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Interpretation, Stratification and Evidence for Sequence Variants Affecting mRNA Splicing in Complete Human Genome Sequences

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Genomics, Proteomics & Bioinformatics 2013年第2期11卷 77-85页

作者： Ben C.Shirley Eliseos J.Mucaki tyson whitehead Paul I.Costea Pelin Akan Peter K.Rogan Department of Computer Science Middlesex CollegeThe University of Western Ontario Department of Biochemistry Schulich School of Medicine and DentistryThe University of Western Ontario SHARCNET Royal Institute of Technology Science for Life Laboratory Cytognomix Inc.

Information theory-based methods have been shown to be sensitive and specific for pre- dicting and quantifying the effects of non-coding mutations in Mendelian diseases. We present the Shannon pipeline software for genome-scale mutation analysis and provide evidence that the soft- ware predicts variants affecting mRNA splicing. Individual information contents （in bits） of refer- ence and variant splice sites are compared and significant differences are annotated and prioritized. The software has been implemented for CLC-Bio Genomics platform. Annotation indicates the context of novel mutations as well as common and rare SNPs with splicing effects. Potential natural and cryptic mRNA splicing variants are identified, and null mutations are distinguished from leaky mutations. Mutations and rare SNPs were predicted in genomes of three cancer cell lines （U2OS, U251 and A431）, which were supported by expression analyses. After filtering, tractable numbers of potentially deleterious variants are predicted by the software, suitable for further laboratory investigation. In these cell lines, novel functional variants comprised 6-17 inactivating mutations, 1 5 leaky mutations and 6-13 cryptic splicing mutations. Predicted effects were validated by RNA-seq analysis of the three aforementioned cancer cell lines, and expression microarray analysis of SNPs in HapMap cell lines.

关键词： Mutation mRNA splicing Information theory Next-generation sequencing Genome interpretation

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Liver-adipose tissue crosstalk in alcohol-associated liver disease: The role of mTOR

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Liver Research 2022年第4期6卷 227-237页

作者： Yssa Rodriguez Jack Dunfield tyson Roderique Hong-Min Ni Department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKSUSA

Background:Alcohol-associated liver disease(ALD)is a major chronic liver disease around the world without successful *** alcoholic hepatitis is one of the most severe forms of ALD with high mortality,which is often associated with binge *** drinking dysregulates lipid metabolism,increases adipose tissue lipolysis,and induces liver steatosis and adipose tissue *** ev-idence implicates that crosstalk of liver and adipose tissue in the pathogenesis of *** target of rapamycin(mTOR)is a phosphatidylinositol 3-kinase(PI3K)-like serine/threonine protein kinase that regulates lipid metabolism,cell proliferation and ***,the role of mTOR in regulating adipose-liver crosstalk in binge drinking-induced organ damage remains ***:We generated liver-specific and adipocyte-specific regulatory-associated protein of mTOR(Rptor)knockout(Rptor LKO and Rptor AKO)as well as Mtor knockout(Mtor LKO and Mtor AKO)mice,by crossing Rptor flox and Mtor flox mice with albumin Cre or adiponectin Cre mice,*** addition,we generated liver and adipocyte double deletion of Rptor or Mtor(Mtor LAKO and Rptor LAKO)*** knockout mice with their matched wild-type littermates(Rptor WT and Mtor WT)were subjected to acute gavage of 7 g/kg ***:Mice with adipocyte deletion of Rptor or Mtor developed hepatomegaly and adipose tissue *** gavage increased liver injury,hepatic steatosis and inflammation in mouse livers as demonstrated by elevated serum alanine aminotransferase activities,increased hepatic levels of tri-glyceride and increased hepatic numbers of CD68 positive macrophages in mouse livers after alcohol *** injury was further exacerbated by deletion of adipocyte Rptor or *** adipokine array analysis revealed that increased levels of pro-inflammatory cytokines IL-6 and TNF a as well as chemokine MCP-1 following acute alcohol gavage in wild-type mice,which were further incr

关键词： Alcohol-associated liver disease(ALD) Liver injury Mechanistic target of rapamycin(mTOR) Adipose atrophy Adipokine Liver-adipose tissue crosstalk

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Cotton stomatal closure under varying temperature and vapor pressure deficit,correlation with the hydraulic conductance trait

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Journal of Cotton Research 2022年第3期5卷 217-227页

作者： WEDEGAERTNER Kurt SHEKOOFA Avat PURDOM Sam WALTERS Kellie DUNCAN Lori RAPER tyson B Department of Plant Sciences University of Tennessee2505 E.J.Chapman Dr.KnoxvilleTN 37996USA Department of Biosystems Engineering and Soil Science University of Tennessee2506 EJ Chapman DriveKnoxvilleTN 37996USA.

Background:Cotton(Gossypium hirsutum L.)is often grown in locations characterized by high atmospheric evaporative *** has been hypothesized that plants which resist hydraulic flow under this condition will limit water use and conserve soil ***,in a series of controlled environment experiments ten cotton cultivars were exposed to two different temperature and vapor pressure deficit(VPD)conditions(i.e.,38℃,>3 kPa and 32℃,1∼1.5 kPa)as well as a progressive soil ***,individual differences in shoot hydraulic conductance(K_(shoot))was measured using a hydraulic conductance flow meter(HCFM).Physiological parameters were reported included leaf area,dry leaf weight,stomatal conductance(g_(s)),and water use efficiency coefficient(WUE_(k)).Results:Differences were observed in K_(shoot) among cultivars under the 38℃,>3 kPa but not the 32℃,1∼1.5 kPa *** the 38℃,>3 kPa environment,correlations were found between K_(shoot),stomatal conductance(gs),VPD breakpoint,WUEk,total leaf area,dry leaf weight,fraction transpirable soil water(FTSW)threshold,and slope of TR decline after FTSW ***:Results show that the ability of some cotton cultivars to restrict water loss under high evaporative demand through early stomatal closure is associated with the cultivars’K_(shoot).The K_(shoot) is influential in the limitation of TR trait under high temperature and VPD.

关键词： Cotton FTSW threshold Shoot hydraulic conductance Temperature Transpiration rate VPD

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Evaluation of the Coordinated Approach to Child Health (CATCH) Program in Third through Fifth Graders in Northern Illinois

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Health 2023年第11期15卷 1191-1201页

作者： Paulina Karecka tyson Copeland Henna Muzaffar School of Health Studies Northern Illinois University DeKalb IL USA College of Health & Human Sciences Northern Illinois University DeKalb IL USA

Background: The Coordinated Approach to Child Health (CATCH) is a school-based health education program, grounded in Social Cognitive Theory (SCT), and designed to improve dietary habits and increase physical activity among children and adolescents. The objective of this study was to evaluate the effectiveness of CATCH program, delivered by dietetic interns and Northern Illinois University (NIU) students, to 3rd-5th graders in Northern Illinois, in increasing their nutrition knowledge and healthy choices behavior. Methods: In total, 167 elementary school children in grades 3 - 5 in Northern Illinois participated in a non-experimental program evaluation study. We delivered 6 CATCH lessons throughout the academic year to five elementary schools. Lessons were focused on “Go, Slow, and Whoa” food categories to help children understand healthier food choices. Validated questionnaires from the CATCH Global Foundation were administered in classrooms and online, pre/post intervention, to assess nutritional knowledge and healthy choices. Results: Children in third through fifth grades significantly increased their knowledge about nutrient dense foods, p th and 5th graders improved their ability to make healthier choices. Conducting evaluations of health promotion programs is imperative to determine the impact of the program, as well as to explore possible improvements in content and delivery for future imp

关键词： Schools Nutrition Knowledge Healthy Choices Social Cognitive Theory

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Deregulation of splicing factors and breast cancer development

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分子细胞生物学报:英文版 2015年第5期7卷 388-401页

作者： Marco Silipo Hannah Gautrey Alison tyson-Capper Institute of Cellular Medicine Faculty of Medical SciencesNewcastle UniversityNewcastle upon Tyne NE24HHUK

It is well known that many genes implicated in the development and progression of breast cancer undergo aberrant alternative splicing events to produce *** changes in alternative splicingcan arise frommutations or single-nucleotide polymorphisms(SNPs)within the DNA sequences of cancer-related genes,which can strongly affect the activity of splicing factors and influence the splice site ***,it is important to note that absence of mutations is not sufficient to prevent misleading choices in splice site *** is nowincreasing evidence to demonstrate that the expression profile of ten splicing factors(including SRs and hnRNPs)and eight RNA-binding proteins changes in breast cancer cells compared with normal *** modifications strongly influence the alternative splicing pattern of many cancer-related genes despite the absence of any detrimental mutations within their DNA ***,a comprehensive assessment of the splicing factor status in breast cancer is important to provide insights into the mechanisms that lead to breast cancer development and *** most studies focus on mutations that affect alternative splicing in cancer-related genes,this review focuses on splicing factors and RNA-binding proteins that are themselves deregulated in breast cancer and implicated in cancer-related alternative splicing events.

关键词： alternative splicing splicing factors RNA-binding proteins breast cancer

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Modeling of a long sand-pack for heavy crude oil through depletion tests utilizing methane gas

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Petroleum 2021年第2期7卷 188-198页

作者： Bashir Busahmin Rama Rao Karri Stephen tyson Morteza Jami Petroleum&Chemical Engineering Universiti Teknologi BruneiBrunei Darussalam

With the enormous increase in the demand for crude oil,and decrease in the resources of conventional oil reservoirs,there is a great need to understand heavy or foamy oil-gas drive mechanism to maximize the oil and gas *** analyze the real movement of non-viscous heavy oil flow,the characteristic features of the oil-gas mixture has to be estimated to forecast the future potential supply from a heavy oil *** important question in heavy oil flow under solution gas drive is whether the behaviour of depletion tests can be simulated to model the heavy oil flow *** main objective of this research is to develop a reliable numerical model for modelling heavy oil flow calibrated with controlled solution gas drive experiments,and that makes a novelty in this *** this paper,CMG-STARS model which is capable of simulating solution gas drive tests that matched the research *** heavy oil recovery model can determine the relative permeability curves for oil and gas in the dualphase system using Corey’s *** a depletion rate of 0.0418 psi/min,the maximum cumulative oil and gas production was observed to be 13,000 cm^(3)and 8500 cm^(3),*** results from the bottom hole pressure and the block pressure simulation runs indicate that the fluid properties such as surface tension plays a significant role in the gas bubble *** results are promising,and helps to understand the complex behaviour of heavy oil reservoirs and thus can improve heavy oil recovery.

关键词： Depletion rate Simulation Gas fluid dual-phase Sand-pack Heavy oil reservoir Methane gas

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Recent, development in low-constraint fracture toughness testing for structural integrity assessment of pipelines

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Frontiers of Mechanical Engineering 2018年第4期13卷 546-553页

作者： Jidong KANG James A. GIANETTO William R. tyson CanmetMATERIALS Hamilton L8P 0A5 Canada

Fracture toughness measurement is an integral part of structural integrity assessment of pipelines. Traditionally, a single-edge-notched bend （SE（B）） specimen with a deep crack is recommended in many existing pipeline structural integrity assessment procedures. Such a test provides high constraint and therefore conservative fracture toughness results. However, for girth welds in service, defects are usually subjected to primarily tensile loading where the constraint is usually much lower than in the three-point bend case. Moreover, there is increasing use of strain-based design of pipelines that allows applied strains above yield. Low-constraint toughness tests represent more realistic loading conditions for girth weld defects, and the corresponding increased toughness can minimize unnecessary conservatism in assessments. In this review, we present recent developments in low-constraint fracture toughness testing, specifically using single-edge- notched tension specimens, SENT or SE（T）. We focus our review on the test procedure development and automation, round-robin test results and some common concerns such as the effect of crack tip, crack size monitoring techniques, and testing at low temperatures. Examples are also given of the integration of fracture toughness data from SE（T） tests into structural integrity assessment.

关键词： fracture toughness constraint effect singleedge-notched tension test pipeline structural integrity assessment

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Allometric relationships between primary size measures and sapwood area for six common tree species in snow-dependent ecosystems in the Southwest United States

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Journal of Forestry Research 2020年第6期31卷 2171-2180页

作者： Bhaskar Mitra Shirley A.Papuga MRoss Alexander tyson Lee Swetnam Nate Abramson School of Natural Resources and Environment University of ArizonaTucsonAZ 85721USA Department of Geology Wayne State UniversityDetroitMI 48202USA Laboratory of Tree-Ring Research University of ArizonaTucsonAZ 85721USA BIO5 Institute University of ArizonaTucsonAZ 85721USA Department of Hydrology and Water Resources University of ArizonaTucsonAZ 85721USA

High-elevation,snow-dependent,semiarid ecosystems across southwestern United States are expected to be vulnerable to climate change,including drought and fi re,with implications for various aspects of the water *** that end,much less is known about the dynamics of transpiration,an important component of the water cycle across this *** the individual-tree scale,transpiration is estimated by scaling mean sap fl ux density by the hydroactive sapwood area(SA).SA also remains a key factor in eff ectively scaling individual tree water-use to stand *** across large spatial scales is normally established by relating SA of a few trees to primary size measures,e.g.,diameter at breast height(DBH),tree height(H),or canopy diameter(CD).Considering the importance of SA in scaling transpiration,the primary objective of this study was therefore to establish six species-specifi c(aspen,maple,white fi r,ponderosa pine,Douglas fi r,Englemann spruce)allometric relationships between SA and three primary size measures(DBH,CD,or H)across two high-elevation,snow-dependent,semiarid ecosystems in New Mexico and *** on multiple statistical criteria(coeffi cient of determination,index of agreement,Nash–Sutcliff e effi-ciency)and ease of measurement in the forest,we identifi ed DBH as the primary independent variable for estimating SA across all *** on group regression analysis,we found allometric relationships to be signifi cantly(p<0.05)diff erent for the same species(ponderosa pine,Douglas-fi r)across diff erent ***,our allometric relationships provide a valuable database for estimating transpiration at diff erent spatial scales from sap fl ow data in some of our most vulnerable ecosystems.

关键词： Allometry Diameter at breast height Mountain ecosystem Sapwood area Southwestern USA

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Transformer2 proteins protect breast cancer cells from accumulating replication stress by ensuring productive splicing of checkpoint kinase 1

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Frontiers of Chemical Science and Engineering 2016年第2期10卷 186-195页

作者： Andrew Best Katherine James Gerald Hysenaj Alison tyson-Capper David J. Elliott Institute of Genetic Medicine Newcastle University Newcastle NE1 3BZ UK Interdisciplinary Computing and Complex BioSystems Research Group and Centre for Bacterial Cell Biology Newcastle University Newcastle NE1 3BZ UK Institute for Cellular Medicine Newcastle University Newcastle NE2 4HH UK

Increased expression levels of the RNA splicing regulator Transformer2fl （abbreviated Tra2fl） have been reported in several types of cancer. Recent work has revealed an intimate cross-regulation between Tra2fl and the highly similar Tra2a protein in human breast cancer cells, though these two proteins are encoded by separate genes created by a gene duplication that occurred over 500 million years ago. This cross-regulation involves splicing control of a special class of exons, called poison exons. Down-regulation of Tra2fl reduces splicing inclu- sion of a poison exon in the mRNA encoding Tra2a, thereby up-regulating Tra2a protein expression. This buffers any splicing changes that might be caused by individual depletion of Tra2fl alone. Discovery of this cross-regulation pathway, and its by-pass by joint deple- tion of both human Tra2 proteins, revealed Tra2 proteins are essential for breast cancer cell viability, and led to the identification of important targets for splicing control. These exons include a critical exon within the checkpoint kinase 1 （CHK1） gene that plays a crucial function in the protection of cancer cells from replication stress. Breast cancer cells depleted for Tra2 proteins have reduced CHK1 protein levels and accumulate DNA damage. These data suggest Tra2 proteins and/or their splicing targets as possible cancer drug targets.

关键词： RNA splicing gene expression breast cancer,DNA damage CHK1

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EFFECT OF RARE EARTH ADDITIONS ON FRACTURE PROPERTIES OF 2.25Cr-1Mo STEELS

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Acta Metallurgica Sinica(English Letters) 1989年第1期2卷 63-68页

作者： W.R.tyson B.FAUCHER Physical Metallurgy Research Laboratories CANMETOttawaCanada

The inclusion parameters,fracture surface morphology and void growth characteristics of ten- sile and fracture toughness specimens of 2.25Cr-1Mo steels with and without rare-earth (RE)additions have been investigated by quantitative metaltography(QTM),scanning elec- tron microscopy(SEM)and energy dispersive spectroscopy(EDS).There is a substantially higher density of inclusions in the RE-treated steel,which has lower values of fracture proper- ties including critical values of COD and J integral(δ_c and J_(IC)),fracture strain(ε_f) and Charpy V-notch energy(CVN).The fracture surface of the RE-treated steel comprises equiaxed dimples of diameters comparable with its inclusion spacing,whereas for the non-RE-treated steels,a wide range of dimple sizes is found with average diameter much smaller than the corresponding inclusion *** investigation indicates that the lower values of fracture properties for the steel with RE at room temperature may be ascribed to its large content of RE-containing inclusions.

关键词： Cr-Mo steel fracture properties inclusion parameters fracture morphology

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