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Critical Involvement (critical + involvement)

Distribution by Scientific Domains

Life Sciences	40%

Selected Abstracts

Deletions of SCN1A 5, genomic region with promoter activity in Dravet syndrome,

HUMAN MUTATION, Issue 7 2010
Tojo Nakayama
Abstract Mutations involving the voltage-gated sodium channel ,I gene SCN1A are major genetic causes of childhood epileptic disorders, as typified by Dravet syndrome. Here we investigated the upstream regions of the SCN1A 5, noncoding exons and found two major regions with promoter activity. These two major promoters were simultaneously active in various brain regions and in most neurons. Using multiplex ligation-dependent probe amplification (MLPA) assays with probes for the 5, noncoding exons, their upstream regions, and all coding exons of SCN1A, we investigated 130 epileptic patients who did not show any SCN1A mutations by sequence analysis of all coding exons and exon,intron boundaries. Among 71 Dravet syndrome patients, we found two patients with heterozygous microdeletions removing the 5, noncoding exons and regions with promoter activity but not affecting the coding exons. We also identified four patients with deletions/duplication in the coding region. One patient with symptomatic focal epilepsy also showed a deletion in the coding region. This study provides the first case of microdeletion limited to the SCN1A 5, promoter region with the coding sequence preserved, and indicates the critical involvement of this upstream region in the molecular pathology of Dravet syndrome. Hum Mutat 31:,11, 2010. © 2010 Wiley-Liss, Inc. [source]

Purification, crystallization and data collection of the apoptotic nuclease endonuclease G

ACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 5 2009
Sei Mee Yoon
Endonuclease G (EndoG) is a mitochondrial enzyme that responds to apoptotic stimuli by translocating to the nucleus and cleaving chromosomal DNA. EndoG is the main apoptotic endonuclease in the caspase-independent pathway. Mouse EndoG without the mitochondrial localization signal (amino-acid residues 1,43) was successfully overexpressed, purified and crystallized using a microbatch method under oil. The initial crystal (type I) was grown in the presence of the detergent CTAB and diffracted to 2.8,Å resolution, with unit-cell parameters a = 72.20, b = 81.88, c = 88.66,Å, , = 97.59° in a monoclinic space group. The crystal contained two monomers in the asymmetric unit, with a predicted solvent content of 46.6%. Subsequent mutation of Cys110 improved the stability of the protein significantly and produced further crystals of types II, III and IV with space groups C2, P41212 (or P43212) and P212121, respectively, in various conditions. This suggests the critical involvement of this conserved cysteine residue in the crystallization process. [source]

Lack of critical involvement of endothelial nitric oxide synthase in vascular nitrate tolerance in mice

BRITISH JOURNAL OF PHARMACOLOGY, Issue 2 2002
Ellen Q Wang
We examined the direct involvement of endothelial nitric oxide (eNOS) in nitrate tolerance using eNOS knockout (eNOS (,/,)) and wild-type (eNOS (+/+)) mice. Animals were treated with either nitroglycerin (NTG, 20 mg kg,1s.c. 3×daily for 3 days) or vehicle (5% dextrose, D5W), and nitrate tolerance was assessed ex vivo in isolated aorta by vascular relaxation studies and cyclic GMP accumulation. Western blot was performed to determine NOS expression after NTG treatment. In both the eNOS (,/,) and (+/+) mice, the EC50 from NTG concentration-response curve was increased by ,3 fold, and vascular cyclic GMP accumulation was similarly decreased after NTG pretreatment. Vascular tolerance did not lead to changes in eNOS protein expression in eNOS (+/+) mice. These results indicate that vascular nitrate tolerance was similarly induced in eNOS (,/,) and (+/+) mice, suggesting that eNOS may not be critically involved in nitrate tolerance development in mice. British Journal of Pharmacology (2002) 135, 299,302; doi:10.1038/sj.bjp.0704532 [source]

IFN, induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein

CELLULAR MICROBIOLOGY, Issue 4 2007
Bastian Opitz
Summary Influenza A virus causes epidemics of respiratory diseases in humans leading to thousands of death annually. One of its major virulence factors, the non-structural protein 1 (NS1), exhibits interferon-antagonistic properties. While epithelial cells of the respiratory tract are the primary targets of influenza virus, the virus-sensing mechanisms in these cells eventually leading to IFN, production are incompletely understood. Here we show that infection of epithelial cells with NS1-deficient influenza A virus upregulated expression of two molecules that have been previously implicated in sensing of RNA viruses, the retinoic acid-inducible gene I (RIG-I) and the melanoma differentiation-associated gene 5 (MDA5). Gene silencing and overexpression experiments demonstrated that RIG-I, its adapter interferon-beta promoter stimulator 1 (IPS-1) and interferon-regulated factor 3 (IRF3) were involved in influenza A virus-mediated production of the antiviral IFN,. In addition, we showed that the NS1 protein is capable to inhibit the RIG-I-induced signalling, a mechanism which corresponded to the observation that only NS1-deficient but not the wild-type virus induced high-level production of IFN,. In conclusion, we demonstrated a critical involvement of RIG-I, IPS-1 and IRF3 in influenza A virus infection of epithelial cells. [source]

Audience Involvement and Entertainment,Education

COMMUNICATION THEORY, Issue 2 2002
Suruchi Sood
The present article explores the role that audience involvement plays in the effectiveness of entertainment,education programs. Utilizing data from a popular 104,episode entertainment,education radio soap opera from India, Tinka Tinka Sukh, it argues that the concept of audience involvement is multidimensional, and serves as a mediator for promoting behavior change. Audience involvement is characterized as being composed of two dimensions: (a) affective,referential involvement, and (b) cognitive,critical involvement. Involvement appears to be a precursor for increasing self,efficacy and collective efficacy, and in promoting interpersonal communication among individuals in the audience. [source]