Genomes and Genes
Experts and Doctors on plasmids in Ithaca, New York, United States
Locale: Ithaca, New York, United States
- Homesley L, Lei M, Kawasaki Y, Sawyer S, Christensen T, Tye B. Mcm10 and the MCM2-7 complex interact to initiate DNA synthesis and to release replication factors from origins. Genes Dev. 2000;14:913-26 pubmed..These results suggest that Mcm10, like Mcm7, is a critical component of the prereplication chromatin and that interaction between Mcm10 and Mcm7 is required for proper replication initiation and prompt release of origin-bound factors. ..
- Chen Y, Tye B. The yeast Mcm1 protein is regulated posttranscriptionally by the flux of glycolysis. Mol Cell Biol. 1995;15:4631-9 pubmed
- Volkova V, Lanzas C, Lu Z, Gröhn Y. Mathematical model of plasmid-mediated resistance to ceftiofur in commensal enteric Escherichia coli of cattle. PLoS ONE. 2012;7:e36738 pubmed publisher..coli, such as the frequency of transfer of plasmids carrying resistance-genes, the rate of replacement of enteric E. coli by ingested E. coli, and the frequency of ceftiofur resistance in the latter. ..
- Parker S, Diaz I, Anderson K, Batt C. Design, production, and characterization of a single-chain variable fragment (ScFv) derived from the prostate specific membrane antigen (PSMA) monoclonal antibody J591. Protein Expr Purif. 2013;89:136-45 pubmed publisher..Our results demonstrate that functional J591 ScFv can be produced in P. pastoris for use in diagnostic and targeted therapeutic applications. ..
- Sun X, Lis J, Wu R. The positive and negative transcriptional regulation of the Drosophila Gapdh-2 gene. Genes Dev. 1988;2:743-53 pubmed..Thus, URS-2 plays a key role in the developmental regulation of Gapdh-2. Additionally, the efficient transcription of Gapdh-2 in larval and adult stages appears to depend on a synergistic function of URS-1 and URS-2. ..
- Parks A, Peters J. Tn7 elements: engendering diversity from chromosomes to episomes. Plasmid. 2009;61:1-14 pubmed publisher..We propose that by decisively moving between mobile and stationary DNA pools, Tn7-like elements accumulate a broad range of genetic material, providing a selective advantage for diverse host bacteria. ..
- Merchant A, Kawasaki Y, Chen Y, Lei M, Tye B. A lesion in the DNA replication initiation factor Mcm10 induces pausing of elongation forks through chromosomal replication origins in Saccharomyces cerevisiae. Mol Cell Biol. 1997;17:3261-71 pubmed..This novel phenotype suggests a unique role for the Mcm10 protein in the initiation of DNA synthesis at replication origins. ..
- Winans S, Burns D, Christie P. Adaptation of a conjugal transfer system for the export of pathogenic macromolecules. Trends Microbiol. 1996;4:64-8 pubmed
- Zheng X, Resnick R, Shalloway D. Mitotic activation of protein-tyrosine phosphatase alpha and regulation of its Src-mediated transforming activity by its sites of protein kinase C phosphorylation. J Biol Chem. 2002;277:21922-9 pubmed
- Batt C, Jamieson A, Vandeyar M. Identification of essential histidine residues in the active site of Escherichia coli xylose (glucose) isomerase. Proc Natl Acad Sci U S A. 1990;87:618-22 pubmed..Replacement of His-271 may render the enzyme thermolabile, since this residue appears to be a ligand for one of the metal ions in the active site of the enzyme. ..
- Park J, Marr M, Roberts J. E. coli Transcription repair coupling factor (Mfd protein) rescues arrested complexes by promoting forward translocation. Cell. 2002;109:757-67 pubmed..Mfd may act through a translocase activity that rewinds upstream DNA, leading either to translocation or to release of RNA polymerase when the enzyme active site cannot continue elongation. ..
- Stewart V, Parales J. Identification and expression of genes narL and narX of the nar (nitrate reductase) locus in Escherichia coli K-12. J Bacteriol. 1988;170:1589-97 pubmed..Analysis of these operon fusions indicated that narL and narX are transcribed counterclockwise with respect to the E. coli genetic map and that narK is transcribed clockwise. ..
- Parrish C. Mapping specific functions in the capsid structure of canine parvovirus and feline panleukopenia virus using infectious plasmid clones. Virology. 1991;183:195-205 pubmed
- Orsi R, Borowsky M, Lauer P, Young S, Nusbaum C, Galagan J, et al. Short-term genome evolution of Listeria monocytogenes in a non-controlled environment. BMC Genomics. 2008;9:539 pubmed publisher..Short-term evolution of L. monocytogenes in non-controlled environments appears to involve limited diversification beyond plasmid gain or loss and prophage diversification, highlighting the importance of phages in bacterial evolution. ..
- Roberson M, Meermann S, Morasso M, Mulvaney Musa J, Zhang T. A role for the homeobox protein Distal-less 3 in the activation of the glycoprotein hormone alpha subunit gene in choriocarcinoma cells. J Biol Chem. 2001;276:10016-24 pubmed..Our studies support the conclusion that Dlx 3 is a placental-specific transcriptional regulator that binds to the JRE and contributes to expression of the alpha subunit gene in cells of trophoblast origin. ..
- Pohlman R, Genetti H, Winans S. Entry exclusion of the IncN plasmid pKM101 is mediated by a single hydrophilic protein containing a lipid attachment motif. Plasmid. 1994;31:158-65 pubmed..The resulting plasmid was sufficient to mediate entry exclusion. The degree of exclusion was greatly enhanced by overexpression of this gene. ..
- Jiang Y, Horner V, Liu J. The HMX homeodomain protein MLS-2 regulates cleavage orientation, cell proliferation and cell fate specification in the C. elegans postembryonic mesoderm. Development. 2005;132:4119-30 pubmed..Furthermore, the C. elegans Myod homolog HLH-1 acts downstream of mls-2 to specify M-derived coelomocyte cell fates. Thus MLS-2 functions in a cell type-specific manner to regulate both cell proliferation and cell fate specification. ..
- den Bakker H, Cummings C, Ferreira V, Vatta P, Orsi R, Degoricija L, et al. Comparative genomics of the bacterial genus Listeria: Genome evolution is characterized by limited gene acquisition and limited gene loss. BMC Genomics. 2010;11:688 pubmed publisher..This information will allow for the development of genetic and genomic criteria for pathogenic strains, including development of assays that specifically detect pathogenic Listeria strains. ..
- Williams E, Perez Martinez X, Fox T. MrpL36p, a highly diverged L31 ribosomal protein homolog with additional functional domains in Saccharomyces cerevisiae mitochondria. Genetics. 2004;167:65-75 pubmed..We propose that MrpL36p represents a highly diverged L31 homolog with derived domains functioning in mRNA selection in yeast mitochondria. ..
- Kalogeraki V, Winans S. Wound-released chemical signals may elicit multiple responses from an Agrobacterium tumefaciens strain containing an octopine-type Ti plasmid. J Bacteriol. 1998;180:5660-7 pubmed..Disruptions of virH, virK, virL, or virM did not affect tumorigenesis of Kalanchöe diagramontiana leaves or carrot disks, suggesting that they may play an entirely different role during pathogenesis...
- Passmore S, Elble R, Tye B. A protein involved in minichromosome maintenance in yeast binds a transcriptional enhancer conserved in eukaryotes. Genes Dev. 1989;3:921-35 pubmed..We have shown that MCM1 binds to the human c-fos SRE in vitro and, like other MCEs, the c-fos SRE exhibits MCM1-mediated upstream activating sequence (UAS) activity in vivo. ..
- Su J, Hirji R, Zhang L, He C, Selvaraj G, Wu R. Evaluation of the stress-inducible production of choline oxidase in transgenic rice as a strategy for producing the stress-protectant glycine betaine. J Exp Bot. 2006;57:1129-35 pubmed
- O BRIEN T, Lis J. Rapid changes in Drosophila transcription after an instantaneous heat shock. Mol Cell Biol. 1993;13:3456-63 pubmed..Both approaches also showed the in vivo rate of movement of the first wave of RNA polymerase through the hsp70 gene to be approximately 1.2 kb/min. ..
- Kalogeraki V, Winans S. The octopine-type Ti plasmid pTiA6 of Agrobacterium tumefaciens contains a gene homologous to the chromosomal virulence gene acvB. J Bacteriol. 1995;177:892-7 pubmed..Finally, mutations in these genes cannot be complemented extracellularly...
- Baird D, Feng Q, Cerione R. The Cool-2/alpha-Pix protein mediates a Cdc42-Rac signaling cascade. Curr Biol. 2005;15:1-10 pubmed..These findings demonstrate that by serving as a target for GTP bound Cdc42 and a GEF for Rac, Cool-2 mediates a GTPase cascade where the activation of Cdc42 is translated into the activation of Rac. ..
- Baek S, Hartsock A, Shapleigh J. Agrobacterium tumefaciens C58 uses ActR and FnrN to control nirK and nor expression. J Bacteriol. 2008;190:78-86 pubmed publisher..Inactivation of paz reduced Nir activity by 55%. These results help explain why Nir activity is very low in the actR mutant even though a nirK promoter with mutations in the ActR binding site showed significant expression...
- Elble R, Tye B. Both activation and repression of a-mating-type-specific genes in yeast require transcription factor Mcm1. Proc Natl Acad Sci U S A. 1991;88:10966-70 pubmed..Mcm1 joins an increasing number of transcription factors involved in both positive and negative regulation of gene expression. ..
- Berg B, Li J, Heider J, Stewart V. Nitrate-inducible formate dehydrogenase in Escherichia coli K-12. I. Nucleotide sequence of the fdnGHI operon and evidence that opal (UGA) encodes selenocysteine. J Biol Chem. 1991;266:22380-5 pubmed..Evidence from sequence and spectral analyses suggest that FdnI encodes cytochrome bFdn556. Implications for the membrane topology of formate dehydrogenase-N and its mechanism of proton translocation are discussed. ..
- Su X, Lin Z, Chen W, Jiang H, Zhang S, Lin H. Chemogenomic approach identified yeast YLR143W as diphthamide synthetase. Proc Natl Acad Sci U S A. 2012;109:19983-7 pubmed publisher..Diphthamide synthetase is evolutionarily conserved in eukaryotes. The previously uncharacterized human gene ATPBD4 is the ortholog of yeast YLR143W and fully rescues the deletion of YLR143W in yeast...
- Feng Q, Albeck J, Cerione R, Yang W. Regulation of the Cool/Pix proteins: key binding partners of the Cdc42/Rac targets, the p21-activated kinases. J Biol Chem. 2002;277:5644-50 pubmed..We conclude that T1 represents a novel regulatory domain that accounts for the specific functional effects on PAK activity exhibited by the different members of the Cool/Pix family. ..
- Ho J, Bretscher A. Ras regulates the polarity of the yeast actin cytoskeleton through the stress response pathway. Mol Biol Cell. 2001;12:1541-55 pubmed..Thus, Ras2p regulates cytoskeletal polarity in yeast under conditions of mild temperature stress through the stress response pathway. ..
- Alani E. The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that specifically binds to duplex oligonucleotides containing mismatched DNA base pairs. Mol Cell Biol. 1996;16:5604-15 pubmed
- Nunez L, Jesch S, Gaspar M, Almaguer C, Villa Garcia M, Ruiz Noriega M, et al. Cell wall integrity MAPK pathway is essential for lipid homeostasis. J Biol Chem. 2008;283:34204-17 pubmed publisher..These results indicate that an intact cell wall integrity pathway is required for maintaining proper lipid homeostasis in yeast, especially when cells are grown in the absence of inositol. ..
- McMullin T, Haffter P, Fox T. A novel small-subunit ribosomal protein of yeast mitochondria that interacts functionally with an mRNA-specific translational activator. Mol Cell Biol. 1990;10:4590-5 pubmed
- He C, Lin Z, McElroy D, Wu R. Identification of a rice actin2 gene regulatory region for high-level expression of transgenes in monocots. Plant Biotechnol J. 2009;7:227-39 pubmed publisher..In addition, two OsAct2-based expression vectors for use in monocot transformation were developed to promote the high-level expression of foreign genes. ..
- Stewart V, Lin J, Berg B. Genetic evidence that genes fdhD and fdhE do not control synthesis of formate dehydrogenase-N in Escherichia coli K-12. J Bacteriol. 1991;173:4417-23 pubmed..Our complementation tests, with cloned E. coli fdhD and fdhE genes, indicate that the S. typhimurium fdnC and fdnB genes are functionally homologous to the E. coli fdhD and fdhE genes, respectively. ..
- Lin R, Teng Y, Park H, Ding L, Black C, Fang P, et al. Discrete and essential roles of the multiple domains of Arabidopsis FHY3 in mediating phytochrome A signal transduction. Plant Physiol. 2008;148:981-92 pubmed publisher..Together, our results reveal discrete roles of the multiple domains of FHY3 and provide functional support for the proposition that FHY3 and FAR1 represent transcription factors derived from a Mutator-like transposase(s). ..
- Muscarella D, Ellison E, Ruoff B, Vogt V. Characterization of I-Ppo, an intron-encoded endonuclease that mediates homing of a group I intron in the ribosomal DNA of Physarum polycephalum. Mol Cell Biol. 1990;10:3386-96 pubmed
- Saliki J, Mizak B, Flore H, Gettig R, Burand J, Carmichael L, et al. Canine parvovirus empty capsids produced by expression in a baculovirus vector: use in analysis of viral properties and immunization of dogs. J Gen Virol. 1992;73 ( Pt 2):369-74 pubmed
- Sonntag Brown M, Lim E, Chen C, Nishant K, Alani E. Genetic analysis of mlh3 mutations reveals interactions between crossover promoting factors during meiosis in baker's yeast. G3 (Bethesda). 2013;3:9-22 pubmed publisher..Together, these observations provide insights for how Mlh1-Mlh3 acts in crossover resolution and MMR and for how chromosome segregation in Meiosis I can occur in the absence of crossing over. ..
- Egan S, Stewart V. Mutational analysis of nitrate regulatory gene narL in Escherichia coli K-12. J Bacteriol. 1991;173:4424-32 pubmed..This finding suggests that narL505(V88A) did not confer molybdate-independent expression of fdnGHI. ..
- Schat K, Pratt W, Morgan R, Weinstock D, Calnek B. Stable transfection of reticuloendotheliosis virus-transformed lymphoblastoid cell lines. Avian Dis. 1992;36:432-9 pubmed..Transfected cell lines were selected using G418 and were maintained for periods up to 137 days. Transfected cell lines were susceptible to MHC class-I restricted lysis by cytotoxic T lymphocytes from REV-infected chickens...
- Chen C, Wang L, Winans S. Characterization of the supervirulent virG gene of the Agrobacterium tumefaciens plasmid pTiBo542. Mol Gen Genet. 1991;230:302-9 pubmed
- Vander Horn P, Zahler S. Cloning and nucleotide sequence of the leucyl-tRNA synthetase gene of Bacillus subtilis. J Bacteriol. 1992;174:3928-35 pubmed..subtilis ilv-leu operon. The DNA of the B. subtilis leuS open reading frame is 48% identical to the leuS gene of Escherichia coli and is predicted to encode a polypeptide with 46% identity to the leucyl-tRNA synthetase of E. coli. ..
- Habeeb L, Wang L, Winans S. Transcription of the octopine catabolism operon of the Agrobacterium tumor-inducing plasmid pTiA6 is activated by a LysR-type regulatory protein. Mol Plant Microbe Interact. 1991;4:379-85 pubmed..The sequence of this gene was determined and analysis of the inferred protein sequence indicates that the gene encodes a member of the LysR family of prokaryotic transcriptional regulatory proteins. ..
- McLeod A, Smart C, Fry W. Core promoter structure in the oomycete Phytophthora infestans. Eukaryot Cell. 2004;3:91-9 pubmed
- Platko J, Willins D, Calvo J. The ilvIH operon of Escherichia coli is positively regulated. J Bacteriol. 1990;172:4563-70 pubmed..We propose that the designation lrp be used in the future instead of oppI or ihb and that Lrp (leucine-responsive regulatory protein) be used in place of IHB. ..
- Chen S, Calvo J. Leucine-induced dissociation of Escherichia coli Lrp hexadecamers to octamers. J Mol Biol. 2002;318:1031-42 pubmed..Mathematical modeling, employed to simulate modulation of Lrp action in response to growth conditions, gave results that are consistent with known patterns of Lrp action on different operons. ..
- Steeg C, Vogt V. RNA-binding properties of the matrix protein (p19gag) of avian sarcoma and leukemia viruses. J Virol. 1990;64:847-55 pubmed..We also found that MA can bind to DNA with an affinity similar to that for RNA. The large quantitative discrepancy between our results and earlier published reports can be traced in part to methods of data analysis...
- Wang J, Wu W, Cerione R. Cdc42 and Ras cooperate to mediate cellular transformation by intersectin-L. J Biol Chem. 2005;280:22883-91 pubmed..Rather, we found that SH3A-C2 exhibited strong transforming activity through its ability to mediate cooperation between Ras and Cdc42. ..
- Coombs J, Franco C, Loria R. Complete sequencing and analysis of pEN2701, a novel 13-kb plasmid from an endophytic Streptomyces sp. Plasmid. 2003;49:86-92 pubmed..This structure and the sequence of the putative Kor protein are similar to the pFQ series of plasmids isolated from Frankia, another endophytic actinomycete...
- Lee S, Liu B, Lee S, Huang S, Shen B, Qian S. Global mapping of translation initiation sites in mammalian cells at single-nucleotide resolution. Proc Natl Acad Sci U S A. 2012;109:E2424-32 pubmed publisher..Our study establishes a practical platform for uncovering the hidden coding potential of the transcriptome and offers a greater understanding of the complexity of translation initiation...
- Butcher B, Fox B, Rommereim L, Kim S, Maurer K, Yarovinsky F, et al. Toxoplasma gondii rhoptry kinase ROP16 activates STAT3 and STAT6 resulting in cytokine inhibition and arginase-1-dependent growth control. PLoS Pathog. 2011;7:e1002236 pubmed publisher..We conclude that encounter between Toxoplasma ROP16 and the host cell STAT signaling cascade has pleiotropic downstream effects that act in multiple and complex ways to direct the course of infection. ..
- Muscarella D, Vogt V. A mobile group I intron in the nuclear rDNA of Physarum polycephalum. Cell. 1989;56:443-54 pubmed..This is the first demonstration of the transposition of a nuclear intron in an experimental setting, and provides a rare example of a protein encoded by an RNA polymerase I transcript...
- den Bakker H, Bowen B, Rodriguez Rivera L, Wiedmann M. FSL J1-208, a virulent uncommon phylogenetic lineage IV Listeria monocytogenes strain with a small chromosome size and a putative virulence plasmid carrying internalin-like genes. Appl Environ Microbiol. 2012;78:1876-89 pubmed publisher..The accessory genes in this plasmid belong to the internalin family, a family of virulence-associated proteins, and therefore this is the first report of a potential virulence plasmid in the genus Listeria. ..
- Glaser R, Thomas G, Siegfried E, Elgin S, Lis J. Optimal heat-induced expression of the Drosophila hsp26 gene requires a promoter sequence containing (CT)n.(GA)n repeats. J Mol Biol. 1990;211:751-61 pubmed..dG-dA) sequence does not form H-DNA in vivo and argue against a role for H-DNA in the heat-induced expression of hsp26. ..
- Reed M, Lyi S, Hanson M. Edited transcripts compete with unedited mRNAs for trans-acting editing factors in higher plant chloroplasts. Gene. 2001;272:165-71 pubmed..This indicates that the C target of editing is not a critical recognition feature for the site-specific trans-acting factor. ..
- Mani S, Rajagopal R, Garfinkel A, Fan X, Wolfner M. A hydrophilic lamin-binding domain from the Drosophila YA protein can target proteins to the nuclear envelope. J Cell Sci. 2003;116:2067-72 pubmed..This hydrophilic YA domain might provide a useful molecular tool for targeting heterologous non-membrane-associated proteins to the nuclear envelope. ..
- Fitch M, Donato J, Tye B. Mcm7, a subunit of the presumptive MCM helicase, modulates its own expression in conjunction with Mcm1. J Biol Chem. 2003;278:25408-16 pubmed..The multiple roles of Mcm7 in replication initiation, replication elongation, and autoregulation parallel those of the oncoprotein, the large T-antigen of the SV40 virus. ..
- Abramovitch R, Kim Y, Chen S, Dickman M, Martin G. Pseudomonas type III effector AvrPtoB induces plant disease susceptibility by inhibition of host programmed cell death. EMBO J. 2003;22:60-9 pubmed..Thus, our results indicate that a type III effector can induce plant susceptibility to bacterial infection by inhibiting host PCD. ..
- Mascher T, Zimmer S, Smith T, Helmann J. Antibiotic-inducible promoter regulated by the cell envelope stress-sensing two-component system LiaRS of Bacillus subtilis. Antimicrob Agents Chemother. 2004;48:2888-96 pubmed..Thus, the reporter derived from P(liaI) (the liaI promoter) provides a tool for the detection and classification of antimicrobial compounds. ..
- McGonigle S, Beall M, Pearce E. Eukaryotic initiation factor 2 alpha subunit associates with TGF beta receptors and 14-3-3 epsilon and acts as a modulator of the TGF beta response. Biochemistry. 2002;41:579-87 pubmed..The interaction of these two regulatory proteins with each other and with the TGF beta receptors and their relative expression levels are likely to be important in fine-tuning the regulation of TGF beta signal transduction. ..
- Rzomp K, Scholtes L, Briggs B, Whittaker G, Scidmore M. Rab GTPases are recruited to chlamydial inclusions in both a species-dependent and species-independent manner. Infect Immun. 2003;71:5855-70 pubmed..trachomatis IncG at the inclusion membrane. Therefore, chlamydiae recruit key regulators of membrane trafficking to the inclusion, which may function to regulate the trafficking or fusogenic properties of the inclusion...
- Chang S, Sgro J, Parrish C. Multiple amino acids in the capsid structure of canine parvovirus coordinately determine the canine host range and specific antigenic and hemagglutination properties. J Virol. 1992;66:6858-67 pubmed..An FPV-specific epitope was affected by aa 323. Amino acids 323 and 375 together determined the pH dependence of HA. Amino acids involved in the various specific properties were all around the threefold spikes of the viral particle...
- Gao L, Liu W, Bretscher A. The yeast formin Bnr1p has two localization regions that show spatially and temporally distinct association with septin structures. Mol Biol Cell. 2010;21:1253-62 pubmed publisher..Overexpression of Bnr1p-L1, but not Bnr1p-L2, disrupts septin organization at the bud neck. Thus Bnr1p has two separable regions that each contribute to its bud neck localization. ..
- Georgieva E, Roy A, Grigoryants V, Borbat P, Earle K, Scholes C, et al. Effect of freezing conditions on distances and their distributions derived from Double Electron Electron Resonance (DEER): a study of doubly-spin-labeled T4 lysozyme. J Magn Reson. 2012;216:69-77 pubmed publisher..The assignment of bimodal distributions to tether rotamers as opposed to protein conformations is aided by comparing results using MTSL and 4-Bromo MTSL spin-labels. The latter usually produce narrower distance distributions. ..
- Rao S, Stewart B, Rivlin P, Vilinsky I, Watson B, Lang C, et al. Two distinct effects on neurotransmission in a temperature-sensitive SNAP-25 mutant. EMBO J. 2001;20:6761-71 pubmed..Our data suggest that at 22 degrees C the mutation causes the SNARE complex to be more fusion competent but, at 37 degrees C the same mutation leads to SNARE multimer instability and fusion incompetence. ..
- Evans E, Sugawara N, Haber J, Alani E. The Saccharomyces cerevisiae Msh2 mismatch repair protein localizes to recombination intermediates in vivo. Mol Cell. 2000;5:789-99 pubmed..These findings argue that Msh2p-Msh3p associates with intermediates early in DSBR to participate in the rejection of homeologous pairing and to stabilize nonhomologous tails for cleavage by Rad1p-Rad10p endonuclease. ..
- Valdivia R, Wang L, Winans S. Characterization of a putative periplasmic transport system for octopine accumulation encoded by Agrobacterium tumefaciens Ti plasmid pTiA6. J Bacteriol. 1991;173:6398-405 pubmed..The OccJ protein was identified by electrophoresis and found to be fully localized in the periplasmic space. When these proteins were expressed in Escherichia coli, radiolabeled octopine became cell-associated...
- Shen T, Han D, Guan J. Association of Grb7 with phosphoinositides and its role in the regulation of cell migration. J Biol Chem. 2002;277:29069-77 pubmed
- Calero M, Winand N, Collins R. Identification of the novel proteins Yip4p and Yip5p as Rab GTPase interacting factors. FEBS Lett. 2002;515:89-98 pubmed