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https://www.readbyqxmd.com/read/28710417/talen-based-hpv-e7-editing-triggers-necrotic-cell-death-in-cervical-cancer-cells
#1
Sumitra Shankar, Deepti Prasad, Rahul Sanawar, Ani V Das, M Radhakrishna Pillai
Human Papillomavirus E7 and E6 oncoproteins have been considered as suitable candidate anti-viral targets since they cause malignant conversion in cervical cancers. Transcription Activator-Like Effector Nucleases (TALENs) are recent editing tools to knockout genes by inducing double stranded breaks at specific sites in the genome. In here, we have designed specific TALENs to target E7 and analyzed their efficiency in inducing cell death in cervical cancer cells. We found that designed TALENs could yield about 10-12% editing activity as observed from T7E1 and nuclease resistance assays...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28708092/the-exact-nuclear-overhauser-enhancement-recent-advances
#2
REVIEW
Parker J Nichols, Alexandra Born, Morkos A Henen, Dean Strotz, Julien Orts, Simon Olsson, Peter Güntert, Celestine N Chi, Beat Vögeli
Although often depicted as rigid structures, proteins are highly dynamic systems, whose motions are essential to their functions. Despite this, it is difficult to investigate protein dynamics due to the rapid timescale at which they sample their conformational space, leading most NMR-determined structures to represent only an averaged snapshot of the dynamic picture. While NMR relaxation measurements can help to determine local dynamics, it is difficult to detect translational or concerted motion, and only recently have significant advances been made to make it possible to acquire a more holistic representation of the dynamics and structural landscapes of proteins...
July 14, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28701243/regulation-of-fetuin-a-gene-expression-in-the-neonatal-pig-liver
#3
T G Ramsay, M J Stoll, L A Blomberg, T J Caperna
Fetuin A (also known as α2-Heremans-Schmid glycoprotein) is a protein primarily expressed by the liver and secreted into the blood. Previous studies have suggested that plasma concentrations of fetuin A are elevated with impaired growth rate in swine. The present study was designed to examine the relationship of porcine fetuin A with growth rate in the pig and to also elucidate the regulation of fetuin A expression by examining the hormonal and cytokine regulation of fetuin A mRNA abundance in hepatocytes prepared from suckling piglets...
July 13, 2017: Animal: An International Journal of Animal Bioscience
https://www.readbyqxmd.com/read/28700644/transcription-of-putative-tonoplast-transporters-in-response-to-glyphosate-and-paraquat-stress-in-conyza-bonariensis-and-conyza-canadensis-and-selection-of-reference-genes-for-qrt-pcr
#4
Marcelo L Moretti, Rocio Alárcon-Reverte, Stephen Pearce, Sarah Morran, Bradley D Hanson
Herbicide resistance is a challenge for modern agriculture further complicated by cases of resistance to multiple herbicides. Conyza bonariensis and Conyza canadensis are invasive weeds of field crops, orchards, and non-cropped areas in many parts of the world. In California, USA, Conyza populations resistant to the herbicides glyphosate and paraquat have recently been described. Although the mechanism conferring resistance to glyphosate and paraquat in these species was not elucidated, reduced translocation of these herbicides was observed under experimental conditions in both species...
2017: PloS One
https://www.readbyqxmd.com/read/28696707/cyclophilin-b-deficiency-causes-abnormal-dentin-collagen-matrix
#5
Masahiko Terajima, Yuki Taga, Wayne A Cabral, Masako Nagasawa, Noriko Sumida, Shunji Hattori, Joan C Marini, Mitsuo Yamauchi
Cyclophilin B (CypB) is an endoplasmic reticulum-resident protein that regulates collagen folding, and also contributes to prolyl 3-hydroxylation (P3H) and lysine (Lys) hydroxylation of collagen. In this study, we characterized dentin type I collagen in CypB null (KO) mice, a model of recessive osteogenesis imperfecta type IX, and compared to those of wild-type (WT) and heterozygous (Het) mice. Mass spectrometric analysis demonstrated that the extent of P3H in KO collagen was significantly diminished compared to WT/Het...
July 11, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28682833/cross-platform-comparison-of-computer-assisted-image-analysis-quantification-of-in-situ-mrna-hybridization-in-investigative-pathology
#6
Timothy R Holzer, Jeffrey C Hanson, Erin M Wray, Jason A Bailey, Kim R Kennedy, Patrick R Finnegan, Aejaz Nasir, Kelly M Credille
Although availability of automated platforms has proliferated, there is no standard practice for computer-assisted generation of scores for mRNA in situ hybridization (ISH) visualized by brightfield microscopic imaging on tissue sections. To address this systematically, an ISH for peptidylprolyl isomerase B (PPIB) (cyclophilin B) mRNA was optimized and applied to a tissue microarray of archival non-small cell lung carcinoma cases, and then automated image analysis for PPIB was refined across 4 commercially available software platforms...
July 4, 2017: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28674997/adolescent-binge-alcohol-exposure-affects-the-brain-function-through-mitochondrial-impairment
#7
Cheril Tapia-Rojas, Francisco J Carvajal, Rodrigo G Mira, Camila Arce, José Manuel Lerma-Cabrera, Juan A Orellana, Waldo Cerpa, Rodrigo A Quintanilla
In the young population, binge drinking is a pattern of problematic alcohol consumption, characterized by a short period of heavy drinking followed by abstinence which is frequently repeated over time. This drinking pattern is associated with mental problems, use of other drugs, and an increased risk of excessive alcohol intake during adulthood. However, little is known about the effects of binge drinking on brain function in adolescents and its neurobiological impact during the adulthood. In the present study, we evaluated the effects of alcohol on hippocampal memory, synaptic plasticity, and mitochondrial function in adolescent rats after a binge drinking episode in vivo...
June 1, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28673552/pushing-the-limits-of-detection-of-weak-binding-using-fragment-based-drug-discovery-identification-of-new-cyclophilin-binders
#8
Charis Georgiou, Iain McNae, Martin Wear, Harris Ioannidis, Julien Michel, Malcolm Walkinshaw
Fragment Based Drug Discovery (FBDD) is an increasingly popular method to identify novel small-molecule drug candidates. One of the limitations of the approach is the difficulty of accurately characterizing weak binding events. This work reports a combination of X-ray diffraction, surface plasmon resonance (SPR) experiments and molecular dynamics (MD) simulations, for the characterisation of binders to different isoforms of the cyclophilin (Cyp) protein family. Although several Cyp inhibitors have been reported in the literature, it has proven challenging to achieve high binding selectivity for different isoforms of this protein family...
June 30, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28671258/selection-of-candidate-reference-genes-and-validation-for-real-time-pcr-studies-in-rice-plants-exposed-to-low-temperatures
#9
P A Auler, L C Benitez, M N do Amaral, I L Vighi, G S Rodrigues, L C da Maia, E J B Braga
Rice is a cereal that presents a great ability to adapt to different soil and climate conditions. However, as it is a tropical crop with C3 metabolism, it performs better in warm temperatures with high solar radiation. Tolerance to stress caused by low temperatures is a highly complex process that involves various metabolic pathways and cellular compartments, resulting in general or specific effects on plant growth and development. In order to observe the true effect of a particular stress on genetic expression, reference genes need to be chosen for real-time PCRs, the expression levels of which should remain stable independent of the situation imposed...
June 29, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28663253/inner-mitochondrial-membrane-disruption-links-apoptotic-and-agonist-initiated-phosphatidylserine-externalization-in-platelets
#10
Hyo-Jung Choo, Andaleb Kholmukhamedov, ChengZing Zhou, Shawn Jobe
OBJECTIVE: Phosphatidylserine exposure mediates platelet procoagulant function and regulates platelet life span. Apoptotic, necrotic, and integrin-mediated mechanisms have been implicated as intracellular determinants of platelet phosphatidylserine exposure. Here, we investigate (1) the role of mitochondrial events in platelet phosphatidylserine exposure initiated by these distinct stimuli and (2) the cellular interactions of the procoagulant platelet in vitro and in vivo. APPROACH AND RESULTS: Key mitochondrial events were examined, including cytochrome c release and inner mitochondrial membrane (IMM) disruption...
June 29, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28660478/drugs-in-development-for-hepatitis-b
#11
REVIEW
Altaf Dawood, Syed Abdul Basit, Mahendran Jayaraj, Robert G Gish
With high morbidity and mortality worldwide, there is great interest in effective therapies for chronic hepatitis B (CHB) virus. There are currently several dozen investigational agents being developed for treatment of CHB. They can be broadly divided into two categories: (1) direct-acting antivirals (DAAs) that interfere with a specific step in viral replication; and (2) host-targeting agents that inhibit viral replication by modifying host cell function, with the latter group further divided into the subcategories of immune modulators and agents that target other host functions...
June 28, 2017: Drugs
https://www.readbyqxmd.com/read/28655872/ca-2-ionophores-are-not-suitable-for-inducing-mptp-opening-in-murine-isolated-adult-cardiac-myocytes
#12
Mathieu Panel, Bijan Ghaleh, Didier Morin
Opening of the mitochondrial permeability transition pore (mPTP) plays a major role in cell death during cardiac ischaemia-reperfusion. Adult isolated rodent cardiomyocytes are valuable cells to study the effect of drugs targeting mPTP. This study investigated whether the use of Ca(2+) ionophores (A23187, ionomycin and ETH129) represent a reliable model to study inhibition of mPTP opening in cardiomyocytes. We monitored mPTP opening using the calcein/cobalt fluorescence technique in adult rat and wild type or cyclophilin D (CypD) knock-out mice cardiomyocytes...
June 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28654636/human-cyclophilin-40-unravels-neurotoxic-amyloids
#13
Jeremy D Baker, Lindsey B Shelton, Dali Zheng, Filippo Favretto, Bryce A Nordhues, April Darling, Leia E Sullivan, Zheying Sun, Parth K Solanki, Mackenzie D Martin, Amirthaa Suntharalingam, Jonathan J Sabbagh, Stefan Becker, Eckhard Mandelkow, Vladimir N Uversky, Markus Zweckstetter, Chad A Dickey, John Koren, Laura J Blair
The accumulation of amyloidogenic proteins is a pathological hallmark of neurodegenerative disorders. The aberrant accumulation of the microtubule associating protein tau (MAPT, tau) into toxic oligomers and amyloid deposits is a primary pathology in tauopathies, the most common of which is Alzheimer's disease (AD). Intrinsically disordered proteins, like tau, are enriched with proline residues that regulate both secondary structure and aggregation propensity. The orientation of proline residues is regulated by cis/trans peptidyl-prolyl isomerases (PPIases)...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28644561/the-redox-sensitive-module-of-cyclophilin-20-3-2-cysteine-peroxiredoxin-and-cysteine-synthase-integrates-sulfur-metabolism-and-oxylipin-signaling-in-the-high-light-acclimation-response
#14
Sara M Müller, Shanshan Wang, Wilena Telman, Michael Liebthal, Helena Schnitzer, Andrea Viehhauser, Carsten Sticht, Carolina Delatorre, Markus Wirtz, Rüdiger Hell, Karl-Josef Dietz
The integration of redox- and reactive oxygen species-dependent signaling and metabolic activities are fundamental to plant acclimation to biotic and abiotic stresses. Previous data suggest the existence of a dynamically interacting module in the chloroplast stroma consisting of cyclophilin 20-3 (Cyp20-3), O-acetylserine(thiol)lyase B (OASTL-B), 2-cysteine peroxiredoxins A/B (2-CysPrx) and serine acetyltransferase 2;1 (SERAT2;1). The functionality of this COPS module is influenced by redox stimuli and oxophytodienoic acid (OPDA) which is the precursor for jasmonic acid...
June 23, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28643580/cyclophilins-less-studied-proteins-with-critical-roles-in-pathogenesis
#15
Khushwant Singh, Mark Winter, Miloslav Zouhar, Pavel Rysanek
Cyclophilins (EC 5.2.1.8) (CYPs) belong to a subgroup of proteins known as immunophilins, which also include FK-506 binding proteins (FKBPs) and parvulins. Members of the immunophilins have two main characteristic properties: I) peptidyl-prolyl cis-trans isomerase activity (PPIases) and II) the ability to bind immunosuppressant molecules of fungal origin. Cyclophilins are some of the most conserved proteins present in eukaryotes and prokaryotes, and they have been implicated in diverse cellular processes and responses to multiple biotic and abiotic stresses...
June 23, 2017: Phytopathology
https://www.readbyqxmd.com/read/28636937/the-conserved-rna-binding-cyclophilin-rct1-regulates-small-rna-biogenesis-and-splicing-independent-of-heterochromatin-assembly
#16
An-Yun Chang, Stephane E Castel, Evan Ernst, Hyun Soo Kim, Robert A Martienssen
RNAi factors and their catalytic activities are essential for heterochromatin assembly in S. pombe. This has led to the idea that siRNAs can promote H3K9 methylation by recruiting the cryptic loci regulator complex (CLRC), also known as recombination in K complex (RIKC), to the nucleation site. The conserved RNA-binding protein Rct1 (AtCyp59/SIG-7) interacts with splicing factors and RNA polymerase II. Here we show that Rct1 promotes processing of pericentromeric transcripts into siRNAs via the RNA recognition motif...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28623276/gag-protease-coevolution-analyses-define-novel-structural-surfaces-in-the-hiv-1-matrix-and-capsid-involved-in-resistance-to-protease-inhibitors
#17
Francisco M Codoñer, Ruth Peña, Oscar Blanch-Lombarte, Esther Jimenez-Moyano, Maria Pino, Thomas Vollbrecht, Bonaventura Clotet, Javier Martinez-Picado, Rika Draenert, Julia G Prado
Despite the major role of Gag in establishing resistance of HIV-1 to protease inhibitors (PIs), very limited data are available on the total contribution of Gag residues to resistance to PIs. To identify in detail Gag residues and structural interfaces associated with the development of HIV-1 resistance to PIs, we traced viral evolution under the pressure of PIs using Gag-protease single genome sequencing and coevolution analysis of protein sequences in 4 patients treated with PIs over a 9-year period. We identified a total of 38 Gag residues correlated with the protease, 32 of which were outside Gag cleavage sites...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619996/farnesoid-x-receptor-and-liver-x-receptor-ligands-initiate-formation-of-coated-platelets
#18
Amanda J Unsworth, Alexander P Bye, Dionne S Tannetta, Michael J R Desborough, Neline Kriek, Tanya Sage, Harriet E Allan, Marilena Crescente, Parveen Yaqoob, Timothy D Warner, Chris I Jones, Jonathan M Gibbins
OBJECTIVES: The liver X receptors (LXRs) and farnesoid X receptor (FXR) have been identified in human platelets. Ligands of these receptors have been shown to have nongenomic inhibitory effects on platelet activation by platelet agonists. This, however, seems contradictory with the platelet hyper-reactivity that is associated with several pathological conditions that are associated with increased circulating levels of molecules that are LXR and FXR ligands, such as hyperlipidemia, type 2 diabetes mellitus, and obesity...
June 15, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28619100/cyclophilin-b-facilitates-the-replication-of-orf-virus
#19
Kui Zhao, Jida Li, Wenqi He, Deguang Song, Ximu Zhang, Di Zhang, Yanlong Zhou, Feng Gao
BACKGROUND: Viruses interact with host cellular factors to construct a more favourable environment for their efficient replication. Expression of cyclophilin B (CypB), a cellular peptidyl-prolyl cis-trans isomerase (PPIase), was found to be significantly up-regulated. Recently, a number of studies have shown that CypB is important in the replication of several viruses, including Japanese encephalitis virus (JEV), hepatitis C virus (HCV) and human papillomavirus type 16 (HPV 16). However, the function of cellular CypB in ORFV replication has not yet been explored...
June 15, 2017: Virology Journal
https://www.readbyqxmd.com/read/28597937/frustration-guided-motion-planning-reveals-conformational-transitions-in-proteins
#20
Dominik Budday, Rasmus Fonseca, Sigrid Leyendecker, Henry van den Bedem
Proteins exist as conformational ensembles, exchanging between substates to perform their function. Advances in experimental techniques yield unprecedented access to structural snapshots of their conformational landscape. However, computationally modeling how proteins use collective motions to transition between substates is challenging owing to a rugged landscape and large energy barriers. Here, we present a new, robotics-inspired motion planning procedure called dCC-RRT that navigates the rugged landscape between substates by introducing dynamic, interatomic constraints to modulate frustration...
June 9, 2017: Proteins
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