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https://www.readbyqxmd.com/read/24998857/cr1-is-potentially-associated-with-rate-of-decline-in-sporadic-alzheimer-s-disease
#1
Christian Schmidt, Martin Wolff, Nicolas von Ahsen, Katharina Lange, Tim Friede, Inga Zerr
The objective of this study was to investigate potential associations of Alzheimer's disease risk single nucleotide polymorphisms (SNP) with disease progression. SNP in ACE, ApoE, BIN1, CLU, CR1, CST3, EXOC3L2, GWA14q32.13, IL8, LDLR, PICALM, and TNK1 were determined in 40 Alzheimer's disease patients who were observed for 2 to 3 years. Annual Mini Mental State Examination (MMSE) loss was used as the outcome parameter in multiple regression analyses. Regarding a CR1 SNP (rs3818361) G-allele carriers featured faster declines (approximately 3 MMSE points per year)...
October 2014: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/24449862/novel-antiviral-host-factor-tnk1-regulates-ifn-signaling-through-serine-phosphorylation-of-stat1
#2
Ee Lyn Ooi, Stephanie T Chan, Noell E Cho, Courtney Wilkins, Jessica Woodward, Meng Li, Ushio Kikkawa, Timothy Tellinghuisen, Michael Gale, Takeshi Saito
In response to viral infection, the host induces over 300 IFN-stimulated genes (ISGs), which are the central component of intracellular antiviral innate immunity. Inefficient induction of ISGs contributes to poor control and persistence of hepatitis C virus infection. Therefore, further understanding of the hepatocytic ISG regulation machinery will guide us to an improved management strategy against hepatitis C virus infection. In this study, comprehensive genome-wide, high-throughput cDNA screening for genes regulating ISG expression identified a tyrosine kinase nonreceptor 1 (TNK1) as a unique player in the ISG induction pathway...
February 4, 2014: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/24405801/comparative-analysis-of-gene-transcripts-for-cell-signaling-receptors-in-bone-marrow-derived-hematopoietic-stem-progenitor-cell-and-mesenchymal-stromal-cell-populations
#3
COMPARATIVE STUDY
Khairul Anam, Thomas A Davis
INTRODUCTION: Knowing the repertoire of cell signaling receptors would provide pivotal insight into the developmental and regenerative capabilities of bone marrow cell (BMC)-derived hematopoietic stem/progenitor cells (HSPCs) and bone marrow mesenchymal stromal cells (BMMSCs). METHODS: Murine HSPCs were enriched from fluorescence-activated cell sorting (FACS)-sorted Lin-c-Kit+Sca-1+ BMCs isolated from the tibia and femoral marrow compartments. Purified BMMSCs (CD73+, CD90+, CD105+, and CD45-, CD34-, CD31-, c-Kit-) with extensive self-renewal potential and multilineage differentiation capacity (into different mesodermal cell lineages including osteocytes, chrondrocytes, adipocytes) were derived from adherent BMC cultures after CD45+ cell depletion...
2013: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/23495751/comparing-immobilized-kinase-inhibitors-and-covalent-atp-probes-for-proteomic-profiling-of-kinase-expression-and-drug-selectivity
#4
COMPARATIVE STUDY
Simone Lemeer, Corina Zörgiebel, Benjamin Ruprecht, Kristian Kohl, Bernhard Kuster
Kinases are involved in the regulation of many cellular processes and aberrant kinase signaling has been implicated in human disease. As a consequence, kinases are attractive drug targets. Assessing kinase function and drug selectivity in a more physiological context is challenging and often hampered by the generally low expression level of kinases and the extensive post-translation modification in vivo. Kinase drug selectivity screens by chemical proteomics have gained attention because they allow the profiling of hundreds of kinases against one drug at the same time...
April 5, 2013: Journal of Proteome Research
https://www.readbyqxmd.com/read/23123741/testosterone-induced-persistent-susceptibility-to-plasmodium-chabaudi-malaria-long-term-changes-of-lincrna-and-mrna-expression-in-the-spleen
#5
Mohamed A Dkhil, Saleh Al-Quraishy, Denis Delic, Abdel-Azeem Abdel-Baki, Frank Wunderlich
Testosterone (T) is known to induce persistent susceptibility to blood-stage malaria of Plasmodium chabaudi in otherwise resistant female C57BL/6 mice, which is associated with permanent changes in mRNA expression of the liver. Here, we investigate the spleen as the major effector against blood-stage malaria for any possible T-induced long-term effects on lincRNA and mRNA expression. Female C57BL/6 mice were treated with T for 3 weeks, then T was withdrawn for 12 weeks before challenging with P. chabaudi. LincRNA and mRNA expression was examined after 12 weeks of T-withdrawal and after subsequent infections using Agilent whole mouse genome oligo microarrays...
February 2013: Steroids
https://www.readbyqxmd.com/read/22521882/global-tyrosine-kinome-profiling-of-human-thyroid-tumors-identifies-src-as-a-promising-target-for-invasive-cancers
#6
Nancy L Cho, Chi-Iou Lin, Jinyan Du, Edward E Whang, Hiromichi Ito, Francis D Moore, Daniel T Ruan
BACKGROUND: Novel therapies are needed for the treatment of invasive thyroid cancers. Aberrant activation of tyrosine kinases plays an important role in thyroid oncogenesis. Because current targeted therapies are biased toward a small subset of tyrosine kinases, we conducted a study to reveal novel therapeutic targets for thyroid cancer using a bead-based, high-throughput system. METHODS: Thyroid tumors and matched normal tissues were harvested from twenty-six patients in the operating room...
May 11, 2012: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/22414550/alzheimer-s-disease-genetic-polymorphisms-and-rate-of-decline
#7
Christian Schmidt, Martin Wolff, Nicolas von Ahsen, Inga Zerr
BACKGROUND/AIM: To investigate the influence of established genetic risk factors for Alzheimer's disease on the speed of disease progression. METHODS: Polymorphisms (in ACE, ApoE, BIN1, CLU, CR1, CST3, EXOC3L2, GWA14q32.13, IL8, LDLR, PICALM, TNK1) of 40 Alzheimer's disease patients from a longitudinal study were analyzed. A standardized loss of Mini-Mental State Examination points was used as the progression parameter. RESULTS: Polymorphisms in CST3 and EXOC3L2 as well as the absence of APOE4 were associated with more aggressive disease courses...
2012: Dementia and Geriatric Cognitive Disorders
https://www.readbyqxmd.com/read/22191060/genetics-of-late-onset-alzheimer-s-disease-update-from-the-alzgene-database-and-analysis-of-shared-pathways
#8
Paolo Olgiati, Antonis M Politis, George N Papadimitriou, Diana De Ronchi, Alessandro Serretti
The genetics of late-onset Alzheimer's disease (LOAD) has taken impressive steps forwards in the last few years. To date, more than six-hundred genes have been linked to the disorder. However, only a minority of them are supported by a sufficient level of evidence. This review focused on such genes and analyzed shared biological pathways. Genetic markers were selected from a web-based collection (Alzgene). For each SNP in the database, it was possible to perform a meta-analysis. The quality of studies was assessed using criteria such as size of research samples, heterogeneity across studies, and protection from publication bias...
2011: International Journal of Alzheimer's Disease
https://www.readbyqxmd.com/read/21536687/high-throughput-rnai-screening-identifies-a-role-for-tnk1-in-growth-and-survival-of-pancreatic-cancer-cells
#9
Meredith C Henderson, Irma M Gonzales, Shilpi Arora, Ashish Choudhary, Jeffrey M Trent, Daniel D Von Hoff, Spyro Mousses, David O Azorsa
To identify novel targets in pancreatic cancer cells, we used high-throughput RNAi (HT-RNAi) to select genes that, when silenced, would decrease viability of pancreatic cancer cells. The HT-RNAi screen involved reverse transfecting the pancreatic cancer cell line BxPC3 with a siRNA library targeting 572 kinases. From replicate screens, approximately 32 kinases were designated as hits, of which 22 kinase targets were selected for confirmation and validation. One kinase identified as a hit from this screen was tyrosine kinase nonreceptor 1 (TNK1), a kinase previously identified as having tumor suppressor-like properties in embryonic stem cells...
June 2011: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/21289309/rnai-screen-of-the-druggable-genome-identifies-modulators-of-proteasome-inhibitor-sensitivity-in-myeloma-including-cdk5
#10
Yuan Xiao Zhu, Rodger Tiedemann, Chang-Xin Shi, Holly Yin, Jessica E Schmidt, Laura A Bruins, Jonathan J Keats, Esteban Braggio, Chris Sereduk, Spyro Mousses, A Keith Stewart
The molecular target(s) cooperating with proteasome inhibition in multiple myeloma (MM) remain unknown. We therefore measured proliferation in MM cells transfected with 13 984 small interfering RNAs in the absence or presence of increasing concentrations of bortezomib. We identified 37 genes, which when silenced, are not directly cytotoxic but do synergistically potentiate the growth inhibitory effects of bortezomib. To focus on bortezomib sensitizers, genes that also sensitized MM to melphalan were excluded...
April 7, 2011: Blood
https://www.readbyqxmd.com/read/21132329/investigation-of-15-of-the-top-candidate-genes-for-late-onset-alzheimer-s-disease
#11
Olivia Belbin, Minerva M Carrasquillo, Michael Crump, Oliver J Culley, Talisha A Hunter, Li Ma, Gina Bisceglio, Fanggeng Zou, Mariet Allen, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, Kevin Morgan, Steven G Younkin
The 12 genome-wide association studies (GWAS) published to-date for late-onset Alzheimer's disease (LOAD) have identified over 40 candidate LOAD risk modifiers, in addition to apolipoprotein (APOE) ε4. A few of these novel LOAD candidate genes, namely BIN1, CLU, CR1, EXOC3L2 and PICALM, have shown consistent replication, and are thus credible LOAD susceptibility genes. To evaluate other promising LOAD candidate genes, we have added data from our large, case-control series (n=5,043) to meta-analyses of all published follow-up case-control association studies for six LOAD candidate genes that have shown significant association across multiple studies (TNK1, GAB2, LOC651924, GWA_14q32...
March 2011: Human Genetics
https://www.readbyqxmd.com/read/20697568/tnk1-kos1-a-novel-tumor-suppressor
#12
REVIEW
William Stratford May, Kishalay Hoare, Sarasija Hoare, Mary K Reinhard, Young J Lee, S Paul Oh
Tnk1/Kos1 is a non-receptor protein tyrosine kinase implicated in negative regulation of cell growth by a mechanism involving inhibition of Ras activation and requiring Tnk1/Kos1's intrinsic catalytic activity. Tnk1/Kos1 null mice were created by homologous recombination by deleting the catalytic domain. Upon aging, both Tnk1+/- and Tnk1-/- mice develop spontaneous tumors, including lymphomas and carcinomas at high rates (i.e. 27%, and 43%, respectively), indicating that Tnk1/Kos1 is a tumor suppressor. Tissues from Tnk1/Kos1-null mice exhibit proportionally higher levels of basal and growth factor-stimulated Ras activation...
2010: Transactions of the American Clinical and Climatological Association
https://www.readbyqxmd.com/read/20413850/systematic-analysis-of-candidate-genes-for-alzheimer-s-disease-in-a-french-genome-wide-association-study
#13
Geoffroy Laumet, Vincent Chouraki, Benjamin Grenier-Boley, Vanessa Legry, Simon Heath, Diana Zelenika, Nathalie Fievet, Didier Hannequin, Marc Delepine, Florence Pasquier, Olivier Hanon, Alexis Brice, Jacques Epelbaum, Claudine Berr, Jean-Francois Dartigues, Christophe Tzourio, Dominique Campion, Mark Lathrop, Lars Bertram, Philippe Amouyel, Jean-Charles Lambert
We selected twenty genes from the "Top Results" list on the AlzGene database website and assessed their association with risk of developing Alzheimer's disease (AD) in a large, genome-wide association study (using 526 SNPs from 2,032 AD cases and 5,328 controls) performed in France. The APOE, CLU, PICALM, and CR1 loci were excluded, since they had already been extensively analyzed. Ten genes/loci (TFAM, SORL1, CHRNB2, SORCS1, DAPK1, MTHFR, GWA 14q32.13, BDNF, NEDD9, and CH25H) showed weak nominal association with AD risk, in line with previous studies...
2010: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/19808789/genome-wide-association-studies-in-alzheimer-s-disease
#14
REVIEW
Lars Bertram, Rudolph E Tanzi
Genome-wide association studies (GWAS) have gained considerable momentum over the last couple of years for the identification of novel complex disease genes. In the field of Alzheimer's disease (AD), there are currently eight published and two provisionally reported GWAS, highlighting over two dozen novel potential susceptibility loci beyond the well-established APOE association. On the basis of the data available at the time of this writing, the most compelling novel GWAS signal has been observed in GAB2 (GRB2-associated binding protein 2), followed by less consistently replicated signals in galanin-like peptide (GALP), piggyBac transposable element derived 1 (PGBD1), tyrosine kinase, non-receptor 1 (TNK1)...
October 15, 2009: Human Molecular Genetics
https://www.readbyqxmd.com/read/19794087/identification-of-protein-tyrosine-kinases-with-oncogenic-potential-using-a-retroviral-insertion-mutagenesis-screen
#15
COMPARATIVE STUDY
Els Lierman, Helen Van Miegroet, Els Beullens, Jan Cools
Protein tyrosine kinases form a large family of signaling proteins implicated in both normal and malignant cell signaling. The aim of this study was to identify protein tyro-sine kinases that can transform hematopoietic cells to growth factor independent proliferation when constitutively activated by homodimerization. We used a modified retroviral insertion mutagenesis screen with a retroviral vector containing the homodimerization domain of ETV6 followed by an artificial splice donor site. Integration of this retroviral vector within a gene of the host genome would generate a fusion transcript containing the dimerization domain and part of the disrupted gene...
October 2009: Haematologica
https://www.readbyqxmd.com/read/19481140/functional-characterization-of-the-murine-tnk1-promoter
#16
Sarasija Hoare, Kishalay Hoare, Mary K Reinhard, Tammy O Flagg, William Stratford May
Tnk1/Kos1 is a non-receptor protein tyrosine kinase found to be a tumor suppressor. It negatively regulates cell growth by indirectly suppressing Ras activity. We identified and characterized the critical cis-elements required for Tnk1/Kos1's promoter activity. Results indicate that the murine Tnk1 promoter lacks a conventional TATA, CAAT or initiator element (Inr) but contains multiple transcription start sites. Transcription is initiated by a TATA-like element composed of an AT rich sequence at -30 (30 bp upstream) from the major transcription start site and an Inr-like element that overlaps the multiple start sites...
September 1, 2009: Gene
https://www.readbyqxmd.com/read/18974114/tnk1-kos1-knockout-mice-develop-spontaneous-tumors
#17
Sarasija Hoare, Kishalay Hoare, Mary K Reinhard, Young J Lee, S Paul Oh, W Stratford May
Tnk1/Kos1 is a non-receptor protein tyrosine kinase implicated in negatively regulating cell growth in a mechanism requiring its intrinsic catalytic activity. Tnk1/Kos1 null mice were created by homologous recombination by deleting the catalytic domain. Both Tnk1(+/-) and Tnk1(-/-) mice develop spontaneous tumors, including lymphomas and carcinomas, at high rates [27% (14 of 52) and 43% (12 of 28), respectively]. Tnk1/Kos1 expression is silenced in tumors that develop in Tnk1(+/-) mice but not in adjacent uninvolved tissue, and silencing occurs in association with Tnk1 promoter hypermethylation...
November 1, 2008: Cancer Research
https://www.readbyqxmd.com/read/18830724/assessment-of-alzheimer-s-disease-case-control-associations-using-family-based-methods
#18
Brit-Maren M Schjeide, Matthew B McQueen, Kristina Mullin, Jason DiVito, Meghan F Hogan, Michele Parkinson, Basavaraj Hooli, Christoph Lange, Deborah Blacker, Rudolph E Tanzi, Lars Bertram
The genetics of Alzheimer's disease (AD) is heterogeneous and remains only ill-defined. We have recently created a freely available and continuously updated online database (AlzGene; http://www.alzgene.org ) for which we collect all published genetic association studies in AD and perform systematic meta-analyses on all polymorphisms with sufficient genotype data. In this study, we tested 27 genes (ACE, BDNF, CH25H, CHRNB2, CST3, CTSD, DAPK1, GALP, hCG2039140, IL1B, LMNA, LOC439999, LOC651924, MAPT, MTHFR, MYH13, PCK1, PGBD1, PRNP, PSEN1, SORCS1, SORL1, TF, TFAM, TNK1, GWA_14q32...
February 2009: Neurogenetics
https://www.readbyqxmd.com/read/17595343/conserved-molecular-portraits-of-bovine-and-human-blastocysts-as-a-consequence-of-the-transition-from-maternal-to-embryonic-control-of-gene-expression
#19
COMPARATIVE STUDY
James Adjaye, Ralf Herwig, Thore C Brink, Doris Herrmann, Boris Greber, Smita Sudheer, Detlef Groth, Joseph W Carnwath, Hans Lehrach, Heiner Niemann
The present study investigated mRNA expression profiles of bovine oocytes and blastocysts by using a cross-species hybridization approach employing an array consisting of 15,529 human cDNAs as probe, thus enabling the identification of conserved genes during human and bovine preimplantation development. Our analysis revealed 419 genes that were expressed in both oocytes and blastocysts. The expression of 1,324 genes was detected exclusively in the blastocyst, in contrast to 164 in the oocyte including a significant number of novel genes...
October 22, 2007: Physiological Genomics
https://www.readbyqxmd.com/read/17471239/thirty-eight-negative-kinase-1-tnk1-facilitates-tnfalpha-induced-apoptosis-by-blocking-nf-kappab-activation
#20
N Azoitei, A Brey, T Busch, S Fulda, G Adler, T Seufferlein
Thirty-eight-negative kinase 1 (TNK1) is a member of the ACK-family of nonreceptor tyrosine kinases and was originally cloned from CD34+/Lin-/CD38-hematopoietic stem/progenitor cells. The signaling pathways induced by TNK1 are largely unknown. Here, we report that expression and consequent activation of TNK1 enables tumor necrosis factor alpha (TNFalpha)-induced apoptosis by selectively inhibiting TNFalpha-induced activation of nuclear factor-kappaB (NF-kappaB). TNK1 has no effect on NF-kappaB DNA binding or the composition of the NF-kappaB complex; however, the kinase markedly prevents TNFalpha-induced NF-kappaB transactivation...
October 4, 2007: Oncogene
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