keyword
MENU ▼
Read by QxMD icon Read
search

Target tractability

keyword
https://www.readbyqxmd.com/read/29656441/a-review-on-current-status-of-antiviral-sirna
#1
REVIEW
Abid Qureshi, Vaqar Gani Tantray, Altaf Rehman Kirmani, Abdul Ghani Ahangar
Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene-silencing phenomenon in which sequence-specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions...
April 15, 2018: Reviews in Medical Virology
https://www.readbyqxmd.com/read/29644620/mine-land-rehabilitation-in-brazil-goals-and-techniques-in-the-context-of-legal-requirements
#2
REVIEW
Markus Gastauer, Pedro Walfir Martins Souza Filho, Silvio Junio Ramos, Cecílio Frois Caldeira, Joyce Reis Silva, José Oswaldo Siqueira, Antonio Eduardo Furtini Neto
Environmental legislation in many countries demands the rehabilitation of degraded areas to minimize environmental impacts. Brazilian laws require the restitution of self-sustaining ecosystems to historical conditions but ignore the emergence of novel ecosystems due to large-scale changes, such as species invasions, extinctions, and land-use or climate changes, although these novel ecosystems might fulfill ecosystem services in similar ways as historic ecosystems. Thorough discussions of rehabilitation goals, target ecosystems, applied methods, and approaches to achieving mine land rehabilitation, as well as dialogues about the advantages and risks of chemical inputs or non-native, non-invasive species that include all political, economic, social, and academic stakeholders are necessary to achieve biological feasibility, sociocultural acceptance, economic viability, and institutional tractability during environmental rehabilitation...
April 11, 2018: Ambio
https://www.readbyqxmd.com/read/29642893/q-a-how-do-gene-regulatory-networks-control-environmental-responses-in-plants
#3
Ying Sun, José R Dinneny
A gene regulatory network (GRN) describes the hierarchical relationship between transcription factors, associated proteins, and their target genes. Studying GRNs allows us to understand how a plant's genotype and environment are integrated to regulate downstream physiological responses. Current efforts in plants have focused on defining the GRNs that regulate functions such as development and stress response and have been performed primarily in genetically tractable model plant species such as Arabidopsis thaliana...
April 11, 2018: BMC Biology
https://www.readbyqxmd.com/read/29629394/organotypic-explants-of-the-embryonic-rodent-hippocampus-an-accessible-system-for-transgenesis
#4
Archana Iyer, Lakshmi Subramanian, Shubha Tole
This protocol describes the technique of ex-vivo electroporation to target embryonic hippocampal progenitors in an organotypic slice preparation. This technique allows gene perturbation for examining developmental processes in the embryonic hippocampus while retaining the environment and connectivity of the cells. Gene perturbation can include Cre-mediated recombination, RNAi-mediated knockdown, gene overexpression, or a combination of any of these. Ex-vivo electroporation can be performed at a wide range of embryonic stages, giving temporal control to the experimenter...
March 20, 2018: Bio-protocol
https://www.readbyqxmd.com/read/29559545/engaging-anaphase-catastrophe-mechanisms-to-eradicate-aneuploid-cancers
#5
REVIEW
Masanori Kawakami, Lisa Maria Mustachio, Xi Liu, Ethan Dmitrovsky
Cancer cells often have supernumerary centrosomes that promote genomic instability, a pathognomonic feature of cancer. During mitosis, cancer cells with supernumerary centrosomes undergo bipolar cell division by clustering centrosomes into two poles. When supernumerary centrosome clustering is antagonized, cancer cells are forced to undergo multipolar division leading to death of daughter cells. This proapoptotic pathway, called anaphase catastrophe, preferentially eliminates aneuploid cancer cells and malignant tumors in engineered mouse models...
March 20, 2018: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29545272/coordination-to-lanthanide-ions-distorts-binding-site-conformation-in-calmodulin
#6
Sean C Edington, Andrea Gonzalez, Thomas R Middendorf, D Brent Halling, Richard W Aldrich, Carlos R Baiz
The Ca2+ -sensing protein calmodulin (CaM) is a popular model of biological ion binding since it is both experimentally tractable and essential to survival in all eukaryotic cells. CaM modulates hundreds of target proteins and is sensitive to complex patterns of Ca2+ exposure, indicating that it functions as a sophisticated dynamic transducer rather than a simple on/off switch. Many details of this transduction function are not well understood. Fourier transform infrared (FTIR) spectroscopy, ultrafast 2D infrared (2D IR) spectroscopy, and electronic structure calculations were used to probe interactions between bound metal ions (Ca2+ and several trivalent lanthanide ions) and the carboxylate groups in CaM's EF-hand ion-coordinating sites...
March 15, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29542088/transgenic-techniques-for-investigating-cell-biology-during-development
#7
Christina D Cota
Ascidians are increasingly being used as a system for investigating cell biology during development. The extreme genetic and cellular simplicity of ascidian embryos in combination with superior experimental tractability make this an ideal system for in vivo analysis of dynamic cellular processes. Transgenic approaches to cellular and sub-cellular analysis of ascidian development have begun to yield new insights into the mechanisms regulating developmental signaling and morphogenesis. This chapter focuses on the targeted expression of fusion proteins in ascidian embryos and how this technique is being deployed to garner new insights into the cell biology of development...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29526280/antisense-therapy-for-a-common-corneal-dystrophy-ameliorates-tcf4-repeat-expansion-mediated-toxicity
#8
Christina Zarouchlioti, Beatriz Sanchez-Pintado, Nathaniel J Hafford Tear, Pontus Klein, Petra Liskova, Kalyan Dulla, Ma'ayan Semo, Anthony A Vugler, Kirithika Muthusamy, Lubica Dudakova, Hannah J Levis, Pavlina Skalicka, Pirro Hysi, Michael E Cheetham, Stephen J Tuft, Peter Adamson, Alison J Hardcastle, Alice E Davidson
Fuchs endothelial corneal dystrophy (FECD) is a common disease for which corneal transplantation is the only treatment option in advanced stages, and alternative treatment strategies are urgently required. Expansion (≥50 copies) of a non-coding trinucleotide repeat in TCF4 confers >76-fold risk for FECD in our large cohort of affected individuals. An FECD subject-derived corneal endothelial cell (CEC) model was developed to probe disease mechanism and investigate therapeutic approaches. The CEC model demonstrated that the repeat expansion leads to nuclear RNA foci, with the sequestration of splicing factor proteins (MBNL1 and MBNL2) to the foci and altered mRNA processing...
March 1, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29522887/quantitative-metrics-for-drug-target-ligandability
#9
REVIEW
Sinisa Vukovic, David J Huggins
Ligandability is a prerequisite for druggability and is a much easier concept to understand, model and predict because it does not depend on the complex pharmacodynamic and pharmacokinetic mechanisms in the human body. In this review, we consider a metric for quantifying ligandability from experimental data. We discuss ligandability in terms of the balance between effort and reward. The metric is evaluated for a standard set of well-studied drug targets - some traditionally considered to be ligandable and some regarded as difficult...
March 6, 2018: Drug Discovery Today
https://www.readbyqxmd.com/read/29515774/unbiased-compound-protein-interface-mapping-and-prediction-of-chemoresistance-loci-through-forward-genetics-in-haploid-stem-cells
#10
Moritz Horn, Virginia Kroef, Kira Allmeroth, Nicole Schuller, Stephan Miethe, Martin Peifer, Josef M Penninger, Ulrich Elling, Martin S Denzel
Forward genetic screens in haploid mammalian cells have recently emerged as powerful tools for the discovery and investigation of recessive traits. Use of the haploid system provides unique genetic tractability and resolution. Upon positive selection, these screens typically employ analysis of loss-of-function (LOF) alleles and are thus limited to non-essential genes. Many relevant compounds, including anti-cancer therapeutics, however, target essential genes, precluding positive selection of LOF alleles. Here, we asked whether the use of random and saturating chemical mutagenesis might enable screens that identify essential biological targets of toxic compounds...
February 9, 2018: Oncotarget
https://www.readbyqxmd.com/read/29514840/the-transcriptional-co-activator-taz-is-a-potent-mediator-of-alveolar-rhabdomyosarcoma-tumorigenesis
#11
Michael D Deel, Katherine K Slemmons, Ashley R Hinson, Katia C Genadry, Breanne A Burgess, Lisa E S Crose, Nina Kuprasertkul, Kristianne M Oristian, Rex C Bentley, Corinne M Linardic
PURPOSE: Alveolar rhabdomyosarcoma (aRMS) is a childhood soft tissue sarcoma driven by the signature PAX3-FOXO1 (P3F) fusion gene. 5-year survival for aRMS is <50%, with no improvement in over four decades. Although the transcriptional co-activator TAZ is oncogenic in carcinomas, the role of TAZ in sarcomas is poorly understood. The aim of this study was to investigate the role of TAZ in P3F-aRMS tumorigenesis. EXPERIMENTAL DESIGN: After determining from public datasets that TAZ is upregulated in human aRMS transcriptomes, we evaluated whether TAZ is also upregulated in our myoblast-based model of P3F-initiated tumorigenesis, and performed IHC staining of 63 human aRMS samples from tissue microarrays...
March 7, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29511174/convergent-genomic-signatures-of-domestication-in-sheep-and-goats
#12
Florian J Alberto, Frédéric Boyer, Pablo Orozco-terWengel, Ian Streeter, Bertrand Servin, Pierre de Villemereuil, Badr Benjelloun, Pablo Librado, Filippo Biscarini, Licia Colli, Mario Barbato, Wahid Zamani, Adriana Alberti, Stefan Engelen, Alessandra Stella, Stéphane Joost, Paolo Ajmone-Marsan, Riccardo Negrini, Ludovic Orlando, Hamid Reza Rezaei, Saeid Naderi, Laura Clarke, Paul Flicek, Patrick Wincker, Eric Coissac, James Kijas, Gwenola Tosser-Klopp, Abdelkader Chikhi, Michael W Bruford, Pierre Taberlet, François Pompanon
The evolutionary basis of domestication has been a longstanding question and its genetic architecture is becoming more tractable as more domestic species become genome-enabled. Before becoming established worldwide, sheep and goats were domesticated in the fertile crescent 10,500 years before present (YBP) where their wild relatives remain. Here we sequence the genomes of wild Asiatic mouflon and Bezoar ibex in the sheep and goat domestication center and compare their genomes with that of domestics from local, traditional, and improved breeds...
March 6, 2018: Nature Communications
https://www.readbyqxmd.com/read/29507229/myeloid-erk5-deficiency-suppresses-tumor-growth-by-blocking-protumor-macrophage-polarization-via-stat3-inhibition
#13
Emanuele Giurisato, Qiuping Xu, Silvia Lonardi, Brian Telfer, Ilaria Russo, Adam Pearson, Katherine G Finegan, Wenbin Wang, Jinhua Wang, Nathanael S Gray, William Vermi, Zhengui Xia, Cathy Tournier
Owing to the prevalence of tumor-associated macrophages (TAMs) in cancer and their unique influence upon disease progression and malignancy, macrophage-targeted interventions have attracted notable attention in cancer immunotherapy. However, tractable targets to reduce TAM activities remain very few and far between because the signaling mechanisms underpinning protumor macrophage phenotypes are largely unknown. Here, we have investigated the role of the extracellular-regulated protein kinase 5 (ERK5) as a determinant of macrophage polarity...
March 5, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29499974/specialized-proresolving-mediators-enhancing-nonalcoholic-steatohepatitis-and-fibrosis-resolution
#14
REVIEW
Giovanni Musso, Roberto Gambino, Maurizio Cassader, Elena Paschetta, Antonio Sircana
The resolution of necroinflammation and fibrosis remains a primary clinical target in nonalcoholic steatohepatitis (NASH), the most common chronic liver disease and a major cause of end-stage liver disease. Our understanding of the basic molecular mechanisms driving inflammation and fibrosis and their resolution in obesity-related conditions, including NASH, have led to the proposal of a novel, tractable therapeutic paradigm involving specialized proresolving mediators (SPMs), namely lipoxins (LXs), resolvins (Rvs), protectins (PDs), and maresins (MaRs)...
February 27, 2018: Trends in Pharmacological Sciences
https://www.readbyqxmd.com/read/29498889/structural-basis-for-g-protein-coupled-receptor-signaling
#15
Sarah C Erlandson, Conor McMahon, Andrew C Kruse
G protein-coupled receptors (GPCRs), which mediate processes as diverse as olfaction and maintenance of metabolic homeostasis, have become the single most effective class of therapeutic drug targets. As a result, understanding the molecular basis for their activity is of paramount importance. Recent technological advances have made GPCR structural biology increasingly tractable, offering views of these receptors in unprecedented atomic detail. Structural and biophysical data have shown that GPCRs function as complex allosteric machines, communicating ligand-binding events through conformational change...
March 2, 2018: Annual Review of Biophysics
https://www.readbyqxmd.com/read/29496691/genetic-landscape-of-acute-myeloid-leukemia-interrogated-by-next-generation-sequencing-a-large-cancer-center-experience
#16
Mohammad Omar Hussaini, Abu-Sayeef Mirza, Rami Komrokji, Jeffrey Lancet, Eric Padron, Jinming Song
BACKGROUND/AIM: Acute myeloid leukemia (AML) represents a heterogeneous disease with varying morphologic, immunophenotypic, and genetic features, along with varying patient outcomes. The genomic tractability of AML makes it amenable for targeted next-generation sequencing (NGS) testing clinically. MATERIALS AND METHODS: One hundred eights-seven unique patients with a diagnosis of acute myeloid leukemia between May 2011 and Oct 2014 and with mutational analysis by NGS were included in this study...
March 2018: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/29478897/an-adeno-associated-virus-based-toolkit-for-preferential-targeting-and-manipulating-quiescent-neural-stem-cells-in-the-adult-hippocampus
#17
Andrew J Crowther, Szu-Aun Lim, Brent Asrican, Blake H Albright, Josh Wooten, Chia-Yu Yeh, Hechen Bao, Domenic H Cerri, Jessica Hu, Yen-Yu Ian Shih, Aravind Asokan, Juan Song
Quiescent neural stem cells (qNSCs) with radial morphology are the only proven source of new neurons in the adult mammalian brain. Our understanding of the roles of newly generated neurons depends on the ability to target and manipulate adult qNSCs. Although various strategies have been developed to target and manipulate adult hippocampal qNSCs, they often suffer from prolonged breeding, low recombination efficiency, and non-specific labeling. Therefore, developing a readily manufactured viral vector that allows flexible packaging and robust expression of various transgenes in qNSCs is a pressing need...
March 13, 2018: Stem Cell Reports
https://www.readbyqxmd.com/read/29446724/inhibitors-of-er-aminopeptidase-1-and-2-from-design-to-clinical-application
#18
Dimitris Georgiadis, Anastasia Mpakali, Despoina Koumantou, Efstratios Stratikos
Endoplasmic Reticulum aminopeptidase 1 and 2 are two homologous enzymes that help generate peptide ligands for presentation by Major Histocompatibility Class I molecules. Their enzymatic activity influences the antigenic peptide repertoire and indirectly controls adaptive immune responses. Accumulating evidence suggests that these two enzymes are tractable targets for the regulation of immune responses with possible applications ranging from cancer immunotherapy to treating inflammatory autoimmune disease. Here, we review the state-of-the-art in the development of inhibitors of ERAP1 and ERAP2 as well as their potential and limitations for clinical applications...
February 13, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29441692/a-conservation-planning-tool-for-greater-sage-grouse-using-indices-of-species-distribution-resilience-and-resistance
#19
Mark A Ricca, Peter S Coates, K Benjamin Gustafson, Brianne E Brussee, Jeanne C Chambers, Shawn P Espinosa, Scott C Gardner, Sherri Lisius, Pilar Ziegler, David J Delehanty, Michael L Casazza
Managers require quantitative yet tractable tools that can identify areas for restoration yielding effective benefits for targeted wildlife species and the ecosystems they inhabit. As a contemporary example of high national significance for conservation, the persistence of greater sage-grouse (Centrocercus urophasianus, hereafter 'sage-grouse') in the Great Basin ecoregion is compromised, in part, by strongly interacting stressors of conifer encroachment, annual grass invasion, and larger and more frequent wildfires occurring in sagebrush ecosystems...
February 14, 2018: Ecological Applications: a Publication of the Ecological Society of America
https://www.readbyqxmd.com/read/29438671/the-structure-of-the-biofilm-controlling-response-regulator-bfmr-from-acinetobacter-baumannii-reveals-details-of-its-dna-binding-mechanism
#20
G Logan Draughn, Morgan E Milton, Erik A Feldmann, Benjamin G Bobay, Braden M Roth, Andrew L Olson, Richele J Thompson, Luis A Actis, Christopher Davies, John Cavanagh
The rise of drug-resistant bacterial infections coupled with decreasing antibiotic efficacy poses a significant challenge to global healthcare. Acinetobacter baumannii is an insidious, emerging bacterial pathogen responsible for severe nosocomial infections aided by its ability to form biofilms. The response regulator BfmR, from the BfmR/S two-component system, is the master regulator of biofilm initiation in A. baumannii and is a tractable therapeutic target. Here we present the structure of A. baumannii BfmR using a hybrid approach combining X-ray crystallography, nuclear magnetic resonance spectroscopy, chemical crosslinking mass spectrometry, and molecular modeling...
February 10, 2018: Journal of Molecular Biology
keyword
keyword
114229
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"