ABSTRACT
Characterization of the novel HLA B*18:79 allele is described.
Subject(s)
Alleles , HLA-B Antigens/genetics , Exons , Humans , Molecular Sequence DataABSTRACT
Characterization of the novel HLA alleles B*35:11:03, B*42:01:03, and B*51:01:35 is described.
Subject(s)
HLA Antigens/genetics , Alleles , Base Sequence , HLA-B Antigens/genetics , HLA-B35 Antigen/genetics , HLA-B51 Antigen/genetics , Humans , Molecular Sequence Data , Polymorphism, Single NucleotideABSTRACT
A*03:132 differs from A*03:01:01:01 at nucleotide 853 (codon 261) in exon 4.
Subject(s)
Alleles , Codon/genetics , Exons/genetics , HLA-A3 Antigen/genetics , HumansABSTRACT
Characterization of the novel HLA alleles A*02:330, A*11:108, B*40:175, and B*40:176 is described.
Subject(s)
Alleles , HLA-A Antigens/genetics , Base Sequence , HLA-B40 Antigen/genetics , Haplotypes , Humans , Molecular Sequence Data , Sequence AlignmentABSTRACT
B*15:228 differs from B*15:01:01:01 at three nucleotides in exon 4.
Subject(s)
Alleles , Exons/genetics , HLA-B Antigens/genetics , Humans , Nucleotides/geneticsABSTRACT
STUDY DESIGN: Cell transplantation strategies are gaining increasing interest for spinal cord injury (SCI) with the objective of promoting spinal cord repair. To avoid allogenic graft rejection, an adequate immune suppression is required, and one of the most potent and commonly used immunosuppressives is cyclosporin A (CsA). In SCI, permanent sensory motor loss is combined with modifications of drug absorption, distribution and elimination. OBJECTIVES: The objectives of this study were to thoroughly explore histological and functional outcomes of CsA treatment in a rat model of spinal cord compression. SETTING: Experiments were carried out at the Institute for Neurosciences of Montpellier (France), the Integrative Biology of Neurodegeneration Laboratory (Spain) and in the Novartis Institutes for BioMedical Research (Switzerland) for CsA blood concentration determination. METHODS: We first evaluated histological outcomes of CsA treatment on kidneys and spinal cord after SCI. We then investigated whether SCI modified CsA blood concentration. Finally, using behavioral analysis, we assessed the potential CsA impact on functional recovery. RESULTS: When spinal-cord-injured rats were treated with a CsA dose of 10 mg kg(-1) per day, we observed deleterious effects on kidneys, associated with modifications of CsA blood concentration. Adding an antibiotic treatment reduced kidney alteration without modifying CsA blood concentration. Finally, we showed that CsA treatment per se modified neither functional recovery nor lesion extension. CONCLUSION: This study pinpoints the absolute requirement of careful CsA monitoring in the clinical setting for patients with SCI to minimize potential unexpected effects and avoid therapeutic failure.
Subject(s)
Cell Transplantation/methods , Cyclosporine/toxicity , Graft Rejection/drug therapy , Kidney Diseases/physiopathology , Spinal Cord Injuries/physiopathology , Animals , Cell Transplantation/adverse effects , Cyclosporine/blood , Cyclosporine/therapeutic use , Disease Models, Animal , Drug Therapy, Combination/methods , Graft Rejection/physiopathology , Graft Rejection/prevention & control , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/toxicity , Kidney Diseases/chemically induced , Male , Rats , Rats, Wistar , Spinal Cord Injuries/surgery , Treatment OutcomeABSTRACT
Cw*0774 differs from Cw*070201 by one nucleotide within the coding sequence of exons 2-4. DQB1*060105 differs from DQB1*060101 by one nucleotide within the coding sequence of exons 2-3.
Subject(s)
Alleles , HLA-C Antigens/genetics , HLA-DQ Antigens/genetics , Hispanic or Latino , Amino Acid Substitution , Asparagine , Base Sequence , Exons , Fetal Blood , HLA-DQ beta-Chains , Humans , Molecular Sequence DataABSTRACT
A sample of 492 full heritage, unrelated residents of the Gila River Indian Community (GRIC) of Arizona were characterized for their high-resolution DNA alleles at the HLA-A, B, C, DRB1, DQA1, and DQB1 loci. Only five allelic categories are found at HLA-A, 10 at HLA-B, 8 at HLA-C and HLA-DR, and 4 at DQA1 and DQB1. There is little evidence for population structure at the 6 loci. Two 'private' alleles, B*5102 and B*4005, which are found nearly exclusively in American Indian populations in the desert southwest and northern Mexico, are likely new mutations after the first inhabitation of the area, the evolution of which are reflected in the contemporary distribution of their respective haplotypes. DRB1*1402 has the highest reported frequency of any specificity at the DRB1 locus, 0.7461, and serves as a sensitive probe for locating related east Asian populations. The haplotypes in this population also exhibit a highly restricted distribution and strong genetic disequilibria, which has important implications for matching solid organ and bone marrow allografts. It is shown that, when one considers HLA-A-B-DRB1 homozygotes as allograft donors for all full heritage members of the GRIC, 50% of the community would find a non-mismatched organ within the homozygotes for the six most common haplotypes. This raises questions about transplantation policy and whether, in the presence of high-frequency private alleles and a restricted number of haplotypes, the full heritage American Indian community of the desert southwest should act as its own pool of donors for its affected members.
Subject(s)
Alleles , Evolution, Molecular , Haplotypes , Indians, North American/genetics , Arizona , Genetic Loci , Genetic Variation , HLA Antigens/genetics , HLA-B Antigens/genetics , HLA-C Antigens/genetics , HLA-DQ Antigens/genetics , HLA-DQ alpha-Chains , HLA-DQ beta-Chains , HLA-DR Antigens/genetics , HLA-DRB1 Chains , HumansABSTRACT
This report describes the discovery and characterization of the human leukocyte antigen-B*4466 allele.
Subject(s)
Blood Donors , HLA-B Antigens/genetics , Hematopoietic Stem Cell Transplantation , Sequence Analysis, DNA , Adult , Alleles , Base Sequence , HLA-B Antigens/blood , Humans , Male , Molecular Sequence Data , Polymerase Chain Reaction , Sequence Homology, Nucleic AcidABSTRACT
This report describes the discovery and characterization of the HLA-Cw*0817 allele.
Subject(s)
Amino Acid Substitution/genetics , HLA-C Antigens/genetics , Alleles , Base Sequence , Exons/genetics , Humans , Molecular Sequence Data , Sequence AlignmentABSTRACT
This report describes the discovery and characterization of the novel Cw*0346 allele.
Subject(s)
Alleles , Gene Deletion , HLA-C Antigens/genetics , Base Sequence , Humans , Korea , Molecular Sequence Data , Polymerase Chain Reaction , Sequence Alignment , Tissue DonorsABSTRACT
This report describes the discovery and characterization of the HLA-Cw*0517 allele.
Subject(s)
HLA-C Antigens/genetics , Alleles , Amino Acid Sequence , Amino Acid Substitution , Base Sequence , Humans , Molecular Sequence Data , Sequence AlignmentABSTRACT
Discovery of the novel HLA-B*5149 allele in a North American Caucasian individual is described. It differs from B*510101 by one nucleotide within the coding sequence of exons 1-6. A substitution at nucleotide position 488 in exon 3 changes alanine to glycine in amino acid position 139.
Subject(s)
Alleles , HLA-B Antigens/genetics , Base Sequence , HLA-B51 Antigen , Humans , Molecular Sequence Data , Sequence Analysis, DNAABSTRACT
Discovery of the novel DRB1*0464 allele is described. This allele contains a nucleotide substitution in codon 13 that changes the amino acid histidine coded for in all other DRB1*04 alleles to tyrosine. This allele was found in a parent and one child of a North American Caucasian family with the haplotype: A*03, B*07, DRB1*0464, DRB4*0103, DQB1*0301.
Subject(s)
Alleles , HLA-DR Antigens/genetics , Amino Acid Substitution , Base Sequence , Child , Codon , DNA Primers , Exons , HLA-DRB1 Chains , Haplotypes , Histocompatibility Testing , Humans , Kidney Transplantation , Middle Aged , Molecular Sequence Data , North America , Sequence Analysis, DNA , Tyrosine/metabolism , White People/geneticsABSTRACT
Motivated by recent experiments, we study the optical conductivity of DNA in its natural environment containing water molecules and counterions. Our density functional theory calculations (using Siesta) for four base pair B-DNA with order 250 surrounding water molecules suggest a thermally activated doping of the DNA by water states which generically leads to an electronic contribution to low-frequency absorption. The main contributions to the doping result from water near DNA ends, breaks, or nicks and are thus potentially associated with temporal or structural defects in the DNA.
Subject(s)
Biophysics/methods , DNA/chemistry , Absorption , Base Pairing , Electrons , Models, Statistical , Nucleic Acid Conformation , Oligonucleotides/chemistry , Water/chemistryABSTRACT
We present a model intended for rapid sampling of ground and excited state potential energy surfaces for first-row transition metal active sites. The method is computationally inexpensive and is suited for dynamics simulations where (1) adiabatic states are required "on-the-fly" and (2) the primary source of the electronic coupling between the diabatic states is the perturbative spin-orbit interaction among the 3d electrons. The model Hamiltonian we develop is a variant of the Anderson impurity model and achieves efficiency through a physically motivated basis set reduction based on the large value of the d-d Coulomb interaction U(d) and a Lanczos matrix diagonalization routine to solve for eigenvalues. The model parameters are constrained by fits to the partial density of states obtained from ab initio density functional theory calculations. For a particular application of our model we focus on electron transfer occurring between cobalt ions solvated by ammonium, incorporating configuration interaction between multiplet states for both metal ions. We demonstrate the capability of the method to efficiently calculate adiabatic potential energy surfaces and the electronic coupling factor we have calculated compares well to previous calculations and experiment. (
ABSTRACT
We present a theory of nonequilibrium long range charge transfer between donor and acceptor centers in a model polymer mediated by magnetic exciton (Kondo) bound states. Our model produces electron tunneling lengths easily exceeding 10 A, as observed recently in DNA and organic charge transfer systems. This long ranged tunneling is effective for weak to intermediate donor-bridge coupling, and is enhanced both by weak to intermediate strength Coulomb hole-electron attraction (through the orthogonality catastrophe) and by coupling to local vibrational modes.
ABSTRACT
The ratio of the electric and magnetic form factors of the proton G(E(p))/G(M(p)), which is an image of its charge and magnetization distributions, was measured at the Thomas Jefferson National Accelerator Facility (JLab) using the recoil polarization technique. The ratio of the form factors is directly proportional to the ratio of the transverse to longitudinal components of the polarization of the recoil proton in the elastic e(-->)p---> e(-->)p reaction. The new data presented span the range 3.5< Q(2)< 5.6 GeV(2) and are well described by a linear Q(2) fit. Also, the ratio sqrt[Q(2)] F(2(p))/F(1(p)) reaches a constant value above Q(2) = 2 GeV(2).
ABSTRACT
Cytotoxic T lymphocytes (CTL) play a vital role in host defense against viral and intracellular bacterial infections. However, nonreplicating vaccines administered by intramuscular injection using a syringe and needle elicit predominantly humoral responses and not CTL responses. Here we report that epidermal powder immunization (EPI), a technology that delivers antigens on 1.5- to 2.5-microm gold particles to the epidermis using a needle-free powder delivery system, elicits CTL responses to nonreplicating antigens. Following EPI, a majority of the antigen-coated gold particles were found in the viable epidermis in the histological sections of the target skin. Further studies using transmission electron microscopy revealed the intracellular localization of the gold particles. Many Langerhans cells (LCs) at the vaccination site contained antigen-coated particles, as revealed by two-color immunofluorescence microscopy, and these cells were found in the draining lymph nodes 20 h later. Immune responses to several viral protein antigens after EPI were studied in mice. EPI with hepatitis B surface antigen (HBsAg) and a synthetic peptide of influenza virus nucleoprotein (NP peptide) elicited antigen-specific CTL responses as well as antibody responses. In an in vitro cell depletion experiment, we demonstrated that the CTL activity against HBsAg elicited by EPI was attributed to CD8(+), not CD4(+), T cells. As controls, needle injections of HBsAg or the NP peptide into deeper tissues elicited solely antibody, not CTL, responses. We further demonstrated that EPI with inactivated A/Aichi/68 (H3N2) or A/Sydney/97 (H3N2) influenza virus elicited complete protection against a mouse-adapted A/Aichi/68 virus. In summary, EPI directly delivers protein antigens to the cytosol of the LCs in the skin and elicits both cellular and antibody responses.