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https://www.readbyqxmd.com/read/29332143/conjunction-of-g-quadruplex-and-stem-loop-in-the-5-untranslated-region-of-mouse-hepatocyte-nuclear-factor-4-alpha1-mediates-strong-inhibition-of-protein-expression
#1
Shangdong Guo, Hong Lu
Hepatocyte nuclear factor 4-alpha (HNF4α) is a well-established master regulator of liver development and function. Restoration of HNF4α can treat multiple liver disorders and liver cancers. To date, HNF4α is still "undruggable" due to lack of known activating ligands. Thus, understanding the regulatory mechanism of HNF4α expression may help develop an alternative approach to modulate HNF4α protein levels. G-quadruplexes (G4) are non-canonical stable secondary structures discovered mostly in the promoters of oncogenes...
January 13, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29329338/pharmacoepidemiological-assessment-of-adherence-and-influencing-co-factors-among-primary-open-angle-glaucoma-patients-an-observational-cohort-study
#2
Stefanie Frech, Daniel Kreft, Rudolf F Guthoff, Gabriele Doblhammer
The goal of this study was to assess the adherence of primary open-angle glaucoma (POAG) patients to medication, and to determine co-factors influencing adherence, using a representative sample of members of the largest German public health insurer. The observational cohort study was based on a longitudinal data set from 2010-2013 and included 250,000 insured persons aged 50 and older with 10,120 diagnosed POAG patients. Uni- and multivariate analysis was performed to investigate several aspects of glaucoma, such as prevalence, adherence, and co-factors influencing adherence...
2018: PloS One
https://www.readbyqxmd.com/read/29321323/hiv-1-vif-s-capacity-to-manipulate-the-cell-cycle-is-species-specific
#3
Edward L Evans, Jordan T Becker, Stephanie L Fricke, Kishan Patel, Nathan M Sherer
Cells derived from mice and other rodents exhibit profound blocks to HIV-1 virion production reflecting species-specific incompatibilities between viral Tat and Rev proteins and essential host factors Cyclin T1 (CCNT1) and Exportin-1 (XPO1, also known as CRM1), respectively. To determine if mouse cell blocks other than CCNT1 and XPO1 affect HIV's post-integration stages, we studied HIV-1NL4-3 gene expression in mouse NIH 3T3 cells modified to constitutively express HIV-1 compatible versions of CCNT1 and XPO1 (3T3...
January 10, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29317714/mechanism-and-structural-diversity-of-exoribonuclease-resistant-rna-structures-in-flaviviral-rnas
#4
Andrea MacFadden, Zoe O'Donoghue, Patricia A G C Silva, Erich G Chapman, René C Olsthoorn, Mark G Sterken, Gorben P Pijlman, Peter J Bredenbeek, Jeffrey S Kieft
Flaviviruses such as Yellow fever, Dengue, West Nile, and Zika generate disease-linked viral noncoding RNAs called subgenomic flavivirus RNAs. Subgenomic flavivirus RNAs result when the 5'-3' progression of cellular exoribonuclease Xrn1 is blocked by RNA elements called Xrn1-resistant RNAs located within the viral genome's 3'-untranslated region that operate without protein co-factors. Here, we show that Xrn1-resistant RNAs can halt diverse exoribonucleases, revealing a mechanism in which they act as general mechanical blocks that 'brace' against an enzyme's surface, presenting an unfolding problem that confounds further enzyme progression...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29311656/defining-murine-organogenesis-at-single-cell-resolution-reveals-a-role-for-the-leukotriene-pathway-in-regulating-blood-progenitor-formation
#5
Ximena Ibarra-Soria, Wajid Jawaid, Blanca Pijuan-Sala, Vasileios Ladopoulos, Antonio Scialdone, David J Jörg, Richard C V Tyser, Fernando J Calero-Nieto, Carla Mulas, Jennifer Nichols, Ludovic Vallier, Shankar Srinivas, Benjamin D Simons, Berthold Göttgens, John C Marioni
During gastrulation, cell types from all three germ layers are specified and the basic body plan is established 1 . However, molecular analysis of this key developmental stage has been hampered by limited cell numbers and a paucity of markers. Single-cell RNA sequencing circumvents these problems, but has so far been limited to specific organ systems 2 . Here, we report single-cell transcriptomic characterization of >20,000 cells immediately following gastrulation at E8.25 of mouse development. We identify 20 major cell types, which frequently contain substructure, including three distinct signatures in early foregut cells...
January 8, 2018: Nature Cell Biology
https://www.readbyqxmd.com/read/29309911/altered-hemoglobin-co-factor-sensitivity-does-not-underlie-the-evolution-of-derived-fossorial-specializations-in-the-family-talpidae
#6
Kevin L Campbell, Michael J Gaudry, Kai He, Hitoshi Suzuki, Ya-Ping Zhang, Xue-Long Jiang, Roy E Weber
The high O2 affinity of European mole (Talpa europaea) blood is postulated to largely arise from the presence of two β-globin chain residues (β4 Ser and β5 Gly) that weaken the interaction of its hemoglobin (Hb) with the red cell organophosphate 2,3-diphosphoglycerate (DPG). This latter trait is generally accepted to be an 'adaptation to subterranean life', despite the fact that no data are available for more basal mole lineages that have no evolutionary history of fossoriality (i.e. the ambulatory, high-elevation shrew-like moles and the semi-aquatic desmans), and which may similarly benefit from an elevated blood O2 affinity...
January 5, 2018: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29307292/the-aliens-inside-us-herv-w-endogenous-retroviruses-and-multiple-sclerosis
#7
Antonina Dolei
Two human endogenous retroviruses of the HERV-W family are proposed as multiple sclerosis (MS) co-factors: MS-associated retrovirus (MSRV) and ERVWE1, whose env proteins showed several potentially neuropathogenic features, in vitro and in animal models. Phase II clinical trials against HERV-Wenv are ongoing. HERV-W/MSRV was repeatedly found in MS patients, in striking parallel with MS stages, active/remission phases, and therapy outcome. The HERV-Wenv protein is highly expressed in active MS plaques. Early MSRV presence in spinal fluids predicted worst MS progression 10 years in advance...
January 2018: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/29307143/prediction-of-metal-ion-binding-sites-in-proteins-from-amino-acid-sequences-by-using-simplified-amino-acid-alphabets-and-random-forest-model
#8
Suresh Kumar
Metal binding proteins or metallo-proteins are important for the stability of the protein and also serve as co-factors in various functions like controlling metabolism, regulating signal transport, and metal homeostasis. In structural genomics, prediction of metal binding proteins help in the selection of suitable growth medium for overexpression's studies and also help in obtaining the functional protein. Computational prediction using machine learning approach has been widely used in various fields of bioinformatics based on the fact all the information contains in amino acid sequence...
December 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/29305158/tbr2-antagonizes-retinoic-acid-dependent-neuronal-differentiation-by-repressing-zfp423-during-corticogenesis
#9
Luca Massimino, Lisbeth Flores-Garcia, Bruno Di Stefano, Gaia Colasante, Cecilia Icoresi-Mazzeo, Mattia Zaghi, Bruce A Hamilton, Alessandro Sessa
During cerebral cortex development, neural progenitors are required to elaborate a variety of cell differentiation signals to which they are continuously exposed. RA acid is a potent inducer of neuronal differentiation as it was found to influence cortical development. We report herein that TBR2, a transcription factor specific to Intermediate (Basal) Neural Progenitors (INPs), represses activation of the RA responsive element and expression of RA target genes in cell lines. This repressive action on RA signaling was functionally confirmed by the decrease of RA-mediated neuronal differentiation in neural stem cells stably overexpressing TBR2...
January 2, 2018: Developmental Biology
https://www.readbyqxmd.com/read/29303380/should-vitamin-k-be-supplemented-instead-of-antagonised-in-patients-with-idiopathic-pulmonary-fibrosis
#10
Bart de Brouwer, Ianthe Piscaer, Jan H von der Thusen, Jan C Grutters, Roger Eg Schutgens, Emiel Fm Wouters, Rob Janssen
There is an ongoing need for additional interventions in idiopathic pulmonary fibrosis (IPF) as antifibrotic drugs currently available only inhibit and do not stall disease progression. Vitamin K is a co-factor for the activation of coagulation factors. However, it is also required to activate proteins with functions outside of the coagulation cascade, such as matrix Gla protein (MGP), a defender against soft tissue calcification. Vitamin K antagonists are anticoagulants that are, for unknown reasons, associated with increased mortality in IPF...
January 5, 2018: Expert Review of Respiratory Medicine
https://www.readbyqxmd.com/read/29297947/loss-of-function-mutations-in-isca2-disrupt-4fe-4s-cluster-machinery-and-cause-a-fatal-leukodystrophy-with-hyperglycinemia-and-mtdna-depletion
#11
Joseph T Alaimo, Arnaud Besse, Charlotte L Alston, Ki Pang, Vivek Appadurai, Monisha Samanta, Patroula Smpokou, Robert McFarland, Robert W Taylor, Penelope E Bonnen
Iron-sulfur (Fe-S) clusters are essential co-factors for proteins that participate in fundamental cellular processes including metabolism, DNA replication and repair, transcriptional regulation, and the mitochondrial electron transport chain (ETC). ISCA2 plays a role in the biogenesis of Fe-S clusters and a recent report described subjects displaying infantile-onset leukodystrophy due to bi-allelic mutation of ISCA2. We present two additional unrelated cases, and provide a more complete clinical description that includes hyperglycinemia, leukodystrophy of the brainstem with longitudinally extensive spinal cord involvement, and mtDNA deficiency...
January 3, 2018: Human Mutation
https://www.readbyqxmd.com/read/29289895/notch-after-cleavage
#12
REVIEW
Sarah J Bray, Maria Gomez-Lamarca
The discovery that Notch activation involves a proteolytic cleavage to release the intracellular domain (NICD) revolutionized the field of Notch signaling. It resulted in a simple model whereby the cleaved NICD enters the nucleus and activates expression of genes by forming a DNA bound complex with CSL. However, is it really this simple? The realization that the outcome from activating Notch varies greatly from cell to cell raised many questions about what governs the target gene selections in different cell types...
December 28, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/29289754/estrogen-regulated-transcription-mammary-gland-and-uterus
#13
Yasmin M Vasquez
Estrogen (E2) plays a central role in the developmental, metabolic and reproductive functions of both males and females. E2 acts via the estrogen receptor alpha (ERα) to regulate transcription of genes involved in numerous cellular functions. The E2-dependent engagement of ERα across the genome, collectively called the ERα 'cistrome', exhibits a high degree of complexity and plasticity. The ERα cistrome is defined by pioneer factors, transcription co-factors, posttranslational modifications of ERα, the chromatin environment, and cross talk with other signaling pathways...
December 29, 2017: Steroids
https://www.readbyqxmd.com/read/29278703/overexpression-of-lhx2-suppresses-proliferation-of-human-t-cell-acute-lymphoblastic-leukemia-derived-cells-partly-by-reducing-lmo2-protein-levels
#14
Kazuya Miyashita, Kenji Kitajima, Susumu Goyama, Toshio Kitamura, Takahiko Hara
T cell acute lymphoblastic leukemia (T-ALL) is a malignant cancer with poor prognosis. The transcriptional co-factor LIM domain only 2 (LMO2) and its target gene HHEX are essential for self-renewal of T cell precursors and T-ALL etiology. LMO2 directly associates with LDB1 in a large DNA-containing nuclear complex and controls the transcription of T-ALL-related genes. Recently, we reported that overexpression of the LIM-homeodomain transcription factor, Lhx2, results in liberation of the Lmo2 protein from the Lmo2-Ldb1 complex, followed by ubiquitin proteasome mediated degradation...
December 23, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29277775/novel-metabolically-stable-pca-1-alkbh3-inhibitor-has-potent-antiproliferative-effects-on-du145-cells-in-vivo
#15
Masahiro Ueda, Tadashi Shimizu, Miyuki Mabuchi, Kota Horiike, Kaori Kitae, Hiroaki Hase, Yuko Ueda, Kazutake Tsujikawa, Akito Tanaka
Novel potent prostate cancer antigen-1 (PCA-1)/alpha-ketoglutarate-dependent dioxygenase alkB homolog 3 (ALKBH3) inhibitors both in vivo and in vivo were designed and evaluated by a stability assay in an S9 mixture, a mixture of rat liver homogenate and co-factors, and oral absorbability assay in rat, as well as enzyme and cell assays, and resulted in the synthesis of a novel potent PCA-1/ALKBH3 inhibitor in vivo. Among them, compound 7l exhibited potent inhibitory activities in a xenograft model bearing DU145 tumor at 10 mg/kg by subcutaneous administration without negative side-effects...
January 2018: Anticancer Research
https://www.readbyqxmd.com/read/29238519/how-to-manage-anaphylaxis-in-primary-care
#16
REVIEW
Alberto Alvarez-Perea, Luciana Kase Tanno, María L Baeza
Anaphylaxis is defined as a severe life-threatening generalized or systemic hypersensitivity reaction characterized by rapidly developing airway and/or circulation problems. It presents with very different combinations of symptoms and apparently mild signs and can progress to fatal anaphylactic shock unpredictably. The difficulty in recognizing anaphylaxis is due, in part, to the variability of diagnostic criteria, which in turn leads to a delay in administration of appropriate treatment, thus increasing the risk of death...
2017: Clinical and Translational Allergy
https://www.readbyqxmd.com/read/29236325/aml1-eto-trans-activates-c-kit-expression-through-the-long-range-interaction-between-promoter-and-intronic-enhancer
#17
Ying Tian, Genjie Wang, Qingzhu Hu, Xichun Xiao, Shuxia Chen
The AML1/ETO onco-fusion protein is crucial for the genesis of t(8;21) acute myeloid leukemia (AML) and is well documented as a transcriptional repressor through dominant-negative effect. However, little is known about the transactivation mechanism of AML1/ETO. Through large cohort of patient's expression level data analysis and a series of experimental validation, we report here that AML1/ETO transactivates c-KIT expression through directly binding to and mediating the long-range interaction between the promoter and intronic enhancer regions of c-KIT...
December 13, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29233227/dna-partitions-into-triplets-under-tension-in-the-presence-of-organic-cations-with-sequence-evolutionary-age-predicting-the-stability-of-the-triplet-phase
#18
Amirhossein Taghavi, Paul van der Schoot, Joshua T Berryman
Using atomistic simulations, we show the formation of stable triplet structure when particular GC-rich DNA duplexes are extended in solution over a timescale of hundreds of nanoseconds, in the presence of organic salt. We present planar-stacked triplet disproportionated DNA (Σ DNA) as a possible solution phase of the double helix under tension, subject to sequence and the presence of stabilising co-factors. Considering the partitioning of the duplexes into triplets of base pairs as the first step of operation of recombinase enzymes like RecA, we emphasise the structure-function relationship in Σ DNA...
January 2017: Quarterly Reviews of Biophysics
https://www.readbyqxmd.com/read/29232865/does-the-short-term-effect-of-air-pollution-influence-the-incidence-of-spontaneous-intracerebral-hemorrhage-in-different-patient-groups-big-data-analysis-in-taiwan
#19
Ting-Ying Chien, Hsien-Wei Ting, Chien-Lung Chan, Nan-Ping Yang, Ren-Hao Pan, K Robert Lai, Su-In Hung
Spontaneous intracerebral hemorrhage (sICH) has a high mortality rate. Research has demonstrated that the occurrence of sICH is related to air pollution. This study used big data analysis to explore the impact of air pollution on the risk of sICH in patients of differing age and geographic location. 39,053 cases were included in this study; 14,041 in the Taipei region (Taipei City and New Taipei City), 5537 in Taoyuan City, 7654 in Taichung City, 4739 in Tainan City, and 7082 in Kaohsiung City. The results of correlation analysis indicated that there were two pollutants groups, the CO and NO₂ group and the PM2...
December 10, 2017: International Journal of Environmental Research and Public Health
https://www.readbyqxmd.com/read/29231738/affinity-purification-and-single-molecule-analysis-of-integral-membrane-proteins-from-crude-cell-membrane-preparations
#20
Anders Oskar Lundgren, Björn Johansson Fast, Stephan Block, Björn Agnarsson, Erik Reimhult, Anders Gunnarsson, Fredrik Höök
The function of integral membrane proteins is critically dependent on their naturally surrounding lipid membrane. Detergent-solubilized and purified membrane proteins are therefore often reconstituted into cell-membrane mimics and analysed for their function with single-molecule microscopy. Expansion of this approach towards a broad range of pharmaceutically interesting drug targets and biomarkers however remains hampered by the fact that these proteins have low expression levels, and that detergent solubilisation and reconstitution often cause protein conformational changes and loss of membrane-specific co-factors, which may impair protein function...
December 12, 2017: Nano Letters
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