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1.
2.
The bias favoring deletion over inversion in DH-JH rearrangement has been
known for years, but the underlying mechanism has yet to be fully defined.
It has been suggested that the ratio of deletion/inversion is determined by
the combined effect of two factors: (i) the relative strengths of 5' and 3'
recombination signal sequences (RSS) of a DH segment, and (ii) the
efficiency with which the deletional product (one joint) forms relative to
the inversional product (two joints). In this study, we analyzed for the
first time the effect of factor 1 alone on the biased 3' RSS utilization in
DH-JH joining by using deletional plasmids in an extrachromosomal substrate
V(D)J recombination assay. It was found that the 3' RSS and associated
coding end (12 bp) mediate recombination more efficiently than the 5'
RSS/coding end DH-JH plasmids. These results demonstrate that the effect of
the RSS/coding end alone can account, at least partially, for the
predominant deletion in DH-JH recombination. The potential effect of the
relative strength of RSS and associated coding end on the ordered
rearrangement of DH-JH followed by VH to DH-JH was also assessed. When
recombination frequencies of D-->J (3' DH to J3) were compared with
frequencies of V-- >D (VHPJ14 to 3' DH or VHOX2 to 3' DH), it was found
that V-->D joining was, if anything, more efficient than D-->J
joining. Therefore, if all three segments were accessible, RSS/coding end
effects would not contribute to the ordered rearrangement of the IgH locus.
相似文献
3.
Yang PY Almofti MR Lu L Kang H Zhang J Li TJ Rui YC Sun LN Chen WS 《第二军医大学学报》2006,27(6):637-637
Polygonum multiflorum stilbeneglycoside (PMS) is a water-soluble fraction of Polygonum multiflorum Thunb. , one of the most famous tonic traditional Chinese medicines, that has protective effects on the cardiovascular system. The purpose of the present study is to elucidate the effects of PMS on macrophage-derived foam cell functions and the reduction of severity of atherosclerosis in hypercholesterolemic New Zealand White (NZW) rabbits. NZW rabbits were fed for 12 weeks with a normal diet, a high cholesterol diet, or a high cholesterol diet associated with irrigation with different doses of PMS (25, 50, or 100 mg/kg). Treatment of NZW rabbits fed with high cholesterol diet with 100 mg/kg PMS attenuated the increase in plasma cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, and plasma triglyceride. Treatment with 50 and 100 mg/kg PMS caused 43% and 60% decrease in atherosclerotic lesioned area ratio to total surface area, respectively. In U937 foam cells, PMS could decrease the high expression of intercellular adhesion molecule (ICAM)-1 protein and the vascular endothelial growth factor (VEGF) protein levels in the medium induced by oxidized lipoprotein when analyzed by flow cytometry. The results proved that PMS is a powerful agent against atherosclerosis and that PMS action could possibly be through the inhibition of the expression of ICAM-1 and VEGF in foam cells. 相似文献
4.
ObjectiveThis meta-evaluation aimed to summarize all available evidence regarding different fissure sealants on occlusal caries prevention, arrest, retention rate, adverse effect, and cost-effectiveness; when compared with no intervention, other preventive or minimally-invasive procedures.Materials and MethodsThe systematic reviews and meta-analyses were identified via four electronic databases and manual searching. Two independent reviewers performed study selection, data extraction, quality assessment with AMSTAR-2.ResultsAmong the 366 records yielded, 38 systematic reviews were identified as eligible 24 of them included meta-analyses. Moderate evidence has supported the efficacies of resin-based sealants (RBS) in occlusal caries prevention, arrest and cost-effectiveness compared to no interventions. Low to very low certainty of evidence suggested similar effectiveness of glass-ionomer cements in caries prevention with RBS and more superior performance of resin infiltration in arresting non-cavitated occlusal lesions.ConclusionThis meta-evaluation supports the use of RBS on permanent molars to reduce occlusal caries occurrence, arrest lesion progression and alleviate oral health inequalities between individuals of different socioeconomic status. This meta-evaluation also advocates further research on glass-ionomer cements and resin infiltration with respect to their efficacies in caries prevention and arrest. 相似文献
5.
6.
A Homozygous PDE6D Mutation in Joubert Syndrome Impairs Targeting of Farnesylated INPP5E Protein to the Primary Cilium
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Sophie Thomas Kevin J. Wright Stéphanie Le Corre Alessia Micalizzi Marta Romani Avinash Abhyankar Julien Saada Isabelle Perrault Jeanne Amiel Julie Litzler Emilie Filhol Nadia Elkhartoufi Mandy Kwong Jean‐Laurent Casanova Nathalie Boddaert Wolfgang Baehr Stanislas Lyonnet Arnold Munnich Lydie Burglen Nicolas Chassaing Ferechté Encha‐Ravazi Michel Vekemans Joseph G. Gleeson Enza Maria Valente Peter K. Jackson Iain A. Drummond Sophie Saunier Tania Attié‐Bitach 《Human mutation》2014,35(1):137-146
Joubert syndrome (JS) is characterized by a distinctive cerebellar structural defect, namely the « molar tooth sign ». JS is genetically heterogeneous, involving 20 genes identified to date, which are all required for cilia biogenesis and/or function. In a consanguineous family with JS associated with optic nerve coloboma, kidney hypoplasia, and polydactyly, combined exome sequencing and mapping identified a homozygous splice‐site mutation in PDE6D, encoding a prenyl‐binding protein. We found that pde6d depletion in zebrafish leads to renal and retinal developmental anomalies and wild‐type but not mutant PDE6D is able to rescue this phenotype. Proteomic analysis identified INPP5E, whose mutations also lead to JS or mental retardation, obesity, congenital retinal dystrophy, and micropenis syndromes, as novel prenyl‐dependent cargo of PDE6D. Mutant PDE6D shows reduced binding to INPP5E, which fails to localize to primary cilia in patient fibroblasts and tissues. Furthermore, mutant PDE6D is unable to bind to GTP‐bound ARL3, which acts as a cargo‐release factor for PDE6D‐bound INPP5E. Altogether, these results indicate that PDE6D is required for INPP5E ciliary targeting and suggest a broader role for PDE6D in targeting other prenylated proteins to the cilia. This study identifies PDE6D as a novel JS disease gene and provides the first evidence of prenyl‐binding‐dependent trafficking in ciliopathies. 相似文献
7.
F. Bouchart A. Tabley P. Y. Litzler C. Haas-Hubscher J. P. Bessou R. Soyer 《European journal of cardio-thoracic surgery》2001,20(6):1157-1162
Objectives: The present study evaluates our experience with coronary bypass grafting in patients with EF ≤25%. Myocardial revascularization in this setting remains controversial because of concerns over operative mortality and morbidity and lack of functional and survival benefit. Materials and methods: One hundred and forty-one patients with coronary artery disease and left ventricular ejection fraction ≤25% underwent coronary artery bypass graft between January 1988 and December 1998. Mean age at operation was 63.3 years and 81.4% were male. The major indication for surgery was angina (114 patients, 80.8%). Ejection fraction (EF), left ventricular end diastolic pressure (LVEDP) and cardiac index (CI) were used to assess left ventricular function. The number of graft was 2.7±1.6/patient. Internal mammary artery was used in 119 patients (84.3%). Intra aortic balloon pump was placed preoperatively in 25 patients (17.7%). Five operative risk factors were associated with a higher mortality: emergency, female sex, LVEDP, CI and NYHA class IV. Results: The operative mortality was 7% (10 patients). Left ventricular ejection fraction (assessed post operatively in 83 patients) improved from 22.2% preoperatively to 33.5% post operatively (P<0.001), mean end diastolic volume index fell from 98 to 83 ml/m2 following surgery. Survival at 2, 5 and 7 years was respectively 84±3%, 70±4% and 50±5%. Two variables were associated with increased long term survival: congestive heart failure (NYHA class lower than IV (P=0.035) and cardiomegaly (P=0.04) Conclusion: In patients with left ventricular dysfunction, myocardial revascularization can be performed relatively safely with good medium term survival and improvement in quality of life and in left ventricular function. Coronary artery bypass graft may be offered to patients with impaired ventricular function, but careful patient selection and management when considering these patients for operation should assess potentially reversible dysfunction. 相似文献
8.
Daniel TP Fong Mak-Ham Lam Miko LM Lao Chad WN Chan Patrick SH Yung Kwai-Yau Fung Pauline PY Lui Kai-Ming Chan 《Journal of orthopaedic surgery and research》2008,3(1):7
Background
Excessive pronation (or eversion) at ankle joint in heel-toe running correlated with lower extremity overuse injuries. Orthotics and inserts are often prescribed to limit the pronation range to tackle the problem. Previous studies revealed that the effect is product-specific. This study investigated the effect of medial arch-heel support in inserts on reducing ankle eversion in standing, walking and running. 相似文献9.
10.
Maggie KM Ma Helen KW Law Kin Sun Tse Kwok Wah Chan Gary CW Chan Desmond YH Yap Maggie MY Mok Lorraine PY Kwan Sydney CW Tang Bo Ying Choy Tak Mao Chan 《International journal of urology》2018,25(5):450-455