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https://www.readbyqxmd.com/read/28530225/a-canonical-neural-mechanism-for-behavioral-variability
#1
Ran Darshan, William E Wood, Susan Peters, Arthur Leblois, David Hansel
The ability to generate variable movements is essential for learning and adjusting complex behaviours. This variability has been linked to the temporal irregularity of neuronal activity in the central nervous system. However, how neuronal irregularity actually translates into behavioural variability is unclear. Here we combine modelling, electrophysiological and behavioural studies to address this issue. We demonstrate that a model circuit comprising topographically organized and strongly recurrent neural networks can autonomously generate irregular motor behaviours...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529475/fragile-x-associated-tremor-ataxia-syndrome-from-molecular-pathogenesis-to-development-of-therapeutics
#2
REVIEW
Ha Eun Kong, Juan Zhao, Shunliang Xu, Peng Jin, Yan Jin
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder caused by a premutation CGG repeat expansion (55-200 repeats) within the 5' UTR of the fragile X gene (FMR1). FXTAS is characterized by intension tremor, cerebellar ataxia, progressive neurodegeneration, parkinsonism and cognitive decline. The development of transgenic mouse and Drosophila melanogaster models carrying an expanded CGG repeat has yielded valuable insight into the pathophysiology of FXTAS. To date, we know of two main molecular mechanisms of this disorder: (1) a toxic gain of function of the expanded CGG-repeat FMR1 mRNA, which results in the binding/sequestration of the CGG-binding proteins; and (2) CGG repeat-associated non-AUG-initiated (RAN) translation, which generates a polyglycine peptide toxic to cells...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28506344/-novel-phex-gene-mutations-in-patients-with-x-linked-hypophosphatemic-rickets-an-analysis-of-2-cases
#3
Qing Ran, Feng Xiong, Min Zhu, Lei-Li Deng, Pei-Yun Lei, Yan-Hong Luo, Yan Zeng, Gao-Hui Zhu, Cui Song
OBJECTIVE: To investigate PHEX gene mutations in 2 patients with X-linked hypophosphatemic rickets (XLH) and their families and to clarify the genetic etiology. METHODS: A retrospective analysis was performed for the clinical data of two patients with XLH. High-throughput sequencing was used to detect the PHEX gene, a pathogenic gene of XLH. PCR-Sanger sequencing was used to verify the distribution of mutations in families. RESULTS: Both patients had novel mutations in the PHEX gene; one patient had a frameshift mutation, c...
May 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28497758/ombitasvir-paritaprevir-and-ritonavir-with-or-without-dasabuvir-plus-ribavirin-for-patients-with-hepatitis-c-virus-genotype-1-or-4-infection-with-cirrhosis-abacus-a-prospective-observational-study
#4
Salvatore Petta, Marco Marzioni, Pierluigi Russo, Alessio Aghemo, Alfredo Alberti, Antonio Ascione, Andrea Antinori, Raffaele Bruno, Savino Bruno, Antonio Chirianni, Giovanni Battista Gaeta, Edoardo G Giannini, Manuela Merli, Vincenzo Messina, Simona Montilla, Carlo Federico Perno, Massimo Puoti, Giovanni Raimondo, Maria Rendina, Francesca Ceccherini Silberstein, Erica Villa, Anna Linda Zignego, Luca Pani, Antonio Craxì
BACKGROUND: We ran a compassionate use nationwide programme (ABACUS) to provide access to ombitasvir, paritaprevir, and ritonavir, with dasabuvir, plus ribavirin for hepatitis C virus (HCV) genotype 1 infection and ombitasvir, paritaprevir, and ritonavir, plus ribavirin for HCV genotype 4 infection in patients with cirrhosis at high risk of decompensation while approval of these regimens was pending in Italy. METHODS: In this prospective observational study, we collected data from a compassionate use nationwide programme from March 17, 2014, to May 28, 2015...
June 2017: Lancet. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28481984/the-dna-damage-response-ddr-is-induced-by-the-c9orf72-repeat-expansion-in-amyotrophic-lateral-sclerosis
#5
Manal A Farg, Anna Konopka, Kai Ying Soo, Daisuke Ito, Julie D Atkin
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease affecting motor neurons. Hexanucleotide (GGGGCC) repeat expansions in a non-coding region of C9orf72 are the major cause of familial ALS and frontotemporal dementia (FTD) worldwide. The C9orf72 repeat expansion undergoes repeat-associated non-ATG (RAN) translation to produce five dipeptide repeat proteins (DRPs), including poly(GR) and poly(PR). Whilst it remains unclear how mutations in C9orf72 lead to neurodegeneration in ALS/FTD, dysfunction to the nucleolus and R loop formation are implicated as pathogenic mechanisms...
May 8, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28477147/high-interspecimen-variability-in-engagement-of-the-anterolateral-ligament-an-in-vitro-cadaveric-study
#6
REVIEW
Robert N Kent, James F Boorman-Padgett, Ran Thein, Jelle P van der List, Danyal H Nawabi, Thomas L Wickiewicz, Carl W Imhauser, Andrew D Pearle
BACKGROUND: Anterolateral ligament (ALL) reconstruction as an adjunct to anterior cruciate ligament (ACL) reconstruction remains a subject of clinical debate. This uncertainty may be driven in part by a lack of knowledge regarding where, within the range of knee motion, the ALL begins to carry force (engages). QUESTIONS/PURPOSES: (1) Does the ALL engage in the ACL-intact knee; and (2) where within the range of anterior tibial translation occurring in the ACL-sectioned knee does the ALL engage? METHODS: A robotic manipulator was used to measure anterior tibial translation, ACL forces, and ALL forces in 10 fresh-frozen cadaveric knees (10 donors; mean age, 41 ± 16 years; range, 20-64 years; eight male) in response to applied multiplanar torques...
May 5, 2017: Clinical Orthopaedics and related Research
https://www.readbyqxmd.com/read/28476886/amyloid-%C3%AE-production-is-regulated-by-%C3%AE-2-adrenergic-signaling-mediated-post-translational-modifications-of-the-ryanodine-receptor
#7
Renaud Bussiere, Alain Lacampagne, Steven Reiken, Xiaoping Liu, Valerie Scheuerman, Ran Zalk, Cécile Martin, Frederic Checler, Andrew R Marks, Mounia Chami
Alteration of ryanodine receptor (RyR)-mediated calcium (Ca(2+)) signaling has been reported in Alzheimer disease (AD) models. However, the molecular mechanisms underlying altered RyR-mediated intracellular Ca(2+) release in AD remain to be fully elucidated. We report here that RyR2 undergoes post-translational modifications (phosphorylation, oxidation, and nitrosylation) in SH-SY5Y neuroblastoma cells expressing the β-amyloid precursor protein (βAPP) harboring the familial double Swedish mutations (APPswe)...
May 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28460002/proteomic-analysis-of-polyribosomes-identifies-splicing-factors-as-potential-regulators-of-translation-during-mitosis
#8
Ranen Aviner, Sarah Hofmann, Tamar Elman, Anjana Shenoy, Tamar Geiger, Ran Elkon, Marcelo Ehrlich, Orna Elroy-Stein
Precise regulation of mRNA translation is critical for proper cell division, but little is known about the factors that mediate it. To identify mRNA-binding proteins that regulate translation during mitosis, we analyzed the composition of polysomes from interphase and mitotic cells using unbiased quantitative mass-spectrometry (LC-MS/MS). We found that mitotic polysomes are enriched with a subset of proteins involved in RNA processing, including alternative splicing and RNA export. To demonstrate that these may indeed be regulators of translation, we focused on heterogeneous nuclear ribonucleoprotein C (hnRNP C) as a test case and confirmed that it is recruited to elongating ribosomes during mitosis...
April 29, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28445616/extract-of-syzygium-aromaticum-suppress-eef1a-protein-expression-and-fungal-growth
#9
Yihe Wang, Yiran Ding, Shunhe Wang, Haiqin Chen, Zhang Hao, Wei Chen, Zhennan Gu, Yong Q Chen
AIMS: Clove extract has therapeutic potential as an antifungal drug, yet the mechanism of action remain ambiguous. Current study aimed to address the molecular process of the antifungal activity exerted by clove extract. METHODS AND RESULTS: The antifungal assays results showed that clove extract had some effects on all of the tested yeast. Propidium iodide staining assay showed cell membrane damage in Saccharomyces cerevisiae after treatment of clove extract for 30 h...
April 26, 2017: Journal of Applied Microbiology
https://www.readbyqxmd.com/read/28440291/identifying-n-6-methyladenosine-sites-using-multi-interval-nucleotide-pair-position-specificity-and-support-vector-machine
#10
Pengwei Xing, Ran Su, Fei Guo, Leyi Wei
N6-methyladenosine (m(6)A) refers to methylation of the adenosine nucleotide acid at the nitrogen-6 position. It plays an important role in a series of biological processes, such as splicing events, mRNA exporting, nascent mRNA synthesis, nuclear translocation and translation process. Numerous experiments have been done to successfully characterize m(6)A sites within sequences since high-resolution mapping of m(6)A sites was established. However, as the explosive growth of genomic sequences, using experimental methods to identify m(6)A sites are time-consuming and expensive...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28388414/transcription-impacts-the-efficiency-of-mrna-translation-via-co-transcriptional-n6-adenosine-methylation
#11
Boris Slobodin, Ruiqi Han, Vittorio Calderone, Joachim A F Oude Vrielink, Fabricio Loayza-Puch, Ran Elkon, Reuven Agami
Transcription and translation are two main pillars of gene expression. Due to the different timings, spots of action, and mechanisms of regulation, these processes are mainly regarded as distinct and generally uncoupled, despite serving a common purpose. Here, we sought for a possible connection between transcription and translation. Employing an unbiased screen of multiple human promoters, we identified a positive effect of TATA box on translation and a general coupling between mRNA expression and translational efficiency...
April 6, 2017: Cell
https://www.readbyqxmd.com/read/28384479/mutant-huntingtin-disrupts-the-nuclear-pore-complex
#12
Jonathan C Grima, J Gavin Daigle, Nicolas Arbez, Kathleen C Cunningham, Ke Zhang, Joseph Ochaba, Charlene Geater, Eva Morozko, Jennifer Stocksdale, Jenna C Glatzer, Jacqueline T Pham, Ishrat Ahmed, Qi Peng, Harsh Wadhwa, Olga Pletnikova, Juan C Troncoso, Wenzhen Duan, Solomon H Snyder, Laura P W Ranum, Leslie M Thompson, Thomas E Lloyd, Christopher A Ross, Jeffrey D Rothstein
Huntington's disease (HD) is caused by an expanded CAG repeat in the Huntingtin (HTT) gene. The mechanism(s) by which mutant HTT (mHTT) causes disease is unclear. Nucleocytoplasmic transport, the trafficking of macromolecules between the nucleus and cytoplasm, is tightly regulated by nuclear pore complexes (NPCs) made up of nucleoporins (NUPs). Previous studies offered clues that mHTT may disrupt nucleocytoplasmic transport and a mutation of an NUP can cause HD-like pathology. Therefore, we evaluated the NPC and nucleocytoplasmic transport in multiple models of HD, including mouse and fly models, neurons transfected with mHTT, HD iPSC-derived neurons, and human HD brain regions...
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28384473/sca31-flies-perform-in-a-balancing-act-between-ran-translation-and-rna-binding-proteins
#13
George R Jackson
In this issue of Neuron, Ishiguro et al. (2017) explore the toxicity of RAN translation in spinocerebellar ataxia 31. Using a Drosophila model, the authors demonstrate that TDP-43 and other RNA-binding proteins act as chaperones to regulate the formation of toxic RNA aggregates.
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28365506/new-developments-in-ran-translation-insights-from-multiple-diseases
#14
REVIEW
John Douglas Cleary, Laura Pw Ranum
Since the discovery of repeat-associated non-ATG (RAN) translation, and more recently its association with amyotrophic lateral sclerosis/frontotemporal dementia, there has been an intense focus to understand how this process works and the downstream effects of these novel proteins. RAN translation across several different types of repeat expansions mutations (CAG, CTG, CCG, GGGGCC, GGCCCC) results in the production of proteins in all three reading frames without an ATG initiation codon. The combination of bidirectional transcription and RAN translation has been shown to result in the accumulation of up to six mutant expansion proteins in a growing number of diseases...
March 30, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28351931/antibodies-inhibit-transmission-and-aggregation-of-c9orf72-poly-ga-dipeptide-repeat-proteins
#15
Qihui Zhou, Carina Lehmer, Meike Michaelsen, Kohji Mori, Dominik Alterauge, Dirk Baumjohann, Martin H Schludi, Johanna Greiling, Daniel Farny, Andrew Flatley, Regina Feederle, Stephanie May, Franziska Schreiber, Thomas Arzberger, Christoph Kuhm, Thomas Klopstock, Andreas Hermann, Christian Haass, Dieter Edbauer
Cell-to-cell transmission of protein aggregates is an emerging theme in neurodegenerative disease. Here, we analyze the dipeptide repeat (DPR) proteins that form neuronal inclusions in patients with hexanucleotide repeat expansion C9orf72, the most common known cause of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Sense and antisense transcripts of the (G4C2)n repeat are translated by repeat-associated non-ATG (RAN) translation in all reading frames into five aggregating DPR proteins...
May 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/28343865/regulatory-role-of-rna-chaperone-tdp-43-for-rna-misfolding-and-repeat-associated-translation-in-sca31
#16
Taro Ishiguro, Nozomu Sato, Morio Ueyama, Nobuhiro Fujikake, Chantal Sellier, Akemi Kanegami, Eiichi Tokuda, Bita Zamiri, Terence Gall-Duncan, Mila Mirceta, Yoshiaki Furukawa, Takanori Yokota, Keiji Wada, J Paul Taylor, Christopher E Pearson, Nicolas Charlet-Berguerand, Hidehiro Mizusawa, Yoshitaka Nagai, Kinya Ishikawa
Microsatellite expansion disorders are pathologically characterized by RNA foci formation and repeat-associated non-AUG (RAN) translation. However, their underlying pathomechanisms and regulation of RAN translation remain unknown. We report that expression of expanded UGGAA (UGGAAexp) repeats, responsible for spinocerebellar ataxia type 31 (SCA31) in Drosophila, causes neurodegeneration accompanied by accumulation of UGGAAexp RNA foci and translation of repeat-associated pentapeptide repeat (PPR) proteins, consistent with observations in SCA31 patient brains...
April 5, 2017: Neuron
https://www.readbyqxmd.com/read/28337854/silk-fibroin-biomaterial-shows-safe-and-effective-wound-healing-in-animal-models-and-a-randomized-controlled-clinical-trial
#17
Wei Zhang, Longkun Chen, Jialin Chen, Lingshuang Wang, Xuexian Gui, Jisheng Ran, Guowei Xu, Hongshi Zhao, Mengfeng Zeng, Junfeng Ji, Li Qian, Jianda Zhou, Hongwei Ouyang, Xiaohui Zou
Due to its excellent biological and mechanical properties, silk fibroin has been intensively explored for tissue engineering and regenerative medicine applications. However, lack of translational evidence has hampered its clinical application for tissue repair. Here a silk fibroin film is developed and its translational potential is investigated for skin repair by performing comprehensive preclinical and clinical studies to fully evaluate its safety and effectiveness. The silk fibroin film fabricated using all green chemistry approaches demonstrates remarkable characteristics, including transmittance, fluid handling capacity, moisture vapor permeability, waterproofness, bacterial barrier properties, and biocompatibility...
May 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28301205/intratendon-delivery-of-leukocyte-poor-platelet-rich-plasma-improves-healing-compared-with-leukocyte-rich-platelet-rich-plasma-in-a-rabbit-achilles-tendinopathy-model
#18
Ruijian Yan, Yanjia Gu, Jisheng Ran, Yejun Hu, Zefeng Zheng, Mengfeng Zeng, Boon Chin Heng, Xiao Chen, Zi Yin, Weishan Chen, Weiliang Shen, Hongwei Ouyang
BACKGROUND: Chronic tendinopathy is a commonly occurring clinical problem that affects both athletes and inactive middle-aged patients. Although some studies have shown that different platelet-rich plasma (PRP) preparations could exert various therapeutic effects in vitro, the role of leukocytes in PRP has not yet been defined under tendinopathy conditions in vivo. PURPOSE: This study compared the effects of the intratendon delivery of leukocyte-poor PRP (Lp-PRP) versus leukocyte-rich PRP (Lr-PRP) in a rabbit chronic tendinopathy model in vivo...
March 1, 2017: American Journal of Sports Medicine
https://www.readbyqxmd.com/read/28297584/improvement-of-in-vitro-three-dimensional-cartilage-regeneration-by-a-novel-hydrostatic-pressure-bioreactor
#19
Jie Chen, Zhaoyuan Yuan, Yu Liu, Rui Zheng, Yao Dai, Ran Tao, Huitang Xia, Hairong Liu, Zhiyong Zhang, Wenjie Zhang, Wei Liu, Yilin Cao, Guangdong Zhou
In vitro three-dimensional (3D) cartilage regeneration is a promising strategy for repair of cartilage defects. However, inferior mechanical strength and tissue homogeneity greatly restricted its clinical translation. Simulation of mechanical stress through a bioreactor is an important approach for improving in vitro cartilage regeneration. The current study developed a hydrostatic pressure (HP) bioreactor based on a novel pressure-transmitting mode achieved by slight deformation of a flexible membrane in a completely sealed stainless steel device...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28297578/%C3%AE-elemene-selectively-inhibits-the-proliferation-of-glioma-stem-like-cells-through-the-downregulation-of-notch1
#20
Hai-Bin Feng, Jing Wang, Hao-Ran Jiang, Xin Mei, Yi-Ying Zhao, Fu-Rong Chen, Yue Qu, Ke Sai, Cheng-Cheng Guo, Qun-Ying Yang, Zong-Ping Zhang, Zhong-Ping Chen
Glioma is the most frequent primary central nervous system tumor. Although the current first-line medicine, temozolomide (TMZ), promotes patient survival, drug resistance develops easily. Thus, it is important to investigate novel therapeutic reagents to solidify the treatment effect. β-Elemene (bELE) is a compound from a Chinese herb whose anticancer effect has been shown in various types of cancer. However, its role in the inhibition of glioma stem-like cells (GSLCs) has not yet been reported. We studied both the in vitro and the in vivo inhibitory effect of bELE and TMZ in GSLCs and parental cells and their combined effects...
March 2017: Stem Cells Translational Medicine
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