong intensity and geometric distortions along the phase-encoding (PE) (i.e., blipped) direction in gradient-echo echo-planar imaging (GE-EPI). Distortion presents a major challenge to conducting reliable data analysis and in interpreting the findings. A recent study showed that the point spread function (PSF) mapping-based reverse gradient approach has a potential to correct for distortions not only in spin-echo EPI, but also in GE-EPI acquired in both the forward and reverse PE directions. In this study, we adapted that approach in order to minimize severe metal-induced susceptibility artifacts for DBS-fMRI, and to evaluate the performance of the approach in a phantom study and a large animal DBS-fMRI study. The method combines the distortion-corrected GE-EPI pair with geometrically different intensity distortions due to the opposing encoding directions. The results demonstrate that the approach can minimize susceptibility artifacts that appear around the metallic electrodes, as well as in the regions near the tissue/air boundaries in the brain. We also demonstrated that an accurate geometric correction is important in improving BOLD contrast in the group dataset, especially in regions where strong susceptibility artifacts appear.



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Chinese versus English: Insights on Cognition during Reading

Publication date: Available online 1 July 2017
Source:Trends in Cognitive Sciences
Author(s): Lili Yu, Erik D. Reichle
Chinese reading experiments have introduced important caveats to theories of reading that have been largely informed by studies of English reading – especially in relation to our understanding of lexical processing and eye-movement control. This article provides a brief primer on Chinese reading and examples of questions that arise from its study.



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Scholar : Chinese Archives of Otolaryngology-Head and Neck Surgery, Year 2017, Issue 05 -New Issue Alert.

New Issue TOC Alert Dear Valued Customer, We are pleased to deliver your requested table of contents alert for Chinese Archives of Otolaryngology-Head and Neck Surgery. Year 2017 Issue 05 is now available on CAOD. In this issue: Diagnosis and therapy of lingual ectopic thyroid (舌异位甲状腺的诊治) XU Hongbo, ,CHEN Xiaohong, ,FANG Jugao, ,LI Pingdong, ,ZHONG Qi, ,ZHANG Yang, ,YANG Zheng, ,HUANG Zhigang ...... page:221-224 One stage surgical treatment of multiple primary carcinoma of hypopharynx and esophagus (下咽及颈胸段食管多原发癌一期手术) ZHANG Binghuang, ,LUO Xianyang, ,HUANG Xuge, ,CHEN Aimin, ,JIANG Yuanqin, ,CAI Chenfu, ,YU Xiuyi ...... page:225-227 Expression of Hox transcript antisense RNA, enhancer of zeste homolog 2 and vascular endothelial growth factor in nasopharyngeal carcinoma tissues and their correlation with prognosis (Hox转录反义RNA、zeste基因增强子同源物2与血管内皮生长因子在鼻咽癌组织中的表达及其预后相关性研究) MA Yun, ,ZOU Hua, ,LIU Xiang, ,TIAN Peng, ,NIE Yan, ,QU Shaohua ...... page:228-232 Clinical research about level Ⅵ-1 lymph nodes and the lymph nodes posterior to the right recurrent laryngeal nerve of the papillary thyroid carcinoma (中央区浅层淋巴结与甲状腺乳头状癌右喉返神经后方淋巴结的相关研究) SHI Jingjing, ,XU Xiaocheng, ,WU Jian, ,DING Jinwang, ,PENG You, ,ZHANG Wo, ,PAN Gang, ,ZHANG Yu, ,LUO Dingcun ...... page:233-236 Research on the relationship between mucoepidermoid carcinoma and human papillomavirus infection (腮腺黏液表皮样癌与人乳头瘤病毒感染的相关性研究) CHEN Shiyan, ,GONG Hongxun, ,WANG Maoxin, ,CHEN Xianming ...... page:237-238 Short term outcome of modified Semont maneuver for posterior semicircular canal benign paroxysmal positional vertigo (改良Semont方法治疗后半规管良性阵发性位置性眩晕的短期疗效研究) LI Jinrang, ,ZOU Shizhen, ,TIAN Shiyu, ,TIAN Congzhe ...... page:239-241 Correlation analysis of the incidence and head position in posterior semicircular canal benign paroxysmal positional vertigo (后半规管良性阵发性位置性眩晕发作与头部睡眠姿势相关性分析) LIN Xikang, ,LI Xiaolu ...... page:242-244 Application of the video of head-eye movement training in vestibular rehabilitation (头-眼运动训练视频在前庭康复中的应用) CAO Chunting, ,LI Qi, ,LIU Yuanyuan, ,TIAN Ying, ,WANG Yuan, ,QI Ke, ,CAO Litang ...... page:245-247 zuo xia xian qian zuo xing yu ci yi wu 1 li (颌下腺迁徙性鱼刺异物1例) ZUO Yanjun, ,ZENG Dongqian, ,WENG Yongcai, ,GU Dongsheng ...... page:248 Clinicopathological comparative analysis of nasal Rosai-Dorfman disease and rhinoscleroma (鼻腔鼻窦Rosai-Dor fman病与鼻硬结病临床病理对比分析) PU Yingshi, ,WANG Chengshuo, ,ZHANG Luo ...... page:249-252 Immunoregulatory role of tolerogenic dendritic cells in allergic rhinitis in mice (免疫耐受型树突状细胞对变应性鼻炎小鼠的调控作用) WEI Jiawei, ,ZHONG Hua, ,LI Hang, ,WEN Weiping ...... page:253-257 Changes and clinical significance of serum Nesfatin-1 in patients with obstructive sleep apnea hypopnea syndrome and type 2 diabetes mellitus (阻塞性睡眠呼吸暂停低通气综合征合并2型糖尿病患者血清Nesfatin-1的变化及意义) ZHENG Guojun, ,WU Xiaoyan, ,SHI Zhengxian, ,WANG Yan, ,LI Rui ...... page:258-261 que yang you dao yin zi 1 xue guan nei pi sheng chang yin zi ji cxcr4 shou ti zai jia zhuang xian ru tou zhuang ai zhong de biao da ji yu zhong liu zhuan yi de guan xi (缺氧诱导因子1α、血管内皮生长因子及CXCR4受体在甲状腺乳头状癌中的表达及与肿瘤转移的关系) RAN Cheng, ,GAO Yongping, ,ZHANG Jianyang, ,RONG Guiyuan ...... page:262-264 shi shi er wei hui jie chao sheng zao ying dui jia zhuang xian e xing jie jie de zhen duan jia zhi (实时二维灰阶超声造影对甲状腺恶性结节的诊断价值) CHEN Mei, ,XIAO Xuping ...... page:265-266 er tong bian tao ti zhai chu shu zhi liao fu fa xing yan hou yan de lin chuang yan jiu (儿童扁桃体摘除术治疗复发性咽喉炎的临床研究) LU Jie ...... page:267-268 bi jie shi ban zhen jun gan ran 2 li (鼻结石伴真菌感染2例) WANG Ming, ,LIU Gang ...... page:269-270 man xing qin xi xing zhen jun xing bi - bi zuo yan bing fa bi zhong ge chuan kong 2 li (慢性侵袭性真菌性鼻-鼻窦炎并发鼻中隔穿孔2例) WANG Beibei, ,YAO Xiaolong, ,ZHANG Fen, ,ZHAO Yuanyang, ,WANG Chunyu, ,LI Zhizuo, ,ZHANG Qingquan ...... page:271-272 bian tao ti fang xian jun bing wu zhen 1 li (扁桃体放线菌病误诊1例) WANG Changqing, ,MA Zhiqiang, ,LIU Pinghua, ,ZHAO Wenmin, ,ZENG Hongbin, ,WANG Zhong, ,WANG Yuelong ...... page:273-274 CAOD TOC Alerts Note Thank you for choosing CAOD Table of Contents (TOC) Alert Service. You are receiving this email because you have requested to receive information from CAOD as a registered user of our Table of Content Alert for journals. To manage your TOC Alerts, please click here. For all enquiries, problems or suggestions regarding this service, please contact info@oriprobe.com. China/Asia on Demand (CAOD) Customer Service

Scholar : West China Journal of Stomatology, Year 2017, Issue 03 -New Issue Alert.

New Issue TOC Alert Dear Valued Customer, We are pleased to deliver your requested table of contents alert for West China Journal of Stomatology. Year 2017 Issue 03 is now available on CAOD. In this issue: Confusion and solution for vital pulp therapy (活髓保存治疗之惑及解决之道) Huang Dingming, ,Lu Qian, ,Liao Qian, ,Ye Ling, ,Zhou Xuedong ...... page:227-231 Difficulties and misunderstandings of root canal filling (根管充填的难点和误区) Zhang Chen ...... page:232-238 Construction of a low-pH-sensing system inStreptococcus mutans (变异链球菌低pH感应系统的构建) Kang Di, ,Li Yuqing, ,Zhou Xuedong ...... page:239-244 Effect of hypoxia on the biological characteristics of human dental follicle cells (低氧对人牙囊细胞生:学特性的影响) LIANG Xi, ,CHEN Guoqing, ,TIAN Weidong ...... page:245-252 Establishment of rat models with altered anterior guidance and observation of histological changes in temporomandi- bular joint synovium (实验性前导斜度改变的大鼠模型的建立及其颞下颌关节滑膜组织病理学观察) Li Yuxuan, ,Zhai Tong, ,Tan Wenhong, ,Bai Le'ang, ,Xiao Min ...... page:253-257 n-cements yi huo jia wei wa deng te gong si tui chu quan xin de shu zhi ji zhan jie lei shui men ting xi lie chan pin (N-Cements——义获嘉伟瓦登特公司推出全新的树脂基粘接类水门汀系列产品) YI Huojiaweiwadengtegongsi ...... page:257 Alteration of metabolic characteristics on the masseter muscle fiber of unilateral chewing rats and its adenosine mono- phosphate activated protein kinase regulatory mechanism (偏侧咀嚼致大鼠咬肌肌纤维代谢特征改变及其腺苷酸活化蛋白激酶调节机制) Shi Andi, ,Zeng Lin, ,Liu Jing ...... page:258-263 Therapeutic effect of enhancer of Zeste homolog 2 inhibitor GSK343 on periodontitis by regulating macrophage diffe- rentiation (Zeste基因增强子人类同源:2抑制剂GSK343调节巨噬细胞分化的作用) Wang Zhongchao, ,Fan Liyuan, ,Tan Dan, ,Zhou Cong, ,Luo Shijun ...... page:264-268 Characterization of microRNAs profiles of induced pluripotent stem cells reprogrammed from human dental pulp stem cells and stem cells from apical papilla (人牙源性多能干细胞重编程前后微小RNAs差异表达谱系分析) Tan Xiaobing, ,Dai Qingyuan ...... page:269-274 Effect of naringin combined with bone morphogenetic protein-2 on the proliferation and differentiation of MC3T3-E1 cells (柚皮苷协同骨形态发生蛋白-2促进小鼠成骨细胞MC3T3-E1增殖和分化的研究) Xu Gaoli, ,Liu Yi, ,Wu Lili, ,Shi Qiutao, ,Huo Guang, ,Gu Zhiyuan ...... page:275-280 Comparison among three translucency parameters (3种半透性测量指标的比较性研究) Xiong Fang, ,Xia Hui ...... page:281-285 Soluble programmed death-1 and soluble programmed death ligand 1 protein expression and immune status in patients with recurrent aphthous ulcer (复发性阿弗他溃疡患者可溶性程序性死亡受体1及可溶性程序性死亡配体1表达与免疫功能的相关性) Jiang Nan, ,Luo Liang, ,Liu Li, ,Sun Xiaoqin, ,Jiang Xing, ,Cai Yang ...... page:286-290 Association between non-syndromic cleft lip with or without cleft palate and environmental factors in Ningxia (宁夏地区非综合征型唇腭裂环境因素的研究) Yu Lili, ,Ma Jian, ,Gao Junpeng, ,Zhai Kun, ,Zhu Jinfang, ,Huang Yongqing ...... page:291-295 Velopharyngeal closure pattern and speech performance among submucous cleft palate patients (黏膜下腭裂的腭咽闭合状态及语音表现分析) Yin Heng, ,Guo Chunli, ,Shi Bing, ,Li Yang, ,Li Jingtao ...... page:296-300 Analysis of the current status of research on human papillomavirus-associated head and neck cancers based on recent Chinese literature (人乳头瘤病毒相关头颈肿瘤的中文文献研究现状分析) Liu Yan, ,Cao Mingxin, ,Wu Jiashun, ,Gao Xiaolei, ,Liang Xinhua ...... page:301-310 Clinical significance of CD44 and CD133 expression in oral potentially malignantdisorder and oral squamous cell carcinoma (CD44和CD133在口腔潜在恶性病变和口腔鳞状细胞癌中的表达及其临床意义) Qi Jiajia, ,Sun Yan, ,Yuan Changqing, ,Jiang Wenjing, ,Zhao Han, ,Cao Yuanpan, ,Liu Qiuyan ...... page:311-316 Inhibitory effect and underlying mechanism of total saponins from Paris polyphylla var. yunnanensis on the prolifera- tion of salivary adenoid cystic carcinoma ACC-83 cellsHe (滇重楼总皂苷对涎腺腺样囊性癌ACC-83细胞增殖抑制及其机制的研究) He Qiumin, ,Xu Biao, ,Wang Weihong, ,Bao Chongyun, ,Hu Shao-wei ...... page:317-321 Relationship between oral and gut microbes (口腔微生物与肠道微生物的关系) Cheng Xingqun, ,Xu Xin, ,Zhou Xuedong ...... page:322-327 Expression and function of microRNAs in enamel development (微小RNAs在牙釉质发育过程中的表达和作用) Zhou Yachuan, ,Zhou Xuedong, ,Zheng Liwei ...... page:328-333 Tumor necrosis factor-α regulates the osteogenic differentiation of bone marrow mesenchymal stem cells in chronic periodontitis (慢性牙周炎中肿瘤坏死因子α对骨髓间充质干细胞成骨分化的调控作用) Li Xiaoguang, ,Wang Yizhu, ,Guo Bin ...... page:334-338 CAOD TOC Alerts Note Thank you for choosing CAOD Table of Contents (TOC) Alert Service. You are receiving this email because you have requested to receive information from CAOD as a registered user of our Table of Content Alert for journals. To manage your TOC Alerts, please click here. For all enquiries, problems or suggestions regarding this service, please contact info@oriprobe.com. China/Asia on Demand (CAOD) Customer Service

Scholar : Chinese Journal of Ophthalmology and otorhinolaryngology, Year 2017, Issue 03 -New Issue Alert.

New Issue TOC Alert Dear Valued Customer, We are pleased to deliver your requested table of contents alert for Chinese Journal of Ophthalmology and otorhinolaryngology. Year 2017 Issue 03 is now available on CAOD. In this issue: European Position Paper on the Anatomical Terminology of the Internal Nose and Paranasal Sinuses (欧洲鼻腔鼻窦解剖术语意见书(二)) LUND Vj, ,STAMMBERGER H, ,FOKKENS Wj, ,BEALE T, ,BERNAL Sprekelsenm, ,ELOY P, ,GEORGALAS C, ,GERSTENBERGER C, ,HELLINGS Pw, ,HERMAN P, ,HOSEMANN Wg, ,JANKOWSKI R, ,JONES N, ,JORISSEN M, ,LEUNIG A, ,ONERCI M, ,RIMMER J, ,ROMBAUX P, ,SIMMEN D, ,TOMAZIC Pv, ,TSCHABITSCHER M, ,WELGE Luessena, ,WANG Dehui, ,YU Huapeng, ,SUN Xicai, ,LI Zuo, ,LIU Zhuofu, ,LIU Quan, ,ZHANG Huankang ...... page:153-156 shi ti yu da an (试题与答案) WANG Sen, ,JIANG Zuo, ,ZUO Renyuan ...... page:156,161,165,212 CT imaging features of congenital external auditory canal stenosis based on Matlab software (基于Matlab软件的先天性外耳道狭窄CT影像特点分析) YIN Dong-ming, ,YANG Lin, ,ZHANG Tian-yu, ,DAI Pei-dong ...... page:157-161 Relationship between cadherin 23 gene polymorphism and noise induced hearing loss in flying cadets (钙黏蛋白23基因多态性与飞行学员噪声性听力损失的关系) ZHENG Chen, ,WANG Jin-lin, ,ZHANG Su-wei, ,LI Da-peng, ,ZHENG Wei, ,LI Xiao-shuai, ,GUO Rui ...... page:162-165 Primary diffuse large B cell lymphoma of nasal cavity and paranasal sinus in 30 cases (原发鼻腔鼻窦弥漫大B细胞淋巴瘤30例) TIAN Shu, ,WANG Wei-fang, ,YANG Gang, ,ZOU Li-fen, ,YUAN Wei, ,ZHANG Hai-yan, ,WANG Sheng-zi, ,DING Hao ...... page:166-169,175 Correlation between human papillomavirus infection and the pathogenesis and prognosis of laryngeal squamous cell carcinoma (人乳头瘤病毒感染与喉鳞状细胞癌发生及预后的关系) LIU Dan-ling, ,XU Ya-nan, ,WANG Jia-dong ...... page:170-175 Behavioral characteristics of visual collinear facilitation in primary open-angle glaucoma (原发性开角型青光眼中同向易化视觉现象的行为特性改变) ZHANG Ting, ,YANG Hong-fang, ,ZHANG Yu-qiu, ,LIU Ting-ting, ,SUN Xing-huai ...... page:176-179 Ocular manifestations of ocular surface squamons cell carcinoma (眼袁鳞状细胞癌的临床表现) ZHANG Rui, ,QIAN Jiang, ,GUO Jie, ,BI Ying-wen, ,YUAN Yi-fei ...... page:180-183 Treatment for dural bone defect of the tegmen of tympanum and tympanic sinus or mastoid in tympanoplasty (鼓室成形术中鼓室、鼓窦及乳突天盖区脑膜裸露的处理及分析) WANG Kai-shi, ,NI Yu-su ...... page:184-186 xin xi dong tai (信息动态) ...... page:186,197 Short-term efficacy of individualized algorithm of transscleral cyclophotocoagulation on refractory glaucoma (个性化睫状体光凝术治疗难治性青光眼的短期观察) OU Wen, ,ZHANG Shao-dan, ,ZHENG Jing-wei, ,PENG Xian-yao, ,XIE Yan-qian, ,FANG Ai-wu, ,LIANG Yuan-bo ...... page:187-190 Clinical research of lens density measurement in grading diagnosis of nuclear cataract in type 2 diabetic patients (晶状体密度测量在2型糖尿病合并白内障患者中的临床应用研究) ZHANG Shao-wei, ,LIU Li, ,HUANG Yi, ,LI Qin ...... page:191-194 Clinical analysis in relevant information of 93 children with frequent blinking (眨眼儿童93例相关因素的临床分析) WANG Chang-hong, ,YE Hong, ,CHEN Hong-yan ...... page:195-197 Study on the management of NasoPore in the operative cavity after endoscopic sinus surgery (鼻内镜术后术腔纳吸绵的处理方式研究) HE Yun-sheng, ,ZHANG Jing-hua, ,CHEN Ying-wu ...... page:198-199 Otoendoscope-assisted repair for large tympanic membrane perforation in 26 cases (耳内镜下鼓膜大穿孔修补26例) WANG Tie-feng, ,XU ya-ping ...... page:200-201 Clinical analysis of percutaneous dilational tracheostomy guided by B ultrasound (B超引导下经皮气管切开105例临床分析) BAI Zheng-qun, ,WU Li-fang, ,JI Zhou-qun, ,JIANG Jian-ju, ,LIU Jian-bing ...... page:202-203 bi bu shou shu hou shi wang mo zhong yang dong mai zu sai 1 li (鼻部手术后视网膜中央动脉阻塞1例) ZHANG Yuanxia, ,LIU Xiaozuo ...... page:204,230 Progress of neurofibromatosis 2 gene and its expression product in the pathogenesis of acoustic neuroma (神经纤维瘤病2型基因及其表达产物在听神经瘤发病机制中的研究进展) XU Jian-hui, ,ZHANG Tian-yu ...... page:205-207 Progress in the treatment of blepharitis (睑缘炎治疗进展) WU Meng-liang, ,WANG Yan ...... page:208-212 Research process in association of human papilloma virus and ocular surface squamous neoplasia (人乳头瘤病毒与眼表鳞状上皮肿瘤关系的研究进展) SHAO Yang-yang, ,ZHANG Chao-ran ...... page:213-216 Relationship between tear glucose and blood glucose and the development of monitoring tear glucose (泪糖与血糖的相关性及泪糖监测的研究进展) RUAN Jia-li, ,QIAN Shao-hong ...... page:217-221 tong kong yi chang de ping gu ji bing yin fen xi (瞳孔异常的评估及病因分析) TIAN Guohong ...... page:222-226 zhong guo zhong xi yi jie he xue hui di qi jie er bi yan hou ke zhuan ye wei yuan hui gai xuan huan jie (中国中西医结合学会第七届耳鼻咽喉科专业委员会改选换届) REN Dongdong, ,HAN Chao ...... page:226 ce lu di shen jing xue guan qu liang xing zhong liu shou shu [ er xian wei wai ke 2007 ban ( wu shi ba )] (侧颅底神经血管区良性肿瘤手术[耳显微外科2007版(五十八)]) WANG Zhengmin ...... page:227-230 CAOD TOC Alerts Note Thank you for choosing CAOD Table of Contents (TOC) Alert Service. You are receiving this email because you have requested to receive information from CAOD as a registered user of our Table of Content Alert for journals. To manage your TOC Alerts, please click here. For all enquiries, problems or suggestions regarding this service, please contact info@oriprobe.com. China/Asia on Demand (CAOD) Customer Service

On the role of classical and novel forms of vitamin D in melanoma progression and management

Publication date: Available online 1 July 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Andrzej T. Slominski, Anna A Brozyna, Cezary Skobowiat, Michal A. Zmijewski, Tae-Kang Kim, Zorica Janjetovic, Allen S. Oak, Wojciech Jozwicki, Anton M. Jetten, Rebecca S. Mason, Craig Elmets, We Li, Robert M. Hoffman, Robert C. Tuckey
Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB. The former activities include inhibitory effects on proliferation, plating efficiency and anchorage-independent growth of cultured human and rodent melanomas in vitro, as well as the in vivo inhibition of tumor growth by 20(OH)D3 after injection of human melanoma cells into immunodeficient mice. The literature indicates that low levels of 25(OH)D3 are associated with more advanced melanomas and reduced patient survivals, while single nucleotide polymorphisms of the vitamin D receptor or the D3 binding protein gene affect development or progression of melanoma, or disease outcome. An inverse correlation of VDR and CYP27B1 expression with melanoma progression has been found, with low or undetectable levels of these proteins being associated with poor disease outcomes. Unexpectedly, increased expression of CYP24A1 was associated with better melanoma prognosis. In addition, decreased expression of retinoic acid orphan receptors α and γ, which can also bind vitamin D3 hydroxyderivatives, showed positive association with melanoma progression and shorter disease-free and overall survival. Thus, inadequate levels of biologically active forms of D3 and disturbances in expression of the target receptors or D3 activating or inactivating enzymes, can affect melanomagenesis and disease progression. We therefore propose that inclusion of vitamin D into melanoma management should be beneficial for patients, at least as an adjuvant approach. The presence of multiple hydroxyderivatives of D3 in skin that show anti-melanoma activity in experimental models and which may act on alternative receptors, will be a future consideration when planning which forms of vitamin D to use for melanoma therapy.



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Vitamin D-deficiency and sex-specific dysregulation of placental inflammation

Publication date: Available online 1 July 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Nancy Q. Liu, Dean P. Larner, Qingqiang Yao, Rene F. Chun, Yuxin Ouyang, Rui Zhou, Jennifer A. Tamblyn, Carol L. Wagner, Martin Hewison
To investigate an immunomodulatory role for vitamin D in pregnancy we used mice raised on vitamin D-sufficient (SUFF), or −deficient (DEF) diets. At embryonic day 14, pregnant mice received intraperitoneal injection of lipopolysaccharide (LPS) or vehicle for 24hrs, with age-matched non-pregnant mice as controls. In non-pregnant mice, 6 serum analytes (IL-1β, IL-18, MDC/CCL22, MIP-1α/CCL3, EGF, IgA) were lower in DEF mice. In pregnant DEF mice only GH was higher. In non-pregnant mice LPS induced 28 analytes, with 5 (IL-18, IP-10/CXCL10, MCP-1/CCL2, MIP-1β/CCL4, MIP-3β/CCL19) being highest in DEF mice. In pregnant SUFF mice 16 serum analytes increased with LPS, and 6 of these (IP-10/CXCL10, MCP-1/CCL2, SAP, TIMP-1, VCAM-1, vWF) were higher and 1 (GCP-2/CXCL6) lower in DEF mice. Parallel analysis of placental mRNAs showed elevated mRNA for Il-6, Ccl2 and Cxcl10 in placentae from male and female fetuses in LPS-DEF mice. However, LPS-induced expression of Ifnγ, Tnfα, and Cxcl6 was only observed in female placentae from DEF mice. LPS-DEF mice also showed smaller litter sizes relative to control SUFF mice. Numbers of female fetuses per dam were significantly lower for DEF mice with or without LPS challenge. LPS had no effect on numbers of male fetuses from DEF mothers, but significantly decreased male fetuses from SUFF mothers. These data indicate that vitamin D is an important component of anti-inflammatory immune responses during pregnancy, with the placenta and fetal sex playing pivotal roles in this process.



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Small molecules to the rescue: Inhibition of cytokine signaling in immune-mediated diseases

Publication date: Available online 1 July 2017
Source:Journal of Autoimmunity
Author(s): Massimo Gadina, Nathalia Gazaniga, Laura Vian, Yasuko Furumoto
Cytokines are small, secreted proteins associated with the maintenance of immune homeostasis but also implicated with the pathogenesis of several autoimmune and inflammatory diseases. Biologic agents blocking cytokines or their receptors have revolutionized the treatment of such pathologies. Nonetheless, some patients fail to respond to these drugs or do not achieve complete remission. The signal transduction originating from membrane-bound cytokine receptors is an intricate network of events that lead to gene expression and ultimately regulate cellular functionality. Our understanding of the intracellular actions that molecules such as interleukins, interferons (IFNs) and tumor necrosis factor (TNF) set into motion has greatly increased in the past few years, making it possible to interfere with cytokines' signaling cascades. The Janus kinase (JAK)/signal transducer and activator of transcription (STAT), the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), the mitogen activated protein kinase (MAPK) and the Phosphatidylinositol-3′-kinases (PI3K) pathways have all been intensively studied and key steps as well as molecules have been identified. These research efforts have led to the development of a new generation of small molecule inhibitors. Drugs capable of blocking JAK enzymatic activity or interfering with the proteasome-mediated degradation of intermediates in the NF-kB pathway have already entered the clinical arena confirming the validity of this approach. In this review, we have recapitulated the biochemical events downstream of cytokine receptors and discussed some of the drugs which have already been successfully utilized in the clinic. Moreover, we have highlighted some of the new molecules that are currently being developed for the treatment of immune-mediated pathologies and malignancies.



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Copyright

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Contributors

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Contents

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Forthcoming Issues

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4





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Kinase Inhibitors in the Treatment of Myeloid Malignancies

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Ann Mullally




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The Treatment of Myeloid Malignancies with Kinase Inhibitors

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Ann Mullally




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Tyrosine Kinase Inhibitor Treatment for Newly Diagnosed Chronic Myeloid Leukemia

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Jerald P. Radich, Michael J. Mauro

Teaser

Chronic myeloid leukemia (CML) is a myeloproliferative disorder that accounts for approximately 10% of new cases of leukemia. The introduction of tyrosine kinase inhibitors has led to a reduction in mortalities. Thus, the estimated prevalence of CML is increasing. The National Comprehensive Cancer Network and the European Leukemia Net guidelines incorporate frequent molecular monitoring of the fusion BCR-ABL transcript to ensure that patients reach and keep treatment milestones. Most patients with CML are diagnosed in the chronic phase, and approximately 10% to 30% of these patients will at some time in their course meet definition criteria of resistance to imatinib.


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Mechanisms of Resistance to ABL Kinase Inhibition in Chronic Myeloid Leukemia and the Development of Next Generation ABL Kinase Inhibitors

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Ami B. Patel, Thomas O'Hare, Michael W. Deininger

Teaser

Chronic myeloid leukemia is increasingly viewed as a chronic illness; most patients have a life expectancy close to that of the general population. Despite progress made using BCR-ABL1 tyrosine kinase inhibitors (TKIs), drug resistance via BCR-ABL1–dependent and BCR-ABL1–independent mechanisms continues to be an issue. BCR-ABL1–dependent resistance is primarily mediated through oncoprotein kinase domain mutations and usually results in overt resistance to TKIs. However, BCR-ABL1–independent resistance in the setting of effective BCR-ABL1 inhibition is recognized as a major contributor to minimal residual disease. Efforts to eradicate persistent leukemic stem cells have focused on combination therapy.


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Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis

Publication date: August 2017
Source:Hematology/Oncology Clinics of North America, Volume 31, Issue 4
Author(s): Jason Gotlib

Teaser

The World Health Organization's semimolecular classification of eosinophilias emphasizes neoplasms driven by fusion tyrosine kinases. More than 80% of patients with systemic mastocytosis carry the KIT D816V mutation, the primary driver of disease pathogenesis. Genetic annotation of these diseases is critical and affords opportunities for targeted therapy. This article discusses our understanding of the mutated tyrosine kinome of eosinophilic neoplasms and systemic mast cell disease, and the successes and limitations of available therapies. Use of tyrosine kinase inhibitors as a bridge to hematopoietic stem cell transplantation, and development of more selective and potent tyrosine kinase inhibitors is also highlighted.


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Muscle synergies reveal impaired trunk muscle coordination strategies in individuals with thoracic spinal cord injury

Publication date: Available online 1 July 2017
Source:Journal of Electromyography and Kinesiology
Author(s): Matija Milosevic, Hikaru Yokoyama, Murielle Grangeon, Kei Masani, Milos R. Popovic, Kimitaka Nakazawa, Dany H. Gagnon
Spinal cord injury (SCI) can result in paralysis of trunk muscles, which can affect sitting balance. The objective of this study was to analyze trunk muscle coordination of individuals with thoracic SCI and compare it to able-body individuals. A total of 27 individuals were recruited and subdivided into: (a) high thoracic SCI; (b) low thoracic SCI; and (c) able-body groups. Participants were seated and asked to lean their trunk in eight directions while trunk muscle activity was recorded. Muscle coordination was assessed using the non-negative matrix factorization (NMF) method to extract muscle modules, which are the synergistic trunk muscle activations, and their directional activation patterns. Our results showed that individuals with SCI used less muscle modules, more co-contractions, and less directional tuning, compared to able-bodied people. These results suggest impaired and simplified muscle coordination due to the loss of supraspinal input after SCI. Observed variability in muscle coordination within SCI groups also suggests that other mechanisms such as spasticity and muscle stretch reflexes or individual factors such as experience and training contributed to the postural muscle synergies. Overall, muscle coordination deficits revealed impaired neuromuscular strategies which provide implications for rehabilitation of trunk muscles during sitting balance after SCI.



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Evaluation of laser fluorescence in monitoring non-cavitated caries lesion progression on smooth surfaces in vitro

Abstract

The aim of this study was to evaluate the performance of a pen-type laser fluorescence (LF) device (LFpen: DIAGNOdent pen) to detect and monitor the progression of caries-like lesions on smooth surfaces. Fifty-two bovine enamel blocks were submitted to three different demineralisation cycles for caries-like lesion induction using Streptococcus mutans, Lactobacillus casei and Actinomyces naeslundii. At baseline and after each cycle, the enamel blocks were analysed under Knoop surface micro-hardness (SMH) and an LFpen. One enamel block after each cycle was randomly chosen for Raman spectroscopy analysis. Cross-sectional micro-hardness (CSMH) was performed at different depths (20, 40, 60, 80 and 100 μm) in 26 enamel blocks after the second cycle and 26 enamel blocks after the third cycle. Average values of SMH (± standard deviation (SD)) were 319.3 (± 21.5), 80.5 (± 31.9), 39.8 (± 12.7), and 29.77 (± 10.34) at baseline and after the first, second and third cycles, respectively. Statistical significant difference was found among all periods (p < 0.01). The LFpen values were 4.3 (± 1.5), 7.5 (± 9.4), 7.1 (± 7.1) and 5.10 (± 3.58) at baseline and after the first, second, and third cycles, respectively, among all periods (p < 0.05). The CSMH values after the second and third cycles at 20, 40, 60, 80 and 100 μm were 182.8 (± 69.8), 226.1 (± 79.6), 247.20 (± 69.36), 262.35 (± 66.36) and 268.45 (± 65.49), and for the third cycle were 193.7 (± 73.4), 239.5 (± 81.5), 262.64 (± 82.46), 287.10 (± 78.44) and 284.79 (± 72.63) (n = 24 and 23), respectively. No correlation was observed between the LFpen and SMH values (p > 0.05). One sample of each cycle was characterised through Raman spectroscopy analysis. It can be concluded that LF was effective in detecting the first demineralisation on enamel; however, the method did not show any effect in monitoring lesion progression after three cycles of in vitro demineralisation.

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Suppressive effects of thermal-treated oyster shells on cadmium and copper translocation in maize plants

Abstract

The effect of varied concentrations of thermal-treated oyster shells (TOS) on the suppression of cadmium (Cd) and copper (Cu) uptake and translocation into the shoots of maize plants was examined. Maize plants were grown in Cd- and Cu-contaminated Andosol for 70 days. The concentration of mobile Cd (extracted with 1 M NH₄NO₃) decreased with increasing TOS applications, whereas an increase in the concentration of mobile Cu in soil resulted from cumulative TOS additions. The addition of 2% TOS had no prohibitive effects on Cd uptake in maize shoots, but the 4 and 8% TOS treatments decreased Cd accumulation in shoots by 41 and 59%, respectively. The possible mechanisms underlying Cd suppression in maize shoots were the enhanced Cd adsorption caused by pH-induced increases in the negative charge of the soil and the antagonistic effects of Ca resulting from competition for exchange sites at the root surface. Cu accumulation in maize shoots increased by 34, 51, and 53% with the addition of 2, 4, and 8% TOS, respectively, but this increase was not observed for Cd accumulation. These results suggested that, in multi-metal-contaminated soils, attention should be paid to the potential mobility of target metals and the pH of the contaminated soil. From a plant physiological perspective, contaminated soils slightly reduced photosynthetic performance. However, the addition of TOS to the soil at levels higher than 4% substantially decreased photosynthetic performance, indicating that CaO-based suppressants at critical loads might damage the net photosynthetic rates of sensitive maize plants.

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Insomnia disorder in adolescence: diagnosis, impact, and treatment

Insomnia disorder is very common in adolescents; it is particularly manifest in older adolescents and girls, with a prevalence comparable to that of other major psychiatric disorders (e.g., depressive disorders). However, insomnia disorder in adolescence is poorly characterized, under-recognized, under-diagnosed, and under-treated, and the reason for the female preponderance for insomnia that emerges after puberty is largely unknown. Insomnia disorder goes beyond an individual complaint of poor sleep or a sleep state misperception, and there is emerging evidence supporting the association of insomnia symptoms in adolescents with alterations in several bio-systems including functional cortical alterations and systemic inflammation.

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Simultaneous effect of dissolved organic carbon, surfactant, and organic acid on the desorption of pesticides investigated by response surface methodology

Abstract

Desorption of pesticides (fenobucarb, endosulfan, and dichlorodiphenyltrichloroethane (DDT)) from soil to aqueous solution with the simultaneous presence of dissolved organic carbon (DOC), sodium dodecyl sulfate (SDS), and sodium oxalate (Oxa) was investigated in batch test by applying a full factorial design and the Box–Behnken response surface methodology (RSM). Five concentration levels of DOC (8 to 92 mg L⁻¹), SDS (0 to 6.4 critical micelle concentration (CMC)), and Oxa (0 to 0.15 M) were used for the experiments with a rice field topsoil. The results of RSM analysis and analysis of variance (ANOVA) have shown that the experimental data could be well described by quadratic regression equations with determination coefficients (R ²) of 0.990, 0.976, and 0.984 for desorption of fenobucarb, endosulfan, and DDT, respectively. The individual effects and interaction of DOC, SDS, and Oxa were evaluated through quadratic regression equations. When the aqueous solution includes 50 mg L⁻¹ DOC, 3.75 CMC SDS, and 0.1 M Oxa, the maximum desorption concentrations of fenobucarb, endosulfan, and DDT were 96, 80, and 75 μg L⁻¹, respectively. The lowest concentration of SDS, DOC, and Oxa caused the minimum desorption. This point at conditions of concern for flooding water is high content of organic compounds causing potentially high contamination by desorption, and the remarkably lower desorption at organic matter-free conditions. The suspended organic matter is one of the common characteristics of flooding and irrigation water in rice fields, and surfactants from pollution increase the problem with desorption of legacy pesticides in the rice fields.

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Modeling Learning in Surgical Practice

Publication date: Available online 30 June 2017
Source:Journal of Surgical Education
Author(s): Epaminondas Markos Valsamis, Rajna Golubic, Thomas E. Glover, Henry Husband, Adnan Hussain, Amir-Reza Jenabzadeh
ObjectiveMethods that model surgical learning curves are frequently descriptive and lack the mathematical rigor required to extract robust, meaningful, and quantitative information. We aimed to formulate a method to model learning that is tailored to dealing with the high variability seen in surgical data and can readily extract important quantitative information such as learning rate, length of learning, and learnt level of performance.MethodsWe developed a method where progressively more complex models are fitted to learning data. These include novel models that split the learning data into 2 linear phases and fit adjoining lines using least squares regression. The models were compared and the least complex model was selected unless a more complex one was significantly better. Significance was tested by Fischer tests. We applied this method to total hip and knee replacements using imageless navigation, analyzing the operative time for a surgeon׳s first 50 and 60 operations, respectively. This method was then tested against 4 sets of simulated learning data.ResultsThe proposed method of progressive model complexity successfully modeled the learning curve among real operative data. It was also effective in reducing the underlying trends in simulated scenarios, created to represent atypical situations that can practically arise in any learning process.ConclusionsThe novel modeling method can be used to extract meaningful and quantitative information from learning data displaying high variability seen in surgical practice. By using simple and intuitive models, the method is accessible to researchers and educators without the need for specialist statistical knowledge.



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Residents and Program Director Perspectives Often Differ on Optimal Preparation Strategies and the Value of the Orthopedic In-Training Examination

Publication date: Available online 30 June 2017
Source:Journal of Surgical Education
Author(s): Christopher L. Camp, Ryan M. Degen, Arlen D. Hanssen, Joshua S. Dines, Matthew D. Karam, Norman S. Turner
ObjectivesThe purpose of this work was to compare resident and program director (PD) perspectives on the value of the Orthopaedic In-Training Examination (OITE), resident study habits, and best resources for optimal performance.DesignA national survey of orthopedic surgery residents and PDs.SettingMayo Clinic, Rochester, MNParticipantsThe survey was completed by 445 (41.5%) eligible orthopedic surgery residents and 37 (77.1%) PDs.ResultsAlthough residents and PDs agreed on when (p = 0.896) and how much (p = 0.171) residents currently study, residents felt that the OITE was not as valuable of an assessment of their knowledge, and also felt their individual scores were less likely to remain confidential compared to PDs (p < 0.001). The mean OITE score below which residents were concerned about their ability to pass American Board of Orthopaedic Surgeons Part 1 was 9.7 percentile points higher than PDs threshold (42.3% vs. 32.6%, respectively, p = 0.003). Both groups agreed that it is important to dedicate focused study time to the OITE (p = 0.680) and to perform well (p = 0.099). Regarding the best resources and preparation strategies, both residents and PDs tended to agree on the value of most (6 of 10) study methods. Residents ranked practice question websites (mean ranking of 2.6 vs. 3.8 of 10, respectively; p < 0.001) and formal rotations in a subspecialty (6.0 vs. 7.7 respectively, p < 0.001) higher than PDs. In contrast, PDs tended to value their program's formal OITE prep program (4.1. vs. 5.3, respectively, p = 0.012) and reading primary literature (5.6 vs. 6.6, respectively, p = 0.012) more than residents.ConclusionResidents and PDs agreed on many critical components of this process; however, a number of key differences in perspectives exist.



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A New Synthetic Model for Microvascular Anastomosis Training? A Randomized Comparative Study Between Silicone and Polyvinyl Alcohol Gelatin Tubes

Publication date: Available online 1 July 2017
Source:Journal of Surgical Education
Author(s): Michael Atlan, Alexandre G. Lellouch, Josette Legagneux, Marc Chaouat, Alain-Charles Masquelet, Didier Letourneur
IntroductionAssessment of a resident's microsurgical competency with the rodent model remains the current gold standard. However, cost and ethical issues related to animal welfare may limit training opportunities. Therefore, synthetic alternatives such as silicone tubes have been developed to provide easy access to training, shorten the learning curve, and have been incorporated into microsurgical courses as a low-fidelity model for basic skills acquisition. This study compares the use of polyvinyl alcohol (PVA) gelatin tubes with silicone for resident microsurgical training.Material and MethodsResidents were randomized into silicone (S) or PVA (P) groups and underwent the same training. Following basic instruction, microsurgical anastomoses were performed with the rat's aorta or carotid artery or both. Performance was assessed using the Objective Structured Assessment of Technical Skills (OSATS) score and 5 different items to assess the quality of the anastomosis. Posttest questionnaires were also conducted for qualitative assessment of both students' and trainers' experience with silicone and PVA in comparison with rat vessels.ResultsOSATS score in Group P was higher than Group S (18.2 ± 2.6 vs 16.6 ± 2.5, p = 0.015). Results of anastomoses were similarly better in Group P based on OSATS score (19.3 ± 1.2 vs 17.7 ± 0.7, p = 0.027). Subjectively, both students and trainers found that PVA tubes resembled the rat aorta more closely than silicone. The number of rats used was also significantly lower in Group P than Group S (65 vs 75 total, p = 0.023).ConclusionPVA gelatin tubes may be a viable alternative to silicone for microsurgical training because this synthetic model mirrors better rat vessels and can improve training performance based on objective assessment while using less animals overall.



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Identification of cytidine-5-triphosphate synthase1-selective inhibitory peptide from random peptide library displayed on T7 phage

Publication date: Available online 1 July 2017
Source:Peptides
Author(s): Kotaro Sakamoto, Yoshihiro Ishibashi, Ryutaro Adachi, Shin-ichi Matsumoto, Hideyuki Oki, Yusuke Kamada, Satoshi Sogabe, Yumi Zama, Jun-ichi Sakamoto, Akiyoshi Tani
Cytidine triphosphate synthase 1 (CTPS1) is an enzyme expressed in activated lymphocytes that catalyzes the conversion of uridine triphosphate (UTP) to cytidine triphosphate (CTP) with ATP-dependent amination, using either L-glutamine or ammonia as the nitrogen source. Since CTP plays an important role in DNA/RNA synthesis, phospholipid synthesis, and protein sialyation, CTPS1-inhibition is expected to control lymphocyte proliferation and size expansion in inflammatory diseases. In contrast, CTPS2, an isozyme of CTPS1 possessing 74% amino acid sequence homology, is expressed in normal lymphocytes. Thus, CTPS1-selective inhibition is important to avoid undesirable side effects. Here, we report the discovery of CTpep-3: Ac-FRLGLLKAFRRLF-OH from random peptide libraries displayed on T7 phage, which exhibited CTPS1-selective binding with a KD value of 210nM in SPR analysis and CTPS1-selective inhibition with an IC50 value of 110nM in the enzyme assay. Furthermore, two fundamentally different approaches, enzyme inhibition assay and HDX-MS, provided the same conclusion that CTpep-3 acts by binding to the amidoligase (ALase) domain on CTPS1. To our knowledge, CTpep-3 is the first CTPS1-selective inhibitor.



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Down-regulated microRNA-375 expression as a predictive biomarker in non-small cell lung cancer brain metastasis and its prognostic significance

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Li-juan Chen, Xing-ya Li, Yan-qiu Zhao, Wen-jing Liu, Hui-juan Wu, Jie Liu, Xiao-qian Mu, Hong-bo Wu
Brain metastases (BM) are common among patients with non-small cell lung cancer (NSCLC) and have been associated with significant morbidity and limited survival. Early and sensitive detection of BM is essential for improving prognosis. Recently,microRNA-375(miR-375) which is specifically expressed in the brain has been found significantly dysregulated in many human cancers. However, there is still no data whether miR-375 is associated with higher risk of BM development in NSCLC. In this study, we detected the miR-375 expression using quantitative real-time PCR (qRT-PCR) and assessed its predictive and prognostic significance. Our result showed that miR-375 expression was significantly down-regulated in NSCLC patients with BM(BM+, N=30) compared with NSCLC without BM(BM-, N=30) (P<0.001). Statistical analysis indicated that low miR-375 expression was linked to advanced disease stage (P<0.001) and brain metastasis (P<0.001) in NSCLC patient. Survival analysis suggested that low-expression group had significantly shorter overall survival than high-expression group in NSCLC patients with BM(log-rank test: P<0.05) as well as the total cases(log-rank test: P<0.01). Multivariate Cox proportional hazards model analysis indicated that low miR-375 expression was independently linked to poor survival of patients with NSCLC (HR=5.48, 95% CI: 1.93-15.56, P=0.001). In addition, we found that VEGF and MMP-9 were over-expressed in down-regulated miR-375 expression cases. Collectively, this study demonstrated that miR-375 may play an important role as a predictive biomarker in brain metastasis and an independent prognostic factor in NSCLC. Over-expression of VEGF and MMP-9 may be the reason for poor prognosis of NSCLC patients with low miR-375 expression.



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Frameshift mutation and loss of expression of PLK2, a serine/threonine kinase-encoding gene, in colorectal cancers

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Ju Hwa Lee, Min Sung Kim, Nam Jin Yoo, Sug Hyung Lee




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Prevalence of Protein C Receptor (PROCR) is Associated with Inferior Clinical Outcome in Breast Invasive Ductal Carcinoma

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Qiu Yan, Zhong Xiaorong, Zhang Zhang, Wei Bing, Ye Feng, Bu Hong
Recently, PROCR is reported to play an important role in cell growth, apoptosis, proliferation and tumor relapse. Some researchers thought that PROCR⁺ cells had cancer stem cell ability, which might contribute to progressive behavior in breast cancer. Our study was to assess the expression of PROCR in invasive ductal carcinoma tissues with their prognostic implications. We enrolled formalin fixed paraffin-embedded tumor tissues of 271 patients diagnosed as invasive ductal breast cancer with clinical stage II or III into our study. Immunohistochemistry staining was performed on all the tissue microarray slides, and result were interpreted by two pathologists with blinded method. We analyzed PROCR expression levels with the clinical characteristics as well as their prognostic values. PROCR expression detected in the cell was interpreted. Chi-square test showed us its positive expression had a close association with distant metastases (p=0.035). Univariate survival analysis indicated that prevalence of PROCR expression in the invasive ductal breast cancer was significantly related with decreased disease-free survival (pDFS=0.010) and overall survival (pOS=0.008). In multivariate survival by Cox proportional hazard model, positive expression group for PROCR was found to have shorter DFS [pDFS=0.028, hazard ratio (95% CI): 1.183(1.069-3.140)].Our findings suggested that breast cancer patients with expression of PROCR is more prone to suffer from distant metastasis and bad clinical outcomes.



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Morphology based scoring of Chromosomal instability and its correlation with cell viability

Publication date: Available online 1 July 2017
Source:Pathology - Research and Practice
Author(s): Shubhlata Yadav, Alka Bhatia
ObjectiveThe aim of this study was to devise the quantitative scoring system for Chromosomal instability (CIN) based on morphological indicators like MPM, NB, NPB, CS, La and MN in cancer cell line and to correlate it with cell viability and death.MethodsHuman hepatocellular carcinoma (HepG2) cells were treated with drugs like Diethylstilbestrol 0- 100μM, Griseofulvin 0–40μg/ml, Vincristine sulphate 0–25μg/ml, Mitomycin C 0–600ng/ml, Bleomycin 0–10μg/ml, Doxorubicin 0–30μg/ml for 24hours. Following this, the CIN was assessed by counting the morphological indicators like Micronuclei (MN), Nuclear Buds (NB), Nucleoplasmic bridges, Laggards, Multipolar mitosis and chromatin strings/1000 cells in Giemsa stained smears by light microscopy and by determining the percentage of aneuploid cells by flow cytometry. The cell viability was assessed by MTT assay and percentage of apoptotic cells was determined by flow cytometry.ResultsThe MN and NB were most frequently seen indicators and main determinants of morphological CIN. However, the morphological CIN score did not show any correlation with cell viability and apoptosis. Aneuploidy however was found to correlate positively with cell viability and NB score in our study (P-value <0.05).ConclusionsThe study for the 1st time attempted to develop a scoring system for CIN based on morphological parameters. However, a no correlation was observed between the later and cell viability or apoptosis. More robust techniques to quantify CIN may perhaps be more helpful in exploring the true link between CIN and cell viability in future.



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The role of ARMC5 in human cell cultures from nodules of primary macronodular adrenocortical hyperplasia (PMAH)

Publication date: Available online 1 July 2017
Source:Molecular and Cellular Endocrinology
Author(s): Isadora P. Cavalcante, Miriam Nishi, Maria Claudia N. Zerbini, Madson Q. Almeida, Vania B. Brondani, Maria Lucia Botelho, Fabio Y. Tanno, Victor Srougi, José Luis Chambo, Berenice B. Mendonça, Jerôme Bertherat, Claudimara Ferini Pacicco Lotfi, Maria Candida B.V. Fragoso
The participation of aberrant receptors and intra-adrenal ACTH in hyperplastic tissue are considered mechanisms that regulate hypercortisolism in PMAH. Additionally, germline ARMC5 mutations have been described as the most frequent genetic abnormality found in patients diagnosed with PMAH. Previous functional studies analyzed ARMC5 role using H295R cells. Therefore, we investigated the role of ARMC5 in cell cultures obtained from PMAH nodules containing steroidogenic cells, aberrant receptors and intra-adrenal ACTH. ARMC5 silencing in non-mutated PMAH cell cultures decreased steroidogenesis-related genes and increased CCNE1 mRNA expression and proliferative capacity without affecting cell viability. Additionally, ARMC5 overexpression induced cell death in PMAH mutated cell cultures, thereby decreasing cell viability. We confirmed the role of ARMC5 as an important pro-apoptotic protein involved in PMAH-related steroidogenesis. We also report for the first time the involvement of ARMC5 in controlling proliferation and regulating cell cycle in PMAH cell cultures; these effects need to be explored further.



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Ecotoxicity of 1,3-dichloropropene, metam sodium, and dazomet on the earthworm Eisenia fetida with modified artificial soil test and natural soil test

Abstract

1,3-Dichloropropene (1,3-D), metam sodium (MS), and dazomet (DZ) are widely used as preplant soil fumigants to solve soilborne problems. To provide a more scientific and accurate evaluation of 1,3-D, MS, and DZ toxicity to the earthworm Eisenia fetida, modified artificial soil test and natural soil test were studied. The suitable soil moisture to maintain over 90% survival of the earthworms after 4 weeks of treatment in an enclosed system for modified artificial soil test and natural soil test were 26.9 to 86.4% of water-holding capacity (WHC) and 66.2 to 84.3% of WHC, respectively. The optimal soil moisture levels for modified artificial soil test and natural soil test (75 and 55% of WHC, respectively) were finally used to evaluate the toxicity of 1,3-D, MS, and DZ on earthworms. Each desiccator with 10 earthworms and natural or artificial soil was stored at 20 ± 1 °C under constant light of 400 to 800 lx for 2 weeks. The modified artificial soil test showed LC₅₀ values for 1,3-D, MS, and DZ of 3.60, 1.69, and 5.41 mg a.i. kg⁻¹ soil, respectively. The modified natural soil test of the fumigants showed similar LC₅₀ values of 2.77 and 0.65 mg a.i. kg⁻¹ soil, except for DZ at 0.98 mg a.i. kg⁻¹ soil. The present study confirms that both modified artificial soil test and modified natural soil test offer standard methods for acute toxicity test of 1,3-D, MS, and DZ on the earthworms and scientific evidences for assessing the effects of soil fumigants on non-target organisms in the soils.

Graphical Abstract

Two novel acute toxicity test methods for soil fumigants on the earthworm Eisenia fetida

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Improved SNR for combined TMS-fMRI: A support device for commercially available body array coil

Publication date: Available online 30 June 2017
Source:Journal of Neuroscience Methods
Author(s): Wen-Tung Wang, Benjamin Xu, John A. Butman
BackgroundTranscranial magnetic stimulation (TMS) is a noninvasive brain stimulation tool extensively used in clinical and cognitive neuroscience research. TMS has been applied during functional magnetic resonance imaging (i.e., concurrent/interleaved TMS-fMRI) to understand neural mechanisms underlying cognitive functions. However, no advanced commercial multi-channel whole-brain array MR coils can fit the large TMS coil. We developed a low-cost and easy-to-configure setup that takes advantage of the superior signal-to-noise ratio (SNR) performance of commercially available flexible body array coils that can accommodate the TMS coil.New methodTwo flexible MRI body array coils (i.e., the Combo coil) were fitted on a simple coil support with a TMS-coil holder. Phantom and in vivo images acquired using the Combo coil with and without a TMS coil were compared with those from a product 12-channel (12CH) form-fit head array coil.ResultsRelative to the 12CH head coil, images acquired using the Combo coil were of similar quality, but with increased noise levels, leading to moderately reduced temporal SNR values.Comparison with existing methodA previous study reported that the temporal SNR of a product 12CH head coil was twice that of a transmit/receive volume birdcage coil commonly used in combined TMS-fMRI. Together with the results of the present work, they indicate that the Combo-coil setup improves SNR performance for combined TMS-fMRI acquisition.ConclusionThe inexpensive and easy-to-configure Combo-coil setup offers an effective and likely superior alternative to transmit/receive birdcage coil for combined TMS-fMRI.



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Scholar : These new articles for The American Journal of Drug and Alcohol Abuse are available online

The online platform for Taylor & Francis Online content New for The American Journal of Drug and Alcohol Abuse and online now on Taylor & Francis Online: Original Articles Surveying the opinions of Pennsylvania Chiefs of Police toward officers carrying and administering naloxone Paul A. Smyser BS & Jeffrey S. Lubin MD, MPH Pages: 1-8 | DOI: 10.1080/00952990.2017.1339053 FREE ACCESS: Health Care for Women International: Research on Women's Health in Africa: Issues, Challenges & Opportunities To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Improving gentamicin B and gentamicin C1a production by engineering the glycosyltransferases that transfer primary metabolites into secondary metabolites biosynthesis

Publication date: Available online 1 July 2017
Source:Microbiological Research
Author(s): Zheng Wu, Wenli Gao, Shaotong Zhou, Zhaolin Wen, Xianpu Ni, Huanzhang Xia
Gentamicin B and gentamicin C1a are the direct precursor for Isepamicin and Etimicin synthesis, respectively. Although producing strains have been improved for many years, both gentamicin B titer and gentamicin C1a titer in the fermentation are still low. Because all gentamicin components are biosynthesized using UDP-N-acetyl-D-glucosamine (UDP-GlcNAc) and UDP-xylose as precursors, we tried to explore strategies for development of strains capable of directing greater fluxes of these precursors into production of gentamicins. The glycosyltransferases KanM1 and GenM2, which are responsible for UDP-GlcNAc and UDP-xylose transfer, respectively, were overexpressed in gentamicin B producing strain Micromonospora echinospora JK4. It was found that gentamicin B could be improved by up to 54% with improvement of KanM1 and GenM2 expression during appropriately glucose feeding. To prove this strategy is widely usable, the KanM1 and GenM2 were also overexpressed in gentamicin C1a producing strain, titers of gentamicin C1a improved by 45% when compared with titers of the starting strain. These results demonstrated overexpression the glycosyltransferases that transfer primary metabolites into secondary metabolites is workable for improvement of gentamicins production.



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Influence of environmental factors on absorption characteristics of suspended particulate matter and CDOM in Liaohe River watershed, northeast China

Abstract

Absorption characteristics of optically active substances, including non-algal particles, phytoplankton, and chromophoric dissolved organic matter (CDOM), were measured in conjunction with environmental factors in five rivers within the Liaohe River watershed. Spectral absorption of non-algal particles [a _NAP(λ)] was similar to that of total particles for most samples, suggesting that the absorption of the total particles [a _p(λ)] was dominated by a _NAP(λ). The CDOM absorption spectra [a _CDOM(λ)] of West Liaohe and Taizihe rivers were easily distinguished from those of Hunhe, Liaohe, and East Liaohe rivers. Redundancy analysis indicated that absorption by optically active substances and anthropogenic nutrient disturbances probably resulted in the diversity of water quality parameters. The environmental variables including dissolved organic carbon, total alkalinity (TAlk), and total nitrogen (TN) had a significant correlation with CDOM absorption at 440 nm [a _CDOM(440)]. There was almost no correlation between a _p(λ) and chlorophyll a, TN, total phosphorus, and TAlk. Moreover, total copper ion concentration and mercury ion concentration had a strong correlation with a _p(440), a _p(675), a _NAP(440), and a _NAP(675). The concentration of total aluminum ions exhibited a positive correlation with a _p(675) and a _NAP(675) (p < 0.05), and a significant correlation was observed between total arsenic concentration and a _CDOM(440). Furthermore, the interaction between metal ions and optically active substances provided an insight into particulates and CDOM properties linked to water quality characteristics for rivers in semiarid areas.

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Spinal muscular atrophy carriers with two SMN1 copies

Publication date: Available online 1 July 2017
Source:Brain and Development
Author(s): Mawaddah Ar Rochmah, Hiroyuki Awano, Tomonari Awaya, Nur Imma Fatimah Harahap, Naoya Morisada, Yoshihiro Bouike, Toshio Saito, Yuji Kubo, Kayoko Saito, Poh San Lai, Ichiro Morioka, Kazumoto Iijima, Hisahide Nishio, Masakazu Shinohara
BackgroundSpinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder. Over 95% of SMA patients have homozygous deletions of the SMA-causative gene, SMN1. Thus, SMA carriers are usually diagnosed based on SMN1 copy number, with one copy indicating SMA carrier status. However, two SMN1 copies do not always exclude carrier status. In this study, we identified SMA carriers with two SMN1 copies.Subjects and methodsFrom 33 families, 65 parents of genetically confirmed SMA patients were tested to determine SMA carrier status. Molecular genetic analyses, including multiplex ligation-dependent probe amplification (MLPA) assay, were performed using blood samples from family members.ResultsOf the 65 parents, three parents from three families had two SMN1 copies. Accordingly, the frequency of carriers with two SMN1 copies was 4.6%. Two of these families were further studied. Patient 1 was homozygous for SMN1 deletion. Patient 1's mother had two SMN1 copies on one chromosome, with deletion of SMN1 on the other chromosome ([2+0] genotype). Patient 1 inherited SMN1-deleted chromosomes from both parents. Patient 2 was compound heterozygous for two SMN1 mutations: whole-gene deletion and intragenic missense mutation, c.826T>C (p.Tyr276His). Patient 2's father had two SMN1 copies with the same intragenic mutation in one copy ([1+1^d] genotype, ^d intragenic mutation). Patient 2 inherited the chromosome with an SMN1 mutation from the father and SMN1-deleted chromosome from the mother.ConclusionSMA carriers with two SMN1 copies may be rare, but its possibility should be taken into consideration in carrier testing and counseling for SMA families or population-based carrier screening.



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β-elemene regulates endoplasmic reticulum stress to induce the apoptosis of NSCLC cells through PERK/IRE1α/ATF6 pathway

Publication date: September 2017
Source:Biomedicine & Pharmacotherapy, Volume 93
Author(s): Ying Liu, Zi-yu Jiang, Yuan-li Zhou, Hui-hui Qiu, Gang Wang, Yi Luo, Jing-bing Liu, Xiong-wei Liu, Wei-quan Bu, Jie Song, Li Cui, Xiao-bin Jia, Liang Feng
Endoplasmic reticulum stress (ERs) has been regarded as an important cause for the pathogenesis of non-small-cell lung cancer (NSCLC). β-elemene is an active component in the essential oil extracted from a medicinal herb, Curcuma wenyujin, and has been reported to be effective against non-small-cell lung cancer (NSCLC). However, the potential effect and underlying mechanisms of β-elemene on regulating ERs to inhibit NSCLC are still unclear. In the present study, A549 cells and Lewis tumor-bearing C57BL/6J mice were established to evaluate this effect. Visualsonics Vevo 2100 Small Animal Dedicated High-frequency Color Ultrasound was performed to observe tumor volume in vivo. 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) was used to evaluate cell vitality of A549 cells. Furthermore, western blotting (WB), immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (q-PCR) were applied to detect the ERs-related proteins. Flow cytometry was also applied to detect cell apoptosis and assay kit for reactive oxygen species (ROS) generation. Our results showed that β-elemene inhibited lung cancer tumor growth and cell vitality in a dose- and time-dependent manner. Not only that, β-elemene could up-regulate ERs-related proteins like PERK, IRE1α, ATF6, ATF4, CHOP and down-regulate the Bcl-2 expression. More importantly, ERs inhibitor 4-PBA, IRE1α inhibitor STF-083010, ATF6 inhibitor Anti-ATF6 and PERK inhibitor GSK2656157 can all reduce the amplitude of protein expression changes and apoptosis rates, then weaken the anti-tumor effect of β-elemene. Therefore, the present in vivo and in vitro study revealed that the anti-NSCLC effect of β-elemene is closely related to the activation of ERs through PERK/IRE1α/ATF6 pathway, and this might be beneficial for clinical therapy of NSCLC.



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Scholar : These new articles for Acta Orthopaedica are available online

The online platform for Taylor & Francis Online content New for Acta Orthopaedica and online now on Taylor & Francis Online: Original Articles Inappropriate use of arthroscopic meniscal surgery in degenerative knee disease An observational study from Switzerland | Leander L S Muheim, Oliver Senn, Mathias Früh, Oliver Reich, Thomas Rosemann & Stefan M Neuner-Jehle Pages: 1-6 | DOI: 10.1080/17453674.2017.1344915 Research-article Is a long leg a risk for hip or knee osteoarthritis? A 29-year follow-up study of 193 individuals | Kaj Tallroth, Leena Ristolainen & Mikko Manninen Pages: 1-4 | DOI: 10.1080/17453674.2017.1348066 To update which email alerts you receive, manage your alerts within the My Account area. You can also unsubscribe from this alert with one click. If you need any further help, please contact us at support@tandfonline.com Please do not reply to this email. To ensure that you receive your alerts and information from Taylor & Francis Online, please add "alerts@tandfonline.com" and "info@tandfonline.com" to your safe senders list. Taylor & Francis, an Informa business. Taylor & Francis is a trading name of Informa UK Limited, registered in England under no. 1072954. Registered office: 5 Howick Place, London, SW1P 1WG.

Pooled Analysis of Clinical Outcome of Patients with Chemorefractory Metastatic Colorectal Cancer Treated within Phase I/II Clinical Studies Based on Individual Biomarkers of Susceptibility: A Single-Institution Experience

Abstract

Background

Patients with metastatic colorectal cancer (mCRC) refractory to standard therapies have a poor prognosis. In this setting, recruitment into clinical trials is warranted, and studies driven by selection according to individual tumor molecular characteristics are expected to provide added value.

Objective

We retrospectively analyzed data from patients with mCRC refractory to or following failure of standard therapies who were enrolled into phase I/II clinical studies at the Niguarda Cancer Center based on the presence of a specific molecular profile expected to represent the target of susceptibility to the experimental drug(s).

Patients and Methods

From June 2011 to May 2016, 2044 patients with mCRC underwent molecular screening. Eighty patients (3.9%) were enrolled in ad hoc studies; the median age was 60 years (range 36–86) and the median number of previous treatment lines was five (range 2–8). Molecular characteristics exploited within these studies were MGMT promoter hypermethylation (48.7%), HER2 amplification (28.8%), BRAF ^V600E mutation (20%), and novel gene fusions involving ALK or NTRK (2.5%).

Results

One patient (1%) had RECIST (Response Evaluation Criteria In Solid Tumors) complete response (CR), 13 patients (16.5%) experienced a partial response (PR), and 28 (35%) stable disease (SD). Median progression-free survival (PFS) was 2.8 months (range 2.63–3.83), with 24% of patients displaying PFS >5 months. Median growth modulation index (GMI) was 0.85 (range 0–15.61) and 32.5% of patients had GMI >1.33. KRAS exon 2 mutations were found in 38.5% of patients, and among the 78 patients with known KRAS status, those with wild-type tumors had longer PFS than those with mutated tumors (3.80 [95% CI 2.80–5.03] vs. 2.13 months [95% CI 1.77–2.87], respectively, p = 0.001). Median overall survival (OS) was 7.83 months (range 7.17–9.33) for all patients, and patients with KRAS wild-type tumors had longer OS than those with mutated tumors (7.83 [95% CI 7.33–10.80] vs. 7.18 months [95% CI 5.63–9.33], respectively, p = 0.06).

Conclusions

This single-institution retrospective study indicates that in a heavily pretreated population approximately 4% of mCRC tumors display a potential actionable molecular context suitable for therapeutic intervention. Application of molecular selection is challenging but improves clinical outcome even in later lines of treatment.

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Sjogren's syndrome: New paradigms and areas for future research

Publication date: Available online 30 June 2017
Source:Clinical Immunology
Author(s): Julian L. Ambrus




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Translocator protein (18 kDa): an update on its function in steroidogenesis

Abstract

Translocator protein (18 kDa), TSPO, is a ubiquitous mitochondrial protein. Studies of its responses to drug and endogenous ligands have shown TSPO to be involved either directly or indirectly in numerous biological functions, including mitochondrial cholesterol transport and steroid hormone biosynthesis, porphyrin transport and heme synthesis, apoptosis, cell proliferation, and anion transport. Localized to the outer mitochondrial membrane of steroidogenic cells, TSPO has been shown to associate with cytosolic and mitochondrial proteins as part of a large multiprotein complex involved in mitochondrial cholesterol transport, the rate-limiting step in steroidogenesis. There is general agreement as to the structure and pharmacology of TSPO. Stimulation of TSPO has been shown to have therapeutic use as anxiolytics by inducing allopregnanolone production in the brain, and also potentially for reestablishing androgen levels in hypogonadal aging animals. Until recently, there has been general agreement as to the role of TSPO in steroidogenesis. However, recent studies involving genetic depletion of TSPO in mice have created controversy about the role of this protein in steroid and heme synthesis. We review herein the data on TSPO's structure and function, and recent results using various genetic animal models. Taken together, these studies suggest that TSPO is a unique mitochondrial pharmacological target for diseases that involve increased mitochondrial activity, including steroidogenesis. Although there is no known mammalian species that lacks TSPO, it is likely that due to the importance of this ancient protein in evolution and mitochondrial function, redundant mechanisms may exist to replace it under circumstances when it is removed.

This article is protected by copyright. All rights reserved.

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