4 resultados para Non-canonical splicing sites
em Brock University, Canada
Resumo:
Whiplash injuries are common yet enigmatic to substantiate clinically. Trigeminal somatosensory evoked potentials (TSEPs) were posited as an indicator of trigeminal nerve conduction damage resulting from whiplash. Alternating polarity square-wave current stimuli were applied transcutaneously in the facial region. 379 recorded pilot trials from 27 participants (8 male and 19 female) were utilized to develop a non-invasive recording capability for TSEPs. Stimulus intensity and artifact, cortical recording sites, stimulation electrode design and placement were explored. Statistically significant differences in amplitude of TSEP waveform components at 13, 19 and 27 ms between uninjured and whiplashed participants were noted. Increased stimulus intensity in whiplashed participants was observed to increase TSEP amplitude. The present methodology and hardware are discussed and directions for future advancement of the current process are outlined.
Resumo:
Alternative splicing (AS) is the predominant mechanism responsible for increasing eukaryotic transcriptome and proteome complexity. In this phenomenon, numerous mRNA transcripts are produced from a single pre-mRNA sequence. AS is reported to occur in 95% of human multi-exon genes; one specific gene that undergoes AS is DNA polymerase beta (POLB). POLB is the main DNA repair gene which performs short patch base excision repair (BER). In primate untransformed primary fibroblast cell lines, it was determined that the splice variant (SV) frequency of POLB correlates positively with species lifespan. To date, AS patterns of POLB have only been examined in mammals primarily through the use of cell lines. However, little attention has been devoted to investigating if such a relationship exists in non-mammals and whether cell lines reflect what is observed in vertebrate tissues. This idea was explored through cloning and characterization of 1,214 POLB transcripts from four non-mammalian species (Gallus gallus domesticus, Larus glaucescens, Xenopus laevis, and Pogona vitticeps) and two mammalian species (Sylvilagus floridanus and Homo sapiens) in two tissue types, liver and brain. POLB SV frequency occurred at low frequencies, < 3.2%, in non-mammalian tissues relative to mammalian (>20%). The highest POLB SV frequency was found in H. sapiens liver and brain tissues, occurring at 65.4% and 91.7%, respectively. Tissue specific AS of POLB was observed in L. glaucescens, P. vitticeps, and H. sapiens, but not G. gallus domesticus, X. laevis and S. floridanus.The AS patterns of a second gene, transient receptor potential cation channel subfamily V member 1 (TRPV1), were compared to those of POLB in liver and brain tissues of G. gallus domesticus, X. laevis and H. sapiens. This comparison was performed to investigate if any changes (either increase or decrease) observed in the AS of POLB were gene specific or if they were tissue specific, in which case similar changes in AS would be seen in POLB and TRPV1. Analysis did not reveal an increase or decrease in both the AS of POLB and TRPV1 in either the liver or brain tissues of G. gallus domesticus and H. sapiens. This result suggested that the AS patterns of POLB were not influenced by tissue specific rates of AS. Interestingly, an increase in the AS of both genes was only observed in X. laevis brain tissue. This result suggests that AS in general may be increased in the X. laevis brain as compared to liver tissue. No positive correlation between POLB SV frequency and species lifespan was found in non-mammalian tissues. The AS patterns of POLB in human primary untransformed fibroblast cell lines were representative of those seen in human liver tissue but not in brain tissue. Altogether, the AS patterns of POLB from vertebrate tissues and primate cell lines revealed a positive correlation between POLB SV frequency and lifespan in mammals, but not in non-mammals. It appears that this positive correlation does not exist in vertebrate species as a whole.
Resumo:
Most human genes undergo alternative splicing and loss of splicing fidelity is associated with disease. Epigenetic silencing of hMLH 1 via promoter cytosine methylation is causally linked to a subset of sporadic non-polyposis colon cancer and is reversible by 5-aza-2' -deoxycytidine treatment. Here I investigated changes in hMLHI mRNA splicing profiles in normal fibroblasts and colon cancer-derived human cell lines. I established the types and frequencies of hMLHI mRNA transcripts generated under baseline conditions, after hydrogen peroxide induced oxidative stress, and in acutely 5-aza-2' -deoxycytidine-treated and stably derepressed cancer cell lines. I found that hMLHI is extensively spliced under all conditions including baseline (50% splice variants), the splice variant distribution changes in response to oxidative stress, and certain splice variants are sensitive to 5- aza-2' -deoxycytidine treatment: Splice variant diversity and frequency of exon 17 skipping correlates with the level of hMLHI promoter methylation suggesting a link between promoter methylation and mRNA splicing.
Resumo:
Dr. Stuart D. Scott has written extensively in the fields of prehistory and history. As an archaeologist, he has traveled to some of the most significant sites in the world, including Pompeii, Stonehenge, the Valley of the Kings, Egypt’s pyramids and the Taj Mahal. He spent nine months excavating with the Tikal Project in Guatemala before returning to the University of Arizona where he received a Ph.D. in 1963. He excavated in New Zealand as a Fulbright scholar in 1963-1964. In the fall of 1964, Dr. Scott started a long career in the Anthropology Department of the State University of New York. He taught graduate and undergraduate archaeology courses and continued his archaeological and historical research. In 1979, Scott established the Old Fort Niagara Archaeology in Progress Project at Old Fort Niagara in Youngstown, New York. For many years, he became involved with historical archaeology in western New York. It was during this work that he became interested in the Upper Canada Rebellion of 1837-1838 and its aftermath. Dr. Scott and his wife, Patricia Kay Scott, would use Christmas breaks, summer vacations, and sabbatical years to travel. They were repeatedly lured back to the South Pacific, conducting research in New Zealand, Australia and many of the Micronesian and Polynesian islands. To tell the whole story of the Rebellion and the prison exiles, they traveled extensively in Canada, the United States, England and Tasmania to collect archival research and to experience the scenes of this remarkable narrative. In 2004, Dr. Scott published To the Outskirts of Habitable Creation: Americans and Canadians Transported to Tasmania in the 1840s, which told the story of the men captured, tried, convicted, and exiled as a result of the Rebellion, also called the Patriot War. Other contributions include: • A collaboration with Dr. Charles Cazeau on the book Exploring the Unknown, Great Mysteries Reexamined published by Plenum Press in 1979 • The Patriot Game: New Yorkers and the Canadian Rebellion of 1837-1838, which appeared in New York History, Vol. 68, No.3. 1987 • A Frontier Spirit: The Life of James Gemmell published in Australiasian Canadian Studies, Vol. 25, No. 2 2007 • To the Outskirts of Habitable Creation which appeared in the Friends of the National Archives, Vol. 20, No. 1 2009 • Numerous academic journal publications • Service on conference panels • Various research papers and proposals Before retiring in 1997 and while still a resident of Buffalo, N.Y., Dr. Scott spent considerable time with Brock University President Emeritus James A. Gibson and History Professor Colin Duquemin. The three shared a love of Rebellion history. It was largely because of this connection that Brock University was chosen as the recipient of Dr. Scott’s research materials.