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https://www.readbyqxmd.com/read/28918404/combined-caesarean-with-splenectomy-in-pregnancy-with-portal-hypertension-defining-plausibility
#1
Manjunath Maruti Pol, Latika Uniyal Chawla, Yashwant Singh Rathore, Ritesh Goel
24-year-old woman at 28 weeks gestation was referred from peripheral hospital with diagnosis of pregnancy with portal hypertension. She had received multiple transfusion for pancytopaenia in the past and had undergone endoscopic sclerotherapy for oesophageal varices. Initially, she was admitted in our hospital at 28 weeks gestation for blood transfusion and was evaluated by multispecialty team of doctors. She was advised splenectomy for transfusion-dependent pancytopaenia secondary to hypersplenism in non-cirrhotic portal hypertension...
September 15, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28915040/elucidating-the-interdependence-of-drug-resistance-from-combinations-of-mutations
#2
Debra A Ragland, Troy W Whitfield, Sook-Kyung Lee, Ronald Swanstrom, Konstantin B Zeldovich, Nese Kurt Yilmaz, Celia A Schiffer
HIV-1 protease is responsible for the cleavage of 12 non-homologous sites within the Gag and Gag-Pro-Pol polyproteins in the viral genome. Under the selective pressure of protease inhibition, the virus evolves mutations within (primary) and outside of (secondary) the active site allowing the protease to process substrates while simultaneously countering inhibition. The primary protease mutations impede inhibitor binding directly, while the secondary mutations are considered accessory mutations that compensate for a loss in fitness...
September 15, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28912369/customized-viral-immunotherapy-for-hpv-associated-cancer
#3
Matthew J Atherton, Kyle B Stephenson, Jonathan Pol, Fuan Wang, Charles Lefebvre, David F Stojdl, Jake K Nikota, Anna Dvorkin-Gheva, Andrew Nguyen, Lan Chen, Stephanie Johnson-Obaseki, Patrick J Villeneuve, Jean-Simon Diallo, Jim Dimitroulakos, Yonghong Wan, Brian D Lichty
The viral transforming proteins E6 and E7 make human papilloma virus positive (HPV+) malignancies an attractive target for cancer immunotherapy. However, therapeutic vaccination exerts limited efficacy in the setting of advanced disease. We designed a strategy to induce substantial specific immune responses against multiple epitopes of E6 and E7 proteins based on an attenuated transgene from HPV serotypes 16 and 18 that is incorporated into MG1-Maraba virotherapy (MG1-E6E7). Mutations introduced to the transgene abrogate the ability of E6 and E7 to perturb p53 and retinoblastoma, respectively, while maintaining the ability to invoke tumor-specific, multi-functional CD8+ T-cell responses...
September 14, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28912271/the-complex-structure-and-function-of-mediator
#4
Thomas M Harper, Dylan J Taatjes
In eukaryotes, RNA polymerase II (pol II) transcribes all protein-coding genes and many non-coding RNAs. Whereas numerous factors contribute to the regulation of pol II activity, the Mediator complex is required for expression of most, if not all, pol II transcripts. Structural characterization of Mediator is challenging due to its large size (~20 subunits in yeast, 26 subunits in humans) and conformational flexibility. However, recent studies have revealed structural details at higher resolution. Here, we summarize recent findings and place in context with previous results, highlighting regions within Mediator that are important for regulating its structure and function...
September 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28911106/unencumbered-pol-%C3%AE-lyase-activity-in-nucleosome-core-particles
#5
Yesenia Rodriguez, Michael J Howard, Matthew J Cuneo, Rajendra Prasad, Samuel H Wilson
Packaging of DNA into the nucleosome core particle (NCP) is considered to exert constraints to all DNA-templated processes, including base excision repair where Pol β catalyzes two key enzymatic steps: 5'-dRP lyase gap trimming and template-directed DNA synthesis. Despite its biological significance, knowledge of Pol β activities on NCPs is still limited. Here, we show that removal of the 5'-dRP block by Pol β is unaffected by NCP constraints at all sites tested and is even enhanced near the DNA ends. In contrast, strong inhibition of DNA synthesis is observed...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28911097/structural-accommodation-of-ribonucleotide-incorporation-by-the-dna-repair-enzyme-polymerase-mu
#6
Andrea F Moon, John M Pryor, Dale A Ramsden, Thomas A Kunkel, Katarzyna Bebenek, Lars C Pedersen
While most DNA polymerases discriminate against ribonucleotide triphosphate (rNTP) incorporation very effectively, the Family X member DNA polymerase μ (Pol μ) incorporates rNTPs almost as efficiently as deoxyribonucleotides. To gain insight into how this occurs, here we have used X-ray crystallography to describe the structures of pre- and post-catalytic complexes of Pol μ with a ribonucleotide bound at the active site. These structures reveal that Pol μ binds and incorporates a rNTP with normal active site geometry and no distortion of the DNA substrate or nucleotide...
September 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28911033/formulation-of-chitosan-with-the-polyepitope-hiv-1-protein-candidate-vaccine-efficiently-boosts-cellular-immune-responses-in-mice
#7
Ehsan Ollah Jazaeri, Atiyeh Mahdavi, Asghar Abdoli
Human immunodeficiency virus-1 (HIV-1) continues to be a major global public health issue and priority. Despite the variety of antiretroviral therapies, it seems that an effective vaccine against HIV-1 is still very necessary. An ideal HIV-1 vaccine should be able to elicit both humoral and cellular immunities. In this respect, polyepitope vaccines, incorporated from several conserved regions of HIV-1 proteins, have received much attention recently. Herein, the immunogenicity of the HIV-1 polyepitope protein-based candidate vaccines was evaluated in BALB/c mice...
November 30, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28906055/the-role-of-genomic-location-and-flanking-3-utr-in-the-generation-of-functional-levels-of-variant-surface-glycoprotein-in-trypanosoma-brucei
#8
Sophie Ridewood, Cher-Pheng Ooi, Belinda Hall, Anna Trenaman, Nadina Vasileva Wand, Georgios Sioutas, Iris Scherwitzl, Gloria Rudenko
Trypanosoma brucei faces relentless immune attack in the mammalian bloodstream, where it is protected by an essential coat of Variant Surface Glycoprotein (VSG) comprising ∼10% total protein. The active VSG gene is in a Pol I-transcribed telomeric expression site (ES). We investigated factors mediating these extremely high levels of VSG expression by inserting ectopic VSG117 into VSG221 expressing T. brucei. Mutational analysis of the ectopic VSG 3'UTR demonstrated the essentiality of a conserved 16-mer for mRNA stability...
September 14, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28905458/phosphorylation-of-ets-1-is-a-critical-event-in-dna-polymerase-iota-induced-invasion-and-metastasis-of-escc
#9
Chao He, Shuhua Wu, Aidi Gao, Ye Su, Han Min, Zeng-Fu Shang, Jinchang Wu, Li Yang, Wei-Qun Ding, Jundong Zhou
An aberrantly elevated expression of DNA polymerase ι (Pol ι) is significantly associated with poor prognosis of patients with esophageal squamous cell carcinoma (ESCC), yet the mechanisms behind remain obscure. Based on the RNA-Seq transcriptome and real-time PCR analysis, we identified ETS-1 as a candidate gene involved in Pol ι-mediated progression of ESCC. Wound-healing and transwell assay indicated that down-regulation of ETS-1 attenuates Pol ι-mediated invasiveness of ESCC. Signaling pathway analysis showed that Pol ι enhances ETS-1 phosphorylation at threonine-38 through the Erk signaling pathway in ESCC cells...
September 14, 2017: Cancer Science
https://www.readbyqxmd.com/read/28904195/vector-order-determines-protection-against-pathogenic-simian-immunodeficiency-virus-infection-in-a-triple-component-vaccine-by-balancing-cd4-and-cd8-t-cell-responses
#10
Ulrike Sauermann, Antonia Radaelli, Nicole Stolte-Leeb, Katharina Raue, Massimiliano Bissa, Carlo Zanotto, Michael Krawczak, Matthias Tenbusch, Klaus Überla, Brandon F Keele, Carlo De Giuli Morghen, Sieghart Sopper, Christiane Stahl-Hennig
An effective AIDS vaccine should elicit strong humoral and cellular immune responses while maintaining low levels of CD4(+) T cell activation to avoid the generation of target cells for viral infection. The present study investigated two prime-boost regimens, both starting vaccination with single cycle immunodeficiency virus, followed by two mucosal boosts either with recombinant adenovirus (rAd) or fowlpox virus (rFWPV) expressing SIVmac239 or SIVmac251 gag/pol and env genes, respectively. Finally, vectors were switched and systemically administered to the reciprocal group of animals...
September 13, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28902753/nonoperative-management-and-novel-imaging-for-posterior-circumflex-humeral-artery-injury-in-volleyball
#11
Daan van de Pol, R Nils Planken, Aart Terpstra, Marja Pannekoek-Hekman, P Paul F M Kuijer, Mario Maas
We report on a 34-yr-old male elite volleyball player with symptomatic emboli in the spiking hand from a partially thrombosed aneurysm of the posterior circumflex humeral artery (PCHA) in his dominant shoulder. At initial diagnosis and follow-up, a combination of time-resolved and high-resolution steady state contrast-enhanced magnetic resonance angiography (CE-MRA) enabled detailed visualization of: (1) emboli that were not detectable by vascular ultrasound; and (2) the PCHA aneurysm, including compression during abduction and external rotation (ABER provocation)...
September 2017: Current Sports Medicine Reports
https://www.readbyqxmd.com/read/28894972/gene-regulation-of-mammalian-long-non-coding-rna
#12
REVIEW
Heeyoun Bunch
RNA polymerase II (Pol II) transcribes two classes of RNAs, protein-coding and non-protein-coding (ncRNA) genes. ncRNAs are also synthesized by RNA polymerases I and III (Pol I and III). In humans, the number of ncRNA genes exceeds more than twice that of protein-coding genes. However, the history of studying Pol II-synthesized ncRNA is relatively short. Since early 2000s, important biological and pathological functions of these ncRNA genes have begun to be discovered and intensively studied. And transcription mechanisms of long non-coding RNA (lncRNA) have been recently reported...
September 11, 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28893909/processive-searching-ability-varies-among-members-of-the-gap-filling-dna-polymerase-x-family
#13
Michael J Howard, Samuel H Wilson
DNA repair proteins must locate rare damaged sites within the genome. DNA polymerase beta (Pol β), a member of the DNA polymerase X family that is involved in base excision repair, uses a processive hopping search mechanism to locate substrates. This effectively enhances its search footprint on DNA, increasing the probability of locating damaged sites. Processive searching has been reported or proposed for many DNA-binding proteins, raising the question of how widespread or specific to certain enzymes the ability to perform this function is...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28893905/lysine-acetylation-stoichiometry-and-proteomics-analyses-reveal-pathways-regulated-by-sirtuin-1-in-human-cells
#14
Jeovanis Gil, Alberto Ramírez-Torres, Diego Chiappe, Juan Luna-Peñaloza, Francis C Fernandez-Reyes, Bolivar Arcos-Encarnación, Sandra Contreras, Sergio Encarnación-Guevara
Lysine acetylation is a widespread posttranslational modification (PTM) affecting many biological pathways. Recent studies indicate that acetylated lysine residues mainly exhibit low acetylation occupancy, but challenges in sample preparation and analysis make it difficult to confidently assign these numbers, limiting understanding of their biological significance. Here, we tested three common sample preparation methods to determine their suitability for assessing acetylation stoichiometry in three human cell lines, identifying the acetylation occupancy in more than 1,300 proteins from each cell line...
September 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28893534/solution-structure-of-the-n-terminal-domain-of-mediator-subunit-med26-and-molecular-characterization-of-its-interaction-with-eaf1-and-taf7
#15
Zoé Lens, François-Xavier Cantrelle, Riccardo Peruzzini, Xavier Hanoulle, Frédérique Dewitte, Elisabeth Ferreira, Jean-Luc Baert, Didier Monté, Marc Aumercier, Vincent Villeret, Alexis Verger, Isabelle Landrieu
MED26 is a subunit of Mediator, a large complex central to the regulation of gene transcription by RNA Polymerase II (RNA Pol II). MED26 plays a role in the switch between the initiation and elongation phases of RNA Pol II-mediated transcription process. Regulation of these steps requires successive binding of MED26 N-Terminal domain (NTD) to TBP-associated factor 7 (TAF7) and EAF1 (Eleven-nineteen lysine-rich in leukemia-Associated Factor 1). In order to investigate the mechanism of regulation by MED26, MED26-NTD structure was solved by nuclear magnetic resonance spectroscopy (NMR), revealing a 4-helix bundle...
September 9, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28892040/structure-of-a-transcribing-rna-polymerase-ii-dsif-complex-reveals-a-multidentate-dna-rna-clamp
#16
Carrie Bernecky, Jürgen M Plitzko, Patrick Cramer
During transcription, RNA polymerase II (Pol II) associates with the conserved elongation factor DSIF. DSIF renders the elongation complex stable and functions during Pol II pausing and RNA processing. We combined cryo-EM and X-ray crystallography to determine the structure of the mammalian Pol II-DSIF elongation complex at a nominal resolution of 3.4 Å. Human DSIF has a modular structure with two domains forming a DNA clamp, two domains forming an RNA clamp, and one domain buttressing the RNA clamp. The clamps maintain the transcription bubble, position upstream DNA, and retain the RNA transcript in the exit tunnel...
September 11, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28891001/characterization-of-a-novel-botybirnavirus-isolated-from-a-phytopathogenic-alternaria-fungus
#17
Jun Xiang, Min Fu, Ni Hong, Lifeng Zhai, Feng Xiao, Guoping Wang
Alternaria fungi are important pathogens infecting a wide variety of organisms. Here, we report a novel double-stranded RNA (dsRNA) mycovirus named Alternaria botybirnavirus 1 (ABRV1) isolated from a phytopathogenic Alternaria sp. strain (SCFS-3) infecting a pear tree in China. ABRV1 has two dsRNA components (dsRNAs 1 and 2) with the sizes of 6,188 and 5,903 bp, containing two putative open reading frames encoding two polyproteins (202 and 192 kDa, respectively). The polyprotein encoded by ABRV1 dsRNA1 shares 41% amino acid (aa) sequence identity with the one encoded by dsRNA2 (instead of dsRNA1) of Sclerotinia sclerotiorum botybirnavirus 1 (SsBRV1)...
September 11, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28890398/functional-characterization-of-pol-iii-u6-promoters-for-gene-knockdown-and-knockout-in-plutella-xylostella
#18
Yuping Huang, Yajun Wang, Baosheng Zeng, Zhaoxia Liu, Xuejiao Xu, Qian Meng, Yongping Huang, Guang Yang, Liette Vasseur, Geoff M Gurr, Minsheng You
RNA polymerase type III (Pol-III) promoters such as U6 are commonly used to express small RNAs, including short hairpin RNAs (shRNAs) and single guide RNAs (sgRNAs). Functional U6 promoters are widely used in CRISPR systems, and their characterization can facilitate genome editing of non-model organisms. In the present study, six U6 small nuclear RNA (snRNA) promoters containing two conserved elements of a proximal sequence element (PSEA) and a TATA box, were identified and characterized in the diamondback moth (Plutella xylostella) genome...
September 7, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28888568/in%C3%A2-vivo-3-dimensional-kinematics-of-thumb-carpometacarpal-joint-during-thumb-opposition
#19
Yohei Kawanishi, Kunihiro Oka, Hiroyuki Tanaka, Kiyoshi Okada, Kazuomi Sugamoto, Tsuyoshi Murase
PURPOSE: This study primarily aimed to demonstrate the screw-home rotation of the thumb carpometacarpal (CMC) joint and the function of surrounding ligaments during thumb oppositional motion. METHODS: A 3-dimensional kinematic analysis of the thumb CMC joint was conducted using data derived from computed tomography of 9 healthy volunteers. Scans were obtained in the neutral forearm and wrist position and the thumb in maximum radial abduction, maximum palmar abduction, and maximum opposition...
September 7, 2017: Journal of Hand Surgery
https://www.readbyqxmd.com/read/28887667/ape1-modulates-cellular-responses-to-organophosphate-pesticide-induced-oxidative-damage-in-non-small-cell-lung-carcinoma-a549-cells
#20
Shweta Thakur, Monisha Dhiman, Anil K Mantha
Monocrotophos (MCP) and chlorpyrifos (CP) are widely used organophosphate pesticides (OPPs), speculated to be linked with human pathologies including cancer. Owing to the fact that lung cells are most vulnerable to the environmental toxins, the development and progression of lung cancer can be caused by the exposure of OPPs. The present study investigates the oxidative DNA damage response evoked by MCP and CP in human non-small cell lung carcinoma A549 cells. A549 cells were exposed to MCP and CP; cytotoxicity and reactive oxygen species (ROS) generation were measured to select the non-toxic dose...
September 8, 2017: Molecular and Cellular Biochemistry
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