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https://www.readbyqxmd.com/read/28437703/antiviral-treatment-strategies-based-on-gene-silencing-and-genome-editing
#1
REVIEW
Roger Badia, Ester Ballana, José A Esté, Eva Riveira-Muñoz
The ability of some viruses to establish latently infected chronic reservoirs that escape to immune control becomes a major roadblock that impedes the cure of these infections. Therefore, new alternatives are needed to pursuit the eradication of viral persistent infections. Gene silencing technologies are in constant evolution and provide an outstanding sequence specificity that allows targeting any coding sequence of interest. Here we provide an overview of the development of gene silencing technologies ranging from initially RNA interference to the recently developed CRISPR/Cas9 and their potential as new antiviral strategies focusing on the eradication of HIV...
April 21, 2017: Current Opinion in Virology
https://www.readbyqxmd.com/read/28437540/characterization-of-gene-expression-phenotype-in-amyotrophic-lateral-sclerosis-monocytes
#2
Weihua Zhao, David R Beers, Kristopher G Hooten, Douglas H Sieglaff, Aijun Zhang, Shanker Kalyana-Sundaram, Christopher M Traini, Wendy S Halsey, Ashley M Hughes, Ganesh M Sathe, George P Livi, Guo-Huang Fan, Stanley H Appel
Importance: Amyotrophic lateral sclerosis (ALS) is a common adult-onset neurodegenerative disease characterized by selective loss of upper and lower motor neurons. Patients with ALS have persistent peripheral and central inflammatory responses including abnormally functioning T cells and activated microglia. However, much less is known about the inflammatory gene profile of circulating innate immune monocytes in these patients. Objective: To characterize the transcriptomics of peripheral monocytes in patients with ALS...
April 24, 2017: JAMA Neurology
https://www.readbyqxmd.com/read/28437094/rational-design-of-an-ultrasensitive-quorum-sensing-switch
#3
Weiqian Zeng, Pei Du, Qiuli Lou, Lili Wu, Haoqian M Zhang, Chunbo Lou, Hongli Wang, Qi Ouyang
One of the purposes of synthetic biology is to develop rational methods that accelerate the design of genetic circuits, saving time and effort spent on experiments and providing reliably predictable circuit performance. We applied a reverse engineering approach to design an ultrasensitive transcriptional quorum-sensing switch. We want to explore how systems biology can guide synthetic biology in the choice of specific DNA sequences and their regulatory relations to achieve a targeted function. The workflow comprises network enumeration that achieves the target function robustly, experimental restriction of the obtained candidate networks, global parameter optimization via mathematical analysis, selection and engineering of parts based on these calculations, and finally, circuit construction based on the principles of standardization and modularization...
April 24, 2017: ACS Synthetic Biology
https://www.readbyqxmd.com/read/28436950/mre11-stability-is-regulated-by-ck2-dependent-interaction-with-r2tp-complex
#4
P von Morgen, K Burdova, T G Flower, N J O'Reilly, S J Boulton, S J Smerdon, L Macurek, Z Hořejší
The MRN (MRE11-RAD50-NBS1) complex is essential for repair of DNA double-strand breaks and stalled replication forks. Mutations of the MRN complex subunit MRE11 cause the hereditary cancer-susceptibility disease ataxia-telangiectasia-like disorder (ATLD). Here we show that MRE11 directly interacts with PIH1D1, a subunit of heat-shock protein 90 cochaperone R2TP complex, which is required for the assembly of large protein complexes, such as RNA polymerase II, small nucleolar ribonucleoproteins and mammalian target of rapamycin complex 1...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28436936/the-u2af1s34f-mutation-induces-lineage-specific-splicing-alterations-in-myelodysplastic-syndromes
#5
Bon Ham Yip, Violetta Steeples, Emmanouela Repapi, Richard N Armstrong, Miriam Llorian, Swagata Roy, Jacqueline Shaw, Hamid Dolatshad, Stephen Taylor, Amit Verma, Matthias Bartenstein, Paresh Vyas, Nicholas C P Cross, Luca Malcovati, Mario Cazzola, Eva Hellström-Lindberg, Seishi Ogawa, Christopher W J Smith, Andrea Pellagatti, Jacqueline Boultwood
Mutations of the splicing factor-encoding gene U2AF1 are frequent in the myelodysplastic syndromes (MDS), a myeloid malignancy, and other cancers. Patients with MDS suffer from peripheral blood cytopenias, including anemia, and an increasing percentage of bone marrow myeloblasts. We studied the impact of the common U2AF1S34F mutation on cellular function and mRNA splicing in the main cell lineages affected in MDS. We demonstrated that U2AF1S34F expression in human hematopoietic progenitors impairs erythroid differentiation and skews granulomonocytic differentiation toward granulocytes...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436605/digeorge-like-syndrome-in-a-child-with-a-3p12-3-deletion-involving-mir4273-gene-born-to-a-mother-with-gestational-diabetes-mellitus
#6
Emilia Cirillo, Giuliana Giardino, Vera Gallo, Giovanni Galasso, Roberta Romano, Roberta D'Assante, Giulia Scalia, Luigi Del Vecchio, Lucio Nitsch, Rita Genesio, Claudio Pignata
Chromosome 22q11.2 deletion is the most common chromosomal alteration associated with DiGeorge syndrome (DGS), even though this is not the only underlying cause of DGS. In rare patients, mutations in a single gene, TBX1, have been described resulting in a DGS phenotype. Recently, it has been reported that at least part of the TBX1 mutant phenotype is due to excessive bone morphogenetic proteins (BMP) signaling. Evidence suggests that miRNA may modulate the expression of critical T-box transcriptional regulators during midface development and Bmp-signaling...
April 24, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28436541/pdx1-mody-and-dorsal-pancreatic-agenesis-new-phenotype-of-a-rare-disease
#7
L A Caetano, L S Santana, A D Costa-Riquetto, A M Lerario, M Nery, G F Nogueira, C D Ortega, M S Rocha, Aal Jorge, M G Teles
Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1-MODY is a rare form of monogenic diabetes caused by heterozygous variants in PDX1. Pancreatic developmental anomalies related to PDX1 are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in two patients with PDX1-MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C-peptide levels after 30 years with diabetes. A diagnosis of MODY was suspected...
April 24, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28436534/a-novel-trpa1-variant-is-associated-with-carbamazepine-responsive-cramp-fasciculation-syndrome
#8
M J Nirenberg, R Chaouni, T M Biller, R M Gilbert, C Paisán-Ruiz
Cramp-fasciculation syndrome (CFS) is a rare muscle hyperexcitability syndrome that presents with muscle cramps, fasciculations, and stiffness, as well as pain, fatigue, anxiety, hyperreflexia, and paresthesias. Although familial cases have been reported, a genetic etiology has not yet been identified. We performed whole-exome sequencing followed by validation and cosegregation analyses on a father-son pair with CFS. Both subjects manifested other hypersensitivity-hyperexcitability symptoms, including asthma, gastroesophageal reflux, migraine, restless legs syndrome, tremor, cold hyperalgesia, and cardiac conduction defects...
April 24, 2017: Clinical Genetics
https://www.readbyqxmd.com/read/28436271/divided-attention-enhances-the-recognition-of-emotional-stimuli-evidence-from-the-attentional-boost-effect
#9
Clelia Rossi-Arnaud, Pietro Spataro, Marco Costanzi, Daniele Saraulli, Vincenzo Cestari
The present study examined predictions of the early-phase-elevated-attention hypothesis of the attentional boost effect (ABE), which suggests that transient increases in attention at encoding, as instantiated in the ABE paradigm, should enhance the recognition of neutral and positive items (whose encoding is mostly based on controlled processes), while having small or null effects on the recognition of negative items (whose encoding is primarily based on automatic processes). Participants were presented a sequence of negative, neutral and positive stimuli (pictures in Experiment 1, words in Experiment 2) associated to target (red) squares, distractor (green) squares or no squares (baseline condition)...
April 23, 2017: Memory
https://www.readbyqxmd.com/read/28435772/self-assembled-bifunctional-peptide-as-effective-drug-delivery-vector-with-powerful-antitumor-activity
#10
Rangrang Fan, Lan Mei, Xiang Gao, Yuelong Wang, Mingli Xiang, Yu Zheng, Aiping Tong, Xiaoning Zhang, Bo Han, Liangxue Zhou, Peng Mi, Chao You, Zhiyong Qian, Yuquan Wei, Gang Guo
E-cadherin/catenin complex is crucial for cancer cell migration and invasion. The histidine-alanine-valine (HAV) sequence has been shown to inhibit a variety of cadherin-based functions. In this study, by fusing HAV and the classical tumor-targeting Arg-Gly-Asp (RGD) motif and Asn-Gly-Arg (NGR) motif to the apoptosis-inducing peptide sequence-AVPIAQK, a bifunctional peptide has been constructed with enhanced tumor targeting and apoptosis effects. This peptide is further processed as a nanoscale vector to encapsulate the hydrophobic drug docetaxel (DOC)...
April 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://www.readbyqxmd.com/read/28435450/exome-sequencing-of-oral-squamous-cell-carcinoma-reveals-molecular-subgroups-and-novel-therapeutic-opportunities
#11
Shih-Chi Su, Chiao-Wen Lin, Yu-Fan Liu, Wen-Lang Fan, Mu-Kuan Chen, Chun-Ping Yu, Wei-En Yang, Chun-Wen Su, Chun-Yi Chuang, Wen-Hsiung Li, Wen-Hung Chung, Shun-Fa Yang
Oral squamous cell carcinoma (OSCC), an epithelial malignancy affecting a variety of subsites in the oral cavity, is prevalent in Asia. The survival rate of OSCC patients has not improved over the past decades due to its heterogeneous etiology, genetic aberrations, and treatment outcomes. Improvement in therapeutic strategies and tailored treatment options is an unmet need. To unveil the mutational spectrum, whole-exome sequencing of 120 OSCC from male individuals in Taiwan was conducted. Analyzing the contributions of the five mutational signatures extracted from the dataset of somatic variations identified four groups of tumors that were significantly associated with demographic and clinical features...
2017: Theranostics
https://www.readbyqxmd.com/read/28435243/peripheral-leukocyte-micrornas-as-novel-biomarkers-for-copd
#12
Ruiying Wang, Jianying Xu, Hu Liu, Zhiping Zhao
COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors. The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue. Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found. For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls...
2017: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/28434989/colorimetric-detection-of-microrna-based-hybridization-chain-reaction-for-signal-amplification-and-enzyme-for-visualization
#13
Na Ying, Taifan Sun, Zhibao Chen, Guangping Song, Bingyao Qi, Shengjun Bu, Xiuwei Sun, Jiayu Wan, Zehong Li
MicroRNAs (miRNAs) have key roles in gene expression and can be employed as biomarkers for early diagnosis of various diseases, especially cancers. Detection of miRNAs remains challenging and often requires detection platforms. Here, a horseradish peroxidase (HRP)-assisted hybridization chain reaction (HCR) for colorimetric detection of miR-155 was described. In the presence of target miRNA, the capture probe immobilized on the microplate sandwiched the target miR-155 with the 3' end of the reporter probe. Another exposed part of the RP at the 5'end triggered HCR producing double-stranded DNA polymers with multiple fluorescein isothiocyanates (FITC) for signal amplification...
April 20, 2017: Analytical Biochemistry
https://www.readbyqxmd.com/read/28434716/a-bioinformatics-analysis-of-3400-lytic-polysaccharide-oxidases-from-family-aa9
#14
Nicolas Lenfant, Matthieu Hainaut, Nicolas Terrapon, Elodie Drula, Vincent Lombard, Bernard Henrissat
Lytic polysaccharide monooxygenases of family AA9 catalyze the oxidative cleavage of glycosidic bonds in cellulose and related polysaccharides. The N-terminal half of AA9 LPMOs displays a huge sequence variability that is in contradiction with the substrate simplicity so far observed for these enzymes. To understand the cause of the high multigenicity that prevails in the family, we have performed a clustering analysis of the N-terminal region of 3400 sequences of family AA9 LPMOs, and have evaluated the coincidence of the clusters with distal visible features that may accompany functional differences...
April 13, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28434495/dysfunction-of-the-cerebral-glucose-transporter-slc45a1-in-individuals-with-intellectual-disability-and-epilepsy
#15
Myriam Srour, Noriaki Shimokawa, Fadi F Hamdan, Christina Nassif, Chantal Poulin, Lihadh Al Gazali, Jill A Rosenfeld, Noriyuki Koibuchi, Guy A Rouleau, Aisha Al Shamsi, Jacques L Michaud
Glucose transport across the blood brain barrier and into neural cells is critical for normal cerebral physiologic function. Dysfunction of the cerebral glucose transporter GLUT1 (encoded by SLC2A1) is known to result in epilepsy, intellectual disability (ID), and movement disorder. Using whole-exome sequencing, we identified rare homozygous missense variants (c.526C>T [p.Arg176Trp] and c.629C>T [p.Ala210Val]) in SLC45A1, encoding another cerebral glucose transporter, in two consanguineous multiplex families with moderate to severe ID, epilepsy, and variable neuropsychiatric features...
April 18, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28434073/direct-downregulation-of-b-cell-translocation-gene-3-by-microrna-93-is-required-for-desensitizing-esophageal-cancer-to-radiotherapy
#16
Hujun Cui, Shengqiang Zhang, Hongbo Zhou, Ling Guo
BACKGROUND: Esophageal squamous carcinoma (ESC) is one of the most fatal malignancies worldwide with increasing occurrences yet poor outcome. MicroRNAs were reported to play roles in ESC. AIMS: We aimed to understand how miRNAs affect the radiotherapy resistance of ESC. METHODS: MicroRNA assays, real-time PCR, and Western blot were performed for expression analysis of miR-93 and BTG3. Luciferase activity assay was conducted with mutated B-cell translocation gene 3 (BTG3) 3'-UTR sequence in the 3' end of luciferase sequence with miR-93 inhibitor...
April 22, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28433919/identification-of-differentially-expressed-mirnas-through-high-throughput-sequencing-in-the-chicken-lung-in-response-to-mycoplasma-gallisepticum-hs
#17
Yabo Zhao, Yue Hou, Kang Zhang, Bo Yuan, Xiuli Peng
Mycoplasma gallisepticum (MG) infects chickens, causes chronic respiratory diseases (CRD) and severely damages the poultry industry. It has been suggested that micro-ribonucleic acids (miRNAs) are involved in microbial pathogenesis. Here, we identified miRNAs that are associated with MG infection in chicken lungs at 3 and 10days post-infection by deep sequencing. Thirty-six down-regulated and 9 up-regulated miRNAs belonging to 31 miRNA families were detected at 3days post-infection, whereas 50 down-regulated and 18 up-regulated miRNAs belonging to 41 miRNA families were found at 10days post-infection...
April 12, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28433723/elimination-of-the-cryptic-plasmid-in-leuconostoc-citreum-by-crispr-cas9-system
#18
Ye-Ji Jang, Seung-Oh Seo, Seul-Ah Kim, Ling Li, Tae-Jip Kim, Sun Chang Kim, Yong-Su Jin, Nam Soo Han
Leuconostoc spp. are important lactic acid bacteria for the fermentation of foods. In particular, L. citreum strains isolated from various foods have been used as host strains for genetic and metabolic engineering studies. In order to develop a food-grade genetic engineering system, L. citreum CB2567 was isolated from Kimchi. However, the isolated bacterium contained a cryptic plasmid which was difficult to eliminate. As the existence of the plasmid might hinder strain engineering, we eliminated the plasmid using an RNA-guided DNA endonuclease CRISPR/Cas9 system...
April 19, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28433602/folfoxiri-regimen-for-metastatic-colorectal-cancer-a-systematic-review-and-meta-analysis
#19
Frederico Leal, Fernanda Proa Ferreira, Andre Deeke Sasse
INTRODUCTION: Cytotoxic chemotherapy is the mainstay treatment for metastatic colorectal cancer (mCRC). Fluoropyrimidines, oxaliplatin, and irinotecan are the most active drugs; however, their optimal sequencing has not yet been established. Some evidence has shown that upfront treatment with 5-fluorouracil, oxaliplatin, and irinotecan (FOLFOXIRI regimen) can improve outcomes for patients with mCRC. MATERIALS AND METHODS: We performed a systematic search in electronic databases...
March 24, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/28433076/identification-of-ntrk3-fusions-in-childhood-melanocytic-neoplasms
#20
Lu Wang, Klaus J Busam, Ryma Benayed, Robert Cimera, Jiajing Wang, Ryan Denley, Mamta Rao, Ruth Aryeequaye, Kerry Mullaney, Long Cao, Marc Ladanyi, Meera Hameed
Spitzoid neoplasms are a distinct group of melanocytic tumors. Genetically, they lack mutations in common melanoma-associated oncogenes. Recent studies have shown that spitzoid tumors may contain a variety of kinase fusions, including ROS1, NTRK1, ALK, BRAF, and RET fusions. We report herein the discovery of recurrent NTRK3 gene rearrangements in childhood melanocytic neoplasms with spitzoid and/or atypical features, based on genome-wide copy number analysis by single-nucleotide polymorphism array, which showed intragenic copy number changes in NTRK3...
May 2017: Journal of Molecular Diagnostics: JMD
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