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https://www.readbyqxmd.com/read/28729824/mouse-models-of-c9orf72-hexanucleotide-repeat-expansion-in-amyotrophic-lateral-sclerosis-frontotemporal-dementia
#1
REVIEW
Ranjan Batra, Chris W Lee
The presence of hexanucleotide repeat expansion (HRE) in the first intron of the human C9orf72 gene is the most common genetic cause underlying both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Studies aimed at elucidating the pathogenic mechanisms associated of C9orf72 FTD and ALS (C9FTD/ALS) have focused on the hypothesis of RNA and protein toxic gain-of-function models, including formation of nuclear RNA foci containing GGGGCC (G4C2) HRE, inclusions containing dipeptide repeat proteins through a non-canonical repeat associated non-ATG (RAN) translation mechanism, and on loss-of-function of the C9orf72 protein...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28711917/interplay-between-apoptosis-and-autophagy-in-colorectal-cancer
#2
REVIEW
Hao-Ran Qian, Zhao-Qi Shi, He-Pan Zhu, Li-Hu Gu, Xian-Fa Wang, Yi Yang
Autophagy and apoptosis are two pivotal mechanisms in mediating cell survival and death. Cross-talk of autophagy and apoptosis has been documented in the tumorigenesis and progression of cancer, while the interplay between the two pathways in colorectal cancer (CRC) has not yet been comprehensively summarized. In this study, we outlined the basis of apoptosis and autophagy machinery firstly, and then reviewed the recent evidence in cellular settings or animal studies regarding the interplay between them in CRC...
June 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28710131/gene-regulatory-networks-for-the-haploid-to-diploid-transition-of-chlamydomonas-reinhardtii
#3
Sunjoo Joo, Yoshiki Nishimura, Evan Cronmiller, Ran Ha Hong, Thamali Kariyawasam, Ming Hsiu Wang, Nai Chun Shao, Saif-El-Din El Akkad, Takamasa Suzuki, Tetsuya Higashiyama, EonSeon Jin, Jae-Hyeok Lee
The sexual cycle of the unicellular Chlamydomonas reinhardtii culminates in the formation of diploid zygotes which differentiate into dormant spores that eventually undergo meiosis. Mating between gametes induces rapid cell wall shedding via the enzyme g-lysin; cell fusion is followed by heterodimerization of sex-specific homeobox transcription factors, GSM1 and GSP1, and initiation of zygote-specific gene expression. To investigate the genetic underpinnings of the zygote developmental pathway, we performed comparative transcriptome analysis of both pre- and post-fertilization samples...
July 14, 2017: Plant Physiology
https://www.readbyqxmd.com/read/28696459/the-origin-of-the-debye-relaxation-in-liquid-water-and-fitting-the-high-frequency-excess-response
#4
Daniel C Elton
We critically review the literature on the Debye absorption peak of liquid water and the excess response found on the high frequency side of the Debye peak. We find a lack of agreement on the microscopic phenomena underlying both of these features. To better understand the molecular origin of Debye peak we ran large scale molecular dynamics simulations and performed several different distance-dependent decompositions of the low frequency dielectric spectra, finding that it involves processes that take place on scales of 1...
July 11, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28688761/long-non-coding-rna-gm4419-promotes-trauma-induced-astrocyte-apoptosis-by-targeting-tumor-necrosis-factor-%C3%AE
#5
Yunhu Yu, Fang Cao, Qishan Ran, Fei Wang
Traumatic brain injury (TBI) remains a life-threatening disease. Accumulating evidences have showed that neuroinflammatory response is a critical biological event in the progression of TBI induced astrocyte damage. However, the exact mechanisms are not well understood. In this study, we demonstrated that long non-coding RNA (lncRNA) Gm4419 promoted trauma-induced astrocyte apoptosis by up-regulating the expression of inflammatory cytokine tumor necrosis factor α (TNF-α). We observed that Gm4419 was aberrantly induced after injury on astroglial cells in vitro...
July 5, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28684048/dihydrocapsaicin-dhc-enhances-the-hypothermia-induced-neuroprotection-following-ischemic-stroke-via-pi3k-akt-regulation-in-rat
#6
Di Wu, Jingfei Shi, Omar Elmadhoun, Yunxia Duan, Hong An, Jun Zhang, Xiaoduo He, Ran Meng, Xiangrong Liu, Xunming Ji, Yuchuan Ding
OBJECTIVE: Hypothermia has demonstrated neuroprotection following ischemia in preclinical studies while its clinical application is still very limited. The aim of this study was to explore whether combining local hypothermia in ischemic territory achieved by intra-arterial cold infusions (IACIs) with pharmacologically induced hypothermia enhances therapeutic outcomes, as well as the underlying mechanism. METHODS: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h using intraluminal hollow filament...
July 3, 2017: Brain Research
https://www.readbyqxmd.com/read/28665301/comparative-proteomic-profiling-reveals-molecular-characteristics-associated-with-oogenesis-and-oocyte-maturation-during-ovarian-development-of-bactrocera-dorsalis-hendel
#7
Dong Wei, Ran Li, Meng-Yi Zhang, Yu-Wei Liu, Zheng Zhang, Guy Smagghe, Jin-Jun Wang
Time-dependent expression of proteins in ovary is important to understand oogenesis in insects. Here, we profiled the proteomes of developing ovaries from Bactrocera dorsalis (Hendel) to obtain information about ovarian development with particular emphasis on differentially expressed proteins (DEPs) involved in oogenesis. A total of 4838 proteins were identified with an average peptide number of 8.15 and sequence coverage of 20.79%. Quantitative proteomic analysis showed that a total of 612 and 196 proteins were differentially expressed in developing and mature ovaries, respectively...
June 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28637321/amino-acid-substrates-impose-polyamine-eif5a-or-hypusine-requirement-for-peptide-synthesis
#8
Byung-Sik Shin, Takayuki Katoh, Erik Gutierrez, Joo-Ran Kim, Hiroaki Suga, Thomas E Dever
Whereas ribosomes efficiently catalyze peptide bond synthesis by most amino acids, the imino acid proline is a poor substrate for protein synthesis. Previous studies have shown that the translation factor eIF5A and its bacterial ortholog EF-P bind in the E site of the ribosome where they contact the peptidyl-tRNA in the P site and play a critical role in promoting the synthesis of polyproline peptides. Using misacylated Pro-tRNAPhe and Phe-tRNAPro, we show that the imino acid proline and not tRNAPro imposes the primary eIF5A requirement for polyproline synthesis...
June 16, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28631094/post-translational-remodeling-of-ryanodine-receptor-induces-calcium-leak-leading-to-alzheimer-s-disease-like-pathologies-and-cognitive-deficits
#9
Alain Lacampagne, Xiaoping Liu, Steven Reiken, Renaud Bussiere, Albano C Meli, Inger Lauritzen, Andrew F Teich, Ran Zalk, Nathalie Saint, Ottavio Arancio, Charlotte Bauer, Fabrice Duprat, Clark A Briggs, Shreaya Chakroborty, Grace E Stutzmann, Michael L Shelanski, Frederic Checler, Mounia Chami, Andrew R Marks
The mechanisms underlying ryanodine receptor (RyR) dysfunction associated with Alzheimer disease (AD) are still not well understood. Here, we show that neuronal RyR2 channels undergo post-translational remodeling (PKA phosphorylation, oxidation, and nitrosylation) in brains of AD patients, and in two murine models of AD (3 × Tg-AD, APP (+/-) /PS1 (+/-)). RyR2 is depleted of calstabin2 (KFBP12.6) in the channel complex, resulting in endoplasmic reticular (ER) calcium (Ca(2+)) leak. RyR-mediated ER Ca(2+) leak activates Ca(2+)-dependent signaling pathways, contributing to AD pathogenesis...
June 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28600321/importin-beta-and-crm1-control-a-ranbp2-spatiotemporal-switch-essential-for-mitotic-kinetochore-function
#10
Eugenia Gilistro, Valeria de Turris, Michela Damizia, Annalisa Verrico, Sara Moroni, Riccardo De Santis, Alessandro Rosa, Patrizia Lavia
Protein conjugation with SUMO is a post-translational modification that modulates protein interactions and localisation. RANBP2 is a large nucleoporin endowed with SUMO E3 ligase and SUMO-stabilising activity and is implicated in some cancer types. RANBP2 is part of a larger complex, comprising SUMO-modified RANGAP1, the GTP-hydrolysis activating factor for the GTPase RAN. During mitosis, the RANBP2/SUMO-RANGAP1 complex localises to the mitotic spindle and to kinetochores after microtubule attachment. Here we have addressed the mechanisms that regulate this localisation and how they affect kinetochore functions...
June 9, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28588297/targeted-patching-and-dendritic-ca-2-imaging-in-nonhuman-primate-brain-in-vivo
#11
Ran Ding, Xiang Liao, Jingcheng Li, Jianxiong Zhang, Meng Wang, Yu Guang, Han Qin, Xingyi Li, Kuan Zhang, Shanshan Liang, Jiangheng Guan, Jia Lou, Hongbo Jia, Bingbo Chen, Hui Shen, Xiaowei Chen
Nonhuman primates provide an important model not only for understanding human brain but also for translational research in neurological and psychiatric disorders. However, many high-resolution techniques for recording neural activity in vivo that were initially established for rodents have not been yet applied to the nonhuman primate brain. Here, we introduce a combination of two-photon targeted patching and dendritic Ca(2+) imaging to the neocortex of adult common marmoset, an invaluable primate model for neuroscience research...
June 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28585149/inhibition-of-adhesion-and-metastasis-of-hepg2-hepatocellular-carcinoma-cells-in-vitro-by-dna-aptamer-against-sialyl-lewis-x
#12
Xiao-Kang Wang, Yan Peng, Hao-Ran Tao, Fen-Fang Zhou, Chi Zhang, Fei Su, Shi-Pei Wang, Qing Liu, Li-Hua Xu, Xue-Kai Pan, Wei Xie, Mao-Hui Feng
The sialyl Lewis X (SLe(x)) antigen encoded by the FUT7 gene is the ligand of endotheliam-selectin (E-selectin). The combination of SLe(x) antigen and E-selectin represents an important way for malignant tumor metastasis. In the present study, the effect of the SLe(x)-binding DNA aptamer on the adhesion and metastasis of hepatocellular carcinoma HepG2 cells in vitro was investigated. Reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence staining were conducted to detect the expression of FUT7 at both transcriptional and translational levels...
June 2017: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/28551903/-against-all-odds-promoting-research-clinical-development-and-medical-services-of-the-conflict-in-the-galilee-medical-center
#13
Jacob Bornstein
The Galilee Medical Center (GMC) is unique in several aspects. Firstly, in the clinical aspect: In recent years, led by the Director of Medical Center, Dr. Masad Barhoum, a considerable momentum of development has taken place to reduce health discrepancies between the center and the periphery. Despite the under- financing of the health system in the Galilee, the GMC opened new clinical departments, introduced advanced medical technology and key staff members were added. This approach is depicted in publications presented in the current issue...
May 2017: Harefuah
https://www.readbyqxmd.com/read/28530225/a-canonical-neural-mechanism-for-behavioral-variability
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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)...
June 16, 2017: Journal of Biological Chemistry
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