WordNet

executed with proper legal authority; "a binding contract"
the protective covering on the front, back, and spine of a book; "the book had a leather binding" (同)book binding, cover, back
strip sewn over or along an edge for reinforcement or decoration
the capacity to attract and hold something
any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
the 18th letter of the Roman alphabet (同)r
the 6th letter of the Roman alphabet (同)f

PrepTutorEJDIC

義務的な,拘束力ある / 〈U〉しばること;〈C〉しばる物 / 〈C〉製本,装丁 / 〈U〉縁(‘ふち')取り材料
蛋白(たんばく)質
resistance / 17歳以下父兄同伴映画の表示 / rook
ribonucleic acid・リボ核酸

UpToDate Contents

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1. 慢性骨髄性白血病の細胞生物学および分子生物学 cellular and molecular biology of chronic myeloid leukemia
2. 転移性大腸癌に対する全身化学療法：終了した臨床試験 systemic chemotherapy for metastatic colorectal cancer completed clinical trials
3. 悪性腫瘍患者における薬剤による血栓症および血管疾患 drug induced thrombosis and vascular disease in patients with malignancy
4. 肝疾患を有する患者における化学療法による肝毒性および用量調整 chemotherapy hepatotoxicity and dose modification in patients with liver disease
5. 乳癌におけるHER2と治療の効果予測 her2 and predicting response to therapy in breast cancer

English Journal

Investigating FUS variation in Parkinson's disease.

Labbé C, Rayaprolu S, Soto-Ortolaza A, Ogaki K, Uitti RJ, Wszolek ZK, Ross OA.Author information Department of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.AbstractMutations of the FUS gene were first reported to cause amyotrophic lateral sclerosis (ALS). Subsequent studies confirmed the role of mutations in ALS and also implicated them in frontotemporal dementia (FTD). Recently, through Next-Generation Exome sequencing approaches a mutation resulting in a substitution (p.Q290X) in the nuclear export domain of the FUS protein was nominated as a cause of autosomal dominant essential tremor (ET) in a large kindred. In addition, recent reports suggest a possible role for TDP-43 mutations in parkinsonism; TDP-43 is another RNA-binding protein implicated in ALS. Given these findings we investigated the role of FUS variants in Parkinson's disease (PD). We sequenced specific regions of the gene encoding three functional domains of the FUS protein in 702 patients with PD. Our sequencing study did not identify any novel non-synonymous variant that would appear to affect the subjects' susceptibility to Parkinson's disease. These findings and previous studies have shown that variants within the FUS gene are not a common cause of PD or ET, in comparison to their role in ALS.
Parkinsonism & related disorders.Parkinsonism Relat Disord.2014 Jan;20 Suppl 1:S147-9. doi: 10.1016/S1353-8020(13)70035-X.
Mutations of the FUS gene were first reported to cause amyotrophic lateral sclerosis (ALS). Subsequent studies confirmed the role of mutations in ALS and also implicated them in frontotemporal dementia (FTD). Recently, through Next-Generation Exome sequencing approaches a mutation resulting in a sub
PMID 24262168

The role of heat shock proteins in Amyotrophic Lateral Sclerosis: The therapeutic potential of Arimoclomol.

Kalmar B1, Lu CH1, Greensmith L2.Author information 1Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London WC1N 3BG, UK.2Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London WC1N 3BG, UK; MRC Centre for Neuromuscular Disorders, UCL Institute of Neurology, London WC1N 3BG, UK. Electronic address: l.greensmith@ucl.ac.uk.AbstractArimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress. Arimoclomol has been found to be neuroprotective in a number of neurodegenerative disease models, including Amyotrophic Lateral Sclerosis (ALS), and in mutant Superoxide Dismutase 1 (SOD1) mice that model ALS, Arimoclomol rescues motor neurons, improves neuromuscular function and extends lifespan. The therapeutic potential of Arimoclomol is currently under investigation in a Phase II clinical trial for ALS patients with SOD1 mutations. In this review we summarize the evidence for the neuroprotective effects of enhanced heat shock protein expression by Arimoclomol and other inducers of the Heat Shock Response. ALS is a complex, multifactorial disease affecting a number of cell types and intracellular pathways. Cells and pathways affected by ALS pathology and which may be targeted by a heat shock protein-based therapy are also discussed in this review. For example, protein aggregation is a characteristic pathological feature of neurodegenerative diseases including ALS. Enhanced heat shock protein expression not only affects protein aggregation directly, but can also lead to more effective clearance of protein aggregates via the unfolded protein response, the proteasome-ubiquitin system or by autophagy. However, compounds such as Arimoclomol have effects beyond targeting protein mis-handling and can also affect additional pathological mechanisms such as oxidative stress. Therefore, by targeting multiple pathological mechanisms, compounds such as Arimoclomol may be particularly effective in the development of a disease-modifying therapy for ALS and other neurodegenerative disorders.
Pharmacology & therapeutics.Pharmacol Ther.2014 Jan;141(1):40-54. doi: 10.1016/j.pharmthera.2013.08.003. Epub 2013 Aug 23.
Arimoclomol is a hydroxylamine derivative, a group of compounds which have unique properties as co-inducers of heat shock protein expression, but only under conditions of cellular stress. Arimoclomol has been found to be neuroprotective in a number of neurodegenerative disease models, including Amyo
PMID 23978556

NKAP is a novel RS-related protein that interacts with RNA and RNA binding proteins.

Burgute BD, Peche VS, Steckelberg AL, Glöckner G, Gaßen B, Gehring NH, Noegel AA.Author information Institute of Biochemistry I, Medical Faculty, Center for Molecular Medicine Cologne (CMMC), 50931 Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University of Cologne, Cologne, Germany, Institute of Genetics, University of Cologne, 50931 Cologne, Germany and Leibniz-Institute of Freshwater Ecology and Inland Fisheries, IGB, Müggelseedamm 301, 12587 Berlin, Germany.AbstractNKAP is a highly conserved protein with roles in transcriptional repression, T-cell development, maturation and acquisition of functional competency and maintenance and survival of adult hematopoietic stem cells. Here we report the novel role of NKAP in splicing. With NKAP-specific antibodies we found that NKAP localizes to nuclear speckles. NKAP has an RS motif at the N-terminus followed by a highly basic domain and a DUF 926 domain at the C-terminal region. Deletion analysis showed that the basic domain is important for speckle localization. In pull-down experiments, we identified RNA-binding proteins, RNA helicases and splicing factors as interaction partners of NKAP, among them FUS/TLS. The FUS/TLS-NKAP interaction takes place through the RS domain of NKAP and the RGG1 and RGG3 domains of FUS/TLS. We analyzed the ability of NKAP to interact with RNA using in vitro splicing assays and found that NKAP bound both spliced messenger RNA (mRNA) and unspliced pre-mRNA. Genome-wide analysis using crosslinking and immunoprecipitation-seq revealed NKAP association with U1, U4 and U5 small nuclear RNA, and we also demonstrated that knockdown of NKAP led to an increase in pre-mRNA percentage. Our results reveal NKAP as nuclear speckle protein with roles in RNA splicing and processing.
Nucleic acids research.Nucleic Acids Res.2013 Dec 17. [Epub ahead of print]
NKAP is a highly conserved protein with roles in transcriptional repression, T-cell development, maturation and acquisition of functional competency and maintenance and survival of adult hematopoietic stem cells. Here we report the novel role of NKAP in splicing. With NKAP-specific antibodies we fou
PMID 24353314

Japanese Journal

Identification of a FUS splicing mutation in a large family with amyotrophic lateral sclerosis

BELZIL Veronique V,ST-ONGE Judith,DAOUD Hussein,DESJARLAIS Anne,BOUCHARD Jean-Pierre,DUPRE Nicolas,CAMU William,DION Patrick A,ROULEAU Guy A
Journal of human genetics 56(3), 247-249, 2011-03-01
NAID 10030658564