ABSTRACT
Adenine nucleotide translocases (ANTs) transport ADP and ATP through mitochondrial inner membrane, thus playing an essential role for energy metabolism of eukaryotic cells. Mice have three ANT paralogs, Ant1 (Slc25a4), Ant2 (Slc25a5) and Ant4 (Slc25a31), which are expressed in a tissue-dependent manner. While knockout mice have been characterized with Ant1 and Ant4 genes, which resulted in exercise intolerance and male infertility, respectively, the role of the ubiquitously expressed Ant2 gene in animal development has not been fully demonstrated. Here, we generated Ant2 hypomorphic mice by targeted disruption of the gene, in which Ant2 expression is largely depleted. The mice showed apparently normal embryonic development except pale phenotype along with a reduced birth rate. However, postnatal growth was severely retarded with macrocytic anemia, B lymphocytopenia, lactic acidosis and bloated stomach, and died within 4 weeks. Ant2 depletion caused anemia in a cell-autonomous manner by maturation arrest of erythroid precursors with increased reactive oxygen species and premature deaths. B-lymphocyte development was similarly affected by Ant2 depletion, and splenocytes showed a reduction in maximal respiration capacity and cellular ATP levels as well as an increase in cell death accompanying mitochondrial permeability transition pore opening. In contrast, myeloid, megakaryocyte and T-lymphocyte lineages remained apparently intact. Erythroid and B-cell development may be particularly vulnerable to Ant2 depletion-mediated mitochondrial dysfunction and oxidative stress.
Subject(s)
Adenine Nucleotide Translocator 2/deficiency , B-Lymphocytes/cytology , Erythrocytes/cytology , Erythropoiesis/physiology , Lymphopoiesis/physiology , Mitochondrial ADP, ATP Translocases/metabolism , Adenine Nucleotide Translocator 2/genetics , Adenine Nucleotide Translocator 2/metabolism , Adenosine Triphosphate/metabolism , Anemia/genetics , Anemia/metabolism , Animals , B-Lymphocytes/metabolism , Erythrocytes/metabolism , Erythropoiesis/genetics , Female , Gene Knockout Techniques , Growth Disorders/genetics , Growth Disorders/metabolism , Humans , Lymphopoiesis/genetics , Male , Mice , Mice, Inbred C57BL , Mice, Knockout , Mitochondria/genetics , Mitochondria/metabolismABSTRACT
Grafting from polymerization was used to synthesize nano-titania/polyurethane (nTiO(2)/polyurethane) composite coatings, where nTiO(2) was chemically attached to the backbone of the polyurethane polymer matrix with a bifunctional monomer, 2,2-bis(hydroxymethyl) propionic acid (DMPA). This bifunctional monomer can coordinate to nTiO(2) through an available -COOH group, with two available hydroxyl groups that can react with diisocyanate terminated pre-polyurethane through step-growth polymerization. The coordination reaction was monitored by FTIR and TGA, with the coordination reaction found to follow first order kinetics. After step-growth polymerization, the polyurethane nanocomposites were found to be stable on standing with excellent distribution of Ti in the polymer matrix without any significant agglomeration compared to simple physical mixtures of nTiO(2) in the polyurethane coatings. The functionalized nTiO(2)-polyurethane composite coatings showed excellent antibacterial activity against gram-negative bacteria Escherichia coli; 99% of E. coli were killed within less than one hour under solar irradiation. Self-cleaning was also demonstrated using stearic acid as a model for 'dirt'.
Subject(s)
Anti-Bacterial Agents/pharmacology , Coated Materials, Biocompatible/pharmacology , Nanocomposites/chemistry , Polyurethanes/chemistry , Titanium/chemistry , Emulsions , Escherichia coli/drug effects , Hydroxy Acids/chemistry , Kinetics , Microbial Sensitivity Tests , Nanocomposites/ultrastructure , Propionates/chemistry , Spectrometry, X-Ray Emission , Spectroscopy, Fourier Transform Infrared , Stearic Acids/chemistry , ThermogravimetryABSTRACT
The major histocompatibility complex (MHC) is located on human Chromosome 6 and includes clusters of class I, class II, and class III genes. Centromeric to the class I region is a cluster of genes designated as MHC class IV encoding genes involved in immunity and inflammation, including the 1C7 gene. The human 1C7 gene has several alternatively spliced forms and potentially codes for proteins with at least three unique carboxy termini. 1C7 mRNA in human (h1C7) is present in spleen, tonsil, B and NK cell lines, and with a different splicing pattern in liver. The 1C7 RNA and protein are present at highest levels in the germinal center of the lymphoid follicles in tonsil. The protein is expressed in NKL cells, tonsil, and unexpectedly in brain. In contrast, the mouse 1C7 gene is transcribed in liver but is predicted to be a pseudogene. However, the 1C7 homologue expressed in rat is predicted to have long stretches of amino acids essentially identical to the human protein.
Subject(s)
Killer Cells, Natural/immunology , Major Histocompatibility Complex , Receptors, Immunologic/genetics , Amino Acid Sequence , Animals , Base Sequence , Blotting, Northern/methods , COS Cells , Cell Line , DNA, Complementary , Gene Expression , Humans , In Situ Hybridization/methods , Liver/metabolism , Liver/pathology , Mice , Molecular Sequence Data , Natural Cytotoxicity Triggering Receptor 3 , Palatine Tonsil/metabolism , Palatine Tonsil/pathology , RNA, Messenger , Rats , Reverse Transcriptase Polymerase Chain Reaction/methods , Staining and Labeling/methods , TransfectionABSTRACT
Malignant mixed mesodermal tumours of the ovary have been described together with a literature review. The characteristic histological pictures of the various representative tissue elements have been demonstrated and patients characteristics analysed in detail. This confirms the classical features of this group of advanced ovarian malignancy that highlight the aggressive nature of the tumour associated with poor survival. Although generally they are managed in the same line as epithelial ovarian carcinomas the appropriate treatment has yet to be established. Because of their rarity they also illustrate the potential problems of instituting prospective randomised controlled trials.
