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https://www.readbyqxmd.com/read/29705539/kir-4-1-inward-rectifier-potassium-channel-is-upregulated-in-astrocytes-in-a-murine-multiple-sclerosis-model
#1
Francisco Mercado, Angélica Almanza, Nazario Rubio, Enrique Soto
Multiple sclerosis (MS) is a high prevalence degenerative disease characterized at the cellular level by glial and neuronal cell death. The causes of cell death during the disease course are not fully understood. In this work we demonstrate that in a MS model induced by Theiler's murine encephalomyelitis virus (TMEV) infection, the inward rectifier (Kir) 4.1 potassium channel subunit is overexpressed in astrocytes. In voltage clamp experiments the inward current density from TMEV-infected astrocytes was significantly larger than in mock-infected ones...
April 26, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29683453/a-blood-based-test-for-the-detection-of-ros1-and-ret-fusion-transcripts-from-circulating-ribonucleic-acid-using-digital-polymerase-chain-reaction
#2
Hestia S Mellert, Kristin E Alexander, Leisa P Jackson, Gary A Pestano
We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR)...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29651275/structural-and-functional-motifs-in-influenza-virus-rnas
#3
REVIEW
Damien Ferhadian, Maud Contrant, Anne Printz-Schweigert, Redmond P Smyth, Jean-Christophe Paillart, Roland Marquet
Influenza A viruses (IAV) are responsible for recurrent influenza epidemics and occasional devastating pandemics in humans and animals. They belong to the Orthomyxoviridae family and their genome consists of eight (-) sense viral RNA (vRNA) segments of different lengths coding for at least 11 viral proteins. A heterotrimeric polymerase complex is bound to the promoter consisting of the 13 5'-terminal and 12 3'-terminal nucleotides of each vRNA, while internal parts of the vRNAs are associated with multiple copies of the viral nucleoprotein (NP), thus forming ribonucleoproteins (vRNP)...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29606300/homozygous-mutations-in-wee2-cause-fertilization-failure-and-female-infertility
#4
Qing Sang, Bin Li, Yanping Kuang, Xueqian Wang, Zhihua Zhang, Biaobang Chen, Ling Wu, Qifeng Lyu, Yonglun Fu, Zheng Yan, Xiaoyan Mao, Yao Xu, Jian Mu, Qiaoli Li, Li Jin, Lin He, Lei Wang
Fertilization is a fundamental process of development and is a prerequisite for successful human reproduction. In mice, although several receptor proteins have been shown to play important roles in the process of fertilization, only three genes have been shown to cause fertilization failure and infertility when deleted in vivo. In clinical practice, some infertility case subjects suffer from recurrent failure of in vitro fertilization and intracytoplasmic sperm injection attempts due to fertilization failure, but the genetic basis of fertilization failure in humans remains largely unknown...
April 5, 2018: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29584756/transcriptional-signature-associated-with-early-rheumatoid-arthritis-and-healthy-individuals-at-high-risk-to-develop-the-disease
#5
N Macías-Segura, J E Castañeda-Delgado, Y Bastian, D Santiago-Algarra, J D Castillo-Ortiz, A L Alemán-Navarro, E Jaime-Sánchez, M Gomez-Moreno, C A Saucedo-Toral, Edgar E Lara-Ramírez, M Zapata-Zuñiga, L Enciso-Moreno, R González-Amaro, C Ramos-Remus, J A Enciso-Moreno
BACKGROUND: Little is known regarding the mechanisms underlying the loss of tolerance in the early and preclinical stages of autoimmune diseases. The aim of this work was to identify the transcriptional profile and signaling pathways associated to non-treated early rheumatoid arthritis (RA) and subjects at high risk. Several biomarker candidates for early RA are proposed. METHODS: Whole blood total RNA was obtained from non-treated early RA patients with <1 year of evolution as well as from healthy first-degree relatives of patients with RA (FDR) classified as ACCP+ and ACCP- according to their antibodies serum levels against cyclic citrullinated peptides...
2018: PloS One
https://www.readbyqxmd.com/read/29566083/targeted-deletion-of-the-aquaglyceroporin-aqp9-is-protective-in-a-mouse-model-of-parkinson-s-disease
#6
Katja Stahl, Soulmaz Rahmani, Agnete Prydz, Nadia Skauli, Nanna MacAulay, Maria N Mylonakou, Reidun Torp, Øivind Skare, Torill Berg, Trygve B Leergaard, Ragnhild E Paulsen, Ole P Ottersen, Mahmood Amiry-Moghaddam
More than 90% of the cases of Parkinson's disease have unknown etiology. Gradual loss of dopaminergic neurons of substantia nigra is the main cause of morbidity in this disease. External factors such as environmental toxins are believed to play a role in the cell loss, although the cause of the selective vulnerability of dopaminergic neurons remains unknown. We have previously shown that aquaglyceroporin AQP9 is expressed in dopaminergic neurons and astrocytes of rodent brain. AQP9 is permeable to a broad spectrum of substrates including purines, pyrimidines, and lactate, in addition to water and glycerol...
2018: PloS One
https://www.readbyqxmd.com/read/29530931/-lithobates-catesbeianus-american-bullfrog-oocytes-a-novel-heterologous-expression-system-for-aquaporins
#7
Jessica Kabutomori, Olivia Beloto-Silva, R Ryan Geyer, Raif Musa-Aziz
Xenopus laevis oocytes are a valuable tool for investigating the function of membrane proteins. However, regulations around the world, specifically in Brazil, render the import of Xenopus laevis frogs impractical, and, in some cases, impossible. Here, as an alternative, we evaluate the usefulness of the North American aquatic bullfrog Lithobates catesebeianus , which is commercially available in Brazil, for the heterologous expression of aquaporin (AQP) proteins. We have developed a method that combines a brief collagenase treatment and mechanical defolliculation for isolating individual oocytes from Lithobates ovaries...
March 29, 2018: Biology Open
https://www.readbyqxmd.com/read/29487159/molecular-and-functional-characterization-of-the-gulf-toadfish-serotonin-transporter-slc6a4
#8
Molly H B Amador, M Danielle McDonald
The serotonin transporter (SERT) functions in the uptake of the neurotransmitter serotonin (5-HT) from the extracellular milieu and is the molecular target of the selective serotonin re-uptake inhibitors (SSRIs), a common group of anti-depressants. The current study comprehensively assesses the sequence, tissue distribution, transport kinetics and physiological function of a teleost SERT. The 2022 bp toadfish SERT sequence encodes a protein of 673 amino acids, which shows 83% similarity to zebrafish SERT and groups with SERT of other teleosts in phylogenetic analysis...
April 6, 2018: Journal of Experimental Biology
https://www.readbyqxmd.com/read/29449648/the-role-of-disease-linked-residue-glutamine-913-in-support-of-the-structure-and-function-of-the-human-electrogenic-sodium-bicarbonate-cotransporter-nbce1-a
#9
Evan J Myers, Aniko Marshall, Mark D Parker
Mutations in the sodium bicarbonate cotransporter NBCe1 (SLC4A4) cause proximal renal tubular acidosis (pRTA). We recently described a novel pRTA mutation p.Gln913Arg (Q913R), inherited in compound heterozygous form with p.Arg510His (R510H). Q913R causes intracellular retention of NBCe1 and a 'gain of function' Cl- leak. To learn more about the importance of glutamine at position 913, we substituted a variety of alternative amino-acid residues (Cys, Glu, Lys, Leu, Ser) at position 913. Studying cRNA-injected Xenopus oocytes by voltage clamp, we find that most de novo mutants exhibit close-to-normal NBCe1 activity; only Q913K expresses a Cl- leak...
February 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29324866/regulation-of-influenza-virus-replication-by-wnt-%C3%AE-catenin-signaling
#10
Sunil More, Xiaoyun Yang, Zhengyu Zhu, Gayan Bamunuarachchi, Yujie Guo, Chaoqun Huang, Keith Bailey, Jordan P Metcalf, Lin Liu
Wnt/β-catenin signaling is an essential pathway in cell cycle control. Dysregulation of the Wnt/β-catenin signaling pathway during viral infection has been reported. In this study, we examined the effect of modulating Wnt/β-catenin signaling during influenza virus infection. The activation of the Wnt/β-catenin pathway by Wnt3a increased influenza virus mRNA and virus production in in vitro in mouse lung epithelial E10 cells and mRNA expresson of influenza virus genes in vivo in the lungs of mice infected with influenza virus A/Puerto Rico/8/34...
2018: PloS One
https://www.readbyqxmd.com/read/29317613/glucose-6-phosphate-dehydrogenase-is-indispensable-in-embryonic-development-by-modulation-of-epithelial-mesenchymal-transition-via-the-nox-smad3-mir-200b-axis
#11
Yi-Hsuan Wu, Ying-Hsuan Lee, Hung-Yu Shih, Shih-Hsiang Chen, Yi-Chuan Cheng, Daniel Tsun-Yee Chiu
Glucose-6-phosphate dehydrogenase (G6PD) is a housekeeping enzyme involved in the pentose phosphate shunt for producing nicotinamide adenine dinucleotide phosphate (NADPH). Severe G6PD deficiency leads to embryonic lethality, but the underlying mechanism is unclear. In the current study, the effects of G6PD on epithelial-mesenchymal transition (EMT), especially during embryonic development, were investigated. The knockdown of G6PD induced morphological changes, accompanied by the suppression of epithelial markers, E-cadherin and β-catenin, in A549 and MDCK cells...
January 9, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29277715/direct-modification-of-the-5-ht-3-receptor-current-by-some-anticancer-drugs
#12
Yukiko Nakamura, Yusuke Ishida, Makoto Kondo, Shoichi Shimada
The serotonin (5-hydroxytryptamine) type 3 (5-HT3 ) receptor is an important target in the control of emesis, and 5-HT3 receptor antagonists are effective against the early phase chemotherapy evoked vomiting. We recently reported that the anticancer drugs irinotecan and topotecan directly modulate the 5-HT-mediated 5-HT3 receptor current in vitro. In addition, the drug response depends on the 5-HT3 subunit composition. Here, we explored the effects of 35 anticancer drugs on the 5-HT3 receptor current. We microinjected Xenopus laevis oocytes with human 5-HT3 A cRNA or a combination of human 5-HT3 A and human 5-HT3 B cRNA, and performed two-electrode voltage clamp recordings of 5-HT3 A and 5-HT3 AB receptor currents in the presence of each of the 35 drugs...
February 15, 2018: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29212456/helicobacter-induced-gastric-inflammation-alters-the-properties-of-gastric-tissue-stem-progenitor-cells
#13
Wataru Shibata, Soichiro Sue, Sachiko Tsumura, Yasuaki Ishii, Takeshi Sato, Eri Kameta, Makoto Sugimori, Hiroaki Yamada, Hiroaki Kaneko, Tomohiko Sasaki, Tomohiro Ishii, Toshihide Tamura, Masaaki Kondo, Shin Maeda
BACKGROUND: Although Helicobacter-induced gastric inflammation is the major predisposing factor for gastric carcinogenesis, the precise mechanism by which chronic gastritis causes gastric cancer remains unclear. Intestinal and spasmolytic polypeptide-expressing metaplasia (SPEM) is considered as precancerous lesions, changes in epithelial tissue stem/progenitor cells after chronic inflammation has not been clarified yet. In this study, we utilized three-dimensional gastric epithelial cell culture systems that could form organoids, mimicking gastric epithelial layer, and characterized the changes in epithelial cells after chronic Helicobacter felis infection...
December 6, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29183588/heterologous-formation-of-neonicotinoid-sensitive-nachrs-containing-unc-38-and-unc-29-subunits-from-bursaphelenchus-xylophilus
#14
Na Yu, Yang Liu, Xuan Wang, Jian Li, Haibo Bao, Zewen Liu
Nicotinic acetylcholine receptor (nAChR) subunits are encoded by a large multigene family and generate a large number of pentameric receptors with various properties. At present, nematode species, such as Caenorhabditis elegans, have the largest number of nAChR subunits. In this study, two nAChR subunits (Bxy-Unc-38 and Bxy-Unc-29) were cloned from Bursaphelenchus xylophilus, a fatal nematode pest on pine trees causing pine wilt disease. When Bxy-Unc-38 and Bxy-Unc-29 were co-expressed in Xenopus oocytes, constructed functional nAChRs showed agonist responses to acetylcholine and imidacloprid, a neonicotinoid insecticide...
November 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/29156097/4-aminopyridine-a-pan-voltage-gated-potassium-channel-inhibitor-that-enhances-k-v-7-4-currents-and-inhibits-noradrenaline-mediated-contraction-of-rat-mesenteric-small-arteries
#15
Makhala M Khammy, Sukhan Kim, Bo H Bentzen, Soojung Lee, Inyeong Choi, Christian Aalkjaer, Thomas A Jepps
BACKGROUND AND PURPOSE: Kv 7.4 and Kv 7.5 channels are regulators of vascular tone. 4-Aminopyridine (4-AP) is considered a broad inhibitor of voltage-gated potassium (KV ) channels, with little inhibitory effect on Kv 7 family members at mmol concentrations. However, the effect of 4-AP on Kv 7 channels has not been systematically studied. The aim of this study was to investigate the pharmacological activity of 4-AP on Kv 7.4 and Kv 7.5 channels and characterize the effect of 4-AP on rat resistance arteries...
February 2018: British Journal of Pharmacology
https://www.readbyqxmd.com/read/29126984/osteopontin-as-a-novel-substrate-for-the-proprotein-convertase-5-6-pcsk5-in-bone
#16
Betty Hoac, Delia Susan-Resiga, Rachid Essalmani, Edwige Marcinkiweicz, Nabil G Seidah, Marc D McKee
Seven proprotein convertases cleave the basic amino acid consensus sequence K/R-Xn -K/R↓ (where n=0, 2, 4 or 6 variable amino acids) to activate precursor proteins. Despite similarities in substrate specificity, basic amino acid-specific proprotein convertases have a distinct tissue distribution allowing for enzymatic actions on tissue-resident substrates. Proprotein convertase 5/6 (PC5/6) has two splice variants - soluble PC5/6A and membrane-bound PC5/6B - and is expressed during mouse development in many tissues including bone and tooth, but little is known about the substrates for PC5/6 therein...
February 2018: Bone
https://www.readbyqxmd.com/read/29118119/a-mechanism-for-prime-realignment-during-influenza-a-virus-replication
#17
Judith Oymans, Aartjan J W Te Velthuis
The influenza A virus genome consists of eight segments of single-stranded RNA. These segments are replicated and transcribed by a viral RNA-dependent RNA polymerase (RdRp) that is made up of the influenza virus proteins PB1, PB2 and PA. To copy the viral RNA (vRNA) genome segments and the complementary RNA (cRNA) segments, the replicative intermediate of viral replication, the RdRp must use two promoters and two different de novo initiation mechanisms. On the vRNA promoter, the RdRp initiates on the 3' terminus, while on the cRNA promoter the RdRp initiates internally and subsequently realigns the nascent vRNA product to ensure that the template is copied in full...
November 8, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29067612/sources-of-sulphate-minerals-in-limestone-cave-a-possible-evidence-of-anthropogenic-activity-a-case-study-in-%C3%A4-rna-jama-cave-slovenia
#18
Simona Jarc, Miloš Miler, Stanka Šebela, Nina Zupančič
In the caves, the formation of cave minerals is a consequence of a variety of chemical reactions, some of them also due to human activity. There are many caves in Slovenia, but sulphate minerals are not very often reported and analysed. In this study, the presence of sulphate minerals is detected by SEM/EDS analysis of speleothems from Črna Jama, a cave near Kočevje (southern Slovenia). The cave is characterised by its dark, almost black colour on cave walls, floor and speleothems. Anthropogenic influence in the cave is still visible, including the remains of a fireplace, some inscriptions on the walls and wooden containers...
December 2017: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29065312/understanding-the-patient-experience-of-cost-related-non-adherence-to-prescription-medications-through-typology-development-and-application
#19
Laurie J Goldsmith, Ashra Kolhatkar, Dominic Popowich, Anne M Holbrook, Steven G Morgan, Michael R Law
Many patients report skipping doses, splitting pills, or not filling prescriptions due to out-of-pocket costs-a phenomenon known as cost-related non-adherence (CRNA). This study investigated CRNA from the patient's perspective, and, to our knowledge, is the first study to undertake a qualitative investigation of CRNA specifically. We report the results from 35 semi-structured interviews conducted in 2014-15 with adults in four Canadian cities across two provinces. We used framework analysis to develop a CRNA typology to characterize major factors in patients' CRNA decisions...
October 9, 2017: Social Science & Medicine
https://www.readbyqxmd.com/read/28978935/a-tomato-spotted-wilt-virus-s-rna-based-replicon-system-in-yeast
#20
Kazuhiro Ishibashi, Eiko Matsumoto-Yokoyama, Masayuki Ishikawa
Tomato spotted wilt virus (TSWV) is a negative-strand RNA virus of the order Bunyavirales, family Tospoviridae, genus Orthotospovirus. TSWV infects a broad range of plant species, causing serious economic losses. Despite its agronomic importance, molecular biological understanding of TSWV has been limited, partly due to the lack of a reverse genetics system, which would enable genetic manipulation of the virus. Here, we report that RNA synthesis by TSWV RNA polymerase occurs in the yeast Saccharomyces cerevisiae using a segment of the TSWV genome, S RNA expressed from cloned cDNA, as a template...
October 4, 2017: Scientific Reports
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