ABSTRACT
The new allele DRB1*13:99 showed one nucleotide difference with DRB1*13:02:01 at codon 51 (ACG/AAG).
Subject(s)
Alleles , Codon/genetics , HLA-DR Antigens , HLA-DRB1 Chains , HumansABSTRACT
The new allele DQB1*05:06 showed one nucleotide difference with DQB1*05:03:01 at codon 40 (TTC/TTG).
Subject(s)
Alleles , Codon/genetics , HLA-DQ Antigens/genetics , Asian People , HLA-DQ beta-Chains , Humans , KoreaABSTRACT
The new allele C*03:93 showed one nucleotide difference with C*03:04:01 at codon 140 (GCT/ACT).
Subject(s)
HLA-C Antigens/genetics , Sequence Analysis, DNA/methods , Alleles , Child, Preschool , Cloning, Molecular , HLA-C Antigens/chemistry , Histocompatibility Testing/methods , Humans , Models, Molecular , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Republic of KoreaABSTRACT
New allele A*31:34 showed one nucleotide difference with A*31:01:02 at codon 166 (GAG/CAG).
Subject(s)
Alleles , HLA-A Antigens/genetics , Histocompatibility Testing , Genotype , Humans , Sequence Analysis, DNAABSTRACT
The DRB1*11:95 showed a single nucleotide difference with the DRB1*11:01:01 allele at codon 10 (TAC/TGC).
Subject(s)
Genetic Variation/genetics , HLA-DR Antigens/genetics , HLA-DR Antigens/metabolism , Base Sequence , HLA-DR Antigens/chemistry , HLA-DRB1 Chains , Humans , Molecular Sequence Data , Peptide Fragments/metabolism , Polymerase Chain Reaction , Sequence Homology, Nucleic AcidABSTRACT
The new allele B*39:60 showed one nucleotide difference with B*39:01:01 at codon 152 (GTG/GCG).
Subject(s)
Genetic Variation/genetics , HLA-B Antigens/genetics , Humans , Polymerase Chain ReactionABSTRACT
BACKGROUND: Despite advances in in vitro manipulation of preimplantation embryos, there is still a reduction in the quality of embryos produced leading to lower pregnancy rates compared with embryos produced in vivo. We hypothesized that a dynamic microfunnel embryo culture system would enhance outcomes by better mimicking the fluid-mechanical and biochemical stimulation embryos experience in vivo from ciliary currents and oviductal contractions. METHODS AND RESULTS: Mouse embryos were cultured in microdrop-static control, microfunnel-static control or microfunnel-dynamic conditions with microfluidics. All groups tested had greater than 90% total blastocyst development from zygotes after 96 h culture. Blastocyst developmental stage was significantly enhanced (P < 0.01) under dynamic microfunnel culture conditions as evidenced by an increased percentage of hatching or hatched blastocysts (Microdrop-control 31%; Microfunnel-control 23%; Microfunnel-pulsatile 71%) and significantly higher (P < 0.01) average number of cells per blastocyst (Microdrop-control 67 +/- 3; Microfunnel-control 60 +/- 3; Microfunnel-pulsatile 109 +/- 5). Blastocyst cell numbers in dynamic microfunnel cultures (109 +/- 5) more closely matched numbers obtained from in vivo grown blastocysts (144 +/- 9). Importantly, dynamic microfunnel culture significantly improved embryo implantation and ongoing pregnancy rates over static culture to levels approaching that of in utero derived preimplantation embryos. CONCLUSIONS: The improved pregnancy outcomes along with the simple and user-friendly design of the microfluidic/microfunnel system has potential to alleviate many inefficiencies in embryo production for biomedical research, genetic gain in domestic species and assisted reproductive technologies in humans.
Subject(s)
Embryo Culture Techniques/veterinary , Embryonic Development/physiology , Microfluidics , Animals , Female , Mice , Pregnancy , Pregnancy RateABSTRACT
Most of the p53 target genes, all except MDM2, COP1 and PIRH2, perform functions in apoptosis, differentiation and cell cycle arrest. The aforementioned oncogenes downregulate p53 through a negative feedback mechanism, and thus contribute to tumor development. In this study, we report a new p53 target, PRL-1, which is believed to be a significant regulator in the development and metastasis of a variety of cancer types. Phosphatase of regenerating liver 1 (PRL-1) overexpression reduced the levels of endogenous and exogenous p53 proteins, and inhibited p53-mediated apoptosis. On the other hand, the ablation of PRL-1 by small interfering RNA (siRNA) increased p53 protein levels. The p53 downregulation was mediated by p53 ubiquitination and subsequent proteasomal degradation. Furthermore, p53 ubiquitination by PRL-1 was achieved through two independent pathways, by inducing PIRH2 transcription and by inducing MDM2 phosphorylation through Akt signaling. In addition, we showed that the PRL-1 gene harbors a p53 response element in the first intron, and its transcription is regulated by the p53 protein. These findings imply that the new oncogenic p53 target, PRL-1, may contribute to tumor development by the downregulation of p53 by a negative feedback mechanism.
Subject(s)
Cell Cycle Proteins/metabolism , Introns , Membrane Proteins/metabolism , Protein Tyrosine Phosphatases/metabolism , Response Elements , Transcription, Genetic , Tumor Suppressor Protein p53/metabolism , Apoptosis/genetics , Cell Cycle Proteins/genetics , Cell Line, Tumor , Humans , Membrane Proteins/genetics , Protein Tyrosine Phosphatases/genetics , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-mdm2/genetics , Proto-Oncogene Proteins c-mdm2/metabolism , Tumor Suppressor Protein p53/genetics , Ubiquitin-Protein Ligases/genetics , Ubiquitin-Protein Ligases/metabolismABSTRACT
New allele B*4617 showed one nucleotide difference with B*460101 at codon 167 (TGG-->TCG).
Subject(s)
HLA-B Antigens/genetics , Alleles , Exons/genetics , Genotype , HLA-B Antigens/chemistry , Humans , Protein ConformationSubject(s)
Alleles , HLA-B Antigens/genetics , Histocompatibility Testing , Sequence Analysis, DNA , Base Pairing , Base Sequence , Carcinoma, Hepatocellular/genetics , Codon , Exons , Genetic Variation , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Leucine/chemistry , Liver Neoplasms/genetics , Models, Molecular , Tyrosine/chemistrySubject(s)
Alleles , HLA-B Antigens/chemistry , HLA-B Antigens/genetics , Amino Acid Motifs , Amino Acid Sequence , Amino Acid Substitution , Aspartic Acid/metabolism , Base Sequence , Exons , Fetal Blood/immunology , HLA-B Antigens/isolation & purification , Histocompatibility Testing , Humans , Infant, Newborn , Korea/epidemiology , Molecular Sequence Data , Protein Structure, Secondary , Serine/metabolismSubject(s)
Genetic Variation , HLA-DR Antigens/chemistry , HLA-DR Antigens/genetics , Amino Acid Sequence , Amino Acid Substitution , Base Sequence , Codon , Exons , Fetal Blood/immunology , HLA-DR Antigens/isolation & purification , Humans , Infant, Newborn , Korea/epidemiology , Molecular Sequence Data , Nucleic Acid Amplification Techniques , Sequence Homology, Amino Acid , Sequence Homology, Nucleic Acid , Tyrosine/metabolismSubject(s)
Alleles , HLA-B Antigens/genetics , Base Sequence , China , Genetic Variation , Humans , Korea , Molecular Sequence Data , Polymorphism, Single Nucleotide , Sequence HomologySubject(s)
Alleles , HLA-B Antigens/chemistry , HLA-B Antigens/genetics , Peptide Fragments/metabolism , Sequence Analysis, DNA , Tryptophan/metabolism , Amino Acid Substitution , Binding Sites , HLA-B Antigens/metabolism , Hematopoietic Stem Cell Transplantation , Histocompatibility Testing , Humans , Hydrogen Bonding , Korea , Models, Molecular , Polymerase Chain Reaction , Protein Binding , Tryptophan/chemistry , Tryptophan/genetics , Water/chemistryABSTRACT
In this report, we describe the identification of an human leucocyte antigen-Cw*06 (HLA-Cw*06) nucleotide sequence variant, a new HLA-Cw*0612. The new allele was detected during routine HLA typing by high-resolution sequence-based typing. Allele Cw*0612 showed one nucleotide difference with Cw*0602 at codon 153 (GCG-->ACG) resulting in an amino acid change from alanine to threonine.
Subject(s)
Alleles , Amino Acid Substitution/genetics , HLA-C Antigens/genetics , Point Mutation/genetics , Amino Acid Substitution/immunology , Base Sequence , HLA-C Antigens/chemistry , HLA-C Antigens/immunology , Humans , Molecular Sequence Data , Point Mutation/immunology , Protein Structure, Tertiary/geneticsABSTRACT
In this report, we describe the identification of a human leucocyte antigen-A*11 (HLA-A*11) nucleotide sequence variant, a new HLA-A*1120 by using sequence-based typing (SBT). The new allele was detected during routine HLA typing by high-resolution SBT. Allele A*1120 showed one nucleotide difference with A*110101 at codon 152 (GCG-->GAG) resulting in an amino acid change from alanine to glutamate. Residue 152 is located on alpha(2)-helix of HLA class I molecule and involved in peptide binding by constructing E pocket of peptide-binding groove, implying that the change of the residue 152 would affect the binding affinity of peptides to A*1120 allele.
Subject(s)
Alleles , Base Sequence , HLA-A Antigens/genetics , HLA-A Antigens/immunology , Asian People/genetics , Exons , Histocompatibility Testing/methods , Humans , Korea/ethnology , Models, Biological , Molecular Sequence Data , Polymorphism, Single Nucleotide , Protein Binding , Sequence AlignmentABSTRACT
Phosphodiesterases (PDEs) are essential regulators of cyclic nucleotide signaling with diverse physiological functions. Because of their great market potential and therapeutic importance, PDE inhibitors became recognized as important therapeutic agents in the treatment of various diseases. Currently, there are seven PDE inhibitors on the market, and the pharmacological and safety evaluations of many drug candidates are in progress. Three-dimensional (3D) structures of catalytic domains of PDE 1, -3, -4, -5 and -9 in the presence of their inhibitors are now available, and can be utilized for rational drug design. Recent advances in molecular pharmacology of PDE isoenzymes resulted in identification of new potential applications of PDE inhibitors in various therapeutic areas, including dementia, depression and schizophrenia. This review will describe the latest advances in PDE research on 3D structural studies, the potential of therapeutic applications and the development of drug candidates.
