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https://www.readbyqxmd.com/read/28223408/inducing-circular-rna-formation-using-the-crispr-endoribonuclease-csy4
#1
Erin K Borchardt, Rita M Meganck, Heather A Vincent, Christopher B Ball, Silvia B V Ramos, Nathaniel J Moorman, William F Marzluff, Aravind Asokan
Circular RNAs (circRNAs) are highly stable, covalently closed RNAs that are regulated in a spatiotemporal manner and whose functions are largely unknown. These molecules have the potential to be incorporated into engineered systems with broad technological implications. Here we describe a switch for inducing backsplicing of an engineered circRNA that relies on the CRISPR endoribonuclease, Csy4, as an activator of circularization. The endoribonuclease activity and 3' end-stabilizing properties of Csy4 are particularly suited for this task...
February 21, 2017: RNA
https://www.readbyqxmd.com/read/28182401/agos-a-plug-and-play-method-for-the-assembly-of-artificial-gene-operons-into-functional-biosynthetic-gene-clusters
#2
Patrick Basitta, Lucia Westrich, Manuela Rösch, Andreas Kulik, Bertolt Gust, Alexander Kristian Apel
The generation of novel secondary metabolites by reengineering or refactoring biochemical pathways is a rewarding but also challenging goal of synthetic biology. For this, the development of tools for the reconstruction of secondary metabolite gene clusters as well as the challenge of understanding the obstacles in this process is of great interest. The artificial gene operon assembly system (AGOS) is a plug-and-play method developed as a tool to consecutively assemble artificial gene operons into a destination vector and subsequently express them under the control of a de-repressed promoter in a Streptomyces host strain...
February 20, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28130827/advanced-glycation-end-products-stimulate-gene-expression-of-fibroblast-growth-factor-23
#3
Ludmilla Bär, Kristin Wächter, Nicole Wege, Alexander Navarrete Santos, Andreas Simm, Michael Föller
SCOPE: Osteoblasts produce fibroblast growth factor 23 (FGF23), a hormone inhibiting renal phosphate reabsorption and the formation of biologically active vitamin D, calcitriol. FGF23-deficient mice age rapidly and develop age-associated diseases at least in part due to massive calcification. Elevated FGF23 serum levels are detected in patients suffering from acute and chronic renal, cardiovascular, inflammatory, and metabolic diseases. Advanced glycation end products (AGEs) are sugar-modified proteins, nucleic acid, and lipids which contribute to these disorders...
January 28, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28117364/selective-inhibition-of-ebola-entry-with-selective-estrogen-receptor-modulators-by-disrupting-the-endolysosomal-calcium
#4
Hanlu Fan, Xiaohong Du, Jingyuan Zhang, Han Zheng, Xiaohui Lu, Qihui Wu, Haifeng Li, Han Wang, Yi Shi, George Gao, Zhuan Zhou, Dun-Xian Tan, Xiangdong Li
The Ebola crisis occurred in West-Africa highlights the urgency for its clinical treatments. Currently, no Food and Drug Administration (FDA)-approved therapeutics are available. Several FDA-approved drugs, including selective estrogen receptor modulators (SERMs), possess selective anti-Ebola activities. However, the inhibitory mechanisms of these drugs remain elusive. By analyzing the structures of SERMs and their incidental biological activity (cholesterol accumulation), we hypothesized that this incidental biological activity induced by SERMs could be a plausible mechanism as to their inhibitory effects on Ebola infection...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28095623/xenopus-as-a-model-for-studies-in-mechanical-stress-and-cell-division
#5
REVIEW
Georgina A Stooke-Vaughan, Lance A Davidson, Sarah Woolner
We exist in a physical world, and cells within biological tissues must respond appropriately to both environmental forces and forces generated within the tissue to ensure normal development and homeostasis. Cell division is required for normal tissue growth and maintenance, but both the direction and rate of cell division must be tightly controlled to avoid diseases of over-proliferation such as cancer. Recent studies have shown that mechanical cues can cause mitotic entry and orient the mitotic spindle, suggesting that physical force could play a role in patterning tissue growth...
January 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28027556/overexpression-of-tp53-tp53i3-and-birc5-alterations-of-gene-regulation-of-apoptosis-and-aging-of-human-immune-cells-in-a-remote-period-after-radiation-exposure
#6
I N Ilienko, D A Bazyka
OBJECTIVE: To identify a contributive role of changes in gene regulation of apoptosis and telomere length at tran scriptional and translational levels to the formation of radiation induced effects in immune system. PATIENTS AND METHODS: Study groups included 310 Chornobyl (Chornobyl) cleanup workers (dose of external expo sure (360.82 ± 32.3) mSv; age 58.9 ± 0.6 (M ± SD) years) and control (n = 77; age (52.9 ± 0.64) (M ± SD) years). Expression of CD95, phosphatidylserine receptors, bcl2 and p53 proteins was studied by flow cytometry; the relative expression (RQ) of BAX, BIRC5, FASLG, MADD, MAPK14, TP53, TP53I3, TERT, TERF1, TERF2 genes was performed using 7900 HT Fast RT PCR System and TagMan technology...
December 2016: Problemy Radiat︠s︡iĭnoï Medyt︠s︡yny Ta Radiobiolohiï
https://www.readbyqxmd.com/read/27977806/integrated-activity-and-genetic-profiling-of-secreted-peptidases-in-cryptococcus-neoformans-reveals-an-aspartyl-peptidase-required-for-low-ph-survival-and-virulence
#7
Starlynn C Clarke, Phillip A Dumesic, Christina M Homer, Anthony J O'Donoghue, Florencia La Greca, Lenka Pallova, Pavel Majer, Hiten D Madhani, Charles S Craik
The opportunistic fungal pathogen Cryptococcus neoformans is a major cause of mortality in immunocompromised individuals, resulting in more than 600,000 deaths per year. Many human fungal pathogens secrete peptidases that influence virulence, but in most cases the substrate specificity and regulation of these enzymes remains poorly understood. The paucity of such information is a roadblock to our understanding of the biological functions of peptidases and whether or not these enzymes are viable therapeutic targets...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27966523/functional-screening-for-anti-cmv-biologics-identifies-a-broadly-neutralizing-epitope-of-an-essential-envelope-protein
#8
Thomas J Gardner, Kathryn R Stein, J Andrew Duty, Toni M Schwarz, Vanessa M Noriega, Thomas Kraus, Thomas M Moran, Domenico Tortorella
The prototypic β-herpesvirus human cytomegalovirus (CMV) establishes life-long persistence within its human host. The CMV envelope consists of various protein complexes that enable wide viral tropism. More specifically, the glycoprotein complex gH/gL/gO (gH-trimer) is required for infection of all cell types, while the gH/gL/UL128/130/131a (gH-pentamer) complex imparts specificity in infecting epithelial, endothelial and myeloid cells. Here we utilize state-of-the-art robotics and a high-throughput neutralization assay to screen and identify monoclonal antibodies (mAbs) targeting the gH glycoproteins that display broad-spectrum properties to inhibit virus infection and dissemination...
December 14, 2016: Nature Communications
https://www.readbyqxmd.com/read/27909017/early-environmental-field-research-career-exploration-an-analysis-of-impacts-on-precollege-apprentices
#9
Susan K Flowers, Katherine M Beyer, Maria Pérez, Donna B Jeffe
Research apprenticeships offer opportunities for deep understanding of scientific practice, transparency about research careers, and possible transformational effects on precollege youth. We examined two consecutive field-based environmental biology apprenticeship programs designed to deliver realistic career exploration and connections to research scientists. The Shaw Institute for Field Training (SIFT) program combines introductory field-skills training with research assistance opportunities, and the subsequent Tyson Environmental Research Fellowships (TERF) program provides immersive internships on university field station-based research teams...
2016: CBE Life Sciences Education
https://www.readbyqxmd.com/read/27905579/selective-tsuji-trost-type-c-allylation-of-hydrazones-a-straightforward-entry-into-4-5-dihydropyrazoles
#10
El Hachemia El Mamouni, Martin Cattoen, Marie Cordier, Janine Cossy, Stellios Arseniyadis, Hocine Ilitki, Laurent El Kaïm
The 4,5-dihydropyrazole motif has drawn considerable attention over the years as it was shown to exhibit a plethora of biological and pharmacological properties, including anticancer, antibacterial, antifungal, antiviral, and anti-inflammatory properties. As such, it has been the target of a number of methods and drug discovery programs. We report here a straightforward and highly selective approach featuring a key palladium-catalysed Tsuji-Trost type C-allylation and subsequent intramolecular 1,4-addition of hydrazones...
December 13, 2016: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/27864597/genome-wide-association-mapping-and-agronomic-impact-of-cowpea-root-architecture
#11
James D Burridge, Hannah M Schneider, Bao-Lam Huynh, Philip A Roberts, Alexander Bucksch, Jonathan P Lynch
Genetic analysis of data produced by novel root phenotyping tools was used to establish relationships between cowpea root traits and performance indicators as well between root traits and Striga tolerance. Selection and breeding for better root phenotypes can improve acquisition of soil resources and hence crop production in marginal environments. We hypothesized that biologically relevant variation is measurable in cowpea root architecture. This study implemented manual phenotyping (shovelomics) and automated image phenotyping (DIRT) on a 189-entry diversity panel of cowpea to reveal biologically important variation and genome regions affecting root architecture phenes...
February 2017: TAG. Theoretical and Applied Genetics. Theoretische und Angewandte Genetik
https://www.readbyqxmd.com/read/27845963/internal-distraction-osteogenesis-with-piezosurgery-oblique-osteotomy-of-supraorbital-margin-of-frontal-bone-for-the-treatment-of-unilateral-coronal-synostosis
#12
Weimin Shen, Jie Cui, Jianbing Chen, Yi Ji, Liangliang Kong
PURPOSE: To assess the utility of internal distraction osteogenesis with Piezosurgery oblique osteotomy of supraorbital margin of frontal bone for the treatment of unilateral coronal synostosis and to study the outcome and complications of this procedure. Oblique osteotomy allows for entry into the cranial cavity, and along with parallel cut to the roof of the orbit, avoids the need to cut into the orbit which forms the frontal flap. METHODS: Oblique osteotomy was performed along the supraorbital rim to do a frontal suture of the glabella (ages of patients were less than 1 year) or on the opposite side of the supraorbital rim (ages of patients were older than 1 year) after performing a suturectomy of the effected coronal suture...
November 15, 2016: Annals of Plastic Surgery
https://www.readbyqxmd.com/read/27769361/development-of-chemical-probes-for-the-bromodomains-of-brd7-and-brd9
#13
REVIEW
Peter G K Clark, Darren J Dixon, Paul E Brennan
The bromodomain family of proteins are 'readers' of acetylated lysines of histones, a key mark in the epigenetic code of gene regulation. Without high quality chemical probes with which to study these proteins, their biological function, and potential use in therapeutics, remains unknown. Recently, a number of chemical ligands were reported for the previously unprobed bromodomain proteins BRD7 and BRD9. Herein the development and characterisation of probes against these proteins is detailed, including the preliminary biological activity of BRD7 and BRD9 assessed using these probes...
March 2016: Drug Discovery Today. Technologies
https://www.readbyqxmd.com/read/27765817/adaptor-protein-cd2ap-and-l-type-lectin-lman2-regulate-exosome-cargo-protein-trafficking-through-the-golgi-complex
#14
Sang-Ho Kwon, Sekyung Oh, Marisa Nacke, Keith E Mostov, Joshua H Lipschutz
Exosomes, 40-150-nm extracellular vesicles, transport biological macromolecules that mediate intercellular communications. Although exosomes are known to originate from maturation of endosomes into multivesicular endosomes (also known as multivesicular bodies) with subsequent fusion of the multivesicular endosomes with the plasma membrane, it remains unclear how cargos are selected for exosomal release. Using an inducible expression system for the exosome cargo protein GPRC5B and following its trafficking trajectory, we show here that newly synthesized GPRC5B protein accumulates in the Golgi complex prior to its release into exosomes...
December 2, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27729659/biosimilars-in-ibd-from-theory-to-practice
#15
REVIEW
Silvio Danese, Stefanos Bonovas, Laurent Peyrin-Biroulet
Biologic agents have revolutionized the care management of many life-threatening and debilitating diseases. As patents for older biologic therapies have begun to expire, the market has opened to copy versions of the originators - commonly referred to as biosimilars, follow-on biologic agents or subsequent-entry biologic agents - which are expected to gain a portion of the market, reduce health-care spending and increase treatment access worldwide. Importantly for patients with IBD, CT-P13 was the first biosimilar to infliximab that obtained regulatory approval by the European Medicines Agency in September 2013 and by the FDA in April 2016...
January 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/27723283/increased-incidence-of-amyotrophic-lateral-sclerosis-in-polymyositis-a-nationwide-cohort-study
#16
Chia-Chun Tseng, Shun-Jen Chang, Wen-Chan Tsai, Tsan-Teng Ou, Cheng-Chin Wu, Wan-Yu Sung, Ming-Chia Hsieh, Jeng-Hsien Yen
OBJECTIVE: Past studies have shown common pathologic characteristics and shared immunologic features between polymyositis (PM) and amyotrophic lateral sclerosis (ALS). To explore the potential relationship between the two diseases, we performed a nationwide cohort study. METHODS: We identified all newly diagnosed PM from Taiwan's Registry of Catastrophic Illness Database between January 1, 1998 and December 31, 2011. Each PM patient was matched to at most 5 control patients from the National Health Insurance Research Database by sex, age, and entry date...
October 9, 2016: Arthritis Care & Research
https://www.readbyqxmd.com/read/27565552/synthesis-and-biological-evaluation-of-novel-pentacyclic-triterpene-%C3%AE-cyclodextrin-conjugates-as-hcv-entry-inhibitors
#17
Sulong Xiao, Qi Wang, Longlong Si, Xiaoshu Zhou, Yongmin Zhang, Lihe Zhang, Demin Zhou
Hepatitis C virus (HCV) entry is a key target for the treatment of chronic HCV infection. In our continuing efforts to identify novel potential anti-HCV entry inhibitors, a series of water-soluble triazole-bridged α-cyclodextrin-pentacyclic triterpene conjugates were easily synthesized with moderate to good yields. These novel compounds were fully identified and characterized by 1D and 2D NMR spectroscopy and ESI-HRMS. The anti-HCV entry activities were determined based on HCVpp/VSVGpp entry assays. The best results were found for compounds 15 and 18, which displayed the most promising anti-HCV entry activities with average IC50 values of 1...
November 29, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27295004/artd1-regulates-cyclin-e-expression-and-consequently-cell-cycle-re-entry-and-g1-s-progression-in-t24-bladder-carcinoma-cells
#18
Karolin Léger, Ann-Katrin Hopp, Monika Fey, Michael O Hottiger
ADP-ribosylation is involved in a variety of biological processes, many of which are chromatin-dependent and linked to important functions during the cell cycle. However, any study on ADP-ribosylation and the cell cycle faces the problem that synchronization with chemical agents or by serum starvation and subsequent growth factor addition already activates ADP-ribosylation by itself. Here, we investigated the functional contribution of ARTD1 in cell cycle re-entry and G1/S cell cycle progression using T24 urinary bladder carcinoma cells, which synchronously re-enter the cell cycle after splitting without any additional stimuli...
August 2, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27174254/the-recombined-cccdna-produced-using-minicircle-technology-mimicked-hbv-genome-in-structure-and-function-closely
#19
Xiaoyan Guo, Ping Chen, Xiaohu Hou, Wenjuan Xu, Dan Wang, Tian-Yan Wang, Liping Zhang, Gang Zheng, Zhi-Liang Gao, Cheng-Yi He, Boping Zhou, Zhi-Ying Chen
HBV covalently closed circular DNA (cccDNA) is drug-resistant and responsible for viral persistence. To facilitate the development of anti-cccDNA drugs, we developed a minicircle DNA vector (MC)-based technology to produce large quantity of recombined cccDNA (rcccDNA) resembling closely to its wild-type counterpart both in structure and function. The rcccDNA differed to the wild-type cccDNA (wtcccDNA) only in that it carried an extra 36-bp DNA recombinant product attR upstream of the preC/C gene. Using a procedure similar to standard plasmid production, milligrams of rcccDNA can be generated in common laboratories conveniently...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27053355/designing-synthetic-rnas-to-determine-the-relevance-of-structural-motifs-in-picornavirus-ires-elements
#20
Javier Fernandez-Chamorro, Gloria Lozano, Juan Antonio Garcia-Martin, Jorge Ramajo, Ivan Dotu, Peter Clote, Encarnacion Martinez-Salas
The function of Internal Ribosome Entry Site (IRES) elements is intimately linked to their RNA structure. Viral IRES elements are organized in modular domains consisting of one or more stem-loops that harbor conserved RNA motifs critical for internal initiation of translation. A conserved motif is the pyrimidine-tract located upstream of the functional initiation codon in type I and II picornavirus IRES. By computationally designing synthetic RNAs to fold into a structure that sequesters the polypyrimidine tract in a hairpin, we establish a correlation between predicted inaccessibility of the pyrimidine tract and IRES activity, as determined in both in vitro and in vivo systems...
2016: Scientific Reports
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