keyword
MENU ▼
Read by QxMD icon Read
search

Knock in

keyword
https://www.readbyqxmd.com/read/28938651/positive-transcription-elongation-factor-b-p-tefb-is-a-therapeutic-target-in-human-multiple-myeloma
#1
Yu Zhang, Liang Zhou, Yun Leng, Yun Dai, Robert Z Orlowski, Steven Grant
The role of the positive RNA Pol II regulator, P-TEFb (positive transcription elongation factor b), in maintenance of the anti-apoptotic protein Mcl-1 and bortezomib (btz) resistance was investigated in human multiple myeloma (MM) cells. Mcl-1 was up-regulated in all MM lines tested, including bortezomib-resistant lines, human MM xenograft mouse models, and primary CD138(+) MM cells. Mcl-1 over-expression significantly reduced bortezomib lethality, indicating a functional role for Mcl-1 in bortezomib resistance...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938492/a-long-noncoding-rna-lncrna-amhr2-plays-a-role-in-amhr2-gene-activation-in-mouse-ovarian-granulosa-cells
#2
Atsushi P Kimura, Ryoma Yoneda, Misuzu Kurihara, Shota Mayama, Shin Matsubara
Anti-Müllerian hormone (AMH) is critical to the regression of Müllerian ducts during mammalian male differentiation and targets ovarian granulosa cells and testicular Sertoli and Leydig cells of adults. Specific effects of AMH are exerted via its receptor, AMH type II receptor (Amhr2), but the mechanism by which the Amhr2 gene is specifically activated is not fully understood. To see whether a proximal promoter was sufficient to Amhr2 gene activation, we generated transgenic mice that bore the enhanced green fluorescent protein (EGFP) gene driven by a 500-bp mouse Amhr2 gene promoter...
September 14, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938487/regulation-of-endogenous-male-rodent-glp-1-secretion-and-human-islet-insulin-secretion-by-antagonism-of-somatostatin-receptor-5
#3
Thomas B Farb, Marta Adeva, Thomas J Beauchamp, Over Cabrera, David A Coates, Tamika DeShea Meredith, Brian A Droz, Alexander Efanov, James V Ficorilli, Susan L Gackenheimer, Maria A Martinez-Grau, Victoriano Molero, Gema Ruano, Michael A Statnick, Todd M Suter, Samreen K Syed, Miguel A Toledo, Francis S Willard, Xin Zhou, Krister B Bokvist, David G Barrett
Incretin and insulin responses to nutrient loads are suppressed in persons with diabetes, resulting in decreased glycemic control. Whereas agents including sulfonylureas and Dipeptidyl peptidase-4 inhibitors (DPP4i) partially reverse these effects and provide therapeutic benefit, their modes of action limit efficacy. Because somatostatin (SST) has been shown to suppress both insulin and GLP-1 secretion through the Gi-coupled SST receptor 5 (SSTR5) isoform in vitro, antagonism of SSTR5 may improve glycemic control via intervention in both pathways...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938484/long-noncoding-rnas-potential-regulators-involved-in-the-pathogenesis-of-polycystic-ovary-syndrome
#4
Yu-Dong Liu, Ying Li, Shu-Xian Feng, De-Sheng Ye, Xin Chen, Xing-Yu Zhou, Shi-Ling Chen
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women of reproductive age, and its etiology remains poorly understood. Altered activities of long noncoding RNAs (lncRNAs) have been associated with human diseases and development. However, the roles of lncRNAs are unknown in reproductive medicine. We investigated the potential role of lncRNAs in the pathogenesis of PCOS, using human granulosa cells (GCs) and the KGN cell line. We used microarrays to compare lncRNA expression profiles in GCs from 7 PCOS patients and 7 matched women...
August 31, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938427/calreticulin-is-involved-in-invasion-of-human-extravillous-trophoblasts-through-functional-regulation-of-integrin-%C3%AE-1
#5
Madoka Yamamoto, Midori Ikezaki, Saori Toujima, Naoyuki Iwahashi, Mika Mizoguchi, Sakiko Nanjo, Sawako Minami, Yoshito Ihara, Kazuhiko Ino
Calreticulin (CRT), a molecular chaperone in the endoplasmic reticulum (ER), plays a variety of roles in cell growth, differentiation, apoptosis, immunity, and cancer biology. It has been reported that CRT is expressed in the human placenta, although its function in placental development is poorly understood. Appropriate invasion of extravillous trophoblasts (EVTs) into the maternal decidua is necessary for successful pregnancy. The objective of the present study was to investigate the expression and functional role of CRT in EVTs by utilizing the human EVT cell line HTR8/SVneo, in which CRT gene expression was knocked down...
August 29, 2017: Endocrinology
https://www.readbyqxmd.com/read/28938092/ctcf-mediated-enhancer-promoter-interaction-is-a-critical-regulator-of-cell-to-cell-variation-of-gene-expression
#6
Gang Ren, Wenfei Jin, Kairong Cui, Joseph Rodrigez, Gangqing Hu, Zhiying Zhang, Daniel R Larson, Keji Zhao
Recent studies indicate that even a homogeneous population of cells display heterogeneity in gene expression and response to environmental stimuli. Although promoter structure critically influences the cell-to-cell variation of gene expression in bacteria and lower eukaryotes, it remains unclear what controls the gene expression noise in mammals. Here we report that CTCF decreases cell-to-cell variation of expression by stabilizing enhancer-promoter interaction. We show that CTCF binding sites are interwoven with enhancers within topologically associated domains (TADs) and a positive correlation is found between CTCF binding and the activity of the associated enhancers...
September 21, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28937653/differential-functional-roles-of-aldh1a1-and-aldh1a3-in-mediating-metastatic-behavior-and-therapy-resistance-of-human-breast-cancer-cells
#7
Alysha K Croker, Mauricio Rodriguez-Torres, Ying Xia, Siddika Pardhan, Hon Sing Leong, John D Lewis, Alison L Allan
Previous studies indicate that breast cancer cells with high aldehyde dehydrogenase (ALDH) activity and CD44 expression (ALDH(hi)CD44⁺) contribute to metastasis and therapy resistance, and that ALDH1 correlates with poor outcome in breast cancer patients. The current study hypothesized that ALDH1 functionally contributes to breast cancer metastatic behavior and therapy resistance. Expression of ALDH1A1 or ALDH1A3 was knocked down in MDA-MB-468 and SUM159 human breast cancer cells using siRNA. Resulting impacts on ALDH activity (Aldefluor(®) assay); metastatic behavior and therapy response in vitro (proliferation/adhesion/migration/colony formation/chemotherapy and radiation) and extravasation/metastasis in vivo (chick choroiallantoic membrane assay) was assessed...
September 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28936224/role-of-crrlk1l-cell-wall-sensors-hercules1-and-2-theseus1-and-feronia-in-growth-adaptation-triggered-by-heavy-metals-and-trace-elements
#8
Julia Richter, Marie Ploderer, Gaëlle Mongelard, Laurent Gutierrez, Marie-Theres Hauser
Cell walls are not only a protective barrier surrounding protoplasts but serve as signaling platform between the extracellular environment and the intracellular physiology. Ions of heavy metals and trace elements, summarized to metal ions, bind to cell wall components, trigger their modification and provoke growth responses. To examine if metal ions trigger cell wall sensing receptor like kinases (RLKs) of the Catharanthus roseus RLK1-like (CrRLK1L) family we employed a molecular genetic approach. Quantitative transcription analyses show that HERCULES1 (HERK1), THESEUS1 (THE1), and FERONIA (FER) were differently regulated by cadmium (Cd), nickel (Ni), and lead (Pb)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28935867/s100a4-contributes-to-colitis-development-by-increasing-the-adherence-of-citrobacter-rodentium-in-intestinal-epithelial-cells
#9
Jinhua Zhang, Ying Jiao, Shasha Hou, Tian Tian, Qi Yuan, Huaijie Hao, Zhenlong Wu, Xuexiang Bao
S100A4 has been implicated in cancer and several inflammatory diseases, but its role in inflammatory bowel disease has not been well investigated. Here, upon infection with Citrobacter rodentium, a model for enteropathogenic Escherichia coli infection in humans, induced the infiltration of a large number of S100A4(+) cells into the colon in wild type (WT) mice. Deficiency of S100A4 reduced weight loss, bacterial colonization and colonic pathology. Furthermore, the expression of inflammatory cytokines and the recruitment of macrophages and neutrophils also decreased significantly in S100A4 knock out (S100A4 (-/-)) mice...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935467/reciprocal-role-of-sirt6-and-hexokinase-2-in-the-regulation-of-autophagy-driven-monocyte-differentiation
#10
Ankita Singh, Ellora Sen
Emerging evidences suggest the impact of autophagy on differentiation but the underlying molecular links between metabolic restructuring and autophagy during monocyte differentiation remain elusive. An increase in PPARγ, HK2 and SIRT6 expression was observed upon PMA induced monocyte differentiation. While PPARγ positively regulated HK2 and SIRT6 expression, the latter served as a negative regulator of HK2. Changes in expression of these metabolic modelers were accompanied by decreased glucose uptake and increase in Chibby, a potent antagonist of β-catenin/Wnt pathway...
September 18, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28934469/hnrnp-l-controls-hpv16-rna-polyadenylation-and-splicing-in-an-akt-kinase-dependent-manner
#11
Naoko Kajitani, Jacob Glahder, Chengjun Wu, Haoran Yu, Kersti Nilsson, Stefan Schwartz
Inhibition of the Akt kinase activates HPV16 late gene expression by reducing HPV16 early polyadenylation and by activating HPV16 late L1 mRNA splicing. We identified 'hot spots' for RNA binding proteins at the early polyA signal and at splice sites on HPV16 late mRNAs. We observed that hnRNP L was associated with sequences at all HPV16 late splice sites and at the early polyA signal. Akt kinase inhibition resulted in hnRNP L dephosphorylation and reduced association of hnRNP L with HPV16 mRNAs. This was accompanied by an increased binding of U2AF65 and Sam68 to HPV16 mRNAs...
September 19, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28934397/a-modifier-of-huntington-s-disease-onset-at-the-mlh1-locus
#12
Jong-Min Lee, Michael J Chao, Denise Harold, Kawther Abu Elneel, Tammy Gillis, Peter Holmans, Lesley Jones, Michael Orth, Richard H Myers, Seung Kwak, Vanessa C Wheeler, Marcy E MacDonald, James F Gusella
Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an expanded CAG repeat in HTT. Many clinical characteristics of HD such as age at motor onset are determined largely by the size of HTT CAG repeat. However, emerging evidence strongly supports a role for other genetic factors in modifying the disease pathogenesis driven by mutant huntingtin. A recent genome-wide association analysis to discover genetic modifiers of HD onset age provided initial evidence for modifier loci on chromosomes 8 and 15 and suggestive evidence for a locus on chromosome 3...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934388/loss-of-slc25a46-causes-neurodegeneration-by-affecting-mitochondrial-dynamics-and-energy-production-in-mice
#13
Zhuo Li, Yanyan Peng, Robert B Hufnagel, Yueh-Chiang Hu, Chuntao Zhao, Luis F Queme, Zaza Khuchua, Ashley M Driver, Fei Dong, Q Richard Lu, Diana M Lindquist, Michael P Jankowski, Rolf W Stottmann, Winston W Y Kao, Taosheng Huang
Recently, we identified biallelic mutations of SLC25A46 in patients with multiple neuropathies. Functional studies revealed that SLC25A46 may play an important role in mitochondrial dynamics by mediating mitochondrial fission. However, the cellular basis and pathogenic mechanism of the SLC25A46-related neuropathies are not fully understood. Thus, we generated a Slc25a46 knock-out mouse model. Mice lacking SLC25A46 displayed severe ataxia, mainly caused by degeneration of Purkinje cells. Increased numbers of small, unmyelinated and degenerated optic nerves as well as loss of retinal ganglion cells indicated optic atrophy...
October 1, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28934293/generation-of-a-pancreatic-cancer-model-using-a-pdx1-flp-recombinase-knock-in-allele
#14
Jinghai Wu, Xin Liu, Sunayana G Nayak, Jason R Pitarresi, Maria C Cuitiño, Lianbo Yu, Blake E Hildreth, Katie A Thies, Daniel J Schilling, Soledad A Fernandez, Gustavo Leone, Michael C Ostrowski
The contribution of the tumor microenvironment to the development of pancreatic adenocarcinoma (PDAC) is unclear. The LSL-KrasG12D/+;LSL-p53R172H/+;Pdx-1-Cre (KPC) tumor model, which is widely utilized to faithfully recapitulate human pancreatic cancer, depends on Cre-mediated recombination in the epithelial lineage to drive tumorigenesis. Therefore, specific Cre-loxP recombination in stromal cells cannot be applied in this model, limiting the in vivo investigation of stromal genetics in tumor initiation and progression...
2017: PloS One
https://www.readbyqxmd.com/read/28934149/oncolytic-reovirus-infection-is-facilitated-by-the-autophagic-machinery
#15
Vera Kemp, Iris J C Dautzenberg, Ronald W Limpens, Diana J M van den Wollenberg, Rob C Hoeben
Mammalian reovirus is a double-stranded RNA virus that selectively infects and lyses transformed cells, making it an attractive oncolytic agent. Despite clinical evidence for anti-tumor activity, its efficacy as a stand-alone therapy remains to be improved. The success of future trials can be greatly influenced by the identification and the regulation of the cellular pathways that are important for reovirus replication and oncolysis. Here, we demonstrate that reovirus induces autophagy in several cell lines, evident from the formation of Atg5-Atg12 complexes, microtubule-associated protein 1 light chain 3 (LC3) lipidation, p62 degradation, the appearance of acidic vesicular organelles, and LC3 puncta...
September 21, 2017: Viruses
https://www.readbyqxmd.com/read/28933784/inhibition-of-the-deubiquitinase-usp5-leads-to-c-maf-protein-degradation-and-myeloma-cell-apoptosis
#16
Siyu Wang, Jiaxiang Juan, Zubin Zhang, Yanyun Du, Yujia Xu, Jiefei Tong, Biyin Cao, Michael F Moran, Yuanying Zeng, Xinliang Mao
The deubiquitinase USP5 stabilizes c-Maf, a key transcription factor in multiple myeloma (MM), but the mechanisms and significance are unclear. In the present study, USP5 was found to interact with c-Maf and prevented it from degradation by decreasing its polyubiquitination level. Specifically, the 308th and 347th lysine residues in c-Maf were critical for USP5-mediated deubiquitination and stability. There are five key domains in the USP5 protein and subsequent studies revealed that the cryptic ZnF domain and the C-box domain interacted with c-Maf but the UBA1/UBA2 domain partly increased its stability...
September 21, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28933560/unintentional-nontraffic-injury-and-fatal-events-threats-to-children-in-and-around-vehicles
#17
Mark R Zonfrillo, Mackenzie L Ramsay, Janette E Fennell, Amber Rollins
Objective There have been substantial reductions in motor vehicle crash-related child fatalities due to advances in legislation, public safety campaigns, and engineering. Less is known about nontraffic injuries and fatalities to children in and around motor vehicles. The objective of this study was to describe the frequency of various nontraffic incidents, injuries, and fatalities to children using a unique surveillance system and database. Methods Instances of nontraffic injuries and fatalities in the United States to children 0-14 years were tracked from January 1990 - December 2014 using a compilation of sources including media reports, individual accounts from families of affected children, medical examiner reports, police reports, child death review teams, coroner reports, medical professionals, legal professionals, and other various modes of publication...
September 21, 2017: Traffic Injury Prevention
https://www.readbyqxmd.com/read/28931858/loss-of-p73-in-ependymal-cells-during-the-perinatal-period-leads-to-aqueductal-stenosis
#18
Masashi Fujitani, Ryohei Sato, Toshihide Yamashita
The p53 family member p73 plays a critical role in brain development. p73 knockout mice exhibit a number of deficits in the nervous system, such as neuronal death, hydrocephalus, hippocampal dysgenesis, and pheromonal defects. Among these phenotypes, the mechanisms of hydrocephalus remain unknown. In this study, we generated a p73 knock-in (KI) mutant mouse and a conditional p73 knockout mouse. The homozygous KI mutants showed aqueductal stenosis. p73 was expressed in the ependymal cell layer and several brain areas...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931820/the-non-canonical-poly-a-polymerase-fam46c-acts-as-an-onco-suppressor-in-multiple-myeloma
#19
Seweryn Mroczek, Justyna Chlebowska, Tomasz M Kuliński, Olga Gewartowska, Jakub Gruchota, Dominik Cysewski, Vladyslava Liudkovska, Ewa Borsuk, Dominika Nowis, Andrzej Dziembowski
FAM46C is one of the most frequently mutated genes in multiple myeloma. Here, using a combination of in vitro and in vivo approaches, we demonstrate that FAM46C encodes an active non-canonical poly(A) polymerase which enhances mRNA stability and gene expression. Reintroduction of active FAM46C into multiple myeloma cell lines, but not its catalytically-inactive mutant, leads to broad polyadenylation and stabilization of mRNAs strongly enriched with those encoding endoplasmic reticulum-targeted proteins and induces cell death...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28931627/the-nitrate-transporter-family-protein-npf8-6-controls-the-n-fixing-nodule-activity
#20
Vladimir Totev Valkov, Ludovico Martins Alves, Stefano Sol, Mélanie Noguero, Sophie Léran, Benoit Lacombe, Maurizio Chiurazzi
N-fixing nodules are new organs formed on legume roots as result of the beneficial interaction with soil bacteria, rhizobia. The nodule functioning is still a poorly characterized step of the symbiotic interaction as only few of the genes induced in N-fixing nodules have been functionally characterized. We present here the characterization of the member of the Lotus japonicus nitrate transporter 1/peptide transporter family LjNPF8.6. The phenotypic characterization carried out in independent L. japonicus LORE1 insertion lines indicates a positive role of LjNPF8...
September 20, 2017: Plant Physiology
keyword
keyword
78004
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"