Adrenoleukodystrophy ; genetics ; therapy ; Animals ; Color Vision Defects ; genetics ; therapy ; Dependovirus ; Gene Transfer Techniques ; Genetic Therapy ; ethics ; trends ; Hematopoietic Stem Cell Transplantation ; Humans ; Leber Congenital Amaurosis ; genetics ; therapy ; Lentivirus

China ; Environmental Exposure ; Health Status ; Humans ; Particulate Matter ; adverse effects ; Weather

Biotechnology ; China ; Cooperative Behavior ; Cuba ; Federal Government ; Translational Medical Research

In June 2013, the first human H6N1 influenza virus infection was confirmed in Taiwan. However, the origin and molecular characterization of this virus, A/Taiwan/2/2013 (H6N1), have not been well studied thus far. In the present report, we performed phylogenetic and coalescent analyses of this virus and compared its molecular profile/characteristics with other closely related strains. Molecular characterization of H6N1 revealed that it is a typical avian influenza virus of low pathogenicity, which might not replicate and propagate well in the upper airway in mammals. Phylogenetic analysis revealed that the virus clusters with A/chicken/Taiwan/A2837/2013 (H6N1) in seven genes, except PB1. For the PB1 gene, A/Taiwan/2/2013 was clustered with a different H6N1 lineage from A/chicken/Taiwan/ A2837/2013. Although a previous study demonstrated that the PB2, PA, and M genes of A/Taiwan/2/2013 might be derived from the H5N2 viruses, coalescent analyses revealed that these H5N2 viruses were derived from more recent strains than that of the ancestor of A/Taiwan/2/2013. Therefore, we propose that A/Taiwan/2/2013 is a reassortant from different H6N1 lineages circulating in chickens in Taiwan. Furthermore, compared to avian isolates, a single P186L (H3 numbering) substitution in the hemagglutinin H6 of the human isolate might increase the mammalian receptor binding and, hence, this strain's pathogenicity in humans. Overall, human infection with this virus seems an accidental event and is unlikely to cause an influenza pandemic. However, its co-circulation and potential reassortment with other influenza subtypes are still worthy of attention.
Amino Acid Sequence ; Amino Acid Substitution ; Animals ; Hemagglutinin Glycoproteins, Influenza Virus ; chemistry ; genetics ; Humans ; Influenza A Virus, H5N2 Subtype ; genetics ; physiology ; Influenza A virus ; genetics ; isolation & purification ; physiology ; Influenza, Human ; epidemiology ; virology ; Laboratories ; Models, Molecular ; Molecular Sequence Data ; Phylogeny ; Poultry ; virology ; Protein Conformation ; Taiwan ; epidemiology ; Viral Proteins ; genetics

PD-L1 is a member of the B7 protein family, most of whose members so far were identified as dimers in a solution and crystalline state, either complexed or uncomplexed with their ligand(s). The binding of PD-L1 with its receptor PD-1 (CD279) delivers an inhibitory signal regulating the T cell function. Simultaneously with the Garboczi group, we successfully solved another structure of human PD-L1 (hPD-L1). Our protein crystallized in the space group of C222(1) with two hPD-L1 molecules per asymmetric unit. After comparison of reported B7 structures, we have found some intrinsic factors involved in the interaction of these two molecules. Based on these results, we tend to believe this uncomplexed hPD-L1 structure demonstrated its potential dimeric state in solution, although it could just be an evolutionary relic, too weak to be detected under present technology, or still a functional unit deserved our attentions.
Antigens, CD ; chemistry ; immunology ; B7-H1 Antigen ; Crystallography, X-Ray ; Evolution, Molecular ; Humans ; Protein Multimerization ; Protein Structure, Quaternary ; Protein Structure, Secondary ; T-Lymphocytes ; chemistry ; immunology

The Met tyrosine kinase receptor is a widely expressed molecule, which mediates pleiotropic cellular responses following activation by its ligand, hepatocyte growth factor/scatter factor (HGF/SF). Previously, one of the authors identified an alternatively spliced form of Met (Met-SM) that lacked a single exon of a 47-amino-acid segment in the juxtamembrane domain. Here we report that Met-SM is a potent transforming gene in NIH3T3 mouse fibroblast cells. Met-SM-transfected NIH3T3 cells show stronger foci-forming activity than wild type-Met-transfected ones. In addition, Met-SM-transfected NIH3T3 cells form colonies in soft agar and are tumorigenic in athymic nu/nu mice. Furthermore, HGF/SF significantly increases the focus-forming activity of Met-SM comparing to wild type Met. The amount of protein and of tyrosine kinase activity of Met-SM accumulates to a high level following HGF/SF treatment. The accumulation of Met-SM correlated well with its delayed ubiquitination and increased stability. These results are consistent with the important role of the juxtamembrane domain in protein stability of Met receptor and suggest that the alternatively-spliced form may contribute to the development and progression of human cancer.
Proto-Oncogene Proteins c-met/*metabolism/*physiology ; Protein Isoforms/metabolism/physiology ; NIH 3T3 Cells ; Mutant Proteins/metabolism/physiology ; Mice, Nude ; Mice ; Hepatocyte Growth Factor/pharmacology ; Female ; Down-Regulation ; Carcinogens/*metabolism ; Carcinogenicity Tests ; Animals ; *Alternative Splicing

Measles virus is an enveloped virus with a non-segmented negative-sense RNA genome. Two envelope glycoproteins on the viral surface, namely hemagglutinin (H) and membrane fusion protein (F), are responsible for the virus entry into susceptible host cells. The specific interaction between H and its cellular receptors is a key step in successful virus infection, determining the infectivity and tissue tropism of the measles virus. Thus far, three H receptors have been identified, including the complement regulatory molecule CD46, the signaling lymphocyte activation molecule (SLAM) and the cell adhesion molecule Nectin-4. Here, we reviewed our molecular understanding on the recognition mechanism of these receptors by the viral H protein, aiming to promote future studies on antiviral drug design and measles virus-based oncolytic therapy.
Animals ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Hemagglutinins, Viral ; metabolism ; Humans ; Measles virus ; pathogenicity ; physiology ; Membrane Cofactor Protein ; metabolism ; Membrane Fusion ; Membrane Fusion Proteins ; metabolism ; Receptors, Cell Surface ; metabolism ; Receptors, Virus ; metabolism ; Signaling Lymphocytic Activation Molecule Family Member 1

Rhesus macaque (Macaca mulatta) is the best model to study of human immunodeficiency virus (HIV) infection and to develop acquired immunodeficiency syndrome (AIDS) vaccine. The crystal structure of its major histocompatibility antigen complex (MHC) is helpful to understand the mechanism of HIV immune evasion. In this study, we cloned the light chain (beta2m) of MHC class I allele of rhesus macaques, Mamu-A*02, and inserted it into pET21a(+) vector. We transfected the recombinant plasmid pET21a(+)-Mamu-beta2m and pET21a(+)-Mamu-alpha into BL21(DE3). Mamu-A*02 and beta2m were expressed in the form of inclusion bodies in BL21 (DE3). We co-refolded the inclusion bodies of Mamu-alpha and Mamu-beta2m with SIV nonapeptide YY9 and obtained the correct refolded protein complex. Then we purified the protein complex by the gel filtration and anion-exchange column. With hanging-drop method, we screened and optimized for the protein crystal. We managed to collect a X-ray diffraction with the resolution to 2.8 angstroms in the condition of 0.1 mol/L BIS-TRIS (pH5.5), 2.0 mol/L(NH4)2SO4. This crystal belong to perpendicular space group P2(1)2(1)2(1), with unit-cell parameters a = 128.99 angstroms, b = 129.01 angstroms, c = 129.03 angstroms. This data is available for the structure determination.
Animals ; Crystallography, X-Ray ; Epitopes ; immunology ; Escherichia coli ; genetics ; metabolism ; Histocompatibility Antigens Class I ; biosynthesis ; genetics ; Macaca mulatta ; Oligopeptides ; biosynthesis ; genetics ; Simian Immunodeficiency Virus ; immunology

Wolynes argued that the track of a protein's folding was directed by the tendency of lowering its energy, and thus when a local minimum of its energy was reached, a relatively stable conformation was formed. However not all of the local minimums will lead the protein to a biologically useful conformation, for those otherwise are called energy traps. Wolynes energy landscape theory and natural selection have well explained the high efficiency of protein folding in vivo, instead of being stuck in energy traps. As to whether a protein can assume different conformations with the same bioactivity, there is no clear answer yet. In this paper, two conformational states of a pHLA-A*2402 are discovered after refolding, and by studying their interactions with TCR and CD8alphaalpha, two conformations of pHLA-A*2402 are confirmed of having escaped from natural selection.
CD8 Antigens ; chemistry ; Energy Metabolism ; HLA-A24 Antigen ; chemistry ; Humans ; Protein Conformation ; Protein Folding ; Receptors, Antigen, T-Cell ; chemistry

For the first time ever, the scientists of J. Craig Venter team have created actual self-replicating synthetic life. The research was just published in the Journal of Science on May 20, 2010. Although this news immediately brings the worry about the possible potential threat to biosecurity and biosafety as well as the ethical disputes, it yet indicates that mankind have made a new step forward in synthetic biology. In the time of post-genome era, we believe the advancement of synthetic biology that might affect or change the future life of human being will be widely used in energy, environment, materials, medication and many other fields.
Biological Science Disciplines ; methods ; Cloning, Organism ; Genome, Human ; genetics ; Human Genome Project ; Humans ; Synthetic Biology ; trends