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https://www.readbyqxmd.com/read/28641400/cytosolic-delivery-of-sirna-by-ultra-high-affinity-dsrna-binding-proteins
#1
Nicole J Yang, Monique J Kauke, Fangdi Sun, Lucy F Yang, Katie F Maass, Michael W Traxlmayr, Yao Yu, Yingda Xu, Robert S Langer, Daniel G Anderson, K Dane Wittrup
Protein-based methods of siRNA delivery are capable of uniquely specific targeting, but are limited by technical challenges such as low potency or poor biophysical properties. Here, we engineered a series of ultra-high affinity siRNA binders based on the viral protein p19 and developed them into siRNA carriers targeted to the epidermal growth factor receptor (EGFR). Combined in trans with a previously described endosome-disrupting agent composed of the pore-forming protein Perfringolysin O (PFO), potent silencing was achieved in vitro with no detectable cytotoxicity...
June 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28641369/markers-of-inflammation-and-incident-breast-cancer-risk-in-the-women-s-health-study
#2
Deirdre K Tobias, Akintunde O Akinkuolie, Paulette D Chandler, Patrick R Lawler, JoAnn E Manson, Julie E Buring, Paul M Ridker, Lu Wang, I-Min Lee, Samia Mora
Chronic inflammation may be a risk factor for breast cancer development and progression, yet which inflammatory biomarkers and pathways are relevant is unknown. The study included 27,071 Women's Health Study participants (mean, 54.5 years old) free of cancer and cardiovascular disease at enrollment (1992 to 1995) with baseline measures of four inflammatory biomarkers: high sensitivity C-reactive protein (hsCRP), fibrinogen, N-acetyl side-chains of acute phase proteins (GlycA), and soluble intercellular adhesion molecule-1 (sICAM-1)...
June 21, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28641336/suppression-of-forkhead-box-protein-o1-foxo1-transcription-factor-may-promote-adrenocortical-tumorigenesis
#3
Adam Stenman, Timothy Murtha, Reju Korah, Tobias Carling
Despite recent comprehensive genetic analyses, molecular evidence for a pathophysiological continuum linking benign adrenocortical adenoma (ACA) and highly aggressive adrenocortical carcinoma (ACC) is still elusive. Using human tumor samples and the established ACC cell line SW-13, this study investigated potential regulatory roles for FOXO transcription factors, in modulating adrenocortical tumorigenesis. Adrenocortical tumor specimens (20 ACAs, 10 ACCs, and 9 normal adrenal tissue samples) obtained from 30 patients were analyzed for ubiquitously expressed FOXO transcription factors, FOXO1 and FOXO3 using qRT-PCR and immunohistochemistry...
June 22, 2017: Hormone and Metabolic Research, Hormon- und Stoffwechselforschung, Hormones et Métabolisme
https://www.readbyqxmd.com/read/28641308/detection-of-phosphatidylserine-positive-exosomes-for-the-diagnosis-of-early-stage-malignancies
#4
Raghava Sharma, Xianming Huang, Rolf A Brekken, Alan J Schroit
BACKGROUND: There has been increasing interest in the detection of tumour exosomes in blood for cancer diagnostics. Most studies have focussed on miRNA and protein signatures that are surrogate markers for specific tumour types. Because tumour cells and tumour-derived exosomes display phosphatidylserine (PS) in their outer membrane leaflet, we developed a highly sensitive ELISA-based system that detects picogram amounts of exosomal phospholipid in plasma as a cancer biomarker. METHODS: This report describes the development of a highly specific and sensitive ELISA for the capture of PS-expressing tumour exosomes in the blood of tumour-bearing mice...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28641185/mechanistic-understanding-of-low-methylmercury-bioaccessibility-from-crayfish-procambarus-clarkii-muscle-tissue
#5
Qian Peng, Ben K Greenfield, Fei Dang, Yu Gong, Wenbo Bu, Huan Zhong
Recent research indicates that dietary exposure to mercury and other metals from crayfish consumption poses a human health concern, particularly in regions with high crayfish-consuming populations. To better understand consumption risk from methylmercury (MeHg), we quantified MeHg bioaccessibility in edible tail muscle of cooked red swamp crayfish (Procambarus clarkii, collected from seven cities in China), versus cooked fillet tissue of two finfish species: yellow croaker (Larimichthys polyactis) and snakehead (Channa argus)...
June 19, 2017: Science of the Total Environment
https://www.readbyqxmd.com/read/28641106/antisense-oligonucleotides-translation-from-mouse-models-to-human-neurodegenerative-diseases
#6
REVIEW
Kathleen M Schoch, Timothy M Miller
Multiple neurodegenerative diseases are characterized by single-protein dysfunction and aggregation. Treatment strategies for these diseases have often targeted downstream pathways to ameliorate consequences of protein dysfunction; however, targeting the source of that dysfunction, the affected protein itself, seems most judicious to achieve a highly effective therapeutic outcome. Antisense oligonucleotides (ASOs) are small sequences of DNA able to target RNA transcripts, resulting in reduced or modified protein expression...
June 21, 2017: Neuron
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#7
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28641032/targeting-rho-gtpase-effector-p21-activated-kinase-4-pak4-suppresses-p-bad-microrna-drug-resistance-axis-leading-to-inhibition-of-pancreatic-ductal-adenocarcinoma-proliferation
#8
Ramzi M Mohammad, Yiwei Li, Irfana Muqbil, Amro Aboukameel, William Senapedis, Erkan Baloglu, Yosef Landesman, Philip A Philip, Asfar S Azmi
Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and therapy resistant malignancy. Mutant K-Ras, found in >90% of refractory PDAC, acts as a molecular switch activating Rho GTPase signaling that in turn promotes a plethora of pro-survival molecules and oncogenic microRNAs. We investigated the impact of Rho GTPase effector protein p21 activated kinase 4 (PAK4) inhibition on pro-survival p-Bad and oncogenic miRNA signaling. We demonstrate that the dual NAMPT and PAK4 modulators (KPT-9274 and KPT-9307) inhibit PDAC cell proliferation through down-regulation of Bad phosphorylation and up-regulation tumor suppressive miRNAs (miR-145, let-7c, let-7d, miR-34c, miR320 and miR-100)...
June 22, 2017: Small GTPases
https://www.readbyqxmd.com/read/28640964/targeted-mutagenesis-in-tetraploid-switchgrass-panicum-virgatum-l-using-crispr-cas9
#9
Yang Liu, Paul Merrick, Zhengzhi Zhang, Chonghui Ji, Bing Yang, Shui-Zhang Fei
The CRISPR/Cas9 system has become a powerful tool for targeted mutagenesis. Switchgrass (Panicum virgatum L.) is a high yielding perennial grass species that has been designated as a model biomass crop by the U.S. Department of Energy. The self infertility and high ploidy level make it difficult to study gene function or improve germplasm. To overcome these constraints, we explored the feasibility of using CRISPR/Cas9 for targeted mutagenesis in a tetraploid cultivar 'Alamo' switchgrass. We first developed a transient assay by which a non-functional green fluorescent protein gene containing a 1 bp frameshift insertion in its 5' coding region was successfully mutated by a Cas9/sgRNA complex resulting in its restored function...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28640934/substrate-specificity-and-safener-inducibility-of-the-plant-udp-glucose-dependent-family-1-glycosyltransferases-super-family
#10
Melissa Brazier-Hicks, Markus Gershater, David Dixon, Robert Edwards
Plants contain large numbers of family 1 UDP-glucose dependent glycosyltransferases (UGTs), including members that conjugate xenobiotics. Arabidopsis contains 107 UGT genes with 99 family members successfully expressed as glutathione transferase (GST)-fusion proteins in E.coli. A high-throughput catalytic screen was developed based on quantification of the fusion by measuring GST activity. UGT activity using UDP-glucose as donor was then determined using 11 synthetic acceptors bearing hydroxyl, amino and thiol groups that had been shown to undergo conjugation in plant extracts...
June 22, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28640877/identification-of-c-ebp%C3%AE-as-a-novel-target-of-the-hpv8-e6-protein-regulating-mir-203-in-human-keratinocytes
#11
Anna M Marthaler, Marta Podgorska, Pascal Feld, Alina Fingerle, Katrin Knerr-Rupp, Friedrich Grässer, Hans Smola, Klaus Roemer, Elke Ebert, Yoo-Jin Kim, Rainer M Bohle, Cornelia S L Müller, Jörg Reichrath, Thomas Vogt, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Patients suffering from Epidermodysplasia verruciformis (EV), a rare inherited skin disease, display a particular susceptibility to persistent infection with cutaneous genus beta-human papillomavirus (beta-HPV), such as HPV type 8. They have a high risk to develop non-melanoma skin cancer at sun-exposed sites. In various models evidence is emerging that cutaneous HPV E6 proteins disturb epidermal homeostasis and support carcinogenesis, however, the underlying mechanisms are not fully understood as yet. In this study we demonstrate that microRNA-203 (miR-203), a key regulator of epidermal proliferation and differentiation, is strongly down-regulated in HPV8-positive EV-lesions...
June 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28640866/diet-induced-adipose-tissue-expansion-is-mitigated-in-mice-with-a-targeted-inactivation-of-mesoderm-specific-transcript-mest
#12
Rea P Anunciado-Koza, Justin Manuel, Randall L Mynatt, Jingying Zhang, Leslie P Kozak, Robert A Koza
Interindividual variation of white adipose tissue (WAT) expression of mesoderm specific transcript (Mest), a paternally-expressed imprinted gene belonging to the α/β-hydrolase fold protein family, becomes apparent among genetically inbred mice fed high fat diet (HFD) and is positively associated with adipose tissue expansion (ATE). To elucidate a role for MEST in ATE, mice were developed with global and adipose tissue inactivation of Mest. Mice with homozygous (MestgKO) and paternal allelic (MestpKO) inactivation of Mest were born at expected Mendelian frequencies, showed no behavioral or physical abnormalities, and did not perturb expression of the Mest locus-derived microRNA miR-335...
2017: PloS One
https://www.readbyqxmd.com/read/28640837/identification-and-prediction-of-alternative-transcription-start-sites-that-generate-rod-photoreceptor-specific-transcripts-from-ubiquitously-expressed-genes
#13
Evgenya Y Popova, Anna C Salzberg, Chen Yang, Samuel Shao-Min Zhang, Colin J Barnstable
Transcriptome complexity is substantially increased by the use of multiple transcription start sites for a given gene. By utilizing a rod photoreceptor-specific chromatin signature, and the RefSeq database of established transcription start sites, we have identified essentially all known rod photoreceptor genes as well as a group of novel genes that have a high probability of being expressed in rod photoreceptors. Approximately half of these novel rod genes are transcribed into multiple mRNA and/or protein isoforms through alternative transcriptional start sites (ATSS), only one of which has a rod-specific epigenetic signature and gives rise to a rod transcript...
2017: PloS One
https://www.readbyqxmd.com/read/28640814/a-novel-algorithm-identifies-stress-induced-alterations-in-mitochondrial-connectivity-and-inner-membrane-structure-from-confocal-images
#14
Mathieu Ouellet, Gérald Guillebaud, Valerie Gervais, David Lupien St-Pierre, Marc Germain
Mitochondria exist as a highly interconnected network that is exquisitely sensitive to variations in nutrient availability, as well as a large array of cellular stresses. Changes in length and connectivity of this network, as well as alterations in the mitochondrial inner membrane (cristae), regulate cell fate by controlling metabolism, proliferation, differentiation, and cell death. Given the key roles of mitochondrial dynamics, the process by which mitochondria constantly fuse and fragment, the measure of mitochondrial length and connectivity provides crucial information on the health and activity of various cell populations...
June 22, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28640809/development-of-elisas-for-diagnosis-of-acute-typhoid-fever-in-nigerian-children
#15
Jiin Felgner, Aarti Jain, Rie Nakajima, Li Liang, Algis Jasinskas, Eduardo Gotuzzo, Joseph M Vinetz, Fabio Miyajima, Munir Pirmohamed, Fatimah Hassan-Hanga, Dominic Umoru, Binta Wudil Jibir, Safiya Gambo, Kudirat Olateju, Philip L Felgner, Stephen Obaro, D Huw Davies
Improved serodiagnostic tests for typhoid fever (TF) are needed for surveillance, to facilitate patient management, curb antibiotic resistance, and inform public health programs. To address this need, IgA, IgM and IgG ELISAs using Salmonella enterica serovar Typhi (S. Typhi) lipopolysaccharide (LPS) and hemolysin E (t1477) protein were conducted on 86 Nigerian pediatric TF and 29 non-typhoidal Salmonella (NTS) cases, 178 culture-negative febrile cases, 28 "other" (i.e., non-Salmonella) pediatric infections, and 48 healthy Nigerian children...
June 22, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28640747/a-single-amino-acid-change-in-the-non-structural-nv-protein-impacts-the-virulence-phenotype-of-viral-hemorrhagic-septicemia-virus-in-trout
#16
Laury Baillon, Emilie Mérour, Joëlle Cabon, Lénaïg Louboutin, Hélène Quenault, Fabrice Touzain, Thierry Morin, Yannick Blanchard, Stéphane Biacchesi, Michel Brémont
Novirhabdoviruses like the Viral hemorrhagic septicemia virus (VHSV) are rhabdoviruses infecting fish. In the current study, RNA genomes of different VHSV field isolates classified as high, medium or low virulent phenotypes have been sequenced by next-generation sequencing and compared. Various amino acid changes, depending on the VHSV phenotype, have been identified in all the VHSV proteins. As a starting point, we focused our study on the non-virion (NV) non-structural protein in which an arginine residue (R116) is present in all the virulent isolates and replaced by a serine/asparagine residue S/N116 in the attenuated isolates...
June 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28640691/the-nesprin-cytoskeleton-interface-probed-directly-on-single-nuclei-is-a-mechanically-rich-system
#17
Daniel A Balikov, Sonia K Brady, Ung Hyun Ko, Jennifer H Shin, Jose M de Pereda, Arnoud Sonnenberg, Hak-Joon Sung, Matthew J Lang
The cytoskeleton provides structure and plays an important role in cellular function such as migration, resisting compression forces, and transport. The cytoskeleton also reacts to physical cues such as fluid shear stress or extracellular matrix remodeling by reorganizing filament associations, most commonly focal adhesions and cell-cell cadherin junctions. These mechanical stimuli can result in genome-level changes, and the physical connection of the cytoskeleton to the nucleus provides an optimal conduit for signal transduction by interfacing with nuclear envelope proteins, called nesprins, within the LINC (linker of the nucleus to the cytoskeleton) complex...
June 22, 2017: Nucleus
https://www.readbyqxmd.com/read/28640644/nebivolol-alleviates-aortic-remodeling-through-enos-upregulation-and-inhibition-of-oxidative-stress-in-l-name-induced-hypertensive-rats
#18
Yan Wang, Fei Zhang, Yu Liu, Sha Yin, Xuefen Pang, Zhidong Li, Zehui Wei
PURPOSE: To investigate the effect and mechanism of nebivolol on aortic remodeling in N-nitro-l-arginine methyl ester (l-NAME)-induced hypertension. METHODS: Male Sprague-Dawley rats were treated with equal volumes of drinking water or l-NAME (60 mg/kg/day), alone or in combination with nebivolol (8 mg/kg/day) or atenolol (80 mg/kg/day) by gavage for 8 weeks. Systolic blood pressure (SBP), aortic morphometry, plasma nitric oxide (NO) levels, nitric oxide synthase (NOS) activity, and relaxation of aorta to acetylcholine were determined...
June 22, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28640632/gut-microbiota-nitric-oxide-and-microglia-as-pre-requisites-for-neurodegenerative-disorders
#19
Joyce Ka Yu Tse
Regulating fluctuating endogenous nitric oxide (NO) levels is necessary for proper physiological functions. Aberrant NO pathways are implicated in a number of neurological disorders, including Alzheimer's Disease (AD) and Parkinson's Disease. The mechanism of NO in oxidative and nitrosative stress with pathological consequences involves reactions with reactive oxygen species (e.g. superoxide) to form the highly reactive peroxynitrite, hydrogen peroxide, hypochloride ions and hydroxyl radical. NO levels are typically regulated by endogenous nitric oxide synthases (NOS), and inflammatory iNOS is implicated in the pathogenesis of neurodegenerative diseases, in which elevated NO mediates axonal degeneration and activates cyclooxygenases to provoke neuroinflammation...
June 22, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28640602/dietary-n-carbamylglutamate-supplementation-in-reduced-protein-diet-affects-carcass-traits-and-profile-of-muscle-amino-acids-and-fatty-acids-in-finishing-pigs
#20
Changchuan Ye, Xiangzhou Zeng, JInlong Zhu, Ying Liu, Qianhong Ye, Shiyan Qiao, Xiangfang Zeng
This aim of this study was to investigate whether dietary N-Carbamylglutamate (NCG) supplementation affected carcass traits and meat quality in finishing pigs. One hundred and twenty gilts were randomly assigned to one of four treatments for 40 d, including standard protein diet (SP), reduced protein diet supplemented 1.7% L-alanine (RP + Ala), reduced protein diet supplemented with 1.0 % L-arginine (RP + Arg) and reduced protein diet supplemented with 0.1% NCG and 1.7% L-alanine (RP + NCG). NCG supplementation increased the endogenous synthesis of L-arginine...
June 22, 2017: Journal of Agricultural and Food Chemistry
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