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https://www.readbyqxmd.com/read/28631844/sonic-hedgehog-wnt-and-brain-derived-neurotrophic-factor-cell-signaling-pathway-crosstalk-potential-therapy-for-depression
#1
REVIEW
Mohd Tayyab, Mehdi H Shahi, Shirin Farheen, Mubeena P M Mariyath, Nabeela Khanam, Javier S Castresana, M Mobarak Hossain
There are various theories to explain the pathophysiology of depression and support its diagnosis and treatment. The roles of monoamines, brain-derived neurotrophic factor (BDNF), and Wnt signaling are well researched, but sonic hedgehog (Shh) signaling and its downstream transcription factor Gli1 are not well studied in depression. Shh signaling plays a fundamental role in embryonic development and adult hippocampal neurogenesis and also involved in the growth of cancer. In this article, we summarize the evidence for the Shh signaling pathway in depression and the potential crosstalk of Shh with Wnt and BDNF...
June 20, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28630165/the-cell-adhesion-molecule-chl1-interacts-with-patched-1-to-regulate-apoptosis-during-postnatal-cerebellar-development
#2
Jelena Katic, Gabriele Loers, Jelena Tosic, Melitta Schachner, Ralf Kleene
The immunoglobulin superfamily adhesion molecule close homolog of L1 (CHL1) plays important roles during nervous system development. Here, we identified the hedgehog receptor patched-1 (PTCH1) as novel CHL1 binding partner and showed that CHL1 interacts with the first extracellular loop of PTCH1 via its extracellular domain. Co-localization and -immunoprecipitation of CHL1 with PTCH1 suggest an association of CHL1 with this major component of the hedgehog signaling pathway. The trans-interaction of CHL1 with PTCH1 promotes neuronal survival in cultures of dissociated cerebellar granule cells and of organotypic cerebellar slices...
June 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28629394/validating-the-who-maternal-near-miss-tool-comparing-high-and-low-resource-settings
#3
Tom Witteveen, Hans Bezstarosti, Ilona de Koning, Ellen Nelissen, Kitty W Bloemenkamp, Jos van Roosmalen, Thomas van den Akker
BACKGROUND: WHO proposed the WHO Maternal Near Miss (MNM) tool, classifying women according to several (potentially) life-threatening conditions, to monitor and improve quality of obstetric care. The objective of this study is to analyse merged data of one high- and two low-resource settings where this tool was applied and test whether the tool may be suitable for comparing severe maternal outcome (SMO) between these settings. METHODS: Using three cohort studies that included SMO cases, during two-year time frames in the Netherlands, Tanzania and Malawi we reassessed all SMO cases (as defined by the original studies) with the WHO MNM tool (five disease-, four intervention- and seven organ dysfunction-based criteria)...
June 19, 2017: BMC Pregnancy and Childbirth
https://www.readbyqxmd.com/read/28626616/discrimination-of-picea-chihuahuana-martinez-populations-on-the-basis-of-climatic-edaphic-dendrometric-genetic-and-population-traits
#4
Iliana Karina Dominguez-Guerrero, Samantha Del Rocío Mariscal-Lucero, José Ciro Hernández-Díaz, Berthold Heinze, José Ángel Prieto-Ruiz, Christian Wehenkel
BACKGROUND: Picea chihuahuana, which is endemic to Mexico, is currently listed as "Endangered" on the Red List. Chihuahua spruce is only found in the Sierra Madre Occidental (SMO), Mexico. About 42,600 individuals are distributed in forty populations. These populations are fragmented and can be classified into three geographically distinct clusters in the SMO. The total area covered by P. chihuahuana populations is less than 300 ha. A recent study suggested assisted migration as an alternative to the ex situ conservation of P...
2017: PeerJ
https://www.readbyqxmd.com/read/28624712/classification-of-ecg-heartbeats-using-nonlinear-decomposition-methods-and-support-vector-machine
#5
Kandala N V P S Rajesh, Ravindra Dhuli
Classifying electrocardiogram (ECG) heartbeats for arrhythmic risk prediction is a challenging task due to minute variations in the amplitude, duration and morphology of the ECG signal. In this paper, we propose two feature extraction approaches to classify five types of heartbeats: normal, premature ventricular contraction, atrial premature contraction, left bundle branch block and right bundle branch block. In the first approach, ECG beats are decomposed into intrinsic mode functions (IMFs) using ensemble empirical mode decomposition (EEMD)...
June 15, 2017: Computers in Biology and Medicine
https://www.readbyqxmd.com/read/28618514/dynamics-of-a-bistable-miura-origami-structure
#6
Hongbin Fang, Suyi Li, Huimin Ji, K W Wang
Origami-inspired structures and materials have shown extraordinary properties and performances originating from the intricate geometries of folding. However, current state of the art studies have mostly focused on static and quasistatic characteristics. This research performs a comprehensive experimental and analytical study on the dynamics of origami folding through investigating a stacked Miura-Ori (SMO) structure with intrinsic bistability. We fabricate and experimentally investigated a bistable SMO prototype with rigid facets and flexible crease lines...
May 2017: Physical Review. E
https://www.readbyqxmd.com/read/28618224/design-synthesis-and-structure-activity-relationship-of-tetrahydropyrido-4-3-d-pyrimidine-derivatives-as-potent-smoothened-antagonists-with-in-vivo-activity
#7
Wenfeng Lu, Yongqiang Liu, Haikuo Ma, Jiyue Zheng, Sheng Tian, Zhijian Sun, Lusong Luo, Jiajun Li, Hongjian Zhang, Zeng-Jie Yang, Xiaohu Zhang
Medulloblastoma is one of the most prevalent brain tumors in children. Aberrant hedgehog (Hh) pathway signaling is thought to be involved in the initiation and development of medulloblastoma. Vismodegib, the first FDA-approved cancer therapy based on inhibition of aberrant hedgehog signaling, targets smoothened (Smo), a G-protein coupled receptor (GPCR) central to the Hh pathway. Although vismodegib exhibits promising therapeutic efficacy in tumor treatment, concerns have been raised from its non-linear pharmacokinetic (PK) profiles at high doses partly due to low aqueous solubility...
June 15, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28611043/arl13b-promotes-gastric-tumorigenesis-by-regulating-smo-trafficking-and-activation-of-the-hedgehog-signaling-pathway
#8
Jia Shao, Linlin Xu, Limin Chen, Quqin Lu, Xinsheng Xie, Wei Shi, Huanting Xiong, Chao Shi, Xuan Huang, Jinhong Mei, Hai Rao, Hua Lu, Nonghua Lu, Shiwen Luo
Inhibitors of the Hedgehog (Hh) pathway transducer Smoothened (Smo) have been approved for cancer treatment, but Smo mutations often lead to tumor resistance and it remains unclear how Smo is regulated. In this study, we identified the small GTPase Arl13b as a novel partner and regulator of Smo. Arl13b regulated Smo stability, trafficking and localization which are each crucial for Hh signaling. In gastric cancer cells, Arl13b stimulated proliferation, migration and invasion in vitro and in vivo. In clinical specimens of gastric cancer, Arl13b expression correlated strongly with tumor size and depth of invasion; patients with high levels of Arl13b had a poor prognosis...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28599282/optimizing-a-machine-learning-based-glioma-grading-system-using-multi-parametric-mri-histogram-and-texture-features
#9
Xin Zhang, Lin-Feng Yan, Yu-Chuan Hu, Gang Li, Yang Yang, Yu Han, Ying-Zhi Sun, Zhi-Cheng Liu, Qiang Tian, Zi-Yang Han, Le-De Liu, Bin-Quan Hu, Zi-Yu Qiu, Wen Wang, Guang-Bin Cui
Current machine learning techniques provide the opportunity to develop noninvasive and automated glioma grading tools, by utilizing quantitative parameters derived from multi-modal magnetic resonance imaging (MRI) data. However, the efficacies of different machine learning methods in glioma grading have not been investigated.A comprehensive comparison of varied machine learning methods in differentiating low-grade gliomas (LGGs) and high-grade gliomas (HGGs) as well as WHO grade II, III and IV gliomas based on multi-parametric MRI images was proposed in the current study...
May 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28591947/-inhibition-of-cigarettes-smoke-induced-epithelial-to-mesenchymal-transition-by-the-smo-inhibitor-pf-5274857-in-beas-2b-epithelial-cells
#10
Wen-Jie Zhou, Jiao Chen, Yun Feng, Ya-Ping Fan, Qian Li, Jian Fu, Ping Zhang
OBJECTIVES: To explore the effects of the Smoothened (Smo) inhibitor PF-5274857 on cigarette smoke (CS)-induced epithelial-mesenchymal transition (EMT) and apply a new idea fororal squamous cell carcinoma (OSCC) treatment. METHODS: Beas-2b cells were used to investigate the CS-induced EMT. Both pretreat and post-treat were performed in the study. In pretreat group, after being pretreated with 3 μmol/L PF-5274857 for 2 h, cells were cultured with CS for 8 d; In post-treat group, cells were treated by 3 μmol/L PF-5274857 for 4 d after CS cultrue...
July 2016: Sichuan da Xue Xue Bao. Yi Xue Ban, Journal of Sichuan University. Medical Science Edition
https://www.readbyqxmd.com/read/28591579/sonic-hedgehog-activates-phospholipase-a2-to-enhance-smoothened-ciliary-translocation
#11
Angela M Arensdorf, Miriam E Dillard, Jacob M Menke, Matthew W Frank, Charles O Rock, Stacey K Ogden
The G protein-coupled receptor Smoothened (Smo) is the signal transducer of the Sonic Hedgehog (Shh) pathway. Smo signals through G protein-dependent and -independent routes, with G protein-independent canonical signaling to Gli effectors requiring Smo accumulation in the primary cilium. The mechanisms controlling Smo activation and trafficking are not yet clear but likely entail small-molecule binding to pockets in its extracellular cysteine-rich domain (CRD) and/or transmembrane bundle. Here, we demonstrate that the cytosolic phospholipase cPLA2α is activated through Gβγ downstream of Smo to release arachidonic acid...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28588207/capping-enzyme-mrna-cap-rngtt-regulates-hedgehog-pathway-activity-by-antagonizing-protein-kinase-a
#12
Ping Chen, Zizhang Zhou, Xia Yao, Shu Pang, Meijing Liu, Weirong Jiang, Jin Jiang, Qing Zhang
Hedgehog (Hh) signaling plays a pivotal role in animal development and its deregulation in humans causes birth defects and several types of cancer. Protein Kinase A (PKA) modulates Hh signaling activity through phosphorylating the transcription factor Cubitus interruptus (Ci) and G protein coupled receptor (GPCR) family protein Smoothened (Smo) in Drosophila, but how PKA activity is regulated remains elusive. Here, we identify a novel regulator of the Hh pathway, the capping-enzyme mRNA-cap, which positively regulates Hh signaling activity through modulating PKA activity...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28581526/the-role-of-canonical-and-non-canonical-hedgehog-signaling-in-tumor-progression-in-a-mouse-model-of-small-cell-lung-cancer
#13
A Szczepny, S Rogers, W S N Jayasekara, K Park, R A McCloy, C R Cochrane, V Ganju, W A Cooper, J Sage, C D Peacock, J E Cain, A Burgess, D N Watkins
Hedgehog (Hh) signaling regulates cell fate and self-renewal in development and cancer. Canonical Hh signaling is mediated by Hh ligand binding to the receptor Patched (Ptch), which in turn activates Gli-mediated transcription through Smoothened (Smo), the molecular target of the Hh pathway inhibitors used as cancer therapeutics. Small cell lung cancer (SCLC) is a common, aggressive malignancy with universally poor prognosis. Although preclinical studies have shown that Hh inhibitors block the self-renewal capacity of SCLC cells, the lack of activating pathway mutations have cast doubt over the significance of these observations...
June 5, 2017: Oncogene
https://www.readbyqxmd.com/read/28574612/basal-cell-carcinoma-pathogenesis-and-therapy-involving-hedgehog-signaling-and-beyond
#14
Anshika Bakshi, Sandeep C Chaudhary, Mehtab Rana, Craig A Elmets, Mohammad Athar
Basal cell carcinoma (BCC) of the skin is driven by aberrant hedgehog signaling. Thus blocking this signaling pathway by small molecules such as vismodegib inhibits tumor growth. Primary cilium in the epidermal cells plays an integral role in the processing of hedgehog signaling related proteins. Recent genomic studies point to the involvement of additional genetic mutations that might be associated with the development of BCCs, suggesting significance of other signaling pathways, such as WNT, NOTCH, mTOR, and Hippo, aside from hedgehog in the pathogenesis of this human neoplasm...
June 2, 2017: Molecular Carcinogenesis
https://www.readbyqxmd.com/read/28565875/smoothened-antagonist-gdc-0449-vismodegib-inhibits-proliferation-and-triggers-apoptosis-in-colon-cancer-cell-lines
#15
Chuanqing Wu, Shaobo Hu, Ji Cheng, Guobin Wang, Kaixiong Tao
The sonic hedgehog (Shh) pathway has been proven to be involved in embryonic development and cancer growth. GDC-0449, an antagonist of the hedgehog signaling receptor Smoothened (Smo), was recently approved by the US Food and Drug Administration as a prescription for skin basal cell carcinoma. However, the efficacy of GDC-0449 in the treatment of colon cancer and other malignancies, such as basal cell carcinoma and pancreatic cancer, has remained to be proven. The present study assessed the effect of GDC-0449 on the colon cancer cell lines Caco-2 and Ht-29...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28564646/constitutive-activation-of-smoothened-in-the-renal-collecting-ducts-leads-to-renal-hypoplasia-hydronephrosis-and-hydroureter
#16
Deepak Prasad Gupta, Jae-Won Hwang, Eui-Sic Cho, Won Kim, Chang Ho Song, Ok Hee Chai
Sonic Hedgehog (Shh) signaling plays a major role in and is essential for regulation, patterning, and proliferation during renal development. Smoothened (Smo) plays a pivot role in transducing the Shh-glioma-associated oncogene Kruppel family member. However, the cellular and molecular mechanism underlying the role of sustained Smo activation in postnatal kidney development is still not clearly understood. Using a conditional knockin mouse model that expresses a constitutively activated form of Smo (SmoM2) upon Homeobox-B7-mediated recombination (Hoxb7-Cre), the effects of Shh signaling were determined in postnatal kidney development...
June 1, 2017: Cells, Tissues, Organs
https://www.readbyqxmd.com/read/28560483/conditional-loss-of-hepatocellular-hedgehog-signaling-in-female-mice-leads-to-the-persistence-of-hepatic-steroidogenesis-androgenization-and-infertility
#17
Christiane Rennert, Franziska Eplinius, Ute Hofmann, Janina Johänning, Franziska Rolfs, Wolfgang Schmidt-Heck, Reinhardt Guthke, Rolf Gebhardt, Albert M Ricken, Madlen Matz-Soja
The Hedgehog signaling pathway is known to be involved in embryogenesis, tissue remodeling, and carcinogenesis. Because of its involvement in carcinogenesis, it seems an interesting target for cancer therapy. Indeed, Sonidegib, an approved inhibitor of the Hedgehog receptor Smoothened (Smo), is highly active against diverse carcinomas, but its use is also reported to be associated with several systemic side effects. Our former work in adult mice demonstrated hepatic Hedgehog signaling to play a key role in the insulin-like growth factor axis and lipid metabolism...
May 30, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28551328/association-of-expression-of-the-hedgehog-signal-with-merkel-cell-polyomavirus-infection-and-prognosis-of-merkel-cell-carcinoma
#18
Teruyuki Kuromi, Michiko Matsushita, Takeshi Iwasaki, Daisuke Nonaka, Satoshi Kuwamoto, Keiko Nagata, Masako Kato, Gen Akizuki, Yukisato Kitamura, Kazuhiko Hayashi
Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. 29 MCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score...
May 24, 2017: Human Pathology
https://www.readbyqxmd.com/read/28548560/microalgal-oil-from-schizochytrium-sp-prevents-hfd-induced-abdominal-fat-accumulation-in-mice
#19
Jinhui Yu, Yong Ma, Jie Sun, Liyuan Ran, Youwei Li, Ning Wang, Tao Yu, Wenting Gao, Wenbin Jia, Rujiao Jiang, Meihua Guo, Yuping Bi, Yingjie Wu
OBJECTIVE: Dietary n-3 polyunsaturated fatty acids (PUFAs), especially eicosapentaenoic acids (EPA) and docosahexaenoic acid (DHA), are proved to be effective in obesity reduction. Microalgal oil (MO) is an important alternative source of n-3 PUFAs that effectively alleviates obesity. The aim of the present study was to explore the anti-obesity effects of microalgal oil from Schizochytrium sp. (SMO) and to compare the effects of 2 SMOs (SMO1 and SMO2) with different levels of purity of n-3 PUFAs on high fat diet (HFD)-induced obesity in male C57BL/6J mice...
May 26, 2017: Journal of the American College of Nutrition
https://www.readbyqxmd.com/read/28527471/the-electron-shuffle-cerium-influences-samarium-4f-orbital-occupancy-in-heteronuclear-ce-sm-oxide-clusters
#20
Jared O Kafader, Josey E Topolski, Vicmarie Marrero-Colon, Srinivasan S Iyengar, Caroline Chick Jarrold
The anion photoelectron (PE) spectra along with supporting results of density functional theory (DFT) calculations on SmO(-), SmCeOy(-), and Sm2Oy(-) (y = 1, 2) are reported and compared to previous results on CeO(-) [M. Ray et al., J. Chem. Phys. 142, 064305 (2015)] and Ce2Oy(-) (y = 1, 2) [J. O. Kafader et al., J. Chem. Phys. 145, 154306 (2016)]. Similar to the results on CexOy(-) clusters, the PE spectra of SmO(-), SmCeOy(-), and Sm2Oy(-) (y = 1, 2) all exhibit electronic transitions to the neutral ground state at approximately 1 eV e(-)BE...
May 21, 2017: Journal of Chemical Physics
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