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https://www.readbyqxmd.com/read/28823056/exploiting-non-canonical-translation-to-identify-new-targets-for-t-cell-based-cancer-immunotherapy
#1
REVIEW
Céline M Laumont, Claude Perreault
Cryptic MHC I-associated peptides (MAPs) are produced via two mechanisms: translation of protein-coding genes in non-canonical reading frames and translation of allegedly non-coding sequences. In general, cryptic MAPs are coded by relatively short open reading frames whose translation can be regulated at the level of initiation, elongation or termination. In contrast to conventional MAPs, the processing of cryptic MAPs is frequently proteasome independent. The existence of cryptic MAPs derived from allegedly non-coding regions enlarges the scope of CD8 T cell immunosurveillance from a mere ~2% to as much as ~75% of the human genome...
August 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28823025/nanomedicine-associated-with-photodynamic-therapy-for-glioblastoma-treatment
#2
REVIEW
Leonardo B de Paula, Fernando L Primo, Antonio C Tedesco
Glioblastoma, also known as glioblastoma multiforme (GBM), is the most recurrent and malignant astrocytic glioma found in adults. Biologically, GBMs are highly aggressive tumors that often show diffuse infiltration of the brain parenchyma, making complete surgical resection difficult. GBM is not curable with surgery alone because tumor cells typically invade the surrounding brain, rendering complete resection unsafe. Consequently, present-day therapy for malignant glioma remains a great challenge. The location of the invasive tumor cells presents several barriers to therapeutic delivery...
August 19, 2017: Biophysical Reviews
https://www.readbyqxmd.com/read/28822984/tbk1-mutations-in-italian-patients-with-amyotrophic-lateral-sclerosis-genetic-and-functional-characterisation
#3
Laura Pozzi, Fabiola Valenza, Lorena Mosca, Andrea Dal Mas, Teuta Domi, Alessandro Romano, Claudia Tarlarini, Yuri Matteo Falzone, Lucio Tremolizzo, Gianni Sorarù, Federica Cerri, Pilar M Ferraro, Silvia Basaia, Federica Agosta, Raffaella Fazio, Mauro Comola, Giancarlo Comi, Maurizio Ferrari, Angelo Quattrini, Christian Lunetta, Silvana Penco, Dario Bonanomi, Paola Carrera, Nilo Riva
BACKGROUND: TANK-binding kinase 1 (TBK1) gene has been recently identified as a causative gene of amyotrophic lateral sclerosis (ALS). METHODS: We sequenced the TBK1 gene in a cohort of 154 Italian patients with ALS with unclear genetic aetiology. We subsequently assessed the pathogenic potential of novel identified TBK1 variants using functional in vitro studies: expression, targeting and activity were evaluated in patient-derived fibroblasts and in cells transfected with mutated-TBK1 plasmids...
August 19, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/28822868/preliminary-profiling-of-microrna-in-the-normal-and-regenerating-liver-of-chiloscyllium-plagiosum
#4
Dandan Cheng, Yanna Chen, Conger Lu, Yuezhong Qian, Zhengbing Lv
Liver is a vital organ present in animals for detoxification, protein synthesis, digestion and other functions and its powerful regenerative capacity is well known. C. plagiosum is an abundant fish that is representative of the cartilaginous class in the southeast coastal region of China and its liver accounts for >70% of the fish's visceral weight and contains many bioactive substances. MicroRNAs (microRNAs) play important roles in a wide range of biological processes in eukaryotes, including cell proliferation, differentiation, apoptosis...
July 27, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/28822858/comparison-of-genome-engineering-using-the-crispr-cas9-system-in-c-glabrata-wild-type-and-lig4-strains
#5
Yuke Cen, Bea Timmermans, Ben Souffriau, Johan M Thevelein, Patrick Van Dijck
Candida glabrata is reported as the second most prevalent human opportunistic fungal pathogen in North America and is threatening patients all over the world. Its incidence is rising, while it has developed resistance to the most widely used antifungal drugs, necessitating new approaches based on better insight into the biology of the organism. Despite its close phylogenetic relationship with Saccharomyces cerevisiae, generating precise genomic alterations in this species is problematic. Previously we have shown that deletion of LIG4, which encodes an enzyme involved in Non-Homologous End Joining (NHEJ), strongly enhances the probability of obtaining correctly modified transformants...
August 16, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28822827/host-genes-regulate-transcription-of-sperm-introduced-hepatitis-b-virus-genes-in-embryo
#6
Ying Zhong, Dong-Ling Liu, Mohamed Morsi M Ahmed, Peng-Hao Li, Xiao-Ling Zhou, Qing-Dong Xie, Xiao-Qing Xu, Ting-Ting Han, Zhi-Wei Hou, Chen-Yao Zhong, Ji-Hua Huang, Fei Zeng, Tian-Hua Huang
Hepatitis B virus (HBV) can invade the male germline, and sperm-introduced HBV genes could be transcribed in embryo. This study was to explore whether viral gene transcription is regulated by host genes. Embryos were produced by in vitro fertilization of hamster oocytes with human sperm containing the HBV genome. Total RNA extracted from test and control embryos were subjected to SMART-PCR, SSH, microarray hybridization, sequencing and BLAST analysis. Twenty-nine sequences showing significant identity to five human gene families were identified, with CSH2, EIF4G2, PCBD2, PSG4 and TTN selected to represent target genes...
August 16, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28822783/the-expression-induction-and-pharmacological-activity-of-cyp1a2-are-post-transcriptionally-regulated-by-microrna-hsa-mir-132-5p
#7
Yinting Chen, Linjuan Zeng, Yong Wang, William H Tolleson, Bridgett Knox, Si Chen, Zhen Ren, Lei Guo, Nan Mei, Feng Qian, Kaihong Huang, David Liu, Weida Tong, Dianke Yu, Baitang Ning
Cytochrome P450 1A2 (CYP1A2) is one of the most abundant and important drug metabolizing enzymes in human liver. However, little is known about the post-transcriptional regulation of CYP1A2, especially the mechanisms involving microRNAs (miRNAs). This study applied a systematic approach to investigate the post-transcriptional regulation of CYP1A2 by miRNAs. Candidate miRNAs targeting the 3'-untranslated region (3'-UTR) of CYP1A2 were screened in silico, resulting in the selection of sixty-two potential miRNAs for further analysis...
August 16, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28822769/somatic-mutation-analysis-in-melanoma-using-targeted-next-generation-sequencing
#8
Allen P Miraflor, Francine B de Abreu, Jason D Peterson, Scott A Turner, Christopher I Amos, Gregory J Tsongalis, Shaofeng Yan
Advanced stage malignant melanoma often responds poorly to therapy with low survival rates. New therapeutic approaches are based upon a growing understanding of the underlying molecular abnormalities. We demonstrate the feasibility of a next generation sequencing (NGS) assay, which targets hotspots in 50 cancer genes, to assess genotypes that may influence therapeutic selection and response. DNA was extracted from formalin fixed paraffin embedded (FFPE) melanoma specimens to create multiplexed libraries which were sequenced...
August 16, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28822440/-analysis-of-variants-in-complement-genes-in-han-chinese-children-with-atypical-hemolytic-uremic-syndrome
#9
C L Yi, F Zhao, H Z Qiu, L M Wang, J Huang, X J Nie, Z H Yu
Objective: To investigate the prevalence and characteristics of pathogenic variants in complement genes in Han Chinese children with atypical hemolytic uremic syndrome (aHUS). Method: Eleven Han Chinese children with aHUS, including 9 boys and 2 girls aged between 1 year and 4 months and 13 years, were investigated in Department of Pediatrics, Fuzhou General Hospital, from November 1998 to February 2014. Analysis of variants of all the exons of 10 complement genes (CFH, MCP, CFI, C3, CFB, CFHR1, CFHR2, CFHR3, CFHR4 and CFHR5), including 25 bases from 3' end and 25 bases from 5' end, was performed in the 11 cases by targeted sequence capture and next generation sequencing...
August 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/28822273/ligand-binding-characterization-of-simulated-%C3%AE-adrenergic-like-octopamine-receptor-in-schistocerca-gregaria-via-progressive-structure-simulation
#10
Hui-Meng Lu, Xiao-Li Lu, Jia-Hui Zhai, Ren-Bin Zhou, Yan-Li Qin, Jing-Di Li, Chen-Yan Zhang, Jian-Yu Shi
It is important to design insecticides having both low drug resistance and less undesirable toxicity for desert locust control. Specific GPCRs of Schistocerca gregaria, especially β-adrenergic-like octopamine receptor (SgOctβR), can be considered as its potential effective insecticide targets. However, either the unavailability of SgOctβR's structure or the inadequate capability of its sequence lead the development of insecticide for Schistocerca gregaria meets its plateau. To relax this difficulty, this paper develops a promising progressive structure simulation from SgOctβR's sequence, to its predicted structure of SgOctβR in vacuum, to its conformation as well as its complex with endogenous ligand octopamine in a solvent-membrane system...
July 27, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28822012/mtor-co-targeting-strategies-for-head-and-neck-cancer-therapy
#11
Zhiyong Wang, Juan Callejas Valera, Xuefeng Zhao, Qianming Chen, J Silvio Gutkind
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignancy worldwide. There is an urgent need to develop effective therapeutic approaches to prevent and treat HNSCC. Recent deep sequencing of the HNSCC genomic landscape revealed a multiplicity and diversity of genetic alterations in this malignancy. Although a large variety of specific molecules were found altered in each individual tumor, they all participate in only a handful of driver signaling pathways. Among them, the PI3K/mTOR pathway is the most frequently activated, which plays a central role in cancer initiation and progression...
August 18, 2017: Cancer Metastasis Reviews
https://www.readbyqxmd.com/read/28821955/targeted-next-generation-sequencing-for-analyzing-the-genetic-alterations-in-atypical-adenomatous-hyperplasia-and-adenocarcinoma-in-situ
#12
Xuan Xu, Na Li, Ruiying Zhao, Lei Zhu, Jinchen Shao, Jie Zhang
PURPOSE: Atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) have been defined as preinvasive pulmonary adenocarcinoma lesions according to the 2015 World Health Organization lung adenocarcinoma classification. We aimed to search for the most common gene mutations in patients with AAH and AIS and investigate the distinctions between the two groups at the molecular level. METHODS: We performed targeted next-generation sequencing on 18 cases with AAH and 28 cases with AIS to screen for mutations with the Ion Torrent Oncomine Solid Tumor DNA panel...
August 18, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28821942/rapid-detection-of-serratia-fonticola-by-taqman-quantitative-real-time-pcr-using-primers-targeting-the-gyrb-gene
#13
Jing Hua Ruan, Wu Jun Wang, Ti Yin Zhang, Quan Yang Bai, Teng Zheng, Zhi Deng Zhang, Li Yun Wu, Yi Fan Huang, Dao Jin Yu
A gyrB gene is present in the majority of bacterial species, and encodes the ATPase domain of DNA gyraseB-subunit protein, which is essential for transcription and replication of bacteria. The gyrB gene exhibits higher nucleotide sequence variability than the 16S rDNA gene and thus could be more reliable in differentiating Serratia fonticola. A species-specific primer pair and probe were designed for quantitative real-time PCR detection of S. fonticola using gyrB as the target gene. Nine members of the Serratia family (representing nine Serratia species) were chosen to verify the specificity of the primers...
August 18, 2017: Current Microbiology
https://www.readbyqxmd.com/read/28821927/control-of-wrist-movement-in-deafferented-man-evidence-for-a-mixed-strategy-of-position-and-amplitude-control
#14
R Chris Miall, P Haggard, J D Cole
There is a continuing debate about control of voluntary movement, with conflicted evidence about the balance between control of movement vectors (amplitude control) that implies knowledge of the starting position for accuracy, and equilibrium point or final position control, that is independent of the starting conditions. We tested wrist flexion and extension movements in a man with a chronic peripheral neuronopathy that deprived him of proprioceptive knowledge of his wrist angles. In a series of experiments, we demonstrate that he could scale the amplitude of his wrist movements in flexion/extension, even without visual feedback, and appeared to adopt a strategy of moving via a central wrist position when asked to reach target angles from unknown start locations...
August 18, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28821885/the-expression-profiles-of-mirna-mrna-of-early-response-in-genetically-improved-farmed-tilapia-oreochromis-niloticus-liver-by-acute-heat-stress
#15
Jun Qiang, Wen J Bao, Fan Y Tao, Jie He, Xia H Li, Pao Xu, Lan Y Sun
Genetically improved farmed tilapia (GIFT, Oreochromis niloticus) are commercially important fish that are cultured in China. GIFT are highly susceptible to diseases when exposed to high temperatures in summer. Better understanding the GIFT regulatory response to heat stress will not only help in determining the relationship between heat stress signalling pathways and adaption mechanisms, but will also contribute to breeding new high-temperature tolerant strains of GIFT. In this study, we built control (28 °C) and heat-treated (37...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821882/identification-of-a-short-sequence-in-the-hcmv-terminase-pul56-essential-for-interaction-with-pul89-subunit
#16
G Ligat, C Jacquet, S Chou, A Couvreux, S Alain, S Hantz
The human cytomegalovirus (HCMV) terminase complex consists of several components acting together to cleave viral DNA into unit length genomes and translocate them into capsids, a critical process in the production of infectious virions subsequent to DNA replication. Previous studies suggest that the carboxyl-terminal portion of the pUL56 subunit interacts with the pUL89 subunit. However, the specific interacting residues of pUL56 remain unknown. We identified a conserved sequence in the C-terminal moiety of pUL56 (671WMVVKYMGFF680)...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821867/identification-of-the-n-terminal-transmembrane-domain-of-stard7-and-its-importance-for-mitochondrial-outer-membrane-localization-and-phosphatidylcholine-transfer
#17
Yasuhiro Horibata, Hiromi Ando, Motoyasu Satou, Hiroaki Shimizu, Satomi Mitsuhashi, Yasuo Shimizu, Masahiko Itoh, Hiroyuki Sugimoto
StarD7 facilitates phosphatidylcholine (PC) transfer to mitochondria, and is essential for mitochondrial homeostasis. However, the molecular mechanism for PC transfer by protein remains poorly understood. Herein, we describe a putative novel transmembrane (TM) domain C-terminal to the mitochondria-targeting signal (MTS) sequence at the N-terminus of StarD7. The mature form of StarD7 is integrated and/or associated onto the outer leaflet of the outer mitochondrial membrane (OMM) in HEPA-1 and HepG2 cells. A truncated form of StarD7 lacking the TM domain is distributed in the inner space of the mitochondria, and cannot reverse mitochondrial abnormalities, such as complex formation and PC content, when re-expressed in StarD7-KO HEPA-1 cells...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821760/a-database-of-breast-oncogenic-specific-sirnas
#18
Atul Tyagi, Manoj Semwal, Ashok Sharma
Breast cancer is a serious problem causing the death of women across the world. At present, one of the major challenges is to design drugs to target breast cancer specific gene(s). RNA interference (RNAi) is an important technique for targeted gene silencing that may lead to promising novel therapeutic strategies for breast cancer. Therefore, identification of such molecules having high oncogene specificity is the need of the hour. Here, we have developed a database named as Breast Oncogenic Specific siRNAs (BOSS, http://bioinformatics...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821645/mutant-huntingtin-is-secreted-via-a-late-endosomal-lysosomal-unconventional-secretory-pathway
#19
Katarina Trajkovic, Hyunkyong Jeong, Dimitri Krainc
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the expansion of a CAG triplet in the gene encoding for huntingtin. The resulting mutant protein huntingtin (mHtt) with extended polyglutamine (polyQ) sequence at the N-terminus leads to neuronal degeneration both in cell-autonomous and non-cell-autonomous manners. Recent studies identified mHtt in the extracellular environment and suggested that its spreading contributes to toxicity, but the mechanism of mHtt release from the cell of origin remains unknown...
August 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28821548/the-transcriptional-regulator-phlh-modulates-2-4-diacetylphloroglucinol-biosynthesis-in-response-to-the-biosynthetic-intermediate-and-end-product
#20
Xu Yan, Rui Yang, Rui-Xue Zhao, Jian-Ting Han, Wen-Juan Jia, Di-Yin Li, Yong Wang, Nannan Zhang, Yi Wu, Li-Qun Zhang, Yong-Xing He
Certain strains of biocontrol Pseudomonas fluorescens produce the secondary metabolite 2,4-diacetylphloroglucinol (2,4-DAPG) to antagonize the soil-borne phytopathogens in the rhizosphere. The gene cluster responsible for the biosynthesis of 2,4-DAPG is named phlACBDEFGH and it is still unclear how the pathway-specific regulator phlH within this gene cluster regulates the metabolism of 2,4-DAPG. Here, we found that PhlH in Pseudomonas fluorescens strain 2P24 represses the expression of the phlG gene encoding the 2,4-DAPG hydrolase by binding to a sequence motif overlapping with the -35 site recognized by σ(70) factors...
August 18, 2017: Applied and Environmental Microbiology
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