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71.
Jae Eun Park Byoung Chul Park Hyun-A Kim Mina Song Sung Goo Park Do Hee Lee Hyeoung-Joon Kim Hyung-Kyoon Choi Jong-Tae Kim Sayeon Cho 《Cellular and molecular life sciences : CMLS》2010,67(15):2619-2629
Apoptosis signal-regulating kinase 1 (ASK1), a member of the MAP kinase kinase kinase, is activated by several death stimuli and is tightly regulated by several mechanisms such as interactions with regulatory proteins and post-translational modifications. Here, we report that dual-specificity phosphatase 13A (DUSP13A) functions as a novel regulator of ASK1. DUSP13A interacts with the N-terminal domain of ASK1 and induces ASK1-mediated apoptosis through the activation of caspase-3. DUSP13A enhances ASK1 kinase activity and thus its downstream factors. Small interfering RNA (siRNA) analyses show that knock-down of DUSP13A in human neuroblastoma SK-N-SH cells reduces ASK1 kinase activity. The phosphatase activity of DUSP13A is not required for the regulation of ASK1. This regulatory action of DSUP13 on ASK1 activity involves competition with Akt1, a negative regulator of ASK1, for binding to ASK1. Taken together, this study provides novel insights into the role of DUSP13A in the precise regulation of ASK1. 相似文献
72.
RNA splicing generates a variant light chain from an aberrantly rearranged kappa gene 总被引:20,自引:0,他引:20
Both C kappa regions in MPC 11 cells are rearranged into active transcripion units, one producing a normal kappa chain and the other an internally deleted kappa fragment lacking a V region. The gene coding for the kappa fragment mRNA is aberrantly rearranged and lacks a site for V leads to C kappa splicing. An alternative splicing event which deletes the V region from the nuclear RNA precursor generates the kappa fragment mRNA. 相似文献
73.
Bowler C Allen AE Badger JH Grimwood J Jabbari K Kuo A Maheswari U Martens C Maumus F Otillar RP Rayko E Salamov A Vandepoele K Beszteri B Gruber A Heijde M Katinka M Mock T Valentin K Verret F Berges JA Brownlee C Cadoret JP Chiovitti A Choi CJ Coesel S De Martino A Detter JC Durkin C Falciatore A Fournet J Haruta M Huysman MJ Jenkins BD Jiroutova K Jorgensen RE Joubert Y Kaplan A Kröger N Kroth PG La Roche J Lindquist E Lommer M Martin-Jézéquel V Lopez PJ Lucas S Mangogna M McGinnis K 《Nature》2008,456(7219):239-244
Diatoms are photosynthetic secondary endosymbionts found throughout marine and freshwater environments, and are believed to be responsible for around one-fifth of the primary productivity on Earth. The genome sequence of the marine centric diatom Thalassiosira pseudonana was recently reported, revealing a wealth of information about diatom biology. Here we report the complete genome sequence of the pennate diatom Phaeodactylum tricornutum and compare it with that of T. pseudonana to clarify evolutionary origins, functional significance and ubiquity of these features throughout diatoms. In spite of the fact that the pennate and centric lineages have only been diverging for 90 million years, their genome structures are dramatically different and a substantial fraction of genes ( approximately 40%) are not shared by these representatives of the two lineages. Analysis of molecular divergence compared with yeasts and metazoans reveals rapid rates of gene diversification in diatoms. Contributing factors include selective gene family expansions, differential losses and gains of genes and introns, and differential mobilization of transposable elements. Most significantly, we document the presence of hundreds of genes from bacteria. More than 300 of these gene transfers are found in both diatoms, attesting to their ancient origins, and many are likely to provide novel possibilities for metabolite management and for perception of environmental signals. These findings go a long way towards explaining the incredible diversity and success of the diatoms in contemporary oceans. 相似文献
74.
Chen Y Takita J Choi YL Kato M Ohira M Sanada M Wang L Soda M Kikuchi A Igarashi T Nakagawara A Hayashi Y Mano H Ogawa S 《Nature》2008,455(7215):971-974
Neuroblastoma in advanced stages is one of the most intractable paediatric cancers, even with recent therapeutic advances. Neuroblastoma harbours a variety of genetic changes, including a high frequency of MYCN amplification, loss of heterozygosity at 1p36 and 11q, and gain of genetic material from 17q, all of which have been implicated in the pathogenesis of neuroblastoma. However, the scarcity of reliable molecular targets has hampered the development of effective therapeutic agents targeting neuroblastoma. Here we show that the anaplastic lymphoma kinase (ALK), originally identified as a fusion kinase in a subtype of non-Hodgkin's lymphoma (NPM-ALK) and more recently in adenocarcinoma of lung (EML4-ALK), is also a frequent target of genetic alteration in advanced neuroblastoma. According to our genome-wide scans of genetic lesions in 215 primary neuroblastoma samples using high-density single-nucleotide polymorphism genotyping microarrays, the ALK locus, centromeric to the MYCN locus, was identified as a recurrent target of copy number gain and gene amplification. Furthermore, DNA sequencing of ALK revealed eight novel missense mutations in 13 out of 215 (6.1%) fresh tumours and 8 out of 24 (33%) neuroblastoma-derived cell lines. All but one mutation in the primary samples (12 out of 13) were found in stages 3-4 of the disease and were harboured in the kinase domain. The mutated kinases were autophosphorylated and displayed increased kinase activity compared with the wild-type kinase. They were able to transform NIH3T3 fibroblasts as shown by their colony formation ability in soft agar and their capacity to form tumours in nude mice. Furthermore, we demonstrate that downregulation of ALK through RNA interference suppresses proliferation of neuroblastoma cells harbouring mutated ALK. We anticipate that our findings will provide new insights into the pathogenesis of advanced neuroblastoma and that ALK-specific kinase inhibitors might improve its clinical outcome. 相似文献
75.
Mutations in kelch-like 3 and cullin 3 cause hypertension and electrolyte abnormalities 总被引:2,自引:0,他引:2
Boyden LM Choi M Choate KA Nelson-Williams CJ Farhi A Toka HR Tikhonova IR Bjornson R Mane SM Colussi G Lebel M Gordon RD Semmekrot BA Poujol A Välimäki MJ De Ferrari ME Sanjad SA Gutkin M Karet FE Tucci JR Stockigt JR Keppler-Noreuil KM Porter CC Anand SK Whiteford ML Davis ID Dewar SB Bettinelli A Fadrowski JJ Belsha CW Hunley TE Nelson RD Trachtman H Cole TR Pinsk M Bockenhauer D Shenoy M Vaidyanathan P Foreman JW Rasoulpour M Thameem F Al-Shahrouri HZ Radhakrishnan J Gharavi AG Goilav B 《Nature》2012,482(7383):98-102
Hypertension affects one billion people and is a principal reversible risk factor for cardiovascular disease. Pseudohypoaldosteronism type II (PHAII), a rare Mendelian syndrome featuring hypertension, hyperkalaemia and metabolic acidosis, has revealed previously unrecognized physiology orchestrating the balance between renal salt reabsorption and K(+) and H(+) excretion. Here we used exome sequencing to identify mutations in kelch-like 3 (KLHL3) or cullin 3 (CUL3) in PHAII patients from 41 unrelated families. KLHL3 mutations are either recessive or dominant, whereas CUL3 mutations are dominant and predominantly de novo. CUL3 and BTB-domain-containing kelch proteins such as KLHL3 are components of cullin-RING E3 ligase complexes that ubiquitinate substrates bound to kelch propeller domains. Dominant KLHL3 mutations are clustered in short segments within the kelch propeller and BTB domains implicated in substrate and cullin binding, respectively. Diverse CUL3 mutations all result in skipping of exon 9, producing an in-frame deletion. Because dominant KLHL3 and CUL3 mutations both phenocopy recessive loss-of-function KLHL3 mutations, they may abrogate ubiquitination of KLHL3 substrates. Disease features are reversed by thiazide diuretics, which inhibit the Na-Cl cotransporter in the distal nephron of the kidney; KLHL3 and CUL3 are expressed in this location, suggesting a mechanistic link between KLHL3 and CUL3 mutations, increased Na-Cl reabsorption, and disease pathogenesis. These findings demonstrate the utility of exome sequencing in disease gene identification despite the combined complexities of locus heterogeneity, mixed models of transmission and frequent de novo mutation, and establish a fundamental role for KLHL3 and CUL3 in blood pressure, K(+) and pH homeostasis. 相似文献
76.
77.
Reconstruction of flood events over the last 150 years in the lower reaches of the Changjiang River 总被引:1,自引:0,他引:1
The reconstruction of paleofloods in the Holocene has become one research highlight for the present global change study. The core sediments from one newly-emerged bar in the lower Changjiang River (Yangtze River) mainstream were collected for grain size and organic elemental measurements, with aim to reconstruct the flood events over the past 150 years. Major grain size parameters such as mean grain size, probability cumulative curve and C-M diagram of the core sediments clearly indicate the flood event deposition. Furthermore, the TOC/TN ratios in the sediments can indicate flood events considering that during the flash floods, strong surface erosion in the upper and lower reaches of the Changjiang River can transport a large amount of undecomposed plant debris and organic components with relatively low C/N ratios into the lower mainstream. Based on 210Pb dating and sedimentary geochemical results, the research profile recorded several large floods happened from 1850 to 1954, which agrees well with the historical documents and hydrological observations. Interesting to note that the flood events since the 1960s cannot be distinctly recognized on the basis of sediment grain size and organic elemental compositions of the profile, which mainly reflects the intensive human activities over the last fifty years, especially condense dam construction, have significantly changed the characters of suspended sediment into the lower mainstream. 相似文献
78.
Choi Il-heung Oh Sang-heon Choi Dae-soo Park Chan-sik Hwang Dong-hwan Lee Sang-jeong 《武汉大学学报:自然科学英文版》2003,8(2):725-730
This paper proposed a design and implementation procedure of the Time Synchronization Module (TSM) for the Automatic Identification System (AIS). The proposed TSM module uses a Temperature Compensated Crystal Oscillator (TCXO) as a local reference clock, and consists of a Digitally Controlled Oscillator (DCO), a divider, a phase discriminator, and register blocks. The TSM measures time difference between the 1 PPS from the Global Navigation Satellite System (GNSS) receiver and the generated transmitter clock. The measured time difference is compensated by controlling the DCO and the transmit clock is synchronized to the Universal Time Coordinated (UTC). The designed TSM can also be synchronized to the reference time derived from the received message. The proposed module is tested using the experimental AIS transponder set. The experimental results show that the proposed module satisfies the functional and timing specification of the AIS technical standard, ITU-R M.1371. 相似文献
79.
A physically-based statistical forecast model for the middle-lower reaches of the Yangtze River Valley summer rainfall 总被引:17,自引:0,他引:17
A new approach to forecast the middle-lower reaches of the Yangtze River Valley summer rainfall in June-August (JJA) is proposed in this paper. The year-to-year increment of the middle-lower reaches of the Yangtze River Valley is forecasted and hence the summer precipitation could be predicted. In this paper, DY is defined as the difference of a variable between the current year and the preceding year (year-to-year increment). YR denotes the seasonal mean precipitation rate of the middle-lower reaches of the Yangtze River Valley summer rainfall. After analyzing the atmospheric circulation anomalies in winter and spring that were associated with the DY of YR, six key predictors for the DY of YR have been identified. Then the forecast model for the DY of YR is established by using the multi-linear regression method. The predictors for the DY of YR are Antarctic Oscillation, the meridional wind shear between 850hPa and 200hPa over the Indo-Australian region, and so on. The prediction model shows a high skill for the hindcast during 1997-2006, with the average relative root mean square error is at 18%. The model can even reproduce the upward and downward trends of YR during 1984--1998 and 1998--2006. Considering that the current operational forecast models of the summer precipitation over the China region have the average forecast scores at 60%--70% and that the prediction skill for the middle-lower reaches of Yangtze River Valley summer precipitation remains quite limited up to now, thus this new approach to predict the year-to-year increment of the summer precipitation over the Yangtze River Valley (and hence the summer precipitation itself) has the potential to significantly increase the operational forecast skill of the summer precipitation. 相似文献
80.
The research outlined here includes a study of methanol production from direct methane conversion by means of thermal and plasma method. The kinetic study, derived from thermal-based approach, was carried out to investigate thoroughly the possible intermediate species likely to be presented in the process. A set of plasma experiments was undertaken by using dielectric barrier discharge (DBD), classified as non-thermal plasma, done at atmospheric pressure and room temperature. Plasma process yields more methanol than thermal process at the same methane conversion rates and methane to oxygen feed ratios. Oxidation reaction of thermal process resulted CO and CO2 as the most dominant products and the selectivity reached 19% and 68%, respectively. Moreover, more CO and less CO2 were produced in plasma process than in thermal process. The selectivity of CO and CO2 by plasma was 47% and 20%, respectively. Ethane (C2H6)was detected as the only higher hydrocarbon with a significant concentration. The concentration of ethane reached 9% of the total products in plasma process and 17% in thermal process. The maximum selectivity of methanol, the target material of this research, was 12% obtained by plasma method and less than 5% by thermal process. In some certain points, the kinetic model closely matched with the experimental results. 相似文献