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

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

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

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

The internet era has brought a dual impact on epidemiological research: on one hand, it has expanded the breadth and depth of public health surveillance, enriching the formulation of strategies for early warning for public health emergencies and infectious disease outbreaks, disease prevention, and health promotion through vast medical information resources. On the other hand, it has triggered the issue of "infodemic", wherein the rapid spread of misinformation disrupts public perception, weakens the effectiveness of public health responses, and adds complexity to the management of public health emergencies. This paper focuses on representative research areas of infodemiology, for example, infodemic caused by inforus, and explores its future development trends and potential challenges with the aim to deepen infodemiology research and optimize public health practice.

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

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

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

Throughout human history, pandemic bacterial diseases such as the plague and tuberculosis have posed an enormous threat to human beings. The discovery of antibiotics has provided us with powerful arsenal for the defense against bacterial infections. However, bacteria are acquiring more and more resistance genes to shield off antibiotics through mutation and horizontal gene transfer. Therefore, novel antibiotics must be produced and the arms race between bacterial pathogens and antibiotics is becoming increasingly intense. Recently, researchers have found that plasmids carrying a new metallo-beta-lactamase gene, blaNDM-1, and many other antibiotics resistance genes can easily spread through bacterial populations and confer recipient stains resistance to nearly all of the current antibiotics. It is a threat to the human health and a great challenge for our medical science, which we are facing. We need to find new ways to fight and win this arms racing.
Anti-Bacterial Agents ; pharmacology ; Bacteria ; drug effects ; genetics ; Drug Resistance, Bacterial ; genetics ; Gene Transfer, Horizontal ; Mutation ; Plasmids ; genetics ; beta-Lactamases ; genetics

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