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https://www.readbyqxmd.com/read/28445987/context-dependent-mir-204-and-mir-211-affect-the-biological-properties-of-amelanotic-and-melanotic-melanoma-cells
#1
Marianna Vitiello, Andrea Tuccoli, Romina D'Aurizio, Samanta Sarti, Laura Giannecchini, Simone Lubrano, Andrea Marranci, Monica Evangelista, Silvia Peppicelli, Chiara Ippolito, Ivana Barravecchia, Elena Guzzolino, Valentina Montagnani, Michael Gowen, Elisa Mercoledi, Alberto Mercatanti, Laura Comelli, Salvatore Gurrieri, Lawrence W Wu, Omotayo Ope, Keith Flaherty, Genevieve M Boland, Marc R Hammond, Lawrence Kwong, Mario Chiariello, Barbara Stecca, Gao Zhang, Alessandra Salvetti, Debora Angeloni, Letizia Pitto, Lido Calorini, Giovanna Chiorino, Marco Pellegrini, Meenhard Herlyn, Iman Osman, Laura Poliseno
Despite increasing amounts of experimental evidence depicting the involvement of non-coding RNAs in cancer, the study of BRAFV600E-regulated genes has thus far focused mainly on protein-coding ones. Here, we identify and study the microRNAs that BRAFV600E regulates through the ERK pathway.By performing small RNA sequencing on A375 melanoma cells and a vemurafenib-resistant clone that was taken as negative control, we discover miR-204 and miR-211 as the miRNAs most induced by vemurafenib. We also demonstrate that, although belonging to the same family, these two miRNAs have distinctive features...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445932/high-cftr-expression-in-philadelphia-chromosome-positive-acute-leukemia-protects-and-maintains-continuous-activation-of-bcr-abl-and-related-signaling-pathways-in-combination-with-pp2a
#2
Xi Yang, Tianyou Yan, Yuping Gong, Xuehua Liu, Huaqin Sun, Wenming Xu, Chunsen Wang, Duolan Naren, Yuhuan Zheng
Cystic fibrosis transmembrane conductance regulator (CFTR) is classified as an anion channel transporter of Cl- and HCO3-. Through interactions with its PDZ domain, CFTR is capable of regulating other proteins, such as protein phosphatase 2A (PP2A). The aberrant expression and mutation of CFTR have been observed in several tumor, but not in philadelphia chromosome-positive(Ph+) acute leukemia, including Ph+ B cell acute lymphoblastic leukemia(Ph+ B-ALL) and chronic myelogenous leukemia blast crisis phases (CML-BC)...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445716/trumping-neurodegeneration-targeting-common-pathways-regulated-by-autosomal-recessive-parkinson-s-disease-genes
#3
REVIEW
Laura Scott, Valina L Dawson, Ted M Dawson
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the progressive loss of dopaminergic (DA) neurons. Most PD cases are sporadic; however, rare familial forms have been identified. Autosomal recessive PD (ARPD) results from mutations in Parkin, PINK1, DJ-1, and ATP13A2, while rare, atypical juvenile ARPD result from mutations in FBXO7, DNAJC6, SYNJ1, and PLA2G6. Studying these genes and their function has revealed mitochondrial quality control, protein degradation processes, and oxidative stress responses as common pathways underlying PD pathogenesis...
April 23, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28445691/tis11-mediated-mrna-decay-promotes-the-reacquisition-of-drosophila-intestinal-stem-cell-quiescence
#4
Lindy McClelland, Heinrich Jasper, Benoît Biteau
Adult stem cell proliferation rates are precisely regulated to maintain long-term tissue homeostasis. Defects in the mechanisms controlling stem cell proliferation result in impaired regeneration and hyperproliferative diseases. Many stem cell populations increase proliferation in response to tissue damage and reacquire basal proliferation rates after tissue repair is completed. Although proliferative signals have been extensively studied, much less is known about the molecular mechanisms that restore stem cell quiescence...
April 23, 2017: Developmental Biology
https://www.readbyqxmd.com/read/28445649/high-serum-stability-of-collagen-hybridizing-peptides-and-their-fluorophore-conjugates
#5
Lucas L Bennink, Daniel J Smith, Catherine A Foss, Martin G Pomper, Yang Li, S Michael Yu
Collagen hybridizing peptides (CHPs) have a great potential for use in targeted drug delivery, diagnostics, and regenerative medicine due to their ability to specifically bind to denatured collagens associated with many pathologic conditions. Since peptides generally suffer from poor enzymatic stability resulting in rapid degradation and elimination in vivo, CHP's serum stability is a critical parameter that may dictate its pharmacokinetic behavior. Here, we report the serum stability of a series of monomeric CHP derivatives and establish how peptide length, amino acid composition, terminal modification, and linker chemistry influence their availability in serum...
April 26, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28445460/polyglutamine-tracts-regulate-beclin-1-dependent-autophagy
#6
Avraham Ashkenazi, Carla F Bento, Thomas Ricketts, Mariella Vicinanza, Farah Siddiqi, Mariana Pavel, Ferdinando Squitieri, Maarten C Hardenberg, Sara Imarisio, Fiona M Menzies, David C Rubinsztein
Nine neurodegenerative diseases are caused by expanded polyglutamine (polyQ) tracts in different proteins, such as huntingtin in Huntington's disease and ataxin 3 in spinocerebellar ataxia type 3 (SCA3). Age at onset of disease decreases with increasing polyglutamine length in these proteins and the normal length also varies. PolyQ expansions drive pathogenesis in these diseases, as isolated polyQ tracts are toxic, and an N-terminal huntingtin fragment comprising exon 1, which occurs in vivo as a result of alternative splicing, causes toxicity...
April 26, 2017: Nature
https://www.readbyqxmd.com/read/28445409/quantification-of-a-novel-photosensitizer-of-chlorin-e6-c15-monomethyl-ester-in-beagle-dog-plasma-using-hplc-application-to-pharmacokinetic-studies
#7
Xiuxiu Li, Jun Wen, Jingjing Jiang, Xin Zhao, Tingting Zhou, Guorong Fan
Chlorin e6-C15-monomethyl ester (CMME) is a novel photosensitizer, which is synthetized from the degradation products of silkworm excrement. Preclinical studies on the promising photosensitizer CMME are necessary to determine its therapeutic efficacy and druglikeness. A high-performance liquid chromatography with UV detection (HPLC-UV) method was established for the determination of CMME in beagle dog plasma. The sample preparation involved a protein-precipitation method with acetonitrile after the addition of tanshinone IIA as an internal standard (IS)...
April 26, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28445205/inhibition-of-microrna-429-in-the-renal-medulla-increased-salt-sensitivity-of-blood-pressure-in-sprague-dawley-rats
#8
Qing Zhu, Junping Hu, Lei Wang, Weili Wang, Zhengchao Wang, Pin-Lan Li, Krishna M Boini, Ningjun Li
BACKGROUND: We have previously shown that high salt intake suppresses the expression of prolyl hydroxylase domain-containing protein 2 (PHD2), an enzyme promoting the degradation of hypoxia-inducible factor (HIF)-1α, and increases HIF-1α along with its target genes in the renal medulla, which promotes sodium excretion and regulate salt sensitivity of blood pressure. However, it remains unknown how high salt inhibits the expression of PHD2. METHOD AND RESULTS: The current study first revealed that high-salt-induced PHD2 inhibition was due to the enhanced decay of mRNA...
April 25, 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28444859/roles-of-samhd1-in-antiviral-defense-autoimmunity-and-cancer
#9
REVIEW
Miaomiao Li, Dong Zhang, Mengying Zhu, Yuxian Shen, Wei Wei, Songcheng Ying, Heinrich Korner, Jun Li
The enzyme, sterile α motif and histidine-aspartic acid domain-containing protein 1 (SAMHD1) diminishes infection of human immunodeficiency virus type 1 (HIV-1) by hydrolyzing intracellular deoxynucleotide triphosphates (dNTPs) in myeloid cells and resting CD4+ T cells. This dNTP degradation reduces the dNTP concentration to a level insufficient for viral cDNA synthesis, thereby inhibiting retroviral replication. This antiviral enzymatic activity can be inhibited by viral protein X (Vpx). The HIV-2/SIV Vpx causes degradation of SAMHD1, thus interfering with the SAMHD1-mediated restriction of retroviral replication...
April 25, 2017: Reviews in Medical Virology
https://www.readbyqxmd.com/read/28444794/protection-of-protein-from-ruminal-degradation-by-alkali-induced-oxidation-of-chlorogenic-acid-in-sunflower-meal
#10
V Bongartz, C Böttger, N Wilhelmy, N Schulze-Kaysers, K-H Südekum, A Schieber
Lactating ruminants require an adequate supply of absorbable amino acids for the synthesis of milk protein from two sources, that is crude protein (CP) synthesized microbially in the rumen and ruminally undegraded CP (RUP) from feed which can both be digested in the small intestine. Several chemical and physical methods have been identified as being effective in increasing the proportion of RUP of total CP of a feedstuff, yet there is a continuing need for developing and establishing methods which protect feed protein from ruminal degradation with acceptable expenditure of labour and other costs...
April 26, 2017: Journal of Animal Physiology and Animal Nutrition
https://www.readbyqxmd.com/read/28444238/high-purity-circular-rna-isolation-method-rpad-reveals-vast-collection-of-intronic-circrnas
#11
Amaresh C Panda, Supriyo De, Ioannis Grammatikakis, Rachel Munk, Xiaoling Yang, Yulan Piao, Dawood B Dudekula, Kotb Abdelmohsen, Myriam Gorospe
High-throughput RNA sequencing methods coupled with specialized bioinformatic analyses have recently uncovered tens of thousands of unique circular (circ)RNAs, but their complete sequences, genes of origin and functions are largely unknown. Given that circRNAs lack free ends and are thus relatively stable, their association with microRNAs (miRNAs) and RNA-binding proteins (RBPs) can influence gene expression programs. While exoribonuclease treatment is widely used to degrade linear RNAs and enrich circRNAs in RNA samples, it does not efficiently eliminate all linear RNAs...
April 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28443724/genetic-diversity-of-hiv-1-gene-vif-among-treatment-na%C3%A3-ve-brazilians
#12
Fabiola Villanova, Marta Barreiros, Luiz Mario Janini, Ricardo Sobhie Diaz, Elcio Leal
HIV-1 has the Vif protein, which binds to human antiviral proteins APOBEC3 to form complexes to be degraded by cellular proteolysis. To further explore HIV-1 diversity at the population level, we analyzed blood samples from 317 treatment-naïve patients in Brazil. Here, we explored the correlations of Vif polymorphisms with clinical parameters of the patients and found that mutation K22H is associated with low CD4+ cell counts and higher viral loads. Phylogenetic analysis of the vif gene indicated that subtype B was predominant in ∼77% (243/317) of the patients, followed by HIV-1 F ∼18% (56/317) and subtype C ∼4% (12/317); five samples were BF recombinants (∼1% of patients), and one was an AG recombinant...
April 26, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28443661/engineering-of-rumb-toward-a-green-catalyst-for-carbene-insertion-reactions
#13
Matthew W Wolf, David A Vargas, Nicolai Lehnert
The small, stable heme protein myoglobin (Mb) was modified through cofactor substitution and mutagenesis to develop a new catalyst for carbene transfer reactions. The native heme was removed from wild-type Mb and several Mb His64 mutants (H64D, H64A, H64V), and the resulting apoproteins were reconstituted with ruthenium mesoporphyrin IX (RuMpIX). The reconstituted proteins (RuMb) were characterized by UV-vis and circular dichroism spectroscopy and were used as catalysts for the N-H insertion of aniline derivatives and the cyclopropanation of styrene derivatives...
April 26, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28443507/synthesis-and-biological-activity-of-unnatural-enediynes
#14
Roberto Romeo, Salvatore V Giofrè, Maria A Chiacchio
The first reports of the natural enediyne anticancer antibiotics date back to the late 1980s; since then, a great deal of interest has been devoted to the chemistry, biology and potential medical applications of this family of compounds. The biological activity of enediynes is linked to the presence of a highly unsaturated hex-1-ene- 1,5-diyne system. The thermally induced transformation of this unit into a benzene  diradical (the Bergman cycloaromatization) is the key step of the antitumor properties of such compounds: 1,4-diaryl radicals are able to abstract H-atoms from the deoxyribose backbone of DNA, thus leading to DNA strand cleavage and ultimately cell death...
April 24, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28443462/biib021-a-novel-inhibitor-to-heat-shock-protein-90-addicted-oncology
#15
Liang Yan, Weiming Zhang, Beibei Zhang, Chao Xuan, Daogang Wang
Heat shock protein 90 is induced in response to the cell stress. Its overexpression has been reported in many cancers with poor prognosis. It acts as a chaperone to the client proteins, especially the activated oncoproteins in malignancies to protect them from degradation. Heat shock protein 90 inhibition represented anti-cancer effects in many studies. Previous natural product-based compounds are limited by their association with target toxicities. BIIB021 is an orally available, fully synthetic novel small-molecule heat shock protein 90 inhibitor that has shown strong antitumor activities in a large number of preclinical models and is now under clinical investigation...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28443115/cytosolic-glyceraldehyde-3-phosphate-dehydrogenase-is-phosphorylated-during-seed-development
#16
Claudia V Piattoni, Danisa M L Ferrero, Ignacio Dellaferrera, Abelardo Vegetti, Alberto Á Iglesias
Cytosolic glyceraldehyde-3-phosphate dehydrogenase (NAD-GAPDH) is involved in a critical energetic step of glycolysis and also has many important functions besides its enzymatic activity. The recombinant wheat NAD-GAPDH was phosphorylated in vitro at Ser205 by a SNF1-Related protein kinase 1 (SnRK1) from wheat heterotrophic (but not from photosynthetic) tissues. The S205D mutant enzyme (mimicking the phosphorylated form) exhibited a significant decrease in activity but similar affinity toward substrates. Immunodetection and activity assays showed that NAD-GAPDH is phosphorylated in vivo, the enzyme depicting different activity, abundance and phosphorylation profiles during development of seeds that mainly accumulate starch (wheat) or lipids (castor oil seed)...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28443108/the-kinase-activity-of-calcineurin-b-like-interacting-protein-kinase-26-cipk26-influences-its-own-stability-and-that-of-the-aba-regulated-ubiquitin-ligase-keep-on-going-keg
#17
Wendy J Lyzenga, Victoria Sullivan, Hongxia Liu, Sophia L Stone
The Really Interesting New Gene (RING)-type E3 ligase, Keep on Going (KEG) plays a critical role in Arabidopsis growth after germination and the connections between KEG and hormone signaling pathways are expanding. With regards to abscisic acid (ABA) signaling, KEG targets ABA-responsive transcription factors abscisic acid insensitive 5, ABF1 and ABF3 for ubiquitination and subsequent degradation through the 26S proteasome. Regulation of E3 ligases through self-ubiquitination is common to RING-type E3 ligases and ABA promotes KEG self-ubiquitination and degradation...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28442916/expression-and-activity-of-the-urokinase-plasminogen-activator-system-in-canine-primary-brain-tumors
#18
John H Rossmeisl, Kelli Hall-Manning, John L Robertson, Jamie N King, Rafael V Davalos, Waldemar Debinski, Subbiah Elankumaran
BACKGROUND: The expression of the urokinase plasminogen activator receptor (uPAR), a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA), have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28442745/phosphorylation-of-the-mitochondrial-autophagy-receptor-nix-enhances-its-interaction-with-lc3-proteins
#19
Vladimir V Rogov, Hironori Suzuki, Mija Marinković, Verena Lang, Ryuichi Kato, Masato Kawasaki, Maja Buljubašić, Matilda Šprung, Natalia Rogova, Soichi Wakatsuki, Anne Hamacher-Brady, Volker Dötsch, Ivan Dikic, Nathan R Brady, Ivana Novak
The mitophagy receptor Nix interacts with LC3/GABARAP proteins, targeting mitochondria into autophagosomes for degradation. Here we present evidence for phosphorylation-driven regulation of the Nix:LC3B interaction. Isothermal titration calorimetry and NMR indicate a ~100 fold enhanced affinity of the serine 34/35-phosphorylated Nix LC3-interacting region (LIR) to LC3B and formation of a very rigid complex compared to the non-phosphorylated sequence. Moreover, the crystal structure of LC3B in complex with the Nix LIR peptide containing glutamic acids as phosphomimetic residues and NMR experiments revealed that LIR phosphorylation stabilizes the Nix:LC3B complex via formation of two additional hydrogen bonds between phosphorylated serines of Nix LIR and Arg11, Lys49 and Lys51 in LC3B...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28442737/structural-and-biochemical-insights-of-cypa-and-aif-interaction
#20
Biancamaria Farina, Gianluigi Di Sorbo, Angela Chambery, Andrea Caporale, Guido Leoni, Rosita Russo, Fabiola Mascanzoni, Domenico Raimondo, Roberto Fattorusso, Menotti Ruvo, Nunzianna Doti
The Cyclophilin A (CypA)/Apoptosis Inducing Factor (AIF) complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury. The pro-apoptotic form of AIF (AIF(Δ1-121)) mainly interacts with CypA through the amino acid region 370-394. The AIF(370-394) synthetic peptide inhibits complex formation in vitro by binding to CypA and exerts neuroprotection in a model of glutamate-mediated oxidative stress. Here, the binding site of AIF(Δ1-121) and AIF(370-394) on CypA has been mapped by NMR spectroscopy and biochemical studies, and a molecular model of the complex has been proposed...
April 25, 2017: Scientific Reports
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