Identification and analysis of mutational hotspots in oncogenes and tumour suppressors

Background: The key to interpreting the contribution of a disease-associated mutation in the development and progression of cancer is an understanding of the consequences of that mutation both on the function of the affected protein and on the pathways in which that protein is involved. Protein domains encapsulate function and position-specific domain based analysis of mutations have been shown to help elucidate their phenotypes. Results: In this paper we examine the domain biases in oncogenes and tumour suppressors, and find that their domain compositions substantially differ. Using data from over 30 different cancers from whole-exome sequencing cancer genomic projects we mapped over one million mutations to their respective Pfam domains to identify which domains are enriched in any of three different classes of mutation; missense, indels or truncations. Next, we identified the mutational hotspots within domain families by mapping small mutations to equivalent positions in multiple sequence alignments of protein domains We find that gain of function mutations from oncogenes and loss of function mutations from tumour suppressors are normally found in different domain families and when observed in the same domain families, hotspot mutations are located at different positions within the multiple sequence alignment of the domain. Conclusions: By considering hotspots in tumour suppressors and oncogenes independently, we find that there are different specific positions within domain families that are particularly suited to accommodate either a loss or a gain of function mutation. The position is also dependent on the class of mutation. We find rare mutations co-located with well-known functional mutation hotspots, in members of homologous domain superfamilies, and we detect novel mutation hotspots in domain families previously unconnected with cancer. The results of this analysis can be accessed through the MOKCa database (http://strubiol.icr.ac.uk/ extra/MOKCa)

Mutational patterns in oncogenes and tumour suppressors

All cancers depend upon mutations in critical genes, which confer a selective advantage to the tumour cell. Knowledge of these mutations is crucial to understanding the biology of cancer initiation and progression, and to the development of targeted therapeutic strategies. The key to understanding the contribution of a disease-associated mutation to the development and progression of cancer, comes from an understanding of the consequences of that mutation on the function of the affected protein, and the impact on the pathways in which that protein is involved. In this paper we examine the mutation patterns observed in oncogenes and tumour suppressors, and discuss different approaches that have been developed to identify driver mutations within cancers that contribute to the disease progress. We also discuss the MOKCa database where we have developed an automatic pipeline that structurally and functionally annotates all proteins from the human proteome that are mutated in cancer

Conflict of interest reporting in dentistry meta-analyses: a systematic review

Objectives: The issue of reporting conflicts of interest (COI) in medical research has come under scrutiny over the past decade. Absolute transparency is important when dealing with conflicts of interest to provide readers with all essential information required to make an informative decision of the results. The key objective of this study was to examine the prevalence of reporting conflicts of interest in therapeutic dental meta-analyses of Randomized Control Trials (RCTs), and to investigate possible associations with other categorical variables. Study Design: We conducted an extensive literature search across multiple databases to search for relevant review articles for this study. We utilized pre-determined key words, and relied on three reviewers to test and review the use of a data extraction form that was used for the meta-analyses. Data regarding study characteristics, direction of results, and the significance of the results from each meta-analysis were extracted. Results: There were 129 meta-analyses used in this review, and the reporting on conflict of interest was low with only 50 (38.8%) of the articles possessing a conflict of interest statement (either confirming of denying COI). Of these 50 articles, there were only 4 (8%) studies that reported an actual conflict of interest. A statement of conflicts of interest was found in 29 (35.3%) of the papers that reported significant findings, whereas 35% of the papers that reported positive results reported on conflict of interest. Prior to 2009, only 17 (25%) papers reported conflicts of interest, but since 2009, 54.1% of papers collected had a conflict of interest statement. Conclusions: Meta-analyses published in the field of dentistry do not routinely report author conflicts of interest. Although few conflicts appear to exist, the field of dentistry should continue to ensure that best evidence reports provide clear and transparent reporting of potential conflicts of interest in academic journals

Rapid and controlled electrochemical synthesis of crystalline niobium oxide microcones

We demonstrate the fabrication by anodization of niobium oxide microcones, several microns long, from aqueous solutions of 1 wt% hydrogen fluoride (HF) with varied sodium fluoride (NaF) concentration (0–1 M). Raman spectroscopy and x-ray diffractometer analysis revealed the as-grown microcones to be crystalline Nb_2O_(5−x) with preferred (1 0 0) and (0 1 0) orientations. The overall Nb_2O_(5−x) formation rate increased with the increasing NaF concentration, and structures as tall as 20 μm were achieved in just 20 min of anodization at 1 M NaF. Rapid formation of niobia microcones was even observed in the absence of HF at this NaF concentration. Photocatalytic activity for water oxidation was highest for microcones grown under the highest NaF concentration

A case study examining perceptions of female Saudi university students regarding the use of asynchronous online discussion boards

This phenomenological case study explored undergraduate Saudi female students\u27 perceptions of using asynchronous online discussion boards (AODB) as a learning tool. In addition, the current study explored factors that helped students learn skills, specifically their language learning. The current study sought to add to knowledge about how asynchronous online discussion forums can benefit undergraduate Saudi female students\u27 development of learning. Data were collected during the Spring 2016 semester through focus group and individual interviews with ten undergraduate students in an online course as well as their narrative reflections and the researcher reflections and notes. Participants were undergraduate Saudi female students at the junior academic year level who were studying English as a second language as a core degree requirement for their business management major. The results showed the three main themes that emerged from the current study included a) students\u27 perceptions of asynchronous online discussion boards, b) learning opportunities offered by AODBs, and c) factors that helped or hindered the participants\u27 learning. Each theme covered some category of students\u27 perceptions toward their experiences of using asynchronous online discussion boards. The first theme of students\u27 perceptions comprised four categories: (a) the value of using AODB, (b) engagement, (c) collaboration, and (d) convenient communication. The second theme, learning opportunities offered by AODB involved two categories: (a) empowerment, and (b) cognitive learning skills. The third theme regarding participants\u27 perceptions of the factors hindered or helped their learning, displayed categories related to: a) challenges of using AODB, b) teacher presence, and c) course structure. Regarding to the current study\u27s findings, dissuasion on participants\u27 perceptions was explored, implications for effective use of AODB along with several recommendations were provided

Technology Innovation for SME Growth: A Perception for the Emerging Economies

Globalization and technological transformations have triggered novel changes in both the developed and developing countries. Technology and entrepreneurship are vital tools used for national economies towards 21st century requirement and growth. Technology based enterprises are specifically smart to policy-makers because of their higher prospective for job creation and wealth-generation through business development as well as their lower disappearance rates compared to non-technology based firms. New technologies are often developed in R&D institutions. This initiative of providing incubation facilities to transfer these new technologies to the market is adopted by all growing institutions. A comprehensive review of the literature on the Technology innovation and SME’s are carried out. This study specifically examines the drivers of technology adoption in SMEs and their impact on SMEs’ performance - profit, growth and market share. In the developed countries technology development drives the incubator movement. Keywords: Technology business incubators, Small and Medium-sized Enterprises (SME’s), Emerging economies

Towards a New Vision for Sustainability of Incubator Best Practices Model in the Years to Come

Incubators are internationally recognized as a premier 21st century location for technology and technology-based economic development. The purpose of this paper is to identify the similarities and differences of business incubation programs worldwide. The study focuses on six key success indicators and points out proposed incubators model in the years to come. The approach to the design methodology is based on survey and interviews implanted on 100 selected incubators. The research findings indicate the similarities of incubators programs that are 1) Creating jobs, 2) Enhancing community’s entrepreneurial climate, and 3) Tangible services and the differences are 1) Incubators type, 2) Finical status, and 3) Incubators age. The research adds value to current literature on new visions for sustainability of incubators best practice models for the coming year. Finally, it provides useful guidelines for implementation to both academies and practitioners involved with incubators worldwide. Keywords: Technology incubators, innovation, entrepreneurship, job creation, economic development

Reprogramming the assembly of unmodified DNA with a small molecule

The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA ‘alphabet’ by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials