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Full-Text Articles in Medicine and Health Sciences
Definition Of An Hla-Dpw2-Restricted Epitope On Ns3, Recognized By A Dengue Virus Serotype-Cross-Reactive Human Cd4+ Cd8- Cytotoxic T-Cell Clone, Ichiro Kurane, Li Chen Dai, Peter G. Livingston, Elaine Reed, Francis A. Ennis
Definition Of An Hla-Dpw2-Restricted Epitope On Ns3, Recognized By A Dengue Virus Serotype-Cross-Reactive Human Cd4+ Cd8- Cytotoxic T-Cell Clone, Ichiro Kurane, Li Chen Dai, Peter G. Livingston, Elaine Reed, Francis A. Ennis
Li Dai
We previously reported that the clone JK34 was cross-reactive for dengue virus types 1, 2, 3, and 4 and recognized NS3 (I. Kurane, M. A. Brinton, A. L. Samson, and F. A. Ennis, J. Virol. 65:1823-1828, 1991). In the present experiments, we defined the epitope at the amino acid level, with 93 15-mer overlapping peptides which cover the entire NS3. A peptide 4 which contains amino acids 251 to 265 of NS3 sensitized the autologous B lymphoblastoid cell line (LCL) to the lysis by JK34. The smallest peptide recognized by JK34 was a 10-mer peptide which contains amino acids 255 …
Mutation Of Human Immunodeficiency Virus Type 1 At Amino Acid 585 On Gp41 Results In Loss Of Killing By Cd8+ A24-Restricted Cytotoxic T Lymphocytes, Li Chen Dai, Kim West, Rebecca A. Littaua, Kazuo Takahashi, Francis A. Ennis
Mutation Of Human Immunodeficiency Virus Type 1 At Amino Acid 585 On Gp41 Results In Loss Of Killing By Cd8+ A24-Restricted Cytotoxic T Lymphocytes, Li Chen Dai, Kim West, Rebecca A. Littaua, Kazuo Takahashi, Francis A. Ennis
Li Dai
A human leukocyte antigen A24-restricted CD8+ cytotoxic T-cell clone specific for gp41 of human immunodeficiency virus type 1 was isolated from an infected individual. The epitope was localized to amino acids 584 to 591 (YLKDQQLL, NL43 env sequence) of gp41 by using a panel of recombinant vaccinia viruses that contain truncated env genes and synthetic peptides. The clone killed autologous B-lymphoblastoid cell lines pulsed with a synthetic peptide reflecting the sequence of the IIIB and MN strains. This clone, however, failed to kill target cells pulsed with the peptides that have a mutation from Lys to Arg or Gln at …
Mutational Analysis Of Residues In The Nucleotide Binding Domain Of Human Terminal Deoxynucleotidyl Transferase., Baoli Yang, K. Gathy, M. Coleman
Mutational Analysis Of Residues In The Nucleotide Binding Domain Of Human Terminal Deoxynucleotidyl Transferase., Baoli Yang, K. Gathy, M. Coleman
Baoli Yang
Human terminal deoxynucleotidyl transferase (TdT) was overexpressed in a baculovirus system. The pure recombinant enzyme was identical in size, activity, kinetic constants, and metal effects to native enzyme. Three amino acids, within either the putative nucleotide binding domain and part of a DNA polymerase consensus sequence, YGDTDSLF, or a TdT consensus sequence, GGFRRGK, were altered by site-directed mutagenesis. The four mutant forms of terminal transferase were also overexpressed in the baculovirus expression system and purified from Trichoplusia ni larvae by a monoclonal antibody affinity column and compared with wild-type enzyme with respect to thermostabilities, secondary structure, metal effects, and kinetic …
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Bromodomain And Histone Acetyltransferase Domain Specificities Control Mixed Lineage Leukemia Phenotype, Donna Santillan, C. Theisler, A. Ryan, R. Popovic, T. Stuart, M. Zhou, S. Alkan, N. Zeleznik-Le
Donna A. Santillan
A critical unanswered question about mixed lineage leukemia (MLL) is how specific MLL fusion partners control leukemia phenotype. The MLL-cyclic AMP-responsive element binding protein-binding protein (CBP) fusion requires both the CBP bromodomain and histone acetyltransferase (HAT) domain for transformation and causes acute myelogenous leukemia (AML), often preceded by a myelodysplastic phase. We did domain-swapping experiments to define whether unique specificities of these CBP domains drive this specific MLL phenotype. Within MLL-CBP, we replaced the CBP bromodomain or HAT domain with P300/CBP-associated factor (P/CAF) or TAF(II)250 bromodomains or the P/CAF or GCN5 HAT domains. HAT, but not bromodomain, substitutions conferred enhanced …
Molecular Analysis Of The Neuropeptide Y1 Receptor Gene In Human Idiopathic Gonadotropin-Dependent Precocious Puberty And Isolated Hypogonadotropic Hypogonadism, K. C. Freitas, Ginny Ryan, V. N. Brito, Y. X. Tao, E. M. Costa, B. B. Mendonca, D. Segaloff, A. C. Latronico
Molecular Analysis Of The Neuropeptide Y1 Receptor Gene In Human Idiopathic Gonadotropin-Dependent Precocious Puberty And Isolated Hypogonadotropic Hypogonadism, K. C. Freitas, Ginny Ryan, V. N. Brito, Y. X. Tao, E. M. Costa, B. B. Mendonca, D. Segaloff, A. C. Latronico
Ginny L. Ryan
OBJECTIVE: To investigate the role of mutations or polymorphisms in the NPY-Y1R gene in human idiopathic central pubertal disorders. DESIGN: Molecular studies. SETTING: University hospital. PATIENT(S): Thirty-three patients with gonadotropin-dependent precocious puberty, 22 with hypogonadotropic hypogonadism, and 50 controls. INTERVENTION(S): Genomic DNA extraction, NPY-Y1R gene sequence analysis, cell-surface expression, and functional activity of an identified receptor variant. MAIN OUTCOME MEASURE(S): Results of sequencing, cell-surface receptor expression, and receptor function. RESULT(S): A heterozygous substitution of lysine (K) by threonine (T) at position 374 in the carboxyl terminal region of NPY-Y1R was identified in a girl with familial GDPP. Her mother, who …
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Xiangbing Meng
Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized …
A Study Of Small Rnas From Cerebral Neocortex Of Pathology-Verified Alzheimer's Disease, Dementia With Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, And Non-Demented Human Controls, Sébastien S. Hébert, Wang-Xia Wang, Qi Zhu, Peter T. Nelson
A Study Of Small Rnas From Cerebral Neocortex Of Pathology-Verified Alzheimer's Disease, Dementia With Lewy Bodies, Hippocampal Sclerosis, Frontotemporal Lobar Dementia, And Non-Demented Human Controls, Sébastien S. Hébert, Wang-Xia Wang, Qi Zhu, Peter T. Nelson
Sanders-Brown Center on Aging Faculty Publications
MicroRNAs (miRNAs) are small (20-22 nucleotides) regulatory non-coding RNAs that strongly influence gene expression. Most prior studies addressing the role of miRNAs in neurodegenerative diseases (NDs) have focused on individual diseases such as Alzheimer's disease (AD), making disease-to-disease comparisons impossible. Using RNA deep sequencing, we sought to analyze in detail the small RNAs (including miRNAs) in the temporal neocortex gray matter from non-demented controls (n = 2), AD (n = 5), dementia with Lewy bodies (n = 4), hippocampal sclerosis of aging (n = 4), and frontotemporal lobar dementia (FTLD) (n = 5) cases, together accounting for the most prevalent …
Camp And Serum And Glucocorticoid-Inducible Kinase (Sgk) Regulate The Epithelial Na(+) Channel Through Convergent Phosphorylation Of Nedd4-2., Peter Snyder, Diane Olson, Rajesh Kabra, Ruifeng Zhou, Jennifer Steines
Camp And Serum And Glucocorticoid-Inducible Kinase (Sgk) Regulate The Epithelial Na(+) Channel Through Convergent Phosphorylation Of Nedd4-2., Peter Snyder, Diane Olson, Rajesh Kabra, Ruifeng Zhou, Jennifer Steines
Jennifer C. Steines Wagemester
The epithelial Na(+) channel (ENaC) functions as a pathway for epithelial Na(+) transport, contributing to Na(+) homeostasis and blood pressure control. Vasopressin increases ENaC expression at the cell surface through a pathway that includes cAMP and cAMP-dependent protein kinase (PKA), but the mechanisms that link PKA to ENaC are unknown. Here we found that cAMP regulates Na(+) transport in part by inhibiting the function of Nedd4-2, an E3 ubiquitin-protein ligase that targets ENaC for degradation. Consistent with this model, we found that cAMP inhibited Nedd4-2 by decreasing its binding to ENaC. Moreover, decreased Nedd4-2 expression (RNA interference) or overexpression of …
Linkage Of Two Human Pregnancy-Specific Beta 1-Glycoprotein Genes: One Is Associated With Hydatidiform Mole., Kimberly Leslie, S. Watanabe, K. Lei, D. Chou, C. Plouzek, H. Deng, J. Torres, J. Chou
Linkage Of Two Human Pregnancy-Specific Beta 1-Glycoprotein Genes: One Is Associated With Hydatidiform Mole., Kimberly Leslie, S. Watanabe, K. Lei, D. Chou, C. Plouzek, H. Deng, J. Torres, J. Chou
Kimberly K. Leslie
A genomic clone containing two linked human pregnancy-specific beta 1-glycoprotein (PS beta G) genes has been isolated and characterized. The two genes are arranged in the same 5'----3' orientation; the 3' region (including the A2 and B-C exons) of the upstream gene, PSGGA, is linked to the 5' region (including the 5'/L and L/N exons) of PSGGB, the downstream gene. Depending upon the domains compared, PSGGA and PSGGB share 92-98% nucleotide and 86-95% amino acid sequence identity with PSG93, the most abundant PS beta G transcript. The 3' exon (B-C) of PSGGA contains four alternative splice sites and three polyadenylylation …
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Cytoplasmic Metadherin (Mtdh) Provides Survival Advantage Under Conditions Of Stress By Acting As Rna-Binding Protein, Xiangbing Meng, Danlin Zhu, Shujie Yang, Xinjun Wang, Zhi Xiong, Yuping Zhang, Pavla Brachova, Kimberly Leslie
Kimberly K. Leslie
Overexpression of metadherin (MTDH) has been documented in many solid tumors and is implicated in metastasis and chemoresistance. MTDH has been detected at the plasma membrane as well as in the cytoplasm and nucleus, and the function of MTDH in these locales remains under investigation. In the nucleus, MTDH acts as a transcription co-factor to induce expression of chemoresistance-associated genes. However, MTDH is predominantly cytoplasmic in prostate tumors, and this localization correlates with poor prognosis. Herein, we used endometrial cancer cells as a model system to define a new role for MTDH in the cytoplasm. First, MTDH was primarily localized …
Cis And Trans Regulatory Mechanisms Control Ap2-Mediated B Cell Receptor Endocytosis Via Select Tyrosine-Based Motifs., Kathleen Busman-Sahay, Lisa Drake, Anand Sitaram, Michael Marks, James R Drake
Cis And Trans Regulatory Mechanisms Control Ap2-Mediated B Cell Receptor Endocytosis Via Select Tyrosine-Based Motifs., Kathleen Busman-Sahay, Lisa Drake, Anand Sitaram, Michael Marks, James R Drake
Department of Pathology, Anatomy, and Cell Biology Faculty Papers
Following antigen recognition, B cell receptor (BCR)-mediated endocytosis is the first step of antigen processing and presentation to CD4+ T cells, a crucial component of the initiation and control of the humoral immune response. Despite this, the molecular mechanism of BCR internalization is poorly understood. Recently, studies of activated B cell-like diffuse large B cell lymphoma (ABC DLBCL) have shown that mutations within the BCR subunit CD79b leads to increased BCR surface expression, suggesting that CD79b may control BCR internalization. Adaptor protein 2 (AP2) is the major mediator of receptor endocytosis via clathrin-coated pits. The BCR contains five putative AP2-binding …
Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly
Identification Of Phosphorylation Sites In The Cooh-Terminal Tail Of The Μ-Opioid Receptor., Ying-Ju Chen, Sue Oldfield, Adrian J. Butcher, Andrew B. Tobin, Kunal Saxena, Vsevolod V. Gurevich, Jeffrey L. Benovic, Graeme Henderson, Eamonn Kelly
Department of Biochemistry and Molecular Biology Faculty Papers
Phosphorylation is considered a key event in the signalling and regulation of the μ opioid receptor (MOPr). Here, we used mass spectroscopy to determine the phosphorylation status of the C-terminal tail of the rat MOPr expressed in human embryonic kidney 293 (HEK-293) cells. Under basal conditions, MOPr is phosphorylated on Ser(363) and Thr(370), while in the presence of morphine or [D-Ala2, NMe-Phe4, Gly-ol5]-enkephalin (DAMGO), the COOH terminus is phosphorylated at three additional residues, Ser(356) , Thr(357) and Ser(375). Using N-terminal glutathione S transferase (GST) fusion proteins of the cytoplasmic, C-terminal tail of MOPr and point mutations of the same, we …