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https://www.readbyqxmd.com/read/29791318/the-inhibitors-a-challenge-for-the-management-of-patients-with-hereditary-haemophilia-a
#1
Romeo-Gabriel Mihăilă
INTRODUCTION: Our research strategy was aimed at evaluating the possible implication of the type of factor VIII product administered as substitution treatment to haemophilia A patients in the occurrence of inhibitors and their consequences on the management. METHODS: Scientific articles from July 2015 to July 2017 were searched using the PubMed and PubMed Central databases. The used search terms included "haemophilia A", "inhibitors", "plasma-derived factor VIII" and "recombinant factor VIII"...
May 1, 2018: Romanian Journal of Internal Medicine, Revue Roumaine de Médecine Interne
https://www.readbyqxmd.com/read/29790084/cloning-and-expression-of-nlpa-gene-as-dna-vaccine-candidate-against-acinetobacter-baumannii
#2
Rassoul Hashemzehi, Abbas Doosti, Mohammad Kargar, Mojtaba Jaafarinia
Acinetobacter baumannii is one of the highly antibiotic-resistant bacteria that cause infections with high rate of death. This bacterium is one the common causes of infection worldwide leading to endemic and epidemic nosocomial infections. Despite many efforts, there is no effective vaccine against A. baumannii. As NlpA is one of the important antigenic factors in biogenesis of outer membrane vesicles, and OMV-based reported vaccines in A. baumannii stimulated the immune responses, this study was aimed to clone and express nlpA gene in eukaryotic HDF cells and evaluate the induced immunization following the administration of resulting construct as DNA vaccine in BALB/c mice...
May 22, 2018: Molecular Biology Reports
https://www.readbyqxmd.com/read/29789437/dynamics-of-reca-mediated-repair-of-replication-dependent-dna-breaks
#3
Vincent Amarh, Martin A White, David R F Leach
Chromosomal replication is the major source of spontaneous DNA double-strand breaks (DSBs) in living cells. Repair of these DSBs is essential for cell viability, and accuracy of repair is critical to avoid chromosomal rearrangements. Repair of replication-dependent DSBs occurs primarily by homologous recombination with a sister chromosome. However, this reaction has never been visualized at a defined chromosomal locus, so little is known about its spatial or temporal dynamics. Repair of a replication-independent DSB generated in Escherichia coli by a rare-cutting endonuclease leads to the formation of a bundle of RecA filaments...
May 22, 2018: Journal of Cell Biology
https://www.readbyqxmd.com/read/29789392/fam35a-associates-with-rev7-and-modulates-dna-damage-responses-of-normal-and-brca1-defective-cells
#4
Junya Tomida, Kei-Ichi Takata, Sarita Bhetawal, Maria D Person, Hsueh-Ping Chao, Dean G Tang, Richard D Wood
To exploit vulnerabilities of tumors, it is urgent to identify associated defects in genome maintenance. One unsolved problem is the mechanism of regulation of DNA double-strand break repair by REV7 in complex with 53BP1 and RIF1, and its influence on repair pathway choice between homologous recombination and non-homologous end-joining. We searched for REV7-associated factors in human cells and found FAM35A, a previously unstudied protein with an unstructured N-terminal region and a C-terminal region harboring three OB-fold domains similar to single-stranded DNA-binding protein RPA, as novel interactor of REV7/RIF1/53BP1...
May 22, 2018: EMBO Journal
https://www.readbyqxmd.com/read/29788454/variation-in-human-chromosome-21-ribosomal-rna-genes-characterized-by-tar-cloning-and-long-read-sequencing
#5
Jung-Hyun Kim, Alexander T Dilthey, Ramaiah Nagaraja, Hee-Sheung Lee, Sergey Koren, Dawood Dudekula, William H Wood Iii, Yulan Piao, Aleksey Y Ogurtsov, Koichi Utani, Vladimir N Noskov, Svetlana A Shabalina, David Schlessinger, Adam M Phillippy, Vladimir Larionov
Despite the key role of the human ribosome in protein biosynthesis, little is known about the extent of sequence variation in ribosomal DNA (rDNA) or its pre-rRNA and rRNA products. We recovered ribosomal DNA segments from a single human chromosome 21 using transformation-associated recombination (TAR) cloning in yeast. Accurate long-read sequencing of 13 isolates covering ∼0.82 Mb of the chromosome 21 rDNA complement revealed substantial variation among tandem repeat rDNA copies, several palindromic structures and potential errors in the previous reference sequence...
May 21, 2018: Nucleic Acids Research
https://www.readbyqxmd.com/read/29788099/biomarkers-for-homologous-recombination-deficiency-in-cancer
#6
Michal M Hoppe, Raghav Sundar, David S P Tan, Anand D Jeyasekharan
Defective DNA repair is a common hallmark of cancer. Homologous recombination is a DNA repair pathway of clinical interest due to the sensitivity of homologous recombination-deficient cells to poly-ADP ribose polymerase (PARP) inhibitors. The measurement of homologous recombination deficiency (HRD) in cancer is therefore vital to the appropriate design of clinical trials incorporating PARP inhibitors. However, methods to identify HRD in tumors are varied and controversial. Understanding existing and new methods to measure HRD is important to their appropriate use in clinical trials and practice...
May 18, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29787435/nhej-contributes-to-the-fast-repair-of-radiation-induced-dna-double-strand-breaks-at-late-prophase-i-telomeres
#7
Emad A Ahmed, Michael Rosemann, Harry Scherthan
Exposure of cells to ionizing radiation induces DNA double-strand breaks. To repair double-strand breaks correctly, cells must distinguish between the ends of chromosomes (telomeres) and DNA double-strand breaks within chromosomes. Double-strand breaks in telomeric DNA may lead to telomere shortening and mutagenesis. Eukaryotic cells repair double-strand breaks primarily by two mechanisms: error-free homologous recombination and error-prone nonhomologous end joining, of which homologous recombination is used in early meiotic prophase I to create recombined haploid gametes by two meiotic cell divisions lacking an intervening S-phase...
July 2018: Health Physics
https://www.readbyqxmd.com/read/29786518/evaluation-of-serum-ige-in-peach-allergic-patients-with-systemic-reaction-by-using-recombinant-pru-p-7-gibberellin-regulated-protein
#8
Y Mori, F Okazaki, C Inuo, Y Yamaguchi, S Masuda, S Sugiura, T Fukuie, M Nagao, I Tsuge, T Yosikawa, A Yagami, K Matsunaga, T Fujisawa, K Ito, H Narita, Y Kondo
BACKGROUND: Lipid transfer protein (LTP) is a major fruit allergen. It has, however, recently been revealed that the systemic reaction in peach-allergic patients is related not only to LTP (Pru p 3) but also to gibberellin-regulated protein (Pru p 7). We investigated recombinant Pru p 7 (rPru p 7) for its potential use in worldwide standardization for the diagnosis of peach allergy. METHODS: Natural Pru p 7 (nPru p 7) was purified from peach crude extract using a monoclonal antibody affinity column...
May 18, 2018: Allergologia et Immunopathologia
https://www.readbyqxmd.com/read/29786106/efficient-delivery-of-hbv-nls-sirnas-into-hepg2-2-15-cells-for-hbv-inhibition-through-novel-recombinant-pres1%C3%A2-tp-proteins
#9
Yanli Zeng, Zixi Li, Jia Shang, Yi Kang
Hepatitis B virus (HBV) infection and related liver complications remain severe public health problems worldwide. Previous investigations have shown that small interfering (si)RNAs can offer an effective strategy for the treatment of chronic hepatitis B. The present study aimed to develop a novel siRNA‑delivering system of therapeutic HBV nuclear localization sequence (NLS) siRNAs using the recombinant preS1‑truncated protamine (tP) proteins. The preS1 region of the LHB was used in place of scFv to construct the recombinant preS1‑tP proteins, which were applied to deliver siRNAs targeting the HBV NLS to inhibit HBV replication and infection in HepG2...
May 16, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29785042/inducible-high-efficiency-crispr-cas9-targeted-gene-editing-and-precision-base-editing-in-african-trypanosomes
#10
Eva Rico, Laura Jeacock, Julie Kovářová, David Horn
The Cas9 endonuclease can be programmed by guide RNA to introduce sequence-specific breaks in genomic DNA. Thus, Cas9-based approaches present a range of novel options for genome manipulation and precision editing. African trypanosomes are parasites that cause lethal human and animal diseases. They also serve as models for studies on eukaryotic biology, including 'divergent' biology. Genome modification, exploiting the native homologous recombination machinery, has been important for studies on trypanosomes but often requires multiple rounds of transfection using selectable markers that integrate at low efficiency...
May 21, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29785023/hiv-vaccine-candidate-activation-of-hypoxia-and-the-inflammasome-in-cd14-monocytes-is-associated-with-a-decreased-risk-of-siv-mac251-acquisition
#11
Monica Vaccari, Slim Fourati, Shari N Gordon, Dallas R Brown, Massimilano Bissa, Luca Schifanella, Isabela Silva de Castro, Melvin N Doster, Veronica Galli, Maria Omsland, Dai Fujikawa, Giacomo Gorini, Namal P M Liyanage, Hung V Trinh, Katherine M McKinnon, Kathryn E Foulds, Brandon F Keele, Mario Roederer, Richard A Koup, Xiaoying Shen, Georgia D Tomaras, Marcus P Wong, Karissa J Munoz, Johannes S Gach, Donald N Forthal, David C Montefiori, David J Venzon, Barbara K Felber, Margherita Rosati, George N Pavlakis, Mangala Rao, Rafick-Pierre Sekaly, Genoveffa Franchini
Qualitative differences in the innate and adaptive responses elicited by different HIV vaccine candidates have not been thoroughly investigated. We tested the ability of the Aventis Pasteur live recombinant canarypox vector (ALVAC)-SIV, DNA-SIV and Ad26-SIV vaccine prime modalities together with two ALVAC-SIV + gp120 protein boosts to reduce the risk of SIVmac251 acquisition in rhesus macaques. We found that the DNA and ALVAC prime regimens were effective, but the Ad26 prime was not. The activation of hypoxia and the inflammasome in CD14+ CD16- monocytes, gut-homing CCR5-negative CD4+ T helper 2 (TH 2) cells and antibodies to variable region 2 correlated with a decreased risk of SIVmac251 acquisition...
May 21, 2018: Nature Medicine
https://www.readbyqxmd.com/read/29784639/tyrosine-kinase-inhibitor-induced-defects-in-dna-repair-sensitize-flt3-itd-positive-leukemia-cells-to-parp1-inhibitors
#12
Silvia Maifrede, Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Bac Viet Le, Martyna Solecka, Zhaorui Lian, Elizaveta A Belyaeva, Alina Nersesyan, Marcin M Machnicki, Monika Toma, Nicolas Chatain, Malgorzata Rydzanicz, Huaqing Zhao, Jaroslav Jelinek, Katarzyna Piwocka, Tomasz Sliwinski, Tomasz Stoklosa, Rafal Ploski, Thomas Fischer, Stephen M Sykes, Steffen Koschmieder, Lars Bullinger, Peter Valent, Mariusz Wasik, Jian Huang, Tomasz Skorski
Mutations in the FMS-like tyrosine-kinase 3 (FLT3) such as internal tandem duplications (ITD) can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i), which are rarely curative. PARP1 inhibitors (PARP1i) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784364/protein-binding-protection-in-combination-with-dna-masking-for-sensitive-and-reliable-transcription-factor-detection
#13
Xiaowen Xu, Lei Wang, Desong Zhu, Yan Wang, Wei Jiang
Sensitive and reliable detection of transcription factors (TFs) is crucial for disease diagnosis and drug discovery. Herein, a protein binding protection in combination with DNA masking-based strategy is developed for sensitive and reliable detection of NF-κB p50. First, NF-κB p50 binds specifically to a hairpin probe to form a protein-DNA complex. Then, the formed complex protects the hairpin probe from hybridization with the masking strand and subsequently triggers the cascade signal amplification of strand displacement amplification (SDA) and exponential rolling circle amplification (ERCA)...
August 15, 2018: Talanta
https://www.readbyqxmd.com/read/29778533/casein-kinase-ii-phosphorylates-the-c-terminal-region-of-lif1-to-promote-the-lif1-xrs2-interaction-needed-for-non-homologous-end-joining
#14
Kenichiro Matsuzaki, Miki Shinohara
A DNA double strand break (DSB) is one of the most cytotoxic DNA lesions, but it can be repaired by non-homologous end joining (NHEJ) or by homologous recombination. The choice between these two repair pathways depends on the cell cycle stage. Although NHEJ constitutes a simple re-ligation reaction, the regulatory mechanism(s) controlling its activity has not been fully characterized. Lif1 is a regulatory subunit of the NHEJ-specific DNA ligase IV and interacts with Xrs2 of the MRX complex which is a key factor in DSB repair...
May 17, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29778513/the-immune-response-of-rhesus-macaques-to-novel-vaccines-comprising-hepatitis-b-virus-s-pres1-and-core-antigens
#15
Xia Chuai, Bangxiang Xie, Hong Chen, Xinyi Tan, Wen Wang, Baoying Huang, Yao Deng, Wenhui Li, Wenjie Tan
Therapeutic vaccines represent a unique approach to hepatitis B virus (HBV) treatment and have the potential to induce long-term control of infection. This study explored the immune responses of rhesus macaques to novel vaccines comprising the S, PreS1, and Core antigens of the HBV that showed promise as prophylactic and therapeutic approaches in a mouse model. The tested vaccines included two DNA vaccines (pVRC-SS1, pVRC-CS1), an HBV particle subunit (HBSS1) vaccine and the recombinant vaccinia virus- (RVJ-) based vaccines (RVJSS1 and RVJCS1) in which SS1 containing S (1-223 aa) and PreS1 (21-47 aa), CS1 containing Core (1-144 aa) and PreS1 (1-42 aa)...
May 16, 2018: Vaccine
https://www.readbyqxmd.com/read/29777592/early-identification-of-unusually-clustered-mutations-and-a-root-cause-in-therapeutic-antibody-development
#16
Yueming Qian, Zhiqiang Chen, Xin Huang, Xuning Wang, Xuankuo Xu, Stefan Kirov, Richard Ludwig, Nan-Xin Qian, Kandasamy Ravi, Li Tao, Michael C Borys, Zheng Jian Li
This study reports findings of an unusual cluster of mutations spanning 22 base pairs in a monoclonal antibody (mAb) expression vector. It was identified by two orthogonal methods: mass spectrometry on expressed protein and next-generation sequencing (NGS) on the plasmid DNA. While the initial NGS analysis confirmed the designed sequence modification, intact mass analysis detected an additional mass of the antibody molecule expressed in CHO cells. The extra mass was eventually found to be associated with unmatched nucleotides in a distal region by checking full-length sequence alignment plots...
May 19, 2018: Biotechnology and Bioengineering
https://www.readbyqxmd.com/read/29777512/discovery-of-an-acidic-thermostable-and-highly-nadp-dependent-formate-dehydrogenase-from-lactobacillus-buchneri-nrrl-b-30929
#17
Saadet Alpdağtaş, Sevil Yücel, Handan Açelya Kapkaç, Siqing Liu, Barış Binay
OBJECTIVES: To identify a robust NADP+ dependent formate dehydrogenase from Lactobacillus buchneri NRRL B-30929 (LbFDH) with unique biochemical properties. RESULTS: A new NADP+ dependent formate dehydrogenase gene (fdh) was cloned from genomic DNA of L. buchneri NRRL B-30929. The recombinant construct was expressed in Escherichia coli BL21(DE3) with 6 × histidine at the C-terminus and the purified protein obtained as a single band of approx. 44 kDa on SDS-PAGE and 90 kDa on native-PAGE...
May 18, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29776991/inversion-variants-in-human-and-primate-genomes
#18
Claudia Rita Catacchio, Flavia Angela Maria Maggiolini, Pietro D'Addabbo, Miriana Bitonto, Oronzo Capozzi, Martina Lepore Signorile, Mattia Miroballo, Nicoletta Archidiacono, Evan E Eichler, Mario Ventura, Francesca Antonacci
For many years, inversions have been proposed to be a direct driving force in speciation since they suppress recombination when heterozygous. Inversions are the most common large-scale differences among humans and great apes. Nevertheless, they represent large events easily distinguishable by classical cytogenetics, whose resolution, however, is limited. Here, we performed a genome-wide comparison between human, great ape, and macaque genomes using the net alignments for the most recent releases of genome assemblies...
May 18, 2018: Genome Research
https://www.readbyqxmd.com/read/29776931/shuffling-the-neutral-drift-of-unspecific-peroxygenase-in-saccharomyces-cerevisiae
#19
Javier Martin-Diaz, Carmen Paret, Eva García-Ruiz, Patricia Molina-Espeja, Miguel Alcalde
Unspecific peroxygenase (UPO) is a highly promiscuous biocatalyst and its selective mono(per)oxygenase activity makes it useful for many synthetic chemistry applications. Among the broad repertory of library creation methods for directed enzyme evolution, genetic drift allows neutral mutations to be accumulated gradually within a polymorphic network of variants. In this study, we conducted a campaign of genetic drift with UPO in Saccharomyces cerevisiae so that neutral mutations were simply added and recombined in vivo With low mutational loading and an activity threshold of 45% of the parent's native function, mutant libraries enriched in folded and active UPO variants were generated...
May 18, 2018: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29776075/encounter-times-of-chromatin-loci-influenced-by-polymer-decondensation
#20
A Amitai, D Holcman
The time for a DNA sequence to find its homologous counterpart depends on a long random search inside the cell nucleus. Using polymer models, we compute here the mean first encounter time (MFET) between two sites located on two different polymer chains and confined locally by potential wells. We find that reducing tethering forces acting on the polymers results in local decondensation, and numerical simulations of the polymer model show that these changes are associated with a reduction of the MFET by several orders of magnitude...
March 2018: Physical Review. E
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