Implications of a RAD54L polymorphism (2290C/T) in human meningiomas as a risk factor and/or a genetic marker

BACKGROUND: RAD54L (OMIM 603615, Locus Link 8438) has been proposed as a candidate oncosupressor in tumours bearing a non-random deletion of 1p32, such as breast or colon carcinomas, lymphomas and meningiomas. In a search for RAD54L mutations in 29 menigiomas with allelic deletions in 1p, the only genetic change observed was a silent C/T transition at nucleotide 2290 in exon 18. In this communication the possible association of the 2290C/T polymorphism with the risk of meningiomas was examined. In addition, the usefulness of this polymorphism as a genetic marker within the meningioma consensus deletion region in 1p32 was also verified. The present study comprises 287 blood control samples and 70 meningiomas from Spain and Ecuador. Matched blood samples were only available from Spanish patients. RESULTS: The frequency of the rare allele-T and heterozygotes for the 2290C/T polymorphism in the blood of Spanish meningioma patients and in the Ecuadorian meningioma tumours was higher than in the control population (P < 0.05). Four other rare variants (2290C/G, 2299C/G, 2313G/A, 2344A/G) were found within 50 bp at the 3' end of RAD54L. Frequent loss of heterozygosity for the 2290C/T SNP in meningiomas allowed to further narrow the 1p32 consensus region of deletion in meningiomas to either 2.08 Mbp – within D1S2713 (44.35 Mbp) and RAD54L (46.43 Mbp) – or to 1.47 Mbp – within RAD54L and D1S2134 (47.90 Mbp) – according to recent gene mapping results. CONCLUSION: The statistical analysis of genotypes at the 2290C/T polymorphism suggest an association between the rare T allele and the development of meningeal tumours. This polymorphism can be used as a genetic marker inside the consensus deletion region at 1p32 in meningiomas

Discovery of permuted and recently split transfer RNAs in Archaea

Background: As in eukaryotes, precursor transfer RNAs in Archaea often contain introns that are removed in tRNA maturation. Two unrelated archaeal species display unique pre-tRNA processing complexity in the form of split tRNA genes, in which two to three segments of tRNAs are transcribed from different loci, then trans-spliced to form a mature tRNA. Another rare type of pre-tRNA, found only in eukaryotic algae, is permuted, where the 3 ’ half is encoded upstream of the 5 ’ half, and must be processed to be functional. Results: Using an improved version of the gene-finding program tRNAscan-SE, comparative analyses and experimental verifications, we have now identified four novel trans-spliced tRNA genes, each in a different species of the Desulfurococcales branch of the Archaea: tRNA Asp(GUC) in Aeropyrum pernix and Thermosphaera aggregans, and tRNA Lys(CUU) in Staphylothermus hellenicus and Staphylothermus marinus. Each of these includes features surprisingly similar to previously studied split tRNAs, yet comparative genomic context analysis and phylogenetic distribution suggest several independent, relatively recent splitting events. Additionally, we identified the first examples of permuted tRNA genes in Archaea: tRNA iMet(CAU) and tRNA Tyr(GUA) in Thermofilum pendens, which appear to be permuted in the same arrangement seen previously in red alga. Conclusions: Our findings illustrate that split tRNAs are sporadically spread across a major branch of the Archaea

Leaderless genes in bacteria: clue to the evolution of translation initiation mechanisms in prokaryotes

<p>Abstract</p> <p>Background</p> <p>Shine-Dalgarno (SD) signal has long been viewed as the dominant translation initiation signal in prokaryotes. Recently, leaderless genes, which lack 5'-untranslated regions (5'-UTR) on their mRNAs, have been shown abundant in archaea. However, current large-scale <it>in silico </it>analyses on initiation mechanisms in bacteria are mainly based on the SD-led initiation way, other than the leaderless one. The study of leaderless genes in bacteria remains open, which causes uncertain understanding of translation initiation mechanisms for prokaryotes.</p> <p>Results</p> <p>Here, we study signals in translation initiation regions of all genes over 953 bacterial and 72 archaeal genomes, then make an effort to construct an evolutionary scenario in view of leaderless genes in bacteria. With an algorithm designed to identify multi-signal in upstream regions of genes for a genome, we classify all genes into SD-led, TA-led and atypical genes according to the category of the most probable signal in their upstream sequences. Particularly, occurrence of TA-like signals about 10 bp upstream to translation initiation site (TIS) in bacteria most probably means leaderless genes.</p> <p>Conclusions</p> <p>Our analysis reveals that leaderless genes are totally widespread, although not dominant, in a variety of bacteria. Especially for <it>Actinobacteria </it>and <it>Deinococcus-Thermus</it>, more than twenty percent of genes are leaderless. Analyzed in closely related bacterial genomes, our results imply that the change of translation initiation mechanisms, which happens between the genes deriving from a common ancestor, is linearly dependent on the phylogenetic relationship. Analysis on the macroevolution of leaderless genes further shows that the proportion of leaderless genes in bacteria has a decreasing trend in evolution.</p

Transcriptional Mutagenesis Induced by 8-Oxoguanine in Mammalian Cells

Most of the somatic cells of adult metazoans, including mammals, do not undergo continuous cycles of replication. Instead, they are quiescent and devote most of their metabolic activity to gene expression. The mutagenic consequences of exposure to DNA–damaging agents are well documented, but less is known about the impact of DNA lesions on transcription. To investigate this impact, we developed a luciferase-based expression system. This system consists of two types of construct composed of a DNA template containing an 8-oxoguanine, paired either with a thymine or a cytosine, placed at defined positions along the transcribed strand of the reporter gene. Analyses of luciferase gene expression from the two types of construct showed that efficient but error-prone transcriptional bypass of 8-oxoguanine occurred in vivo, and that this lesion was not repaired by the transcription-coupled repair machinery in mammalian cells. The analysis of luciferase activity expressed from 8OG:T-containing constructs indicated that the magnitude of erroneous transcription events involving 8-oxoguanine depended on the sequence contexts surrounding the lesion. Additionally, sequencing of the transcript population expressed from these constructs showed that RNA polymerase II mostly inserted an adenine opposite to 8-oxoguanine. Analysis of luciferase expression from 8OG:C-containing constructs showed that the generated aberrant mRNAs led to the production of mutant proteins with the potential to induce a long-term phenotypical change. These findings reveal that erroneous transcription over DNA lesions may induce phenotypical changes with the potential to alter the fate of non-replicating cells

The Mutyh Base Excision Repair Gene Influences the Inflammatory Response in a Mouse Model of Ulcerative Colitis

BACKGROUND: The Mutyh DNA glycosylase is involved in the repair of oxidized DNA bases. Mutations in the human MUTYH gene are responsible for colorectal cancer in familial adenomatous polyposis. Since defective DNA repair genes might contribute to the increased cancer risk associated with inflammatory bowel diseases, we compared the inflammatory response of wild-type and Mutyh(-/-) mice to oxidative stress. METHODOLOGY/PRINCIPAL FINDINGS: The severity of colitis, changes in expression of genes involved in DNA repair and inflammation, DNA 8-oxoguanine levels and microsatellite instability were analysed in colon of mice treated with dextran sulfate sodium (DSS). The Mutyh(-/-) phenotype was associated with a significant accumulation of 8-oxoguanine in colon DNA of treated mice. A single DSS cycle induced severe acute ulcerative colitis in wild-type mice, whereas lesions were modest in Mutyh(-/-) mice, and this was associated with moderate variations in the expression of several cytokines. Eight DSS cycles caused chronic colitis in both wild-type and Mutyh(-/-) mice. Lymphoid hyperplasia and a significant reduction in Foxp3(+) regulatory T cells were observed only in Mutyh(-/-) mice. CONCLUSIONS: The findings indicate that, in this model of ulcerative colitis, Mutyh plays a major role in maintaining intestinal integrity by affecting the inflammatory response

Пристрій для вивірення колон на вертикальність

Problem statement. The introduction of scientific and technological progress in modern construction is a major lever for increasing the efficiency of construction production. Its development is based on the principles of industrialization, which is based on the mechanization and automation of the main and auxiliary processes, as well as the introduction of flexible robotic systems and the use of modern computer systems. One of the main installations of the working equipment is the exhibition of verticality on the foundations and supports of various types of technological equipment and constructions. Particular attention is devoted to it with the industrial method of installation, the essence of which is the mechanized installation of buildings and structures from prefabricated structures of factory production. The exhibition can be visual or instrumental, which is executed using the ruler, theodolites, levelers, etc. The quality of the assembly and the laboriousness of the installation work depend on the method of exhibition. Laser theodolites have been widely used, of which theodolites with the visual system are more common, which are used for application in exhibitionof building structures. Ensuring the accuracy of the installation in the project position within the limits of permissible deviations in height, horizontal or vertical plane depends not only on the accuracy of the equipment, but also on the quality of work to determine their spatial orientation. The durability of equipment depends on many factors, for example, on the accuracy of exhibition the structures, the rate of wear of individual units and parts, the level of oscillations in the joints and fasteners. Purpose. To solve the technical problem of improving the accuracy of exhibition of building structures in a vertical position, a device based on accelerometers is proposed. Conclusion. It is proposed to use the device on the basis of two uniaxial accelerometers for installing the column in a vertical position. The offered device is a universal means that helps to shorten the time of exhibition of building constructions, and also allows to receive measurement information about the spatial position of constructions during the process of installation works and the operation of construction objects.Постановка проблемы. Внедрение научно-технического прогресса в современном строительстве является основным рычагом повышения эффективности строительного производства. Его развитие базируется на принципах индустриализации, основаных на механизации и автоматизации основных и вспомогательных процессов, а также внедрении гибких роботизированных систем и использовании современных средств вычислительной техники. Одной из главных монтажных операций строительства является выверка на фундаментах и опорах различных видов технологического оборудования и конструкций. Особое внимание ей уделено при индустриальном методе монтажа, сущность которого заключается в механизированном монтаже зданий и сооружений из сборных конструкций заводского изготовления. Выверка может быть визуальной или инструментальной, которая выполняется с использованием линейки, нивелиров и т. п. От способа выверки зависит качество сборки и трудоемкость монтажных работ. Широкое применение получили лазерные теодолиты, из них более распространены теодолиты с визуальной системой, которые служат для применения при выверке строительных конструкций. Обеспечение точности установки в проектное положение в пределах допустимых отклонений по высоте, горизонтальной или вертикальной плоскости зависит не только от точности изготовления оборудования, но также от качества выполнения работ по определению их пространственной ориентации. Долговечность оборудования зависит от многих факторов, например, от точности выверки конструкций, темпа износа отдельных узлов и деталей, уровня колебаний в соединениях и крепежных деталях. Вывод. Предлагается для выверки колонн на вертикальность использовать устройство на основе двух одноосных акселерометрических преобразователей. Предлагаемое устройство является универсальным средством, которое способствует сокращению времени выверки строительных конструкций, а также позволяет получить измерительную информацию о пространственном положении конструкций в процессе монтажных работ и при эксплуатации строительных объектов.Постановка проблеми. Впровадження науково-технічного прогресу в сучасному будівництві ‑ основний важіль підвищення ефективності будівельного виробництва. Його розвиток базується на принципах індустріалізації, заснованих на механізації та автоматизації основних та допоміжних процесів, а також упровадженні гнучких роботизованих систем і використанні сучасних засобів обчислювальної техніки. Одна з головних монтажних операцій будівництва – це вивірення вивірка на фундаментах і опорах різних видів технологічного обладнання та конструкцій. Особливу увагу їй приділено у разі індустріального методу монтажу, сутність якого полягає в механізованому монтажі будівель та споруд зі збірних конструкцій заводського виготовлення. Вивірювання може бути візуальним або інструментальним, що виконується з використанням лінійки, теодолітів, нівелірів тощо. Від способу вивірення залежить якість складання і трудомісткість монтажних робіт. Широке застосування отримали лазерні теодоліти, з яких більш поширені теодоліти з візуальною системою, що служать для вивірення будівельних конструкцій. Забезпечення точності установлення в проектне положення в межах допустимих відхилень по висоті, горизонтальній або вертикальній площині залежить не тільки від точності виготовлення устаткування, а й від якості виконання робіт із визначення їх просторової орієнтації. Довговічність обладнання залежить від багатьох факторів, наприклад, від точності вивірення конструкцій, темпу зносу окремих вузлів і деталей, рівня коливань у з'єднаннях і кріпильних деталях. Висновок. Пропонується для вивірення колон на вертикальність використовувати пристрій на основі двох одновісних акселерометричних перетворювачів. Це універсальний засіб, який скорочує час вивірення будівельних конструкцій, а також дозволяє отримати вимірювальну інформацію про просторове положення конструкцій у процесі монтажних робіт і експлуатації будівельних об'єктів