Sensitivity analysis and design and of reinforced concrete cantilever retaining walls using bacterial foraging optimization algorithm

Risk and Reliability in Geotechnical Engineerin

Tissue Specific Expression Levels of Apoptosis Involved Genes Have Correlations with Codon and Amino Acid Usage

Different mechanisms, including transcriptional and post transcriptional processes, regulate tissue specific expression of genes. In this study, we report differences in gene/protein compositional features between apoptosis involved genes selectively expressed in human tissues. We found some correlations between codon/amino acid usage and tissue specific expression level of genes. The findings can be significant for understanding the translational selection on these features. The selection may play an important role in the differentiation of human tissues and can be considered for future studies in diagnosis of some diseases such as cancer

The long non-coding RNA HOTAIR is transcriptionally activated by HOXA9 and is an independent prognostic marker in patients with malignant glioma

The lncRNA HOTAIR has been implicated in several human cancers. Here, we evaluated the molecular alterations and upstream regulatory mechanisms of HOTAIR in glioma, the most common primary brain tumors, and its clinical relevance. HOTAIR gene expression, methylation, copy-number and prognostic value were investigated in human gliomas integrating data from online datasets and our cohorts. High levels of HOTAIR were associated with higher grades of glioma, particularly IDH wild-type cases. Mechanistically, HOTAIR was overexpressed in a gene dosage-independent manner, while DNA methylation levels of particular CpGs in HOTAIR locus were associated with HOTAIR expression levels in GBM clinical specimens and cell lines. Concordantly, the demethylating agent 5-Aza-2'-deoxycytidine affected HOTAIR transcriptional levels in a cell line-dependent manner. Importantly, HOTAIR was frequently co-expressed with HOXA9 in high-grade gliomas from TCGA, Oncomine, and our Portuguese and French datasets. Integrated in silico analyses, chromatin immunoprecipitation, and qPCR data showed that HOXA9 binds directly to the promoter of HOTAIR. Clinically, GBM patients with high HOTAIR expression had a significantly reduced overall survival, independently of other prognostic variables. In summary, this work reveals HOXA9 as a novel direct regulator of HOTAIR, and establishes HOTAIR as an independent prognostic marker, providing new therapeutic opportunities to treat this highly aggressive cancer.Fundação Para A Ciência e Tecnologia (PTDC/ SAU-GMG/113795/2009; SFRH/BPD/33612/2009 and IF/00601/2012 to B.M.C.; SFRH/BD/88220/2012 to A.X.M.; SFRH/BD/92786/2013 to C.S.G; SFRH/BD/81042/2011 to M.P.; and SFRH/BD/51996/2012 to T.L.), Project co-financed by Programa Operacional Regional do Norte (ON.2 – O Novo Norte), Quadro de Referência Estratégico Nacional (QREN), Fundo Europeu de Desenvolvimento Regional (FEDER); Fundação Calouste Gulbenkian (B.M.C.); and Liga Portuguesa Contra o Cancro, Portugal (B.M.C.). This article has been developed under the scope of the projects NORTE-01-0246-FEDER-000012, NORTE-01-0145-FEDER-000023 and NORTE-01-0145FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the project POCI01-0145-FEDER-007038. C.J. acknowledges NHS funding to the Biomedical Research Centre. P.A. acknowledges the Plan Cancer-INSERM (CS14085CS‘Gliobiv’, PA), the Cancéropole CLARA (Oncostarter «Gliohoxas»; PA), Fonds de dotation Patrick Brou de Lauriére (PA).info:eu-repo/semantics/publishedVersio

The potential role of PHF6 as an oncogene: a genotranscriptomic/proteomic meta-analysis

<div><div><p>Epigenetic complexes control various pathways within the cells. Their abnormalities can be involved in the initiation and the progression of different types of cancer. Nucleosome remodeling and deacetylase (NuRD) is an epigenetic complex that comprises several subunits such as PHF6. Although PHF6 is reported as a tumor suppressor in some of the hematopoietic malignancies, its function is still challenging in other cancers. Our study aimed at investigating the role of PHF6 in different types of cancer. We conducted a meta-analysis of PHF6 in human cancers at genomic, transcriptomic, and proteomic levels. For this purpose, we acquired the data from several databases, and tried to statistically integrate and analyze the data in order to find the potential role of PHF6 in different tumors. The results demonstrated that although PHF6 has been previously known as a tumor suppressor gene, it was remarkably overexpressed in many cancer types such as breast and colorectal cancers. Notably, PHF6 was under-expressed in a few types of cancer, including esophageal tumors. Moreover, the results indicated that although the mutation rate of PHF6 is relatively low, it is mutated in some tumor types.  In addition, our data for 40 epigenetic genes showed that missense and nonsense mutations were associated with overexpression and under-expression, respectively. Our results suggest that PHF6 may function as an oncogenic factor in several types of cancer. We also hypothesize that PHF6 may also play its role in a tissue-specific manner. Our findings suggest further investigations regarding the exact role of PHF6 in tumor types.</p></div></div><div></div

Tissue Specific Expression Levels of Apoptosis Involved Genes Have Correlations with Codon and Amino Acid Usage

Different mechanisms, including transcriptional and post transcriptional processes, regulate tissue specific expression of genes. In this study, we report differences in gene/protein compositional features between apoptosis involved genes selectively expressed in human tissues. We found some correlations between codon/amino acid usage and tissue specific expression level of genes. The findings can be significant for understanding the translational selection on these features. The selection may play an important role in the differentiation of human tissues and can be considered for future studies in diagnosis of some diseases such as cancer.<br

Application of nanobioinformatics in drug design and delivery systems

<div><div>Nanobioinformatics is a convergent field which integrates the science of nanotechnology with bioinformatics. Nanobioinformatics has the potential to solve problems regarding high throughput genomics data, novel biomarker discovery, complex biological systems, computer-aided drug design (CADD), and nanobiology. Also, nanobioinformatics can be used for devising and designing of different nanosystems. In this context, for instance, bioinformatics can efficiently facilitate identification of multiplexed probes in a nanoparticle. Nano drugs are capable of cell targeting, penetration, and controlled release. Today, the application of nanobiotechnology in drug delivery systems is well-known. Bioinformatics is an important predictive approach for designing nano-transport systems for specific drugs. Also, integration of the power of two chem/bioinformatic techniques, molecular dynamics (MD) and docking, with statistics can help prediction of the efficiency of drug loading in nanoparticles. In addition, in the context of in-silico drug design, nano-design through nanoscale simulation and modeling requires cheminformatic and bioinformatic techniques such as MD simulations, quantitative structure–activity relationship (QSAR), molecular mechanics and quantum mechanics. A growing number of publically available databases such as NanoParticle Ontology and Chemical Entities of Biological Interest can be used to retrieve required data for nanobioinformatic drug design. Altogether, nanobioinformatics is a novel multidisciplinary field with many potential capabilities in drug design and delivery systems which may significantly accelerate the treatment many deadly diseases including cancer.</div></div

Carcinogenic effects of circadian disruption: an epigenetic viewpoint

<p>Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modifications and the formation of circadian epigenomes. Aberrant epigenetic modifications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I first discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modifications that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.</p

Meta-analysis of RAG2 using a genotranscriptomic/proteomic approach: Suggestive of its oncogenic role

<p>Epigenetic modifications are implicated in various intracellular changes that altogether result in regulation of proteinic content within the cells. These epigenetic modifications are exerted mostly by epigenetic complexes such as PRC2 and ASCOM which their misregulation is implicated in development of different diseases including cancer. Herein a genotranscriptomic/proteomic metaanalysis is done using different databases such as COSMIC, cBioPortal and The Human Protein Atlas to investigate the oncogenic role of RAG2, a component of ASCOM complex. In addition, the similarities between mutation distribution of RAG2 and JARID2, a component of PRC2 and also between their over/under expression may be suggestive of the association between PRC2 and ASCOM.</p> <p> </p

Application of nanobioinformatics in drug design and delivery systems

<div><div>Nanobioinformatics is a convergent field which integrates the science of nanotechnology with bioinformatics. Nanobioinformatics has the potential to solve problems regarding high throughput genomics data, novel biomarker discovery, complex biological systems, computer-aided drug design (CADD), and nanobiology. Also, nanobioinformatics can be used for devising and designing of different nanosystems. In this context, for instance, bioinformatics can efficiently facilitate identification of multiplexed probes in a nanoparticle. Nano drugs are capable of cell targeting, penetration, and controlled release. Today, the application of nanobiotechnology in drug delivery systems is well-known. Bioinformatics is an important predictive approach for designing nano-transport systems for specific drugs. Also, integration of the power of two chem/bioinformatic techniques, molecular dynamics (MD) and docking, with statistics can help prediction of the efficiency of drug loading in nanoparticles. In addition, in the context of in-silico drug design, nano-design through nanoscale simulation and modeling requires cheminformatic and bioinformatic techniques such as MD simulations, quantitative structure–activity relationship (QSAR), molecular mechanics and quantum mechanics. A growing number of publically available databases such as NanoParticle Ontology and Chemical Entities of Biological Interest can be used to retrieve required data for nanobioinformatic drug design. Altogether, nanobioinformatics is a novel multidisciplinary field with many potential capabilities in drug design and delivery systems which may significantly accelerate the treatment many deadly diseases including cancer.</div></div

HOTAIR: an oncogenic long non-coding RNA in different cancers

<p>Long non-coding RNAs (lncRNAs) refer to a group of RNAs that are usually more than 200 nucleotides and are not involved in protein generation. Instead, lncRNAs are involved in different regulatory processes, such as regulation of gene expression. Different lncRNAs exist throughout the genome. LncRNAs are also known for their roles in different human diseases such as cancer. HOTAIR is an lncRNA that plays a role as an oncogenic molecule in different cancer cells, such as breast, gastric, colorectal, and cervical cancer cells. Therefore, HOTAIR expression level is a potential biomarker for diagnostic and therapeutic purposes in several cancers. This RNA takes part in epigenetic regulation of genes and plays an important role in different cellular pathways by interacting with Polycomb Repressive Complex 2 (PRC2). In this review, we describe the molecular function and regulation of HOTAIR and its role in different types of cancers.</p> <p> </p