ABSTRACT
Spinocerebellar ataxia type 2 (SCA2) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders, caused or modified by an unstable CAG-repeat expansion in the SCA2 gene, which encodes a polyglutamine (polyQ) domain expansion in ataxin-2 (ATXN2). ATXN2 is an RNA-binding protein and interacts with the poly(A)-binding protein PABPC1, localizing to ribosomes at the rough endoplasmic reticulum. Under cell stress, ATXN2, PABPC1 and small ribosomal subunits are relocated to stress granules, where mRNAs are protected from translation and from degradation. It is unknown whether ATXN2 associates preferentially with specific mRNAs or how it modulates RNA processing. Here, we investigated the RNA profile of the liver and cerebellum from Atxn2 knockout (Atxn2 (-/-)) mice at two adult ages, employing oligonucleotide microarrays. Prominent increases were observed for Lsm12/Paip1 (>2-fold), translation modulators known as protein interactor/competitor of ATXN2 and for Plin3/Mttp (>1.3-fold), known as apolipoprotein modulators in agreement with the hepatosteatosis phenotype of the Atxn2 (-/-) mice. Consistent modest upregulations were also observed for many factors in the ribosome and the translation/secretion apparatus. Quantitative reverse transcriptase PCR in liver tissue validated >1.2-fold upregulations for the ribosomal biogenesis modulator Nop10, the ribosomal components Rps10, Rps18, Rpl14, Rpl18, Gnb2l1, the translation initiation factors Eif2s2, Eif3s6, Eif4b, Pabpc1 and the rER translocase factors Srp14, Ssr1, Sec61b. Quantitative immunoblots substantiated the increased abundance of NOP10, RPS3, RPS6, RPS10, RPS18, GNB2L1 in SDS protein fractions, and of PABPC1. In mouse embryonal fibroblasts, ATXN2 absence also enhanced phosphorylation of the ribosomal protein S6 during growth stimulation, while impairing the rate of overall protein synthesis rates, suggesting a block between the enhanced translation drive and the impaired execution. Thus, the physiological role of ATXN2 subtly modifies the abundance of cellular translation factors as well as global translation.
Subject(s)
Ataxin-2/genetics , RNA/metabolism , Transcriptome , Animals , Cerebellum/metabolism , Gene Expression Profiling , Liver/metabolism , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Poly(A)-Binding Protein I/metabolism , Protein Biosynthesis , RNA, Messenger/metabolism , Transcription, GeneticABSTRACT
An analysis of the immediate postoperative period in 295 newborns after putting intestinal anastomoses was made. Postoperative surgical complications were found in 38 children who required 47 relaparotomies. Surgical tactics was determined for the complications of the postoperative period as well as the indications for relaparotomy.
Subject(s)
Intestines/surgery , Laparotomy , Anastomosis, Surgical , Humans , Infant, Newborn , Postoperative Complications/surgery , Reoperation , Time FactorsSubject(s)
Cysts/surgery , Omentum/surgery , Cysts/congenital , Humans , Infant , Male , Peritoneal Diseases/congenital , Peritoneal Diseases/surgeryABSTRACT
The analysis of clinical course of the immediate postoperative period in 295 newborns who had the intestinal anastomosis placed was carried out. In 31 (10.5%) child, a failure of the anastomotic sutures was revealed. A dependence of the clinical course of this complication on manifestations of peritonitis, concomitant diseases and degree of an organism maturity was determined. A difficulty to diagnose the anastomotic suture leakage is shown. The indications for operative and conservative treatment were established. Causes of the complication development were revealed.
Subject(s)
Intestinal Diseases/surgery , Anastomosis, Surgical/adverse effects , Humans , Infant, Newborn , Reoperation , Suture Techniques/adverse effectsABSTRACT
The genes coding for 20-kDa lymphotoxin (TNF-beta) and tumor necrosis factor (TNF-alpha) have been cloned from a rabbit genomic library. The two genes are tandemly arranged and separated by only 1 kb of DNA, as previously observed in human and mouse genomes. We have sequenced the entire rabbit lymphotoxin-encoding gene and inferred the primary structure of rabbit TNF-beta, whose cDNA is not yet cloned. We also analysed the upstream sequences of the rabbit TNF-beta and TNF-alpha genes and identified a number of potential binding sites for known nuclear transcription factors, and in particular several putative kappa B-type sequences.
Subject(s)
Lymphotoxin-alpha/genetics , Tumor Necrosis Factor-alpha/genetics , Amino Acid Sequence , Animals , Base Sequence , Binding Sites , Cloning, Molecular , Consensus Sequence , Gene Library , Genes , Humans , Molecular Sequence Data , Rabbits , Regulatory Sequences, Nucleic Acid , Restriction Mapping , Sequence Alignment , Transcription Factors/metabolismSubject(s)
Chromosomes, Human , Cloning, Molecular/methods , Genes/genetics , Genetic Code , Receptors, Cell Surface/genetics , Tumor Necrosis Factor-alpha/genetics , Base Sequence , DNA, Recombinant/genetics , Humans , Molecular Sequence Data , Oligonucleotides/genetics , Receptors, Tumor Necrosis Factor , Restriction MappingABSTRACT
Genes, coding for tumor necrosis factor (TNF-alpha) and lymphotoxin (TNF-beta), have been cloned from the rabbit genomic library. The two genes are tandemly arranged and separated only by 1 kb of DNA as previously observed in human and mouse genomes. We have sequenced the entire rabbit lymphotoxin gene (LT) and calculated the amino acid sequence of the rabbit LT whose cDNA is not yet cloned. We also analyzed the upstream sequences of this gene and revealed a number of recognition sites for the known transcriptional factors. The rabbit TNF gene comprised in the cloned genomic region has been sequenced earlier.
Subject(s)
Cloning, Molecular , Lymphotoxin-alpha/genetics , Tumor Necrosis Factor-alpha/genetics , Amino Acid Sequence , Animals , Base Sequence , DNA/genetics , Genetic Linkage , Molecular Sequence Data , Rabbits , Restriction Mapping , Sequence Homology, Nucleic AcidSubject(s)
Postoperative Complications/surgery , Shoulder Dislocation/surgery , Adult , Female , Humans , Joint Instability/etiology , Joint Instability/physiopathology , Joint Instability/surgery , Male , Methods , Postoperative Complications/etiology , Postoperative Complications/physiopathology , Recurrence , Reoperation , Shoulder Dislocation/etiology , Shoulder Dislocation/physiopathology , Shoulder Joint/physiopathology , Shoulder Joint/surgery , Systems AnalysisSubject(s)
Joint Instability/surgery , Postoperative Complications/surgery , Shoulder Dislocation/surgery , Shoulder Joint/surgery , Adult , Female , Humans , Joint Instability/classification , Joint Instability/complications , Male , Postoperative Complications/etiology , Recurrence , Shoulder Dislocation/etiologySubject(s)
Cytotoxins/genetics , Genes , Glycoproteins/genetics , Animals , Base Sequence , Cell Survival/drug effects , Cloning, Molecular , Escherichia coli/genetics , Glycoproteins/isolation & purification , Glycoproteins/pharmacology , Humans , L Cells/drug effects , Mice , Recombinant Proteins/isolation & purification , Transcription, Genetic , Tumor Necrosis Factor-alphaSubject(s)
Dental Alloys/pharmacology , Denture, Partial , Holography/methods , Interferometry/methods , Dental Abutments , Elasticity , Humans , Lasers , Stress, MechanicalABSTRACT
The analysis of immediate results of 271 correcting operations for congenital hydronephrosis in children has shown that the operations may be followed by such complications at the early postoperative period as aggravation of pyelonephritis (10 patients), urinal fistulas (8 patients), urinary leakage (4 patients), paraureteral abscesses (3 cases) as well as postoperative bleedings (5 cases) and suppuration of the operative wound (4 cases). The exact performance of plastic operations according to the elaborated method, strict observation of indications and contraindications, complex therapy in the postoperative period were found to reduce the amount of complications.
