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https://www.readbyqxmd.com/read/28231034/upscaling-of-hips-cell-derived-neurons-for-high-throughput-screening
#1
Stefanie Traub, Heiko Stahl, Holger Rosenbrock, Eric Simon, Ralf Heilker
The advent of human-induced pluripotent stem (hiPS) cell-derived neurons promised to provide better model cells for drug discovery in the context of the central nervous system. This work demonstrates both the upscaling of cellular expansion and the acceleration of neuronal differentiation to accommodate the immense material needs of a high-throughput screening (HTS) approach. Using GRowth factor-driven expansion and INhibition of NotCH (GRINCH) during maturation, the derived cells are here referred to as GRINCH neurons...
March 2017: SLAS Discov
https://www.readbyqxmd.com/read/28230741/high-frequency-repetitive-transcranial-magnetic-stimulation-rtms-improves-functional-recovery-by-enhancing-neurogenesis-and-activating-bdnf-trkb-signaling-in-ischemic-rats
#2
Jing Luo, Haiqing Zheng, Liying Zhang, Qingjie Zhang, Lili Li, Zhong Pei, Xiquan Hu
Repetitive transcranial magnetic stimulation (rTMS) has rapidly become an attractive therapeutic approach for stroke. However, the mechanisms underlying this remain elusive. This study aimed to investigate whether high-frequency rTMS improves functional recovery mediated by enhanced neurogenesis and activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase B (TrkB) pathway and to compare the effect of conventional 20 Hz rTMS and intermittent theta burst stimulation (iTBS) on ischemic rats...
February 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28216317/tropomyosin-isoforms-specify-functionally-distinct-actin-filament-populations-in%C3%A2-vitro
#3
Gergana Gateva, Elena Kremneva, Theresia Reindl, Tommi Kotila, Konstantin Kogan, Laurène Gressin, Peter W Gunning, Dietmar J Manstein, Alphée Michelot, Pekka Lappalainen
Actin filaments assemble into a variety of networks to provide force for diverse cellular processes [1]. Tropomyosins are coiled-coil dimers that form head-to-tail polymers along actin filaments and regulate interactions of other proteins, including actin-depolymerizing factor (ADF)/cofilins and myosins, with actin [2-5]. In mammals, >40 tropomyosin isoforms can be generated through alternative splicing from four tropomyosin genes. Different isoforms display non-redundant functions and partially non-overlapping localization patterns, for example within the stress fiber network [6, 7]...
February 14, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/28216067/the-antidepressant-like-effects-of-biperiden-may-involve-bdnf-trkb-signaling-mediated-bicc1-expression-in-the-hippocampus-and-prefrontal-cortex-of-mice
#4
Dongsheng Zhou, Zhongmin Zhang, Lingjiang Liu, Chenli Li, Mengmeng Li, Hanjie Yu, Xiongxiong Cai, Xin Sun, Xinbei Shen, Jinting Wang, Jiacheng Geng, Chuang Wang, Yaosheng Shi
Preclinical and clinical studies suggest that neuronal muscarinic acetylcholine receptor (M-AchR) antagonists have antidepressant-like properties. Despite the recent interest in bicaudal C homolog 1 gene (BICC1) as a target for the treatment of depression, the upstream signaling molecules that regulate BICC1 are unknown, and very few studies have addressed the involvement of BICC1 in the antidepressant-like effects of the selective M1-AchR inhibitor, biperiden. Growing evidence indicates that activation of brain-derived neurotrophic factor (BDNF)/tropomyosin-related kinase receptor B (TrkB) signaling may be involved in antidepressant-like activities...
February 16, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28208669/the-role-of-nerve-growth-factor-ngf-and-its-precursor-forms-in-oral-wound-healing
#5
REVIEW
Karl Schenck, Olav Schreurs, Katsuhiko Hayashi, Kristen Helgeland
Nerve growth factor (NGF) and its different precursor forms are secreted into human saliva by salivary glands and are also produced by an array of cells in the tissues of the oral cavity. The major forms of NGF in human saliva are forms of pro-nerve growth factor (pro-NGF) and not mature NGF. The NGF receptors tropomyosin-related kinase A (TrkA) and p75 neurotrophin receptor (p75(NTR)) are widely expressed on cells in the soft tissues of the human oral cavity, including keratinocytes, endothelial cells, fibroblasts and leukocytes, and in ductal and acinar cells of all types of salivary glands...
February 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28197073/association-of-trka-and-app-is-promoted-by-ngf-and-reduced-by-cell-death-promoting-agents
#6
Nadia Canu, Ilaria Pagano, Luca Rosario La Rosa, Marsha Pellegrino, Maria Teresa Ciotti, Delio Mercanti, Fabiola Moretti, Valentina Sposato, Viviana Triaca, Carla Petrella, Ichiro N Maruyama, Andrea Levi, Pietro Calissano
The amyloid precursor protein (APP) interacts with the tropomyosin receptor kinase A (TrkA) in normal rat, mouse, and human brain tissue but not in Alzheimer's disease (AD) brain tissue. However, it has not been reported whether the two proteins interact directly, and if so, which domains are involved. Clarifying these points will increase our understanding of the role and regulation of the TrkA/APP interaction in normal brain functioning as well as in AD. Here we addressed these questions using bimolecular fluorescence complementation (BiFC) and the proximity ligation assay (PLA)...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28196470/proteasome-impairment-in-neural-cells-derived-from-hmsn-p-patient-ipscs
#7
Nagahisa Murakami, Keiko Imamura, Yuishin Izumi, Naohiro Egawa, Kayoko Tsukita, Takako Enami, Takuya Yamamoto, Toshitaka Kawarai, Ryuji Kaji, Haruhisa Inoue
Hereditary motor and sensory neuropathy with proximal dominant involvement (HMSN-P) is caused by a heterozygous mutation (P285L) in Tropomyosin-receptor kinase Fused Gene (TFG), histopathologically characterized by progressive spinal motor neuron loss with TFG cytosolic aggregates. Although the TFG protein, found as a type of fusion oncoprotein, is known to facilitate vesicle transport from endoplasmic reticulum (ER) to Golgi apparatus at ER exit site, it is unclear how mutant TFG causes motor neuron degeneration...
February 15, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28193719/brain-specific-ablation-of-efr3a-promotes-adult-hippocampal-neurogenesis-via-the-brain-derived-neurotrophic-factor-pathway
#8
Qi Qian, Qiuji Liu, Dongming Zhou, Hongyu Pan, Zhiwei Liu, Fangping He, Suying Ji, Dongpi Wang, Wangxiao Bao, Xinyi Liu, Zhaoling Liu, Heng Zhang, Xiaoqin Zhang, Ling Zhang, Mingkai Wang, Ying Xu, Fude Huang, Benyan Lao, Binggui Sun
Efr3 is a newly identified plasma membrane protein and plays an important role in the phosphoinositide metabolism on the plasma membrane. However, although it is highly expressed in the brain, the functional significance of Efr3 in the brain is not clear. In the present study, we generated Efr3a(f/f) mice and then crossed them with Nestin-Cre mice to delete Efr3a, one of the Efr3 isoforms, specifically in the brain. We found that brain-specific ablation of Efr3a promoted adult hippocampal neurogenesis by increasing survival and maturation of newborn neurons without affecting their dendritic tree morphology...
February 13, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28192031/neural-crest-stem-cells-can-differentiate-to-a-cardiomyogenic-lineage-with-an-ability-to-contract-in-response-to-pulsed-infrared-stimulation
#9
Jordan M Greenberg, Vicente Lumbreras, Daniel Pelaez, Suhrud M Rajguru, Herman S Cheung
INTRODUCTION: Cellular cardiomyoplasty has rapidly risen to prominence in the clinic following a myocardial infarction; however, low engraftment of transplanted cells limits the therapeutic benefit to these procedures. Recently, lineage-specific stem cells differentiated into cardiomyocytes have gained much attention to assist in the repair of an injured heart tissue; however, questions regarding the ideal cell source remain. In the present study, we have identified a source that is easy to extract stem cells from and show that the cells present have a high plasticity toward the cardiomyogenic lineage...
October 2016: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28191711/bioinformatic-screening-and-detection-of-allergen-cross-reactive-ige-binding-epitopes
#10
Scott McClain
Protein allergens can be related by cross-reactivity. Allergens that share relevant sequence can cross-react, those lacking similarity in their IgE antibody-binding epitopes do not cross-react. Cross-reactivity is based on shared epitopes which is due to shared sequence and higher level structure (charge and shape). Epitopes can be important in predicting cross-reactivity potential and may provide the potential to establish criteria that identify homology among allergens. Selected allergen's IgE binding epitope sequences were used to determine how the FASTA algorithm could be used to identify a threshold of significance...
February 13, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28191488/measurement-of-mechanical-tension-at-cell-cell-junctions-using-two-photon-laser-ablation
#11
Xuan Liang, Magdalene Michael, Guillermo A Gomez
The cortical actomyosin cytoskeleton is found in all non-muscle cells where a key function is to control mechanical force (Salbreux et al., 2012). When coupled to E-cadherin cell-cell adhesion, cortical actomyosin generates junctional tension that influences many aspects of tissue function, organization and morphogenesis (Lecuit and Yap, 2015). Uncovering the molecular mechanisms underlying the generation of junctional tension requires tools for measuring it in live cells with a high spatio-temporal resolution...
December 20, 2016: Bio-protocol
https://www.readbyqxmd.com/read/28182650/tropomyosin-1-acts-as-a-potential-tumor-suppressor-in-human-oral-squamous-cell-carcinoma
#12
Hao Pan, Liqun Gu, Binjie Liu, Yiping Li, Yuehong Wang, Xinna Bai, Long Li, Baisheng Wang, Qian Peng, Zhigang Yao, Zhangui Tang
It is widely accepted that oral squamous cell carcinoma (OSCC) is a major contributor to the incidence and mortality of neck and head cancer. Tropomyosin-1 (TPM1), which is expressed at a low level, has been considered a prominent tumor-suppressing gene in a variety of solid tumors, although the precise mechanism of the TPM1 gene in OSCC progression remains unknown. We found that TPM1 expression levels decreased in OSCC patients and OSCC cell lines. The overall and cancer-specific survival of patients who exhibited low TPM1 levels were inferior to those of patients who had high TPM1 levels...
2017: PloS One
https://www.readbyqxmd.com/read/28174090/targeting-trk-family-proteins-in-cancer
#13
REVIEW
Yekaterina B Khotskaya, Vijaykumar R Holla, Anna F Farago, Kenna R Mills Shaw, Funda Meric-Bernstam, David S Hong
The tropomyosin receptor kinase (TRK) family includes TRKA, TRKB, and TRKC proteins, which are encoded by NTRK1, NTRK2 and NTRK3 genes, respectively. Binding of neurotrophins to TRK proteins induces receptor dimerization, phosphorylation, and activation of the downstream signaling cascades via PI3K, RAS/MAPK/ERK, and PLC-gamma. TRK pathway aberrations, including gene fusions, protein overexpression, and single nucleotide alterations, have been implicated in the pathogenesis of many cancer types, with NTRK gene fusions being the most well validated oncogenic events to date...
February 4, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28167232/integrative-network-analysis-reveals-time-dependent-molecular-events-underlying-left-ventricular-remodeling-in-post-myocardial-infarction-patients
#14
Florence Pinet, Marie Cuvelliez, Thomas Kelder, Philippe Amouyel, Marijana Radonjic, Christophe Bauters
To elucidate the time-resolved molecular events underlying the LV remodeling (LVR) process, we developed a large-scale network model that integrates the 24 molecular variables (plasma proteins and non-coding RNAs) collected in the REVE-2 study at four time points (baseline, 1month, 3months and 1year) after MI. The REVE-2 network model was built by extending the set of REVE-2 variables with their mechanistic context based on known molecular interactions (1310 nodes and 8639 edges). Changes in the molecular variables between the group of patients with high LVR (>20%) and low LVR (<20%) were used to identify active network modules within the clusters associated with progression of LVR, enabling assessment of time-resolved molecular changes...
February 3, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28161413/relaxed-and-active-thin-filament-structures-a-new-structural-basis-for-the-regulatory-mechanism
#15
Danielle M Paul, John M Squire, Edward P Morris
The structures of muscle thin filaments reconstituted using skeletal actin and cardiac troponin and tropomyosin have been determined with and without bound Ca(2+) using electron microscopy and reference-free single particle analysis. The resulting density maps have been fitted with atomic models of actin, tropomyosin and troponin showing that: (i) the polarity of the troponin complex is consistent with our 2009 findings, with large shape changes in troponin between the two states; (ii) without Ca(2+) the tropomyosin pseudo-repeats all lie at almost equivalent positions in the 'blocked' position on actin (over subdomains 1 and 2); (iii) in the active state the tropomyosin pseudo-repeats are all displaced towards subdomains 3 and 4 of actin, but the extent of displacement varies within the regulatory unit depending upon the axial location of the pseudo-repeats with respect to troponin...
February 1, 2017: Journal of Structural Biology
https://www.readbyqxmd.com/read/28159414/the-juxtamembrane-region-of-trka-kinase-is-critical-for-inhibitor-selectivity
#16
Noritaka Furuya, Takaki Momose, Kenji Katsuno, Nobuhiko Fushimi, Hideyuki Muranaka, Chiaki Handa, Tomonaga Ozawa, Takayoshi Kinoshita
Although numerous crystal structures for protein kinases have been reported, many include only the kinase domain but not the juxtamembrane (JM) region, a critical activity-controlling segment of receptor tyrosine kinases (RTKs). In this study, we determined the X-ray crystal structure of the tropomyosin receptor kinase (Trk) A selective inhibitor A1 complexed with the TrkA kinase domain and the JM region. This structure revealed that the unique inhibitor-binding pocket created by a novel JM configuration yields significant potency and high selectivity against TrkB and TrkC...
January 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28138712/proteomic-analysis-indicates-the-importance-of-tpm3-in-esophageal-squamous-cell-carcinoma-invasion-and-metastasis
#17
Shao-Bin Yu, Qin Gao, Wen-Wei Lin, Ming-Qiang Kang
Numerous esophageal squamous cell carcinoma (ESCC) patients exhibit tumor recurrence following radical resection. Invasion and metastasis are key factors in poor prognosis following esophagectomy. In the present study, two‑dimensional gel electrophoresis (2-DE) and matrix‑assisted laser desorption/ionization time-of-flight mass spectrometry were used to define patterns of protein expression in ESCC tissues at different pathological stages. The expression levels of identified proteins were determined by immunohistochemistry and western blotting...
January 25, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28138157/forebrain-specific-ablation-of-phospholipase-c%C3%AE-1-causes-manic-like-behavior
#18
Y R Yang, J H Jung, S-J Kim, K Hamada, A Suzuki, H J Kim, J H Lee, O-B Kwon, Y K Lee, J Kim, E-K Kim, H-J Jang, D-S Kang, J-S Choi, C J Lee, J Marshall, H-Y Koh, C-J Kim, H Seok, S H Kim, J H Choi, Y-B Choi, L Cocco, S H Ryu, J-H Kim, P-G Suh
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1(f/f); CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses...
January 31, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28138113/increased-levels-of-c1q-in-the-prefrontal-cortex-of-adult-offspring-after-maternal-immune-activation-prevention-by-7-8-dihydroxyflavone
#19
Mei Han, Ji-Chun Zhang, Kenji Hashimoto
Objective: Prenatal infection is implicated in the etiology of schizophrenia. The objective of this paper is to study the role of complement protein C1q in the psychosis of adult offspring after maternal immune activation (MIA). In addition, effect of 7,8-dihydroxyflavone (7,8-DHF: a tropomyosin receptor kinase B [TrkB] agonist) was also examined. Methods: Western blot analysis of C1q in the brain regions from adult offspring after prenatal poly(I:C) (5.0 mg/kg/day from E12 to E17) exposure was performed...
February 28, 2017: Clinical Psychopharmacology and Neuroscience: the Official Scientific Journal of the Korean College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28134845/integral-characterization-of-defective-bdnf-trkb-signalling-in-neurological-and-psychiatric-disorders-leads-the-way-to-new-therapies
#20
REVIEW
Gonzalo S Tejeda, Margarita Díaz-Guerra
Enhancement of brain-derived neurotrophic factor (BDNF) signalling has great potential in therapy for neurological and psychiatric disorders. This neurotrophin not only attenuates cell death but also promotes neuronal plasticity and function. However, an important challenge to this approach is the persistence of aberrant neurotrophic signalling due to a defective function of the BDNF high-affinity receptor, tropomyosin-related kinase B (TrkB), or downstream effectors. Such changes have been already described in several disorders, but their importance as pathological mechanisms has been frequently underestimated...
January 28, 2017: International Journal of Molecular Sciences
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