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https://www.readbyqxmd.com/read/29475001/regulation-of-tak1-alternative-splicing-by-splice-switching-oligonucleotides
#1
Donghu Zhou, Qianqian Shao, Xu Fan, Peng Wu, Weiran Lin, Handong Wei, Fuchu He, Ying Jiang
Alternative splicing (AS) generates multiple isoforms from a single precursor mRNA, and these isoforms usually exhibit different tissue distributions and functions. Aberrant protein isoforms can lead to abnormalities in protein function and may even result in genetic disorders or cancer. In recent years, splice-switching oligonucleotides (SSOs) have emerged as a promising therapeutic strategy for several neurological diseases, but the efficacy of this strategy in other organs is less reported. In this study, we designed and synthesized SSOs targeting the splicing regulators of exon 12 of the Tak1 gene, inducing variant switching between Tak1-A and Tak1-B...
February 20, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29474909/mapping-the-mouse-cell-atlas-by-microwell-seq
#2
Xiaoping Han, Renying Wang, Yincong Zhou, Lijiang Fei, Huiyu Sun, Shujing Lai, Assieh Saadatpour, Zimin Zhou, Haide Chen, Fang Ye, Daosheng Huang, Yang Xu, Wentao Huang, Mengmeng Jiang, Xinyi Jiang, Jie Mao, Yao Chen, Chenyu Lu, Jin Xie, Qun Fang, Yibin Wang, Rui Yue, Tiefeng Li, He Huang, Stuart H Orkin, Guo-Cheng Yuan, Ming Chen, Guoji Guo
Single-cell RNA sequencing (scRNA-seq) technologies are poised to reshape the current cell-type classification system. However, a transcriptome-based single-cell atlas has not been achieved for complex mammalian systems. Here, we developed Microwell-seq, a high-throughput and low-cost scRNA-seq platform using simple, inexpensive devices. Using Microwell-seq, we analyzed more than 400,000 single cells covering all of the major mouse organs and constructed a basic scheme for a mouse cell atlas (MCA). We reveal a single-cell hierarchy for many tissues that have not been well characterized previously...
February 22, 2018: Cell
https://www.readbyqxmd.com/read/29474870/improving-revised-international-prognostic-scoring-system-ipss-r-pre-allogeneic-stem-cell-transplant-does-not-translate-into-better-post-transplant-outcomes-for-patients-with-myelodysplastic-syndromes-a-single-center-experience
#3
Musa Alzahrani, Maryse Power, Yasser Abou Mourad, Michael Barnett, Raewyn Broady, Donna Forrest, Alina Gerrie, Donna Hogge, Stephen Nantel, David Sanford, Kevin Song, Heather Sutherland, Cynthia Toze, Thomas Nevill, Sujaatha Narayanan
BACKGROUND: The natural history of patients with myelodysplastic syndromes (MDS) is variable. The revised international prognostic score (IPSS-R) is commonly used in practice to predict outcome in patients with MDS both at diagnosis and pre-transplant. However the effect of change in IPSS-R pre-allogeneic stem cell transplant with chemotherapy or hypomethylating agents on post-transplant outcomes is currently unknown. AIM: We assessed if improvement in IPSS-R prognostic score pre HSCT would result in improvement in clinical outcomes post-transplant...
February 20, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29474435/sumo-polymeric-chains-are-involved-in-nuclear-foci-formation-and-chromatin-organization-in-trypanosoma-brucei-procyclic-forms
#4
Paula Ana Iribarren, Lucía Ayelén Di Marzio, María Agustina Berazategui, Javier Gerardo De Gaudenzi, Vanina Eder Alvarez
SUMOylation is a post-translational modification conserved in eukaryotic organisms that involves the covalent attachment of the small ubiquitin-like protein SUMO to internal lysine residues in target proteins. This tag usually alters the interaction surface of the modified protein and can be translated into changes in its biological activity, stability or subcellular localization, among other possible outputs. SUMO can be attached as a single moiety or as SUMO polymers in case there are internal acceptor sites in SUMO itself...
2018: PloS One
https://www.readbyqxmd.com/read/29474376/using-single-index-odes-to-study-dynamic-gene-regulatory-network
#5
Qi Zhang, Yao Yu, Jun Zhang, Hua Liang
With the development of biotechnology, high-throughput studies on protein-protein, protein-gene, and gene-gene interactions become possible and attract remarkable attention. To explore the interactions in dynamic gene regulatory networks, we propose a single-index ordinary differential equation (ODE) model and develop a variable selection procedure. We employ the smoothly clipped absolute deviation penalty (SCAD) penalized function for variable selection. We analyze a yeast cell cycle gene expression data set to illustrate the usefulness of the single-index ODE model...
2018: PloS One
https://www.readbyqxmd.com/read/29474364/%C3%AE-glucuronidase-use-as-a-single-internal-control-gene-may-confound-analysis-in-fmr1-mrna-toxicity-studies
#6
Claudine M Kraan, Kim M Cornish, Quang M Bui, Xin Li, Howard R Slater, David E Godler
Relationships between Fragile X Mental Retardation 1 (FMR1) mRNA levels in blood and intragenic FMR1 CGG triplet expansions support the pathogenic role of RNA gain of function toxicity in premutation (PM: 55-199 CGGs) related disorders. Real-time PCR (RT-PCR) studies reporting these findings normalised FMR1 mRNA level to a single internal control gene called β-glucuronidase (GUS). This study evaluated FMR1 mRNA-CGG correlations in 33 PM and 33 age- and IQ-matched control females using three normalisation strategies in peripheral blood mononuclear cells (PBMCs): (i) GUS as a single internal control; (ii) the mean of GUS, Eukaryotic Translation Initiation Factor 4A2 (EIF4A2) and succinate dehydrogenase complex flavoprotein subunit A (SDHA); and (iii) the mean of EIF4A2 and SDHA (with no contribution from GUS)...
2018: PloS One
https://www.readbyqxmd.com/read/29474158/soluble-expression-in-escherichia-coli-of-a-single-domain-antibody-tumor-necrosis-factor-%C3%AE-fusion-protein-specific-for-epidermal-growth-factor-receptor
#7
Tomohiro Osaki, Takeshi Nakanishi, Motoshi Aoki, Takahiro Omizu, Daisuke Nishiura, Masaya Kitamura
Tumor-targeted antibody-cytokine fusion proteins, called immunocytokines, are expected to be a useful platform for the development of effective antitumor therapeutic agents; however, their design and cost-efficient production remain as challenges. In this study, we constructed an antibody-cytokine fusion protein (Ia1-TNFα) comprising the single-domain antibody Ia1, which targets epidermal growth factor receptor (EGFR) overexpressed in epithelial tumors and a tumor necrosis factor α (TNFα) domain, which has antitumor activity...
February 2018: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/29473994/rapid-analysis-of-cell-nanoparticle-interaction-using-single-cell-raman-trapping-microscopy
#8
Maria Steinke, Florian Zunhammer, Elisavet Chatzopoulou, Henrik Teller, Karin Schütze, Heike Walles, Joachim Rädler, Cordula Grüttner
Iron oxide nanoparticles have been used in preclinical studies to label stem cells for non-invasive tracking and homing. There is continuous search for novel particle candidates that are suitable for clinical applications. Since standard analyses to investigate cell-particle interaction and safety are labor-intensive, an efficient procedure is required to guide future particle development and to exclude adverse health effects. Here, we report the application of combined Raman trapping microscopy with fluidic chips to analyze single cells that were labeled with different aminated iron oxide particle types...
February 23, 2018: Angewandte Chemie
https://www.readbyqxmd.com/read/29473973/expression-quantitative-trait-locus-study-of-bone-mineral-density-gwas-variants-in-human-osteoclasts
#9
Benjamin H Mullin, Kun Zhu, Jiake Xu, Suzanne J Brown, Shelby Mullin, Jennifer Tickner, Nathan J Pavlos, Frank Dudbridge, John P Walsh, Scott G Wilson
Osteoporosis is a complex disease with a strong genetic component. Genome-wide association studies (GWAS) have been very successful at identifying common genetic variants associated with bone parameters. A recently published study documented the results of the largest GWAS for bone mineral density (BMD) performed to date (n = 142,487), identifying 307 conditionally independent single-nucleotide polymorphisms (SNPs) as associated with estimated BMD (eBMD) at the genome-wide significance level. The vast majority of these variants are non-coding SNPs...
February 23, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/29473376/can-re-cturbt-be-useful-in-pt1hg-disease-as-a-risk-indicator-of-recurrence-and-progression-a-single-centre-experience
#10
Roberto Giulianelli, Barbara Cristina Gentile, Gabriella Mirabile, Luca Albanesi, Paola Tariciotti, Giorgio Rizzo, Maurizio Buscarini, Mauro Vermiglio
INTRODUCTION: Understaging after initial transurethral resection is common in patients with high-risk non muscle infiltrating bladder cancer (NMIBC) and can delay accurate diagnosis and definitive treatment. The rate of upstaging from T1 to T2 disease after repeated transurethral resection ranges from 0 to 28%, although the rate of upstaging may be even higher up to 49% when muscularis propria is absent in the first specimen. A restaging classic transurethral resection of bladder tumour (re-cTURBT) is the better predictor of early stage progression...
December 31, 2017: Archivio Italiano di Urologia, Andrologia
https://www.readbyqxmd.com/read/29473141/the-trypanosoma-cruzi-rna-binding-protein-rbp42-is-expressed-in-the-cytoplasm-throughout-the-life-cycle-of-the-parasite
#11
R Tyler Weisbarth, Anish Das, Paul Castellano, Michael A Fisher, Han Wu, Vivian Bellofatto
Trypanosoma cruzi, the protozoan parasite that causes Chagas disease in humans, has a complex life cycle that promotes survival in disparate environments. In each environment, the parasite must fine-tune its metabolic pathways to divide and multiply. In the absence of recognizable transcriptional gene regulation, it is apparent that protein levels are determined by post-transcriptional mechanisms. Post-transcriptional gene control is influenced by RNA-binding proteins that target mRNAs in the cell's cytoplasm...
February 23, 2018: Parasitology Research
https://www.readbyqxmd.com/read/29473062/an-ultrasensitive-microchip-electrophoresis-assay-based-on-separation-assisted-double-cycling-signal-amplification-strategy-for-microrna-detection-in-cell-lysate
#12
Kaiji Wei, Jingjin Zhao, Xiaoshu Luo, Senghui Qiu, Fuyun He, Shuting Li, Shulin Zhao
Microchip electrophoresis (MCE) assay is an analysis technique with low consumption and high automation. It is a useful tool in biomedical research and clinical diagnosis. However, the low detection sensitivity limits its application in trace biomarker analysis because of its extremely small sample size. To address the need for high sensitivity in MCE, we have developed an ultrasensitive MCE method based on a separation-assisted double cycling signal amplification strategy for the detection of microRNA (miRNA) in cell lysate...
February 23, 2018: Analyst
https://www.readbyqxmd.com/read/29472906/the-dna-methylome-of-the-hyperthermoacidophilic-crenarchaeon-sulfolobus-acidocaldarius
#13
Mohea Couturier, Ann-Christin Lindås
DNA methylation is the most common epigenetic modification observed in the genomic DNA (gDNA) of prokaryotes and eukaryotes. Methylated nucleobases, N6 -methyl-adenine (m6A), N4 -methyl-cytosine (m4C), and 5-methyl-cytosine (m5C), detected on gDNA represent the discrimination mark between self and non-self DNA when they are part of restriction-modification systems in prokaryotes (Bacteria and Archaea). In addition, m5C in Eukaryotes and m6A in Bacteria play an important role in the regulation of key cellular processes...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29472563/non-invasive-radiofrequency-field-treatment-of-4t1-breast-tumors-induces-t-cell-dependent-inflammatory-response
#14
Jared M Newton, Jose H Flores-Arredondo, Sarah Suki, Matthew J Ware, Martyna Krzykawska-Serda, Mahdi Agha, Justin J Law, Andrew G Sikora, Steven A Curley, Stuart J Corr
Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response...
February 22, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29472308/systematic-complex-haploinsufficiency-based-genetic-analysis-of-candida-albicans-transcription-factors-tools-and-applications-to-virulence-associated-phenotypes
#15
Virginia E Glazier, Thomas Murante, Kristy Koselny, Daniel Murante, Marisol Esqueda, Gina A Wall, Melanie Wellington, Chiung-Yu Hung, Anuj Kumar, Damian J Krysan
Genetic interaction analysis is a powerful approach to the study of complex biological processes that are dependent on multiple genes. Because of the largely diploid nature of the human fungal pathogen Candida albicans , genetic interaction analysis has been limited to a small number of large-scale screens and a handful for gene-by-gene studies. Complex haploinsufficiency, which occurs when a strain containing two heterozygous mutations at distinct loci shows a phenotype that is distinct from either of the corresponding single heterozygous mutants, is an expedient approach to genetic interactions analysis in diploid organisms...
February 22, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29471865/a-multicentre-randomised-non-inferiority-clinical-trial-comparing-a-nifurtimox-eflornithine-combination-to-standard-eflornithine-monotherapy-for-late-stage-trypanosoma-brucei-gambiense-human-african-trypanosomiasis-in-uganda
#16
Freddie Kansiime, Seraphine Adibaku, Charles Wamboga, Franklin Idi, Charles Drago Kato, Lawrence Yamuah, Michel Vaillant, Deborah Kioy, Piero Olliaro, Enock Matovu
BACKGROUND: While the combination of nifurtimox and eflornithine (NECT) is currently recommended for the treatment of the late stage human African trypansomiasis (HAT), single-agent eflornithine was still the treatment of choice when this trial commenced. This study intended to provide supportive evidence to complement previous trials. METHODS: A multi-centre randomised, open-label, non-inferiority trial was carried out in the Trypanosoma brucei gambiense endemic districts of North-Western Uganda to compare the efficacy and safety of NECT (200 mg/kg eflornithine infusions every 12 h for 7 days and 8 hourly oral nifurtimox at 5 mg/kg for 10 days) to the standard eflornithine regimen (6 hourly at 100 mg/kg for 14 days)...
February 22, 2018: Parasites & Vectors
https://www.readbyqxmd.com/read/29471656/cumulant-expansions-for-measuring-water-exchange-using-diffusion-mri
#17
Lipeng Ning, Markus Nilsson, Samo Lasič, Carl-Fredrik Westin, Yogesh Rathi
The rate of water exchange across cell membranes is a parameter of biological interest and can be measured by diffusion magnetic resonance imaging (dMRI). In this work, we investigate a stochastic model for the diffusion-and-exchange of water molecules. This model provides a general solution for the temporal evolution of dMRI signal using any type of gradient waveform, thereby generalizing the signal expressions for the Kärger model. Moreover, we also derive a general nth order cumulant expansion of the dMRI signal accounting for water exchange, which has not been explored in earlier studies...
February 21, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29471497/increased-nk-cell-function-after-cessation-of-long-term-nucleos-t-ide-analogue-treatment-in-chronic-hepatitis-b-associates-with-liver-damage-and-hbsag-loss
#18
Christine L Zimmer, Franziska Rinker, Christoph Höner Zu Siederdissen, Michael P Manns, Heiner Wedemeyer, Markus Cornberg, Niklas K Björkström
Background: Treatment with nucleos(t)ide analogues (NA) efficiently suppress HBV DNA but rarely leads to functional cure of chronic hepatitis B (CHB). Following NA cessation, a fraction of HBeAg-negative CHB-patients experience HBsAg loss. Cellular immune responses, including those by natural killer cells, innate lymphocytes known to respond in CHB, explaining the virological events transpiring following NA treatment cessation remain elusive. Methods: In a single-center prospective trial, 15 HBeAg-negative CHB-patients on long-term NA treatment underwent structured NA cessation and were studied longitudinally...
February 17, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29471395/origin-and-composition-of-cell-free-dna-in-spent-medium-from-human-embryo-culture-during-preimplantation-development
#19
M Vera-Rodriguez, A Diez-Juan, J Jimenez-Almazan, S Martinez, R Navarro, V Peinado, A Mercader, M Meseguer, D Blesa, I Moreno, D Valbuena, C Rubio, C Simon
STUDY QUESTION: What is the origin and composition of cell-free DNA in human embryo spent culture media? SUMMARY ANSWER: Cell-free DNA from human embryo spent culture media represents a mix of maternal and embryonic DNA, and the mixture can be more complex for mosaic embryos. WHAT IS KNOWN ALREADY: In 2016, ~300 000 human embryos were chromosomally and/or genetically analyzed using preimplantation genetic testing for aneuploidies (PGT-A) or monogenic disorders (PGT-M) before transfer into the uterus...
February 20, 2018: Human Reproduction
https://www.readbyqxmd.com/read/29470969/neuromodulation-of-attention
#20
REVIEW
Alexander Thiele, Mark A Bellgrove
Attention is critical to high-level cognition and attention deficits are a hallmark of neurologic and neuropsychiatric disorders. Although years of research indicates that distinct neuromodulators influence attentional control, a mechanistic account that traverses levels of analysis (cells, circuits, behavior) is missing. However, such an account is critical to guide the development of next-generation pharmacotherapies aimed at forestalling or remediating the global burden associated with disorders of attention...
February 21, 2018: Neuron
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