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Genomics Pathologys

Jiangtao Lei, Ruxi Qi, Yegen Tang, Wenning Wang, Guanghong Wei, Ruth Nussinov, Buyong Ma
p53 is a tumor suppressor protein that maintains genome stability, but its Δ133p53β and Δ160p53β isoforms promote breast cancer cell invasion. The sequence truncations in the p53 core domain raise key questions related to their physicochemical properties, including structural stabilities, interaction mechanisms, and DNA-binding abilities. Herein, we investigated the conformational dynamics of Δ133p53β and Δ160p53β with and without binding to p53-specific DNA by using molecular dynamics simulations. We observed that the core domains of the 2 truncated isoforms are much less stable than wild-type (wt) p53β, and the increased solvent exposure of their aggregation-triggering segment indicates their higher aggregation propensities than wt p53...
December 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Guoying Zhang, Mingxing Bi, Shaolai Li, Qingchen Wang, Dong Teng
Objective: We expected to demonstrate a practical framework for oral squamous cell carcinoma (OSCC) candidate biomarker analysis at the pathway level based on the attract method, so as to give great insights to reveal the pathological mechanism underlying this disease at its early stage. Methods: First, gene expression profile of OSCC was recruited and preprocessed. Then, Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis was conducted. Next, attract method, an approach that begins its analysis from the "foundation knowledge sets" to discriminate the cell-phenotypes by those well-annotated gene-sets, then expands the syn-expression groups via decomposing each significant pathway into correlated subsets and extends the analysis to the entire expression was applied to identify core pathways...
December 2018: Journal of Cancer Research and Therapeutics
Shino Magaki, Seyed A Hojat, Bowen Wei, Alexandra So, William H Yong
Immunohistochemistry (IHC) is a powerful technique that exploits the specific binding between an antibody and antigen to detect and localize specific antigens in cells and tissue, most commonly detected and examined with the light microscope. A standard tool in many fields in the research setting, IHC has become an essential ancillary technique in clinical diagnostics in anatomic pathology (Lin F, Chen Z. Arch Pathol Lab Med 138:1564-1577, 2014) with the advent of antigen retrieval methods allowing it to be performed conveniently on formalin fixed paraffin embedded (FFPE) tissue (Taylor CR, Shi S-R, Barr NJ...
2019: Methods in Molecular Biology
Abbas Karimi, Roghayeh Sheervalilou, Houman Kahroba
Human endogenous retroviruses (HERVs) are semi-conserved subtypes of long-terminal repeats containing retrotransposons that constitute approximately 8% of the genome. Under pathological conditions, the expression of HERVs is also affected by epigenetic modifications. The extent to which the activation of human endogenous retroviruses can be influenced upon exposure to copper remains to be evaluated. Thus, the present study was designed to evaluate the effects of CuSO4 administration on the transcriptional activity of three HERV families (H, K, and W) in human malignant melanoma cells...
December 11, 2018: Biological Trace Element Research
Abiodun Joseph Fatoba, Matthew Adekunle Adeleke
Coccidiosis is a deadly disease that hampers chicken's productivity and welfare. Thus, the disease is a major menace to the global poultry industry. Coccidiosis which is caused by the apicomplexan parasite of the genus Eimeria has seven known species which affect the different parts of the intestinal tract of chickens. The disease which occurs by ingestion of sporulated oocyst has been associated with poor poultry management system. Mixed infection among the species of this parasite contributes to both pathogenicity and misdiagnosis of the disease...
December 2018: Journal of Parasitic Diseases: Official Organ of the Indian Society for Parasitology
Gan-Xun Li, Ze-Yang Ding, Yu-Wei Wang, Tong-Tong Liu, Wei-Xun Chen, Jing-Jing Wu, Wei-Qi Xu, Peng Zhu, Bi-Xiang Zhang
DNA methylation is a crucial regulator of gene transcription in the etiology and pathogenesis of hepatocellular carcinoma (HCC). Thus, it is reasonable to identify DNA methylation-related prognostic markers. Currently, we aimed to make an integrative epigenetic analysis of HCC to identify the effectiveness of epigenetic drivers in predicting prognosis for HCC patients. By the software pipeline TCGA-Assembler 2, RNA-seq, and methylation data were downloaded and processed from The Cancer Genome Atlas. A bioconductor package MethylMix was utilized to incorporate gene expression and methylation data on all 363 samples and identify 589 epigenetic drivers with transcriptionally predictive...
December 7, 2018: Journal of Cellular Physiology
Wen-Bin Liu, Fei Han, Yong-Sheng Huang, Hong-Qiang Chen, Jian-Ping Chen, Dan-Dan Wang, Xiao Jiang, Li Yin, Jia Cao, Jin-Yi Liu
Emerging evidences have revealed tumor-specific gene methylation is considered to be a promising non-invasive biomarker for many different types of cancers. This study was determined whether TMEM196 gene hypermethylation and downregulation are considered to be promising biomarkers for early diagnosis and prognosis in lung cancer. Methylation status was detected with methylation-specific PCR. Kaplan-Meier survival curves and Cox regression analysis were used to determine the significance of prognosis. TMEM196 gene was hypermethylated in 68...
December 11, 2018: Molecular Carcinogenesis
Kay Boulton, Matthew J Nolan, Zhiguang Wu, Valentina Riggio, Oswald Matika, Kimberley Harman, Paul M Hocking, Nat Bumstead, Pat Hesketh, Andrew Archer, Stephen C Bishop, Pete Kaiser, Fiona M Tomley, David A Hume, Adrian L Smith, Damer P Blake, Androniki Psifidi
Coccidiosis in poultry, caused by protozoan parasites of the genus Eimeria , is an intestinal disease with substantial economic impact. With the use of anticoccidial drugs under public and political pressure, and the comparatively higher cost of live-attenuated vaccines, an attractive complementary strategy for control is to breed chickens with increased resistance to Eimeria parasitism. Prior infection with Eimeria maxima leads to complete immunity against challenge with homologous strains, but only partial resistance to challenge with antigenically diverse heterologous strains...
2018: Frontiers in Genetics
Edoardo D'Angelo, Marco Agostini
Currently available high-throughput technologies combined with bioinformatics analyses revealed that nearly 80% of the genome is transcribed, whereas only 2% of the genetic code is translated in proteins. In the landscape of non-coding RNA, the long non-coding RNA (>200 nucleotides) is a newer class of ncRNAs, with a potential pivotal role in homeostatic and pathological mechanisms, confirmed by increasing emerging evidences in different diseases, especially in cancer. In parallel, recent studies have demonstrated that as cancer progresses, extracellular matrix co-evolves into an activated state through continuous biochemical and structural modifications...
December 2018: Non-Coding RNA Research
Lucie Mádrová, Matyáš Krijt, Veronika Barešová, Jan Václavík, David Friedecký, Dana Dobešová, Olga Součková, Václava Škopová, Tomáš Adam, Marie Zikánová
Purines are essential molecules for all forms of life. In addition to constituting a backbone of DNA and RNA, purines play roles in many metabolic pathways, such as energy utilization, regulation of enzyme activity, and cell signaling. The supply of purines is provided by two pathways: the salvage pathway and de novo synthesis. Although purine de novo synthesis (PDNS) activity varies during the cell cycle, this pathway represents an important source of purines, especially for rapidly dividing cells. A method for the detailed study of PDNS is lacking for analytical reasons (sensitivity) and because of the commercial unavailability of the compounds...
2018: PloS One
Taiki Mori, Yasushi Hamaya, Takahiro Uotani, Mihoko Yamade, Moriya Iwaizumi, Takahisa Furuta, Hiroaki Miyajima, Satoshi Osawa, Ken Sugimoto
Pancreatic ductal adenocarcinoma (PDAC) prognosis remains poor even after complete resection owing to no valuable biomarkers for recurrence and chemosensitivity. Tumors not expressing MSH3 show elevated microsatellite alterations at selected tetranucleotide repeats (EMAST). EMAST reportedly occurs in several tumors. In colorectal cancer (CRC), EMAST was reportedly correlated with 5-fluorouracil (5-FU) sensitivity. However, EMAST prevalence in PDAC and its significance as a prognostic biomarker are unknown. This study aimed to investigate EMAST prevalence in PDAC and the associations between EMAST and pathological factors, EMAST and prognosis, and EMAST and MSH3 expression via immunohistochemistry (IHC)...
2018: PloS One
Yo-Taro Shirai, Anna Mizutani, Saori Nishijima, Masafumi Horie, Chisato Kikuguchi, Olga Elisseeva, Tadashi Yamamoto
Lung cancer is one of the major causes of cancer death and clarification of its molecular pathology is highly prioritized. The physiological importance of mRNA degradation through the CCR4-NOT deadenylase has recently been highlighted. For example, mutation in CNOT3, a gene coding for CNOT3 subunit of the CCR4-NOT complex, is found to be associated with T-cell acute lymphoblastic leukemia, T-ALL, though its contribution to other cancers has not been reported. Here, we provide evidence suggesting that CNOT3 is required for the growth of non-small cell lung cancer...
December 10, 2018: Oncogene
Lijuan Zhao, Hong Chang, Dong-Sheng Zhou, Jun Cai, Weixing Fan, Wei Tang, Wenxin Tang, Xingxing Li, Weiqing Liu, Fang Liu, Yuanfang He, Yan Bai, Yan Sun, Jiapei Dai, Lingyi Li, Xiao Xiao, Chen Zhang, Ming Li
Genetic analyses of psychiatric illnesses, such as bipolar disorder (BPD), have revealed essential information regarding the underlying pathological mechanisms. While such studies in populations of European ancestry have achieved prominent success, understanding the genetic risk factors of these illnesses (especially BPD) in Chinese population remains an urgent task. Given the lack of genome-wide association study (GWAS) of BPD in Chinese population from Mainland China, replicating the previously reported GWAS hits in distinct populations will provide valuable information for future GWAS analysis in Han Chinese...
December 7, 2018: Translational Psychiatry
C Schwartz, O Rohr, C Wallet
The DNA-PK complex is the major component of the predominant mechanism of DSB repair in humans. In addition, this complex is involved in many other processes such as DNA recombination, genome maintenance, apoptosis and transcription regulation. Several studies have linked the decrease of the DNA-PK activity with cancer initiation, due to defects in the repair. On another hand, higher DNA-PK expression and activity have been observed in various other tumor cells and have been linked with a decrease of the efficiency of anti-tumor drugs...
December 6, 2018: Biochemical Pharmacology
Matheus Garcia, Marilia Seelaender, Athanassia Sotiropoulos, Dario Coletti, Antonio Herbert Lancha
The relevance of vitamin D to skeletal muscle metabolism has been highlighted in recent years. The interest arises from the important findings of studies demonstrating multiple effects of vitamin D on this tissue, which can be divided into genomic (direct effects) and non-genomic effects (indirect effects). Another important aspect to be considered in the study of vitamin D and muscle fiber metabolism is related to different expression of vitamin D receptor (VDR), which varies in muscle tissue depending on age, sex, and pathology...
October 7, 2018: Nutrition
Laura Pellegrini, Eleonora Foglio, Elena Pontemezzo, Antonia Germani, Matteo Antonio Russo, Federica Limana
High-mobility group box 1 (HMGB1) is one of the most abundant proteins in eukaryotes and the best characterized damage-associated molecular pattern (DAMP). The biological activities of HMGB1 depend on its subcellular location, context and post-translational modifications. Inside the nucleus, HMGB1 is engaged in many DNA events such as DNA repair, transcription regulation and genome stability; in the cytoplasm, its main function is to regulate the autophagic flux while in the extracellular environment, it possesses more complicated functions and it is involved in a large variety of different processes such as inflammation, migration, invasion, proliferation, differentiation and tissue regeneration...
December 5, 2018: Pharmacology & Therapeutics
Seitaro Nomura
Cardiomyopathy, a leading cause of death worldwide, is etiologically and phenotypically heterogeneous and is caused by a combination of genetic and non-genetic factors. Major genomic determinants of dilated cardiomyopathy (DCM) are titin truncating mutations and lamin A/C mutations. Patients with these two genotypes show critically different phenotypes, including penetrance, coexistence with a conduction system abnormality, cardiac prognosis, and treatment response. The transcriptomic and epigenomic characteristics of DCM include activation of the DNA damage response, metabolic reprogramming, and dedifferentiation...
December 4, 2018: Journal of Cardiology
Daniel Kazdal, Alexander Harms, Volker Endris, Roland Penzel, Cristiano Oliveira, Mark Kriegsmann, Rémi Longuespée, Hauke Winter, Marc A Schneider, Thomas Muley, Nicole Pfarr, Wilko Weichert, Albrecht Stenzinger, Arne Warth
OBJECTIVES: The potential role of cancer associated somatic mutations of the mitochondrial genome (mtDNA) is controversial and still poorly understood. Our group and others recently challenged a direct tumorigenic impact and suggested a passenger-like character. In combination with the known increased mutation rate, somatic mtDNA mutations account for an interesting tool to delineate tumor evolution. Here, we comprehensively analyzed the spatial distribution of somatic mtDNA mutations throughout whole tumor sections of pulmonary adenocarcinoma (ADC)...
December 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Denis M Nyaga, Mark H Vickers, Craig Jefferies, Jo K Perry, Justin M O'Sullivan
Type 1 diabetes (T1D) is a chronic metabolic disorder characterized by the autoimmune destruction of insulin-producing pancreatic islet beta cells in genetically predisposed individuals. Genome-wide association studies (GWAS) have identified over 60 risk regions across the human genome, marked by single nucleotide polymorphisms (SNPs), which confer genetic predisposition to T1D. There is increasing evidence that disease-associated SNPs can alter gene expression through spatial interactions that involve distal loci, in a tissue- and development-specific manner...
2018: Frontiers in Genetics
John Hung, Vladislav Miscianinov, Judith C Sluimer, David E Newby, Andrew H Baker
Only recently have we begun to appreciate the importance and complexity of the non-coding genome, owing in some part to truly significant advances in genomic technology such as RNA sequencing and genome-wide profiling studies. Previously thought to be non-functional transcriptional "noise," non-coding RNAs (ncRNAs) are now known to play important roles in many diverse biological pathways, not least in vascular disease. While microRNAs (miRNA) are known to regulate protein-coding gene expression principally through mRNA degradation, long non-coding RNAs (lncRNAs) can activate and repress genes by a variety of mechanisms at both transcriptional and translational levels...
2018: Frontiers in Physiology
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