Sample records for genetic alterations affecting

  1. Functional synergies yet distinct modulators affected by genetic alterations in common human cancers.

    PubMed

    Bessarabova, Marina; Pustovalova, Olga; Shi, Weiwei; Serebriyskaya, Tatiana; Ishkin, Alex; Polyak, Kornelia; Velculescu, Victor E; Nikolskaya, Tatiana; Nikolsky, Yuri

    2011-05-15

    An important general concern in cancer research is how diverse genetic alterations and regulatory pathways can produce common signaling outcomes. In this study, we report the construction of cancer models that combine unique regulation and common signaling. We compared and functionally analyzed sets of genetic alterations, including somatic sequence mutations and copy number changes, in breast, colon, and pancreatic cancer and glioblastoma that had been determined previously by global exon sequencing and SNP (single nucleotide polymorphism) array analyses in multiple patients. The genes affected by the different types of alterations were mostly unique in each cancer type, affected different pathways, and were connected with different transcription factors, ligands, and receptors. In our model, we show that distinct amplifications, deletions, and sequence alterations in each cancer resulted in common signaling pathways and transcription regulation. In functional clustering, the impact of the type of alteration was more pronounced than the impact of the kind of cancer. Several pathways such as TGF-?/SMAD signaling and PI3K (phosphoinositide 3-kinase) signaling were defined as synergistic (affected by different alterations in all four cancer types). Despite large differences at the genetic level, all data sets interacted with a common group of 65 "universal cancer genes" (UCG) comprising a concise network focused on proliferation/apoptosis balance and angiogenesis. Using unique nodal regulators ("overconnected" genes), UCGs, and synergistic pathways, the cancer models that we built could combine common signaling with unique regulation. Our findings provide a novel integrated perspective on the complex signaling and regulatory networks that underlie common human cancers. PMID:21398405

  2. Environmentally alterable additive genetic effects Root Gorelick*

    E-print Network

    Gorelick, Root

    Environmentally alterable additive genetic effects Root Gorelick* School of Life Sciences, Arizona environmentally alterable additive genetic variance confounds prediction of evolutionary trajectories, but (1 phenotypically plastic than animals. Conclusion: Environmentally alterable additive genetic effects place

  3. Human genetic variation altering anthrax toxin sensitivity

    E-print Network

    Tang, Hua

    Human genetic variation altering anthrax toxin sensitivity Mikhail Martchenkoa , Sophie I for review October 31, 2011) The outcome of exposure to infectious microbes or their toxins is influenced affecting capillary morphogenesis gene 2 (CMG2), which encodes a host membrane protein exploited by anthrax

  4. How much do genetic covariances alter the rate of adaptation?

    E-print Network

    Stinchcombe, John

    How much do genetic covariances alter the rate of adaptation? Aneil F. Agrawal1,* and John R Genetically correlated traits do not evolve independently, and the covariances between traits affect the rate at which a population adapts to a specified selection regime. To measure the impact of genetic covariances

  5. Comprehensive genomic analysis of rhabdomyosarcoma reveals a landscape of alterations affecting a common genetic axis in fusion-positive and fusion-negative tumors

    PubMed Central

    Shern, Jack F.; Chen, Li; Chmielecki, Juliann; Wei, Jun S.; Patidar, Rajesh; Rosenberg, Mara; Ambrogio, Lauren; Auclair, Daniel; Wang, Jianjun; Song, Young K.; Tolman, Catherine; Hurd, Laura; Liao, Hongling; Zhang, Shile; Bogen, Dominik; Brohl, Andrew S.; Sindiri, Sivasish; Catchpoole, Daniel; Badgett, Thomas; Getz, Gad; Mora, Jaume; Anderson, James R.; Skapek, Stephen X.; Barr, Frederic G.; Meyerson, Matthew; Hawkins, Douglas S.; Khan, Javed

    2015-01-01

    Despite gains in survival, outcomes for patients with metastatic or recurrent rhabdomyosarcoma (RMS) remain dismal. In a collaboration between the National Cancer Institute, Children's Oncology Group, and Broad Institute, we performed whole-genome, whole-exome and transcriptome sequencing to characterize the landscape of somatic alterations in 147 tumor/normal pairs. Two genotypes are evident in RMS tumors; those characterized by the PAX3 or PAX7 fusion and those that lack these fusions but harbor mutations in key signaling pathways. The overall burden of somatic mutations in RMS is relatively low, especially in tumors that harbor a PAX3/7 gene fusion. In addition to previously reported mutations of NRAS, KRAS, HRAS, FGFR4, PIK3CA, CTNNB1, we found novel recurrent mutations in FBXW7, and BCOR providing potential new avenues for therapeutic intervention. Furthermore, alteration of the receptor tyrosine kinase/RAS/PIK3CA axis affects 93% of cases providing a framework for genomics directed therapies that might improve outcomes for RMS patients. PMID:24436047

  6. Molecular and genetic analyses of the Caenorhabditis elegans dpy-2 and dpy-10 collagen genes: a variety of molecular alterations affect organismal morphology.

    PubMed

    Levy, A D; Yang, J; Kramer, J M

    1993-08-01

    We have identified and cloned the Caenorhabditis elegans dpy-2 and dpy-10 genes and determined that they encode collagens. Genetic data suggested that these genes are important in morphogenesis and possibly other developmental events. These data include the morphologic phenotypes exhibited by mutants, unusual genetic interactions with the sqt-1 collagen gene, and suppression of mutations in the glp-1 and mup-1 genes. The proximity of the dpy-2 and dpy-10 genes (3.5 kilobase) and the structural similarity of their encoded proteins (41% amino acid identity) indicate that dpy-2 and dpy-10 are the result of a gene duplication event. The genes do not, however, appear to be functionally redundant, because a dpy-10 null mutant is not rescued by the dpy-2 gene. In addition, full complementation between dpy-2 and dpy-10 can be demonstrated with all recessive alleles tested in trans. Sequence analysis of several mutant alleles of each gene was performed to determine the nature of the molecular defects that can cause the morphologic phenotypes. Glycine substitutions within the Gly-X-Y portion of the collagens can result in dumpy (Dpy), dumpy, left roller (DLRol), or temperature-sensitive DLRol phenotypes. dpy-10(cn64), a dominant temperature-sensitive DLRol allele, creates an Arg-to-Cys substitution in the amino non-Gly-X-Y portion of the protein. Three dpy-10 alleles contain Tc1 insertions in the coding region of the gene. dpy-10(cg36) (DRLol) creates a nonsense codon near the end of the Gly-X-Y region. The nature of this mutation, combined with genetic data, indicates that DLRol is the null phenotype of dpy-10. The Dpy phenotype results from reduced function of the dpy-10 collagen gene. Our results indicate that a variety of molecular defects in these collagens can result in severe morphologic changes in C. elegans. PMID:8241567

  7. Molecular and genetic analyses of the Caenorhabditis elegans dpy-2 and dpy-10 collagen genes: a variety of molecular alterations affect organismal morphology.

    PubMed Central

    Levy, A D; Yang, J; Kramer, J M

    1993-01-01

    We have identified and cloned the Caenorhabditis elegans dpy-2 and dpy-10 genes and determined that they encode collagens. Genetic data suggested that these genes are important in morphogenesis and possibly other developmental events. These data include the morphologic phenotypes exhibited by mutants, unusual genetic interactions with the sqt-1 collagen gene, and suppression of mutations in the glp-1 and mup-1 genes. The proximity of the dpy-2 and dpy-10 genes (3.5 kilobase) and the structural similarity of their encoded proteins (41% amino acid identity) indicate that dpy-2 and dpy-10 are the result of a gene duplication event. The genes do not, however, appear to be functionally redundant, because a dpy-10 null mutant is not rescued by the dpy-2 gene. In addition, full complementation between dpy-2 and dpy-10 can be demonstrated with all recessive alleles tested in trans. Sequence analysis of several mutant alleles of each gene was performed to determine the nature of the molecular defects that can cause the morphologic phenotypes. Glycine substitutions within the Gly-X-Y portion of the collagens can result in dumpy (Dpy), dumpy, left roller (DLRol), or temperature-sensitive DLRol phenotypes. dpy-10(cn64), a dominant temperature-sensitive DLRol allele, creates an Arg-to-Cys substitution in the amino non-Gly-X-Y portion of the protein. Three dpy-10 alleles contain Tc1 insertions in the coding region of the gene. dpy-10(cg36) (DRLol) creates a nonsense codon near the end of the Gly-X-Y region. The nature of this mutation, combined with genetic data, indicates that DLRol is the null phenotype of dpy-10. The Dpy phenotype results from reduced function of the dpy-10 collagen gene. Our results indicate that a variety of molecular defects in these collagens can result in severe morphologic changes in C. elegans. Images PMID:8241567

  8. PRODUCTION OF EXTRACELLULAR NUCLEIC ACIDS BY GENETICALLY ALTERED BACTERIA IN AQUATIC-ENVIRONMENT MICROCOSMS

    EPA Science Inventory

    Factors which affect the production of extracellular DNA by genetically altered strains of Escherichia coli, Pseudomonas aeruginosa, pseudomonas cepacia, and Bradyrhizobium japonicum in aquatic environments were investigated. he presence or absence of the ambient microbial commun...

  9. Low temperature alteration processes affecting ultramafic bodies

    USGS Publications Warehouse

    Nesbitt, H.W.; Bricker, O.P.

    1978-01-01

    At low temperatures, in the presence of an aqueous solution, olivine and orthopyroxene are not stable relative to the hydrous phases brucite, serpentine and talc. Alteration of dunite and peridotite to serpentine or steatite bodies must therefore proceed via non-equilibrium processes. The compositions of natural solutions emanating from dunites and peridotites demonstrate that the dissolution of forsterite and/or enstatite is rapid compared with the precipitation of the hydrous phases; consequently, dissolution of anhydrous minerals controls the chemistry of such solutions. In the presence of an aqueous phase, precipitation of hydrous minerals is the rate-controlling step. Brucite-bearing and -deficient serpentinites alter at low temperature by non-equilibrium processes, as evidenced by the composition of natural solutions from these bodies. The solutions approach equilibrium with the least stable hydrous phase and, as a consequence, are supersaturated with other hydrous phases. Dissolution of the least stable phase is rapid compared to precipitation of other phases, so that the dissolving mineral controls the solution chemistry. Non-equilibrium alteration of anhydrous ultramafic bodies continues until at least one anhydrous phase equilibrates with brucite, chrysotile or talc. The lowest temperature (at a given pressure) at which this happens is defined by the reaction: 3H2O + 2Mg2SiO4 ??? Mg3Si2O5(OH)4 + Mg(OH)2 (Johannes, 1968, Contrib. Mineral. Petrol. 19, 309-315) so that non-equilibrium alteration may occur well into greenschist facies metamorphic conditions. ?? 1978.

  10. Genetic Programming: Parametric Analysis of Structure Altering Mutation Techniques

    E-print Network

    Fernandez, Thomas

    Genetic Programming: Parametric Analysis of Structure Altering Mutation Techniques Alan Piszcz;cally parameters controlling mutation, and performance is non-linear in genetic programs. Genetic pro. The hypothesized nonlinear behavior of genetic programming creates diculty in selecting parameter values for many

  11. Elevated COâ alters genetic composition in plant populations: Parallel results from two model systems

    Microsoft Academic Search

    F. A. Bazzaz; M. Jasienski; S. C. Thomas

    1995-01-01

    Rising atmospheric COâ concentrations, in addition to affecting global climate and carbon balance, may also have a direct impact on genetic compositions of plant populations by altering microevolutionary processes. In two model systems, an annual plant and a temperate forest tree, performance under elevated COâ was both density-dependent and strongly genotype-specific. In dense stands, pronounced shifts in genetic composition occurred

  12. Raman spectroscopic study of a genetically altered kidney cell

    NASA Astrophysics Data System (ADS)

    Joshi, Joel; Garcia, Francisco; Centeno, Silvia P.; Joshi, N. V.

    2008-02-01

    A Raman spectroscopic investigation of a genetically altered Human Embryonic Kidney Cell (HEK293) along with a pathologically normal cell has been carried out by a conventional method. The genetic alteration was carried out with a standard protocol by using a Green Fluorescence Protein (GFP). Raman spectra show that there are dramatic differences between the spectrum obtained from a genetically altered cell and that obtained from a pathologically normal cell. The former shows three broad bands; meanwhile the latter shows several sharp peaks corresponding to the ring vibrational modes of Phen, GFP and DNA. The present analysis provides an indication that the force field near Phen located at 64, 65 and 66 was altered during the genetic transformation. The Raman spectrum could be a direct experimental evidence for substantial modifications triggered due to the expression of specific genes.

  13. Genetic alterations of multiple tumor suppressors and oncogenes in the carcinogenesis and progression of lung cancer

    Microsoft Academic Search

    Hirotaka Osada; Takashi Takahashi

    2002-01-01

    Lung cancer has become the leading cause of cancer death in many economically well-developed countries. Recent molecular biological studies have revealed that overt lung cancers frequently develop through sequential morphological steps, with the accumulation of multiple genetic and epigenetic alterations affecting both tumor suppressor genes and dominant oncogenes. Cell cycle progression needs to be properly regulated, while cells have built-in

  14. Genetic alterations in syndromes with oral manifestations.

    PubMed

    Anuthama, Krishnamurthy; Prasad, Harikrishnan; Ramani, Pratibha; Premkumar, Priya; Natesan, Anuja; Sherlin, Herald J

    2013-11-01

    Ever since Gregor Johan Mendel proposed the law of inheritance, genetics has transcended the field of health and has entered all walks of life in its application. Thus, the gene is the pivoting factor for all happenings revolving around it. Knowledge of gene mapping in various diseases would be a valuable tool in prenatally diagnosing the condition and averting the future disability and stigma for the posterity. This article includes an array of genetically determined conditions in patients seen at our college out-patient department with complete manifestation, partial manifestation and array of manifestations not fitting into a particular syndrome. PMID:24379857

  15. Genetic alterations in syndromes with oral manifestations

    PubMed Central

    Anuthama, Krishnamurthy; Prasad, Harikrishnan; Ramani, Pratibha; Premkumar, Priya; Natesan, Anuja; Sherlin, Herald J.

    2013-01-01

    Ever since Gregor Johan Mendel proposed the law of inheritance, genetics has transcended the field of health and has entered all walks of life in its application. Thus, the gene is the pivoting factor for all happenings revolving around it. Knowledge of gene mapping in various diseases would be a valuable tool in prenatally diagnosing the condition and averting the future disability and stigma for the posterity. This article includes an array of genetically determined conditions in patients seen at our college out-patient department with complete manifestation, partial manifestation and array of manifestations not fitting into a particular syndrome. PMID:24379857

  16. The relevance of genetically altered mouse models of human disease.

    PubMed

    Bhogal, Nirmala; Combes, Robert

    2006-08-01

    The impetus to develop useful models of human disease and toxicity has resulted in a number of large-scale mouse mutagenesis programmes. This, in turn, has stimulated considerable concern regarding the scientific validity and welfare of genetically altered mice, and the large numbers of mice that are required by such programmes. In this paper, the scientific advantages and limitations of genetically altered mice as models of several human diseases are discussed. We conclude that, while the use of some such mouse models has contributed considerably to an understanding of human disease and toxicity, other genetically altered mouse models have limited scientific relevance, and fewer have positively contributed to the development of novel human medicines. Suggestions for improving this unsatisfactory situation are made. PMID:16945009

  17. Calcium Channel Alterations in Genetic Hypertension

    Microsoft Academic Search

    Kent Hermsmeyer; Nancy J. Rusch

    2010-01-01

    We proposed earlier that voltage-dependent calcium (Ca 2+ ) current is altered in single azygos venous cells from Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). In this study, the effects of different intracellular concentrations of ethylene glycol-bis- N,A',JV',A'Vtetraacetic acid (EGTA) on Ca 2+ currents were investigated. Vascular muscle cells from SHR and WKY rats were equilibrated with pipette solution

  18. Distinct Genetic Alterations in Colorectal Cancer

    PubMed Central

    Ashktorab, Hassan; Schäffer, Alejandro A.; Daremipouran, Mohammad; Smoot, Duane T.; Lee, Edward; Brim, Hassan

    2010-01-01

    Background Colon cancer (CRC) development often includes chromosomal instability (CIN) leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs) and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. Methodology/Principal Findings We applied genome-wide array comparative genome hybridization (aCGH) using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes). There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. Conclusions/Significance Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs. PMID:20126641

  19. Novel ALPL genetic alteration associated with an odontohypophosphatasia phenotype

    PubMed Central

    Martins, Luciane; Rodrigues, Thaisângela L.; Ribeiro, Mariana Martins; Saito, Miki Taketomi; Giorgetti, Ana Paula Oliveira; Casati, Márcio Z; Sallum, Enilson A; Foster, Brian L.; Somerman, Martha J.; Nociti, Francisco H.

    2013-01-01

    Hypophosphatasia (HPP) is an inherited disorder of mineral metabolism caused by mutations in ALPL, encoding tissue non-specific alkaline phosphatase (TNAP). Here, we report the molecular findings from monozygotic twins, clinically diagnosed with tooth-specific odontohypophosphatasia (odonto-HPP). Sequencing of ALPL identified two genetic alterations in the probands, including a heterozygous missense mutation c.454C>T, leading to change of arginine 152 to cysteine (p.R152C), and a novel heterozygous gene deletion c.1318_1320delAAC, leading to the loss of an asparagine residue at codon 440 (p.N440del). Clinical identification of low serum TNAP activity, dental abnormalities, and pedigree data strongly suggest a genotype-phenotype correlation between p.N440del and odonto-HPP in this family. Computational analysis of the p.N440del protein structure revealed an alteration in tertiary structure affecting the collagen-binding site (loop 422-452), which could potentially impair the mineralization process. Nevertheless, the Probands (compound heterozygous: p.[N440del];[R152C]) feature early-onset and severe odonto-HPP phenotype, whereas the father (p.[N440del];[=]) has only moderate symptoms, suggesting p.R152C may contribute or predispose to a more severe dental phenotype in combination with the deletion. These results assist in defining the genotype-phenotype associations for odonto-HPP, and further identify the collagen-binding site as a region of potential structural importance for TNAP function in the biomineralization. PMID:23791648

  20. Fuel properties of oil from genetically altered Cuphea viscosissima

    Microsoft Academic Search

    Daniel P. Geller; John W. Goodrum; Steven J. Knapp

    1999-01-01

    A genetically altered plant strain (Cuphea viscosissima VS-320) was identified which produces an oil with elevated levels of medium- and short-chain triglycerides. Previous studies have suggested that such an oil may be appropriate for use as a substitute for diesel fuel without chemical conversion of component triglycerides to methyl esters. This oil is also of interest for other industrial applications.

  1. Genetic and epigenetic alterations in differentiated thyroid carcinoma

    PubMed Central

    Brehar, AC; Brehar, FM; Bulgar, AC; Dumitrache, C

    2013-01-01

    Abstract Differentiated thyroid carcinoma (DTC) has a favorable prognosis, but it is important to identify those patients who have a high risk of progressive disease and DTC-related death at the time of diagnosis. Analyzing genetic and epigenetic alterations in thyroid cancer may play a role in tumor diagnosis, prognostic and therapeutic strategies. PMID:24868250

  2. Phenotypic and Evolutionary Consequences of Social Behaviours: Interactions among Individuals Affect Direct Genetic Effects

    PubMed Central

    Trubenová, Barbora; Hager, Reinmar

    2012-01-01

    Traditional quantitative genetics assumes that an individual's phenotype is determined by both genetic and environmental factors. For many animals, part of the environment is social and provided by parents and other interacting partners. When expression of genes in social partners affects trait expression in a focal individual, indirect genetic effects occur. In this study, we explore the effects of indirect genetic effects on the magnitude and range of phenotypic values in a focal individual in a multi-member model analyzing three possible classes of interactions between individuals. We show that social interactions may not only cause indirect genetic effects but can also modify direct genetic effects. Furthermore, we demonstrate that both direct and indirect genetic effects substantially alter the range of phenotypic values, particularly when a focal trait can influence its own expression via interactions with traits in other individuals. We derive a function predicting the relative importance of direct versus indirect genetic effects. Our model reveals that both direct and indirect genetic effects can depend to a large extent on both group size and interaction strength, altering group mean phenotype and variance. This may lead to scenarios where between group variation is much higher than within group variation despite similar underlying genetic properties, potentially affecting the level of selection. Our analysis highlights key properties of indirect genetic effects with important consequences for trait evolution, the level of selection and potentially speciation. PMID:23226195

  3. ORIGINAL PAPER Biotic and abiotic factors affecting the genetic structure

    E-print Network

    ORIGINAL PAPER Biotic and abiotic factors affecting the genetic structure and diversity. To manage the remaining pop- ulations effectively, information regarding how butternut's population genetic structure is affected by environmental and historical factors is needed. In this study, we assessed genetic

  4. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia

    Cancer.gov

    Activated kinase-like B-ALL does not harbor the BCR-ABL translocation, but it exhibits a very similar gene expression profile. The genetic alterations discovered in this study, which were validated by recurrence testing in a larger cohort, specifically affect cytokine receptors and regulators of kinase signaling. Moreover, several of the novel or rare alterations identified in this study induced cancerous phenotypes in cell lines and mouse xenograft models, and demonstrated sensitivity to tyrosine kinase inhibitors that are already used in the clinic.

  5. High-Resolution Genome-Wide Mapping of Genetic Alterations in Human Glial Brain Tumors

    E-print Network

    Ford, James

    High-Resolution Genome-Wide Mapping of Genetic Alterations in Human Glial Brain Tumors Markus and showed that gliomas can be clustered into distinct genetic subgroups. A subset of detected alterations are key genetic events in gliomagenesis. Recurrent genomic regions of alteration in copy number, including

  6. Edinburgh Research Explorer Somatic retrotransposition alters the genetic landscape of the

    E-print Network

    MacDonald, Andrew

    Edinburgh Research Explorer Somatic retrotransposition alters the genetic landscape of the human alters the genetic landscape of the human brain' Nature, vol 479, no. 7374, pp. 534-537., 10.1038/nature. 2014 #12;Somatic retrotransposition alters the genetic landscape of the human brain J. Kenneth Baillie1

  7. Altered genetic code in Paramecium mitochondria: Possible evolutionary trends

    Microsoft Academic Search

    Jeffrey J. Seilhamer; Donald J. Cummings

    1982-01-01

    The sequence and presumptive structure of a tRNA trp gene from Paramecium tetraaurelia are given. The gene is located 1,500 bp downstream from the 13S rRNA gene, in about the middle of the genome. Paramecium tRNA trp has a completely normal T?C loop and stem, however its anticodon (UCA) constitutes an alteration in the “universal” genetic code, similar to those

  8. Genetic Alterations in Poorly Differentiated and Undifferentiated Thyroid Carcinomas

    PubMed Central

    Soares, Paula; Lima, Jorge; Preto, Ana; Castro, Patricia; Vinagre, João; Celestino, Ricardo; Couto, Joana P; Prazeres, Hugo; Eloy, Catarina; Máximo, Valdemar; Sobrinho-Simões, M

    2011-01-01

    Thyroid gland presents a wide spectrum of tumours derived from follicular cells that range from well differentiated, papillary and follicular carcinoma (PTC and FTC, respectively), usually carrying a good prognosis, to the clinically aggressive, poorly differentiated (PDTC) and undifferentiated thyroid carcinoma (UTC). It is usually accepted that PDTC and UTC occur either de novo or progress from a pre-existing well differentiated carcinoma through a multistep process of genetic and epigenetic changes that lead to clonal expansion and neoplastic development. Mutations and epigenetic alterations in PDTC and UTC are far from being totally clarified. Assuming that PDTC and UTC may derive from well differentiated thyroid carcinomas (WDTC), it is expected that some PDTC and UTC would harbour genetic alterations that are typical of PTC and FTC. This is the case for some molecular markers (BRAF and NRAS) that are present in WDTC, PDTC and UTC. Other genes, namely P53, are almost exclusively detected in less differentiated and undifferentiated thyroid tumours, supporting a diagnosis of PDTC or, much more often, UTC. Thyroid-specific rearrangements RET/PTC and PAX8/PPAR?, on the other hand, are rarely found in PDTC and UTC, suggesting that these genetic alterations do not predispose cells to dedifferentiation. In the present review we have summarized the molecular changes associated with the two most aggressive types of thyroid cancer. PMID:22654560

  9. Genetic alterations in renal cell carcinoma with rhabdoid differentiation.

    PubMed

    Perrino, Carmen M; Hucthagowder, Vishwanathan; Evenson, Michael; Kulkarni, Shashikant; Humphrey, Peter A

    2015-01-01

    Renal cell carcinoma with rhabdoid differentiation (RCC-R) in adult patients is an aggressive variant of renal cancer with no known specific genetic alterations. The aim of this study was to characterize genome-wide genetic aberrations in RCC-R via utilization of high-density single-nucleotide polymorphism (SNP) arrays. We identified 20 cases of RCC-R, which displayed both clear cell renal cell carcinoma and rhabdoid histomorphologic components. DNA was extracted from formalin-fixed, paraffin-embedded tissue (from clear cell renal cell carcinoma and RCC-R areas from each case) and subjected to high-density SNP array assay. Genetic aberrations present in 10% of cases were considered significant. In areas with clear cell histomorphology, gains were most commonly observed in chromosomes 5q (66.7%, 10/15), 7 (46.7%, 7/15), and 8q (46.7%, 7/15); and losses were most commonly identified in chromosomes 14 (60%, 9/15), 8p (46.7%, 7/15), and 22 (46.7%, 7/15). In areas with rhabdoid differentiation, gains were most commonly observed in chromosome 7 (58.8%, 10/17); and losses were most commonly identified in chromosomes 9 (70.6%, 12/17), 14 (58.8%, 10/17), 4 (52.9%, 9/17), and 17p (52.9%, 9/17). Rhabdoid cells shared many chromosomal abnormalities and exhibited a greater number of copy number variations in comparison with coexisting clear cells. Loss of 11p was specific for rhabdoid differentiation, with loss found in 29.4% of rhabdoid components compared with 0% of clear cell areas. The greater number of overall genetic alterations in the rhabdoid cells and the shared genetic background between rhabdoid and clear cell areas suggest genetic evolution of the rhabdoid cells that correlates with histomorphologic progression. PMID:25439741

  10. Homeostasis of Synaptic Transmission in Drosophila with Genetically Altered Nerve Terminal Morphology

    E-print Network

    Stewart, Bryan

    Homeostasis of Synaptic Transmission in Drosophila with Genetically Altered Nerve Terminal through analy- sis of synaptic transmission at Drosophila neuromuscular junc- tions with a genetically for genetic perturbations, thereby maintaining optimal syn- aptic transmission. Key words: synaptic

  11. Safety assessment of genetically modified plants with deliberately altered composition.

    PubMed

    Halford, Nigel G; Hudson, Elizabeth; Gimson, Amy; Weightman, Richard; Shewry, Peter R; Tompkins, Steven

    2014-08-01

    The development and marketing of 'novel' genetically modified (GM) crops in which composition has been deliberately altered poses a challenge to the European Union (EU)'s risk assessment processes, which are based on the concept of substantial equivalence with a non-GM comparator. This article gives some examples of these novel GM crops and summarizes the conclusions of a report that was commissioned by the European Food Safety Authority on how the EU's risk assessment processes could be adapted to enable their safety to be assessed. PMID:24735114

  12. Safety assessment of genetically modified plants with deliberately altered composition

    PubMed Central

    Halford, Nigel G; Hudson, Elizabeth; Gimson, Amy; Weightman, Richard; Shewry, Peter R; Tompkins, Steven

    2014-01-01

    The development and marketing of ‘novel’ genetically modified (GM) crops in which composition has been deliberately altered poses a challenge to the European Union (EU)'s risk assessment processes, which are based on the concept of substantial equivalence with a non-GM comparator. This article gives some examples of these novel GM crops and summarizes the conclusions of a report that was commissioned by the European Food Safety Authority on how the EU's risk assessment processes could be adapted to enable their safety to be assessed. PMID:24735114

  13. Human genetic variation influences vitamin C homeostasis by altering vitamin C transport and antioxidant enzyme function.

    PubMed

    Michels, Alexander J; Hagen, Tory M; Frei, Balz

    2013-01-01

    New evidence for the regulation of vitamin C homeostasis has emerged from several studies of human genetic variation. Polymorphisms in the genes encoding sodium-dependent vitamin C transport proteins are strongly associated with plasma ascorbate levels and likely impact tissue cellular vitamin C status. Furthermore, genetic variants of proteins that suppress oxidative stress or detoxify oxidatively damaged biomolecules, i.e., haptoglobin, glutathione-S-transferases, and possibly manganese superoxide dismutase, affect ascorbate levels in the human body. There also is limited evidence for a role of glucose transport proteins. In this review, we examine the extent of the variation in these genes, their impact on vitamin C status, and their potential role in altering chronic disease risk. We conclude that future epidemiological studies should take into account genetic variation in order to successfully determine the role of vitamin C nutriture or supplementation in human vitamin C status and chronic disease risk. PMID:23642198

  14. Large-scale natural disturbance alters genetic population structure of the sailfin molly, Poecilia latipinna.

    PubMed

    Apodaca, Joseph J; Trexler, Joel C; Jue, Nathaniel K; Schrader, Matthew; Travis, Joseph

    2013-02-01

    Many inferences about contemporary rates of gene flow are based on the assumption that the observed genetic structure among populations is stable. Recent studies have uncovered several cases in which this assumption is tenuous. Most of those studies have focused on the effects that regular environmental fluctuations can have on genetic structure and gene flow patterns. Occasional catastrophic disturbances could also alter either the distribution of habitat or the spatial distribution of organisms in a way that affects population structure. However, evidence of such effects is sparse in the literature because it is difficult to obtain. Hurricanes, in particular, have the potential to exert dramatic effects on population structure of organisms found on islands or coral reefs or in near shore and coastal habitats. Here we draw on a historic genetic data set and new data to suggest that the genetic structure of sailfin molly (Poecilia latipinna) populations in north Florida was altered dramatically by an unusually large and uncommon type of storm surge associated with Hurricane Dennis in 2005. We compare the spatial pattern of genetic variation in these populations after Hurricane Dennis to the patterns described in an earlier study in this same area. We use comparable genetic data from another region of Florida, collected in the same two periods, to estimate the amount of change expected from typical temporal variation in population structure. The comparative natural history of sailfin mollies in these two regions indicates that the change in population structure produced by the storm surge is not the result of many local extinctions with recolonization from a few refugia but emerged from a pattern of mixing and redistribution. PMID:23348779

  15. Molecular reconstruction of a fungal genetic code alteration

    PubMed Central

    Mateus, Denisa D.; Paredes, João A.; Español, Yaiza; Ribas de Pouplana, Lluís; Moura, Gabriela R.; Santos, Manuel A.S.

    2013-01-01

    Fungi of the CTG clade translate the Leu CUG codon as Ser. This genetic code alteration is the only eukaryotic sense-to-sense codon reassignment known to date, is mediated by an ambiguous serine tRNA (tRNACAGSer), exposes unanticipated flexibility of the genetic code and raises major questions about its selection and fixation in this fungal lineage. In particular, the origin of the tRNACAGSer and the evolutionary mechanism of CUG reassignment from Leu to Ser remain poorly understood. In this study, we have traced the origin of the tDNACAGSer gene and studied critical mutations in the tRNACAGSer anticodon-loop that modulated CUG reassignment. Our data show that the tRNACAGSer emerged from insertion of an adenosine in the middle position of the 5?-CGA-3?anticodon of a tRNACGASer ancestor, producing the 5?-CAG-3? anticodon of the tRNACAGSer, without altering its aminoacylation properties. This mutation initiated CUG reassignment while two additional mutations in the anticodon-loop resolved a structural conflict produced by incorporation of the Leu 5?-CAG-3?anticodon in the anticodon-arm of a tRNASer. Expression of the mutant tRNACAGSer in yeast showed that it cannot be expressed at physiological levels and we postulate that such downregulation was essential to maintain Ser misincorporation at sub-lethal levels during the initial stages of CUG reassignment. We demonstrate here that such low level CUG ambiguity is advantageous in specific ecological niches and we propose that misreading tRNAs are targeted for degradation by an unidentified tRNA quality control pathway. PMID:23619021

  16. Landscape location affects genetic variation of Canada lynx (Lynx canadensis).

    PubMed

    Schwartz, M K; Mills, L S; Ortega, Y; Ruggiero, L F; Allendorf, F W

    2003-07-01

    The effect of a population's location on the landscape on genetic variation has been of interest to population genetics for more than half a century. However, most studies do not consider broadscale biogeography when interpreting genetic data. In this study, we propose an operational definition of a peripheral population, and then explore whether peripheral populations of Canada lynx (Lynx canadensis) have less genetic variation than core populations at nine microsatellite loci. We show that peripheral populations of lynx have fewer mean numbers of alleles per population and lower expected heterozygosity. This is surprising, given the lynx's capacity to move long distances, but can be explained by the fact that peripheral populations often have smaller population sizes, limited opportunities for genetic exchange and may be disproportionately affected by ebbs and flows of species' geographical range. PMID:12803633

  17. Bcl-2-mediated alterations in endoplasmic reticulum analyzed with an improved genetically

    E-print Network

    Tsien, Roger Y.

    Bcl-2-mediated alterations in endoplasmic reticulum Ca2 analyzed with an improved genetically [Ca2 ]ER directly in individual cells. We created a genetically en- coded Ca2 indicator by redesigning and (ii) alters Ca2 oscilla- tions induced by ATP, and that acute inhibition of Bcl-2 by the green tea

  18. Use of Automatically Defined Functions and Architecture-Altering Operations in Automated Circuit Synthesis with Genetic

    E-print Network

    Fernandez, Thomas

    -passband filter is genetically evolved in which the architecture-altering operations discover a suitable programUse of Automatically Defined Functions and Architecture- Altering Operations in Automated Circuit Synthesis with Genetic Programming John R. Koza Computer Science Dept. 258 Gates Building Stanford

  19. Genome-wide profiling of genetic alterations in acute lymphoblastic leukemia: recent insights and future directions

    Microsoft Academic Search

    C G Mullighan; J R Downing

    2009-01-01

    Until recently, our understanding of the genetic factors contributing to the pathogenesis of acute lymphoblastic leukemia (ALL) has relied on the detection of gross chromosomal alterations and mutational analysis of individual genes. Although these approaches have identified many important abnormalities, they have been unable to identify the full repertoire of genetic alterations in ALL. The advent of high-resolution, microarray-based techniques

  20. An Approach to Family Therapy: An Affective Rule-Altering Model

    ERIC Educational Resources Information Center

    Turner, Marcia B.; Gross, Steven Jay

    1976-01-01

    An affective rele-altering model of family therapy is outlined. The role of affect, conflict, and demand-making are examined to note similarities and differences with other approaches to family intervention. Terms utilized within the model are defined and illustrations provided. The implications for the affective therapist's use of self are…

  1. Alteration of oligosaccharide biosynthesis by genetic manipulation of glycosyltransferases.

    PubMed

    Youakim, A; Shur, B D

    1994-11-30

    The alteration of oligosaccharide structures through genetic manipulation of glycosyltransferase activities is now a reality. It is apparent that this technique has greater consequences on oligosaccharide structure when an exogenous enzyme is introduced into cells, and in particular when this enzyme is responsible for a terminal glycosylation step. By contrast, only one study has examined the effects of overexpressing an endogenous glycosyltransferase, in which there was no detectable effect on glycosylation. However, there are still other key regulatory biosynthetic enzymes, such as GlcNAc transferase V and beta 1,3 GlcNAc transferase, whose overexpression may alter glycosylation. Both of these enzymes are required for the biosynthesis of polylactosaminoglycans (polymers of N-acetyllactosamine disaccharides), and their elevation in tumor cells correlates with increased expression of polylactosaminoglycans. Recently, the gene encoding GlcNAc transferase V has been isolated, but its transfection into cells and characterization of the resulting oligosaccharides awaits further study. Alternate strategies for modifying oligosaccharide structures could involve the introduction of more than one glycosyltransferase into cells to ensure the availability of biosynthetic intermediates. Alternatively, the disruption of specific glycosyltransferase genes by homologous recombination could be used to eliminate competing glycosyltransferases that act on a common substrate. Although oligosaccharide biosynthesis is directly dependent upon the presence or absence of specific glycosyltransferases, other factors also contribute to glycosylation. For example, the transport rate of a glycoprotein through the endoplasmic reticulum and Golgi complex, the levels of processing glycosidases, the availability of substrates, the host cell, and ultimately, the peptide backbone of the particular glycoprotein of interest are important contributors to the final outcome of oligosaccharide structure. Despite these complications, further study into the manipulation of glycosyltransferase genes may ultimately allow the controlled and predictable biosynthesis of glycoprotein sugar chains. PMID:7832520

  2. Preliminary observations on genetic alterations in pilocytic astrocytomas associated with neurofibromatosis 1.

    PubMed Central

    Tada, Kenji; Kochi, Masato; Saya, Hideyuki; Kuratsu, Jun-ichi; Shiraishi, Shoji; Kamiryo, Takanori; Shinojima, Naoki; Ushio, Yukitaka

    2003-01-01

    Neurofibromatosis 1 (NF1) is an autosomal dominant disorder that predisposes sufferers to various forms of neoplasia. Among affected individuals, 15%-20% develop astrocytomas, especially pilocytic astrocytomas (PA), which are benign and classified as grade I by the World Health Organization. They are generally well circumscribed, and their progression is slow. NF1-associated PAs (NF1-PAs) occasionally behave as aggressive tumors. To elucidate underlying genetic events in clinically progressive NF1-PAs, we performed molecular genetic analysis on 12 PAs, including 3 NF1-PAs, for pS3, p16, and epidermal growth factor receptor genes, as well as loss of heterozygosity (LOH) on chromosome 1p, 10, 17, and 19q. None of the obvious genetic alterations typically seen in higher grade astrocytomas were found in 9 sporadic PAs. However, in 2 of 3 NF1-PAs, microsatellite analysis showed LOH10, including the PTEN (phosphatase and tensin homolog deleted on chromosome 10) gene locus, despite the diagnosis of pilocytic astrocytoma;one of these also manifested homozygous deletion of the p16 gene. The other NF1-PA harbored only LOH of the NF1 gene locus (17q). Our preliminary results support the hypothesis that some NF1-PAs differ genetically from sporadic PAs. PMID:14565158

  3. The temporal order of genetic and pathway alterations in tumorigenesis.

    PubMed

    Gerstung, Moritz; Eriksson, Nicholas; Lin, Jimmy; Vogelstein, Bert; Beerenwinkel, Niko

    2011-01-01

    Cancer evolves through the accumulation of mutations, but the order in which mutations occur is poorly understood. Inference of a temporal ordering on the level of genes is challenging because clinically and histologically identical tumors often have few mutated genes in common. This heterogeneity may at least in part be due to mutations in different genes having similar phenotypic effects by acting in the same functional pathway. We estimate the constraints on the order in which alterations accumulate during cancer progression from cross-sectional mutation data using a probabilistic graphical model termed Hidden Conjunctive Bayesian Network (H-CBN). The possible orders are analyzed on the level of genes and, after mapping genes to functional pathways, also on the pathway level. We find stronger evidence for pathway order constraints than for gene order constraints, indicating that temporal ordering results from selective pressure acting at the pathway level. The accumulation of changes in core pathways differs among cancer types, yet a common feature is that progression appears to begin with mutations in genes that regulate apoptosis pathways and to conclude with mutations in genes involved in invasion pathways. H-CBN models provide a quantitative and intuitive model of tumorigenesis showing that the genetic events can be linked to the phenotypic progression on the level of pathways. PMID:22069497

  4. ABSTRACTS | Carcinogenesis and Cancer Genetics Chromothripsis and focal copy number alterations determine poor outcome in malignant

    E-print Network

    Cai, Long

    ABSTRACTS | Carcinogenesis and Cancer Genetics 326 Chromothripsis and focal copy number alterations Meltzer1 and T Ried1 1 Genetics Branch, National Institutes of Health, Bethesda, MD, 2 Institute, Germany Genetic changes during tumorigenesis are usually acquired sequentially. However, a recent study

  5. The Problem. Genetic Pest Management (GPM) offers the potential to alter and control

    E-print Network

    Ferrara, Katherine W.

    The Problem. Genetic Pest Management (GPM) offers the potential to alter and control mosquitoes to that system. Students will receive a PhD in a home doctoral program and a graduate minor in Genetic on the program and application process see: http://GeneticEngSoc.ncsu.edu/ email questions to: GES

  6. Genetic and environmental factors that affect gestation length

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic and environmental factors that might affect gestation length (GL) were investigated so that more accurate predictions of calving dates could be provided to dairy producers. Data from >8 million calvings from 1999 through 2005 for 5 dairy breeds were assembled from lactation, reproduction, an...

  7. Genetic alterations activating kinase and cytokine receptor signaling in high-risk acute lymphoblastic leukemia | Office of Cancer Genomics

    Cancer.gov

    Activated kinase-like B-ALL does not harbor the BCR-ABL translocation, but it exhibits a very similar gene expression profile. The genetic alterations discovered in this study, which were validated by recurrence testing in a larger cohort, specifically affect cytokine receptors and regulators of kinase signaling. Moreover, several of the novel or rare alterations identified in this study induced cancerous phenotypes in cell lines and mouse xenograft models, and demonstrated sensitivity to tyrosine kinase inhibitors that are already used in the clinic.

  8. Transcriptional Programs following Genetic Alterations in p53, INK4A, and H-Ras Genes along Defined Stages

    E-print Network

    Domany, Eytan

    Transcriptional Programs following Genetic Alterations in p53, INK4A, and H-Ras Genes along Defined the genetic alterations in p53, Ras, INK4A locus, and telomerase, introduced in a stepwise manner into primary human fibroblasts. Here, we show that these are the minimally required genetic alterations

  9. Docosahexaenoic acid affects cell signaling by altering lipid rafts.

    PubMed

    Stillwell, William; Shaikh, Saame Raza; Zerouga, Mustafa; Siddiqui, Rafat; Wassall, Stephen R

    2005-01-01

    With 22 carbons and 6 double bonds docosahexaenoic acid (DHA) is the longest and most unsaturated fatty acid commonly found in membranes. It represents the extreme example of a class of important human health promoting agents known as omega-3 fatty acids. DHA is particularly abundant in retinal and brain tissue, often comprising about 50% of the membrane's total acyl chains. Inadequate amounts of DHA have been linked to a wide variety of abnormalities ranging from visual acuity and learning irregularities to depression and suicide. The molecular mode of action of DHA, while not yet understood, has been the focus of our research. Here we briefly summarize how DHA affects membrane physical properties with an emphasis on membrane signaling domains known as rafts. We report the uptake of DHA into brain phosphatidylethanolamines and the subsequent exclusion of cholesterol from the DHA-rich membranes. We also demonstrate that DHA-induced apoptosis in MDA-MB-231 breast cancer cells is associated with externalization of phosphatidylserine and membrane disruption ("blebbing"). We conclude with a proposal of how DHA incorporation into membranes may control cell biochemistry and physiology. PMID:16188208

  10. Alteration of proteoglycan sulfation affects bone growth and remodeling.

    PubMed

    Gualeni, Benedetta; de Vernejoul, Marie-Christine; Marty-Morieux, Caroline; De Leonardis, Fabio; Franchi, Marco; Monti, Luca; Forlino, Antonella; Houillier, Pascal; Rossi, Antonio; Geoffroy, Valerie

    2013-05-01

    Diastrophic dysplasia (DTD) is a chondrodysplasia caused by mutations in the SLC26A2 gene, leading to reduced intracellular sulfate pool in chondrocytes, osteoblasts and fibroblasts. Hence, proteoglycans are undersulfated in the cartilage and bone of DTD patients. To characterize the bone phenotype of this skeletal dysplasia we used the Slc26a2 knock-in mouse (dtd mouse), that was previously validated as an animal model of DTD in humans. X-rays, bone densitometry, static and dynamic histomorphometry, and in vitro studies revealed a primary bone defect in the dtd mouse model. We showed in vivo that this primary bone defect in dtd mice is due to decreased bone accrual associated with a decreased trabecular and periosteal appositional rate at the cell level in one month-old mice. Although the osteoclast number evaluated by histomorphometry was not different in dtd compared to wild-type mice, urine analysis of deoxypyridinoline cross-links and serum levels of type I collagen C-terminal telopeptides showed a higher resorption rate in dtd mice compared to wild-type littermates. Electron microscopy studies showed that collagen fibrils in bone were thinner and less organized in dtd compared to wild-type mice. These data suggest that the low bone mass observed in mutant mice could possibly be linked to the different bone matrix compositions/organizations in dtd mice triggering changes in osteoblast and osteoclast activities. Overall, these results suggest that proteoglycan undersulfation not only affects the properties of hyaline cartilage, but can also lead to unbalanced bone modeling and remodeling activities, demonstrating the importance of proteoglycan sulfation in bone homeostasis. PMID:23369989

  11. Genetic, epigenetic and stem cell alterations in endometriosis: new insights and potential therapeutic perspectives.

    PubMed

    Forte, Amalia; Cipollaro, Marilena; Galderisi, Umberto

    2014-01-01

    Human endometrium is a highly dynamic tissue, undergoing periodic growth and regression at each menstrual cycle. Endometriosis is a frequent chronic pathological status characterized by endometrial tissue with an ectopic localization, causing pelvic pain and infertility and a variable clinical presentation. In addition, there is well-established evidence that, although endometriosis is considered benign, it is associated with an increased risk of malignant transformation in approximately 1.0% of affected women, with the involvement of multiple pathways of development. Increasing evidence supports a key contribution of different stem/progenitor cell populations not only in the cyclic regeneration of eutopic endometrium, but also in the pathogenesis of at least some types of endometriosis. Evidence has arisen from experiments in animal models of disease through different kinds of assays (including clonogenicity, the label-retaining cell approach, the analysis of undifferentiation markers), as well as from descriptive studies on ectopic and eutopic tissue samples harvested from affected women. Changes in stem cell populations in endometriotic lesions are associated with genetic and epigenetic alterations, including imbalance of miRNA expression, histone and DNA modifications and chromosomal aberrations. The present short review mainly summarizes the latest observations contributing to the current knowledge regarding the presence and the potential contribution of stem/progenitor cells in eutopic endometrium and the aetiology of endometriosis, together with a report of the most recently identified genetic and epigenetic alterations in endometriosis. We also describe the potential advantages of single cell molecular profiling in endometrium and in endometriotic lesions. All these data can have clinical implications and provide a basis for new potential therapeutic applications. PMID:24059589

  12. Genetic Analysis of Central Carbon Metabolism Unveils an Amino Acid Substitution That Alters Maize NAD-

    E-print Network

    Flint-Garcia, Sherry

    was the NAD-dependent isocitrate dehydrogenase (IDH, E.C. 1.1.1.41), in which we identified a novel amino-acidGenetic Analysis of Central Carbon Metabolism Unveils an Amino Acid Substitution That Alters Maize Carbon Metabolism Unveils an Amino Acid Substitution That Alters Maize NAD-Dependent Isocitrate

  13. Early Alteration in Glomerular Reserve in Humans at Genetic Risk of Essential Hypertension Mechanisms and Consequences

    Microsoft Academic Search

    Daniel T. O'Connor; Elizabeth A. Tyrell; Mala T. Kailasam; Lucy M. Miller; Joseph A. Martinez; Robert R. Henry; Robert J. Parmer; Francis B. Gabbai

    Essential hypertension has a familial predisposition, but the phenotype of elevated blood pressure has delayed penetrance. Because the kidney is a crucial determinant of blood pressure homeostasis, we studied early glomerular alterations in still-normotensive young subjects at genetic risk of hypertension. Thirty-nine normotensive adults (mean age 29 to 31 years), stratified by genetic risk (parental family history (FH)) of hypertension

  14. Evidence that disease-induced population decline changes genetic structure and alters dispersal patterns in the Tasmanian devil

    PubMed Central

    Lachish, S; Miller, K J; Storfer, A; Goldizen, A W; Jones, M E

    2011-01-01

    Infectious disease has been shown to be a major cause of population declines in wild animals. However, there remains little empirical evidence on the genetic consequences of disease-mediated population declines, or how such perturbations might affect demographic processes such as dispersal. Devil facial tumour disease (DFTD) has resulted in the rapid decline of the Tasmanian devil, Sarcophilus harrisii, and threatens to cause extinction. Using 10 microsatellite DNA markers, we compared genetic diversity and structure before and after DFTD outbreaks in three Tasmanian devil populations to assess the genetic consequences of disease-induced population decline. We also used both genetic and demographic data to investigate dispersal patterns in Tasmanian devils along the east coast of Tasmania. We observed a significant increase in inbreeding (FIS pre/post-disease ?0.030/0.012, P<0.05; relatedness pre/post-disease 0.011/0.038, P=0.06) in devil populations after just 2–3 generations of disease arrival, but no detectable change in genetic diversity. Furthermore, although there was no subdivision apparent among pre-disease populations (?=0.005, 95% confidence interval (CI) ?0.003 to 0.017), we found significant genetic differentiation among populations post-disease (?=0.020, 0.010–0.027), apparently driven by a combination of selection and altered dispersal patterns of females in disease-affected populations. We also show that dispersal is male-biased in devils and that dispersal distances follow a typical leptokurtic distribution. Our results show that disease can result in genetic and demographic changes in host populations over few generations and short time scales. Ongoing management of Tasmanian devils must now attempt to maintain genetic variability in this species through actions designed to reverse the detrimental effects of inbreeding and subdivision in disease-affected populations. PMID:20216571

  15. Somatic Genetic Alterations and Implications for Targeted Therapies in Cancer (GIST, CML, Lung Cancer)

    Microsoft Academic Search

    Alice T. Shaw; Eyal C. Attar; Edwin Choy; Jeffrey Engelman

    \\u000a The last decade has witnessed tremendous advances in the treatment of patients with cancer. Chief among these is the discovery\\u000a and successful development of new, targeted cancer therapies. These therapies are highly effective in genetically defined\\u000a subsets of patients, i.e., patients whose tumors harbor specific genetic abnormalities. In contrast to previous chapters focusing\\u000a on germline genetic alterations that increase the

  16. Tooth dentin defects reflect genetic disorders affecting bone mineralization

    PubMed Central

    Vital, S. Opsahl; Gaucher, C.; Bardet, C.; Rowe, P.S.; George, A.; Linglart, A.; Chaussain, C.

    2012-01-01

    Several genetic disorders affecting bone mineralization may manifest during dentin mineralization. Dentin and bone are similar in several aspects, especially pertaining to the composition of the extracellular matrix (ECM) which is secreted by well-differentiated odontoblasts and osteoblasts, respectively. However, unlike bone, dentin is not remodelled and is not involved in the regulation of calcium and phosphate metabolism. In contrast to bone, teeth are accessible tissues with the shedding of deciduous teeth and the extractions of premolars and third molars for orthodontic treatment. The feasibility of obtaining dentin makes this a good model to study biomineralization in physiological and pathological conditions. In this review, we focus on two genetic diseases that disrupt both bone and dentin mineralization. Hypophosphatemic rickets is related to abnormal secretory proteins involved in the ECM organization of both bone and dentin, as well as in the calcium and phosphate metabolism. Osteogenesis imperfecta affects proteins involved in the local organization of the ECM. In addition, dentin examination permits evaluation of the effects of the systemic treatment prescribed to hypophosphatemic patients during growth. In conclusion, dentin constitutes a valuable tool for better understanding of the pathological processes affecting biomineralization. PMID:22296718

  17. Altered Emotional Interference Processing in Affective and Cognitive-Control Brain Circuitry in Major

    E-print Network

    . However, it is not yet clear whether this bias represents 1) impaired top-down cognitive control over, this bias may reflect an enhanced bottom-up response to emotional stimuli that dysregulates cognitiveAltered Emotional Interference Processing in Affective and Cognitive-Control Brain Circuitry

  18. Linking neocortical, cognitive, and genetic variability in autism with alterations of brain plasticity: the Trigger-Threshold-Target model.

    PubMed

    Mottron, Laurent; Belleville, Sylvie; Rouleau, Guy A; Collignon, Olivier

    2014-11-01

    The phenotype of autism involves heterogeneous adaptive traits (strengths vs. disabilities), different domains of alterations (social vs. non-social), and various associated genetic conditions (syndromic vs. nonsyndromic autism). Three observations suggest that alterations in experience-dependent plasticity are an etiological factor in autism: (1) the main cognitive domains enhanced in autism are controlled by the most plastic cortical brain regions, the multimodal association cortices; (2) autism and sensory deprivation share several features of cortical and functional reorganization; and (3) genetic mutations and/or environmental insults involved in autism all appear to affect developmental synaptic plasticity, and mostly lead to its upregulation. We present the Trigger-Threshold-Target (TTT) model of autism to organize these findings. In this model, genetic mutations trigger brain reorganization in individuals with a low plasticity threshold, mostly within regions sensitive to cortical reallocations. These changes account for the cognitive enhancements and reduced social expertise associated with autism. Enhanced but normal plasticity may underlie non-syndromic autism, whereas syndromic autism may occur when a triggering mutation or event produces an altered plastic reaction, also resulting in intellectual disability and dysmorphism in addition to autism. Differences in the target of brain reorganization (perceptual vs. language regions) account for the main autistic subgroups. In light of this model, future research should investigate how individual and sex-related differences in synaptic/regional brain plasticity influence the occurrence of autism. PMID:25155242

  19. Methods to determine DNA structural alterations and genetic instability

    PubMed Central

    Wang, Guliang; Zhao, Junhua; Vasquez, Karen M.

    2009-01-01

    Chromosomal DNA is a dynamic structure that can adopt a variety of non-canonical (i.e. non-B) conformations. In this regard, at least ten different forms of non-B DNA conformations have been identified, and many of them have been found to be mutagenic, and associated with human disease development. Despite the importance of non-B DNA structures in genetic instability and DNA metabolic processes, mechanisms remain largely undefined. The purpose of this review is to summarize current methodologies that are used to address questions in the field of non-B DNA structure-induced genetic instability. Advantages and disadvantages of each method will be discussed. A focused effort to further elucidate the mechanisms of non-B DNA-induced genetic instability will lead to a better understanding of how these structure-forming sequences contribute to the development of human disease. PMID:19245837

  20. Dissociating motivational direction and affective valence: specific emotions alter central motor processes.

    PubMed

    Coombes, Stephen A; Cauraugh, James H; Janelle, Christopher M

    2007-11-01

    We aimed to clarify the relation between affective valence and motivational direction by specifying how central and peripheral components of extension movements are altered according to specific unpleasant affective states. As predicted, premotor reaction time was quicker for extension movements initiated during exposure to attack than for extension movements initiated during exposure to all other valence categories (mutilation, erotic couples, opposite-sex nudes, neutral humans, household objects, blank). Exposure to erotic couples and mutilations yielded greater peak force than exposure to images of attack, neutral humans, and household objects. Finally, motor reaction time and peak electromyographic amplitude were not altered by valence. These findings indicate that unpleasant states do not unilaterally prime withdrawal movements, and that the quick execution of extension movements during exposure to threatening images is due to rapid premotor, rather than motor, reaction time. Collectively, our findings support the call for dissociating motivational direction and affective valence. PMID:17958705

  1. Genetic by environment interactions affect plant–soil linkages

    PubMed Central

    Pregitzer, Clara C; Bailey, Joseph K; Schweitzer, Jennifer A

    2013-01-01

    The role of plant intraspecific variation in plant–soil linkages is poorly understood, especially in the context of natural environmental variation, but has important implications in evolutionary ecology. We utilized three 18- to 21-year-old common gardens across an elevational gradient, planted with replicates of five Populus angustifolia genotypes each, to address the hypothesis that tree genotype (G), environment (E), and G × E interactions would affect soil carbon and nitrogen dynamics beneath individual trees. We found that soil nitrogen and carbon varied by over 50% and 62%, respectively, across all common garden environments. We found that plant leaf litter (but not root) traits vary by genotype and environment while soil nutrient pools demonstrated genotype, environment, and sometimes G × E interactions, while process rates (net N mineralization and net nitrification) demonstrated G × E interactions. Plasticity in tree growth and litter chemistry was significantly related to the variation in soil nutrient pools and processes across environments, reflecting tight plant–soil linkages. These data overall suggest that plant genetic variation can have differential affects on carbon storage and nitrogen cycling, with implications for understanding the role of genetic variation in plant–soil feedback as well as management plans for conservation and restoration of forest habitats with a changing climate. PMID:23919173

  2. Alterations in coagulation parameters in dairy cows affected with acute mastitis caused by E. coli and S. aureus pathogens

    Microsoft Academic Search

    Zuhair A. Bani Ismail; Charles Dickinson

    2010-01-01

    This study was conducted to evaluate alterations in coagulation parameters in dairy cows affected with acute Escherichia coli (E. coli) mastitis and to compare those values to cows affected with Staphylococcus aureus (S. aureus ) mastitis. Twenty-four, adult Holstein-Friesian dairy cows affected with acute E. coli mastitis and 17 cows affected with S. aureus mastitis were studied. Cows affected with

  3. Gene flow in genetically altered crops helps progress transgenic turfgrass.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Numerous useful traits are being imparted into transgenic and non-transgenic plants. Gene flow as indicated in a recent publication from the Council for Agricultural Science and Technology (CAST 2007) is the successful transfer of genetic information between different individuals, populations, and g...

  4. Genetic/molecular alterations of meningiomas and the signaling pathways targeted

    PubMed Central

    Domingues, Patrícia; González-Tablas, María; Otero, Álvaro; Pascual, Daniel; Ruiz, Laura; Miranda, David; Sousa, Pablo; Gonçalves, Jesús María; Lopes, María Celeste; Orfao, Alberto; Tabernero, María Dolores

    2015-01-01

    Meningiomas are usually considered to be benign central nervous system tumors; however, they show heterogenous clinical, histolopathological and cytogenetic features associated with a variable outcome. In recent years important advances have been achieved in the identification of the genetic/molecular alterations of meningiomas and the signaling pathways involved. Thus, monosomy 22, which is often associated with mutations of the NF2 gene, has emerged as the most frequent alteration of meningiomas; in addition, several other genes (e.g. AKT1, KLF4, TRAF7, SMO) and chromosomes have been found to be recurrently altered often in association with more complex karyotypes and involvement of multiple signaling pathways. Here we review the current knowledge about the most relevant genes involved and the signaling pathways targeted by such alterations. In addition, we summarize those proposals that have been made so far for classification and prognostic stratification of meningiomas based on their genetic/genomic features. PMID:25965831

  5. Genetic Alterations in Medullary Thyroid Cancer: Diagnostic and Prognostic Markers

    PubMed Central

    A, Taccaliti; F, Silvetti; G, Palmonella; M, Boscaro

    2011-01-01

    Medullary thyroid carcinoma (MTC) is a rare calcitonin producing neuroendocrine tumour that originates from the parafollicular C-cells of the thyroid gland. The RET proto-oncogene encodes the RET receptor tyrosine kinase, with consequently essential roles in cell survival, differentiation and proliferation. Somatic or germline mutations of the RET gene play an important role in this neoplasm in development of sporadic and familial forms, respectively. Genetic diagnosis has an important role in differentiating sporadic from familiar MTC. Furthermore, depending on the location of the mutation, patients can be classified into risk classes. Therefore, genetic screening of the RET gene plays a critical role not only in diagnosis but also in assessing the prognosis and course of MTC. PMID:22654561

  6. Methods to determine DNA structural alterations and genetic instability

    Microsoft Academic Search

    Guliang Wang; Junhua Zhao; Karen M. Vasquez

    2009-01-01

    Chromosomal DNA is a dynamic structure that can adopt a variety of non-canonical (i.e., non-B) conformations. In this regard, at least 10 different forms of non-B DNA conformations have been identified; many of them have been found to be mutagenic, and associated with human disease development. Despite the importance of non-B DNA structures in genetic instability and DNA metabolic processes,

  7. Genetic alterations associated with hepatocellular carcinomas define distinct pathways of hepatocarcinogenesis

    Microsoft Academic Search

    Pierre Laurent-Puig; Patricia Legoix; Olivier Bluteau; Jacques Belghiti; Dominique Franco; Frederic Binot; Geneviève Monges; Gilles Thomas; Paulette Bioulac-Sage; Jessica Zucman-Rossi

    2001-01-01

    Background & Aims: To evaluate how characterization of genetic alterations can help in the elucidation of liver carcinogenesis pathways, 137 tumors were analyzed. Methods: High-density allelotype, p53, Axin1, and b-catenin gene mutations were determined. Alterations were analyzed according to clinical parameters. Results: Tumors could be divided into 2 groups according to chromosome stability status. In the first group, demon- strating

  8. Environmental and genetic factors affecting cow survival of Israeli Holsteins.

    PubMed

    Weller, J I; Ezra, E

    2015-01-01

    The objectives were to investigate the effects of various environmental factors that may affect herd-life of Israeli Holsteins, including first-calving age and season, calving ease, number of progeny born, and service sire for first calving in complete and truncated records; and to estimate heritabilities and genetic correlations between herd-life and the other traits included in the Israeli breeding index. The basic data set consisted of 590,869 cows in milk recording herds with first freshening day between 1985 and at least 8 yr before the cut-off date of September 15, 2013. Herd-life was measured as days from first calving to culling. The phenotypic and genetic trends for herd-life were 5.7 and 16.8d/yr. The genetic trend was almost linear, whereas the phenotypic trend showed 4 peaks and 3 valleys. Cows born in February and March had the shortest herd-life, whereas cows born in September had the longest herd-life. Herd-life was maximal with calving age of 23mo, which is 1mo less than the mean calving age, and minimal at 19 and 31mo of calving age. Dystocia and twinning on first-parity calving reduced herd-life by approximately180 and 120d, but the interaction effect increased herd-life by 140d. Heritability for herd-life was 0.14. Despite the fact that the service sire effect was significant in the fixed model analysis, service sire effect accounted for <0.05% of the total variance. In the analysis of 1,431,938 truncated records, the effects of dystocia and twinning rate were very similar but less than 50% of the effects found in the analysis of complete records. Pregnancy at the truncation date increased expected herd-life by 432d. The correlation between actual herd-life and predicted herd-life based on truncated records was 0.44. Genetic correlations between the truncated records and actual herd-life were 0.75 for records truncated after 6mo but approached unity for records truncated after 3 yr. The genetic correlations of herd-life with first-parity milk, fat, and protein production, somatic cell score (SCS), and female fertility were all positive, except for SCS, in which negative values are economically favorable. The highest correlations with herd-life in absolute value were with female fertility and SCS. PMID:25468704

  9. Early Alteration in Glomerular Reserve in Humans at Genetic Risk of Essential Hypertension

    Microsoft Academic Search

    Daniel T. O'connor; Elizabeth A. Tyrell; Mala T. Kailasam; Lucy M. Miller; Joseph A. Martinez; Robert R. Henry; Robert J. Parmer; Francis B. Gabbai

    Abstract—Essential hypertension has a familial predisposition, but the phenotype of elevated blood pressure has delayed penetrance. Because the kidney is a crucial determinant of blood pressure homeostasis, we studied early glomerular alterations in still-normotensive young subjects at genetic risk of hypertension. Thirty-nine normotensive,adults (mean age 29 to 31 years), stratified by genetic risk (parental family history [FH]) of hypertension (26

  10. Genetics

    NSDL National Science Digital Library

    National Science Teachers Association (NSTA)

    2005-04-01

    What affects how physical characteristics are transmitted from parent to offspring? This is a question that can be answered at many levels. Molecular biologists examine the pattern of nucleotides in deoxyribonucleic acid (DNA) and the effect of mutations on the proteins produced. Classical geneticists explore the patterns by which traits are transmitted through families. Medical geneticists attempt to describe and develop treatments for diseases that have a genetic component. Genetic engineers analyze how traits can be altered in organisms through modern technology. These are only a few of the strategies that scientists employ to explain the nature of heredity. Explore historical perspectives on the study of genetics and investigate how cutting-edge technology is being used to expand our understanding of heredity.

  11. Subchronic arsenic exposure through drinking water alters vascular redox homeostasis and affects physical health in rats.

    PubMed

    Waghe, Prashantkumar; Sarath, Thengumpallil Sasindran; Gupta, Priyanka; Kutty, Harikumar Sankaran; Kandasamy, Kannan; Mishra, Santosh Kumar; Sarkar, Souvendra Nath

    2014-12-01

    We evaluated whether arsenic can alter vascular redox homeostasis and modulate antioxidant status, taking rat thoracic aorta as a model vascular tissue. In addition, we evaluated whether the altered vascular biochemical homeostasis could be associated with alterations in the physical indicators of toxicity development. Rats were exposed to arsenic as 25, 50, and 100 ppm of sodium arsenite through drinking water for 90 consecutive days. Body weight, food intake, and water consumption were recorded weekly. On the 91st day, rats were sacrificed; vital organs and thoracic aorta were collected. Lipid peroxidation, reactive oxygen species generation, and antioxidants were assessed in the thoracic aorta. Arsenic increased aortic lipid peroxidation and hydrogen peroxide generation while decreased reduced glutathione content in a dose-dependent manner. The activities of the enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase were decreased. Further, arsenic at 100 ppm decreased feed intake, water consumption, and body weight from the 11th week onward. At this concentration, arsenic increased the relative weights of the liver and kidney. The results suggest that arsenic causes dose-dependent oxidative stress, reduction in antioxidative defense systems, and body weight loss with alteration in hepato-renal organosomatic indices. Overall, subchronic arsenic exposure through drinking water causes alteration in vascular redox homeostasis and at high concentration affects physical health. PMID:25209654

  12. Melanoma: From Melanocyte to Genetic Alterations and Clinical Options

    PubMed Central

    Bertolotto, Corine

    2013-01-01

    Metastatic melanoma remained for decades without any effective treatment and was thus considered as a paradigm of cancer resistance. Recent progress with understanding of the molecular mechanisms underlying melanoma initiation and progression revealed that melanomas are genetically and phenotypically heterogeneous tumors. This recent progress has allowed for the development of treatment able to improve for the first time the overall disease-free survival of metastatic melanoma patients. However, clinical responses are still either too transient or limited to restricted patient subsets. The complete cure of metastatic melanoma therefore remains a challenge in the clinic. This review aims to present the recent knowledge and discoveries of the molecular mechanisms involved in melanoma pathogenesis and their exploitation into clinic that have recently facilitated bench to bedside advances. PMID:24416617

  13. Altered gene dosage confirms the genetic interaction between FIAT and ?NAC.

    PubMed

    Hekmatnejad, Bahareh; Mandic, Vice; Yu, Vionnie W C; Akhouayri, Omar; Arabian, Alice; St-Arnaud, René

    2014-04-01

    Factor inhibiting ATF4-mediated transcription (FIAT) interacts with Nascent polypeptide associated complex and coregulator alpha (?NAC). In cultured osteoblastic cells, this interaction contributes to maximal FIAT-mediated inhibition of Osteocalcin (Ocn) gene transcription. We set out to demonstrate the physiological relevance of this interaction by altering gene dosage in compound Fiat and Naca (encoding ?NAC) heterozygous mice. Compound Naca(+/-); Fiat(+/-) heterozygous animals were viable, developed normally, and exhibited no significant difference in body weight compared with control littermate genotypes. Animals with a single Fiat allele had reduced Fiat mRNA expression without changes in the expression of related family members. Expression of the osteocyte differentiation marker Dmp1 was elevated in compound heterozygotes. Static histomorphometry parameters were assessed at 8weeks of age using microcomputed tomography (?CT). Trabecular measurements were not different between genotypes. Cortical thickness and area were not affected by gene dosage, but we measured a significant increase in cortical porosity in compound heterozygous mice, without changes in biomechanical parameters. The bone phenotype of compound Naca(+/-); Fiat(+/-) heterozygotes confirms that FIAT and ?NAC are part of a common genetic pathway and support a role for the FIAT/?NAC interaction in normal bone physiology. PMID:24440290

  14. Verbal fluency deficits and altered lateralization of language brain areas in individuals genetically predisposed to schizophrenia

    Microsoft Academic Search

    Tejas S Bhojraj; Alan N Francis; Rajaprabhakaran Rajarethinam; Shaun Eack; Shreedhar Kulkarni; Konasale M Prasad; Debra M Montrose; Diana Dworakowski; Vaibhav Diwadkar; Matcheri S Keshavan

    2009-01-01

    Alterations of verbal fluency may correlate with deficits of gray matter volume and hemispheric lateralization of language brain regions like the pars triangularis (PT) in schizophrenia. Examining non-psychotic individuals at high genetic risk (HR) for schizophrenia may clarify if these deficits represent heritable trait markers or state dependent phenomena. We assessed adolescent and young adult HR subjects (N=60) and healthy

  15. Genetic expression profiles and chromosomal alterations in sporadic breast cancer in Mexican women

    Microsoft Academic Search

    Adán Valladares; Normand García Hernández; Fabio Salamanca Gómez; Everardo Curiel-Quezada; Eduardo Madrigal-Bujaidar; Ma. Dolores Vergara; Mónica Sierra Martínez; Diego J. Arenas Aranda

    2006-01-01

    Breast cancer is the second-leading cause of death among Mexican women >35 years of age. At the molecular level, changes in many genetic pathways have been reported to be associated with this neoplasm. To analyze these changes, we determined gene expression profiles and chromosomal structural alterations in tumors from Mexican women. We obtained mRNA to identify expression profiles with microarray

  16. Molecular genetic alterations and gene expression profile of a malignant rhabdoid tumor of the kidney

    Microsoft Academic Search

    Toshihito Nagata; Yasuo Takahashi; Yukimoto Ishii; Satoshi Asai; Megumi Sugahara-Kobayashi; Yayoi Nishida; Akiko Murata; Shunji Yamamori; Yoshiyasu Ogawa; Takeshi Nakamura; Hitohiko Murakami; Masanori Nakamura; Hiroyuki Shichino; Motoaki Chin; Kiminobu Sugito; Taro Ikeda; Tsugumichi Koshinaga; Hideo Mugishima

    2005-01-01

    Malignant rhabdoid tumor of the kidney (MRTK) is a rare but highly aggressive tumor in children, and knowledge about the molecular signature of this tumor is limited. We report the molecular genetic alterations and gene expression profile of an MRTK tumor that arose in a 4-month-old Japanese girl. Fluorescence in situ hybridization and Southern blot analyses revealed a homozygous deletion

  17. Torn at the Genes One Family's Debate Over Genetically Altered Plants

    NSDL National Science Digital Library

    Jennifer Nelson

    2000-01-01

    The setting for this case is the family dinner table, where a heated discussion about genetically altered foods is taking place. Marsha Cumberland’s brother-in-law has joined the family for dinner. Ed is an industry official whose job it is to decide whether or not new products need pre-market approval by the FDA. He has just returned from a conference on transgenic foods.  When it turns out that some of the food on the dinner table is genetically modified, a debate ensues with different members of the family at different ends of the spectrum. Written for an introductory biology course, the case considers the scientific and ethical issues of genetically altered plants.

  18. Patterns of genetic alterations in pancreatic cancer: a pooled analysis.

    PubMed

    Blanck, H M; Tolbert, P E; Hoppin, J A

    1999-01-01

    Both K-ras and p53 gene mutations are found commonly in pancreatic tumors. Analysis of the mutational patterns may provide insight into disease etiology. To further describe the mutational patterns of pancreatic cancer and to assess the evidence to date, we performed a pooled analysis of the published data on genetic mutations associated with pancreatic ductal adenocarcinoma. We included data from studies that evaluated point mutations in the two genes most studied in pancreatic cancer, K-ras and p53. A majority of the 204 tumors had mutations in at least one gene, with 29% having both K-ras and p53 mutations, 39% with K-ras mutation alone, and 16% having p53 mutation alone. Sixteen percent of tumors lacked mutation in either gene. K-ras mutations were present in high frequencies in all tumor grades (>69%). A statistically significant trend was observed for p53 mutation with higher tumor grade (P = 0.04). For K-ras, G2 and G3 grades, combined, had notably higher prevalences of mutation than G1 (P = 0.004). CGT mutations in K-ras codon 12 were marginally associated with lower tumor grade (P for trend = 0.09), and these tumors were somewhat less likely to have a p53 mutation than tumors with other K-ras mutations (P = 0.06). In the 59 K-ras+/p53+ tumors, 64% had the same type of mutation (transition or transversion) in both genes, suggesting a common mechanism. The mutational pattern of p53 in pancreatic cancer is similar to bladder cancer, another smoking-related cancer, but not to lung cancer. Analyses of molecular data, such as that performed here, present new avenues for epidemiologists in the study of the etiology of specific cancers. PMID:10217065

  19. Landscape location affects genetic variation of Canada lynx (Lynx canadensis)

    Microsoft Academic Search

    M. K. S CHWARTZ; L. S. M ILLS; Y. O RTEGA; L. F. R UGGIERO; F. W. A LLENDORF

    2003-01-01

    The effect of a population's location on the landscape on genetic variation has been of interest to population genetics for more than half a century. However, most studies do not consider broadscale biogeography when interpreting genetic data. In this study, we propose an operational definition of a peripheral population, and then explore whether peripheral populations of Canada lynx (Lynx canadensis)

  20. Dim light at night interacts with intermittent hypoxia to alter cognitive and affective responses

    PubMed Central

    Weil, Zachary M.; Magalang, Ulysses J.; Nelson, Randy J.

    2013-01-01

    Obstructive sleep apnea (OSA) and dim light at night (dLAN) have both been independently associated with alterations in mood and cognition. We aimed to determine whether dLAN would interact with intermittent hypoxia (IH), a condition characteristic of OSA, to alter the behavioral, cognitive, and affective responses. Adult male mice were housed in either standard lighting conditions (14:10-h light-dark cycle; 150 lux:0 lux) or dLAN (150 lux:5 lux). Mice were then exposed to IH (15 cycles/h, 8 h/day, FiO2 nadir of 5%) for 3 wk, then tested in assays of affective and cognitive responses; brains were collected for dendritic morphology and PCR analysis. Exposure to dLAN and IH increased anxiety-like behaviors, as assessed in the open field, elevated plus maze, and the light/dark box. dLAN and IH increased depressive-like behaviors in the forced swim test. IH impaired learning and memory performance in the passive avoidance task; however, no differences were observed in spatial working memory, as assessed by y-maze or object recognition. IH combined with dLAN decreased cell body area in the CA1 and CA3 regions of the hippocampus. Overall, IH decreased apical spine density in the CA3, whereas dLAN decreased spine density in the CA1 of the hippocampus. TNF-? gene expression was not altered by IH or lighting condition, whereas VEGF expression was increased by dLAN. The combination of IH and dLAN provokes negative effects on hippocampal dendritic morphology, affect, and cognition, suggesting that limiting nighttime exposure to light in combination with other established treatments may be of benefit to patients with OSA. PMID:23657638

  1. Genetic diversity of a dominant C4 grass is altered with increased precipitation variability.

    PubMed

    Avolio, Meghan L; Beaulieu, Jeremy M; Smith, Melinda D

    2013-02-01

    Climate change has the potential to alter the genetic diversity of plant populations with consequences for community dynamics and ecosystem processes. Recent research focused on changes in climatic means has found evidence of decreased precipitation amounts reducing genetic diversity. However, increased variability in climatic regimes is also predicted with climate change, but the effects of this aspect of climate change on genetic diversity have yet to be investigated. After 10 years of experimentally increased intra-annual variability in growing season precipitation regimes, we report that the number of genotypes of the dominant C(4) grass, Andropogon gerardii Vitman, has been significantly reduced in native tallgrass prairie compared with unmanipulated prairie. However, individuals showed a different pattern of genomic similarity with increased precipitation variability resulting in greater genome dissimilarity among individuals when compared to unmanipulated prairie. Further, we found that genomic dissimilarity was positively correlated with aboveground productivity in this system. The increased genomic dissimilarity among individuals in the altered treatment alongside evidence for a positive correlation of genomic dissimilarity with phenotypic variation suggests ecological sorting of genotypes may be occurring via niche differentiation. Overall, we found effects of more variable precipitation regimes on population-level genetic diversity were complex, emphasizing the need to look beyond genotype numbers for understanding the impacts of climate change on genetic diversity. Recognition that future climate change may alter aspects of genetic diversity in different ways suggests possible mechanisms by which plant populations may be able to retain a diversity of traits in the face of declining biodiversity. PMID:22907523

  2. Campylobacter jejuni pdxA Affects Flagellum-Mediated Motility to Alter Host Colonization

    PubMed Central

    Asakura, Hiroshi; Hashii, Noritaka; Uema, Masashi; Kawasaki, Nana; Sugita-Konishi, Yoshiko; Igimi, Shizunobu; Yamamoto, Shigeki

    2013-01-01

    Vitamin B6 (pyridoxal-5'-phosphate, PLP) is linked to a variety of biological functions in prokaryotes. Here, we report that the pdxA (putative 4-hydroxy-L-threonine phosphate dehydrogenase) gene plays a pivotal role in the PLP-dependent regulation of flagellar motility, thereby altering host colonization in a leading foodborne pathogen, Campylobacter jejuni. A C. jejuni pdxA mutant failed to produce PLP and exhibited a coincident loss of flagellar motility. Mass spectrometric analyses showed a 3-fold reduction in the main flagellar glycan pseudaminic acid (Pse) associated with the disruption of pdxA. The pdxA mutant also exhibited reduced growth rates compared with the WT strain. Comparative metabolomic analyses revealed differences in respiratory/energy metabolism between WT C. jejuni and the pdxA mutant, providing a possible explanation for the differential growth fitness between the two strains. Consistent with the lack of flagellar motility, the pdxA mutant showed impaired motility-mediated responses (bacterial adhesion, ERK1/2 activation, and IL-8 production) in INT407 cells and reduced colonization of chickens compared with the WT strain. Overall, this study demonstrated that the pdxA gene affects the PLP-mediated flagellar motility function, mainly through alteration of Pse modification, and the disruption of this gene also alters the respiratory/energy metabolisms to potentially affect host colonization. Our data therefore present novel implications regarding the utility of PLP and its dependent enzymes as potent target(s) for the control of this pathogen in the poultry host. PMID:23936426

  3. Use of Genetically Altered Stem Cells for the Treatment of Huntington’s Disease

    PubMed Central

    Crane, Andrew T.; Rossignol, Julien; Dunbar, Gary L.

    2014-01-01

    Transplantation of stem cells for the treatment of Huntington’s disease (HD) garnered much attention prior to the turn of the century. Several studies using mesenchymal stem cells (MSCs) have indicated that these cells have enormous therapeutic potential in HD and other disorders. Advantages of using MSCs for cell therapies include their ease of isolation, rapid propagation in culture, and favorable immunomodulatory profiles. However, the lack of consistent neuronal differentiation of transplanted MSCs has limited their therapeutic efficacy to slowing the progression of HD-like symptoms in animal models of HD. The use of MSCs which have been genetically altered to overexpress brain derived neurotrophic factor to enhance support of surviving cells in a rodent model of HD provides proof-of-principle that these cells may provide such prophylactic benefits. New techniques that may prove useful for cell replacement therapies in HD include the use of genetically altering fate-restricted cells to produce induced pluripotent stem cells (iPSCs). These iPSCs appear to have certain advantages over the use of embryonic stem cells, including being readily available, easy to obtain, less evidence of tumor formation, and a reduced immune response following their transplantation. Recently, transplants of iPSCs have shown to differentiate into region-specific neurons in an animal model of HD. The overall successes of using genetically altered stem cells for reducing neuropathological and behavioral deficits in rodent models of HD suggest that these approaches have considerable potential for clinical use. However, the choice of what type of genetically altered stem cell to use for transplantation is dependent on the stage of HD and whether the end-goal is preserving endogenous neurons in early-stage HD, or replacing the lost neurons in late-stage HD. This review will discuss the current state of stem cell technology for treating the different stages of HD and possible future directions for stem-cell therapy in HD. PMID:24961705

  4. Stocking Fingerling Largemouth Bass to Alter Genetic Composition: Efficacy and Efficiency of Three Stocking Rates

    Microsoft Academic Search

    David L. Buckmeier; J. Warren Schlechte; Robert K. Betsill

    2003-01-01

    The Texas Parks and Wildlife Department (TPWD) has stocked Florida largemouth bass Micropterus salmoides floridanus to alter the genetic composition of largemouth bass populations since 1972. Because most stocked fingerling largemouth bass remain within 1 km of their stocking site, TPWD's current stocking procedures and standard stocking rates of 10–41 fingerlings\\/surface ha typically yield 10,000–100,000 fish\\/stocked site (i.e., 2 km

  5. Genetic alterations associated with the evolution and progression of astrocytic brain tumours

    Microsoft Academic Search

    H. Ohgaki; P. Kleihues; B. Schäuble; A. Hausen; K. Ammon

    1995-01-01

    Diffusely infiltrating low-grade astrocytomas (WHO grade II) have an intrinsic tendency for progression to anaplastic astrocytoma (WHO grade III) and glioblastoma (WHO grade IV). This change is due to the sequential acquisition of genetic alterations, several of which have recently been identified. In low-grade astrocytomas, p53 mutations with or without loss of heterozygosity on chromosome 17p are the principal detectable

  6. Do Knowledge Arrangements Affect Student Reading Comprehension of Genetics?

    ERIC Educational Resources Information Center

    Wu, Jen-Yi; Tung, Yu-Neng; Hwang, Bi-Chi; Lin, Chen-Yung; Che-Di, Lee; Chang, Yung-Ta

    2014-01-01

    Various sequences for teaching genetics have been proposed. Three seventh-grade biology textbooks in Taiwan share similar key knowledge assemblages but have different knowledge arrangements. To investigate the influence of knowledge arrangements on student understanding of genetics, we compared students' reading comprehension of the three…

  7. Population genetic dynamics of three-spined sticklebacks (Gasterosteus aculeatus) in anthropogenic altered habitats

    PubMed Central

    Scharsack, Joern P; Schweyen, Hannah; Schmidt, Alexander M; Dittmar, Janine; Reusch, Thorsten BH; Kurtz, Joachim

    2012-01-01

    In industrialized and/or agriculturally used landscapes, inhabiting species are exposed to a variety of anthropogenic changes in their environments. Genetic diversity may be reduced if populations encounter founder events, bottlenecks, or isolation. Conversely, genetic diversity may increase if populations adapt to changes in selective regimes in newly created habitats. With the present study, genetic variability of 918 sticklebacks from 43 samplings (21.3 ± 3.8 per sample) at 36 locations from cultivated landscapes in Northwest Germany was analyzed at nine neutral microsatellite loci. To test if differentiation is influenced by habitat alterations, sticklebacks were collected from ancient running waters and adjacent artificial stagnant waters, from brooks with salt water inflow of anthropogenic and natural origin and adjacent freshwater sites. Overall population structure was dominated by isolation by distance (IBD), which was significant across all populations, and analysis of molecular variance (AMOVA) revealed that 10.6% of the variation was explained by river catchment area. Populations in anthropogenic modified habitats deviated from the general IBD structure and in the AMOVA, grouping by habitat type running/stagnant water explained 4.9% of variation and 1.4% of the variation was explained by salt-/freshwater habitat. Sticklebacks in salt-polluted water systems seem to exhibit elevated migratory activity between fresh- and saltwater habitats, reducing IBD. In other situations, populations showed distinct signs of genetic isolation, which in some locations was attributed to mechanical migration barriers, but in others to potential anthropogenic induced bottleneck or founder effects. The present study shows that anthropogenic habitat alterations may have diverse effects on the population genetic structure of inhabiting species. Depending on the type of habitat change, increased genetic differentiation, diversification, or isolation are possible consequences. PMID:22833789

  8. Genetic alterations of hepatocellular carcinoma by random amplified polymorphic DNA analysis and cloning sequencing of tumor differential DNA fragment

    Microsoft Academic Search

    Zhi-Hong Xian; Wen-Ming Cong; Shu-Hui Zhang; Meng-Chao Wu

    2005-01-01

    Abstract Abstract Abstract Abstract Abstract AIM:T o study the genetic alterations and their association with clinicopathological characteristics of hepatocellular carcinoma (HCC), and to find the tumor related DNA fragments. METHODS:DNA isolated from tumors and corresponding

  9. Tumor Derived Mutations of Protein Tyrosine Phosphatase Receptor Type K Affect Its Function and Alter Sensitivity to Chemotherapeutics in Glioma

    PubMed Central

    Agarwal, Supreet; Al-Keilani, Maha S.; Alqudah, Mohammad A. Y.; Sibenaller, Zita A.; Ryken, Timothy C.; Assem, Mahfoud

    2013-01-01

    Poor prognosis and resistance to therapy in malignant gliomas is mainly due to the highly dispersive nature of glioma cells. This dispersive characteristic results from genetic alterations in key regulators of cell migration and diffusion. A better understanding of these regulatory signals holds promise to improve overall survival and response to therapy. Using mapping arrays to screen for genomic alterations in gliomas, we recently identified alterations of the protein tyrosine phosphatase receptor type kappa gene (PTPRK) that correlate to patient outcomes. These PTPRK alterations are very relevant to glioma biology as PTPRK can directly sense cell–cell contact and is a dephosphorylation regulator of tyrosine phosphorylation signaling, which is a major driving force behind tumor development and progression. Subsequent sequencing of the full length PTPRK transcripts revealed novel PTPRK gene deletion and missense mutations in numerous glioma biopsies. PTPRK mutations were cloned and expressed in PTPRK-null malignant glioma cells. The effect of these mutations on PTPRK anti-oncogenic function and their association with response to anti-glioma therapeutics, such as temozolomide and tyrosine kinase inhibitors, was subsequently analyzed using in vitro cell-based assays. These genetic variations altered PTPRK activity and its post-translational processing. Reconstitution of wild-type PTPRK in malignant glioma cell lines suppressed cell growth and migration by inhibiting EGFR and ?-catenin signaling and improved the effect of conventional therapies for glioma. However, PTPRK mutations abrogated tumor suppressive effects of wild-type PTPRK and altered sensitivity of glioma cells to chemotherapy. PMID:23696788

  10. A genetic algorithms approach for altering the membership functions in fuzzy logic controllers

    NASA Technical Reports Server (NTRS)

    Shehadeh, Hana; Lea, Robert N.

    1992-01-01

    Through previous work, a fuzzy control system was developed to perform translational and rotational control of a space vehicle. This problem was then re-examined to determine the effectiveness of genetic algorithms on fine tuning the controller. This paper explains the problems associated with the design of this fuzzy controller and offers a technique for tuning fuzzy logic controllers. A fuzzy logic controller is a rule-based system that uses fuzzy linguistic variables to model human rule-of-thumb approaches to control actions within a given system. This 'fuzzy expert system' features rules that direct the decision process and membership functions that convert the linguistic variables into the precise numeric values used for system control. Defining the fuzzy membership functions is the most time consuming aspect of the controller design. One single change in the membership functions could significantly alter the performance of the controller. This membership function definition can be accomplished by using a trial and error technique to alter the membership functions creating a highly tuned controller. This approach can be time consuming and requires a great deal of knowledge from human experts. In order to shorten development time, an iterative procedure for altering the membership functions to create a tuned set that used a minimal amount of fuel for velocity vector approach and station-keep maneuvers was developed. Genetic algorithms, search techniques used for optimization, were utilized to solve this problem.

  11. Genetic expression profiles and chromosomal alterations in sporadic breast cancer in Mexican women.

    PubMed

    Valladares, Adán; Hernández, Normand García; Gómez, Fabio Salamanca; Curiel-Quezada, Everardo; Madrigal-Bujaidar, Eduardo; Vergara, Ma Dolores; Martínez, Mónica Sierra; Arenas Aranda, Diego J

    2006-10-15

    Breast cancer is the second-leading cause of death among Mexican women >35 years of age. At the molecular level, changes in many genetic pathways have been reported to be associated with this neoplasm. To analyze these changes, we determined gene expression profiles and chromosomal structural alterations in tumors from Mexican women. We obtained mRNA to identify expression profiles with microarray technology, and DNA to determine amplifications and deletions, in 10 fresh sporadic breast tumor biopsies without treatment, as well as in 10 nonaffected breast tissues. Expression profiles were compared with genetic changes observed by comparative genomic hybridization (CGH). We compared the expression profiles against the structural alterations from the studied genes by means of microarrays; at least 17 of these genes correlated with DNA copy number alterations. We found that the following genes were overexpressed: LAMC1, PCTK3, CCNC, CCND1, FGF3, PCTK2, L1CAM, BGN, and PLXNB3 (alias PLEXR). Underexpressed genes included CASP9, FGR, TP73, HSPG2, and ERCC1; genes turned off included FRAP1, EPHA2 (previously ECK), IL12A, E2F5, TNFRSF10B, TNFRSF10A, EFNB3, and BCL2. The results will allow us, in the near future, to outline genes that could serve as diagnostic, prognostic, or target therapy markers for the Mexican population. PMID:17011986

  12. Alteration of soil rhizosphere communities following genetic transformation of white spruce.

    PubMed

    LeBlanc, Philippe M; Hamelin, Richard C; Filion, Martin

    2007-07-01

    The application of plant genetic manipulations to agriculture and forestry with the aim of alleviating insect damage through Bacillus thuringiensis transformation could lead to a significant reduction in the release of pesticides into the environment. However, many groups have come forward with very valid and important questions related to potentially adverse effects, and it is crucial to assess and better understand the impact that this technology might have on ecosystems. In this study, we analyzed rhizosphere soil samples collected from the first B. thuringiensis-transformed trees [with insertion of the CryIA(b) toxin-encoding gene] grown in Canada (Val-Cartier, QC, Canada) as part of an ecological impact assessment project. Using a robust amplified rRNA gene restriction analysis approach coupled with 16S rRNA gene sequencing, the rhizosphere-inhabiting microbial communities of white spruce (Picea glauca) genetically modified by biolistic insertion of the cryIA(b), uidA (beta-glucuronidase), and nptII genes were compared with the microbial communities associated with non-genetically modified counterparts and with trees in which only the genetic marker genes uidA and nptII have been inserted. Analysis of 1,728 rhizosphere bacterial clones (576 clones per treatment) using a Cramér-von Mises statistic analysis combined with a Monte Carlo comparison clearly indicated that there was a statistically significant difference (P < 0.05) between the microbial communities inhabiting the rhizospheres of trees carrying the cryIA(b), uidA, and nptII transgenes, trees carrying only the uidA and nptII transgenes, and control trees. Clear rhizosphere microbial community alterations due to B. thuringiensis tree genetic modification have to our knowledge never been described previously and open the door to interesting questions related to B. thuringiensis genetic transformation and also to the impact of commonly used uidA and nptII genetic marker genes. PMID:17468272

  13. Signs of Selective Pressure on Genetic Variants Affecting Human Height

    Microsoft Academic Search

    Roberto Amato; Gennaro Miele; Antonella Monticelli; Sergio Cocozza

    2011-01-01

    Many decades of scientific investigation have proved the role of selective pressure in Homo Sapiens at least at the level of individual genes or loci. Nevertheless, there are examples of polygenic traits that are bound to be under selection, but studies devoted to apply population genetics methods to unveil such occurrence are still lacking. Stature provides a relevant example of

  14. Genetic variation among females affects paternity in a dioecious plant

    Microsoft Academic Search

    Sara Teixeira; Anne Burkhardt; Giorgina Bernasconi

    2008-01-01

    Flowering plants rely on vectors for pollen transfer, and cannot choose their mates. Although recipient plants are unable to choose which pollen they receive, post-pollination selection (acting pre- or post-zygotically) may modify the outcome of pollination. Here we show that genetic variation among pollen recipients can predict the outcome of pollen competition (seed paternity) in the dioecious white campion. To

  15. Genetics and infertility II Affected sib-pair analysis in endometriosis

    Microsoft Academic Search

    Stephen Kennedy; Simon Bennett

    2001-01-01

    This paper (i) reviews the current clinical and molecular genetic data which strongly suggest that endometriosis has a genetic basis; (ii) outlines the general principles of affected-sib pair analysis; and (iii) describes the Oxford Endometriosis Gene (OXEGENE) Study which aims, using a positional cloning approach, to identify susceptibility genes involved in the development of the disease.

  16. Genetic and environmental factors affecting growth and reproduction characters of Morada Nova sheep in Northeastern Brazil 

    E-print Network

    Fernandes, Antonio Amaury Oria

    1985-01-01

    GENETIC AND ENVIRONMENTAL FACTORS AFFECTING GROWTH AND REPRODUCTION CHARACTERS OF MORADA NOVA SHEEP IN NORTHEASTERN BRAZIL A Thesis by ANTONIO AMAURV ORIA FERNANDES Submitted to the Graduate College of Texas A&M University in partial... fulfillment of the requirements for the degree of MASTER OF SCIENCE May 1985 Major Subject: Animal Breeding GENETIC AND ENVIRONMENTAL FACTORS AFFECTING GROWTH AND REPRODUCTION CHARACTERS OF MORADA NOVA SHEEP IN NORTHEASTERN BRAZIL A Thesis by ANTONIO...

  17. Process-induced extracellular matrix alterations affect the mechanisms of soft tissue repair and regeneration

    PubMed Central

    Xu, Hui; Sandor, Maryellen; Lombardi, Jared

    2013-01-01

    Extracellular matrices derived from animal tissues for human tissue repairs are processed by various methods of physical, chemical, or enzymatic decellularization, viral inactivation, and terminal sterilization. The mechanisms of action in tissue repair vary among bioscaffolds and are suggested to be associated with process-induced extracellular matrix modifications. We compared three non-cross-linked, commercially available extracellular matrix scaffolds (Strattice, Veritas, and XenMatrix), and correlated extracellular matrix alterations to in vivo biological responses upon implantation in non-human primates. Structural evaluation showed significant differences in retaining native tissue extracellular matrix histology and ultrastructural features among bioscaffolds. Tissue processing may cause both the condensation of collagen fibers and fragmentation or separation of collagen bundles. Calorimetric analysis showed significant differences in the stability of bioscaffolds. The intrinsic denaturation temperature was measured to be 51°C, 38°C, and 44°C for Strattice, Veritas, and XenMatrix, respectively, demonstrating more extracellular matrix modifications in the Veritas and XenMatrix scaffolds. Consequently, the susceptibility to collagenase degradation was increased in Veritas and XenMatrix when compared to their respective source tissues. Using a non-human primate model, three bioscaffolds were found to elicit different biological responses, have distinct mechanisms of action, and yield various outcomes of tissue repair. Strattice permitted cell repopulation and was remodeled over 6 months. Veritas was unstable at body temperature, resulting in rapid absorption with moderate inflammation. XenMatrix caused severe inflammation and sustained immune reactions. This study demonstrates that extracellular matrix alterations significantly affect biological responses in soft tissue repair and regeneration. The data offer useful insights into the rational design of extracellular matrix products and bioscaffolds of tissue engineering. PMID:24555005

  18. Restriction and sequence alterations affect DNA uptake sequence-dependent transformation in Neisseria meningitidis.

    PubMed

    Ambur, Ole Herman; Frye, Stephan A; Nilsen, Mariann; Hovland, Eirik; Tønjum, Tone

    2012-01-01

    Transformation is a complex process that involves several interactions from the binding and uptake of naked DNA to homologous recombination. Some actions affect transformation favourably whereas others act to limit it. Here, meticulous manipulation of a single type of transforming DNA allowed for quantifying the impact of three different mediators of meningococcal transformation: NlaIV restriction, homologous recombination and the DNA Uptake Sequence (DUS). In the wildtype, an inverse relationship between the transformation frequency and the number of NlaIV restriction sites in DNA was observed when the transforming DNA harboured a heterologous region for selection (ermC) but not when the transforming DNA was homologous with only a single nucleotide heterology. The influence of homologous sequence in transforming DNA was further studied using plasmids with a small interruption or larger deletions in the recombinogenic region and these alterations were found to impair transformation frequency. In contrast, a particularly potent positive driver of DNA uptake in Neisseria sp. are short DUS in the transforming DNA. However, the molecular mechanism(s) responsible for DUS specificity remains unknown. Increasing the number of DUS in the transforming DNA was here shown to exert a positive effect on transformation. Furthermore, an influence of variable placement of DUS relative to the homologous region in the donor DNA was documented for the first time. No effect of altering the orientation of DUS was observed. These observations suggest that DUS is important at an early stage in the recognition of DNA, but does not exclude the existence of more than one level of DUS specificity in the sequence of events that constitute transformation. New knowledge on the positive and negative drivers of transformation may in a larger perspective illuminate both the mechanisms and the evolutionary role(s) of one of the most conserved mechanisms in nature: homologous recombination. PMID:22768309

  19. Genetic strain and reproductive status affect endometrial fatty acid concentrations

    Microsoft Academic Search

    S. Meier; A. J. Peterson; M. D. Mitchell; M. Littlejohn; C. G. Walker; J. R. Roche

    2009-01-01

    Poor reproductive performance limits cow longevity in seasonal, pasture-based dairy systems. Few differ- ences in ovarian dynamics have been reported in dif- ferent strains of Holstein-Friesian cows, implying that the uterine environment may be a key component de- termining reproductive success. To test the hypothesis that the uterine environment differs among genetic strains of the Holstein-Friesian cow, endometrial fatty acids

  20. NS Reassortment of an H7-Type Highly Pathogenic Avian Influenza Virus Affects Its Propagation by Altering the Regulation of Viral RNA Production and Antiviral Host Response? †

    PubMed Central

    Wang, Zhongfang; Robb, Nicole C.; Lenz, Eva; Wolff, Thorsten; Fodor, Ervin; Pleschka, Stephan

    2010-01-01

    Highly pathogenic avian influenza viruses (HPAIV) with reassorted NS segments from H5- and H7-type avian virus strains placed in the genetic background of the A/FPV/Rostock/34 HPAIV (FPV; H7N1) were generated by reverse genetics. Virological characterizations demonstrated that the growth kinetics of the reassortant viruses differed from that of wild-type (wt) FPV and depended on whether cells were of mammalian or avian origin. Surprisingly, molecular analysis revealed that the different reassortant NS segments were not only responsible for alterations in the antiviral host response but also affected viral genome replication and transcription as well as nuclear ribonucleoprotein (RNP) export. RNP reconstitution experiments demonstrated that the effects on accumulation levels of viral RNA species were dependent on the specific NS segment as well as on the genetic background of the RNA-dependent RNA polymerase (RdRp). Beta interferon (IFN-?) expression and the induction of apoptosis were found to be inversely correlated with the magnitude of viral growth, while the NS allele, virus subtype, and nonstructural protein NS1 expression levels showed no correlation. Thus, these results demonstrate that the origin of the NS segment can have a dramatic effect on the replication efficiency and host range of HPAIV. Overall, our data suggest that the propagation of NS reassortant influenza viruses is affected at multiple steps of the viral life cycle as a result of the different effects of the NS1 protein on multiple viral and host functions. PMID:20739516

  1. Altering the axial light gradient affects photomorphogenesis in emerging seedlings of Zea mays L

    NASA Technical Reports Server (NTRS)

    Parks, B. M.; Poff, K. L.

    1986-01-01

    The axial (longitudinal) red light gradient (632 nanometers) of 4 day old dark-grown maize seedlings is increased by staining the peripheral cells of the coleoptile. The magnitude of increase in the light gradient is dependent solely on the light-absorbing qualities of the stain used. Metanil yellow has no effect on the axial red-light gradient, while methylene blue causes a large increase in this light gradient. These stains did not affect growth in darkness or the sensitivity of mesocotyl elongation to red light. However, mesocotyl elongation was altered for the dark-grown seedlings stained with methylene blue when these seedlings were transplanted, covered with soil, and permitted to emerge under natural lighting conditions. These observations are consistent with the idea that there is a single perceptive site below the coleoptilar node, and suggest that this perceptive site gives the actinic light which has traveled downward through the length of the shoot from an entry point in the plant tip region.

  2. Alterations in welding process voltage affect the generation of ultrafine particles, fume composition, and pulmonary toxicity.

    PubMed

    Antonini, James M; Keane, Michael; Chen, Bean T; Stone, Samuel; Roberts, Jenny R; Schwegler-Berry, Diane; Andrews, Ronnee N; Frazer, David G; Sriram, Krishnan

    2011-12-01

    The goal was to determine if increasing welding voltage changes the physico-chemical properties of the fume and influences lung responses. Rats inhaled 40 mg/m³ (3 h/day × 3 days) of stainless steel (SS) welding fume generated at a standard voltage setting of 25 V (regular SS) or at a higher voltage (high voltage SS) of 30 V. Particle morphology, size and composition were characterized. Bronchoalveolar lavage was performed at different times after exposures to assess lung injury. Fumes collected from either of the welding conditions appeared as chain-like agglomerates of nanometer-sized primary particles. High voltage SS welding produced a greater number of ultrafine-sized particles. Fume generated by high voltage SS welding was higher in manganese. Pulmonary toxicity was more substantial and persisted longer after exposure to the regular SS fume. In summary, a modest raise in welding voltage affected fume size and elemental composition and altered the temporal lung toxicity profile. PMID:21281223

  3. Phenotypic integration of skeletal traits during growth buffers genetic variants affecting the slenderness of femora in inbred mouse strains

    PubMed Central

    Jepsen, Karl J.; Hu, Bin; Tommasini, Steven M.; Courtland, Hayden-William; Price, Christopher; Cordova, Matthew; Nadeau, Joseph H.

    2009-01-01

    Compensatory interactions among adult skeletal traits are critical for establishing strength but complicate the search for fracture susceptibility genes by allowing many genetic variants to exist in a population without loss of function. A better understanding of how these interactions arise during growth will provide new insight into genotype-phenotype relationships and the biological controls that establish skeletal strength. We tested the hypothesis that genetic variants affecting growth in width relative to growth in length (slenderness) are coordinated with movement of the inner bone surface and matrix mineralization to match stiffness with weight-bearing loads during postnatal growth. Midshaft femoral morphology and tissue-mineral density were quantified at ages of 1 day and at 4, 8, and 16 weeks for a panel of 20 female AXB/BXA recombinant inbred mouse strains. Path Analyses revealed significant compensatory interactions among outer-surface expansion rate, inner-surface expansion rate, and tissue-mineral density during postnatal growth, indicating that genetic variants affecting bone slenderness were buffered mechanically by the precise regulation of bone surface movements and matrix mineralization. Importantly, the covariation between morphology and mineralization resulted from a heritable constraint limiting the amount of tissue that could be used to construct a functional femur. The functional interactions during growth explained 56-99% of the variability in adult traits and mechanical properties. These functional interactions provide quantitative expectations of how genetic or environmental variants affecting one trait should be compensated by changes in other traits. Variants that impair this process or that cannot be fully compensated are expected to alter skeletal growth leading to underdesigned (weak) or overdesigned (bulky) structures. PMID:19082857

  4. Genetic alterations in epithelial ovarian tumors analyzed by comparative genomic hybridization.

    PubMed

    Hauptmann, Steffen; Denkert, Carsten; Koch, Ines; Petersen, Simone; Schlüns, Karsten; Reles, Angela; Dietel, Manfred; Petersen, Iver

    2002-06-01

    The genetic changes involved in the pathogenesis of ovarian carcinoma are not completely understood. To investigate this matter, we studied paraffin-embedded, microdissected tissue of 47 ovarian epithelial tumors (9 adenomas, 11 tumors of low malignant potential [LMP], 14 serous carcinomas, and 13 nonserous carcinomas) using comparative genomic hybridization (CGH). (The primary data used in this study are available at our CGH online tumor database at http://amba.charite.de/cgh.) Chromosomal imbalances were found in 1 serous adenoma and in 7 LMP tumors. In the latter the alterations appeared randomly and showed no overlap with alterations found in invasive carcinomas. Although the mean aberration number of low-grade serous carcinomas was comparable to LMP tumors, the imbalances of the former occurred with high incidence (>50%) and were found at different localizations. High-grade serous carcinomas had more than twice as much chromosomal imbalances as low-grade serous carcinomas and also had pronounced alterations. In serous carcinomas, gains were found on 3q, 6p, 7, 8q, and 20, and losses were found on 4q, 6q, 12q, 13q, and 16q. Comparing serous and nonserous carcinomas, the mean aberration number was comparable, but the number of high incidence changes was lower, and the most frequent imbalances were losses on 13q and gains on 20p. Overlapping alterations occurring in serous and nonserous carcinomas were gains on 3q and 6p, as well as losses on 4q. Chromosomal imbalances associated with poor prognosis of ovarian carcinomas were gains on 6p, 7q, and 13q and losses on 15q, 17p, 18q, and 21q. Our data indicate that serous LMP tumors and invasive carcinomas have different genetic aberrations, indicating that invasive carcinomas do not arise from preexisting serous LMP tumors. On the other hand, there are common genetic abnormalities in serous and nonserous carcinomas, suggesting that they have very early lesions in common but take different paths of further development. PMID:12152163

  5. Alteration of Genetic Make-up in Karnal Bunt Pathogen (Tilletia indica) of Wheat in Presence of Host Determinants

    PubMed Central

    Gupta, Atul K.; Seneviratne, J. M.; Bala, Ritu; Jaiswal, J. P.; Kumar, Anil

    2015-01-01

    Alteration of genetic make-up of the isolates and monosporidial strains of Tilletia indica causing Karnal bunt (KB) disease in wheat was analyzed using DNA markers and SDS-PAGE. The generation of new variation with different growth characteristics is not a generalized feature and is not only dependant on the original genetic make up of the base isolate/monosporidial strains but also on interaction with host. Host determinant(s) plays a significant role in the generation of variability and the effect is much pronounced in monosporidial strains with narrow genetic base as compared to broad genetic base. The most plausible explanation of genetic variation in presence of host determinant(s) are the recombination of genetic material from two different mycelial/sporidia through sexual mating as well as through para-sexual means. The morphological and development dependent variability further suggests that the variation in T. indica strains predominantly derived through the genetic rearrangements. PMID:26060428

  6. Manipulation of in vivo iron levels can alter resistance to oxidative stress without affecting ageing in the nematode C. elegans

    E-print Network

    Gems, David

    Manipulation of in vivo iron levels can alter resistance to oxidative stress without affecting, London WC1H 0AH,UK 1. Introduction 1.1. The oxidative damage theory of ageing The mechanisms underlying., 2007; Perez et al., 2009). A number of tests of the oxidative damage theory have used the short

  7. Genetic and Clinical Factors Affecting Plasma Clozapine Concentration

    PubMed Central

    Edman, Gunnar; Bertilsson, Leif; Hukic, Dzana Sudic; Lavebratt, Catharina; Eriksson, Sven V.; Ösby, Urban

    2015-01-01

    Objective: To assess (1) the variance of plasma clozapine levels; (2) the relative importance of sex, smoking habits, weight, age, and specific genetic variants of cytochrome P450 1A2 (CYP1A2), uridine diphosphate glucuronosyltransferase 1A4 (UGT1A4), and multidrug resistance protein 1 (MDR1) on plasma levels of clozapine; and (3) the relation between plasma clozapine levels, fasting glucose levels, and waist circumference. Method: There were 113 patients on clozapine treatment recruited from psychosis outpatient clinics in Stockholm County, Sweden. Patients had genotype testing for single nucleotide polymorphisms: 2 in MDR1, 3 in CYP1A2, and 1 in UGT1A4. Multiple and logistic regression were used to analyze the relations. Results: There was a wide variation in plasma concentrations of clozapine (mean = 1,615 nmol/L, SD = 1,354 nmol/L), with 37% of the samples within therapeutic range (1,100–2,100 nmol/L). Smokers had significantly lower plasma clozapine concentrations than nonsmokers (P ? .03). There was a significant association between the rs762551 A allele of CYP1A2 and lower plasma clozapine concentration (P ? .05). Increased fasting glucose level was 3.7-fold more frequent in CC and CA genotypes than AA genotype (odds ratio = 0.27; 95% confidence interval, 0.10–0.72). There was no significant relation between higher fasting glucose levels, larger waist circumference, and higher clozapine levels. Conclusions: It is difficult to predict plasma clozapine concentration, even when known individual and genetic factors are considered. Therefore, therapeutic drug monitoring is recommended in patients who are treated with clozapine.

  8. Forest Stand Characteristics Altered by Restoration Affect Western Bluebird Habitat Quality

    Microsoft Academic Search

    Catherine S. Wightman; Stephen S. Germaine

    2006-01-01

    Forest managers are setting Ponderosa pine (Pinus pon- derosa) forests in the southwestern United States on a tra- jectory toward a restored ecosystem by reducing tree densities and managing with prescribed fire. The process of restoration dramatically alters forest stands, and the ef- fects of these changes on wildlife remain unclear. Our research evaluated which aspects of habitat alteration from

  9. Comparative genomic hybridization reveals population-based genetic alterations in hepatoblastomas

    PubMed Central

    Gray, S G; Kytölä, S; Matsunaga, T; Larsson, C; Ekström, T J

    2000-01-01

    Hepatoblastoma is a malignant paediatric liver tumour. In order to approach the genetic background of this malignancy we have screened a panel of eighteen cases from Europe and Japan for chromosomal imbalances using comparative genomic hybridization (CGH). The most frequent losses included chromosomal regions 13q21–q22 (28%) and 9p22-pter (22%), while the most frequent gains occurred on 2q23–q24 (33%), 20q (28%) and 1q24–q25 (28%). A significant difference in CGH alterations between the tumours from patients of Caucasian and Japanese was revealed where loss of 13q was found only in the Japanese samples. In conclusion, the findings indicate several candidate regions for suppressor genes and oncogenes potentially involved in the hepatoblastomas of different ethnic origin. © 2000 Cancer Research Campaign PMID:10993649

  10. Shimmer: detection of genetic alterations in tumors using next-generation sequence data

    PubMed Central

    Hansen, Nancy F.; Gartner, Jared J.; Mei, Lan; Samuels, Yardena; Mullikin, James C.

    2013-01-01

    Motivation: Extensive DNA sequencing of tumor and matched normal samples using exome and whole-genome sequencing technologies has enabled the discovery of recurrent genetic alterations in cancer cells, but variability in stromal contamination and subclonal heterogeneity still present a severe challenge to available detection algorithms. Results: Here, we describe publicly available software, Shimmer, which accurately detects somatic single-nucleotide variants using statistical hypothesis testing with multiple testing correction. This program produces somatic single-nucleotide variant predictions with significantly higher sensitivity and accuracy than other available software when run on highly contaminated or heterogeneous samples, and it gives comparable sensitivity and accuracy when run on samples of high purity. Availability: http://www.github.com/nhansen/Shimmer Contact: nhansen@mail.nih.gov Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23620360

  11. Cell type of origin as well as genetic alterations contribute to breast cancer phenotypes

    PubMed Central

    West, William W.; Qiu, Fang; Band, Hamid; Band, Vimla

    2015-01-01

    Breast cancer is classified into different subtypes that are associated with different patient survival outcomes, underscoring the importance of understanding the role of precursor cell and genetic alterations in determining tumor subtypes. In this study, we evaluated the oncogenic phenotype of two distinct mammary stem/progenitor cell types designated as K5+/K19? or K5+/K19+ upon introduction of identical combinations of oncogenes-mutant H-Ras (mRas) and mutant p53 (mp53), together with either wild-type ErbB2(wtErbB2) or wild-type EGFR (wtEGFR). We examined their tumor forming and metastasis potential, using both in-vitro and in-vivo assays. Both the combinations efficiently transformed K5+/K19? or K5+/K19+ cells. Xenograft tumors formed by these cells were histologically heterogeneous, with variable proportions of luminal, basal-like and claudin-low type components depending on the cell types and oncogene combinations. Notably, K5+/K19? cells transformed with mRas/mp53/wtEGFR combination had a significantly longer latency for primary tumor development than other cell lines but more lung metastasis incidence than same cells expressing mRas/mp53/wtErbB2. K5+/K19+ cells exhibit shorter overall tumor latency, and high metastatic potential than K5+/K19? cells, suggesting that these K19+ progenitors are more susceptible to oncogenesis and metastasis. Our results suggest that both genetic alterations and cell type of origin contribute to oncogenic phenotype of breast tumors. PMID:25940703

  12. Alterations in coagulation parameters in dairy cows affected with acute mastitis caused by E. coli and S. aureus pathogens.

    PubMed

    Ismail, Zuhair A Bani; Dickinson, Charles

    2010-08-01

    This study was conducted to evaluate alterations in coagulation parameters in dairy cows affected with acute Escherichia coli (E. coli) mastitis and to compare those values to cows affected with Staphylococcus aureus (S. aureus ) mastitis. Twenty-four, adult Holstein-Friesian dairy cows affected with acute E. coli mastitis and 17 cows affected with S. aureus mastitis were studied. Cows affected with E. coli mastitis had significantly prolonged activated partial thromboplastin time (APTT) (P < 0.01), prothrombin time (PT) (P < 0.05) and decreased (P < 0.05) platelets numbers. Cows with S. aureus mastitis had only significantly prolonged APTT (P < 0.05) and decreased (P < 0.05) platelet counts. In the hematology evaluation, cows affected with E. coli and those affected with S. aureus mastitis had elevated hematocrit values but only significantly (P < 0.05) so in mastitic cows caused by E. coli. Both groups of mastitic cows had significantly (P < 0.05) lower leukocyte counts. Only cows with E. coli mastitis had significantly (P < 0.05) lower neutrophil count. In the plasma biochemical evaluation, creatinine concentrations were significantly (P < 0.05) elevated in both groups of cows. Blood urea nitrogen (BUN) concentration was only significantly elevated in cows affected with E. coli mastitis. Results of this study indicated that dairy cows affected with acute E. coli mastitis are more likely to develop clinical manifestations of disseminated intravascular coagulation than cows affected with S. aureus mastitis. PMID:20607398

  13. Genetic variations and treatments that affect the lifespan of the NPC1 mouse

    Microsoft Academic Search

    Benny Liu; Hao Li; Joyce J. Repa; Stephen D. Turley; John M. Dietschy

    2008-01-01

    Niemann-Pick type C (NPC) disease is a multisys- tem disorder caused primarily by a mutation in the npc1 gene. These studies evaluated the effect of genetic back- ground, deletion of additional genes, and administration of several agents on the age at death in a murine model of this disorder. Such factors as differing strain background or geneticdriftwithinagivenbackgroundinthenpc12\\/2mouse significantly altered the

  14. Genetical and comparative genomics of Brassica under altered Ca supply identifies Arabidopsis Ca-transporter orthologs.

    PubMed

    Graham, Neil S; Hammond, John P; Lysenko, Artem; Mayes, Sean; O Lochlainn, Seosamh; Blasco, Bego; Bowen, Helen C; Rawlings, Chris J; Rios, Juan J; Welham, Susan; Carion, Pierre W C; Dupuy, Lionel X; King, Graham J; White, Philip J; Broadley, Martin R

    2014-07-01

    Although Ca transport in plants is highly complex, the overexpression of vacuolar Ca(2+) transporters in crops is a promising new technology to improve dietary Ca supplies through biofortification. Here, we sought to identify novel targets for increasing plant Ca accumulation using genetical and comparative genomics. Expression quantitative trait locus (eQTL) mapping to 1895 cis- and 8015 trans-loci were identified in shoots of an inbred mapping population of Brassica rapa (IMB211 × R500); 23 cis- and 948 trans-eQTLs responded specifically to altered Ca supply. eQTLs were screened for functional significance using a large database of shoot Ca concentration phenotypes of Arabidopsis thaliana. From 31 Arabidopsis gene identifiers tagged to robust shoot Ca concentration phenotypes, 21 mapped to 27 B. rapa eQTLs, including orthologs of the Ca(2+) transporters At-CAX1 and At-ACA8. Two of three independent missense mutants of BraA.cax1a, isolated previously by targeting induced local lesions in genomes, have allele-specific shoot Ca concentration phenotypes compared with their segregating wild types. BraA.CAX1a is a promising target for altering the Ca composition of Brassica, consistent with prior knowledge from Arabidopsis. We conclude that multiple-environment eQTL analysis of complex crop genomes combined with comparative genomics is a powerful technique for novel gene identification/prioritization. PMID:25082855

  15. Genetic barcode sequencing for screening altered population dynamics of hematopoietic stem cells transduced with lentivirus

    PubMed Central

    Zanatta, Daniela B; Tsujita, Maristela; Borelli, Primavera; Aguiar, Rodrigo B; Ferrari, Daniel G; Strauss, Bryan E

    2014-01-01

    Insertional mutagenesis has been associated with malignant cell transformation in gene therapy protocols, leading to discussions about vector security. Therefore, clonal analysis is important for the assessment of vector safety and its impact on patient health. Here, we report a unique approach to assess dynamic changes in clonality of lentivirus transduced cells upon Sanger sequence analysis of a specially designed genetic barcode. In our approach, changes in the electropherogram peaks are measured and compared between successive time points, revealing alteration in the cell population. After in vitro validation, barcoded lentiviral libraries carrying IL2RG or LMO2 transgenes, or empty vector were used to transduce mouse hematopoietic (ckit+) stem cells, which were subsequently transplanted in recipient mice. We found that neither the empty nor IL2RG encoding vector had an effect on cell dynamics. In sharp contrast, the LMO2 oncogene was associated with altered cell dynamics even though hematologic counts remained unchanged, suggesting that the barcode could reveal changes in cell populations not observed by the frontline clinical assay. We describe a simple and sensitive method for the analysis of clonality, which could be easily used by any laboratory for the assessment of cellular behavior upon lentiviral transduction. PMID:26052520

  16. Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer

    PubMed Central

    Ye, Qin; Holowatyj, Andreana; Wu, Jack; Liu, Hui; Zhang, Lihong; Suzuki, Takayoshi; Yang, Zeng-Quan

    2015-01-01

    The histone lysine demethylase KDM4 subfamily, comprised of four members (A, B, C, and D), play critical roles in controlling transcription, chromatin architecture and cellular differentiation. We previously demonstrated that KDM4C is significantly amplified and overexpressed in aggressive basal-like breast cancers and functions as a transforming oncogene. However, information regarding the genomic and transcriptomic alterations of the KDM4 subfamily in different subtypes of breast cancer remains largely incomplete. Here, we conducted a meta-analysis of KDM4A, B, C and D in breast cancer and identified associations among recurrent copy number alterations, gene expression and breast cancer subtypes. We demonstrated that KDM4A and D are also significantly overexpressed in basal-like breast cancer, whereas KDM4B overexpression is more dominant in estrogen-receptor-positive, luminal breast cancer. Next, we investigated the therapeutic potential of a novel histone demethylase inhibitor, NCDM-32B, in breast cancer. The treatment of basal breast cancer cell lines with NCDM-32B resulted in the decrease of cell viability and anchorage independent growth in soft agar. Furthermore, we found that NCDM-32B impaired several critical pathways that drive cellular proliferation and transformation in breast cancer. Our findings demonstrate genetic amplification and overexpression of the KDM4 demethylases in different subtypes of breast cancer. Furthermore, histone methylation is reversible and KDM4 demethylases are druggable targets. Thus, KDM4 inhibitors may serve as a novel therapeutic approach for a subset of aggressive breast cancer.

  17. Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

    PubMed

    Wu, T T; Rezai, B; Rashid, A; Luce, M C; Cayouette, M C; Kim, C; Sani, N; Mishra, L; Moskaluk, C A; Yardley, J H; Hamilton, S R

    1997-03-01

    Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome. PMID:9060832

  18. Genetic alterations and epithelial dysplasia in juvenile polyposis syndrome and sporadic juvenile polyps.

    PubMed Central

    Wu, T. T.; Rezai, B.; Rashid, A.; Luce, M. C.; Cayouette, M. C.; Kim, C.; Sani, N.; Mishra, L.; Moskaluk, C. A.; Yardley, J. H.; Hamilton, S. R.

    1997-01-01

    Juvenile polyps are regarded as hamartomatous polyps and occur in sporadic and familial syndromic settings. There is increased risk of gastrointestinal neoplasia in patients with juvenile polyposis syndrome, but the molecular mechanisms are not known. We therefore studied 78 colorectal juvenile polyposis from 12 patients with juvenile polyps syndrome and 34 sporadic juvenile polyps for epithelial dysplasia and genetic changes associated with colorectal neoplasia. Dysplasia occurred in 31% of syndromic juvenile polyps but not in sporadic juvenile polyps (P < 0.0001). Topographic control of proliferation and expression of the cyclin-dependent kinase inhibitor p21(WAFI/CIP1) seen in native colorectal epithelium was lost in 79% of dysplastic juvenile polyps and in 8% of nondysplastic juvenile polyps (P < 0.000001). Somatic mutations in the adenomatous polyposis coli (APC) gene were demonstrated in 50% of dysplastic juvenile polyps (3 of 6) but not in any of 16 juvenile polyps without dysplasia (P = 0.01). Both sporadic and syndromic juvenile polyps had K-ras mutations (14%) and there was no relationship to dysplasia. p53 gene product overexpression identified by immunohistochemical staining occurred rarely in dysplastic juvenile polyps (2 of 24, 8%). Our results indicate that the multiple genetic alterations involved in usual colorectal neoplasia also play a role in neoplastic transformation of juvenile polyps, predominantly in juvenile polyposis syndrome. Images Figure 1 Figure 2 Figure 3 PMID:9060832

  19. Genetic and environmental factors affecting growth characters of Charolais cattle in Southeastern Brazil 

    E-print Network

    Barbosa, Pedro Franklin

    1982-01-01

    G=NETIC AND ENVIRONMENTAL FACTORS AFFECTING GROWTH CHARACTERS OF CHAROLAIS CATTLE IN SOUTHEASTERN BRAZIL A Thesis by PEDRO FRANKLIN BARBOSA Submitted to the Graduate College of Texas ASM University in partial fulfillment of the requirement... for the degree of MASTER OF SCIENCE December 1982 Major Subject: Animal Breeding GENETIC AND ENVIRONMENTAL FACTORS AFFECTING GROWTH CHARACTERS OF CHAROLAIS CATTLE IN SOUTHEASTERN BRAZIL A Thesis by PEDRO FRANKLIN BARBOSA Approved as to style and content...

  20. The experience of altered states of consciousness in shamanic ritual: the role of pre-existing beliefs and affective factors.

    PubMed

    Polito, Vince; Langdon, Robyn; Brown, Jac

    2010-12-01

    Much attention has been paid recently to the role of anomalous experiences in the aetiology of certain types of psychopathology, e.g. in the formation of delusions. We examine, instead, the top-down influence of pre-existing beliefs and affective factors in shaping an individual's characterisation of anomalous sensory experiences. Specifically we investigated the effects of paranormal beliefs and alexithymia in determining the intensity and quality of an altered state of consciousness (ASC). Fifty five participants took part in a sweat lodge ceremony, a traditional shamanic ritual which was unfamiliar to them. Participants reported significant alterations in their state of consciousness, quantified using the 'APZ' questionnaire, a standardized measure of ASC experience. Participants endorsing paranormal beliefs compatible with shamanic mythology, and those showing difficulty identifying feelings scored higher on positive dimensions of ASC experience. Our findings demonstrate that variation in an individual's characterisation of anomalous experiences is nuanced by pre-existing beliefs and affective factors. PMID:20558090

  1. Behavioral Studies and Genetic Alterations in Corticotropin-Releasing Hormone (CRH) Neurocircuitry: Insights into Human Psychiatric Disorders

    PubMed Central

    Laryea, Gloria; Arnett, Melinda G.; Muglia, Louis J.

    2012-01-01

    To maintain well-being, all organisms require the ability to re-establish homeostasis in the presence of adverse physiological or psychological experiences. The regulation of the hypothalamic-pituitary adrenal (HPA) axis during stress is important in preventing maladaptive responses that may increase susceptibility to affective disorders. Corticotropin-releasing hormone (CRH) is a central stress hormone in the HPA axis pathway and has been implicated in stress-induced psychiatric disorders, reproductive and cardiac function, as well as energy metabolism. In the context of psychiatric disorders, CRH dysfunction is associated with the occurrence of post-traumatic stress disorder, major depression, anorexia nervosa, and anxiety disorders. Here, we review the synthesis, molecular signaling and regulation, as well as synaptic activity of CRH. We go on to summarize studies of altered CRH signaling in mutant animal models. This assembled data demonstrate an important role for CRH in neuroendocrine, autonomic, and behavioral correlates of adaptation and maladaptation. Next, we present findings regarding human genetic polymorphisms in CRH pathway genes that are associated with stress and psychiatric disorders. Finally, we discuss a role for regulators of CRH activity as potential sites for therapeutic intervention aimed at treating maladaptive behaviors associated with stress. PMID:23077729

  2. Fear induced neuronal alterations in a genetic model of depression: An fMRI study on awake animals

    Microsoft Academic Search

    Wei Huang; Meghan E. Heffernan; Zhixin Li; Nanyin Zhang; David H. Overstreet; Jean A. King

    2011-01-01

    Previous human imaging studies used facial stimuli to explore the potential association between depression and fear. This study aimed at investigating brain alterations in a rodent model of depression when innate fear was induced in the form of the predator odor trimethylthiazoline (TMT). Flinders sensitive line (FSL) rats, a genetic animal model of depression, and their control counterpart Flinders resistant

  3. Brief Genetics Report Variation in the Calpain-10 Gene Affects Blood Glucose

    E-print Network

    Cox, Nancy J.

    Brief Genetics Report Variation in the Calpain-10 Gene Affects Blood Glucose Levels in the British resistance, and individuals with the G/G-genotype had significantly higher fasting plasma glucose and 2-h insulin concentrations after a 75-g oral glucose tolerance test (OGTT). We have ex- amined the effect

  4. Comparative evolutionary genetics of spontaneous mutations affecting fitness in rhabditid nematodes

    E-print Network

    Lynch, Michael

    Comparative evolutionary genetics of spontaneous mutations affecting fitness in rhabditid nematodes-wide rate of mutation and the effects of new mutations on fitness, but the degree to which genomic variation in the rate of decay of fitness because of new mutations between strains and between species

  5. Genetic variation among females affects paternity in a dioecious Sara Teixeira, Anne Burkhardt and Giorgina Bernasconi

    E-print Network

    Teixeira, Sara

    Genetic variation among females affects paternity in a dioecious plant Sara Teixeira, Anne. of Neuchatel, CHÁ2009, Neuchatel, Switzerland. Flowering plants rely on vectors for pollen transfer, and cannot choose their mates. Although recipient plants are unable to choose which pollen they receive, post

  6. Intracolonial genetic variation affects reproductive skew and colony productivity during colony foundation in a parthenogenetic termite

    PubMed Central

    2014-01-01

    Background In insect societies, intracolonial genetic variation is predicted to affect both colony efficiency and reproductive skew. However, because the effects of genetic variation on these two colony characteristics have been tested independently, it remains unclear whether they are affected by genetic variation independently or in a related manner. Here we test the effect of genetic variation on colony efficiency and reproductive skew in a rhinotermitid termite, Reticulitermes speratus, a species in which female-female pairs can facultatively found colonies. We established colonies using two types of female-female pairs: colonies founded by sisters (i.e., sister-pair colonies) and those founded by females from different colonies (i.e., unrelated-pair colonies). Colony growth and reproductive skew were then compared between the two types of incipient colonies. Results At 15 months after colony foundation, unrelated-pair colonies were larger than sister-pair colonies, although the caste ratio between workers and nymphs, which were alternatively differentiated from young larvae, did not differ significantly. Microsatellite DNA analyses of both founders and their parthenogenetically produced offspring indicated that, in both sister-pair and unrelated-pair colonies, there was no significant skew in the production of eggs, larvae, workers and soldiers. Nymph production, however, was significantly more skewed in the sister-pair colonies than in unrelated-pair colonies. Because nymphs can develop into winged adults (alates) or nymphoid reproductives, they have a higher chance of direct reproduction than workers in this species. Conclusions Our results support the idea that higher genetic variation among colony members could provide an increase in colony productivity, as shown in hymenopteran social insects. Moreover, this study suggests that low genetic variation (high relatedness) between founding females increases reproductive skew via one female preferentially channeling her relatives along the reproductive track. This study thus demonstrated that, in social insects, intracolonial genetic variation can simultaneously affect both colony efficiency and reproductive skew. PMID:25123355

  7. Autism spectrum disorders: perceptions of genetic etiology and recurrence risk among Taiwanese parents of affected children.

    PubMed

    Chen, L S; Li, C; Wang, C H; Amuta, A; Li, M; Huang, T Y; Dhar, S U; Talwar, D; Jung, E

    2015-08-01

    In Taiwan, autism spectrum disorders (ASDs) are an emerging public health concern. The ongoing scientific progress for understanding the genetic etiology of ASD makes it increasingly important to examine how parents of children with ASD perceive the causes and recurrence risk of having another child with ASD. These perceptions may influence their family planning, attitudes toward genetic services, and willingness to take their children for ASD genetic testing. However, previous studies addressing this issue were conducted primarily in Western countries. As culture might shape an individual's views of genetic/genomic disorders, this first-of-its-kind study examined the perceptions of the genetic etiology for ASD and the recurrence risk among Taiwanese parents of children affected with ASD. In-depth, semi-structured interviews were conducted among 39 parents having at least one child with ASD. Although the majority of participants believed that ASD has a genetic link, less than half perceived genetic factors as the cause of their own child's ASD. Moreover, most participants articulated their recurrence risk incorrectly. Some parents were concerned about their doctors' limited genomic competencies. To provide parents with better education, counseling, and support for making reproductive decisions, ASD-related genomic education among Taiwanese physicians is needed. PMID:25267333

  8. Altered Expression of SPINDLY Affects Gibberellin Response and Plant Development1

    Microsoft Academic Search

    Stephen M. Swain; Tong-seung Tseng; Neil E. Olszewski

    2001-01-01

    Gibberellins (GAs) are plant hormones with diverse roles in plant growth and development. SPINDLY (SPY) is one of several genes identified in Arabidopsis that are involved in GA response and it is thought to encode an O-GlcNAc transferase. Genetic analysis suggests that SPY negatively regulates GA response. To test the hypothesis that SPY acts specifically as a negatively acting component

  9. Does natural selection alter genetic architecture? An evaluation of quantitative genetic variation among populations of Allonemobiussocius and A. fasciatus

    Microsoft Academic Search

    Roff; Mousseau

    1999-01-01

    To make long-term predictions using present quantitative genetic theory it is necessary to assume that the genetic variance-covariance matrix (G) remains constant or at least changes by a constant fraction. In this paper we examine the stability of the genetic architecture of two traits known to be subject to natural selection; femur length and ovipositor length in two species of

  10. Tree species affect atmospheric CH 4 oxidation without altering community composition of soil methanotrophs

    Microsoft Academic Search

    Oleg V. Menyailo; Wolf-Rainer Abraham; Ralf Conrad

    2010-01-01

    Plant species exert strong effects on ecosystem functions and one of the emerging, and difficult to test hypotheses, is that plants alter soil functions through changing the community structure of soil microorganisms. We tested the hypothesis for atmospheric CH4 oxidation by using soil samples from a Siberian afforestation experiment and exposing them to 13C–CH4. We determined the activity of the

  11. Genetic Association and Altered Gene Expression of Osteoprotegerin in Otosclerosis Patients.

    PubMed

    Priyadarshi, Saurabh; Ray, Chinmay Sundar; Biswal, Narayan Chandra; Nayak, Soumya Ranjan; Panda, Khirod Chandra; Desai, Ashim; Ramchander, Puppala Venkat

    2015-07-01

    Otosclerosis (OTSC) is a late-onset hearing disorder characterized by increased bone turnover in the otic capsule. Disturbed osteoprotegerin expression has been found in the otosclerotic foci which may have an important role in the pathogenesis of OTSC. To identify the genetic risk factors, we sequenced the coding region and exon-intron boundaries of the OPG gene in 254 OTSC patients and 262 controls. Sequence analysis identified five known polymorphisms c.9C>G, c.30+15C>T, c.400+4C>T, c.768A>G, and c.817+8A>C. Testing of these SNPs revealed sex specific association with c.9C>G in males and c.30+15C>T in females after multiple correction. Furthermore, meta-analysis provided evidence of association of the c.9C>G polymorphism with OTSC. In secondary analysis, we investigated the mRNA expression of OPG and associated genes RANK and RANKL in otosclerotic tissues compared to controls. Expression analysis revealed significantly missing/reduced OPG expression only in otosclerotic tissues. However, the signal sequence polymorphism c.9C>G has shown no effect on OPG mRNA expression. In conclusion, our results suggest that the risk of OTSC is influenced by variations in the OPG gene along with other factors which might regulate its altered expression in otosclerotic tissues. Further research is warranted to elucidate the mechanisms underlying these observations. PMID:25998045

  12. Durable tumor regression in genetically altered malignant rhabdoid tumors by inhibition of methyltransferase EZH2

    PubMed Central

    Knutson, Sarah K.; Warholic, Natalie M.; Wigle, Tim J.; Klaus, Christine R.; Allain, Christina J.; Raimondi, Alejandra; Porter Scott, Margaret; Chesworth, Richard; Moyer, Mikel P.; Copeland, Robert A.; Richon, Victoria M.; Pollock, Roy M.; Kuntz, Kevin W.; Keilhack, Heike

    2013-01-01

    Inactivation of the switch/sucrose nonfermentable complex component SMARCB1 is extremely prevalent in pediatric malignant rhabdoid tumors (MRTs) or atypical teratoid rhabdoid tumors. This alteration is hypothesized to confer oncogenic dependency on EZH2 in these cancers. We report the discovery of a potent, selective, and orally bioavailable small-molecule inhibitor of EZH2 enzymatic activity, (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4?-(morpholinomethyl)-[1,1?-biphenyl]-3-carboxamide). The compound induces apoptosis and differentiation specifically in SMARCB1-deleted MRT cells. Treatment of xenograft-bearing mice with (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(ethyl(tetrahydro-2H-pyran-4-yl)amino)-4-methyl-4?-(morpholinomethyl)-[1,1?-biphenyl]-3-carboxamide) leads to dose-dependent regression of MRTs with correlative diminution of intratumoral trimethylation levels of lysine 27 on histone H3, and prevention of tumor regrowth after dosing cessation. These data demonstrate the dependency of SMARCB1 mutant MRTs on EZH2 enzymatic activity and portend the utility of EZH2-targeted drugs for the treatment of these genetically defined cancers. PMID:23620515

  13. Ex situ cultivation affects genetic structure and diversity in arable plants.

    PubMed

    Brütting, C; Hensen, I; Wesche, K

    2013-05-01

    Worldwide, botanical gardens cultivate around 80,000 taxa, corresponding to approximately one-quarter of all vascular plants. Most cultivated taxa are, however, held in a small number of collections, and mostly only in small populations. Lack of genetic exchange and stochastic processes in small populations make them susceptible to detrimental genetic effects, which should be most severe in annual species, as sowing cycles are often short. In order to assess whether ex situ cultivation affects genetic diversity of annuals, five annual arable species with similar breeding systems were assessed with 42 in situ populations being compared to 20 ex situ populations using a random amplified polymorphic DNA (RAPD) analysis approach. Population sizes tended to be lower under ex situ cultivation and levels of genetic diversity also tended to be lower in four of the five species, with differences being significant in only two. Ex situ populations showed incomplete representation of alleles found in the wild. The duration of cultivation did not indicate any effect on genetic diversity. This implies that cultivation strategies resulted in different genetic structures in the garden populations. Although not unequivocally pronounced, differences nonetheless imply that conservation strategies in the involved gardens may need improvement. One option is cold storage of seeds, a practice that is not currently followed in the studied ex situ collections. This may reflect that the respective gardens focus on displaying living plant populations. PMID:22882447

  14. Dioecy, more than monoecy, affects plant spatial genetic structure: the case study of Ficus.

    PubMed

    Nazareno, Alison G; Alzate-Marin, Ana L; Pereira, Rodrigo Augusto S

    2013-09-01

    In this analysis, we attempt to understand how monoecy and dioecy drive spatial genetic structure (SGS) in plant populations. For this purpose, plants of the genus Ficus were used as a comparative model due to their particular characteristics, including high species diversity, variation in life histories, and sexual systems. One of the main issues we assessed is whether dioecious fig tree populations are more spatially genetically structured than monoecious populations. Using the Sp statistic, which allows for quantitative comparisons among different studies, we compared the extent of SGS between monoecious and dioecious Ficus species. To broaden our conclusions we used published data on an additional 27 monoecious and dioecious plant species. Furthermore, genetic diversity analyses were performed for two monoecious Ficus species using 12 microsatellite markers in order to strengthen our conclusions about SGS. Our results show that dioecy, more than monoecy, significantly contributes to SGS in plant populations. On average, the estimate of Sp was six times higher for dioecious Ficus species than monoecious Ficus species and it was two times higher in dioecious than monoecious plant species. Considering these results, we emphasize that the long-distance pollen dispersal mechanism in monoecious Ficus species seems to be the dominant factor in determining weak spatial genetic structure, high levels of genetic diversity, and lack of inbreeding. Although Ficus constitute a model species to study SGS, a more general comparison encompassing a wider range of plants is required in order to better understand how sexual systems affect genetic structure. PMID:24223285

  15. Experimental alteration of DNA methylation affects the phenotypic plasticity of ecologically relevant traits in Arabidopsis thaliana

    Microsoft Academic Search

    Oliver Bossdorf; Davide Arcuri; Christina L. Richards; Massimo Pigliucci

    2010-01-01

    Heritable phenotypic variation in plants can be caused not only by underlying genetic differences, but also by variation in\\u000a epigenetic modifications such as DNA methylation. However, we still know very little about how relevant such epigenetic variation\\u000a is to the ecology and evolution of natural populations. We conducted a greenhouse experiment in which we treated a set of\\u000a natural genotypes

  16. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation

    PubMed Central

    Mantua, Janna; Mahan, Keenan M.; Henry, Owen S.; Spencer, Rebecca M. C.

    2015-01-01

    Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18–22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation. PMID:26097451

  17. Altered sleep composition after traumatic brain injury does not affect declarative sleep-dependent memory consolidation.

    PubMed

    Mantua, Janna; Mahan, Keenan M; Henry, Owen S; Spencer, Rebecca M C

    2015-01-01

    Individuals with a history of traumatic brain injury (TBI) often report sleep disturbances, which may be caused by changes in sleep architecture or reduced sleep quality (greater time awake after sleep onset, poorer sleep efficiency, and sleep stage proportion alterations). Sleep is beneficial for memory formation, and herein we examine whether altered sleep physiology following TBI has deleterious effects on sleep-dependent declarative memory consolidation. Participants learned a list of word pairs in the morning or evening, and recall was assessed 12-h later, following an interval awake or with overnight sleep. Young adult participants (18-22 years) were assigned to one of four experimental groups: TBI Sleep (n = 14), TBI Wake (n = 12), non-TBI Sleep (n = 15), non-TBI Wake (n = 15). Each TBI participant was >1 year post-injury. Sleep physiology was measured with polysomnography. Memory consolidation was assessed by comparing change in word-pair recall over 12-h intersession intervals. The TBI group spent a significantly greater proportion of the night in SWS than the non-TBI group at the expense of NREM1. The TBI group also had marginally lower EEG delta power during SWS in the central region. Intersession changes in recall were greater for intervals with sleep than without sleep in both groups. However, despite abnormal sleep stage proportions for individuals with a TBI history, there was no difference in the intersession change in recall following sleep for the TBI and non-TBI groups. In both Sleep groups combined, there was a positive correlation between Intersession Change and the proportion of the night in NREM2 + SWS. Overall, sleep composition is altered following TBI but such deficits do not yield insufficiencies in sleep-dependent memory consolidation. PMID:26097451

  18. Genetic polymorphisms affect efficacy and adverse drug reactions of DMARDs in rheumatoid arthritis.

    PubMed

    Zhang, Ling Ling; Yang, Sen; Wei, Wei; Zhang, Xue Jun

    2014-11-01

    Disease-modifying antirheumatic drugs (DMARDs) and biological agents are critical in preventing the severe complications of rheumatoid arthritis (RA). However, the outcome of treatment with these drugs in RA patients is quite variable and unpredictable. Drug-metabolizing enzymes (dihydrofolate reductase, cytochrome P450 enzymes, N-acetyltransferases, etc.), drug transporters (ATP-binding cassette transporters), and drug targets (tumor necrosis factor-? receptors) are coded for by variant alleles. These gene polymorphisms may influence the pharmacokinetics, pharmacodynamics, and side effects of medicines. The cause for differences in efficacy and adverse drug reactions may be genetic variation in drug metabolism among individuals. Polymorphisms in drug transporter genes may change the distribution and excretion of medicines, and the sensitivity of the targets to drugs is strongly influenced by genetic variations. In this article, we review the genetic polymorphisms that affect the efficacy of DMARDs or the occurrence of adverse drug reactions associated with DMARDs in RA. PMID:25144752

  19. Alterations in affective processing of attack images following September 11, 2001.

    PubMed

    Tso, Ivy F; Chiu, Pearl H; King-Casas, Brooks R; Deldin, Patricia J

    2011-10-01

    The events of September 11, 2001 created unprecedented uncertainty about safety in the United States and created an aftermath with significant psychological impact across the world. This study examined emotional information encoding in 31 healthy individuals whose stress response symptoms ranged from none to a moderate level shortly after the attacks as assessed by the Impact of Event Scale-Revised. Participants viewed attack-related, negative (but attack-irrelevant), and neutral images while their event-related brain potentials (ERPs) were recorded. Attack images elicited enhanced P300 relative to negative and neutral images, and emotional images prompted larger slow waves than neutral images did. Total symptoms were correlated with altered N2, P300, and slow wave responses during valence processing. Specifically, hyperarousal and intrusion symptoms were associated with diminished stimulus discrimination between neutral and unpleasant images; avoidance symptoms were associated with hypervigilance, as suggested by reduced P300 difference between attack and other images and reduced appraisal of attack images as indicated by attenuated slow wave. The findings in this minimally symptomatic sample are compatible with the alterations in cognition in the posttraumatic stress disorder (PTSD) literature and are consistent with a dimensional model of PTSD. PMID:21882249

  20. A novel in-frame deletion affecting the BAR domain of OPHN1 in a family with intellectual disability and hippocampal alterations

    PubMed Central

    Santos-Rebouças, Cíntia Barros; Belet, Stefanie; Guedes de Almeida, Luciana; Ribeiro, Márcia Gonçalves; Medina-Acosta, Enrique; Bahia, Paulo Roberto Valle; Alves da Silva, Antônio Francisco; Lima dos Santos, Flávia; Borges de Lacerda, Glenda Corrêa; Pimentel, Márcia Mattos Gonçalves; Froyen, Guy

    2014-01-01

    Oligophrenin-1 (OPHN1) is one of at least seven genes located on chromosome X that take part in Rho GTPase-dependent signaling pathways involved in X-linked intellectual disability (XLID). Mutations in OPHN1 were primarily described as an exclusive cause of non-syndromic XLID, but the re-evaluation of the affected individuals using brain imaging displayed fronto-temporal atrophy and cerebellar hypoplasia as neuroanatomical marks. In this study, we describe clinical, genetic and neuroimaging data of a three generation Brazilian XLID family co-segregating a novel intragenic deletion in OPHN1. This deletion results in an in-frame loss of exon 7 at transcription level (c.781_891del; r.487_597del), which is predicted to abolish 37 amino acids from the highly conserved N-terminal BAR domain of OPHN1. cDNA expression analysis demonstrated that the mutant OPHN1 transcript is stable and no abnormal splicing was observed. Features shared by the affected males of this family include neonatal hypotonia, strabismus, prominent root of the nose, deep set eyes, hyperactivity and instability/intolerance to frustration. Cranial MRI scans showed large lateral ventricles, vermis hypoplasia and cystic dilatation of the cisterna magna in all affected males. Interestingly, hippocampal alterations that have not been reported in patients with loss-of-function OPHN1 mutations were found in three affected individuals, suggesting an important function for the BAR domain in the hippocampus. This is the first description of an in-frame deletion within the BAR domain of OPHN1 and could provide new insights into the role of this domain in relation to brain and cognitive development or function. PMID:24105372

  1. Factors affecting Agrobacterium tumefaciens -mediated genetic transformation of Lycium barbarum L

    Microsoft Academic Search

    Zhong Hu; Yi-Rui Wu; Wei Li; Huan-Huan Gao

    2006-01-01

    Summary  Using the system for genetic transformation and transgenic plant regeneration via somatic embryogenesis (SE) of Lycium barbarum established in this laboratory, this study reports the optimization of the factors affecting the efficiency of transformation,\\u000a including pre-culture period, leaf explant source, use of acetosyringone, strains and density of Agrobacterium, and temperature of co-cultivation. The optimized transformation protocol for L. barbarum included

  2. Examination of Genetic Alterations in Preneoplastic and Neoplastic Lesions of the Lung From Uranium Miners. Final Technical Report

    SciTech Connect

    Anderson, Marshall

    2000-07-12

    Lung cancer is one of the leading causes of death in the United States and in Western Europe. The incidence of lung cancer in developing countries is rising as their cigarette smoking habits increase. The objectives of this proposed research are to analyze genetic alterations associated with the development and progression on non-small cell lung carcinoma (MSCLC). Endpoints that may be realized from this proposed research are: (1) detection of early genetic and/or cellular alterations which ultimately could lead to diagnostic modalities for the early detection of lung cancer; and (2) detection of novel tumor suppressor genes on chromosome 9p. This proposal will analyze both tumor specimens and sputum samples.

  3. Early Experiences Can Alter Gene Expression and Affect Long-Term Development. Working Paper #10

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2010

    2010-01-01

    New scientific research shows that environmental influences can actually affect whether and how genes are expressed. Thus, the old ideas that genes are "set in stone" or that they alone determine development have been disproven. In fact, scientists have discovered that early experiences can determine how genes are turned on and off and even…

  4. A large-scale genetic screen for mutants with altered salicylic acid accumulation in Arabidopsis

    PubMed Central

    Ding, Yezhang; Shaholli, Danjela; Mou, Zhonglin

    2014-01-01

    Salicylic acid (SA) is a key defense signal molecule against biotrophic and hemibiotrophic pathogens in plants, but how SA is synthesized in plant cells still remains elusive. Identification of new components involved in pathogen-induced SA accumulation would help address this question. To this end, we performed a large-scale genetic screen for mutants with altered SA accumulation during pathogen infection in Arabidopsis using a bacterial biosensor Acinetobacter sp. ADPWH_lux-based SA quantification method. A total of 35,000 M2 plants in the npr1-3 mutant background have been individually analyzed for the bacterial pathogen Pseudomonas syringae pv. maculicola (Psm) ES4326-induced SA accumulation. Among the mutants isolated, 19 had SA levels lower than npr1 (sln) and two exhibited increased SA accumulation in npr1 (isn). Complementation tests revealed that seven of the sln mutants are new alleles of eds5/sid1, two are sid2/eds16 alleles, one is allelic to pad4, and the remaining seven sln and two isn mutants are new non-allelic SA accumulation mutants. Interestingly, a large group of mutants (in the npr1-3 background), in which Psm ES4326-induced SA levels were similar to those in the wild-type Columbia plants, were identified, suggesting that the signaling network fine-tuning pathogen-induced SA accumulation is complex. We further characterized the sln1 single mutant and found that Psm ES4326-induced defense responses were compromised in this mutant. These defense response defects could be rescued by exogenous SA, suggesting that SLN1 functions upstream of SA. The sln1 mutation was mapped to a region on the north arm of chromosome I, which contains no known genes regulating pathogen-induced SA accumulation, indicating that SLN1 likely encodes a new regulator of SA biosynthesis. Thus, the new sln and isn mutants identified in this genetic screen are valuable for dissecting the molecular mechanisms underlying pathogen-induced SA accumulation in plants. PMID:25610446

  5. Targeted next-generation sequencing of head and neck squamous cell carcinoma identifies novel genetic alterations in HPV+ and HPV- tumors

    PubMed Central

    2013-01-01

    Background Human papillomavirus positive (HPV+) head and neck squamous cell carcinoma (HNSCC) is an emerging disease, representing a distinct clinical and epidemiological entity. Understanding the genetic basis of this specific subtype of cancer could allow therapeutic targeting of affected pathways for a stratified medicine approach. Methods Twenty HPV+ and 20 HPV- laser-capture microdissected oropharyngeal carcinomas were used for paired-end sequencing of hybrid-captured DNA, targeting 3,230 exons in 182 genes often mutated in cancer. Copy number alteration (CNA) profiling, Sequenom MassArray sequencing and immunohistochemistry were used to further validate findings. Results HPV+ and HPV- oropharyngeal carcinomas cluster into two distinct subgroups. TP53 mutations are detected in 100% of HPV negative cases and abrogation of the G1/S checkpoint by CDKN2A/B deletion and/or CCND1 amplification occurs in the majority of HPV- tumors. Conclusion These findings strongly support a causal role for HPV, acting via p53 and RB pathway inhibition, in the pathogenesis of a subset of oropharyngeal cancers and suggest that studies of CDK inhibitors in HPV- disease may be warranted. Mutation and copy number alteration of PI3 kinase (PI3K) pathway components appears particularly prevalent in HPV+ tumors and assessment of these alterations may aid in the interpretation of current clinical trials of PI3K, AKT, and mTOR inhibitors in HNSCC. PMID:23718828

  6. Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression.

    PubMed

    Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D

    2014-03-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters. PMID:24434437

  7. THE ESTROGENIC AND ANTIANDROGENIC PESTICIDE METHOXYCHLOR ALTERS THE REPRODUCTIVE TRACT AND BEHAVIOR WITHOUT AFFECTING PITUITARY SIZE OR LH AND PROLACTIN SECRETION IN MALE RATS

    EPA Science Inventory

    The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats. Gray LE Jr, Ostby J, Cooper RL, Kelce WR. Endocrinology Branch, United States Environment...

  8. Handing the pen to the patient: reflective writing for children and families affected by genetic conditions.

    PubMed

    Murali, Chaya; Fernbach, Susan D; Potocki, Lorraine

    2014-12-01

    Genetic diagnoses impact the Quality of Life (QoL) of patients and their families. While some patients and families report a positive impact on QoL, others are affected negatively by a genetic diagnosis. No matter the impact, it is clear that social support is needed for this population. Genetic healthcare providers should be aware of the need for psychosocial support and be equipped to provide or direct patients and families to the appropriate resources. Reflective writing offers a unique opportunity for families and health care providers to engage in self-reflection and expression, activities which have the potential to enhance QoL in a positive manner. The therapeutic potential of writing has been studied in many populations, from caregivers of elderly individuals with dementia, to cancer survivors, to survivors of traumatic experiences. Some of these interventions have shown promise for improving participants' QoL. However, reflective writing has never been studied in patients and families affected by genetic conditions. We propose that reflective writing therapy is a feasible, reproducible, and enjoyable approach to providing psychosocial support for our patients. Get it Write is a reflective writing workshop pilot project for those who have a personal or family history of a genetic diagnosis. Our hypothesis is that reflective writing will help engender acceptance and alleviate feelings of isolation. Get it Write does not focus on the stressful factors in the participants' lives, rather it serves to facilitate interactions with peers facing the same struggles, and with medical students in a non-medical context. PMID:25256956

  9. Anthropogenic alterations of genetic diversity within tree populations: Implications for forest ecosystem resilience

    Microsoft Academic Search

    Paul G. Schaberg; Donald H. DeHayes; Gary J. Hawley; Samuel E. Nijensohn

    2008-01-01

    Healthy forests provide many of the essential ecosystem services upon which all life depends. Genetic diversity is an essential component of long-term forest health because it provides a basis for adaptation and resilience to environmental stress and change. In addition to natural processes, numerous anthropogenic factors deplete forest genetic resources. Genetic losses could be particularly consequential now because robust resilience

  10. Alterations in affective behavior during the time course of alcohol hangover.

    PubMed

    Karadayian, Analía G; Busso, María J; Feleder, Carlos; Cutrera, Rodolfo A

    2013-09-15

    Alcohol hangover is a temporary state described as the unpleasant next-day effects after binge-like drinking. Hangover begins when ethanol is absent in plasma and is characterized by physical and psychological symptoms. Affective behavior is impaired during the acute phase of alcohol intoxication; however, no reports indicate if similar effects are observed during withdrawal. The aim of this work was to study the time-extension and possible fluctuations in affective behavior during a hangover episode. Male Swiss mice were injected i.p. either with saline (control group) or with ethanol (3.8g/kg BW) (hangover group). Anxiety, fear-related behavior and despair phenotype were evaluated at a basal point (ZT0) and every 2h up to 20h after blood alcohol levels were close to zero (hangover onset). Also, anhedonia signs and pain perception disabilities were studied. Mice exhibited an increase in anxiety-like behavior during 4h and 14h after hangover onset when evaluated by the elevated-plus maze and open field test respectively (p<0.05). Fear-related behavior was detected in hangover animals by the increase of freezing and decrease of line crossings and rearing frequency during 16h after hangover onset (p<0.001). Depression signs were found in hangover mice during 14h (p<0.05). Hangover mice showed a significant decrease in pain perception when tested by tail immersion test at the beginning of hangover (p<0.05). Our findings demonstrate a time-extension between 14 and 16h for hangover affective impairments. This study shows the long lasting effects of hangover over the phase of ethanol intoxication. PMID:23850352

  11. Aniracetam Does Not Alter Cognitive and Affective Behavior in Adult C57BL/6J Mice

    PubMed Central

    Elston, Thomas W.; Pandian, Ashvini; Smith, Gregory D.; Holley, Andrew J.; Gao, Nanjing; Lugo, Joaquin N.

    2014-01-01

    There is a growing community of individuals who self-administer the nootropic aniracetam for its purported cognitive enhancing effects. Aniracetam is believed to be therapeutically useful for enhancing cognition, alleviating anxiety, and treating various neurodegenerative conditions. Physiologically, aniracetam enhances both glutamatergic neurotransmission and long-term potentiation. Previous studies of aniracetam have demonstrated the cognition-restoring effects of acute administration in different models of disease. No previous studies have explored the effects of aniracetam in healthy subjects. We investigated whether daily 50 mg/kg oral administration improves cognitive performance in naïve C57BL/6J mice in a variety of aspects of cognitive behavior. We measured spatial learning in the Morris water maze test; associative learning in the fear conditioning test; motor learning in the accelerating rotarod test; and odor discrimination. We also measured locomotion in the open field test, anxiety through the elevated plus maze test and by measuring time in the center of the open field test. We measured repetitive behavior through the marble burying test. We detected no significant differences between the naive, placebo, and experimental groups across all measures. Despite several studies demonstrating efficacy in impaired subjects, our findings suggest that aniracetam does not alter behavior in normal healthy mice. This study is timely in light of the growing community of healthy humans self-administering nootropic drugs. PMID:25099639

  12. Altered amphiregulin expression induced by diverse luteinizing hormone receptor reactivity in granulosa cells affects IVF outcomes.

    PubMed

    Huang, Ying; Zhao, Yue; Yu, Yang; Li, Rong; Lin, Shengli; Zhang, Chunmei; Liu, Ping; Qiao, Jie

    2015-06-01

    The expression of specific genes (LHR, AREG, EREG, EGFR, NPPC and NPR2) involved in peri-ovulatory signalling pathways induced by LH surge in granulosa cells was investigated, and their relationships with IVF outcomes analysed. mRNA levels of the genes of 147 infertile women undergoing IVF and intracytoplasmic sperm injection (ICSI) with embryo transfer were evaluated. Compared with non-pregnant women, amphiregulin (AREG) mRNA levels in mural and cumulus graunulosa cells were significantly higher (P < 0.05) in pregnant women, and were positively correlated with number of oocytes retrieved and good-quality embryos. No significant differences were found between the two groups in the remaining detected genes. To investigate the reason for the differences in AREG expression, mural granulosa cells were cultured and stimulated with human chorionic gonadotrophin (HCG) for 2-24?h. At 4?h after HCG stimulation, AREG and epiregulin mRNA expression peaked, with much greater increases in the pregnant group. The fold-change of AREG expression was positively correlated with number of good-quality embryos. No obvious correlation, however, was found between NPPC/Npr2 expression levels in granulosa cells and IVF outcomes. Altered AREG expression induced by diverse luteinizing hormone receptor reactivity in granulosa cells may provide a useful marker for oocyte developmental competency. PMID:25911599

  13. Altered executive function in obesity. Exploration of the role of affective states on cognitive abilities.

    PubMed

    Cserjési, Renáta; Luminet, Olivier; Poncelet, Anne-Sophie; Lénárd, László

    2009-04-01

    There is a growing evidence that obesity is not only a weight problem, but it is linked to adverse neurocognitive outcomes. Besides obesity, frontal lobe based cognitive deficits in depressed patients are confirmed, and interactions between depression and obesity are known. In our study we investigated the relationship between cognitive functioning, mood and female obesity. Our findings revealed reduced mental flexibility and sustained attention capacity in obesity together with the presence of depressive mood. The mediating role of depression is confirmed. Positive emotion was associated with cognitive functions independently from BMI. Positive affectivity in obesity treatment is discussed. PMID:19260167

  14. Altered regulatory mechanisms governing cell survival in children affected with clustering of autoimmune disorders

    PubMed Central

    2012-01-01

    Clustering of Autoimmune Diseases (CAD) is now emerging as a novel clinical entity within monogenic immune defects with a high familial occurrence. Aim of this study is to evaluate the regulatory mechanisms governing cell survival, paying a particular attention to Fas-induced apoptosis, in a cohort of 23 children affected with CAD. In 14 patients, Fas stimulation failed to induce cell apoptosis and in 1 case it was associated with Fas gene mutation. Our study highlights the importance to evaluate cell apoptosis in the group of children with CAD, which, with this regard, represents a distinct clinical entity. PMID:22971828

  15. Altered regulatory mechanisms governing cell survival in children affected with clustering of autoimmune disorders.

    PubMed

    Palamaro, Loredana; Giardino, Giuliana; Santamaria, Francesca; Ramenghi, Ugo; Dianzani, Umberto; Pignata, Claudio

    2012-01-01

    Clustering of Autoimmune Diseases (CAD) is now emerging as a novel clinical entity within monogenic immune defects with a high familial occurrence. Aim of this study is to evaluate the regulatory mechanisms governing cell survival, paying a particular attention to Fas-induced apoptosis, in a cohort of 23 children affected with CAD. In 14 patients, Fas stimulation failed to induce cell apoptosis and in 1 case it was associated with Fas gene mutation. Our study highlights the importance to evaluate cell apoptosis in the group of children with CAD, which, with this regard, represents a distinct clinical entity. PMID:22971828

  16. Genetic analysis of traits affecting the success of embryo transfer in dairy cattle.

    PubMed

    König, S; Bosselmann, F; von Borstel, U U; Simianer, H

    2007-08-01

    The primary aim of this study was to estimate variance components for traits related to embryo transfer (ET) by applying generalized linear mixed models (GLMM) for different distributions of traits (normal, binomial, and Poisson) in a synergistic context. Synergistic models were originally developed for traits affected by several genotypes, denoted as maternal, paternal, and direct effects. In the case of ET, the number of flushed ova (FO) only depends on a donor's maternal genetic effect, whereas paternal fertility must be considered for other embryo survival traits, such as the number of transferable embryos (TE), the number of degenerated embryos (DE), the number of unfertilized oocytes (UO), and the percentage of transferable embryos (PTE). Data for these traits were obtained from 4,196 flushes of 2,489 Holstein cows within 4 regions of northwest Germany from January 1998 through October 2004. Estimates of maternal heritability were 0.231 for FO, 0.096 for TE, 0.021 for DE, 0.135 for UO, and 0.099 for PTE, whereas the relative genetic impact of the paternal component was near zero. Estimates of the genetic correlations between the maternal and the paternal component were slightly negative, indicating a genetic antagonism. For the analysis of pregnancy after ET, 8,239 transfers to 6,819 different Holstein-Friesian recipients were considered by applying threshold methodology. The direct heritability for pregnancy in the recipient after ET was 0.056. The relative genetic impact of maternal and paternal components on pregnancy of recipients describing a donor's and a sire's ability to produce viable embryos was below 1%. The genetic correlations of the direct effect of the recipient with the sire of embryos (paternal effect) and the donor cow (maternal effect) for pregnancy after ET were -0.32 and -0.14, respectively. With the exception of FO and PTE (-0.17), estimates of genetic correlations among traits for the maternal site were distinctly positive, especially between FO and TE (0.74). Based on this high genetic correlation and due to the higher heritability for FO, indirect selection on FO will increase selection response in TE by about 22% compared with direct selection on TE. The negative genetic correlation of -0.27 between TE and lactation milk yield indicates the need for development of an index for bull dams in multiple ovulation and embryo transfer (MOET) breeding schemes combining production as well as traits related to ET. PMID:17639006

  17. Non-conscious visual cues related to affect and action alter perception of effort and endurance performance

    PubMed Central

    Blanchfield, Anthony; Hardy, James; Marcora, Samuele

    2014-01-01

    The psychobiological model of endurance performance proposes that endurance performance is determined by a decision-making process based on perception of effort and potential motivation. Recent research has reported that effort-based decision-making during cognitive tasks can be altered by non-conscious visual cues relating to affect and action. The effects of these non-conscious visual cues on effort and performance during physical tasks are however unknown. We report two experiments investigating the effects of subliminal priming with visual cues related to affect and action on perception of effort and endurance performance. In Experiment 1 thirteen individuals were subliminally primed with happy or sad faces as they cycled to exhaustion in a counterbalanced and randomized crossover design. A paired t-test (happy vs. sad faces) revealed that individuals cycled significantly longer (178 s, p = 0.04) when subliminally primed with happy faces. A 2 × 5 (condition × iso-time) ANOVA also revealed a significant main effect of condition on rating of perceived exertion (RPE) during the time to exhaustion (TTE) test with lower RPE when subjects were subliminally primed with happy faces (p = 0.04). In Experiment 2, a single-subject randomization tests design found that subliminal priming with action words facilitated a significantly longer TTE (399 s, p = 0.04) in comparison to inaction words. Like Experiment 1, this greater TTE was accompanied by a significantly lower RPE (p = 0.03). These experiments are the first to show that subliminal visual cues relating to affect and action can alter perception of effort and endurance performance. Non-conscious visual cues may therefore influence the effort-based decision-making process that is proposed to determine endurance performance. Accordingly, the findings raise notable implications for individuals who may encounter such visual cues during endurance competitions, training, or health related exercise. PMID:25566014

  18. Nuclear DNA content affects the productivity of conifer forests by altering hydraulic architecture

    NASA Astrophysics Data System (ADS)

    Alday, Josu; Resco de Dios, Víctor

    2014-05-01

    Predictions of future global climate rely on feedbacks between terrestrial vegetation and the global carbon cycle, but the exact mechanisms underlying this relationship are still being discussed. One of the key knowledge gaps lies on the scaling of cellular processes to the ecosystem level. Here we examine whether an under-explored plant trait, inter-specific variation in the bulk amount of DNA in unreplicated somatic cells (2C DNA content), can explain inter-specific variation in the maximum productivity of conifer forests. We expected 2C DNA content to be negatively related to conifer productivity because: 1) it is positively correlated with cell volume (which, in turn, potentially affects structural features such as leaf mass area, a strong predictor of photosynthetic capacity); 2) it is positively correlated with stomatal size (with larger stomata leading to lower overall stomatal conductance and, by extension, lower CO2 uptake); and 3) larger genome sizes may reduce P availability in RNA (which has been hypothesized to slow growth). We present the results of regression and independent contrasts in different monospecific forests encompassing a 52º latitudinal gradient, each being dominated by 1 of 35 different conifer species. Contrary to expectations, we observed a positive correlation between genome size and maximum Gross Primary Productivity (R2 = 0.47) and also between genome size maximum tree height (R2 = 0.27). This correlation was apparently driven by the effects of genome size on stem hydraulics, since 2C DNA was positively correlated with wood density (R2 = 0.40) and also with resistance to cavitation (P50, R2 = 0.28). That is, increased genome sizes have a positive effect on the productivity of conifer forests by affecting the vascular tissues to increase their capacity for water transport. Our results shed a new light on the evolution of the vascular system of conifer forests and how they affect ecosystem productivity, and indicate the potential to further explore the trait of genome size for understanding global patterns of forest productivity.

  19. Maternal environment affects the genetic basis of seed dormancy in Arabidopsis thaliana.

    PubMed

    Postma, Froukje M; Ågren, Jon

    2015-02-01

    The genetic basis of seed dormancy, a key life history trait important for adaptive evolution in plant populations, has yet been studied only using seeds produced under controlled conditions in greenhouse environments. However, dormancy is strongly affected by maternal environmental conditions, and interactions between seed genotype and maternal environment have been reported. Consequently, the genetic basis of dormancy of seeds produced under natural field conditions remains unclear. We examined the effect of maternal environment on the genetic architecture of seed dormancy using a recombinant inbred line (RIL) population derived from a cross between two locally adapted populations of Arabidopsis thaliana from Italy and Sweden. We mapped quantitative trait loci (QTL) for dormancy of seeds produced in the greenhouse and at the native field sites of the parental genotypes. The Italian genotype produced seeds with stronger dormancy at fruit maturation than did the Swedish genotype in all three environments, and the maternal field environments induced higher dormancy levels compared to the greenhouse environment in both genotypes. Across the three maternal environments, a total of nine dormancy QTL were detected, three of which were only detected among seeds matured in the field, and six of which showed significant QTL × maternal environment interactions. One QTL had a large effect on dormancy across all three environments and colocalized with the candidate gene DOG1. Our results demonstrate the importance of studying the genetic basis of putatively adaptive traits under relevant conditions. PMID:25640699

  20. Altering the primacy bias--how does a prior task affect mismatch negativity?

    PubMed

    Mullens, Daniel; Woodley, Jessica; Whitson, Lisa; Provost, Alexander; Heathcote, Andrew; Winkler, István; Todd, Juanita

    2014-05-01

    The role in which two tones are first encountered in an unattended oddball sequence affects how deviance detection, reflected by mismatch negativity, treats them later when the roles reverse: a "primacy bias." We tested whether this effect is modulated by previous behavioral relevance assigned to the two tones. To this end, sequences in which the roles of the two tones alternated were preceded by a go/no-go task in which tones were presented with equal probability. Half of the participants were asked to respond to the short sounds, the other half to long sounds. Primacy bias was initially abolished but returned dependent upon the go-stimulus that the participant was assigned. Results demonstrate a long-term impact of prior learning on deviance detection, and that even when prior importance/equivalence is learned, the bias ultimately returns. Results are discussed in terms of persistent go-stimulus specific changes in responsiveness to sound. PMID:24611446

  1. Cytoplasmic genome substitution in wheat affects the nuclear-cytoplasmic cross-talk leading to transcript and metabolite alterations

    PubMed Central

    2013-01-01

    Background Alloplasmic lines provide a unique tool to study nuclear-cytoplasmic interactions. Three alloplasmic lines, with nuclear genomes from Triticum aestivum and harboring cytoplasm from Aegilops uniaristata, Aegilops tauschii and Hordeum chilense, were investigated by transcript and metabolite profiling to identify the effects of cytoplasmic substitution on nuclear-cytoplasmic signaling mechanisms. Results In combining the wheat nuclear genome with a cytoplasm of H. chilense, 540 genes were significantly altered, whereas 11 and 28 genes were significantly changed in the alloplasmic lines carrying the cytoplasm of Ae. uniaristata or Ae. tauschii, respectively. We identified the RNA maturation-related process as one of the most sensitive to a perturbation of the nuclear-cytoplasmic interaction. Several key components of the ROS chloroplast retrograde signaling, together with the up-regulation of the ROS scavenging system, showed that changes in the chloroplast genome have a direct impact on nuclear-cytoplasmic cross-talk. Remarkably, the H. chilense alloplasmic line down-regulated some genes involved in the determination of cytoplasmic male sterility without expressing the male sterility phenotype. Metabolic profiling showed a comparable response of the central metabolism of the alloplasmic and euplasmic lines to light, while exposing larger metabolite alterations in the H. chilense alloplasmic line as compared with the Aegilops lines, in agreement with the transcriptomic data. Several stress-related metabolites, remarkably raffinose, were altered in content in the H. chilense alloplasmic line when exposed to high light, while amino acids, as well as organic acids were significantly decreased. Alterations in the levels of transcript, related to raffinose, and the photorespiration-related metabolisms were associated with changes in the level of related metabolites. Conclusion The replacement of a wheat cytoplasm with the cytoplasm of a related species affects the nuclear-cytoplasmic cross-talk leading to transcript and metabolite alterations. The extent of these modifications was limited in the alloplasmic lines with Aegilops cytoplasm, and more evident in the alloplasmic line with H. chilense cytoplasm. We consider that, this finding might be linked to the phylogenetic distance of the genomes. PMID:24320731

  2. Plant hybrid zones affect biodiversity: Tools for a genetic-based understanding of community structure

    SciTech Connect

    Whitham, T.G.; Martinsen, G.D.; Keim, P. [Northern Arizona Univ., Flagstaff, AZ (United States); Floate, K.D. [Agriculture and Agri-Food Canada, Lethbridge, Alberta (Canada); Dungey, H.S. [Univ. of Tasmania, Hobart, Tasmania (Australia)]|[Queensland Forest Research Inst., Gympie, Queensland (Australia); Potts, B.M. [Univ. of Tasmania, Hobart, Tasmania (Australia)

    1999-03-01

    Plant hybrid zones are dynamic centers of ecological and evolutionary processes for plants and their associated communities. Studies in the wild and in gardens with synthetic crosses showed that hybrid eucalypts supports the greatest species richness and abundances of insect and fungal taxa. In an updated review of 152 case studies of taxa associated with diverse hybridizing systems, there were 43 (28%) cases of hybrids being more susceptible than their parent species, 7 (5%) resistant, 35 (23%) additive, 35 (23%) dominant, and 32 (21%) showed no response to hybridization. Thus, most taxa respond to hybrids in ways that result in equal or greater abundance, and hybrids tend to accumulate the taxa of their parent species. These studies suggest that genetic-based plant traits affect the distribution of many species and that the variation in hybrids can be used as tools to examine the genetic components of community structure and biodiversity.

  3. Genetic diversity, but not hatching success, is jointly affected by postglacial colonization and isolation in the threatened frog, Rana latastei

    Microsoft Academic Search

    GENTILE FRANCESCO F ICETOLA; TRENTON W. J. G ARNER; FIORENZA DE; B ERNARDI

    2007-01-01

    Both postglacial colonization and habitat fragmentation can reduce the genetic diversity of populations, which in turn can affect fitness. However, since these processes occur at different spatial and temporal scales, the consequences of either process may differ. To disentangle the relative role of isolation and postglacial colonization in determining genetic diversity and fitness, we studied microsatellite diversity of 295 individuals

  4. Copyright 2001 by the Genetics Society of America Genes Affecting the Activity of Nicotinic Receptors Involved in

    E-print Network

    Schafer, William R.

    Copyright © 2001 by the Genetics Society of America Genes Affecting the Activity of Nicotinic of nicotinic acetylcholine receptors such as nicotine and levamisole stimulate egg laying; however, the genetic of levamisole-sensitive nicotinic receptors in nematodes. Seven of these genes, including the nicotinic receptor

  5. ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia and

    E-print Network

    Gaser, Christian

    ZNF804A genetic variation (rs1344706) affects brain grey but not white matter in schizophrenia, Jena, Germany Background. Genetic variation in the gene encoding ZNF804A, a risk gene for schizophrenia, magnetic resonance imaging, psychosis, schizophrenia, voxel-based morphometry, ZNF804A. Introduction

  6. Historical and anthropogenic factors affecting the population genetic structure of Ontario's inland lake populations of Walleye (Sander vitreus).

    PubMed

    Walter, Ryan P; Cena, Christopher J; Morgan, George E; Heath, Daniel D

    2012-01-01

    Populations existing in formerly glaciated areas often display composite historical and contemporary patterns of genetic structure. For Canadian freshwater fishes, population genetic structure is largely reflective of dispersal from glacial refugia and isolation within drainage basins across a range of scales. Enhancement of sport fisheries via hatchery stocking programs and other means has the potential to alter signatures of natural evolutionary processes. Using 11 microsatellite loci genotyped from 2182 individuals, we analyzed the genetic structure of 46 inland lake walleye (Sander vitreus) populations spanning five major drainage basins within the province of Ontario, Canada. Population genetic analyses coupled with genotype assignment allowed us to: 1) characterize broad- and fine-scale genetic structure among Ontario walleye populations; and 2) determine if the observed population divergence is primarily due to natural or historical processes, or recent anthropogenic events. The partitioning of genetic variation revealed higher genetic divergence among lakes than among drainage basins or proposed ancestries-indicative of relatively high isolation among lakes, study-wide. Walleye genotypes were clustered into three major groups, likely reflective of Missourian, Mississippian, and Atlantic glacial refugial ancestry. Despite detectable genetic signatures indicative of anthropogenic influences, province-wide spatial genetic structure remains consistent with the hypothesis of dispersal from distinct glacial refugia and subsequent isolation of lakes within primary drainage basins. Our results provide a novel example of minimal impacts from fishery enhancement to the broad-scale genetic structure of inland fish populations. PMID:23125407

  7. An AscI Boundary Library for the Studies of Genetic and Epigenetic Alterations in CpG Islands

    PubMed Central

    Dai, Zunyan; Weichenhan, Dieter; Wu, Yue-Zhong; Hall, Julia L; Rush, Laura J.; Smith, Laura T.; Raval, Aparna; Yu, Li; Kroll, Daniela; Muehlisch, Joerg; Frühwald, Michael C.; de Jong, Pieter; Catanese, Joe; Davuluri, Ramana V.; Smiraglia, Dominic J.; Plass, Christoph

    2002-01-01

    Knudson's two-hit hypothesis postulates that genetic alterations in both alleles are required for the inactivation of tumor-suppressor genes. Genetic alterations include small or large deletions and mutations. Over the past years, it has become clear that epigenetic alterations such as DNA methylation are additional mechanisms for gene silencing. Restriction Landmark Genomic Scanning (RLGS) is a two-dimensional gel electrophoresis that assesses the methylation status of thousands of CpG islands. RLGS has been applied successfully to scan cancer genomes for aberrant DNA methylation patterns. So far, the majority of this work was done using NotI as the restriction landmark site. Here, we describe the development of RLGS using AscI as the restriction landmark site for genome-wide scans of cancer genomes. The availability of AscI as a restriction landmark for RLGS allows for scanning almost twice as many CpG islands in the human genome compared with using NotI only. We describe the development of an AscI–EcoRV boundary library that supports the cloning of novel methylated genes. Feasibility of this system is shown in three tumor types, medulloblastomas, lung cancers, and head and neck cancers. We report the cloning of 178 AscI RLGS fragments via two methods by use of this library. [Supplemental material is available online at http://www.genome.org.] PMID:12368252

  8. Fc Engineering of Human IgG1 for Altered Binding to the Neonatal Fc Receptor Affects Fc Effector Functions

    PubMed Central

    Grevys, Algirdas; Bern, Malin; Foss, Stian; Bratlie, Diane Bryant; Moen, Anders; Gunnarsen, Kristin Støen; Aase, Audun; Michaelsen, Terje Einar; Sandlie, Inger

    2015-01-01

    Engineering of the constant Fc part of monoclonal human IgG1 (hIgG1) Abs is an approach to improve effector functions and clinical efficacy of next-generation IgG1-based therapeutics. A main focus in such development is tailoring of in vivo half-life and transport properties by engineering the pH-dependent interaction between IgG and the neonatal Fc receptor (FcRn), as FcRn is the main homeostatic regulator of hIgG1 half-life. However, whether such engineering affects binding to other Fc-binding molecules, such as the classical Fc?Rs and complement factor C1q, has not been studied in detail. These effector molecules bind to IgG1 in the lower hinge–CH2 region, structurally distant from the binding site for FcRn at the CH2–CH3 elbow region. However, alterations of the structural composition of the Fc may have long-distance effects. Indeed, in this study we show that Fc engineering of hIgG1 for altered binding to FcRn also influences binding to both the classical Fc?Rs and complement factor C1q, which ultimately results in alterations of cellular mechanisms such as Ab-dependent cell-mediated cytotoxicity, Ab-dependent cellular phagocytosis, and Ab-dependent complement-mediated cell lysis. Thus, engineering of the FcRn–IgG1 interaction may greatly influence effector functions, which has implications for the therapeutic efficacy and use of Fc-engineered hIgG1 variants. PMID:25904551

  9. Altered brain activation in dorsolateral prefrontal cortex in adolescents and young adults at genetic risk for schizophrenia: An fMRI study of working memory

    Microsoft Academic Search

    Larry J. Seidman; Heidi W. Thermenos; Russell A. Poldrack; Nicole K. Peace; Jennifer K. Koch; Stephen V. Faraone; Ming T. Tsuang

    2006-01-01

    ObjectiveAdult first-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness, demonstrate working memory (WM) impairments, and manifest alterations in dorsolateral prefrontal cortical (DLPFC) function during WM. Because substantially less is known about these phenotypes in adolescent subjects we sought to demonstrate that young relatives of persons with schizophrenia manifest impaired WM and altered prefrontal activation.

  10. [Altered intestinal P-glycoprotein expression levels affect pharmacodynamics under diabetic condition].

    PubMed

    Nawa, Ayaka; Fujita-Hamabe, Wakako; Kisioka, Shiroh; Tokuyama, Shogo

    2012-01-01

    P-glycoprotein (P-gp), one of the important drug-efflux pumps, is known to affect pharmacokinetics and pharmacodynamics of P-gp substrate drugs. We have previously reported that intestinal P-gp expression levels are transiently decreased in streptozotocin (STZ)-induced type 1 diabetic mouse model. Herein, we examined the analgesic effects of orally administered morphine and its pharmacokinetic properties under diabetic conditions, specifically focusing on the involvement of intestinal P-gp in a type 1 diabetic mouse model. Type 1 diabetes was induced in male ddY mice by an i.p. injection of STZ (230 mg/kg). We assessed the oral morphine analgesia using the tail-flick test. Serum and brain morphine content were determined on a HPLC-ECD system. Intestinal P-gp expression levels were significantly decreased on day 9 after STZ administration. On the other hands, oral morphine analgesia, and serum and brain morphine content were significantly increased on day 9 after STZ administration. The decrease in the intestinal P-gp expression levels were suppressed by aminoguanidine, a specific iNOS inhibitor. Interestingly, the increase in the analgesic effect of morphine, as well as serum and brain morphine content, was suppressed by aminoguanidine. Conversely, there was no change in the analgesic effect obtained with subcutaneous morphine in STZ-treated mice. In conclusions, our findings suggest that the oral morphine analgesia is dependent on intestinal P-gp expression, and that may be one of the problems against obtaining stable pharmacological effects of morphine in diabetic patients. PMID:22293693

  11. Altered Cerebral Perfusion in Executive, Affective, and Motor Networks During Adolescent Depression

    PubMed Central

    Ho, Tiffany C.; Wu, Jing; Shin, David D.; Liu, Thomas T.; Tapert, Susan F.; Yang, Guang; Connolly, Colm G.; Frank, Guido K.W.; Max, Jeffrey E.; Wolkowitz, Owen; Eisendrath, Stuart; Hoeft, Fumiko; Banerjee, Dipavo; Hood, Korey; Hendren, Robert L.; Paulus, Martin P.; Simmons, Alan N.; Yang, Tony T.

    2013-01-01

    Objective While substantial literature has reported regional cerebral blood flow (rCBF) abnormalities in adults with depression, these studies commonly necessitated the injection of radioisotopes into subjects. The recent development of arterial spin labeling (ASL), however, allows for noninvasive measurements of rCBF. Currently, no published ASL studies have examined cerebral perfusion in adolescents with depression. Thus, the aim of the present study was to examine baseline cerebral perfusion in adolescent depression using a newly developed ASL technique: pseudocontinuous arterial spin labeling (PCASL). Method 25 medication-naive adolescents (ages 13–17 years) diagnosed with major depressive disorder (MDD) and 26 well-matched controls underwent functional magnetic resonance imaging. Baseline rCBF was measured via a novel PCASL method that optimizes tagging efficiency. Results Voxel-based whole brain analyses revealed significant frontal, limbic, paralimbic, and cingulate hypoperfusion in the group with depression (p<0.05, corrected). Hyperperfusion was also observed within the subcallosal cingulate, putamen, and fusiform gyrus (p<0.05, corrected). Similarly, region-of-interest analyses revealed amygdalar and insular hypoperfusion in the group with depression, as well as hyperperfusion in the putamen and superior insula (p<0.05, corrected). Conclusions Adolescents with depression and healthy adolescents appear to differ on rCBF in executive, affective, and motor networks. Dysfunction in these regions may contribute to the cognitive, emotional, and psychomotor symptoms commonly present in adolescent depression. These findings point to possible biomarkers for adolescent depression that could inform early interventions and treatments and establishes a methodology for using PCASL to noninvasively measure rCBF in clinical and healthy adolescent populations. PMID:24074474

  12. Evaluating alterations of genetic diversity in sunfish populations exposed to contaminants using RAPD assay

    Microsoft Academic Search

    Susan G Nadig; K. L Lee; S. M Adams

    1998-01-01

    Bioindicators of pollutant exposure can be more sensitive and ecologically relevant than simply measuring levels of pollutants in the environment and are applied here as a tool for assessing environmental stress on aquatic organisms. DNA polymorphisms, detected by using the randomly amplified polymorphic DNA (RAPD) technique, are used as biomarkers to assess genetic diversity and genetic distance among populations of

  13. Polluted water concentrates: Induction of genetic alterations in Saccharomyces cerevisiae D7 strain

    Microsoft Academic Search

    J. Moretton; P. Baró; A. Zelazny; M. D'Aquino

    1991-01-01

    In a previous paper the authors showed that samples of raw water obtained from the Riachuelo (a heavily polluted watercourse) induced genetic effects in Saccharomyces cerevisiae D7 strain. In those tests the raw water samples were assayed within 24 hr and only the mutagenic activity of the non-volatile, water soluble constituents could be detected. The detection and quantitation of genetic

  14. Genetic variations alter physiological responses following heat stress in two laying hen strains

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heat stress (HS) is a major problem experienced by the poultry industry during high temperature conditions. The ability to manage the detrimental effects of HS can be attributed to multiple factors, including genetic background of flocks. The objective of the present study was to determine the genet...

  15. Stem and progenitor cells in myelodysplastic syndromes show aberrant stage-specific expansion and harbor genetic and epigenetic alterations

    PubMed Central

    Will, Britta; Zhou, Li; Vogler, Thomas O.; Ben-Neriah, Susanna; Schinke, Carolina; Tamari, Roni; Yu, Yiting; Bhagat, Tushar D.; Bhattacharyya, Sanchari; Barreyro, Laura; Heuck, Christoph; Mo, Yonkai; Parekh, Samir; McMahon, Christine; Pellagatti, Andrea; Boultwood, Jacqueline; Montagna, Cristina; Silverman, Lewis; Maciejewski, Jaroslaw; Greally, John M.; Ye, B. Hilda; List, Alan F.; Steidl, Christian

    2012-01-01

    Even though hematopoietic stem cell (HSC) dysfunction is presumed in myelodysplastic syndrome (MDS), the exact nature of quantitative and qualitative alterations is unknown. We conducted a study of phenotypic and molecular alterations in highly fractionated stem and progenitor populations in a variety of MDS subtypes. We observed an expansion of the phenotypically primitive long-term HSCs (lineage?/CD34+/CD38?/CD90+) in MDS, which was most pronounced in higher-risk cases. These MDS HSCs demonstrated dysplastic clonogenic activity. Examination of progenitors revealed that lower-risk MDS is characterized by expansion of phenotypic common myeloid progenitors, whereas higher-risk cases revealed expansion of granulocyte-monocyte progenitors. Genome-wide analysis of sorted MDS HSCs revealed widespread methylomic and transcriptomic alterations. STAT3 was an aberrantly hypomethylated and overexpressed target that was validated in an independent cohort and found to be functionally relevant in MDS HSCs. FISH analysis demonstrated that a very high percentage of MDS HSC (92% ± 4%) carry cytogenetic abnormalities. Longitudinal analysis in a patient treated with 5-azacytidine revealed that karyotypically abnormal HSCs persist even during complete morphologic remission and that expansion of clonotypic HSCs precedes clinical relapse. This study demonstrates that stem and progenitor cells in MDS are characterized by stage-specific expansions and contain epigenetic and genetic alterations. PMID:22753872

  16. Genetic factors involved in the effects of developmental low-level alcohol induced behavioral alterations in rats.

    PubMed

    Cagiano, Raffaele; Cassano, Tommaso; Coluccia, Addolorata; Gaetani, Silvana; Giustino, Arcangela; Steardo, Luca; Tattoli, Maria; Trabace, Luigia; Cuomo, Vincenzo

    2002-02-01

    Behavioral and neurochemical effects of perinatal alcohol exposure (3% v/v solution from Day 15 of gestation to Day 7 after parturition) have been investigated in Sardinian alcohol-preferring (sP) and alcohol-nonpreferring (sNP) rat lines, selectively bred for opposite alcohol preference and consumption. In an elevated zero-maze model of anxiety, sucrose-exposed sP rats (sP-S): (i) spent significantly less time on the open arms (TO); (ii) exhibited a significantly lower number of head dips (HDIPS); and (iii) showed a higher number of stretched attend-postures (SAP) than sucrose-exposed sNP rats (sNP-S) at 90 and 180 days of age. The two rat lines displayed different emotional reactivity in response to alcohol exposure. Subtle differences in sexual behavior and ultrasonic emission (latency to the first intromission and to the first 50 kHz call) were observed between sP-S and sNP-S rats. sP-alcohol exposed (sP-A) offspring exhibited a higher latency to the first intromission than sNP-alcohol (sNP-A) treated rats. Moreover, a lower number of sP-A rats exhibited both intromission and ejaculation with respect to sNP-A animals. sP-S rats were significantly slower in recover of the righting reflex than sNP-S animals after a challenge dose of alcohol (3 g/kg, i.p.). Perinatal alcohol did not affect either onset or duration of sleep time in either line. Neurochemical experiments have shown that perinatal alcohol did not influence basal dopamine levels or amphetamine-induced dopamine increase in the prefrontal cortex of either sP or sNP offspring. These results, showing an endpoint-specific differential sensitivity of sP and sNP lines to perinatal low alcohol exposure, indicate that genetic factors could be responsible for selective susceptibility to behavioral alterations induced by developmental treatment with this drug of abuse. PMID:11790515

  17. Drug-induced and genetic alterations in stress-responsive systems: Implications for specific addictive diseases

    Microsoft Academic Search

    Yan Zhou; Dmitri Proudnikov; Vadim Yuferov; Mary Jeanne Kreek

    2010-01-01

    From the earliest work in our laboratory, we hypothesized, and with studies conducted in both clinical research and animal models, we have shown that drugs of abuse, administered or self-administered, on a chronic basis, profoundly alter stress-responsive systems. Alterations of expression of specific genes involved in stress responsivity, with increases or decreases in mRNA levels, receptor, and neuropeptide levels, and

  18. Mutationally altered 3' ends of yeast CYC1 mRNA affect transcript stability and translational efficiency.

    PubMed

    Zaret, K S; Sherman, F

    1984-07-25

    The cyc1-512 mutant of the yeast Saccharomyces cerevisiae contains a 38 base-pair deletion in the 3' non-coding region of the CYC1 gene, which encodes iso-1-cytochrome c. The deletion affects the CYC1 terminator, causing CYC1 mRNAs to be much longer and more unstable than normal. Previous genetic analysis of revertants of the cyc1-512 mutant indicated that the defect could be completely or partially restored by three classes of genetic events: chromosomal rearrangements; local genetic changes near the original cyc1-512 mutation; and suppressors at unlinked loci. We show that all the revertants with chromosomal rearrangements have breakpoints 3' to the CYC1 locus, resulting in the formation of CYC1 mRNA with new 3' non-coding regions and new 3' mRNA termini. One spontaneous cyc1-512 revertant has a 3' insertion that resembles a repetitive, transposable yeast sequence (Ty1); CYC1 transcripts end just within the bounds of this element. This study reveals that the different 3' non-coding sequences, which arose by chromosomal rearrangements, increase the stability of CYC1 mRNA and have varying effects upon the mRNA translational efficiency. Many of the cyc1-512 revertants contain only local genetic changes that create stronger terminators from the weak terminators observed in the cyc1-512 mutant. Several types of terminators in these revertants have been identified; some cause discrete termination over a relatively small region, while others cause heterogeneous termination over a 200 base-pair region. The DNA sequence changes for two cyc1-512 revertants occur in a region with homology to a consensus sequence for transcription termination in yeast that was proposed by Zaret & Sherman (1982). Two classes of extragenic suppressors of the cyc1-512 mutation have been identified. One class of the suppressors appears specifically to enhance termination at weak terminator sites, while the other class of suppressors appears to increase the stability of aberrantly long CYC1 mRNA. The results from this study support our previous suggestion (Zaret & Sherman, 1982) that, in contrast to the usual situation in higher eukaryotes, transcription termination and polyadenylation may be coupled processes in yeast. PMID:6086937

  19. STABILITY IN A MODEL FOR GENETICALLY ALTERED MOSQUITOS WITH PERIODIC Hubertus F. von Bremen1

    E-print Network

    Sacker, Robert J.

    with more than one million deaths attributed to it every year. Yellow fever, dengue fever, West Nile virus that success in genetically modifying the Mediter- ranean fruit fly, the yellow fever mosquito (Aedes aegypti

  20. Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron–sulfur deficiency and pulmonary hypertension

    PubMed Central

    White, Kevin; Lu, Yu; Annis, Sofia; Hale, Andrew E; Chau, B Nelson; Dahlman, James E; Hemann, Craig; Opotowsky, Alexander R; Vargas, Sara O; Rosas, Ivan; Perrella, Mark A; Osorio, Juan C; Haley, Kathleen J; Graham, Brian B; Kumar, Rahul; Saggar, Rajan; Saggar, Rajeev; Wallace, W Dean; Ross, David J; Khan, Omar F; Bader, Andrew; Gochuico, Bernadette R; Matar, Majed; Polach, Kevin; Johannessen, Nicolai M; Prosser, Haydn M; Anderson, Daniel G; Langer, Robert; Zweier, Jay L; Bindoff, Laurence A; Systrom, David; Waxman, Aaron B; Jin, Richard C; Chan, Stephen Y

    2015-01-01

    Iron–sulfur (Fe-S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR-210-ISCU1/2 axis cause Fe-S deficiencies in vivo and promote PH. In pulmonary vascular cells and particularly endothelium, hypoxic induction of miR-210 and repression of the miR-210 targets ISCU1/2 down-regulated Fe-S levels. In mouse and human vascular and endothelial tissue affected by PH, miR-210 was elevated accompanied by decreased ISCU1/2 and Fe-S integrity. In mice, miR-210 repressed ISCU1/2 and promoted PH. Mice deficient in miR-210, via genetic/pharmacologic means or via an endothelial-specific manner, displayed increased ISCU1/2 and were resistant to Fe-S-dependent pathophenotypes and PH. Similar to hypoxia or miR-210 overexpression, ISCU1/2 knockdown also promoted PH. Finally, cardiopulmonary exercise testing of a woman with homozygous ISCU mutations revealed exercise-induced pulmonary vascular dysfunction. Thus, driven by acquired (hypoxia) or genetic causes, the miR-210-ISCU1/2 regulatory axis is a pathogenic lynchpin causing Fe-S deficiency and PH. These findings carry broad translational implications for defining the metabolic origins of PH and potentially other metabolic diseases sharing similar underpinnings. PMID:25825391

  1. Chemical-genetic profile analysis in yeast suggests that a previously uncharacterized open reading frame, YBR261C, affects protein synthesis

    PubMed Central

    Alamgir, Md; Eroukova, Veronika; Jessulat, Matthew; Xu, Jianhua; Golshani, Ashkan

    2008-01-01

    Background Functional genomics has received considerable attention in the post-genomic era, as it aims to identify function(s) for different genes. One way to study gene function is to investigate the alterations in the responses of deletion mutants to different stimuli. Here we investigate the genetic profile of yeast non-essential gene deletion array (yGDA, ~4700 strains) for increased sensitivity to paromomycin, which targets the process of protein synthesis. Results As expected, our analysis indicated that the majority of deletion strains (134) with increased sensitivity to paromomycin, are involved in protein biosynthesis. The remaining strains can be divided into smaller functional categories: metabolism (45), cellular component biogenesis and organization (28), DNA maintenance (21), transport (20), others (38) and unknown (39). These may represent minor cellular target sites (side-effects) for paromomycin. They may also represent novel links to protein synthesis. One of these strains carries a deletion for a previously uncharacterized ORF, YBR261C, that we term TAE1 for Translation Associated Element 1. Our focused follow-up experiments indicated that deletion of TAE1 alters the ribosomal profile of the mutant cells. Also, gene deletion strain for TAE1 has defects in both translation efficiency and fidelity. Miniaturized synthetic genetic array analysis further indicates that TAE1 genetically interacts with 16 ribosomal protein genes. Phenotypic suppression analysis using TAE1 overexpression also links TAE1 to protein synthesis. Conclusion We show that a previously uncharacterized ORF, YBR261C, affects the process of protein synthesis and reaffirm that large-scale genetic profile analysis can be a useful tool to study novel gene function(s). PMID:19055778

  2. Rare 'de novo' Mutation Causes Schizophrenia: Study -International Business Times http://www.ibtimes.com/articles/194140/20110808/schizophrenia-cause-mutation-genetics-study-research-de-novo-protein-altering.htm[8/10/2011 11:11:41 AM

    E-print Network

    ://www.ibtimes.com/articles/194140/20110808/schizophrenia-cause-mutation-genetics-study-research-de-novo-protein-altering.htm[8 that they are caused by rare "de novo", protein-altering mutations-genetic errors that are present in patients a family history of the disease. In fact, a new study published in Nature Genetics establishes

  3. PI3K isoform dependence of PTEN-deficient tumors can be altered by the genetic context

    PubMed Central

    Schmit, Fabienne; Utermark, Tamara; Zhang, Sen; Wang, Qi; Von, Thanh; Roberts, Thomas M.; Zhao, Jean J.

    2014-01-01

    There has been increasing interest in the use of isoform-selective inhibitors of phosphatidylinositide-3-kinase (PI3K) in cancer therapy. Using conditional deletion of the p110 catalytic isoforms of PI3K to predict sensitivity of cancer types to such inhibitors, we and others have demonstrated that tumors deficient of the phosphatase and tensin homolog (PTEN) are often dependent on the p110? isoform of PI3K. Because human cancers usually arise due to multiple genetic events, determining whether other genetic alterations might alter the p110 isoform requirements of PTEN-null tumors becomes a critical question. To investigate further the roles of p110 isoforms in PTEN-deficient tumors, we used a mouse model of ovarian endometrioid adenocarcinoma driven by concomitant activation of the rat sarcoma protein Kras, which is known to activate p110?, and loss of PTEN. In this model, ablation of p110? had no effect on tumor growth, whereas p110? ablation blocked tumor formation. Because ablation of PTEN alone is often p110? dependent, we wondered if the same held true in the ovary. Because PTEN loss alone in the ovary did not result in tumor formation, we tested PI3K isoform dependence in ovarian surface epithelium (OSE) cells deficient in both PTEN and p53. These cells were indeed p110? dependent, whereas OSEs expressing activated Kras with or without PTEN loss were p110? dependent. Furthermore, isoform-selective inhibitors showed a similar pattern of the isoform dependence in established KrasG12D/PTEN-deficient tumors. Taken together, our data suggest that, whereas in some tissues PTEN-null tumors appear to inherently depend on p110?, the p110 isoform reliance of PTEN-deficient tumors may be altered by concurrent mutations that activate p110?. PMID:24737887

  4. Spatial memory alterations in children with epilepsy of genetic origin or unknown cause.

    PubMed

    Cimadevilla, José Manuel; Lizana, Julio Ramos; Roldán, Maria Dolores; Cánovas, Rosa; Rodríguez, Eva

    2014-06-01

    Genetic generalised epilepsy or epilepsy of unknown cause can remit before adolescence. In many children, the disease does not interfere with their academic achievement. Although there are neuropsychological studies characterising the cognitive profile, there are no studies in this population focused on spatial orientation abilities. In this study, we compared children with genetic generalised epilepsy or epilepsy of unknown cause with a control group using a virtual spatial learning task. Children with epilepsy showed worse performance on the spatial orientation task, although their visuo-spatial memory, attention, and working memory were normal. These results confirm that genetic generalised epilepsy or epilepsy of unknown cause is associated with more cognitive deficits. Virtual reality technologies can complement clinical assessment. PMID:24913814

  5. Embryonic PCB exposure alters phenotypic, genetic, and epigenetic profiles in turtle sex determination, a biomarker of environmental contamination.

    PubMed

    Matsumoto, Yuiko; Hannigan, Brette; Crews, David

    2014-11-01

    In species with temperature-dependent sex determination, embryonic gonadal differentiation can be modified by exposure to exogenous chemicals such as environmental contaminants. Although phenotypic outcomes of such events are well documented, the underlying molecular mechanisms are rarely described. Here we examine the genetic and epigenetic effect of the embryonic exposure to polychlorinated biphenyls (PCBs) on gonad differentiation in red-eared slider turtles (Trachemys scripta). Some PCB congeners are without effect whereas others synergize to alter sex determination in this species. Application of two potent PCB congeners alter the physiological processes of gonad development normally dictated by the male-producing temperature (MPT), resulting sex ratios significantly biased toward female hatchlings. Of these PCB-induced females, oviduct formation is prominently distorted regardless of ovary development. Further, gonadal expression of ovarian markers, aromatase, FoxL2, and Rspo1, is activated whereas testicular markers, Dmrt1 and Sox9, are suppressed compared with typical expression patterns observed at MPT. DNA methylation profiles of the aromatase promoter in PCB-treated gonads do not follow the typical methylation pattern observed in embryos incubating at female-producing temperature. Rather, the MPT-typical methylation profiles is retained despite the induced ovarian formation. Overall, our studies demonstrate that PCB exposure alters the transcriptional profiles of genes responsible for gonadal differentiation but does not re-establish the epigenetic marks of the aromatase promoter normally set by incubation temperatures in embryonic gonads. PMID:25105783

  6. Concurrent genetic alterations in DNA polymerase proofreading and mismatch repair in human colorectal cancer

    Microsoft Academic Search

    Rintaro Yoshida; Kaname Miyashita; Mayuko Inoue; Akiyoshi Shimamoto; Zhao Yan; Akinori Egashira; Eiji Oki; Yoshishiro Kakeji; Shinya Oda; Yoshihiko Maehara

    2011-01-01

    Genomic sequences encoding the 3? exonuclease (proofreading) domains of both replicative DNA polymerases, pol delta and pol epsilon, were explored simultaneously in human colorectal carcinomas including six established cell lines. Three unequivocal sequence alterations, including one previously reported, were found, and all these were considered as dysfunctional mutations in light of the local amino-acid sequences. In particular, the F367S mutation

  7. Alterations of Venous Drug Reactivity in Humans: Acquired and Genetic Factors

    Microsoft Academic Search

    Bela Szekacs; William Dachman; Zoltan Vajo

    2000-01-01

    Until recently, studies dealing with veins have almost always been the neglected part of vascular research. Recent data show an increasing rate of venous disease, and increasing evidence supports a role for veins in systemic diseases. The authors discuss and comment on findings of recent studies on venous drug reactivity. Alterations in venous reactivity to alpha- and beta-adrenergic, NO-dependent, and

  8. Genetic obesity alters recruitment of TANK-binding kinase 1 and AKT into hypothalamic lipid rafts domains.

    PubMed

    Delint-Ramirez, Ilse; Maldonado Ruiz, Roger; Torre-Villalvazo, Ivan; Fuentes-Mera, Lizeth; Garza Ocañas, Lourdes; Tovar, Armando; Camacho, Alberto

    2015-01-01

    Lipid rafts (LRs) are membrane subdomains enriched in cholesterol, glycosphingolipids and sphingolipids containing saturated fatty acid. Signaling proteins become concentrated in these microdomains mainly by saturated fatty acid modification, thus facilitating formation of protein complexes and activation of specific signaling pathways. High intake of saturated fatty acids promotes inflammation and insulin resistance, in part by disrupting insulin signaling pathway. Here we investigate whether lipid-induced toxicity in obesity correlates with altered composition of insulin signaling proteins in LRs in the brain. Our results showed that insulin receptor (IR) is highly concentrated in LRs fraction in comparison with soluble or postsynaptic density (PSD) fractions. Analysis of LRs domains from hippocampus of obese mouse showed a significant decrease of IR and its downstream signaling protein AKT, while in the PSD fraction we detected partial decrease of AKT and no changes in the IR concentration. No changes were shown in the soluble extract. In hypothalamus, genetic obesity also decreases interaction of AKT, but we did not detect changes in the IR distribution. However, in this structure genetic obesity increases recruitment of the IR negative regulator TANK-binding kinase 1 (TBK1) into LRs and PSD fraction. No changes of AKT, IR and TBK1 were found in soluble fractions of obese in comparison with lean mice. In vitro studies showed that incubation with saturated palmitic acid but not with unsaturated docosahexaenoic acid (DHA) or palmitoleic acid decreases association of IR and AKT and increases TBK1 recruitment into LRs and PSD domains, emulating what happens in the obese mice. TBK1 recruitment to insoluble domains correlates with decreases of IR tyrosine phosphorylation and ser473 AKT phosphorylation, markers of insulin resistance. These data support the hypothesis that hyperlipidemia associated with genetic obesity alters targeting of TBK1 and insulin signaling proteins into insoluble LRs domains. PMID:25447767

  9. Solar ultraviolet radiation alters alder and birch litter chemistry that in turn affects decomposers and soil respiration.

    PubMed

    Kotilainen, Titta; Haimi, Jari; Tegelberg, Riitta; Julkunen-Tiitto, Riitta; Vapaavuori, Elina; Aphalo, Pedro Jose

    2009-10-01

    Solar ultraviolet (UV)-A and UV-B radiation were excluded from branches of grey alder (Alnus incana) and white birch (Betula pubescens) trees in a field experiment. Leaf litter collected from these trees was used in microcosm experiments under laboratory conditions. The aim was to evaluate the effects of the different UV treatments on litter chemical quality (phenolic compounds, C, N and lignin) and the subsequent effects of these changes on soil fauna and decomposition processes. We measured the decomposition rate of litter, growth of woodlice (Porcellio scaber), soil microbial respiration and abundance of nematodes and enchytraeid worms. In addition, the chemical quality of woodlice feces was analyzed. The exclusion of both UV-A and UV-B had several effects on litter chemistry. Exclusion of UV-B radiation decreased the C content in litter in both tree species. In alder litter, UV exclusion affected concentration of phenolic groups variably, whereas in birch litter there were no significant differences in phenolic compounds. Moreover, further effects on microbial respiration and chemical quality of woodlice feces were apparent. In both tree species, microbial CO(2) evolution was lower in soil with litter produced under exclusion of both UV-A and UV-B radiation when compared to soil with control litter. The N content was higher in the feces of woodlice eating alder litter produced under exclusion of both UV-A and UV-B compared to the control. In addition, there were small changes in the concentration of individual phenolic compounds analyzed from woodlice feces. Our results demonstrate that both UV-A and UV-B alter litter chemistry which in turn affects decomposition processes. PMID:19597848

  10. Altered sucrose synthase and invertase expression affects the local and systemic sugar metabolism of nematode-infected Arabidopsis thaliana plants

    PubMed Central

    Hofmann, Julia

    2014-01-01

    Sedentary endoparasitic nematodes of plants induce highly specific feeding cells in the root central cylinder. From these, the obligate parasites withdraw all required nutrients. The feeding cells were described as sink tissues in the plant’s circulation system that are supplied with phloem-derived solutes such as sugars. Currently, there are several publications describing mechanisms of sugar import into the feeding cells. However, sugar processing has not been studied so far. Thus, in the present work, the roles of the sucrose-cleaving enzymes sucrose synthases (SUS) and invertases (INV) in the development of Heterodera schachtii were studied. Gene expression analyses indicate that both enzymes are regulated transcriptionally. Nematode development was enhanced on multiple INV and SUS mutants. Syncytia of these mutants were characterized by altered enzyme activity and changing sugar pool sizes. Further, the analyses revealed systemically affected sugar levels and enzyme activities in the shoots of the tested mutants, suggesting changes in the source–sink relationship. Finally, the development of the root-knot nematode Meloidogyne javanica was studied in different INV and SUS mutants and wild-type Arabidopsis plants. Similar effects on the development of both sedentary endoparasitic nematode species (root-knot and cyst nematode) were observed, suggesting a more general role of sucrose-degrading enzymes during plant–nematode interactions. PMID:24187419

  11. Partial genetic deletion of neuregulin 1 and adolescent stress interact to alter NMDA receptor binding in the medial prefrontal cortex

    PubMed Central

    Chohan, Tariq W.; Nguyen, An; Todd, Stephanie M.; Bennett, Maxwell R.; Callaghan, Paul; Arnold, Jonathon C.

    2014-01-01

    Schizophrenia is thought to arise due to a complex interaction between genetic and environmental factors during early neurodevelopment. We have recently shown that partial genetic deletion of the schizophrenia susceptibility gene neuregulin 1 (Nrg1) and adolescent stress interact to disturb sensorimotor gating, neuroendocrine activity and dendritic morphology in mice. Both stress and Nrg1 may have converging effects upon N-methyl-D-aspartate receptors (NMDARs) which are implicated in the pathogenesis of schizophrenia, sensorimotor gating and dendritic spine plasticity. Using an identical repeated restraint stress paradigm to our previous study, here we determined NMDAR binding across various brain regions in adolescent Nrg1 heterozygous (HET) and wild-type (WT) mice using [3H] MK-801 autoradiography. Repeated restraint stress increased NMDAR binding in the ventral part of the lateral septum (LSV) and the dentate gyrus (DG) of the hippocampus irrespective of genotype. Partial genetic deletion of Nrg1 interacted with adolescent stress to promote an altered pattern of NMDAR binding in the infralimbic (IL) subregion of the medial prefrontal cortex. In the IL, whilst stress tended to increase NMDAR binding in WT mice, it decreased binding in Nrg1 HET mice. However, in the DG, stress selectively increased the expression of NMDAR binding in Nrg1 HET mice but not WT mice. These results demonstrate a Nrg1-stress interaction during adolescence on NMDAR binding in the medial prefrontal cortex. PMID:25324742

  12. Phytoplasmal infection derails genetically preprogrammed meristem fate and alters plant architecture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the life cycle of higher plants, it is the fate of meristem cells that determines the pattern of growth and development, and therefore plant morphotype and fertility. Floral transition, the turning point from vegetative growth to reproductive development, is achieved via genetically-programmed s...

  13. An rRNA Fragment and Its Antisense Can Alter Decoding of Genetic Information

    Microsoft Academic Search

    ALEXEY L. ARKOV; ALEXANDER MANKIN; EMANUEL J. MURGOLA

    1998-01-01

    rRNA plays a central role in protein synthesis and is intimately involved in the initiation, elongation, and termination stages of translation. However, the mode of its participation in these reactions, particularly as to the decoding of genetic information, remains elusive. In this paper, we describe a new approach that allowed us to identify an rRNA segment whose function is likely

  14. The hyperactive syndrome: Metanalysis of genetic alterations, pharmacological treatments and brain lesions which increase locomotor activity

    Microsoft Academic Search

    Davide Viggiano

    2008-01-01

    The large number of transgenic mice realized thus far with different purposes allows addressing new questions, such as which animals, over the entire set of transgenic animals, show a specific behavioural abnormality. In the present study, we have used a metanalytical approach to organize a database of genetic modifications, brain lesions and pharmacological interventions that increase locomotor activity in animal

  15. Silviculture alters the genetic structure of an eastern hemlock forest in Maine, USA

    Microsoft Academic Search

    Gary J. Hawley; Paul G. Schaberg; Donald H. DeHayes; John C. Brissette

    2005-01-01

    We evaluated the influence of long-term silvicultural selection on the genetic structure of an eastern hemlock (Tsuga canadensis (L.) Carr.) forest at the Penobscot Experimental Forest, in Maine, USA. Plots in this forest received one of the following three treatments: (1) selection cuts in which small and poorly formed trees were preferentially re- moved in 1957 and 1977; (2) diameter-limit

  16. Is the Genetic Landscape of the Deep Subsurface Biosphere Affected by Viruses?

    PubMed Central

    Anderson, Rika E.; Brazelton, William J.; Baross, John A.

    2011-01-01

    Viruses are powerful manipulators of microbial diversity, biogeochemistry, and evolution in the marine environment. Viruses can directly influence the genetic capabilities and the fitness of their hosts through the use of fitness factors and through horizontal gene transfer. However, the impact of viruses on microbial ecology and evolution is often overlooked in studies of the deep subsurface biosphere. Subsurface habitats connected to hydrothermal vent systems are characterized by constant fluid flux, dynamic environmental variability, and high microbial diversity. In such conditions, high adaptability would be an evolutionary asset, and the potential for frequent host–virus interactions would be high, increasing the likelihood that cellular hosts could acquire novel functions. Here, we review evidence supporting this hypothesis, including data indicating that microbial communities in subsurface hydrothermal fluids are exposed to a high rate of viral infection, as well as viral metagenomic data suggesting that the vent viral assemblage is particularly enriched in genes that facilitate horizontal gene transfer and host adaptability. Therefore, viruses are likely to play a crucial role in facilitating adaptability to the extreme conditions of these regions of the deep subsurface biosphere. We also discuss how these results might apply to other regions of the deep subsurface, where the nature of virus–host interactions would be altered, but possibly no less important, compared to more energetic hydrothermal systems. PMID:22084639

  17. Genetic Alteration of the c-myc Protooncogene (MYC) in Human Primary Breast Carcinomas

    Microsoft Academic Search

    Chantal Escot; Charles Theillet; Rosette Lidereau; Frederique Spyratos; Marie-Helene Champeme; Jean Gest; Robert Callahan

    1986-01-01

    We have studied the genomic organization of the c-myc locus (MYC) from 121 human primary breast carcinomas. Two types of alterations were observed: (i) the c-myc protooncogene appeared to be amplified 2- to 15-fold in 38 (32%) of the carcinoma DNAs and (ii) a non-germ-line c-myc-related fragment of variable size was detected in 5 primary breast carcinoma DNAs. With three

  18. Tuning to the significant: neural and genetic processes underlying affective enhancement of visual perception and memory.

    PubMed

    Markovic, Jelena; Anderson, Adam K; Todd, Rebecca M

    2014-02-01

    Emotionally arousing events reach awareness more easily and evoke greater visual cortex activation than more mundane events. Recent studies have shown that they are also perceived more vividly and that emotionally enhanced perceptual vividness predicts memory vividness. We propose that affect-biased attention (ABA) - selective attention to emotionally salient events - is an endogenous attentional system tuned by an individual's history of reward and punishment. We present the Biased Attention via Norepinephrine (BANE) model, which unifies genetic, neuromodulatory, neural and behavioural evidence to account for ABA. We review evidence supporting BANE's proposal that a key mechanism of ABA is locus coeruleus-norepinephrine (LC-NE) activity, which interacts with activity in hubs of affective salience networks to modulate visual cortex activation and heighten the subjective vividness of emotionally salient stimuli. We further review literature on biased competition and look at initial evidence for its potential as a neural mechanism behind ABA. We also review evidence supporting the role of the LC-NE system as a driving force of ABA. Finally, we review individual differences in ABA and memory including differences in sensitivity to stimulus category and valence. We focus on differences arising from a variant of the ADRA2b gene, which codes for the alpha2b adrenoreceptor as a way of investigating influences of NE availability on ABA in humans. PMID:24269973

  19. Fire alters patterns of genetic diversity among three lizard species in Florida Scrub habitat

    Microsoft Academic Search

    A W Schrey; K G Ashton; S Heath; R Mushinsky

    2011-01-01

    The Florida Sand Skink (Plestiodon reynoldsi), the Florida Scrub Lizard (Sceloporus woodi), and the Six-lined Racerunner (Aspidoscelis sexlineata) occur in the threatened and fire-maintained Florida scrub habitat. Fire may have different consequences to local genetic diversity of these species because they each have different microhabitat preference. We collected tissue samples of each species from 3 sites with different time-since-fire: Florida

  20. Development of a certified reference material for genetically modified potato with altered starch composition.

    PubMed

    Broothaerts, Wim; Corbisier, Philippe; Emons, Hendrik; Emteborg, Håkan; Linsinger, Thomas P J; Trapmann, Stefanie

    2007-06-13

    The presence of genetically modified organisms (GMOs) in food and feed products is subject to regulation in the European Union (EU) and elsewhere. As part of the EU authorization procedure for GMOs intended for food and feed use, reference materials must be produced for the quality control of measurements to quantify the GMOs. Certified reference materials (CRMs) are available for a range of herbicide- and insect-resistant genetically modified crops such as corn, soybean, and cotton. Here the development of the first CRM for a GMO that differs from its non-GMO counterpart in a major compositional constituent, that is, starch, is described. It is shown that the modification of the starch composition of potato (Solanum tuberosum L.) tubers, together with other characteristics of the delivered materials, have important consequences for the certification strategy. Moreover, the processing and characterization of the EH92-527-1 potato material required both new and modified procedures, different from those used routinely for CRMs produced from genetically modified seeds. PMID:17508757

  1. Genetic variants in ABCA1 promoter affect transcription activity and plasma HDL level in pigs.

    PubMed

    Dang, Xiao-yong; Chu, Wei-wei; Shi, Heng-chuan; Yu, Shi-gang; Han, Hai-yin; Gu, Shu-Hua; Chen, Jie

    2015-01-25

    Excess accumulation of cholesterol in plasma may result in coronary artery disease. Numerous studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for plasma high density lipoprotein (HDL) formation. Higher plasma levels of HDL are associated with lower risk for cardiovascular disease. Studies of human disease and animal models had shown that an increased hepatic ABCA1 activity relates to an enhanced plasma HDL level. In this study, we hypothesized that functional mutations in the ABCA1 promoter in pigs may affect gene transcription activity, and consequently the HDL level in plasma. The promoter region of ABCA1 was comparatively scanned by direct sequencing with pool DNA of high- and low-HDL groups (n=30 for each group). Two polymorphisms, c. - 608A>G and c. - 418T>A, were revealed with reverse allele distribution in the two groups. The two polymorphisms were completely linked and formed only G-A or A-T haplotypes when genotyped in a larger population (n=526). Furthermore, we found that the G-A/G-A genotype was associated with higher HDL and ABCA1 mRNA level than A-T/A-T genotype. Luciferase assay also revealed that G-A haplotype promoter had higher activity than A-T haplotype. Single-nucleotide mutant assay showed that c.-418T>A was the causal mutation for ABCA1 transcription activity alteration. Conclusively, we identified two completely linked SNPs in porcine ABCA1 promoter region which have influence on the plasma HDL level by altering ABCA1 gene transcriptional activity. PMID:25445391

  2. Impact of Genetic Risk Information and Type of Disease on Perceived Risk, Anticipated Affect, and Expected Consequences of Genetic Tests

    Microsoft Academic Search

    Linda D. Cameron; Kerry A. Sherman; Theresa M. Marteau; Paul M. Brown

    2009-01-01

    Objective: Genetic tests vary in their prediction of disease occurrence, with some mutations conferring relatively low risk and others indicating near certainty. The authors assessed how increments in absolute risk of disease influence risk perceptions, interest, and expected consequences of genetic tests for diseases of varying severity. Design: Adults (N = 752), recruited from New Zealand, Australia, and the United

  3. ALTERING THE PHYSICAL ENVIRONMENT AFFECTS GROWTH, MORPHOGENESIS AND ESSENTIAL OIL PRODUCTION IN MENTHA SPICATA L. SHOOTS IN VITRO

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Altering the physical environment profoundly alters the growth (fresh weight), morphogenesis (leave, root and shoot numbers) and secondary metabolism [i.e., production of the monoterpene (-)-carvone] of Mentha spicata L. (spearmint) shoots cultured on Murashige and Skoog medium. The type of physica...

  4. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses

    Cancer.gov

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation. The use of isogenic cell lines also helped identify synthetic lethal relationships, or tumor gene dependencies.

  5. Quantitative Chemical-Genetic Interaction Map Connects Gene Alterations to Drug Responses | Office of Cancer Genomics

    Cancer.gov

    In a recent Cancer Discovery report, CTD2 researchers at the University of California in San Francisco developed a new quantitative chemical-genetic interaction mapping approach to evaluate drug sensitivity or resistance in isogenic cell lines. Performing a high-throughput screen with isogenic cell lines allowed the researchers to explore the impact of a panel of emerging and established drugs on cells overexpressing a single cancer-associated gene in isolation. The use of isogenic cell lines also helped identify synthetic lethal relationships, or tumor gene dependencies.

  6. Does wheat genetically modified for disease resistance affect root-colonizing pseudomonads and arbuscular mycorrhizal fungi?

    PubMed

    Meyer, Joana Beatrice; Song-Wilson, Yi; Foetzki, Andrea; Luginbühl, Carolin; Winzeler, Michael; Kneubühler, Yvan; Matasci, Caterina; Mascher-Frutschi, Fabio; Kalinina, Olena; Boller, Thomas; Keel, Christoph; Maurhofer, Monika

    2013-01-01

    This study aimed to evaluate the impact of genetically modified (GM) wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF). Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denaturing gradient gel electrophoresis (DGGE) method to characterize the diversity of the pqqC gene, which is involved in Pseudomonas phosphate solubilization. A major result was that in the first field season Pseudomonas abundances and diversity on roots of GM pm3b lines, but also on non-GM sister lines were different from those of the parental lines and conventional wheat cultivars. This indicates a strong effect of the procedures by which these plants were created, as GM and sister lines were generated via tissue cultures and propagated in the greenhouse. Moreover, Pseudomonas population sizes and DGGE profiles varied considerably between individual GM lines with different genomic locations of the pm3b transgene. At individual time points, differences in Pseudomonas and AMF accumulation between GM and control lines were detected, but they were not consistent and much less pronounced than differences detected between young and old plants, different conventional wheat cultivars or at different locations and field seasons. Thus, we conclude that impacts of GM wheat on plant-beneficial root-colonizing microorganisms are minor and not of ecological importance. The cultivation-independent pqqC-DGGE approach proved to be a useful tool for monitoring the dynamics of Pseudomonas populations in a wheat field and even sensitive enough for detecting population responses to altered plant physiology. PMID:23372672

  7. Does Wheat Genetically Modified for Disease Resistance Affect Root-Colonizing Pseudomonads and Arbuscular Mycorrhizal Fungi?

    PubMed Central

    Foetzki, Andrea; Luginbühl, Carolin; Winzeler, Michael; Kneubühler, Yvan; Matasci, Caterina; Mascher-Frutschi, Fabio; Kalinina, Olena; Boller, Thomas; Keel, Christoph; Maurhofer, Monika

    2013-01-01

    This study aimed to evaluate the impact of genetically modified (GM) wheat with introduced pm3b mildew resistance transgene, on two types of root-colonizing microorganisms, namely pseudomonads and arbuscular mycorrhizal fungi (AMF). Our investigations were carried out in field trials over three field seasons and at two locations. Serial dilution in selective King's B medium and microscopy were used to assess the abundance of cultivable pseudomonads and AMF, respectively. We developed a denaturing gradient gel electrophoresis (DGGE) method to characterize the diversity of the pqqC gene, which is involved in Pseudomonas phosphate solubilization. A major result was that in the first field season Pseudomonas abundances and diversity on roots of GM pm3b lines, but also on non-GM sister lines were different from those of the parental lines and conventional wheat cultivars. This indicates a strong effect of the procedures by which these plants were created, as GM and sister lines were generated via tissue cultures and propagated in the greenhouse. Moreover, Pseudomonas population sizes and DGGE profiles varied considerably between individual GM lines with different genomic locations of the pm3b transgene. At individual time points, differences in Pseudomonas and AMF accumulation between GM and control lines were detected, but they were not consistent and much less pronounced than differences detected between young and old plants, different conventional wheat cultivars or at different locations and field seasons. Thus, we conclude that impacts of GM wheat on plant-beneficial root-colonizing microorganisms are minor and not of ecological importance. The cultivation-independent pqqC-DGGE approach proved to be a useful tool for monitoring the dynamics of Pseudomonas populations in a wheat field and even sensitive enough for detecting population responses to altered plant physiology. PMID:23372672

  8. Copyright 0 1991 by the GeneticsSocietyof America New SNF Genes, GAL11 and GRRl Affect SUC2 Expressionin

    E-print Network

    Vallier, Laura

    Copyright 0 1991 by the GeneticsSocietyof America New SNF Genes, GAL11 and GRRl Affect SUC2 in raffinose utilization.In addition to mutations in SUCP and previously identified SNF genes, we recovered in previous mutant searches (CARLSON,OSMONDand BOTSTEIN1981;NEIGEBORNand CARLSON1984).The SNF (sucrose

  9. Detecting somatic genetic alterations in tumor specimens by exon capture and massively parallel sequencing.

    PubMed

    Won, Helen H; Scott, Sasinya N; Brannon, A Rose; Shah, Ronak H; Berger, Michael F

    2013-01-01

    Efforts to detect and investigate key oncogenic mutations have proven valuable to facilitate the appropriate treatment for cancer patients. The establishment of high-throughput, massively parallel "next-generation" sequencing has aided the discovery of many such mutations. To enhance the clinical and translational utility of this technology, platforms must be high-throughput, cost-effective, and compatible with formalin-fixed paraffin embedded (FFPE) tissue samples that may yield small amounts of degraded or damaged DNA. Here, we describe the preparation of barcoded and multiplexed DNA libraries followed by hybridization-based capture of targeted exons for the detection of cancer-associated mutations in fresh frozen and FFPE tumors by massively parallel sequencing. This method enables the identification of sequence mutations, copy number alterations, and select structural rearrangements involving all targeted genes. Targeted exon sequencing offers the benefits of high throughput, low cost, and deep sequence coverage, thus conferring high sensitivity for detecting low frequency mutations. PMID:24192750

  10. Genetic and molecular alterations in pancreatic cancer: Implications for personalized medicine

    PubMed Central

    Fang, Yantian; Yao, Qizhi; Chen, Zongyou; Xiang, Jianbin; William, Fisher E.; Gibbs, Richard A.; Chen, Changyi

    2013-01-01

    Recent advances in human genomics and biotechnologies have profound impacts on medical research and clinical practice. Individual genomic information, including DNA sequences and gene expression profiles, can be used for prediction, prevention, diagnosis, and treatment for many complex diseases. Personalized medicine attempts to tailor medical care to individual patients by incorporating their genomic information. In a case of pancreatic cancer, the fourth leading cause of cancer death in the United States, alteration in many genes as well as molecular profiles in blood, pancreas tissue, and pancreas juice has recently been discovered to be closely associated with tumorigenesis or prognosis of the cancer. This review aims to summarize recent advances of important genes, proteins, and microRNAs that play a critical role in the pathogenesis of pancreatic cancer, and to provide implications for personalized medicine in pancreatic cancer. PMID:24172537

  11. REGENERATION METHODS AFFECT GENETIC VARIATION AND STRUCTURE IN SHORTLEAF PINE (PINK3 ECHZNATA MILL.)

    Microsoft Academic Search

    Rajiv G. Raja; Charles G. Tauer; Robert F. Wittwer; Yinghua Huang

    1998-01-01

    The effects of regeneration methods on genetic diversity and structure in shortleaf pine (Pinrrs echinafu >lill.) were examined by quantifying the changes in genetic composition of shortleaf pine stands following harvest by monitoring changes in allele number and frequency at heterozygous loci over time. The results were also compared to the genetic composition ofseed used for artificial regeneration following clear-cutting.

  12. Variation in chlorobenzoate catabolism by Pseudomonas putida P111 as a consequence of genetic alterations

    SciTech Connect

    Brenner, V.; Focht, D.D. (Univ. of California, Riverside, CA (United States)); Hernandez, B.S. (Univ. of Panama (Panama))

    1993-09-01

    Chlorobenzoates are key intermediates in the degradative pathways of polychlorinated biphenyls and benzoate herbicides. Bacteria that cometabolize these pollutants generally accumulate chlorobenzoates because they are not able to grow on them. Special interest has been focused on ortho-chlorobenzoates because they are more refractory to biodegradation. In all of these studies the enzyme responsible for the first attack on the ortho-chlorobenzoates possesses minimal or negligible activity with meta- or para-chlorobenzoates. This study reports evidence for the existence of two separate benzoate dioxygenases in Pseudomonas putida P111 and for the transpostional nature of the clc operon, on the basis of genetic investigations of different phenotypic variants of this strain. 42 refs., 4 figs., 1 tab.

  13. A logistic regression mixture model for interval mapping of genetic trait loci affecting binary phenotypes.

    PubMed

    Deng, Weiping; Chen, Hanfeng; Li, Zhaohai

    2006-02-01

    Often in genetic research, presence or absence of a disease is affected by not only the trait locus genotypes but also some covariates. The finite logistic regression mixture models and the methods under the models are developed for detection of a binary trait locus (BTL) through an interval-mapping procedure. The maximum-likelihood estimates (MLEs) of the logistic regression parameters are asymptotically unbiased. The null asymptotic distributions of the likelihood-ratio test (LRT) statistics for detection of a BTL are found to be given by the supremum of a chi2-process. The limiting null distributions are free of the null model parameters and are determined explicitly through only four (backcross case) or nine (intercross case) independent standard normal random variables. Therefore a threshold for detecting a BTL in a flanking marker interval can be approximated easily by using a Monte Carlo method. It is pointed out that use of a threshold incorrectly determined by reading off a chi2-probability table can result in an excessive false BTL detection rate much more severely than many researchers might anticipate. Simulation results show that the BTL detection procedures based on the thresholds determined by the limiting distributions perform quite well when the sample sizes are moderately large. PMID:16272416

  14. Abundance and Genetic Diversity of nifH Gene Sequences in Anthropogenically Affected Brazilian Mangrove Sediments

    PubMed Central

    Dias, Armando Cavalcante Franco; Pereira e Silva, Michele de Cassia; Cotta, Simone Raposo; Dini-Andreote, Francisco; Soares, Fábio Lino; Salles, Joana Falcão; Azevedo, João Lúcio; van Elsas, Jan Dirk

    2012-01-01

    Although mangroves represent ecosystems of global importance, the genetic diversity and abundance of functional genes that are key to their functioning scarcely have been explored. Here, we present a survey based on the nifH gene across transects of sediments of two mangrove systems located along the coast line of São Paulo state (Brazil) which differed by degree of disturbance, i.e., an oil-spill-affected and an unaffected mangrove. The diazotrophic communities were assessed by denaturing gradient gel electrophoresis (DGGE), quantitative PCR (qPCR), and clone libraries. The nifH gene abundance was similar across the two mangrove sediment systems, as evidenced by qPCR. However, the nifH-based PCR-DGGE profiles revealed clear differences between the mangroves. Moreover, shifts in the nifH gene diversities were noted along the land-sea transect within the previously oiled mangrove. The nifH gene diversity depicted the presence of nitrogen-fixing bacteria affiliated with a wide range of taxa, encompassing members of the Alphaproteobacteria, Betaproteobacteria, Gammaproteobacteria, Firmicutes, and also a group of anaerobic sulfate-reducing bacteria. We also detected a unique mangrove-specific cluster of sequences denoted Mgv-nifH. Our results indicate that nitrogen-fixing bacterial guilds can be partially endemic to mangroves, and these communities are modulated by oil contamination, which has important implications for conservation strategies. PMID:22941088

  15. Citrus Leaf Volatiles as Affected by Developmental Stage and Genetic Type

    PubMed Central

    Azam, Muhammad; Jiang, Qian; Zhang, Bo; Xu, Changjie; Chen, Kunsong

    2013-01-01

    Major volatiles from young and mature leaves of different citrus types were analyzed by headspace-solid phase microextraction (HS-SPME)-GC-MS. A total of 123 components were identified form nine citrus cultivars, including nine aldehydes, 19 monoterpene hydrocarbons, 27 oxygenated monoterpenes, 43 sesquiterpene hydrocarbons, eight oxygenated sesquiterpenes, two ketones, six esters and nine miscellaneous. Young leaves produced higher amounts of volatiles than mature leaves in most cultivars. The percentage of aldehyde and monoterpene hydrocarbons increased, whilst oxygenated monoterpenes and sesquiterpenes compounds decreased during leaf development. Linalool was the most abundant compound in young leaves, whereas limonene was the chief component in mature ones. Notably, linalool content decreased, while limonene increased, during leaf development in most cultivars. Leaf volatiles were also affected by genetic types. A most abundant volatile in one or several genotypes can be absent in another one(s), such as limonene in young leaves of lemon vs. Satsuma mandarin and ?-terpinene in mature leaves of three genotypes vs. the other four. Compositional data was subjected to multivariate statistical analysis, and variations in leaf volatiles were identified and clustered into six groups. This research determining the relationship between production of major volatiles from different citrus varieties and leaf stages could be of use for industrial and culinary purposes. PMID:23994837

  16. QTL mapping reveals the genetic architecture of loci affecting pre- and post-zygotic isolating barriers in Louisiana Iris

    PubMed Central

    2012-01-01

    Background Hybridization among Louisiana Irises has been well established and the genetic architecture of reproductive isolation is known to affect the potential for and the directionality of introgression between taxa. Here we use co-dominant markers to identify regions where QTL are located both within and between backcross maps to compare the genetic architecture of reproductive isolation and fitness traits across treatments and years. Results QTL mapping was used to elucidate the genetic architecture of reproductive isolation between Iris fulva and Iris brevicaulis. Homologous co-dominant EST-SSR markers scored in two backcross populations between I. fulva and I. brevicaulis were used to generate genetic linkage maps. These were used as the framework for mapping QTL associated with variation in 11 phenotypic traits likely responsible for reproductive isolation and fitness. QTL were dispersed throughout the genome, with the exception of one region of a single linkage group (LG) where QTL for flowering time, sterility, and fruit production clustered. In most cases, homologous QTL were not identified in both backcross populations, however, homologous QTL for flowering time, number of growth points per rhizome, number of nodes per inflorescence, and number of flowers per node were identified on several linkage groups. Conclusions Two different traits affecting reproductive isolation, flowering time and sterility, exhibit different genetic architectures, with numerous QTL across the Iris genome controlling flowering time and fewer, less distributed QTL affecting sterility. QTL for traits affecting fitness are largely distributed across the genome with occasional overlap, especially on LG 4, where several QTL increasing fitness and decreasing sterility cluster. Given the distribution and effect direction of QTL affecting reproductive isolation and fitness, we have predicted genomic regions where introgression may be more likely to occur (those regions associated with an increase in fitness and unlinked to loci controlling reproductive isolation) and those that are less likely to exhibit introgression (those regions linked to traits decreasing fitness and reproductive isolation). PMID:22702308

  17. Recent and projected increases in atmospheric CO2 concentration can enhance gene flow between wild and genetically altered rice (Oryza sativa)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although recent and projected increases in atmospheric carbon dioxide can alter plant phenological development, these changes have not been quantified in terms of floral outcrossing rates or gene transfer. Could differential phenological development in response to rising CO2 between genetically mod...

  18. Targeting the genetic alterations of the PI3K-AKT-mTOR pathway: its potential use in the treatment of bladder cancers.

    E-print Network

    Boyer, Edmond

    Targeting the genetic alterations of the PI3K-AKT-mTOR pathway: its potential use in the treatment involved in the PI3K/AKT/mTOR signaling pathway that occupies a major place in the etiology of these tumors. Here, we describe the mutations leading to constitutive activation of the PI3K/AKT/mTOR pathway

  19. Changes in Dietary Fat Content Rapidly Alters the Mouse Plasma Coagulation Profile without Affecting Relative Transcript Levels of Coagulation Factors

    PubMed Central

    van Diepen, Janna A.; Verhoef, Daniël; Voshol, Peter J.; Reitsma, Pieter H.; van Vlijmen, Bart J. M.

    2015-01-01

    Background Obesity is associated with a hypercoagulable state and increased risk for thrombotic cardiovascular events. Objective Establish the onset and reversibility of the hypercoagulable state during the development and regression of nutritionally-induced obesity in mice, and its relation to transcriptional changes and clearance rates of coagulation factors as well as its relation to changes in metabolic and inflammatory parameters. Methods Male C57BL/6J mice were fed a low fat (10% kcal as fat; LFD) or high fat diet (45% kcal as fat; HFD) for 2, 4, 8 or 16 weeks. To study the effects of weight loss, mice were fed the HFD for 16 weeks and switched to the LFD for 1, 2 or 4 weeks. For each time point analyses of plasma and hepatic mRNA levels of coagulation factors were performed after overnight fasting, as well as measurements of circulating metabolic and inflammatory parameters. Furthermore, in vivo clearance rates of human factor (F) VII, FVIII and FIX proteins were determined after 2 weeks of HFD-feeding. Results HFD feeding gradually increased the body and liver weight, which was accompanied by a significant increase in plasma glucose levels from 8 weeks onwards, while insulin levels were affected after 16 weeks. Besides a transient rise in cytokine levels at 2 weeks after starting the HFD, no significant effect on inflammation markers was present. Increased plasma levels of fibrinogen, FII, FVII, FVIII, FIX, FXI and FXII were observed in mice on a HFD for 2 weeks, which in general persisted throughout the 16 weeks of HFD-feeding. Interestingly, with the exception of FXI the effects on plasma coagulation levels were not paralleled by changes in relative transcript levels in the liver, nor by decreased clearance rates. Switching from HFD to LFD reversed the HFD-induced procoagulant shift in plasma, again not coinciding with transcriptional modulation. Conclusions Changes in dietary fat content rapidly alter the mouse plasma coagulation profile, thereby preceding plasma metabolic changes, which cannot be explained by changes in relative expression of coagulation factors or decreased clearance rates. PMID:26176620

  20. A subcellular analysis of genetic modulation of PINK1 on mitochondrial alterations, autophagy and cell death.

    PubMed

    Lenzi, P; Marongiu, R; Falleni, A; Gelmetti, V; Busceti, C L; Michiorri, S; Valente, E M; Fornai, F

    2012-01-01

    Mutations in the PTEN-induced putative kinase1 (PINK1) represent the second most frequent cause of autosomal recessive Parkinson's disease. The PINK1 protein mainly localizes to mitochondria and interacts with a variety of proteins, including the pro-autophagy protein beclin1 and the ubiquitin-ligase parkin. Upon stress conditions, PINK1 is known to recruit parkin at the surface of dysfunctional mitochondria and to activate the mitophagy cascade. Aim of this study was to use a simple and highly reproducible catecholamine cell model and transmission electron microscopy to characterize whether PINK1 could affect mitochondrial homeostasis, the recruitment of specific proteins at mitochondria, mitophagy and apoptosis. Samples were analyzed both in baseline conditions and following treatment with methamphetamine (METH), a neurotoxic compound which strongly activates autophagy and produces mitochondrial damage. Our data provide robust sub-cellular evidence that the modulation of PINK1 levels dramatically affects the morphology and number of mitochondria and the amount of cell death. In particular, especially upon METH exposure, PINK1 is able to increase the total number of mitochondria, concurrently recruit beclin1, parkin and ubiquitin and enhance the clearance of damaged mitochondria. In the absence of functional PINK1 and upon autophagy stress, we observe a failure of the autophagy system at large, with marked accumulation of dysfunctional mitochondria and dramatic increase of apoptotic cell death. These findings highlight the strong neuroprotective role of PINK1 as a key protein in the surveillance and regulation of mitochondrial homeostasis. PMID:23165879

  1. Medea selfish genetic elements as tools for altering traits of wild populations: a theoretical analysis.

    PubMed

    Ward, Catherine M; Su, Jessica T; Huang, Yunxin; Lloyd, Alun L; Gould, Fred; Hay, Bruce A

    2011-04-01

    One strategy for controlling transmission of insect-borne disease involves replacing the native insect population with transgenic animals unable to transmit disease. Population replacement requires a drive mechanism to ensure the rapid spread of linked transgenes, the presence of which may result in a fitness cost to carriers. Medea selfish genetic elements have the feature that when present in a female, only offspring that inherit the element survive, a behavior that can lead to spread. Here, we derive equations that describe the conditions under which Medea elements with a fitness cost will spread, and the equilibrium allele frequencies are achieved. Of particular importance, we show that whenever Medea spreads, the non-Medea genotype is driven out of the population, and we estimate the number of generations required to achieve this goal for Medea elements with different fitness costs and male-only introduction frequencies. Finally, we characterize two contexts in which Medea elements with fitness costs drive the non-Medea allele from the population: an autosomal element in which not all Medea-bearing progeny of a Medea-bearing mother survive, and an X-linked element in species in which X/Y individuals are male. Our results suggest that Medea elements can drive population replacement under a wide range of conditions. PMID:21062278

  2. Heteroplasmy of mouse mtDNA is genetically unstable and results in altered behavior and cognition.

    PubMed

    Sharpley, Mark S; Marciniak, Christine; Eckel-Mahan, Kristin; McManus, Meagan; Crimi, Marco; Waymire, Katrina; Lin, Chun Shi; Masubuchi, Satoru; Friend, Nicole; Koike, Maya; Chalkia, Dimitra; MacGregor, Grant; Sassone-Corsi, Paolo; Wallace, Douglas C

    2012-10-12

    Maternal inheritance of mtDNA is the rule in most animals, but the reasons for this pattern remain unclear. To investigate the consequence of overriding uniparental inheritance, we generated mice containing an admixture (heteroplasmy) of NZB and 129S6 mtDNAs in the presence of a congenic C57BL/6J nuclear background. Analysis of the segregation of the two mtDNAs across subsequent maternal generations revealed that proportion of NZB mtDNA was preferentially reduced. Ultimately, this segregation process produced NZB-129 heteroplasmic mice and their NZB or 129 mtDNA homoplasmic counterparts. Phenotypic comparison of these three mtDNA lines demonstrated that the NZB-129 heteroplasmic mice, but neither homoplasmic counterpart, had reduced activity, food intake, respiratory exchange ratio; accentuated stress response; and cognitive impairment. Therefore, admixture of two normal but different mouse mtDNAs can be genetically unstable and can produce adverse physiological effects, factors that may explain the advantage of uniparental inheritance of mtDNA. PMID:23063123

  3. Genetic variation in CNTNAP2 alters brain function during linguistic processing in healthy individuals.

    PubMed

    Whalley, Heather C; O'Connell, Garret; Sussmann, Jessika E; Peel, Anna; Stanfield, Andrew C; Hayiou-Thomas, Marianna E; Johnstone, Eve C; Lawrie, Stephen M; McIntosh, Andrew M; Hall, Jeremy

    2011-12-01

    Language impairments are a characteristic feature of autism and related autism spectrum disorders (ASDs). Autism is also highly heritable and one of the most promising candidate genes implicated in its pathogenesis is contactin-associated protein-like 2 (CNTNAP2), a gene also associated with language impairment. In the current study we investigated the functional effects of variants of CNTNAP2 associated with autism and language impairment (rs7794745 and rs2710102; presumed risk alleles T and C, respectively) in healthy individuals using functional magnetic resonance imaging (fMRI) during performance of a language task (n = 66). Against a background of normal performance and lack of behavioral abnormalities, healthy individuals with the putative risk allele versus those without demonstrated significant increases in activation in the right inferior frontal gyrus (Broca's area homologue) and right lateral temporal cortex. These findings demonstrate that risk associated variation in the CNTNAP2 gene impacts on brain activation in healthy non-autistic individuals during a language processing task providing evidence of the effect of genetic variation in CNTNAP2 on a core feature of ASDs. PMID:21987501

  4. Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells

    PubMed Central

    Subramanian, Hariharan; Pradhan, Prabhakar; Liu, Yang; Capoglu, Ilker R.; Li, Xu; Rogers, Jeremy D.; Heifetz, Alexander; Kunte, Dhananjay; Roy, Hemant K.; Taflove, Allen; Backman, Vadim

    2008-01-01

    Recently, there has been a major thrust to understand biological processes at the nanoscale. Optical microscopy has been exceedingly useful in imaging cell microarchitecture. Characterization of cell organization at the nanoscale, however, has been stymied by the lack of practical means of cell analysis at these small scales. To address this need, we developed a microscopic spectroscopy technique, single-cell partial-wave spectroscopy (PWS), which provides insights into the statistical properties of the nanoscale architecture of biological cells beyond what conventional microscopy reveals. Coupled with the mesoscopic light transport theory, PWS quantifies the disorder strength of intracellular architecture. As an illustration of the potential of the technique, in the experiments with cell lines and an animal model of colon carcinogenesis we show that increase in the degree of disorder in cell nanoarchitecture parallels genetic events in the early stages of carcinogenesis in otherwise microscopically/histologically normal-appearing cells. These data indicate that this advance in single-cell optics represented by PWS may have significant biomedical applications. PMID:19073935

  5. Indirect genetic effects for growth rate in domestic pigs alter aggressive and manipulative biting behaviour.

    PubMed

    Camerlink, Irene; Ursinus, Winanda W; Bijma, Piter; Kemp, Bas; Bolhuis, J Elizabeth

    2015-01-01

    Indirect genetic effects (IGEs) are heritable effects of an individual on phenotypic values of others, and may result from social interactions. We determined the behavioural consequences of selection for IGEs for growth (IGEg) in pigs in a G × E treatment design. Pigs (n = 480) were selected for high versus low IGEg with a contrast of 14 g average daily gain and were housed in either barren or straw-enriched pens (n = 80). High IGEg pigs showed from 8 to 23 weeks age 40% less aggressive biting (P = 0.006), 27% less ear biting (P = 0.03), and 40% less biting on enrichment material (P = 0.005). High IGEg pigs had a lower tail damage score (high 2.0; low 2.2; P = 0.004), and consumed 30 % less jute sacks (P = 0.002). Selection on high IGEg reduced biting behaviours additive to the, generally much larger, effects of straw-bedding (P < 0.01), with no G × E interactions. These results show opportunities to reduce harmful biting behaviours in pigs. PMID:25227986

  6. Detection of ultrastructural changes in genetically altered and exercised skeletal muscle using PS-OCT

    NASA Astrophysics Data System (ADS)

    Pasquesi, James J.; Schlachter, Simon C.; Boppart, Marni D.; Chaney, Eric; Kaufman, Stephen J.; Boppart, Stephen A.

    2006-02-01

    Birefringence of skeletal muscle has been associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Murine skeletal muscle (gastrocnemius) was imaged with a fiber-based PS-OCT imaging system to determine the level of birefringence present in the tissue under various conditions. In addition to muscle controls from wild-type mice, muscle from abnormal mice included: genetically-modified (mdx) mice which model human muscular dystrophy, transgenic mice exhibiting an overexpression of integrin (?7?1), and transgenic integrin (?7?1)knockout mice. Comparisons were also made between rested and exercised muscles to determine the effects of exercise on muscle birefringence for each of these normal and abnormal conditions. The PS-OCT images revealed that the presence of birefringence was similar in the rested muscle with dystrophy-like features (i.e., lacking the structural protein dystrophin - mdx) and in the integrin (?7?1)knockout muscle when compared to the normal (wild-type) control. However, exercising these abnormal muscle tissues drastically reduced the presence of birefringence detected by the PS-OCT system. The muscle exhibiting an overexpression of integrin (?7?1) remained heavily birefringent before and after exercise, similar to the normal (wild-type) muscle. These results suggest that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.

  7. Genetic Association and Altered Gene Expression of Mir-155 in Multiple Sclerosis Patients

    PubMed Central

    Paraboschi, Elvezia Maria; Soldà, Giulia; Gemmati, Donato; Orioli, Elisa; Zeri, Giulia; Benedetti, Maria Donata; Salviati, Alessandro; Barizzone, Nadia; Leone, Maurizio; Duga, Stefano; Asselta, Rosanna

    2011-01-01

    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system characterized by chronic inflammation, demyelination, and axonal damage. As microRNA (miRNA)-dependent alterations in gene expression in hematopoietic cells are critical for mounting an appropriate immune response, miRNA deregulation may result in defects in immune tolerance. In this frame, we sought to explore the possible involvement of miRNAs in MS pathogenesis by monitoring the differential expression of 22 immunity-related miRNAs in peripheral blood mononuclear cells of MS patients and healthy controls, by using a microbead-based technology. Three miRNAs resulted >2 folds up-regulated in MS vs controls, whereas none resulted down-regulated. Interestingly, the most up-regulated miRNA (mir-155; fold change = 3.30; P = 0.013) was previously reported to be up-regulated also in MS brain lesions. Mir-155 up-regulation was confirmed by qPCR experiments. The role of mir-155 in MS susceptibility was also investigated by genotyping four single nucleotide polymorphisms (SNPs) mapping in the mir-155 genomic region. A haplotype of three SNPs, corresponding to a 12-kb region encompassing the last exon of BIC (the B-cell Integration Cluster non-coding RNA, from which mir-155 is processed), resulted associated with the disease status (P = 0.035; OR = 1.36, 95% CI = 1.05–1.77), suggesting that this locus strongly deserves further investigations. PMID:22272099

  8. Titanium Mass-balance Analysis of Paso Robles Soils: Elemental Gains and Losses as Affected by Acid Alteration Fluids

    NASA Technical Reports Server (NTRS)

    Sutter, Brad; Ming, Douglas W.

    2010-01-01

    The Columbia Hills soils have been exposed to aqueous alteration in alkaline [1] as well as acid conditions [2,3]. The Paso Robles class soils are bright soils that possess the highest S concentration of any soil measured on Mars [2]. Ferric-sulfate detection by Moessbauer analysis indicated that acid solutions were involved in forming these soils [4]. These soils are proposed to have formed by alteration of nearby rock by volcanic hydrothermal or fumarolic activity. The Paso Robles soils consist of the original Paso Robles-disturbed-Pasadena (PR-dist), Paso Robles- PasoLight (PR-PL), Arad-Samra, Arad-Hula, Tyrone- Berker Island1 and Tyrone-MountDarwin [2 ,3. ]Chemical characteristics indicate that the PR-dist and PR-PL soils could be derived from acid weathering of local Wishstone rocks while the Samra and Hula soils are likely derived from local Algonquin-Iroquet rock [3]. The Paso Robles soils were exposed to acidic sulfur bearing fluids; however, little else is known about the chemistry of the alteration fluid and its effects on the alteration of the proposed parent materials. The objectives of this work are to conduct titanium normalized mass-balance analysis to1) assess elemental gains and losses from the parent materials in the formation of the Paso Robles soils and 2) utilize this information to indicate the chemical nature of the alteration fluids.

  9. Genetic merit for fertility traits in Holstein cows: V. Factors affecting circulating progesterone concentrations.

    PubMed

    Moore, S G; Scully, S; Browne, J A; Fair, T; Butler, S T

    2014-09-01

    This study investigated the factors affecting circulating progesterone (P4) concentrations in cows with similar genetic merit for milk production traits, but with extremes of good (Fert+) or poor (Fert-) genetic merit for fertility traits. Study 1: 28 cows were enrolled in an ovulation synchronization protocol at 61±13 (±standard deviation) days postpartum, and data are presented for 13 Fert+ and 9 Fert- cows that remained in the study. Progesterone concentrations were determined from d 0 to 9 (d 0=estrus) and on d 7, corpus luteum (CL) volume and blood flow area (BFA) were measured by B-mode and Doppler ultrasonography, respectively. Cows were administered PGF2? on d 7 in the p.m. and d 8 in the a.m. to regress the CL, and 2 controlled internal drug release devices were inserted per vaginum on d 8 in the a.m. Liver biopsies were collected on d 9 and hepatic mRNA abundance of genes involved in P4 catabolism was determined. On d 10, the controlled internal drug release inserts were removed and frequent blood samples were collected to measure the rate of decline in circulating P4. The Fert+ cows tended to have greater dry matter intake compared with Fert- cows (+0.79kg of dry matter/d), but similar milk production (29.82kg/d). After synchronized ovulation, the rate of increase in circulating P4 concentrations was greater in Fert+ cows compared with Fert- cows. No effect of genotype on CL volume was detected, but BFA was 42% greater in Fert+ cows compared with Fert- cows. The Fert- cows had greater mRNA abundance of cytochrome P450, family 3, subfamily A (CYP3A) compared with Fert+ cows, but the mRNA abundance of aldo-keto reductase family 1, member C1 (AKR1C1), AKR1C3, AKR1C4, and cytochrome P450, family 2, subfamily C (CYP2C) were similar. The half-life and metabolic clearance rate of P4 were similar in Fert+ cows and Fert- cows. Study 2: 23 cows were enrolled in an ovulation synchronization protocol at 55±7 (±standard deviation) d postpartum, and data are presented for 13 Fert+ and 8 Fert- cows that remained in the study. On d 4, 7, 10, and 13 (d 0=estrus), CL volume and BFA were measured as in study 1. Progesterone concentrations were measured from d 1 to 13. Corpus luteum volume was 41% greater in Fert+ cows compared with Fert- cows but no effect of genotype on BFA was detected. Mean circulating P4 concentrations were 79% greater in Fert+ cows compared with Fert- cows. Milk yield was similar in both genotypes. The results indicate that greater circulating P4 concentrations were primarily due to greater CL P4 synthetic capacity rather than differences in P4 clearance in this lactating cow genetic model of fertility. PMID:24952779

  10. Genetic background, and not ontogenetic effects, affects avian seasonal timing of reproduction.

    PubMed

    Gienapp, P; van Noordwijk, A J; Visser, M E

    2013-10-01

    Avian seasonal timing is a life-history trait with important fitness consequences and which is currently under directional selection due to climate change. To predict micro-evolution in this trait, it is crucial to properly estimate its heritability. Heritabilities are often estimated from pedigreed wild populations. As these are observational data, it leaves the possibility that the resemblance between related individuals is not due to shared genes but to ontogenetic effects; when the environment for the offspring provided by early laying pairs differs from that by late pairs and the laying dates of these offspring when they reproduce themselves is affected by this environment, this may lead to inflated heritability estimates. Using simulation studies, we first tested whether and how much such an early environmental effect can inflate heritability estimates from animal models, and we showed that pedigree structure determines by how much early environmental effects inflate heritability estimates. We then used data from a wild population of great tits (Parus major) to compare laying dates of females born early in the season in first broods and from sisters born much later, in second broods. These birds are raised under very different environmental conditions but have the same genetic background. The laying dates of first and second brood offspring do not differ when they reproduce themselves, clearly showing that ontogenetic effects are very small and hence, family resemblance in timing is due to genes. This finding is essential for the interpretation of the heritabilities reported from wild populations and for predicting micro-evolution in response to climate change. PMID:23837446

  11. Paradoxical role of C1561T glutamate carboxypeptidase II (GCPII) genetic polymorphism in altering disease susceptibility.

    PubMed

    Divyya, Shree; Naushad, Shaik Mohammad; Addlagatta, Anthony; Murthy, P V L N; Reddy, Ch Ram; Digumarti, Raghunadha Rao; Gottumukkala, Suryanarayana Raju; Kumar, Ajit; Rammurti, S; Kutala, Vijay Kumar

    2012-04-15

    Glutamate carboxypeptidase II (GCPII) is predominantly expressed in brain, intestinal mucosa and prostate cancer in the form of three splice variants i.e. N-acetylated-?-linked acidic dipeptidase (NAALADase), folyl poly-?-glutamate carboxypeptidase (FGCP) and prostate specific membrane antigen (PSMA) respectively. Its inhibition was found to confer protection against certain neurological disorders and cancer. Despite the pivotal role of this enzyme, the most common polymorphism i.e. H475Y has not been explored comprehensively in all its splice variants. In this study, we have determined the role of this variant in different disease conditions such as breast and prostate cancers, autism, coronary artery disease (CAD) and miscarriages (N=1561). Genotyping was done by PCR-RFLP and dideoxy sequencing. Plasma folate levels were estimated by Axysm folate kit. GCPII expression was studied by semi-quantitative RT-PCR. In silico model was developed using PYMOL. We observed the protective role of H475Y variant in cancers [breast cancer; OR (95% CI): 0.81 (0.55-1.19), prostate cancer: OR (95% CI): 0.00 (0.00-0.66)], and in autism (OR (95% CI): 0.47 (0.21-1.03), whereas inflated risk was observed in CAD (OR (95% CI): 1.69 (1.20-2.37) and miscarriages [Maternal OR (95% CI): 3.26 (2.11-5.04); Paternal OR(95% CI): 1.99 (1.23-3.21)]. Further, this variant was found to impair the intestinal folate absorption in subjects with dietary folate intake in the lowest tertile (CC vs. CT in lowest tertile; 7.56±0.85ng/ml vs. 2.73±045ng/ml, p=0.005). In silico model of GCPII showed steric hindrance with H475Y resulting in stereochemical alteration of catalytic site, thus interfering with ligand binding. Statistically significant association was not observed between dietary folate levels and GCPII expression. However, a positive correlation was seen between plasma folate levels and GCPII expression (r=0.70, p<0.05). To conclude, our data suggests that GCPII H475Y variant shows inverse association with autism and cancer while showing positive association with CAD and miscarriages. PMID:22310383

  12. Biofortification of plants with altered antioxidant content and composition: genetic engineering strategies.

    PubMed

    Zhu, Changfu; Sanahuja, Georgina; Yuan, Dawei; Farré, Gemma; Arjó, Gemma; Berman, Judit; Zorrilla-López, Uxue; Banakar, Raviraj; Bai, Chao; Pérez-Massot, Eduard; Bassie, Ludovic; Capell, Teresa; Christou, Paul

    2013-02-01

    Antioxidants are protective molecules that neutralize reactive oxygen species and prevent oxidative damage to cellular components such as membranes, proteins and nucleic acids, therefore reducing the rate of cell death and hence the effects of ageing and ageing-related diseases. The fortification of food with antioxidants represents an overlap between two diverse environments, namely fortification of staple foods with essential nutrients that happen to have antioxidant properties (e.g. vitamins C and E) and the fortification of luxury foods with health-promoting but non-essential antioxidants such as flavonoids as part of the nutraceuticals/functional foods industry. Although processed foods can be artificially fortified with vitamins, minerals and nutraceuticals, a more sustainable approach is to introduce the traits for such health-promoting compounds at source, an approach known as biofortification. Regardless of the target compound, the same challenges arise when considering the biofortification of plants with antioxidants, that is the need to modulate endogenous metabolic pathways to increase the production of specific antioxidants without affecting plant growth and development and without collateral effects on other metabolic pathways. These challenges become even more intricate as we move from the engineering of individual pathways to several pathways simultaneously. In this review, we consider the state of the art in antioxidant biofortification and discuss the challenges that remain to be overcome in the development of nutritionally complete and health-promoting functional foods. PMID:22970850

  13. Response to Dietary Phosphate Deficiency is Affected by Genetic Background in Growing Pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Concern over the environmental impact of phosphate (P) excretion from pig production has led to reduced dietary P supplementation. To examine how genetics influence P utilization, 94 gilts sired by 2 genetic lines (PIC337 and PIC280) were fed either a P adequate diet (PA) or a 20% P deficient diet ...

  14. The Affects of Alteration and Porosity on Seismic Velocities in Oceanic Basalts (and Diabases) Based on Logging Results and Laboratory Studies of Samples Recovered by Drilling

    NASA Astrophysics Data System (ADS)

    Carlson, R.

    2014-12-01

    Seismic velocities in the lavas that cap normal oceanic crust are affected by both crack porosity and alteration of the primary mineral phases, chiefly to clays. Porosity accounts for 75-80% of the velocity variation in sonic log velocities in the lava sections of Holes 504B and 1256D, but the effect of alteration on the properties of the basalts has not been assessed. In this analysis, the grain velocities in basalt and diabase samples have been estimated from an empirical linear relationship between grain density and the P-wave modulus. The estimated velocity in fresh, zero-porosity basalt is 6.96±0.07 km/sec. In basalts, alteration reduces the average grain velocity to 6.74±0.02 km/sec; cracks at the sample scale further reduce the velocity to 5.86±0.03 km/sec, and large-scale cracks in the lava pile reduce the average in situ velocity to 5.2±0.3 km/sec. Cracks thus account for nearly 90% of the difference between seismic (in situ) velocities and the intrinsic velocity in the unaltered solid material. Alteration also accounts for a small, but statistically significant increase of velocity with depth in the lavas. Grain velocities in the diabase samples are statistically indistinguishable from the intrinsic velocity, and show no variation with depth; alteration does not significantly affect the velocities in the diabase samples from Hole 504B. This result is consistent with previous analyses, which have demonstrated that velocities in the dikes are controlled by crack porosity. Except in the uppermost part, velocities in diabase samples measured at 20 MPa match sonic log velocities, indicating that velocities in the dike section are controlled by cracks at the scale of lab samples, as opposed to large-scale cracks in the formation.

  15. Genetic and Phenotypic Analyses of a Papaver somniferum T-DNA Insertional Mutant with Altered Alkaloid Composition.

    PubMed

    Kawano, Noriaki; Kiuchi, Fumiyuki; Kawahara, Nobuo; Yoshimatsu, Kayo

    2012-01-01

    The in vitro shoot culture of a T-DNA insertional mutant of Papaver somniferum L. established by the infection of Agrobacterium rhizogenes MAFF03-01724 accumulated thebaine instead of morphine as a major opium alkaloid. To develop a non-narcotic opium poppy and to gain insight into its genetic background, we have transplanted this mutant to soil, and analyzed its alkaloid content along with the manner of inheritance of T-DNA insertion loci among its selfed progenies. In the transplanted T0 primary mutant, the opium (latex) was found to be rich in thebaine (16.3% of dried opium) by HPLC analysis. The analyses on T-DNA insertion loci by inverse PCR, adaptor-ligation PCR, and quantitative real-time PCR revealed that as many as 18 copies of T-DNAs were integrated into a poppy genome in a highly complicated manner. The number of copies of T-DNAs was decreased to seven in the selected T3 progenies, in which the average thebaine content was 2.4-fold that of the wild type plant. This may indicate that the high thebaine phenotype was increasingly stabilized as the number of T-DNA copies was decreased. In addition, by reverse transcription PCR analysis on selected morphine biosynthetic genes, the expression of codeine 6-O-demethylase was clearly shown to be diminished in the T0 in vitro shoot culture, which can be considered as one of the key factors of altered alkaloid composition. PMID:24288085

  16. Autism spectrum disorders: a qualitative study of attitudes toward prenatal genetic testing and termination decisions of affected pregnancies.

    PubMed

    Chen, L S; Xu, L; Dhar, S U; Li, M; Talwar, D; Jung, E

    2015-08-01

    In the United States, prenatal genetic testing (PGT) for Autism Spectrum Disorders (ASD) is currently available via clinical genetic services. Such testing may inform parents about their unborn child's risk for ASD, prepare parents for the birth of an affected infant, and allow them to arrange for early interventions. Although PGT for autism has potential benefits, the associated ethical, legal, and social implications (ELSI) should be considered. This first qualitative study employed a hypothetical scenario to explore the attitudes toward PGT and termination decisions of 42 parents of children with ASD. Over half of the participants expressed willingness to undergo PGT for autism. Reasons included better preparation for birth, early and better treatment, termination of affected pregnancy, contribution to research, and curiosity. Of the 31 parents who were either willing or unsure about undergoing the PGT, approximately three-fourths would continue their hypothetical affected pregnancies. Explanations included preparation for birth of the child, bonding or acceptance of existing ASD-affected children, apprehensions about test limitations, and religious concerns. Parents who reported they would terminate the affected pregnancy in this hypothetical situation were primarily Asians. This study contributes to the growing understanding of the ELSI aspects of PGT in clinical practice. PMID:25251361

  17. Alterations in lignin content and phenylpropanoids pathway in date palm (Phoenix dactylifera L.) tissues affected by brittle leaf disease.

    PubMed

    Saidi, Mohammed Najib; Bouaziz, Donia; Hammami, Ines; Namsi, Ahmed; Drira, Noureddine; Gargouri-Bouzid, Radhia

    2013-10-01

    Brittle leaf disease or Maladie de la Feuille Cassante (MFC) is a lethal disorder of date palm that has assumed epidemic proportions in the oases of Tunisia and Algeria. No pathogen could ever be associated with the disease, while leaflets of affected palms have been previously shown to be deficient in manganese. The work reported here aims to understand the biochemical basis of the date palm response to this disorder. Since the typical disease symptom is the leaf fragility, we have investigated lignin content in leaves and roots. Strong decrease in total lignin content was observed in affected leaves, while lignin content increased in affected roots. Histochemical analyses showed hyperlignification thicker suberin layer in roots cortical cells. The phenylpropanoids pathway was also disrupted in leaves and roots, cinnamoyl-CoA reductase and cinnamyl-alcohol dehydrogenase gene expression was affected by the disease which severely affects the cell wall integrity. PMID:23987806

  18. Spinocerebellar Ataxia: Patient and Health Professional Perspectives on Whether and How Patents Affect Access to Clinical Genetic Testing

    PubMed Central

    Powell, Ashton; Chandrasekharan, Subhashini; Cook-Deegan, Robert

    2011-01-01

    Genetic testing for spinocerebellar ataxia (SCA) is used in diagnosis of rare movement disorders. Such testing generally does not affect treatment, but confirmation of mutations in a known gene can confirm diagnosis and end an often years-long quest for the cause of distressing and disabling symptoms. Through interviews and a web forum hosted by the National Ataxia Foundation, patients and health professionals related their experiences with patents’ impact on access to genetic testing for SCA. In the United States, Athena Diagnostics holds either a patent or an exclusive license to a patent in the case of 6 SCA variants (SCA1-3 & 6-8) and two other hereditary ataxias (Friedreich’s Ataxia and Early Onset Ataxia). Athena has enforced its exclusive rights to SCA-related patents by sending cease and desist letters to multiple laboratories offering genetic testing for inherited neurological conditions, including SCA. Roughly half of web forum respondents had decided not to get genetic tests. Price, coverage and reimbursement by insurers and health plans, and fear of genetic discrimination were the main reasons cited for deciding not to get tested. Price was cited as an access concern by the physicians, and as sole US provider, coverage and reimbursement depend on having payment agreements between Athena and payers. In cases where payers do not reimburse, the patient is responsible for payment, although some patients can apply to the voluntary Athena Access and Patient Protection Programs offered by the company. PMID:20393313

  19. Sequence Variations of MicroRNAs in Human Cancer: Alterations in Predicted Secondary Structure Do Not Affect Processing

    Microsoft Academic Search

    Sven Diederichs; Daniel A. Haber

    2006-01-01

    Expression levels of microRNAs (miRNAs) are globally reduced in cancer compared with matched normal tissues, and miRNA function has recently been implicated in tumorigenesis. To test whether epigenetic silencing contributes to miRNA suppression in tumors, lung cancer cells were treated with inhibitors of DNA methylation or histone deacetylation. No significant alteration in miRNA expression was detected using microarray profiling. To

  20. Spinal cord injury markedly altered protein expression patterns in the affected rat urinary bladder during healing stages.

    PubMed

    Lee, Ji-Young; Kim, Bong Jo; Sim, Gyujin; Kim, Gyu-Tae; Kang, Dawon; Jung, Jae Hun; Hwa, Jeong Seok; Kwak, Yeon Ju; Choi, Yeon Jin; Park, Young Sook; Han, Jaehee; Lee, Cheol Soon; Kang, Kee Ryeon

    2011-06-01

    The influence of spinal cord injury (SCI) on protein expression in the rat urinary bladder was assessed by proteomic analysis at different time intervals post-injury. After contusion SCI between T9 and T10, bladder tissues were processed by 2-DE and MALDI-TOF/MS at 6 hr to 28 days after SCI to identify proteins involved in the healing process of SCI-induced neurogenic bladder. Approximately 1,000 spots from the bladder of SCI and sham groups were visualized and identified. At one day after SCI, the expression levels of three protein were increased, and seven spots were down-regulated, including heat shock protein 27 (Hsp27) and heat shock protein 20 (Hsp20). Fifteen spots such as S100-A11 were differentially expressed seven days post-injury, and seven proteins including transgelin had altered expression patterns 28 days after injury. Of the proteins with altered expression levels, transgelin, S100-A11, Hsp27 and Hsp20 were continuously and variably expressed throughout the entire post-SCI recovery of the bladder. The identified proteins at each time point belong to eight functional categories. The altered expression patterns identified by 2-DE of transgelin and S100-A11 were verified by Western blot. Transgelin and protein S100-A11 may be candidates for protein biomarkers in the bladder healing process after SCI. PMID:21655070

  1. Genetic variation responsible for mouse strain differences in integrin {alpha}{sub 2} expression is associated with altered platelet responses to collagen

    SciTech Connect

    Li, Tong-Tong; Larrucea, Susana; Souza, Shiloe; Leal, Suzanne M.; Lopez, Jose A.; Rubin, Edward M.; Nieswandt, Bernhard; Bray, Paul F.

    2003-11-01

    Formation of a thrombus at the site of an injured vessel requires the coordinated action of critical platelet plasma membrane adhesion molecules. The most important initial contact of platelets with the exposed endothelial collagen and von Willebrand factor (VWF) involves the binding of glycoprotein (GP) Ib{alpha} to immobilized VWF. The VWF-GPIb{alpha} interaction is ''fast-on'' and relatively ''fast-off,'' and results in a rolling of platelets along the exposed subendothelium. This slowing of the platelets allows binding of the activating collagen-receptor, GPVI, to its ligand, resulting in activation of platelet integrins and subsequent firm adhesion, where the reactions between receptor and ligand are relatively ''slow-on'' but irreversible. The binding of integrin {alpha}{sub 2} {beta}{sub 1} underlying firm adhesion. Intracellular signaling between and through these adhesive receptors plays a crucial role in platelet adhesion and aggregation. The importance of the GPIb-IX-V and {alpha}{sub IIb} {beta}{sub 3} in normal hemostasis is under scored by the bleeding diatheses that have been reported in patients with quantitative or qualitative deficiencies of the genes that encode them. Mouse models are now commonplace for studying hemostasis and thrombosis, and important insights pertaining to the major platelet adhesive receptors have been gleaned from mouse studies involving targeted disruptions of the genes for GPIb{alpha}, GPVI, and integrin chains 2,9,10 1,4 IIb 11 and 3.12 A variety of different mouse strains have been used to assess hemostasis. For example, the FVB strain is typically used for transgenic experiments, the 129/Sv strain is used to derive embryonic stem (ES) cells, and the C57 strain is used for uniform background breeding studies. Different strains may exhibit different levels of gene expression, a feature that has been used to elucidate crucial gene regions regulating transcription. We and others have previously studied how genetic changes exert quantitative and qualitative alterations in human platelet adhesive receptors. Polymorphisms of both integrin {alpha}{sub 2} and GPIb have been associated with quantitative differences in receptor levels in healthy individuals. The variation of integrin {alpha}{sub 2} in the normal population is 5-fold, and some portion of this variability has been associated with a C/T polymorphism at nucleotide 807. Individuals homozygous for the 807C or 807T alleles have an average 2-fold difference in platelet {alpha}{sub 2} {beta}{sub 1} levels, and this difference has been linked to increased adhesion to collagen and clinical thrombotic events. Comparable alterations in platelet adhesion receptor expression have not been assessed in different mouse strains. Assessing the functional consequences of subtle genetic variations in humans is challenged by numerous gene-gene and gene environment interactions, and studies in mice can greatly minimize these confounding variables. In addition, comparative sequence analyses between species and between nonhuman primates have proved useful for identifying sequences that affect function and expression. Thus, in the case of platelet adhesion receptors, knowing mouse strain differences in expression levels might be valuable for defining the responsible quantitative trait loci as well as affecting strain choice for particular functional experiments.

  2. How do population genetic parameters affect germination of the heterocarpic species Atriplex tatarica (Amaranthaceae)?

    PubMed Central

    Kochánková, Jana; Mandák, Bohumil

    2009-01-01

    Background and Aims The heterocarpic species Atriplex tatarica produces two types of seeds. In this study, how basic population genetic parameters correlate with seed germinability under various experimental conditions was tested. Methods Population genetic diversity was ascertained in eight populations of A. tatarica by assessing patterns of variation at nine allozyme loci. Germinability of both seed types from all sampled populations was determined by a common laboratory experiment under different salinity levels. Basic population genetic parameters, i.e. percentage of polymorphic loci, average number of alleles per locus and observed heterozygosity were correlated with observed population germination characteristics. Key Results Atriplex tatarica possesses a remarkable heterocarpy, i.e. one type of seed is non-dormant and the other shows different dormancy levels in relation to experimental conditions. Significant negative correlations have been detected between germination of both seed types and the coefficient of inbreeding, and a significant negative correlation between germination of dormant seeds and other population genetic parameters, i.e. percentage of polymorphic loci and average number of alleles per polymorphic locus. Moreover, populations from the region characterized by a shorter growing season manifested higher germinability, i.e. had lower dormancy, than those from the lower-latitude one. Conclusions In general, germination of non-dormant seeds is probably not under strong genetic control. Hence, they germinate as soon as conditions are favourable, thus ensuring survival in the short term, but populations risk local extinction if conditions become adverse (i.e. a high-risk strategy). In contrast, germination of the dormant type of seeds is under stronger genetic control and is significantly correlated with basic population genetic parameters. These seeds ensure long-term reproduction and survival in the field by protracted germination, albeit in low quantities (i.e. A. tatarica also adopts a low-risk strategy). PMID:19339299

  3. Genomic alterations on 8p21-p23 are the most frequent genetic events in stage I squamous cell carcinoma of the lung

    PubMed Central

    KANG, JIUN

    2015-01-01

    Genetic alterations in the early stages of cancer have a close correlation with tumor initiation and potentially activate downstream pathways implicated in tumor progression; however, the method of initiation in sporadic neoplasias is largely unknown. In this study, whole-genome microarray-comparative genomic hybridization was performed to identify the early genetic alterations that define the prognosis of patients with stage I squamous cell carcinoma (SCC) of the lung. The most striking finding was the high frequency of copy number losses and hemizygous deletions on chromosome 8p, which occurred in 94.7% (18/19) and 63.2% (12/19) of the cases, respectively, with a delineated minimal common region of 8p21.1-p23.3. More specifically, three loci of homozygous deletions at 8p23.1 were noted in 21.1% (4/19) of the cases. This region contains the following possible target genes, which have previously not been implicated to play a pathogenic role in stage I SCCs: MSRA, MFHAS1, CLDN23, DEFB106A, DEFB105A, LOC441316, FAM90A7P and LOC441318. These findings indicate that genetic alterations on chromosome 8p may be the first step in the initiation of genomic instability in early SCCs, and the newly identified genes in the 8p23.1 chromosomal region might be of interest for the study of the pathophysiology of stage I SCC, as potential targets for therapeutic measures. PMID:25574196

  4. Synergistic ablation does not affect atrophy or altered myosin heavy chain expression in the non-weight bearing soleus muscle

    NASA Technical Reports Server (NTRS)

    Linderman, J. K.; Talmadge, R. J.; Gosselink, K. L.; Tri, P. N.; Roy, R. R.; Grindeland, R. E.

    1996-01-01

    The purpose of this study was to investigate whether the soleus muscle undergoes atrophy and alterations in myosin heavy chain (MHC) composition during non-weight bearing in the absence of synergists. Thirty-two female rats were randomly assigned to four groups: control (C), synergistic ablation (ABL) of the gastrocnemius and plantaris muscles to overload the soleus muscle, hindlimb suspension (HLS), or a combination of synergistic ablation and hindlimb suspension (HLS-ABL). After 28 days of hindlimb suspension, soleus atrophy was more pronounced in HLS (58%) than in HLS-ABL (43%) rats. Compared to C rats, non-weight bearing decreased mixed and myofibrillar protein contents and Type I MHC 49%, 45%, and 7%, respectively, in HLS animals. In addition, de novo expression of fast Type IIx and Type IIb MHC (5% and 2%, respectively) was observed in HLS animals. Similarly, when compared to C rats, mixed and myofibrillar protein contents and Type I MHC decreased 43%, 46%, and 4%, respectively, in HLS-ABL animals. Also, de novo expression of Type IIx (4%) and IIb (1%) MHC was observed. Collectively, these data indicate that the loss of muscle protein and Type I MHC, and the de novo expression of Type IIx and Type IIb MHC in the rat soleus occur independently of the presence of synergists during non-weight bearing. Furthermore, these results confirm the contention that soleus mass and MHC expression are highly sensitive to alterations in mechanical load.

  5. Comparative evaluation of non-genetic factors affecting milk yield and composition of Red Dane and Jersey cattle in Zimbabwe.

    PubMed

    Nyamushamba, Godfrey Bernard; Halimani, Tinyiko Edward; Imbayarwo-Chikosi, Venancio Edward; Tavirimirwa, Bruce

    2014-01-01

    A study was carried out to evaluate non genetic factors affecting milk yield and milk composition in Zimbabwean Red Dane and Jersey cattle cattle. A total of 1004 and 10 986 unedited Red Dane and Jersey 305-day lactation records respectively, were obtained from Livestock Identification Trust (LIT) containing 22 herds (1 Red Dane herd and 21 Jersey herds), with Red Dane calving in the period 2004 to 2009 (giving year of birth from 1998 to 2007) and Jersey cows calving in the period 1996 to 2008 (giving year of birth from 1994 to 2005). The General Linear Model (GLM) procedure of the Statistical Analysis System (SAS, 2004) version 9.1.3 was used to determine the genetic parameters and environmental factors. Calving interval, month of calving, parity and quadratic effects of age at calving fitted as covariates significantly (P?affected the milk, fat and protein yields. Milk, fat and protein yields obtained increased with an increase in calving interval. There was a linear and quadratic relationship between the production traits and age at calving of the Jersey cattle implying that milk, fat and protein yields increase with age of the animal. It is thus important to preadjust data for these environmental factors when carrying out genetic evaluations of production traits in dairy cattle. PMID:24600545

  6. Pubertal Onset in Girls is Strongly Influenced by Genetic Variation Affecting FSH Action

    PubMed Central

    Hagen, Casper P.; Sørensen, Kaspar; Aksglaede, Lise; Mouritsen, Annette; Mieritz, Mikkel G.; Tinggaard, Jeanette; Wohlfart-Veje, Christine; Petersen, Jørgen Holm; Main, Katharina M.; Meyts, Ewa Rajpert-De; Almstrup, Kristian; Juul, Anders

    2014-01-01

    Age at pubertal onset varies substantially in healthy girls. Although genetic factors are responsible for more than half of the phenotypic variation, only a small part has been attributed to specific genetic polymorphisms identified so far. Follicle-stimulating hormone (FSH) stimulates ovarian follicle maturation and estradiol synthesis which is responsible for breast development. We assessed the effect of three polymorphisms influencing FSH action on age at breast deveopment in a population-based cohort of 964 healthy girls. Girls homozygous for FSHR -29AA (reduced FSH receptor expression) entered puberty 7.4 (2.5–12.4) months later than carriers of the common variants FSHR -29GG+GA, p = 0.003. To our knowledge, this is the strongest genetic effect on age at pubertal onset in girls published to date. PMID:25231187

  7. Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children

    Microsoft Academic Search

    V A Belo; D C Souza-Costa; M R Luizon; C M M Lanna; P C Carneiro; T C Izidoro-Toledo; K C Ferraz; J E Tanus-Santos

    2012-01-01

    Objective:Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression\\/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA)(14?24) (rs2234681) and Q279R (rs17576)), or haplotypes, affect

  8. Highthroughput soybean gene expression analysis The changes in the atmosphere are altering gene expression and affecting the interaction

    E-print Network

    DeLucia, Evan H.

    silencing in soybean. A short sequence of targeted plant gene is cloned into the vector. Soybean unifoliate expression and affecting the interaction between plants and pathogens and insects. We are using Affymetrix soybean oligoarrays to analyze changes in the gene expression profile. Affymetrix GeneChip® Soybean Genome

  9. Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay

    Microsoft Academic Search

    Laurent G Deluc; David R Quilici; Alain Decendit; Jérôme Grimplet; Matthew D Wheatley; Karen A Schlauch; Jean-Michel Mérillon; John C Cushman; Grant R Cramer

    2009-01-01

    BACKGROUND: Water deficit has significant effects on grape berry composition resulting in improved wine quality by the enhancement of color, flavors, or aromas. While some pathways or enzymes affected by water deficit have been identified, little is known about the global effects of water deficit on grape berry metabolism. RESULTS: The effects of long-term, seasonal water deficit on berries of

  10. Up-Regulation of the Error-Prone DNA Polymerase K Promotes Pleiotropic Genetic Alterations and Tumorigenesis

    Microsoft Academic Search

    Clarisse Bavoux; Andreia Machado Leopoldino; Valerie Bergoglio; Jiyang O-Wang; Tomoo Ogi; Anne Bieth; Jean-Gabriel Judde; Marie-France Poupon; Thomas Helleday; Masatoshi Tagawa; CarlosRenato Machado; Jean-Sebastien Hoffmann; Christophe Cazaux

    2005-01-01

    It is currently widely accepted that genetic instability is key to cancer development. Many types of cancers arise as a consequence of a gradual accumulation of nucleotide aberra- tions, each mutation conferring growth and\\/or survival advantage. Genetic instability could also proceed in sudden bursts leading to a more drastic upheaval of structure and organization of the genome. Genetic instability, as

  11. Specific Alterations in Complement Protein Activity of Little Brown Myotis (Myotis lucifugus) Hibernating in White-Nose Syndrome Affected Sites

    PubMed Central

    Moore, Marianne S.; Reichard, Jonathan D.; Murtha, Timothy D.; Zahedi, Bita; Fallier, Renee M.; Kunz, Thomas H.

    2011-01-01

    White-nose syndrome (WNS) is the most devastating condition ever reported for hibernating bats, causing widespread mortality in the northeastern United States. The syndrome is characterized by cutaneous lesions caused by a recently identified psychrophilic and keratinophylic fungus (Geomyces destructans), depleted fat reserves, atypical behavior, and damage to wings; however, the proximate cause of mortality is still uncertain. To assess relative levels of immunocompetence in bats hibernating in WNS-affected sites compared with levels in unaffected bats, we describe blood plasma complement protein activity in hibernating little brown myotis (Myotis lucifugus) based on microbicidal competence assays using Escherichia coli, Staphylococcus aureus and Candida albicans. Blood plasma from bats collected during mid-hibernation at WNS-affected sites had higher bactericidal ability against E. coli and S. aureus, but lower fungicidal ability against C. albicans when compared with blood plasma from bats collected at unaffected sites. Within affected sites during mid-hibernation, we observed no difference in microbicidal ability between bats displaying obvious fungal infections compared to those without. Bactericidal ability against E. coli decreased significantly as hibernation progressed in bats collected from an affected site. Bactericidal ability against E. coli and fungicidal ability against C. albicans were positively correlated with body mass index (BMI) during late hibernation. We also compared complement activity against the three microbes within individuals and found that the ability of blood plasma from hibernating M. lucifugus to lyse microbial cells differed as follows: E. coli>S. aureus>C. albicans. Overall, bats affected by WNS experience both relatively elevated and reduced innate immune responses depending on the microbe tested, although the cause of observed immunological changes remains unknown. Additionally, considerable trade-offs may exist between energy conservation and immunological responses. Relationships between immune activity and torpor, including associated energy expenditure, are likely critical components in the development of WNS. PMID:22140440

  12. Long-term NMDA receptor inhibition affects NMDA receptor expression and alters glutamatergic activity in developing rat hippocampal neurons.

    PubMed

    Sinner, Barbara; Friedrich, Oliver; Lindner, Regina; Bundscherer, Anika; Graf, Bernhard M

    2015-07-01

    Ketamine and its stereoisomer S(+)-ketamine are widely used for sedation in pediatric anesthesia and intensive care medicine. Numerous experimental studies indicate that ketamine is potentially toxic to the developing brain. Here, we examined the long-term effects of NMDA receptor blockade on NMDA receptor subunit expression, alterations in neuronal Ca(2+)-oscillations and apoptosis. Hippocampal neurons, 15 days in culture, were exposed to either S(+)-ketamine or the NMDA receptor blocker MK801 for 24h. Cytosolic Ca(2+)-concentration was determined by fluorescence microscopy and the expression of the NMDA subunits NR1, NR2A and 2B was assessed by qRT-PCR, whereas Western blots and activated Caspase-3 served to measure the extent of apoptosis. Long-term incubation with MK801 or higher doses of S(+)-ketamine resulted in a dose-dependent decreased ability of MK801 to reduce amplitude and frequency of the Ca(2+)-oscillations 15min following washout of the drug. This was accompanied by an increase in NR1 mRNA but not the NR2A and B subunit expression at the same time point. 24h following washout of the specific drug, a significant elevation of the pro-apoptotic marker BAX, as well as activated Caspase-3 positive neurons, could be detected in cultures exposed to 100?M MK801 and 25?M S(+)-ketamine. Here, we show that long-term blockade of the NMDA receptor in developing rat hippocampal neurons significantly increased NR1 subunit expression, and that this was associated with an alteration in neuronal activity. Apoptosis was only induced 24h after withdrawal of long-term blockade for high doses of S(+)-ketamine. PMID:25937004

  13. Alterations in leukotriene synthase activity of the human 5-lipoxygenase by site-directed mutagenesis affecting its positional specificity.

    PubMed

    Schwarz, K; Gerth, C; Anton, M; Kuhn, H

    2000-11-28

    The positional specificity of arachidonic acid oxygenation is currently the decisive parameter for classification of lipoxygenases. Although the mechanistic basis of lipoxygenase specificity is not completely understood, sequence determinants for the positional specificity have been identified for various isoenzymes. In this study we altered the positional specificity of the human 5-lipoxygenase by multiple site-directed mutagenesis and assayed the leukotriene A(4) synthase activity of the mutant enzyme species with (5S,6E,8Z,11Z,14Z)-5-hydroperoxy-6,8,11,14-eicos atetraenoic acid (5S-HpETE) as substrate. The wild-type 5-lipoxygenase converts 5S-HpETE almost exclusively to leukotriene A(4) as indicated by the dominant formation of leukotriene A(4) hydrolysis products. Since leukotriene synthesis involves a hydrogen abstraction from C(10), it was anticipated that the 15-lipoxygenating quadruple mutant F359W + A424I + N425M + A603I might not exhibit a major leukotriene A(4) synthase activity. Surprisingly, we found that this quadruple mutant exhibited a similar leukotriene synthase activity as the wild-type enzyme in addition to its double oxygenation activity. The leukotriene synthase activity of the 8-lipoxygenating double mutant F359W + A424I was almost twice as high, and similar amounts of leukotriene A(4) hydrolysis products and double oxygenation derivatives were detected with this enzyme species. These data indicate that site-directed mutagenesis of the human 5-lipoxygenase that leads to alterations in the positional specificity favoring arachidonic acid 15-lipoxygenation does not suppress the leukotriene synthase activity of the enzyme. The residual 8-lipoxygease activity of the mutant enzyme and its augmented rate of 5-HpETE conversion may be discussed as major reasons for this unexpected result. PMID:11087405

  14. Negative Affect Shares Genetic and Environmental Influences with Symptoms of Childhood Internalizing and Externalizing Disorders

    ERIC Educational Resources Information Center

    Mikolajewski, Amy J.; Allan, Nicholas P.; Hart, Sara A.; Lonigan, Christopher J.; Taylor, Jeanette

    2013-01-01

    The co-occurrence of internalizing and externalizing disorders suggests that they may have common underlying vulnerability factors. Research has shown that negative affect is moderately positively correlated with both internalizing and externalizing disorders in children. The present study is the first to provide an examination of negative affect

  15. Genetic and Environmental Factors Affect Bone Density Variances of Families of Men and Women with Osteoporosis

    Microsoft Academic Search

    C. BAUDOIN; M. E. COHEN-SOLAL; J. BEAUDREUIL; M. C. DE VERNEJOUL

    2010-01-01

    Our aim was to assess the relative impacts of genetics and environment in the families of osteoporotic patients and iden- tify the best subgroup of patients to investigate the genes associated with osteoporosis. We recruited 36 men and 47 women with osteoporosis (probands), median age of 52 and 68 yr, and all their siblings (90) and offspring (83). The families

  16. X-linked recessive genetic defects - how girls are affected (image)

    MedlinePLUS

    ... inherited through a genetic defect on an X chromosome. A female has 2 X chromosomes, one she inherited from her mother and one ... the way a boy would, because she has 2 X chromosomes, and the dominant X will compensate for the ...

  17. Non-genetic factors affecting live weight and daily gain weight in Serrana Transmontano kids

    Microsoft Academic Search

    M. R. Jiménez-Badillo; S. Rodrigues; C. Sañudo; A. Teixeira

    2009-01-01

    The objective of this study was to evaluate the effect of some non-genetic factors on birth weight, weaning weight and daily gain weight in Serrana Transmontano kids. Data from 8930 records were analysed. Results showed that birth weight (BW), adjusted live weight at 30 days of age (W30), adjusted weaning weight at 60 days of age (WW), average daily gain

  18. THE LOCATION OF GENETIC FACTORS AFFECTING A QUANTITATIVE CHARACTER IN WHEAT

    Microsoft Academic Search

    C. N. LAW

    a proper understanding of the genetics of continuous variation. it cannot FfeRdoubted that the genes responsible for the control of metrical characters must be isolated so that their individual properties may be investigated. THODAY (1961 ) has emphasised this point of view and has described methods by which genes of this kind can be located. Essentially these methods involve two

  19. Altered Subcellular Localization of Tumor-Specific Cyclin E Isoforms Affects Cyclin-Dependent Kinase 2 Complex Formation and Proteasomal Regulation

    PubMed Central

    Delk, Nikki A.; Hunt, Kelly K.; Keyomarsi, Khandan

    2009-01-01

    In tumors, alternative translation and posttranslational proteolytic cleavage of full-length cyclin E (EL) produces tumorigenic low molecular weight cyclin E (LMW-E) isoforms that lack a portion of the EL amino-terminus containing a nuclear localization sequence. Therefore, we hypothesized that LMW-E isoforms have altered subcellular localization. To explore our hypothesis, we compared EL versus LMW-E localization in cell lysates and in vivo using fractionation and protein complementation assays. Our results reveal that LMW-E isoforms preferentially accumulate in the cytoplasm where they bind the cyclin E kinase partner, cyclin-dependent kinase 2 (Cdk2), and have associated kinase activity. The nuclear ubiquitin ligase Fbw7 targets Cdk2-bound cyclin E for degradation; thus, we examined if altered subcellular localization affected LMW-E degradation. We found that cytoplasmic LMW-E/Cdk2 was less susceptible to Fbw7-mediated degradation. One implication of our findings is that altered LMW-E and LMW-E/Cdk2 subcellular localization may lead to aberrant LMW-E protein interactions, regulation, and activity, ultimately contributing to LMW-E tumorigenicity. PMID:19318554

  20. Classroom norms of bullying alter the degree to which children defend in response to their affective empathy and power.

    PubMed

    Peets, Kätlin; Pöyhönen, Virpi; Juvonen, Jaana; Salmivalli, Christina

    2015-07-01

    This study examined whether the degree to which bullying is normative in the classroom would moderate associations between intra- (cognitive and affective empathy, self-efficacy beliefs) and interpersonal (popularity) factors and defending behavior. Participants were 6,708 third- to fifth-grade children (49% boys; Mage = 11 years) from 383 classrooms. Multilevel modeling analyses revealed that children were more likely to defend in response to their affective empathy in classrooms with high levels of bullying. In addition, popular students were more likely to support victims in classrooms where bullying was associated with social costs. These findings highlight the importance of considering interactions among individual and contextual influences when trying to understand which factors facilitate versus inhibit children's inclinations to defend others. (PsycINFO Database Record PMID:25961871

  1. Genetics

    MedlinePLUS

    Homozygous; Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  2. The inhibition of aromatase alters the mechanical and rheological properties of non-small-cell lung cancer cell lines affecting cell migration.

    PubMed

    Giannopoulou, E; Siatis, K E; Metsiou, D; Kritikou, I; Papachristou, D J; Kalofonou, M; Koutras, A; Athanassiou, G; Kalofonos, H P

    2015-02-01

    Tumor invasion and metastasis are key aspects of non-small cell lung cancer (NSCLC). During migration, cells undergo mechanical alterations. The mechanical phenotype of breast cancer cells is correlated with aromatase gene expression. We have previously shown that targeting aromatase is a promising strategy for NSCLC. The aim of this study was to examine morphological and mechanical changes of NSCLC cells, upon treatment with aromatase inhibitor and correlate their ability to migrate and invade. In vitro experiments were performed using H23 and A549 NSCLC cell lines and exemestane was used for aromatase inhibition. We demonstrated that exemestane reduced H23 cell migration and invasion and caused changes in cell morphology including increased vacuolar structures and greater pleomorphism. In addition, exemestane changed the distribution of ?-tubulin in H23 and A549 cells in a way that might destabilize microtubules polymerization. These effects were associated with increased cell viscosity and decreased elastic shear modulus. Although exemestane caused similar effects in A549 cells regarding viscosity and elastic shear modulus, it did not affect A549 cell migration and caused an increase in invasion. The increased invasion was in line with vimentin perinuclear localization. Our data show that the treatment of NSCLC cells with an aromatase inhibitor not only affects cell migration and invasion but also alters the mechanical properties of the cells. It suggests that the different origin of cancer cells is associated with different morphological characteristics and mechanical behavior. PMID:25450981

  3. Magnolol causes alterations in the cell cycle in androgen insensitive human prostate cancer cells in vitro by affecting expression of key cell cycle regulatory proteins.

    PubMed

    McKeown, Brendan T; McDougall, Luke; Catalli, Adriana; Hurta, Robert A R

    2014-01-01

    Prostate cancer, one of the most common cancers in the Western world, affects many men worldwide. This study investigated the effects of magnolol, a compound found in the roots and bark of the magnolia tree Magnolia officinalis, on the behavior of 2 androgen insensitive human prostate cancer cell lines, DU145 and PC3, in vitro. Magnolol, in a 24-h exposure at 40 and 80 ?M, was found to be cytotoxic to cells. Magnolol also affected cell cycle progression of DU145 and PC3 cells, resulting in alterations to the cell cycle and subsequently decreasing the proportion of cells entering the G2/M-phase of the cell cycle. Magnolol inhibited the expression of cell cycle regulatory proteins including cyclins A, B1, D1, and E, as well as CDK2 and CDK4. Protein expression levels of pRBp107 decreased and pRBp130 protein expression levels increased in response to magnolol exposure, whereas p16(INK4a), p21, and p27 protein expression levels were apparently unchanged post 24-h exposure. Magnolol exposure at 6 h did increase p27 protein expression levels. This study has demonstrated that magnolol can alter the behavior of androgen insensitive human prostate cancer cells in vitro and suggests that magnolol may have potential as a novel anti-prostate cancer agent. PMID:25264561

  4. Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain

    PubMed Central

    Harper, Kathryn M.; Hiramoto, Takeshi; Tanigaki, Kenji; Kang, Gina; Suzuki, Go; Trimble, William; Hiroi, Noboru

    2012-01-01

    Social behavior dysfunction is a symptomatic element of schizophrenia and autism spectrum disorder (ASD). Although altered activities in numerous brain regions are associated with defective social cognition and perception, the causative relationship between these altered activities and social cognition and perception—and their genetic underpinnings—are not known in humans. To address these issues, we took advantage of the link between hemizygous deletion of human chromosome 22q11.2 and high rates of social behavior dysfunction, schizophrenia and ASD. We genetically manipulated Sept5, a 22q11.2 gene, and evaluated its role in social interaction in mice. Sept5 deficiency, against a high degree of homogeneity in a congenic genetic background, selectively impaired active affiliative social interaction in mice. Conversely, virally guided overexpression of Sept5 in the hippocampus or, to a lesser extent, the amygdala elevated levels of active affiliative social interaction in C57BL/6J mice. Congenic knockout mice and mice overexpressing Sept5 in the hippocampus or amygdala were indistinguishable from control mice in novelty and olfactory responses, anxiety or motor activity. Moreover, post-weaning individual housing, an environmental condition designed to reduce stress in male mice, selectively raised levels of Sept5 protein in the amygdala and increased active affiliative social interaction in C57BL/6J mice. These findings identify this 22q11.2 gene in the hippocampus and amygdala as a determinant of social interaction and suggest that defective social interaction seen in 22q11.2-associated schizophrenia and ASD can be genetically and environmentally modified by altering this 22q11.2 gene. PMID:22589251

  5. EARLY MATERNAL SEPARATION AFFECTS ETHANOL-INDUCED CONDITIONING IN A nor-BNI INSENSITIVE MANNER, BUT DOES NOT ALTER ETHANOL-INDUCED LOCOMOTOR ACTIVITY

    PubMed Central

    Pautassi, Ricardo Marcos; Nizhnikov, Michael E.; Fabio, Ma. Carolina; Spear, Norman E.

    2011-01-01

    Early environmental stress significantly affects the development of offspring. This stress has been modeled in rats through the maternal separation (MS) paradigm, which alters the functioning of the HPA axis and can enhance ethanol intake at adulthood. Infant rats are sensitive to ethanol’s reinforcing effects, which modulate ethanol seeking and intake. Little is known about the impact of MS on sensitivity to ethanol’s appetitive and aversive effects during infancy. The present study assessed ethanol-induced conditioned place preference established through second-order conditioning (SOC), spontaneous or ethanol-induced locomotor activity and ethanol intake in preweanling rats that experienced normal animal facility rearing (AFR) or daily episodes of maternal separation (MS) during postnatal days 1-13 (PDs 1-13). Low-ethanol dose (0.5 g/kg) induced appetitive conditioned place preference (via SOC) in control rats given conventional rearing but not in rats given maternal separation in early infancy, whereas 2.0 g/kg ethanol induced aversive conditioned place preference in the former but not the latter. The administration of a kappa antagonist at PD1 or immediately before testing did not alter ethanol-induced reinforcement. High (i.e., 2.5 and 2.0 g/kg) but not low (i.e., 0.5 g/kg) ethanol dose induced reliable motor stimulation, which was independent of early maternal separation. Ethanol intake and blood alcohol levels during conditioning were unaffected by rearing conditions. Pups given early maternal separation had lower body weights than controls and showed an altered pattern of exploration when placed in an open field. These results indicate that, when assessed in infant rats, earlier maternal separation alters the balance between the appetitive and aversive motivational effects of ethanol but has no effect on the motor activating effects of the drug. PMID:22108648

  6. Altering HIF-1? through 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure affects coronary vessel development.

    PubMed

    Wikenheiser, Jamie; Karunamuni, Ganga; Sloter, Eddie; Walker, Mary K; Roy, Debashish; Wilson, David L; Watanabe, Michiko

    2013-06-01

    Differential tissue hypoxia drives normal cardiogenic events including coronary vessel development. This requirement renders cardiogenic processes potentially susceptible to teratogens that activate a transcriptional pathway that intersects with the hypoxia-inducible factor (HIF-1) pathway. The potent toxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to cause cardiovascular defects by way of reduced myocardial hypoxia, inhibition of angiogenic stimuli, and alterations in responsiveness of endothelial cells to those stimuli. Our working hypothesis is that HIF-1 levels and thus HIF-1 signaling in the developing myocardium will be reduced by TCDD treatment in vivo during a critical stage and in particularly sensitive sites during heart morphogenesis. This inadequate HIF-1 signaling will subsequently result in outflow tract (OFT) and coronary vasculature defects. Our current data using the chicken embryo model showed a marked decrease in the intensity of immunostaining for HIF-1? nuclear expression in the OFT myocardium of TCDD-treated embryos. This area at the base of the OFT is particularly hypoxic during normal development; where endothelial cells initially form a concentrated anastomosing network known as the peritruncal ring; and where the left and right coronary arteries eventually connect to the aortic lumen. Consistent with this finding, anomalies of the proximal coronaries were detected after TCDD treatment and HIF-1? protein levels decreased in a TCDD dose-dependent manner. PMID:23264063

  7. Water deficit alters differentially metabolic pathways affecting important flavor and quality traits in grape berries of Cabernet Sauvignon and Chardonnay

    PubMed Central

    Deluc, Laurent G; Quilici, David R; Decendit, Alain; Grimplet, Jérôme; Wheatley, Matthew D; Schlauch, Karen A; Mérillon, Jean-Michel; Cushman, John C; Cramer, Grant R

    2009-01-01

    Background Water deficit has significant effects on grape berry composition resulting in improved wine quality by the enhancement of color, flavors, or aromas. While some pathways or enzymes affected by water deficit have been identified, little is known about the global effects of water deficit on grape berry metabolism. Results The effects of long-term, seasonal water deficit on berries of Cabernet Sauvignon, a red-wine grape, and Chardonnay, a white-wine grape were analyzed by integrated transcript and metabolite profiling. Over the course of berry development, the steady-state transcript abundance of approximately 6,000 Unigenes differed significantly between the cultivars and the irrigation treatments. Water deficit most affected the phenylpropanoid, ABA, isoprenoid, carotenoid, amino acid and fatty acid metabolic pathways. Targeted metabolites were profiled to confirm putative changes in specific metabolic pathways. Water deficit activated the expression of numerous transcripts associated with glutamate and proline biosynthesis and some committed steps of the phenylpropanoid pathway that increased anthocyanin concentrations in Cabernet Sauvignon. In Chardonnay, water deficit activated parts of the phenylpropanoid, energy, carotenoid and isoprenoid metabolic pathways that contribute to increased concentrations of antheraxanthin, flavonols and aroma volatiles. Water deficit affected the ABA metabolic pathway in both cultivars. Berry ABA concentrations were highly correlated with 9-cis-epoxycarotenoid dioxygenase (NCED1) transcript abundance, whereas the mRNA expression of other NCED genes and ABA catabolic and glycosylation processes were largely unaffected. Water deficit nearly doubled ABA concentrations within berries of Cabernet Sauvignon, whereas it decreased ABA in Chardonnay at véraison and shortly thereafter. Conclusion The metabolic responses of grapes to water deficit varied with the cultivar and fruit pigmentation. Chardonnay berries, which lack any significant anthocyanin content, exhibited increased photoprotection mechanisms under water deficit conditions. Water deficit increased ABA, proline, sugar and anthocyanin concentrations in Cabernet Sauvignon, but not Chardonnay berries, consistent with the hypothesis that ABA enhanced accumulation of these compounds. Water deficit increased the transcript abundance of lipoxygenase and hydroperoxide lyase in fatty metabolism, a pathway known to affect berry and wine aromas. These changes in metabolism have important impacts on berry flavor and quality characteristics. Several of these metabolites are known to contribute to increased human-health benefits. PMID:19426499

  8. Epidermal growth factor receptor signaling pathway is frequently altered in ampullary carcinoma at protein and genetic levels.

    PubMed

    Mikhitarian, Kaidi; Pollen, Maressa; Zhao, Zhiguo; Shyr, Yu; Merchant, Nipun B; Parikh, Alexander; Revetta, Frank; Washington, M Kay; Vnencak-Jones, Cindy; Shi, Chanjuan

    2014-05-01

    Our objective was to explore alteration of the epidermal growth factor receptor (EGFR) signaling pathway in ampullary carcinoma. Immunohistochemical studies were employed to evaluate expression of amphiregulin as well as expression and activation of EGFR. A lab-developed assay was used to identify mutations in the EGFR pathway genes, including KRAS, BRAF, PIK3CA, PTEN, and AKT1. A total of 52 ampullary carcinomas were identified, including 25 intestinal-type and 24 pancreatobiliary-type tumors, with the intestinal type being associated with a younger age at diagnosis (P=0.03) and a better prognosis (P<0.01). Expression of amphiregulin correlated with better differentiation (P<0.01), but no difference was observed between two major histologic types. Expression and activation of EGFR was more commonly seen in the pancreatobiliary type (P<0.01). Mutations were detected in 50% of the pancreatobiliary type and 60% of the intestinal type. KRAS was the most common gene mutated in the pancreatobiliary type (42%) as well as the intestinal type (52%). Other mutations detected included PIK3CA, SMAD4 and BRAF. KRAS mutations at codons 12 and 13 did not adversely affect overall survival. In conclusion, EGFR expression and activation were different between intestinal- and pancreatobiliary-type ampullary carcinoma. KRAS mutation was common in both histologic types; however, the incidence appeared to be lower in the pancreatobiliary type compared with its pancreatic counterpart, pancreatic ductal adenocarcinoma. Mutational analysis of the EGFR pathway genes may provide important insights into personalized treatment for patients with ampullary carcinoma. PMID:24186143

  9. Genetic and environmental factors affecting bone mineral density in large families.

    PubMed Central

    Yeap, S. S.; Beaumont, M.; Bennett, A.; Keating, N. A.; White, D. A.; Hosking, D. J.

    1998-01-01

    This study assessed whether relatives with low bone mineral density (BMD) could be identified in five large families using historical, biochemical, and genetic markers for osteoporosis. Fifty of 65 relatives had their bone density and bone turnover markers measured, together with an assessment of their risk factors for osteoporosis. Only 33% (5/15) of siblings, 50% (6/12) of children and 43% (10/23) of nephews and nieces had entirely normal BMD. There was no difference in life-style risk factors for osteoporosis, history of previous fractures or body mass index between normal subjects and those with osteopenia or osteoporosis. Osteopenic individuals had a significantly higher than normal osteocalcin value. Within families, there was no clear association between BMD and any of the genetic markers (vitamin D receptor gene polymorphisms, COL 1A1 and COL 1A2 polymorphisms of the collagen gene), either alone or in combination. The addition of genetic markers to the other risk factors for low BMD did not improve the prediction of BMD. In conclusion, we suggest that the presence of osteoporosis in a first degree relative should be one of the clinical indications for bone density measurement as the individuals at risk would not be picked up by other methods. PMID:9799889

  10. Why Control Activity? Evolutionary Selection Pressures Affecting the Development of Physical Activity Genetic and Biological Regulation

    PubMed Central

    2013-01-01

    The literature strongly suggests that daily physical activity is genetically and biologically regulated. Potential identities of the responsible mechanisms are unclear, but little has been written concerning the possible evolutionary selection pressures leading to the development of genetic/biological controls of physical activity. Given the weak relationship between exercise endurance and activity levels and the differential genomic locations associated with the regulation of endurance and activity, it is probable that regulation of endurance and activity evolved separately. This hypothesis paper considers energy expenditures and duration of activity in hunter/gatherers, pretechnology farmers, and modern Western societies and considers the potential of each to selectively influence the development of activity regulation. Food availability is also considered given the known linkage of caloric restriction on physical activity as well as early data relating food oversupply to physical inactivity. Elucidating the selection pressures responsible for the genetic/biological control of activity will allow further consideration of these pressures on activity in today's society, especially the linkages between food and activity. Further, current food abundance is removing the cues for activity that were present for the first 40,000 years of human evolution, and thus future research should investigate the effects of this abundance upon the mechanisms regulating activity. PMID:24455728

  11. Twins and virtual twins: Do genetic (as well as experiential) factors affect developmental risks?

    PubMed

    Segal, Nancy L; Tan, Tony Xing; Graham, Jamie L

    2015-08-01

    Factors underlying developmental delays and psychosocial risks are of interest to international adoption communities. The current study administered a Pre-Adoption Adversity (PAA) Questionnaire to mostly American parents raising (a) adopted Chinese twins or (b) same-age unrelated adopted siblings. A goal was to replicate earlier analyses of pre-adoption adversity/adjustment among adopted preschool-age Chinese girls. A second goal was to conduct genetic analyses of four content areas (Developmental Delays at Adoption, Initial Adaptation to Adoption, Crying/Clinging, and Refusal/Avoidance) derived from the PAA Questionnaire. A key finding was that age at adoption added less than other predictors to adoptees' externalizing and internalizing behaviors. Family factors (e.g., parental education) contributed significantly to behavioral outcomes among the adopted Chinese twins. Genetic effects were indicated for all four content areas, with shared environmental effects evident for Developmental Delays at Adoption and Crying/Clinging. Future investigators should consider incorporating genetically sensitive designs into developmental research programs. PMID:25900540

  12. Diet-induced alterations of host cholesterol metabolism are likely to affect the gut microbiota composition in hamsters.

    PubMed

    Martínez, Inés; Perdicaro, Diahann J; Brown, Andrew W; Hammons, Susan; Carden, Trevor J; Carr, Timothy P; Eskridge, Kent M; Walter, Jens

    2013-01-01

    The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota. PMID:23124234

  13. Diet-Induced Alterations of Host Cholesterol Metabolism Are Likely To Affect the Gut Microbiota Composition in Hamsters

    PubMed Central

    Martínez, Inés; Perdicaro, Diahann J.; Brown, Andrew W.; Hammons, Susan; Carden, Trevor J.; Carr, Timothy P.; Eskridge, Kent M.

    2013-01-01

    The gastrointestinal microbiota affects the metabolism of the mammalian host and has consequences for health. However, the complexity of gut microbial communities and host metabolic pathways make functional connections difficult to unravel, especially in terms of causation. In this study, we have characterized the fecal microbiota of hamsters whose cholesterol metabolism was extensively modulated by the dietary addition of plant sterol esters (PSE). PSE intake induced dramatic shifts in the fecal microbiota, reducing several bacterial taxa within the families Coriobacteriaceae and Erysipelotrichaceae. The abundance of these taxa displayed remarkably high correlations with host cholesterol metabolites. Most importantly, the associations between several bacterial taxa with fecal and biliary cholesterol excretion showed an almost perfect fit to a sigmoidal nonlinear model of bacterial inhibition, suggesting that host cholesterol excretion can shape microbiota structure through the antibacterial action of cholesterol. In vitro experiments suggested a modest antibacterial effect of cholesterol, and especially of cholesteryl-linoleate, but not plant sterols when included in model bile micelles. The findings obtained in this study are relevant to our understanding of gut microbiota-host lipid metabolism interactions, as they provide the first evidence for a role of cholesterol excreted with the bile as a relevant host factor that modulates the gut microbiota. The findings further suggest that the connections between Coriobacteriaceae and Erysipelotrichaceae and host lipid metabolism, which have been observed in several studies, could be caused by a metabolic phenotype of the host (cholesterol excretion) affecting the gut microbiota. PMID:23124234

  14. The estrogenic and antiandrogenic pesticide methoxychlor alters the reproductive tract and behavior without affecting pituitary size or LH and prolactin secretion in male rats.

    PubMed

    Gray, L E; Ostby, J; Cooper, R L; Kelce, W R

    1999-01-01

    This study was designed to determine if long-term exposure to high doses of methoxychlor (M) would alter pituitary or testicular endocrine functions in either an estrogenic or antiandrogenic manner. Weanling male Long-Evans hooded rats were dosed daily with M (po) at 0, 200, 300, or 400 mg kg-1 day-1 for 10 months. Methoxychlor treatment delayed puberty by as much as 10 weeks and reduced fertility and copulatory plug formation in a dose-related manner at the initial mating. During mating, M-treated males exhibited shorter latencies to mount and ejaculate versus control males, but the number of intromissions prior to ejaculation was unaffected, indicating that M enhanced the arousal level in the males in an estrogen-dependent manner. Most treated males eventually mated but time-to-pregnancy was lengthened. Very low sperm counts were associated with infertility, while prolonged delays in puberty reduced fecundity. Methoxychlor treatment with 200 to 400 mg kg-1 day-1 failed to mimic the chronic effects of a sustained (8 months) low dose of estradiol-17 beta (3-mm silastic implants) on pituitary or testicular hormone levels. Estradiol administration increased pituitary weight 4-fold, serum levels of luteinizing hormone (LH) were reduced by almost 50%, and serum prolactin was increased 40-fold, while M did not affect any of these measures. These data demonstrate that M affects the CNS, epididymal sperm numbers, and the accessory sex glands and delays mating without significantly affecting the secretion of LH, prolactin, or testosterone. These data indicate that M did not alter pituitary endocrine function in either an estrogenic or antiandrogenic manner. To our knowledge, these data provide the first in vivo example of such a pronounced degree of target tissue selectivity to an environmental endocrine-disrupting chemical. PMID:10188190

  15. Evidence that Altered Cis Element Spacing Affects PpsR Mediated Redox Control of Photosynthesis Gene Expression in Rubrivivax gelatinosus

    PubMed Central

    Shimizu, Takayuki; Cheng, Zhuo; Matsuura, Katsumi; Masuda, Shinji; Bauer, Carl E.

    2015-01-01

    PpsR is a major regulator of photosynthesis gene expression among all characterized purple photosynthetic bacteria. This transcription regulator has been extensively characterized in Rhodobacter (Rba.) capsulatus and Rba. sphaeroides which are members of the ?-proteobacteria lineage. In this study, we have investigated the biochemical properties and mutational effects of a ppsR deletion strain in the ?-proteobacterium Rubrivivax (Rvi.) gelatinosus in order to reveal phylogenetically conserved mechanisms and species-specific characteristics. A deletion of the ppsR gene resulted in de-repression of photosystem synthesis showing that PpsR functions as a repressor of photosynthesis genes in this species. We also constructed a Rvi. gelatinosus PpsR mutant in which a conserved cysteine at position 436 was changed to an alanine to examine whether or not this residue is important for sensing redox, as reported in Rhodobacter species. Surprisingly, the Cys436 Ala mutant retained the ability to repress photosynthesis gene expression under aerobic conditions, suggesting that PpsR from Rvi. gelatinosus has different redox-responding characteristics. Furthermore, biochemical analyses demonstrated that Rvi. gelatinosus PpsR only shows redox-dependent binding to promoters with 9-bp spacing, but not 8-bp spacing, between two PpsR-recognition sequences. These results indicate that redox-dependent binding of PpsR requires appropriate cis configuration of PpsR target sequences in Rvi. gelatinosus. These results also indicate that PpsR homologs from different species regulate photosynthesis genes with altered biochemical properties. PMID:26030916

  16. Beta-adrenergic blockade affects initial drug distribution due to decreased cardiac output and altered blood flow distribution.

    PubMed

    Avram, Michael J; Krejcie, Tom C; Henthorn, Thomas K; Niemann, Claus U

    2004-11-01

    Beta-adrenergic receptor blockers decrease intravenous anesthetic dose requirements. The present study determined the effect of propranolol on indocyanine green and antipyrine disposition from the moment of rapid intravenous injection. Anti-pyrine is a physiological marker that distributes to a volume as large as total body water in a blood flow-dependent manner and is a pharmacokinetic surrogate for many lipophilic drugs, including intravenous anesthetics. Antipyrine and indocyanine green disposition were determined twice in five healthy adult males in this Institutional Review Board-approved study, once during propranolol infusion. After rapid indocyanine green and antipyrine injection, arterial blood samples were collected frequently for 2 min and less frequently thereafter. Plasma indocyanine green and antipyrine concentrations were measured by high-performance liquid chromatography. Indocyanine green and antipyrine disposition were characterized, using SAAM II, by a recirculatory pharmacokinetic model that describes drug disposition from the moment of injection. Parameters were compared using the paired t test. The disposition of indocyanine green demonstrated that propranolol decreased cardiac output at the expense of the fast peripheral (nonsplanchnic) intravascular circuit. The area under the antipyrine concentration versus time relationship was doubled for at least the first 3 min after injection due to both decreased cardiac output and maintenance of nondistributive blood flow at the expense of a two-thirds reduction of blood flow (intercompartmental clearance) to the rapidly equilibrating (fast, splanchnic) tissue volume. The increase in antipyrine area under the curve due to propranolol-induced alteration of initial antipyrine disposition could explain decreased intravenous anesthetic dose requirements in the presence of beta-adrenergic receptor blockade. PMID:15197245

  17. Evolution of male genitalia: environmental and genetic factors affect genital morphology in two Drosophila sibling species and their hybrids

    PubMed Central

    Soto, Ignacio M; Carreira, Valeria P; Fanara, Juan J; Hasson, Esteban

    2007-01-01

    Background The rapid evolution of genital morphology is a fascinating feature that accompanies many speciation events. However, the underlying patterns and explanatory processes remain to be settled. In this work we investigate the patterns of intraspecific variation and interspecific divergence in male genitalic morphology (size and shape) in the cactophilic sibling species Drosophila buzzatii and D. koepferae. Genital morphology in interspecific hybrids was examined and compared to the corresponding parental lines. Results Despite of being siblings, D. buzzatii and D. koepferae showed contrasting patterns of genital morphological variation. Though genitalic size and shape variation have a significant genetic component in both species, shape varied across host cacti only in D. buzzatii. Such plastic expression of genital shape is the first evidence of the effect of rearing substrate on genitalic morphology in Drosophila. Hybrid genital morphology was not intermediate between parental species and the morphological resemblance to parental strains was cross-dependent. Conclusion Our results suggest the evolution of different developmental networks after interspecific divergence and the existence of a complex genetic architecture, involving genetic factors with major effects affecting genital morphology. PMID:17504529

  18. Alteration of BRCA1 expression affects alcohol-induced transcription of RNA Pol III-dependent genes.

    PubMed

    Zhong, Qian; Shi, Ganggang; Zhang, Yanmei; Lu, Lei; Levy, Daniel; Zhong, Shuping

    2015-02-01

    Emerging evidence has indicated that alcohol consumption is an established risk factor for breast cancer. Deregulation of RNA polymerase III (Pol III) transcription enhances cellular Pol III gene production, leading to an increase in translational capacity to promote cell transformation and tumor formation. We have reported that alcohol intake increases Pol III gene transcription to promote cell transformation and tumor formation in vitro and in vivo. Studies revealed that tumor suppressors, pRb, p53, PTEN and Maf1 repress the transcription of Pol III genes. BRCA1 is a tumor suppressor and its mutation is tightly related to breast cancer development. However, it is not clear whether BRCA1 expression affects alcohol-induced transcription of Pol III genes. At the present studies, we report that restoring BRCA1 in HCC 1937 cells, which is a BRCA1 deficient cell line, represses Pol III gene transcription. Expressing mutant or truncated BRCA1 in these cells does not affect the ability of repression on Pol III genes. Our analysis has demonstrated that alcohol induces Pol III gene transcription. More importantly, overexpression of BRCA1 in estrogen receptor positive (ER+) breast cancer cells (MCF-7) decreases the induction of tRNA(Leu) and 5S rRNA genes by alcohol, whereas reduction of BRCA1 by its siRNA slightly increases the transcription of the class of genes. This suggests that BRCA1 is associated with alcohol-induced deregulation of Pol III genes. These studies for the first time demonstrate the role of BRCA1 in induction of Pol III genes by alcohol and uncover a novel mechanism of alcohol-associated breast cancer. PMID:25447904

  19. Genetic mapping of quantitative trait loci affecting susceptibility to Marek's disease virus induced tumors in F2 intercross chickens.

    PubMed Central

    Vallejo, R L; Bacon, L D; Liu, H C; Witter, R L; Groenen, M A; Hillel, J; Cheng, H H

    1998-01-01

    Marek's disease (MD) is a lymphoproliferative disease caused by the MD virus (MDV), which costs the poultry industry nearly $1 billion annually. To identify quantitative trait loci (QTL) affecting MD susceptibility, the inbred lines 6(3) (MD resistant) and 7(2) (MD susceptible) were mated to create more than 300 F2 chickens. The F2 chickens were challenged with MDV JM strain, moderately virulent) at 1 wk of age and assessed for MD susceptibility. The QTL analysis was divided into three stages. In stage 1, 65 DNA markers selected from the chicken genetic maps were typed on the 40 most MD-susceptible and the 40 most MD-resistant F2 chickens, and 21 markers residing near suggestive QTL were revealed by analysis of variance (ANOVA). In stage 2, the suggestive markers plus available flanking markers were typed on 272 F2 chickens, and three suggestive QTL were identified by ANOVA. In stage 3, using the interval mapping program Map Manager and permutation tests, two significant and two suggestive MD QTL were identified on four chromosomal subregions. Three to five loci collected explained between 11 and 23% of the phenotypic MD variation, or 32-68% of the genetic variance. This study constitutes the first report in the domestic chicken on the mapping of non-major histocompatibility complex QTL affecting MD susceptibility. PMID:9475745

  20. Genetic manipulation of polyphosphate metabolism affects cadmium tolerance in Escherichia coli.

    PubMed Central

    Keasling, J D; Hupf, G A

    1996-01-01

    The polyphosphate metabolic pathways in Escherichia coli were genetically manipulated to test the effect of polyphosphate on tolerance to cadmium. A polyphosphate kinase (ppk) and polyphosphatase (ppx) mutant strain produced no polyphosphate, whereas the same strain carrying multiple copies of ppk on a high-copy plasmid produced significant quantities. The doubling times of both strains increased with increasing cadmium concentrations. In contrast, the mutant strain carrying multiple copies of ppk and ppx produced 1/20 of the polyphosphate found in the strain carrying multiple copies of ppk only and showed no significant increase in doubling time over the same cadmium concentration range. PMID:8593078

  1. Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau.

    PubMed

    Leng, Shuguang; Picchi, Maria A; Liu, Yushi; Thomas, Cynthia L; Willis, Derall G; Bernauer, Amanda M; Carr, Teara G; Mabel, Padilla T; Han, Younghun; Amos, Christopher I; Lin, Yong; Stidley, Christine A; Gilliland, Frank D; Jacobson, Marty R; Belinsky, Steven A

    2013-05-01

    Epidemiological studies of underground miners suggested that occupational exposure to radon causes lung cancer with squamous cell carcinoma (SCC) as the predominant histological type. However, the genetic determinants for susceptibility of radon-induced SCC in miners are unclear. Double-strand breaks induced by radioactive radon daughters are repaired primarily by non-homologous end joining (NHEJ) that is accompanied by the dynamic changes in surrounding chromatin, including nucleosome repositioning and histone modifications. Thus, a molecular epidemiological study was conducted to assess whether genetic variation in 16 genes involved in NHEJ and related histone modification affected susceptibility for SCC in radon-exposed former miners (267 SCC cases and 383 controls) from the Colorado plateau. A global association between genetic variation in the haplotype block where SIRT1 resides and the risk for SCC in miners (P = 0.003) was identified. Haplotype alleles tagged by the A allele of SIRT1 rs7097008 were associated with increased risk for SCC (odds ratio = 1.69, P = 8.2 × 10(-5)) and greater survival in SCC cases (hazard ratio = 0.79, P = 0.03) in miners. Functional validation of rs7097008 demonstrated that the A allele was associated with reduced gene expression in bronchial epithelial cells and compromised DNA repair capacity in peripheral lymphocytes. Together, these findings substantiate genetic variation in SIRT1 as a risk modifier for developing SCC in miners and suggest that SIRT1 may also play a tumor suppressor role in radon-induced cancer in miners. PMID:23354305

  2. Genetic variation in SIRT1 affects susceptibility of lung squamous cell carcinomas in former uranium miners from the Colorado plateau

    PubMed Central

    Leng, Shuguang; Picchi, Maria A.; Liu, Yushi; Thomas, Cynthia L.; Willis, Derall G.; Bernauer, Amanda M.; Carr, Teara G.; Mabel, Padilla T.; Han, Younghun; Amos, Christopher I.; Lin, Yong; Stidley, Christine A.; Gilliland, Frank D.; Jacobson, Marty R.; Belinsky, Steven A.

    2013-01-01

    Epidemiological studies of underground miners suggested that occupational exposure to radon causes lung cancer with squamous cell carcinoma (SCC) as the predominant histological type. However, the genetic determinants for susceptibility of radon-induced SCC in miners are unclear. Double-strand breaks induced by radioactive radon daughters are repaired primarily by non-homologous end joining (NHEJ) that is accompanied by the dynamic changes in surrounding chromatin, including nucleosome repositioning and histone modifications. Thus, a molecular epidemiological study was conducted to assess whether genetic variation in 16 genes involved in NHEJ and related histone modification affected susceptibility for SCC in radon-exposed former miners (267 SCC cases and 383 controls) from the Colorado plateau. A global association between genetic variation in the haplotype block where SIRT1 resides and the risk for SCC in miners (P = 0.003) was identified. Haplotype alleles tagged by the A allele of SIRT1 rs7097008 were associated with increased risk for SCC (odds ratio = 1.69, P = 8.2×10?5) and greater survival in SCC cases (hazard ratio = 0.79, P = 0.03) in miners. Functional validation of rs7097008 demonstrated that the A allele was associated with reduced gene expression in bronchial epithelial cells and compromised DNA repair capacity in peripheral lymphocytes. Together, these findings substantiate genetic variation in SIRT1 as a risk modifier for developing SCC in miners and suggest that SIRT1 may also play a tumor suppressor role in radon-induced cancer in miners. PMID:23354305

  3. Altered environment and risk of malaria outbreak in South Andaman, Andaman & Nicobar Islands, India affected by tsunami disaster

    PubMed Central

    Krishnamoorthy, Kaliannagoun; Jambulingam, Purushothaman; Natarajan, R; Shriram, AN; Das, Pradeep K; Sehgal, SC

    2005-01-01

    Background Pools of salt water and puddles created by giant waves from the sea due to the tsunami that occurred on 26th December 2004 would facilitate increased breeding of brackish water malaria vector, Anopheles sundaicus. Land uplifts in North Andaman and subsidence in South Andaman have been reported and subsidence may lead to environmental disturbances and vector proliferation. This warrants a situation analysis and vector surveillance in the tsunami hit areas endemic for malaria transmitted by brackish water mosquito, An. sundaicus to predict the risk of outbreak. Methods An extensive survey was carried out in the tsunami-affected areas in Andaman district of the Andaman and Nicobar Islands, India to assess the extent of breeding of malaria vectors in the habitats created by seawater flooding. Types of habitats in relation to source of seawater inundation and frequency were identified. The salinity of the water samples and the mosquito species present in the larval samples collected from these habitats were recorded. The malaria situation in the area was also analysed. Results South Andaman, covering Port Blair and Ferrargunj sub districts, is still under the recurring phenomenon of seawater intrusion either directly from the sea or through a network of creeks. Both daily cycles of high tides and periodical spring tides continue to cause flooding. Low-lying paddy fields and fallow land, with a salinity ranging from 3,000 to 42,505 ppm, were found to support profuse breeding of An. sundaicus, the local malaria vector, and Anopheles subpictus, a vector implicated elsewhere. This area is endemic for both vivax and falciparum malaria. Malaria slide positivity rate has started increasing during post-tsunami period, which can be considered as an indication of risk of malaria outbreak. Conclusion Paddy fields and fallow land with freshwater, hitherto not considered as potential sites for An. sundaicus, are now major breeding sites due to saline water. Consequently, there is a risk of vector abundance with enhanced malaria transmission potential, due to the vastness of these tsunami-created breeding grounds and likelihood of them becoming permanent due to continued flooding in view of land subsidence. The close proximity of the houses and paucity of cattle may lead to a higher degree of man/vector contact causing a threat of malaria outbreak in this densely populated area. Measures to prevent the possible outbreak of malaria in this tsunami-affected area are discussed. PMID:16029514

  4. Sampling issues affecting accuracy of likelihood-based classification using genetical data

    USGS Publications Warehouse

    Guinand, B.; Scribner, K.T.; Topchy, A.; Page, K.S.; Punch, W.; Burnham-Curtis, M. K.

    2004-01-01

    We demonstrate the effectiveness of a genetic algorithm for discovering multi-locus combinations that provide accurate individual assignment decisions and estimates of mixture composition based on likelihood classification. Using simulated data representing different levels of inter-population differentiation (Fst ~ 0.01 and 0.10), genetic diversities (four or eight alleles per locus), and population sizes (20, 40, 100 individuals in baseline populations), we show that subsets of loci can be identified that provide comparable levels of accuracy in classification decisions relative to entire multi-locus data sets, where 5, 10, or 20 loci were considered. Microsatellite data sets from hatchery strains of lake trout, Salvelinus namaycush, representing a comparable range of inter-population levels of differentiation in allele frequencies confirmed simulation results. For both simulated and empirical data sets, assignment accuracy was achieved using fewer loci (e.g., three or four loci out of eight for empirical lake trout studies). Simulation results were used to investigate properties of the 'leave-one-out' (L1O) method for estimating assignment error rates. Accuracy of population assignments based on L1O methods should be viewed with caution under certain conditions, particularly when baseline population sample sizes are low (<50).

  5. Genome-wide discovery of genetic variants affecting tamoxifen sensitivity and their clinical and functional validation

    PubMed Central

    Weng, L.; Ziliak, D.; Im, H. K.; Gamazon, E. R.; Philips, S.; Nguyen, A. T.; Desta, Z.; Skaar, T. C.; Flockhart, D. A.; Huang, R. S.

    2013-01-01

    Background Beyond estrogen receptor (ER), there are no validated predictors for tamoxifen (TAM) efficacy and toxicity. We utilized a genome-wide cell-based model to comprehensively evaluate genetic variants for their contribution to cellular sensitivity to TAM. Design Our discovery model incorporates multidimensional datasets, including genome-wide genotype, gene expression, and endoxifen-induced cellular growth inhibition in the International HapMap lymphoblastoid cell lines (LCLs). Genome-wide findings were further evaluated in NCI60 cancer cell lines. Gene knock-down experiments were performed in four breast cancer cell lines. Genetic variants identified in the cell-based model were examined in 245 Caucasian breast cancer patients who underwent TAM treatment. Results We identified seven novel single-nucleotide polymorphisms (SNPs) associated with endoxifen sensitivity through the expression of 10 genes using the genome-wide integrative analysis. All 10 genes identified in LCLs were associated with TAM sensitivity in NCI60 cancer cell lines, including USP7. USP7 knock-down resulted in increasing resistance to TAM in four breast cancer cell lines tested, which is consistent with the finding in LCLs and in the NCI60 cells. Furthermore, we identified SNPs that were associated with TAM-induced toxicities in breast cancer patients, after adjusting for other clinical factors. Conclusion Our work demonstrates the utility of a cell-based model in genome-wide identification of pharmacogenomic markers. PMID:23508821

  6. Inbreeding uncovers fundamental differences in the genetic load affecting male and female fertility in a butterfly.

    PubMed

    Saccheri, Ilik J; Lloyd, Hywel D; Helyar, Sarah J; Brakefield, Paul M

    2005-01-01

    Inbreeding depression is most pronounced for traits closely associated with fitness. The traditional explanation is that natural selection eliminates deleterious mutations with additive or dominant effects more effectively than recessive mutations, leading to directional dominance for traits subject to strong directional selection. Here we report the unexpected finding that, in the butterfly Bicyclus anynana, male sterility contributes disproportionately to inbreeding depression for fitness (complete sterility in about half the sons from brother-sister matings), while female fertility is insensitive to inbreeding. The contrast between the sexes for functionally equivalent traits is inconsistent with standard selection arguments, and suggests that trait-specific developmental properties and cryptic selection play crucial roles in shaping genetic architecture. There is evidence that spermatogenesis is less developmentally stable than oogenesis, though the unusually high male fertility load in B. anynana additionally suggests the operation of complex selection maintaining male sterility recessives. Analysis of the precise causes of inbreeding depression will be needed to generate a model that reliably explains variation in directional dominance and reconciles the gap between observed and expected genetic loads carried by populations. This challenging evolutionary puzzle should stimulate work on the occurrence and causes of sex differences in fertility load. PMID:15875568

  7. The genetic and molecular bases of monogenic disorders affecting proteolytic systems

    PubMed Central

    Richard, I

    2005-01-01

    Complete and limited proteolysis represents key events that regulate many biological processes. At least 5% of the human genome codes for components of proteolytic processes if proteases, inhibitors, and cofactors are taken into account. Accordingly, disruption of proteolysis is involved in numerous pathological conditions. In particular, molecular genetic studies have identified a growing number of monogenic disorders caused by mutations in protease coding genes, highlighting the importance of this class of enzymes in development, organogenesis, immunity, and brain function. This review provides insights into the current knowledge about the molecular genetic causes of these disorders. It should be noted that most are due to loss of function mutations, indicating absolute requirement of proteolytic activities for normal cellular functions. Recent progress in understanding the function of the implicated proteins and the disease pathogenesis is detailed. In addition to providing important clues to the diagnosis, treatment, and pathophysiology of disease, functional characterisation of mutations in proteolytic systems emphasises the pleiotropic functions of proteases in the body homeostasis. PMID:15994873

  8. Mutations altering the gammaretrovirus endoproteolytic motif affect glycosylation of the envelope glycoprotein and early events of the virus life cycle.

    PubMed

    Argaw, Takele; Wilson, Carolyn A

    2015-01-15

    Previously, we found that mutation of glutamine to proline in the endoproteolytic cleavage signal of the PERV-C envelope (RQKK to RPKK) resulted in non-infectious vectors. Here, we show that RPKK results in a non-infectious vector when placed in not only a PERV envelope, but also the envelope of a related gammaretrovirus, FeLV-B. The amino acid substitutions do not prevent envelope precursor cleavage, viral core and genome assembly, or receptor binding. Rather, the mutations result in the formation of hyperglycosylated glycoprotein and a reduction in the reverse transcribed minus strand synthesis and undetectable 2-LTR circular DNA in cells exposed to vectors with these mutated envelopes. Our findings suggest novel functions associated with the cleavage signal sequence that may affect trafficking through the glycosylation machinery of the cell. Further, the glycosylation status of the envelope appears to impact post-binding events of the viral life cycle, either membrane fusion, internalization, or reverse transcription. PMID:25462351

  9. Altering the rest interval during high-intensity interval training does not affect muscle or performance adaptations.

    PubMed

    Edge, Johann; Eynon, Nir; McKenna, Michael J; Goodman, Craig A; Harris, Roger C; Bishop, David J

    2013-02-01

    It has been hypothesized that exercise-induced changes in metabolites and ions are crucial in the adaptation of contracting muscle. We tested this hypothesis by comparing adaptations to two different interval-training protocols (differing only in the rest duration between intervals), which provoked different perturbations in muscle metabolites and acid-base status. Prior to and immediately after training, 12 women performed the following tests: (1) a graded exercise test to determine peak oxygen uptake (V(O2)); (2) a high-intensity exercise bout (followed 60 s later by a repeated-sprint-ability test; and (3) a repeat of the high-intensity exercise bout alone with muscle biopsies pre-exercise, immediately postexercise and after 60 s of recovery. Subjects performed 5 weeks (3 days per week) of training, with either a short (1 min; HIT-1) or a long rest period (3 min; HIT-3) between intervals; training intensity and volume were matched. Muscle [H(+)] (155 ± 15 versus 125 ± 8 nmol l(-1); P < 0.05) and muscle lactate content (84.2 ± 7.9 versus 46.9 ± 3.1 mmol (g wet weight)(-1)) were both higher after HIT-1, while muscle phosphocreatine (PCr) content (52.8 ± 8.3 versus 63.4 ± 9.8 mmol (g wet weight)(-1)) was lower. There were no significant differences between the two groups regarding the increases in , repeated-sprint performance or muscle Na(+),K(+)-ATPase content. Following training, both groups had a significant decrease in postexercise muscle [H(+)] and lactate content, but not postexercise ATP or PCr. Postexercise PCr resynthesis increased following both training methods. In conclusion, intense interval training results in marked improvements in muscle Na(+),K(+)-ATPase content, PCr resynthesis and . However, manipulation of the rest period during intense interval training did not affect these changes. PMID:22923232

  10. Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation

    PubMed Central

    2010-01-01

    Background Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Results Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Conclusion Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing. PMID:20707912

  11. Genetic linkage between X-chromosome markers and bipolar affective illness

    Microsoft Academic Search

    Miron Baron; Neil Risch; Rahel Hamburger; Batsheva Mandel; Stuart Kushner; Michael Newman; Dov Drumer; Robert H. Belmaker

    1987-01-01

    A pedigree study shows close linkage of bipolar affective illness (manic depression) to the X-chromosome markers colour blindness and glucose-6-phosphate dehydrogenase deficiency. The maximum lod score ranges from 7.52 (assuming homogeneity) to 9.17 (assuming heterogeneity); that is, the odds in favour of linkage range between 3×107 to 1 and 109 to 1. These results provide confirmation that a major psychiatric

  12. Modelling genetic reorganization in the mouse spinal cord affecting left–right coordination during locomotion

    PubMed Central

    Rybak, Ilya A; Shevtsova, Natalia A; Kiehn, Ole

    2013-01-01

    The spinal neural circuit contains inhibitory (CINi) and excitatory (CINe) commissural interneurons with axons crossing the mid-line. Direction of these axons to the other side of the cord is controlled by axon guidance molecules, such as Netrin-1 and DCC. The cord also contains glutamatergic interneurons, whose axon guidance involves the EphA4 receptor. In EphA4 knockout (KO) and Netrin-1 KO mice, the normal left–right alternating pattern is replaced with a synchronized hopping gait, and the cord of DCC KO mice exhibits uncoordinated left and right oscillations. To investigate the effects of these genetic transformations, we used a computational model of the spinal circuits containing left and right rhythm-generating neuron populations (RGs), each with a subpopulation of EphA4-positive neurons, and CINi and CINe populations mediating mutual inhibition and excitation between the left and right RGs. In the EphA4 KO circuits, half of the EphA4-positive axons crossed the mid-line and excited the contralateral RG neurons. In the Netrin-1 KO model, the number of contralateral CINi projections was significantly reduced, while in the DCC KO model, the numbers of both CINi and CINe connections were reduced. In our simulations, the EphA4 and Netrin-1 KO circuits switched from the left–right alternating pattern to a synchronized hopping pattern, and the DCC KO network exhibited uncoordinated left–right activity. The amplification of inhibitory interactions re-established an alternating pattern in the EphA4 and DCC KO circuits, but not in the Netrin-1 KO network. The model reproduces the genetic transformations and provides insights into the organization of the spinal locomotor network. PMID:24081162

  13. Expression profiling of the RPE in zebrafish smarca4 mutant revealed altered signals that potentially affect RPE and retinal differentiation

    PubMed Central

    Ma, Ping; Collery, Ross; Trowbridge, Sara; Zhong, Wenxuan; Leung, Yuk Fai

    2014-01-01

    Purpose The purpose of this study was to develop a framework for analyzing retinal pigment epithelium (RPE) expression profiles from zebrafish eye mutants. Methods The fish model we used was SWI/SNF-related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (smarca4), a retinal dystrophic mutant with a previously described retinal phenotype and expression profiles. Histological and Affymetrix GeneChip analyses were conducted to characterize the RPE defects and underlying differential expression, respectively. Results Histological analysis revealed that smarca4 RPE was formed, but its differentiation was abnormal. In particular, ultrastructural analysis of smarca4 RPE by transmission electron microscopy demonstrated several defects in melanogenesis. The nature of these defects also suggests that the cytoskeletal dynamics, which are tightly linked with melanogenesis, were impaired in smarca4 RPE. To compare the expression profile of normal wild-type (WT) and smarca4 RPE, the gene expression profiles of microdissected retinas and RPE-attached retinas were measured with Affymetrix GeneChip analysis. The RPE expression values were then estimated from these samples by subtracting the retinal expression values from the expression values of the RPE-attached retinas. A factorial analysis was conducted using the expression values of the RPE, retinal, and whole-embryo samples. Specific rules (contrasts) were built using the coefficients of the resulting fitted models to select for three groups of genes: 1) smarca4-regulated RPE genes, 2) smarca4-regulated retinal genes, and 3) smarca4-regulated RPE genes that are not differentially expressed in the retina. Interestingly, the third group consists of 39 genes that are highly related to cytoskeletal dynamics, melanogenesis, and paracrine and intracellular signal transduction. Conclusions Our analytical framework provides an experimental approach to identify differentially-regulated genes in the retina and the RPE of zebrafish mutants in which both of these tissues are affected by the underlying mutation. Specifically, we have used the method to identify a group of 39 genes that can potentially explain the melanogenesis defect in the smarca4 RPE. In addition, several genes in this group are secreted signaling molecules. Thus, this observation further implicates that the smarca4 RPE might play a role in the retinal dystrophic phenotype in smarca4. PMID:24426776

  14. The transcript elongation factor FACT affects Arabidopsis vegetative and reproductive development and genetically interacts with HUB1/2.

    PubMed

    Lolas, Ihab B; Himanen, Kristiina; Grønlund, Jesper T; Lynggaard, Carina; Houben, Andreas; Melzer, Michael; Van Lijsebettens, Mieke; Grasser, Klaus D

    2010-02-01

    The facilitates chromatin transcription (FACT) complex, consisting of the SSRP1 and SPT16 proteins, is a histone chaperone that assists the progression of transcribing RNA polymerase on chromatin templates by destabilizing nucleosomes. Here, we examined plants that harbour mutations in the genes encoding the subunits of Arabidopsis FACT. These experiments revealed that (i) SSRP1 is critical for plant viability, and (ii) plants with reduced amounts of SSRP1 and SPT16 display various defects in vegetative and reproductive development. Thus, mutant plants display an increased number of leaves and inflorescences, show early bolting, have abnormal flower and leaf architecture, and their seed production is severely affected. The early flowering of the mutant plants is associated with reduced expression of the floral repressor FLC in ssrp1 and spt16 plants. Compared to control plants, reduced amounts of FACT in mutant plants are detected at the FLC locus as well as at the locations of housekeeping genes (whose expression is not affected in the mutants), suggesting that expression of FLC is particularly sensitive to reduced FACT activity. Analysis of double mutants that are affected in the expression of both FACT subunits and factors catalysing the mono-ubiquitination of histone H2B (HUB1/2) demonstrates that they genetically interact to regulate various developmental processes (i.e. branching, leaf venation pattern, silique development) but independently regulate the growth of leaves and the induction of flowering. PMID:19947984

  15. Genetic and environmental factors affecting growth and reproduction characters of Morada Nova sheep in Northeastern Brazil

    E-print Network

    Fernandes, Antonio Amaury Oria

    1985-01-01

    of Morada Nova sheep. Data were obtained from 1, 338 ewes and 989 lambs sired by 50 rams at the Iracema Farm ? EPACE ? Quixada, Ceaza, Brazil from 1979 to 1984. The growth traits studied were birth weight (BW), weaning weight (WW), and yearling weight... (YW). Environmental factors con- sidered were year and location of birth, age of dam, sex of lamb, and type of birth and rearing. All environmental factors significantly affected (P & . 01) BW, WW and YW. Some factors, such as age of dam, had great...

  16. Genetic variants in PCSK9 affect the cholesterol level in Japanese.

    PubMed

    Shioji, Keisuke; Mannami, Toshifumi; Kokubo, Yoshihiro; Inamoto, Nozomu; Takagi, Shuichi; Goto, Yoichi; Nonogi, Hiroshi; Iwai, Naoharu

    2004-01-01

    Mutations in the proprotein convertase subtilisin/kexin 9 ( PCSK9) gene have been reported in affected members of two families with autosomal dominant hypercholesterolemia. To investigate the effects of common variants in PCSK9 on the cholesterol level, we conducted an association study using a large cohort representing the general population in Japan (n=1,793). Direct sequencing in all of the exonic regions identified 21 polymorphisms. After consideration of linkage disequilibrium among these polymorphisms, we selected and genotyped nine polymorphisms by the TaqMan method. The intron 1/C(-161)T and exon 9/I474 V polymorphisms were associated with levels of total cholesterol (TC) [C(-161)T, P=0.0285; I474 V, P=0.0069] and low-density lipoprotein cholesterol (LDL-C) [C(-161)T, P=0.0257; I474 V, P=0.0007]. The distributions of these polymorphisms in subjects with miocardial infarction (MI) (n=649) were not different from those in the control population. These results provide the first evidence that common variants intron 1/C(-161)T and exon 9/I474 V in PCSK9 significantly affect TC and LDL-C levels in the general population in Japan. PMID:14727156

  17. Characterization and genetic mapping of a mutation affecting apurinic endonuclease activity in Staphylococcus aureus

    SciTech Connect

    Tam, J.E.; Pattee, P.A.

    1986-11-01

    Protoplast fusion between the Rec- mutant RN981 (L. Wyman, R. V. Goering, and R. P. Novick, Genetics 76:681-702, 1974) of Staphylococcus aureus NCTC 8325 and a Rec+ NCTC 8325 derivative yielded Rec+ recombinants that exhibited the increased sensitivity to N-methyl-N'-nitro-N-nitrosoguanidine characteristic of RN981. Transformation analyses identified a specific mutation, designated ngr-374, that was responsible not only for N-methyl-N'-nitro-N-nitrosoguanidine sensitivity, but also sensitivity to methyl methanesulfonate, ethyl methanesulfonate, nitrous acid, and UV irradiation. However, ngr-374-carrying recombinants showed no significant increase in their sensitivity to mitomycin C or 4-nitroquinoline 1-oxide and were unaffected in recombination proficiency. In vitro assays showed that ngr-374-carrying strains had lower apurinic/apyrimidinic endonuclease activities than the wild type. The chromosomal locus occupied by ngr-374 was shown to exist in the gene order omega(Chr::Tn551)40-ngr-374-thrB106.

  18. Genetic Manipulation of The Cardiac Mitochondrial Phosphate Carrier does not affect Permeability Transition

    PubMed Central

    Gutiérrez-Aguilar, Manuel; Douglas, Diana L.; Gibson, Anne K.; Domeier, Timothy L.; Molkentin, Jeffery D.; Baines, Christopher P.

    2014-01-01

    The Mitochondrial Permeability Transition (MPT) pore is a voltage-sensitive unselective channel known to instigate necrotic cell death during cardiac disease. Recent models suggest that the isomerase cyclophilin D (CypD) regulates the MPT pore by binding to either the F0F1-ATP synthase lateral stalk or the mitochondrial phosphate carrier (PiC). Here we confirm that CypD, through its N-terminus, can directly bind PiC. We then generated cardiac-specific mouse strains overexpressing or with decreased levels of mitochondrial PiC to assess the functionality of such interaction. While PiC overexpression had no observable pathologic phenotype, PiC knockdown resulted in cardiac hypertrophy along with decreased ATP levels. Mitochondria isolated from hearts of these mouse lines and their respective non-transgenic controls had no divergent phenotype in terms of oxygen consumption and Ca2+-induced MPT, as assessed by swelling and Ca2+-retention measurements. These results provide genetic evidence indicating that the mitochondrial PiC is not a critical component of the MPT pore. PMID:24768964

  19. ‘Faceness’ and Affectivity: Evidence for Genetic Contributions to Distinct Components of Electrocortical Response to Human Faces

    PubMed Central

    Shannon, Robert W.; Patrick, Christopher J.; Venables, Noah C.; He, Sheng

    2014-01-01

    The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. PMID:23769918

  20. Strain-specific nuclear genetic background differentially affects mitochondria-related phenotypes in Saccharomyces cerevisiae

    PubMed Central

    Montanari, Arianna; Francisci, Silvia; Fazzi D'Orsi, Mario; Bianchi, Michele Maria

    2014-01-01

    In the course of our studies on mitochondrial defects, we have observed important phenotypic variations in Saccharomyces cerevisiae strains suggesting that a better characterization of the genetic variability will be essential to define the relationship between the mitochondrial efficiency and the presence of different nuclear backgrounds. In this manuscript, we have extended the study of such relations by comparing phenotypic assays related to mitochondrial functions of three wild-type laboratory strains. In addition to the phenotypic variability among the wild-type strains, important differences have been observed among strains bearing identical mitochondrial tRNA mutations that could be related only to the different nuclear background of the cells. Results showed that strains exhibited an intrinsic variability in the severity of the effects of the mitochondrial mutations and that specific strains might be used preferentially to evaluate the phenotypic effect of mitochondrial mutations on carbon metabolism, stress responses, and mitochondrial DNA stability. In particular, while W303-1B and MCC123 strains should be used to study the effect of severe mitochondrial tRNA mutations, D273-10B/A1 strain is rather suitable for studying the effects of milder mutations. PMID:24700775

  1. The kinesin-13 KLP10A motor regulates oocyte spindle length and affects EB1 binding without altering microtubule growth rates

    PubMed Central

    Do, Kevin K.; Hoàng, Kim Liên; Endow, Sharyn A.

    2014-01-01

    ABSTRACT Kinesin-13 motors are unusual in that they do not walk along microtubules, but instead diffuse to the ends, where they remove tubulin dimers, regulating microtubule dynamics. Here we show that Drosophila kinesin-13 klp10A regulates oocyte meiosis I spindle length and is haplo-insufficient – KLP10A, reduced by RNAi or a loss-of-function P element insertion mutant, results in elongated and mispositioned oocyte spindles, and abnormal cortical microtubule asters and aggregates. KLP10A knockdown by RNAi does not significantly affect microtubule growth rates in oocyte spindles, but, unexpectedly, EB1 binding and unbinding are slowed, suggesting a previously unobserved role for kinesin-13 in mediating EB1 binding interactions with microtubules. Kinesin-13 may regulate spindle length both by disassembling subunits from microtubule ends and facilitating EB1 binding to plus ends. We also observe an increased number of paused microtubules in klp10A RNAi knockdown spindles, consistent with a reduced frequency of microtubule catastrophes. Overall, our findings indicate that reduced kinesin-13 decreases microtubule disassembly rates and affects EB1 interactions with microtubules, rather than altering microtubule growth rates, causing spindles to elongate and abnormal cortical microtubule asters and aggregates to form. PMID:24907370

  2. Alterations in the cerebral white matter of genetic high risk offspring of patients with schizophrenia spectrum disorder.

    PubMed

    Francis, Alan N; Bhojraj, Tejas S; Prasad, Konasale M; Montrose, Debra; Eack, Shaun M; Rajarethinam, Rajaprabhakaran; van Elst, Ludger T; Keshavan, Matcheri S

    2013-01-10

    Alterations in white matter (WM) may be seen in young relatives at risk and may underlie vulnerability to schizophrenia. We were interested in exploring which of the WM regions were altered in adolescent offspring at familial risk for schizophrenia. We examined structural alterations in the offspring of subjects with schizophrenia or schizoaffective disorder (HR; n=65; 36 males) and healthy controls (HC; n=80: 37 males) matched for age and education. MRI images were collected using a GE 1.5 T scanner at the University of Pittsburgh Medical Center. Image processing was done using FreeSurfer (MGH) by an experienced rater blind to clinical data. We used multivariate analysis of covariance, with intracranial volume (p>0.05) and age as covariates. High Risk offspring had significant reductions in total WM, hemispheric WM and WM within left parietal and left cingulate cortices. Male offspring had more pronounced right hemisphere WM reductions than females. PMID:22910323

  3. Neuropsychological Functioning in Adolescents and Young Adults at Genetic Risk for Schizophrenia and Affective Psychoses: Results from the Harvard and Hillside Adolescent High Risk Studies

    Microsoft Academic Search

    Larry J. Seidman; Anthony J. Giuliano; Christopher W. Smith; William S. Stone; Stephen J. Glatt; Eric Meyer; Stephen V. Faraone; Ming T. Tsuang; Barbara Cornblatt

    2006-01-01

    Siblings and offspring of persons with schizophrenia carry elevated genetic risk for the illness and manifest attentional and memory impairments. Because less is known about other neuropsychological functions and their specificity in adolescents, we conducted a genetic high-risk (HR) study of schizophrenia (HR-SCZ) and affective psychosis (HR- AFF). Participants (ages 12-25) were from the Harvard Adolescent High-Risk and Hillside Family

  4. Genetic disruption of the On visual pathway affects cortical orientation selectivity and contrast sensitivity in mice.

    PubMed

    Sarnaik, Rashmi; Chen, Hui; Liu, Xiaorong; Cang, Jianhua

    2014-06-01

    The retina signals stimulus contrast via parallel On and Off pathways and sends the information to higher visual centers. Here we study the role of the On pathway using mice that have null mutations in the On-specific GRM6 receptor in the retina (Pinto LH, Vitaterna MH, Shimomura K, Siepka SM, Balannik V, McDearmon EL, Omura C, Lumayag S, Invergo BM, Brandon M, Glawe B, Cantrell DR, Donald R, Inayat S, Olvera MA, Vessey KA, Kirstan A, McCall MA, Maddox D, Morgans CW, Young B, Pletcher MT, Mullins RF, Troy JB, Takahashi JS. Vis Neurosci 24: 111-123, 2007; Maddox DM, Vessey KA, Yarbrough GL, Invergo BM, Cantrell DR, Inayat S, Balannik V, Hicks WL, Hawes NL, Byers S, Smith RS, Hurd R, Howell D, Gregg RG, Chang B, Naggert JK, Troy JB, Pinto LH, Nishina PM, McCall MA. J Physiol 586: 4409-4424, 2008). In these "nob" mice, single unit recordings in the primary visual cortex (V1) reveal degraded selectivity for orientations due to an increased response at nonpreferred orientations. Contrast sensitivity in the nob mice is reduced with severe deficits at low contrast, consistent with the phenotype of night blindness in human patients with mutations in Grm6. These cortical deficits can be largely explained by reduced input drive and increased response variability seen in nob V1. Interestingly, increased variability is also observed in the superior colliculus of these mice but does not affect its tuning properties. Further, the increased response variability in the nob mice is traced to the retina, a result phenocopied by acute pharmacological blockade of the On pathway in wild-type retina. Together, our results suggest that the On and Off pathways normally interact to increase response reliability in the retina, which in turn propagates to various central visual targets and affects their functional properties. PMID:24598523

  5. Genetic disruption of the On visual pathway affects cortical orientation selectivity and contrast sensitivity in mice

    PubMed Central

    Sarnaik, Rashmi; Chen, Hui; Liu, Xiaorong

    2014-01-01

    The retina signals stimulus contrast via parallel On and Off pathways and sends the information to higher visual centers. Here we study the role of the On pathway using mice that have null mutations in the On-specific GRM6 receptor in the retina (Pinto LH, Vitaterna MH, Shimomura K, Siepka SM, Balannik V, McDearmon EL, Omura C, Lumayag S, Invergo BM, Brandon M, Glawe B, Cantrell DR, Donald R, Inayat S, Olvera MA, Vessey KA, Kirstan A, McCall MA, Maddox D, Morgans CW, Young B, Pletcher MT, Mullins RF, Troy JB, Takahashi JS. Vis Neurosci 24: 111–123, 2007; Maddox DM, Vessey KA, Yarbrough GL, Invergo BM, Cantrell DR, Inayat S, Balannik V, Hicks WL, Hawes NL, Byers S, Smith RS, Hurd R, Howell D, Gregg RG, Chang B, Naggert JK, Troy JB, Pinto LH, Nishina PM, McCall MA. J Physiol 586: 4409–4424, 2008). In these “nob” mice, single unit recordings in the primary visual cortex (V1) reveal degraded selectivity for orientations due to an increased response at nonpreferred orientations. Contrast sensitivity in the nob mice is reduced with severe deficits at low contrast, consistent with the phenotype of night blindness in human patients with mutations in Grm6. These cortical deficits can be largely explained by reduced input drive and increased response variability seen in nob V1. Interestingly, increased variability is also observed in the superior colliculus of these mice but does not affect its tuning properties. Further, the increased response variability in the nob mice is traced to the retina, a result phenocopied by acute pharmacological blockade of the On pathway in wild-type retina. Together, our results suggest that the On and Off pathways normally interact to increase response reliability in the retina, which in turn propagates to various central visual targets and affects their functional properties. PMID:24598523

  6. Assessment of factors affecting Agrobacterium-mediated genetic transformation of the unicellular green alga, Chlorella vulgaris.

    PubMed

    Cha, Thye San; Yee, Willy; Aziz, Ahmad

    2012-04-01

    The successful establishment of an Agrobacterium-mediated transformation method and optimisation of six critical parameters known to influence the efficacy of Agrobacterium T-DNA transfer in the unicellular microalga Chlorella vulgaris (UMT-M1) are reported. Agrobacterium tumefaciens strain LBA4404 harbouring the binary vector pCAMBIA1304 containing the gfp:gusA fusion reporter and a hygromycin phosphotransferase (hpt) selectable marker driven by the CaMV35S promoter were used for transformation. Transformation frequency was assessed by monitoring transient ?-glucuronidase (GUS) expression 2 days post-infection. It was found that co-cultivation temperature at 24°C, co-cultivation medium at pH 5.5, 3 days of co-cultivation, 150 ?M acetosyringone, Agrobacterium density of 1.0 units (OD(600)) and 2 days of pre-culture were optimum variables which produced the highest number of GUS-positive cells (8.8-20.1%) when each of these parameters was optimised individually. Transformation conducted with the combination of all optimal parameters above produced 25.0% of GUS-positive cells, which was almost a threefold increase from 8.9% obtained from un-optimised parameters. Evidence of transformation was further confirmed in 30% of 30 randomly-selected hygromycin B (20 mg L(-1)) resistant colonies by polymerase chain reaction (PCR) using gfp:gusA and hpt-specific primers. The developed transformation method is expected to facilitate the genetic improvement of this commercially-important microalga. PMID:22805959

  7. Genetic variation of the RASGRF1 regulatory region affects human hippocampus-dependent memory

    PubMed Central

    Barman, Adriana; Assmann, Anne; Richter, Sylvia; Soch, Joram; Schütze, Hartmut; Wüstenberg, Torsten; Deibele, Anna; Klein, Marieke; Richter, Anni; Behnisch, Gusalija; Düzel, Emrah; Zenker, Martin; Seidenbecher, Constanze I.; Schott, Björn H.

    2014-01-01

    The guanine nucleotide exchange factor RASGRF1 is an important regulator of intracellular signaling and neural plasticity in the brain. RASGRF1-deficient mice exhibit a complex phenotype with learning deficits and ocular abnormalities. Also in humans, a genome-wide association study has identified the single nucleotide polymorphism (SNP) rs8027411 in the putative transcription regulatory region of RASGRF1 as a risk variant of myopia. Here we aimed to assess whether, in line with the RASGRF1 knockout mouse phenotype, rs8027411 might also be associated with human memory function. We performed computer-based neuropsychological learning experiments in two independent cohorts of young, healthy participants. Tests included the Verbal Learning and Memory Test (VLMT) and the logical memory section of the Wechsler Memory Scale (WMS). Two sub-cohorts additionally participated in functional magnetic resonance imaging (fMRI) studies of hippocampus function. 119 participants performed a novelty encoding task that had previously been shown to engage the hippocampus, and 63 subjects participated in a reward-related memory encoding study. RASGRF1 rs8027411 genotype was indeed associated with memory performance in an allele dosage-dependent manner, with carriers of the T allele (i.e., the myopia risk allele) showing better memory performance in the early encoding phase of the VLMT and in the recall phase of the WMS logical memory section. In fMRI, T allele carriers exhibited increased hippocampal activation during presentation of novel images and during encoding of pictures associated with monetary reward. Taken together, our results provide evidence for a role of the RASGRF1 gene locus in hippocampus-dependent memory and, along with the previous association with myopia, point toward pleitropic effects of RASGRF1 genetic variations on complex neural function in humans. PMID:24808846

  8. TNF? altered inflammatory responses, impaired health and productivity, but did not affect glucose or lipid metabolism in early-lactation dairy cows.

    PubMed

    Yuan, Kai; Farney, Jaymelynn K; Mamedova, Laman K; Sordillo, Lorraine M; Bradford, Barry J

    2013-01-01

    Inflammation may be a major contributing factor to peripartum metabolic disorders in dairy cattle. We tested whether administering an inflammatory cytokine, recombinant bovine tumor necrosis factor-? (rbTNF?), affects milk production, metabolism, and health during this period. Thirty-three Holstein cows (9 primiparous and 24 multiparous) were randomly assigned to 1 of 3 treatments at parturition. Treatments were 0 (Control), 1.5, or 3.0 µg/kg body weight rbTNF?, which were administered once daily by subcutaneous injection for the first 7 days of lactation. Statistical contrasts were used to evaluate the treatment and dose effects of rbTNF? administration. Plasma TNF? concentrations at 16 h post-administration tended to be increased (P<0.10) by rbTNF? administration, but no dose effect (P>0.10) was detected; rbTNF? treatments increased (P<0.01) concentrations of plasma haptoglobin. Most plasma eicosanoids were not affected (P>0.10) by rbTNF? administration, but 6 out of 16 measured eicosanoids changed (P<0.05) over the first week of lactation, reflecting elevated inflammatory mediators in the days immediately following parturition. Dry matter and water intake, milk yield, and milk fat and protein yields were all decreased (P<0.05) by rbTNF? treatments by 15 to 18%. Concentrations of plasma glucose, insulin, ?-hydroxybutyrate, non-esterified fatty acids, triglyceride, 3-methylhistidine, and liver triglyceride were unaffected (P>0.10) by rbTNF? treatment. Glucose turnover rate was unaffected (P=0.18) by rbTNF? administration. The higher dose of rbTNF? tended to increase the risk of cows developing one or more health disorders (P=0.08). Taken together, these results indicate that administration of rbTNF? daily for the first 7 days of lactation altered inflammatory responses, impaired milk production and health, but did not significantly affect liver triglyceride accumulation or nutrient metabolism in dairy cows. PMID:24260367

  9. TNF? Altered Inflammatory Responses, Impaired Health and Productivity, but Did Not Affect Glucose or Lipid Metabolism in Early-Lactation Dairy Cows

    PubMed Central

    Mamedova, Laman K.; Sordillo, Lorraine M.; Bradford, Barry J.

    2013-01-01

    Inflammation may be a major contributing factor to peripartum metabolic disorders in dairy cattle. We tested whether administering an inflammatory cytokine, recombinant bovine tumor necrosis factor-? (rbTNF?), affects milk production, metabolism, and health during this period. Thirty-three Holstein cows (9 primiparous and 24 multiparous) were randomly assigned to 1 of 3 treatments at parturition. Treatments were 0 (Control), 1.5, or 3.0 µg/kg body weight rbTNF?, which were administered once daily by subcutaneous injection for the first 7 days of lactation. Statistical contrasts were used to evaluate the treatment and dose effects of rbTNF? administration. Plasma TNF? concentrations at 16 h post-administration tended to be increased (P<0.10) by rbTNF? administration, but no dose effect (P>0.10) was detected; rbTNF? treatments increased (P<0.01) concentrations of plasma haptoglobin. Most plasma eicosanoids were not affected (P>0.10) by rbTNF? administration, but 6 out of 16 measured eicosanoids changed (P<0.05) over the first week of lactation, reflecting elevated inflammatory mediators in the days immediately following parturition. Dry matter and water intake, milk yield, and milk fat and protein yields were all decreased (P<0.05) by rbTNF? treatments by 15 to 18%. Concentrations of plasma glucose, insulin, ?-hydroxybutyrate, non-esterified fatty acids, triglyceride, 3-methylhistidine, and liver triglyceride were unaffected (P>0.10) by rbTNF? treatment. Glucose turnover rate was unaffected (P?=?0.18) by rbTNF? administration. The higher dose of rbTNF? tended to increase the risk of cows developing one or more health disorders (P?=?0.08). Taken together, these results indicate that administration of rbTNF? daily for the first 7 days of lactation altered inflammatory responses, impaired milk production and health, but did not significantly affect liver triglyceride accumulation or nutrient metabolism in dairy cows. PMID:24260367

  10. Identification and mapping of genetic loci affecting the free-threshing habit and spike compactness in wheat ( Triticum aestivum L.).

    PubMed

    Jantasuriyarat, C; Vales, M I; Watson, C J W; Riera-Lizarazu, O

    2004-01-01

    Recombinant inbred lines of the International Triticeae Mapping Initiative (ITMI) mapping population were used to localize genetic loci that affect traits related to the free-threshing habit (percent threshability, glume tenacity, and spike fragility) and to spike morphology (spike length, spikelet number, and spike compactness) of wheat ( Triticum aestivum L.). The ITMI population was planted in three environments during 1999 and 2000, and phenotypic and genotypic data were used for composite interval mapping. Two quantitative trait loci (QTL) that consistently affected threshability-associated traits were localized on chromosomes 2D and 5A. Coincident QTL on the short arm of 2D explained 44% of the variation in threshability, 17% of the variation in glume tenacity, and 42% of the variation in rachis fragility. QTL on chromosomes 2D probably represent the effect of Tg, a gene for tenacious glumes. Coincident QTL on the long arm of 5A explained 21% and 10% of the variation in glume tenacity and rachis fragility, respectively. QTL on 5A are believed to represent the effect of Q. Overall, free-threshing-related characteristics were predominantly affected by Tg and to a lesser extent by Q. Other QTL that were significantly associated with threshability-related traits in at least one environment were localized on chromosomes 2A, 2B, 6A, 6D, and 7B. Four QTL on chromosomes 1B, 4A, 6A, and 7A consistently affected spike characteristics. Coincident QTL on the short arm of chromosome 1B explained 18% and 7% of the variation in spike length and spike compactness, respectively. QTL on the long arm of 4A explained 11%, 14%, and 12% of the variation in spike length, spike compactness, and spikelet number, respectively. A QTL on the short arm of 6A explained 27% of the phenotypic variance for spike compactness, while a QTL on the long arm of 7A explained 18% of the variation in spikelet number. QTL on chromosomes 1B and 6A appear to affect spike dimensions by modulating rachis internode length, while QTL on chromosomes 4A and 7A do so by affecting the formation of spikelets. Other QTL that were significantly associated with spike morphology-related traits, in at least one environment, were localized on chromosomes 2B, 3A, 3D, 4D, and 5A. PMID:13679977

  11. FADS2 Genetic Variance in Combination with Fatty Acid Intake Might Alter Composition of the Fatty Acids in Brain.

    PubMed

    Rizzi, Thais S; van der Sluis, Sophie; Derom, Catherine; Thiery, Evert; van Kesteren, Ronald E; Jacobs, Nele; Van Gestel, Sofie; Vlietinck, Robert; Verhage, Matthijs; Heutink, Peter; Posthuma, Danielle

    2013-01-01

    Multiple lines of evidence suggest that fatty acids (FA) play an important role in cognitive function. However, little is known about the functional genetic pathways involved in cognition. The main goals of this study were to replicate previously reported interaction effects between breast feeding (BF) and FA desaturase (FADS) genetic variation on IQ and to investigate the possible mechanisms by which these variants might moderate BF effect, focusing on brain expression. Using a sample of 534 twins, we observed a trend in the moderation of BF effects on IQ by FADS2 variation. In addition, we made use of publicly available gene expression databases from both humans (193) and mice (93) and showed that FADS2 variants also correlate with FADS1 brain expression (P-value<1.1E-03). Our results provide novel clues for the understanding of the genetic mechanisms regulating FA brain expression and improve the current knowledge of the FADS moderation effect on cognition. PMID:23826354

  12. Genetic Factors Affecting Susceptibility to Low Dose & Low Dose-Rate Radiation

    SciTech Connect

    Bedford, Joel

    2014-04-18

    Our laboratory has, among other things, developed and used the gamma H2AX focus assay and other chromosomal and cell killing assays to show that differences in this DNA double strand break (dsb) related response can be clearly and distinctly demonstrated for cells which are mildly hyper-radiosensitive such as those associated with A-T heterozygosity. We have found this level of mild hypersensitivity for cells from some 20 to 30 % of apparently normal individuals and from apparently normal parents of Retinoblastoma patients. We found significant differences in gene expression in somatic cells from unaffected parents of Rb patients as compared with normal controls, suggesting that these parents may harbor some as yet unidentified genetic abnormality. In other experiments we sought to determine the extent of differences in normal human cellular reaponses to radiation depending on their irradiation in 2D monolayer vs 3D organized acinar growth conditions. We exmined cell reproductive death, chromosomal aberration induction, and the levels of ?-H2AX foci in cells after single acute gamma-ray doses and immediately after 20 hours of irradiation at a dose rate of 0.0017 Gy/min. We found no significant differences in the dose-responses of these cells under the 2D or 3D growth conditions. While this does not mean such differences cannot occur in other situations, it does mean that they do not generally or necessarily occur. In another series of studies in collaboration with Dr Chuan Li, with supprt from this current grant. We reported a role for apoptotic cell death in promoting wound healing and tissue regeneration in mice. Apoptotic cells released growth signals that stimulated the proliferation of progenitor or stem cells. In yet another collaboration with Dr, B. Chen with funds from this grant, the relative radiosensitivity to cell killing as well as chromosomal instability of 13 DNA-PKcs site-directed mutant cell lines (defective at phosphorylation sites or kinase activity) were examined after exposure of synchronized G1 cells to 137Cs c rays. DNA-PKcs mutant cells defective in phosphorylation at multiple sites withinthe T2609 cluster or within the PI3K domain displayed extreme radiosensitivity. Cells defective at the S2056 cluster or T2609 single site alone were only mildly radiosensitive, but cells defective at even one site in both the S2056 and T2609 clusters were maximally radiosensitive. Thus a synergism between the capacity for phosphorylation at the S2056 and T2609 clusterswas found to be critical for induction of radiosensitivity.

  13. Lessons learned from whole exome sequencing in multiplex families affected by a complex genetic disorder, intracranial aneurysm.

    PubMed

    Farlow, Janice L; Lin, Hai; Sauerbeck, Laura; Lai, Dongbing; Koller, Daniel L; Pugh, Elizabeth; Hetrick, Kurt; Ling, Hua; Kleinloog, Rachel; van der Vlies, Pieter; Deelen, Patrick; Swertz, Morris A; Verweij, Bon H; Regli, Luca; Rinkel, Gabriel J E; Ruigrok, Ynte M; Doheny, Kimberly; Liu, Yunlong; Broderick, Joseph; Foroud, Tatiana

    2015-01-01

    Genetic risk factors for intracranial aneurysm (IA) are not yet fully understood. Genomewide association studies have been successful at identifying common variants; however, the role of rare variation in IA susceptibility has not been fully explored. In this study, we report the use of whole exome sequencing (WES) in seven densely-affected families (45 individuals) recruited as part of the Familial Intracranial Aneurysm study. WES variants were prioritized by functional prediction, frequency, predicted pathogenicity, and segregation within families. Using these criteria, 68 variants in 68 genes were prioritized across the seven families. Of the genes that were expressed in IA tissue, one gene (TMEM132B) was differentially expressed in aneurysmal samples (n=44) as compared to control samples (n=16) (false discovery rate adjusted p-value=0.023). We demonstrate that sequencing of densely affected families permits exploration of the role of rare variants in a relatively common disease such as IA, although there are important study design considerations for applying sequencing to complex disorders. In this study, we explore methods of WES variant prioritization, including the incorporation of unaffected individuals, multipoint linkage analysis, biological pathway information, and transcriptome profiling. Further studies are needed to validate and characterize the set of variants and genes identified in this study. PMID:25803036

  14. Genetic and biochemical characterization of mutations affecting the ability of the yeast Pachysolen tannophilus to metabolize D-xylose

    SciTech Connect

    James, A.P.; Zahab, D.M.; Mahmourides, G.; Maleszka, R.; Schneider, H. (National Research Council of Canada, Ottawa, Ontario (Canada))

    1989-11-01

    Induced mutants, selected for their defective growth on D-xylose while retaining the ability to grow normally on D-glucose, were studied in Pachysolen tannophilus, a yeast capable of converting D-xylose to ethanol. Fourteen of the mutations were found to occur at nine distinct loci, and data indicated that many more loci remain to be detected. Most of the mutations were pleiotropic in character, and the expression of some of them was much affected by nutritional conditions and by genetic background. Mutations at several loci resulted in poor growth on at least one compound that was either an intermediate of the tricarboxylic acid cycle, succinate or {alpha}-ketoglutarate, or on compounds metabolizable via this cycle, ethanol or glycerol. An initial biochemical characterization of the mutants was undertaken. Analysis for xylose reductase, xylitol dehydrogenase, and xylulose kinase activity showed that one or more of these activities was affected in 12 of 13 mutants. However, drastic reduction in activity of a single enzyme was confined to that of xylitol dehydrogenase by mutations at three different loci and to that of D-xylose reductase by mutation at another locus. Growth of these latter four mutants was normal on all carbon sources tested that were not five-carbon sugars.

  15. Genetic and management factors affecting beef quality in grazing Hereford steers.

    PubMed

    Melucci, L M; Panarace, M; Feula, P; Villarreal, E L; Grigioni, G; Carduza, F; Soria, L A; Mezzadra, C A; Arceo, M E; Papaleo Mazzucco, J; Corva, P M; Irurueta, M; Rogberg-Muñoz, A; Miquel, M C

    2012-12-01

    Attributes contributing to differences in beef quality of 206 Hereford steers finished on pasture were assessed. Beef quality traits evaluated were: Warner-Bratzler meat tenderness and muscle and fat color at one and seven days after slaughter and trained sensory panel traits (tenderness, juiciness, flavor, and marbling) at seven days. Molecular markers were CAPN1 316 and an SNP in exon 2 on the leptin gene (E2FB). Average daily live weight gain, ultrasound monthly backfat thickness gain and rib-eye area gain were estimated. Molecular markers effects on meat quality traits were analyzed by mixed models. Association of meat quality with post weaning growth traits was analyzed by canonical correlations. Muscle color and marbling were affected by CAPN1 316 and E2FB and Warner-Bratzler meat tenderness by the former. The results confirm that marker assisted selection for tenderness is advisable only when beef aging is a common practice. The most important sources of variation in tenderness and color of meat remained unaccounted for. PMID:22818350

  16. Missing Heritability in the Tails of Quantitative Traits? A Simulation Study on the Impact of Slightly Altered True Genetic Models

    Microsoft Academic Search

    Carolin Pütter; Sonali Pechlivanis; Markus M. Nöthen; Karl-Heinz Jöckel; Heinz-Erich Wichmann; André Scherag

    2011-01-01

    Objective: Genome-wide association studies have identified robust associations between single nucleotide polymorphisms and complex traits. As the proportion of phenotypic variance explained is still limited for most of the traits, larger and larger meta-analyses are being conducted to detect additional associations. Here we investigate the impact of the study design and the underlying assumption about the true genetic effect in

  17. The application of alterable parameter genetic algorithm in optimum firepower distribution for caboodle of air defense force

    Microsoft Academic Search

    Wang Yunfeng; Pan Wei; Diao Huazong; Wang Dezhi

    2011-01-01

    Optimum firepower distribution model for caboodle of air defense force based on genetic algorithm is established by using the battlefield object value and air defense firepower distribution. The model can exert the highest point of firepower unit efficiency of weapon and realize the most damage effect. The steps includes adopting real number to code, creating original community through building chromosome;

  18. Genetic characterization of healthy and sebaceous adenitis affected Standard Poodles from the United States and the United Kingdom.

    PubMed

    Pedersen, N C; Liu, H; McLaughlin, B; Sacks, B N

    2012-07-01

    The degree of heterogeneity associated with geographic origin and sebaceous adenitis (SA) status in Standard Poodles from the United States (US) and the United Kingdom (UK) was assessed. Healthy and SA-affected Standard Poodles from the US and the UK shared a major mitochondrial DNA (mtDNA) haplotype and a single Y chromosome haplotype. However, minor mtDNA haplotypes and frequencies were somewhat different between US and UK dogs and were significantly less associated with SA than major haplotypes across both populations. The US and UK populations exhibited recent divergence from a common gene pool, based on allele frequencies of 24 highly polymorphic short tandem repeats and principle coordinates and cluster analyses of genotype frequencies. However, there was no differentiation between SA affected and unaffected dogs. Over 90% of US and UK Poodles shared a common dog leukocyte antigen (DLA) class II haplotype, but showed some differentiation in minor haplotype frequency. No difference was observed in haplotype heterozygosity between SA affected and unaffected dogs from the same country and no disease association for SA was found within the DLA region by a high density single nucleotide polymorphism (SNP) scan. Zygosity mapping in the DLA region of Poodles indicated much lower site-specific diversity than in an outbred population of street dogs from Bali, Indonesia, reflecting the degree that breed associated historical bottlenecks have reduced diversity in a polymorphic region of the genome. This study shows possible pitfalls in more extensive genome-wide association studies, such as case and control numbers, population stratification, the involvement of multiple genes, and/or the possibility that SA susceptibility is fixed or nearly fixed within the breed, which can reduce power to detect genetic associations. PMID:22512808

  19. Multiple Genetic Alterations within the PI3K Pathway Are Responsible for AKT Activation in Patients with Ovarian Carcinoma

    PubMed Central

    De Marco, Carmela; Rinaldo, Nicola; Bruni, Paola; Malzoni, Carmine; Zullo, Fulvio; Fabiani, Fernanda; Losito, Simona; Scrima, Marianna; Marino, Federica Zito; Franco, Renato; Quintiero, Alfina; Agosti, Valter; Viglietto, Giuseppe

    2013-01-01

    The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is activated in multiple cancers including ovarian carcinoma (OC). However, the relative contribution of the single components within the PI3K pathway to AKT activation in OC is still unclear. We examined 98 tumor samples from Italian OC patients for alterations in the members of the PI3K pathway. We report that AKT is significantly hyperactive in OC compared to normal tissue (n?=?93; p<0.0001) and that AKT activation is preferentially observed in the elderly (>58 years old; n?=?93; p<0.05). The most frequent alteration is the overexpression of the p110? catalytic subunit of PI3K (63/93, ?68%); less frequent alterations comprise the loss of PTEN (24/89, 27%) and the overexpression of AKT1 (18/96, 19%) or AKT2 (11/88,12.5%). Mutations in the PIK3CA or KRAS genes were detected at lower frequency (12% and 10%, respectively) whereas mutations in AKT1 or AKT2 genes were absent. Although many tumors presented a single lesion (28/93, of which 23 overexpressed PIK3CA, 1 overexpressed AKT and 4 had lost PTEN), many OC (35/93) presented multiple alterations within the PI3K pathway. Apparently, aberrant PI3K signalling was mediated by activation of the canonical downstream AKT-dependent mTOR/S6K1/4EBP1 pathway and by regulation of expression of oncogenic transcription factors that include HMGA1, JUN-B, FOS and MYC but not by AKT-independent activation of SGK3. FISH analysis indicated that gene amplification of PIK3CA, AKT1 and AKT2 (but not of PI3KR1) and the loss of PTEN are common and may account for changes in the expression of the corresponding proteins. In conclusion, our results indicate that p110? overexpression represents the most frequent alteration within the PI3K/AKT pathway in OC. However, p110? overexpression may not be sufficient to activate AKT signalling and drive ovarian tumorigenesis since many tumors overexpressing PI3K presented at least one additional alteration. PMID:23408974

  20. Alteration of sexual reproduction and genetic diversity in the kelp species Laminaria digitata at the southern limit of its range.

    PubMed

    Oppliger, Luz Valeria; von Dassow, Peter; Bouchemousse, Sarah; Robuchon, Marine; Valero, Myriam; Correa, Juan A; Mauger, Stéphane; Destombe, Christophe

    2014-01-01

    Adaptation to marginal habitats at species range-limits has often been associated with parthenogenetic reproduction in terrestrial animals and plants. Laboratory observations have shown that brown algae exhibit a high propensity for parthenogenesis by various mechanisms. The kelp Laminaria digitata is an important component of the ecosystem in Northern European rocky intertidal habitats. We studied four L. digitata populations for the effects of marginality on genetic diversity and sexual reproduction. Two populations were marginal: One (Locquirec, in Northern Brittany) was well within the geographic range, but was genetically isolated from other populations by large stretches of sandy beaches. Another population was at the range limits of the species (Quiberon, in Southern Brittany) and was exposed to much higher seasonal temperature changes. Microsatellite analyses confirmed that these populations showed decreased genetic and allelic diversity, consistent with marginality and genetic isolation. Sporophytes from both marginal populations showed greatly diminished spore-production compared to central populations, but only the southern-limit population (Quiberon) showed a high propensity for producing unreduced (2N) spores. Unreduced 2N spores formed phenotypically normal gametophytes with nuclear area consistent with ?2N DNA contents, and microsatellite studies suggested these were produced at least in part by automixis. However, despite this being the dominant path of spore production in Quiberon sporophyte individuals, the genetic evidence indicated the population was maintained mostly by sexual reproduction. Thus, although spore production and development showed the expected tendency of geographical parthenogenesis in marginal populations, this appeared to be a consequence of maladaptation, rather than an adaptation to, life in a marginal habitat. PMID:25019953

  1. Alteration of Sexual Reproduction and Genetic Diversity in the Kelp Species Laminaria digitata at the Southern Limit of Its Range

    PubMed Central

    Oppliger, Luz Valeria; von Dassow, Peter; Bouchemousse, Sarah; Robuchon, Marine; Valero, Myriam; Correa, Juan A.; Mauger, Stéphane; Destombe, Christophe

    2014-01-01

    Adaptation to marginal habitats at species range-limits has often been associated with parthenogenetic reproduction in terrestrial animals and plants. Laboratory observations have shown that brown algae exhibit a high propensity for parthenogenesis by various mechanisms. The kelp Laminaria digitata is an important component of the ecosystem in Northern European rocky intertidal habitats. We studied four L. digitata populations for the effects of marginality on genetic diversity and sexual reproduction. Two populations were marginal: One (Locquirec, in Northern Brittany) was well within the geographic range, but was genetically isolated from other populations by large stretches of sandy beaches. Another population was at the range limits of the species (Quiberon, in Southern Brittany) and was exposed to much higher seasonal temperature changes. Microsatellite analyses confirmed that these populations showed decreased genetic and allelic diversity, consistent with marginality and genetic isolation. Sporophytes from both marginal populations showed greatly diminished spore-production compared to central populations, but only the southern-limit population (Quiberon) showed a high propensity for producing unreduced (2N) spores. Unreduced 2N spores formed phenotypically normal gametophytes with nuclear area consistent with ?2N DNA contents, and microsatellite studies suggested these were produced at least in part by automixis. However, despite this being the dominant path of spore production in Quiberon sporophyte individuals, the genetic evidence indicated the population was maintained mostly by sexual reproduction. Thus, although spore production and development showed the expected tendency of geographical parthenogenesis in marginal populations, this appeared to be a consequence of maladaptation, rather than an adaptation to, life in a marginal habitat. PMID:25019953

  2. Do recent US Supreme Court rulings on patenting of genes and genetic diagnostics affect the practice of genetic screening and diagnosis in prenatal and reproductive care?

    PubMed

    Chandrasekharan, Subhashini; McGuire, Amy L; Van den Veyver, Ignatia B

    2014-10-01

    Thousands of patents have been awarded that claim human gene sequences and their uses, and some have been challenged in court. In a recent high-profile case, Association for Molecular Pathology, et al. v. Myriad Genetics, Inc., et al., the US Supreme Court ruled that genes are natural occurring substances and therefore not patentable through 'composition of matter' claims. The consequences of this ruling will extend well beyond ending Myriad's monopoly over BRCA testing and may affect similar monopolies of other commercial laboratories for tests involving other genes. It could also simplify intellectual property issues surrounding genome-wide clinical sequencing, which can generate results for genes covered by intellectual property. Non-invasive prenatal testing (NIPT) for common aneuploidies using cell-free fetal (cff) DNA in maternal blood is currently offered through commercial laboratories and is also the subject of ongoing patent litigation. The recent Supreme Court decision in the Myriad case has already been invoked by a lower district court in NIPT litigation and resulted in invalidation of primary claims in a patent on currently marketed cffDNA-based testing for chromosomal aneuploidies. PMID:24989832

  3. Housing systems interacting with sex and genetic line affect broiler growth and carcass traits.

    PubMed

    Zhao, Xiaoling; Ren, Wenshi; Siegel, Paul B; Li, Juan; Yin, Huadong; Liu, Yiping; Wang, Yan; Zhang, Yao; Honaker, Christa F; Zhu, Qing

    2015-07-01

    Housing systems used in the production of poultry meat vary worldwide dependent on climate, land availability, and other resources essential for production. Reported here are comparisons between pen and cage rearing (the housing system, denoted HS: ), line crosses LC: ), two native Chinese lines (EM males were mated to Y1 and Y2 and their offspring denoted as EMY1 and EMY2), and sex in determining broiler traits. At hatch, 320 males and 320 females from each LC (giving a total of 1,280 chicks) were randomly assigned within each subgroup to 16 battery pens. There were 4 replicates for each combination of LC by sex. On d 28, half of the chicks were transferred to indoor floor pens, and the others were raised in single cages from d 29 to 91. Weekly body weights, livability, and feed conversion ratios ( FCR: ) were obtained to d 91, the age at which the broilers were slaughtered for carcass measurements. The caged males and females were heavier (P < 0.05) than their penned counterparts (2,292 vs 2,219 g). Except for females from line EMY1 (94.9%), the livability for each unit from 1 to 28 d, and 29 to 91 d was greater than 95%. Penned EMY2 broilers had the highest FCR (3.02), whereas penned EMY1 broilers had the lowest FCR (2.96) among the housing systems by LC combinations (P < 0.05). Caged chickens had thicker subcutaneous fat (7.24 mm), a higher percentages of abdominal fat (5.01%) and liver mass (3.13%) , but lower eviscerated carcass (60.63%) and breast muscle weights (pectoralis major and minor, 17.10%). Males were heavier and had higher percentages of leg muscle (boneless drum plus thigh, 24.22%) and heart muscle (1.08%) than the females (P < 0.05). However, the females had thicker subcutaneous fat (7.19 mm) and higher percentages of carcass weight (87.28%), breast muscle (18.11%), abdominal fat (6.54%), and liver mass (3.15%) than males. Penned females had the highest percentage of breast muscle (18.94%), and caged females had the highest percentage of liver mass (3.72%). Females of EMY1 had the highest percentage of breast muscle (18.40%). Generally, the housing system employed and the sex of the broilers greatly affect the carcass traits. PMID:26009754

  4. Common genetic variants of the ?2-adrenergic receptor affect its translational efficiency and are associated with human longevity.

    PubMed

    Zhao, Ling; Yang, Fan; Xu, Ke; Cao, Huiqing; Zheng, Gu-Yan; Zhang, Yan; Li, Jianxin; Cui, Hanbin; Chen, Xiaomin; Zhu, Zhiming; He, Hongbo; Mo, Xianming; Kennedy, Brian K; Suh, Yousin; Zeng, Yi; Tian, Xiao-Li

    2012-12-01

    ?-adrenoceptors are the common pharmacological targets for the treatment of cardiovascular diseases and asthma. Genetic modifications of ?-adrenergic system in engineered mice affect their lifespan. Here, we tested whether genes encoding for key components of the ?-adrenergic signaling pathway are associated with human longevity. We performed a 10-year follow-up study of the Chinese longitudinal healthy longevity survey. The Han Chinese population in this study consisted of 963 long-lived and 1028 geography-matched young individuals. Sixteen SNPs from ADRB1, ADRB2, ADCY5, ADCY6, and MAPK1 were selected and genotyped. Two SNPs, rs1042718 (C/A) and rs1042719 (G/C), of ADRB2 in linkage disequilibrium (D' = 1.0; r2 = 0.67) were found to be associated with enhanced longevity in men in two geographically isolated populations. Bonferroni-corrected P-values in a combined analysis were 0.00053-0.010. Men with haplotype A-C showed an increased probability to become centenarians (the frequency of A-C in long-lived and young individuals are 0.332 and 0.250, respectively, OR = 1.49, CI 95% = 1.17-1.88, P = 0.0007), in contrast to those with haplotype C-G (the frequency of C-G in long-lived and young individuals are 0.523 and 0.635, respectively, OR = 0.63, CI 95% = 0.51-0.78, P = 0.000018). The permuted P-values were 0.00005 and 0.0009, respectively. ADRB2 encodes the ?2-adrenergic receptor; the haplotype A-C markedly reduced its translational efficiency compared with C-G (P = 0.002) in transfected HEK293 cells. Thus, our data indicate that enhanced production of ?2-adrenergic receptors caused by genetic variants is inversely associated with human lifespan. PMID:23020224

  5. Genetic homogeneity of Pelizaeus-Merzbacher disease: Tight linkage to the proteolipoprotein locus in 16 affected families

    SciTech Connect

    Boespflug-Tanguy, O.; Mimault, C.; Cavagna, A.; Giraud, G.; Dastugue, B. [INSERM U.384, Clermont Ferrand (France); Melki, J.; Dinh, D.P.; Dautigny, A.

    1994-09-01

    Among the numerous leukodystrophies that have an early onset and no biochemical markers, Pelizaeus-Merzbacher disease (PMD) is one that can be identified using strict clinical criteria and demonstrating an abnormal formation of myelin that is restricted to the CNS in electrophysiological studies and brain magnetic resonance imaging (MRI). In PMD, 12 different base substitutions and one total deletion of the genomic region containing the PLP gene have been reported, but, despite extensive analysis, PLP exon mutations have been found in only 10%-25% of the families analyzed. To test the genetic homogeneity of this disease, the authors have carried out linkage analysis with polymorphic markers of the PLP genomic region in 16 families selected on strict diagnostic criteria of PMD. They observed a tight linkage of the PMD locus with markers of the PLP gene (cDNA PLP, exon IV polymorphism) and of the Xq22 region (DXS17, DXS94, and DXS287), whereas the markers located more proximally (DXYS1X and DXS3) or distally (DXS11) were not linked to the PMD locus. Multipoint analysis gave a maximal location score for the PMD locus (13.98) and the PLP gene (8.32) in the same interval between DXS94 and DXS287, suggesting that in all families PMD is linked to the PLP locus. Mutations of the extraexonic PLP gene sequences or of another unknown close gene could be involved in PMD. In an attempt to identify molecular defects of this genomic region that are responsible for PMD, these results meant that RFLP analysis could be used to improve genetic counseling for the numerous affected families in which a PLP exon mutation could not be demonstrated. 39 refs., 2 figs., 2 tabs.

  6. Selection Based on Indirect Genetic Effects for Growth, Environmental Enrichment and Coping Style Affect the Immune Status of Pigs

    PubMed Central

    Reimert, Inonge; Rodenburg, T. Bas; Ursinus, Winanda W.; Kemp, Bas; Bolhuis, J. Elizabeth

    2014-01-01

    Pigs living in intensive husbandry systems may experience both acute and chronic stress through standard management procedures and limitations in their physical and social environment, which may have implications for their immune status. Here, the effect of a new breeding method where pigs were selected on their heritable influence on their pen mates' growth, and environmental enrichment on the immune status of pigs was investigated. Hereto, 240 pigs with a relatively positive genetic effect on the growth of their pen mates (+SBV) and 240 pigs with a relatively negative genetic effect on the growth of their pen mates (?SBV) were housed in barren or straw-enriched pens from 4 to 23 weeks of age (n ?=? 80 pens in total). A blood sample was taken from the pigs before, three days after a 24 h regrouping test, and at week 22. In addition, effects of coping style, as assessed in a backtest, and gender were also investigated. Mainly, +SBV were found to have lower leukocyte, lymphocyte and haptoglobin concentrations than -SBV pigs. Enriched housed pigs had a lower neutrophil to lymphocyte (N:L) ratio and lower haptoglobin concentrations, but had higher antibody titers specific for Keyhole Limpet Hemocyanin (KLH) than barren housed pigs. No interactions were found between SBV class and housing. Furthermore, pigs with a proactive coping style had higher alternative complement activity and, in the enriched pens, higher antibody titers specific for KLH than pigs with a reactive coping style. Lastly, females tended to have lower leukocyte, but higher haptoglobin concentrations than castrated males. Overall, these results suggest that +SBV pigs and enriched housed pigs were less affected by stress than -SBV and barren housed pigs, respectively. Moreover, immune activation might be differently organized in individuals with different coping styles and to a lesser extent in individuals of opposite genders. PMID:25275507

  7. FLT1 Genetic Variation Predisposes to Neovascular AMD in Ethnically Diverse Populations and Alters Systemic FLT1 Expression

    PubMed Central

    Owen, Leah A.; Morrison, Margaux A.; Ahn, Jeeyun; Woo, Se Joon; Sato, Hajime; Robinson, Rosann; Morgan, Denise J.; Zacharaki, Fani; Simeonova, Marina; Uehara, Hironori; Chakravarthy, Usha; Hogg, Ruth E.; Ambati, Balamurali K.; Kotoula, Maria; Baehr, Wolfgang; Haider, Neena B.; Silvestri, Giuliana; Miller, Joan W.; Tsironi, Evangelia E.; Farrer, Lindsay A.; Kim, Ivana K.; Park, Kyu Hyung; DeAngelis, Margaret M.

    2014-01-01

    Purpose. Current understanding of the genetic risk factors for age-related macular degeneration (AMD) is not sufficiently predictive of the clinical course. The VEGF pathway is a key therapeutic target for treatment of neovascular AMD; however, risk attributable to genetic variation within pathway genes is unclear. We sought to identify single nucleotide polymorphisms (SNPs) associated with AMD within the VEGF pathway. Methods. Using a tagSNP, direct sequencing and meta-analysis approach within four ethnically diverse cohorts, we identified genetic risk present in FLT1, though not within other VEGF pathway genes KDR, VEGFA, or VASH1. We used ChIP and ELISA in functional analysis. Results. The FLT1 SNPs rs9943922, rs9508034, rs2281827, rs7324510, and rs9513115 were significantly associated with increased risk of neovascular AMD. Each association was more significant after meta-analysis than in any one of the four cohorts. All associations were novel, within noncoding regions of FLT1 that do not tag for coding variants in linkage disequilibrium. Analysis of soluble FLT1 demonstrated higher expression in unaffected individuals homozygous for the FLT1 risk alleles rs9943922 (P = 0.0086) and rs7324510 (P = 0.0057). In silico analysis suggests that these variants change predicted splice sites and RNA secondary structure, and have been identified in other neovascular pathologies. These data were supported further by murine chromatin immunoprecipitation demonstrating that FLT1 is a target of Nr2e3, a nuclear receptor gene implicated in regulating an AMD pathway. Conclusions. Although exact variant functions are not known, these data demonstrate relevancy across ethnically diverse genetic backgrounds within our study and, therefore, hold potential for global efficacy. PMID:24812550

  8. Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls

    Microsoft Academic Search

    H Ono; O Shirakawa; N Kitamura; T Hashimoto; N Nishiguchi; A Nishimura; H Nushida; Y Ueno; K Maeda

    2002-01-01

    Several lines of evidence suggest that a partly genetically controlled serotonergic dysfunction is involved in the biological pathogenesis of suicide. In this study, we measured tryptophan hydroxylase (TPH) immunoreactivity as a pre-synaptic marker, and serotonin receptor 2A (5HT2A receptor) density as a post-synaptic marker in the serotonergic system in 10 postmortem brains of suicide victims. We also examined whether TPH

  9. Germline Genetic Variants Disturbing the Let7\\/LIN28 Double-Negative Feedback Loop Alter Breast Cancer Susceptibility

    Microsoft Academic Search

    Ao-Xiang Chen; Ke-Da Yu; Lei Fan; Ji-Yu Li; Chen Yang; A-Ji Huang; Zhi-Ming Shao

    2011-01-01

    Previous studies have shown that let-7 can repress the post-transcriptional translation of LIN28, and LIN28 in turn could block the maturation of let-7, forming a double-negative feedback loop. In this study, we investigated the effect of germline genetic variants on regulation of the homeostasis of the let-7\\/LIN28 loop and breast cancer risk. We initially demonstrated that the T\\/C variants of

  10. Electric stimulation of the tuberomamillary nucleus affects epileptic activity and sleep-wake cycle in a genetic absence epilepsy model.

    PubMed

    Blik, Vitaliya

    2015-01-01

    Deep brain stimulation (DBS) is a promising approach for epilepsy treatment, but the optimal targets and parameters of stimulation are yet to be investigated. Tuberomamillary nucleus (TMN) is involved in EEG desynchronization-one of the proposed mechanisms for DBS action. We studied whether TMN stimulation could interfere with epileptic spike-wave discharges (SWDs) in WAG/Rij rats with inherited absence epilepsy and whether such stimulation would affect sleep-wake cycle. EEG and video registration were used to determine SWD occurrence and stages of sleep and wake during three-hours recording sessions. Stimulation (100Hz) was applied in two modes: closed-loop (with previously determined interruption threshold intensity) or open-loop mode (with 50% or 70% threshold intensity). Closed-loop stimulation successfully interrupted SWDs but elevated their number by 148 ± 54% compared to baseline. It was accompanied by increase in number of episodes but not total duration of both active and passive wakefulness. Open-loop stimulation with amplitude 50% threshold did not change measured parameters, though 70% threshold stimulation reduced SWDs number by 40 ± 9%, significantly raised the amount of active wakefulness and decreased the amount of both slow-wave and rapid eye movement sleep. These results suggest that the TMN is unfavorable as a target for DBS as its stimulation may cause alterations in sleep-wake cycle. A careful choosing of parameters and control of sleep-wake activity is necessary when applying DBS in epilepsy. PMID:25524851

  11. have been affected by their sparse population coverage. The median line of the Eurasian genetic landscape appears

    E-print Network

    Xu, Shuhua

    ­15, 2008, Philadelphia. Available at the following URL: http://www.ashg.org/2008meeting/abstracts/ fulltext Genetics I, No. 60]. Presented at the annual meeting of The American Society of Human Genetics, November 11

  12. Genetics

    NSDL National Science Digital Library

    Jennifer Doherty

    This activity helps students to understand basic principles of genetics, including relationships of genotype to phenotype, concepts of recessive and dominant alleles, and how understanding meiosis and fertilization provides the basis for understanding inheritance, as summarized in Punnett squares. The Student Handout includes an analysis of the inheritance of albinism that teaches all of these concepts, a Coin Toss Genetics activity that helps students understand the probabilistic nature of Punnett square predictions, and an analysis of the inheritance of sickle cell anemia that reinforces the basic concepts and introduces some of the complexities of genetics. The Genetics Supplement includes two additional activities, an analysis of student data on the sex makeup of sibships and pedigree analyses of recessive and dominant alleles with challenge questions that introduce the role of mutations and an evaluation of Punnett squares and pedigrees as models of inheritance.

  13. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis.

    PubMed

    Kaftanovskaya, Elena M; Lopez, Carolina; Ferguson, Lydia; Myhr, Courtney; Agoulnik, Alexander I

    2015-06-01

    It is commonly accepted that androgen-producing fetal Leydig cells (FLC) are substituted by adult Leydig cells (ALC) during perinatal testis development. The mechanisms influencing this process are unclear. We used mice with a retinoid acid receptor 2 promoter-Cre recombinase transgene (Rarb-cre) expressed in embryonic FLC precursors, but not in postnatal testis, and a dual fluorescent Cre recombinase reporter to label FLC and ALC in vivo. All FLC in newborn testis had the recombinant, whereas the majority of LC in adult testis had the nonrecombinant reporter. Primary LC cultures from adult testis had either recombinant (20%) or nonrecombinant (80%) cells, demonstrating that the FLC survive in adult testis and their ontogeny is distinct from ALC. Conditional inactivation of androgen receptor (AR) allele using the Rarb-cre transgene resulted in a 50% increase of AR-negative LC in adult testis. The mutant males became infertile with age, with all LC in older testis showing signs of incomplete differentiation, such as a large number of big lipid droplets, an increase of finger-like protrusions, and a misexpression of steroidogenic or FLC- and ALC-specific genes. We propose that the antiandrogenic exposure during early development may similarly result in an increase of FLC in adult testis, leading to abnormal LC differentiation.-Kaftanovskaya, E. M., Lopez, C., Ferguson, L., Myhr, C., Agoulnik, A. I. Genetic ablation of androgen receptor signaling in fetal Leydig cell lineage affects Leydig cell functions in adult testis. PMID:25713029

  14. Kiss of the Mutant Mouse: How Genetically Altered Mice Advanced Our Understanding of Kisspeptin's Role in Reproductive Physiology

    PubMed Central

    Elias, Carol F.

    2012-01-01

    The kisspeptin system has emerged as one of the most important circuits within the central network governing reproduction. Although kisspeptin physiology has been examined in many species, much of our understanding of this system has come from mice. Recently, the study of several innovative strains of genetically engineered mouse models has revealed intriguing and unexpected insights into the functions of kisspeptin signaling in the hypothalamus. Here, we review the advancements in our knowledge of the central kisspeptin system through the use of mutant mice. PMID:23011921

  15. Chemical diversity of polyene macrolides produced by Streptomyces noursei ATCC 11455 and recombinant strain ERD44 with genetically altered polyketide synthase NysC.

    PubMed

    Bruheim, Per; Borgos, Sven E F; Tsan, Pascale; Sletta, Håvard; Ellingsen, Trond E; Lancelin, Jean-Marc; Zotchev, Sergey B

    2004-11-01

    The gram-positive bacterium Streptomyces noursei ATCC 11455 produces a complex mixture of polyene macrolides generally termed nystatins. Although the structures for nystatins A(1) and A(3) have been reported, the identities of other components of the nystatin complex remain obscure. Analyses of the culture extract from the S. noursei wild type revealed the presence of several nystatin-related compounds for which chemical structures could be suggested on the basis of their molecular weights, their UV spectra, and knowledge of the nystatin biosynthetic pathway. Nuclear magnetic resonance (NMR) studies with one of these polyene macrolides identified it as a nystatin analogue containing a mycarose moiety at C-35. A similar investigation was performed with the culture extract of the ERD44 mutant, which has a genetically altered polyketide synthase (PKS) NysC and which was previously shown to produce a heptaene nystatin analogue. The latter compound, tentatively named S44HP, and its derivative, which contains two deoxysugar moieties, were purified; and their structures were confirmed by NMR analysis. Nystatin analogues with an expanded macrolactone ring were also observed in the extract of the ERD44 mutant, suggesting that the altered PKS can "stutter" during the polyketide chain assembly. These data provide new insights into the biosynthesis of polyene macrolide antibiotics and the functionalities of PKSs and post-PKS modification enzymes. PMID:15504830

  16. Alterations in Oral [1-14C] 18:1n-9 Distribution in Lean Wild-Type and Genetically Obese (ob/ob) Mice

    PubMed Central

    Wang, Xinxia; Feng, Jie; Yu, Caihua; Shen, Qingwu W.; Wang, Yizhen

    2015-01-01

    Obesity may result from altered fatty acid (FA) disposal. Altered FA distribution in obese individuals is poorly understood. Lean wild-type C57BL/6J and obese C57BL/6Job/ob mice received an oral dose of [1-14C]18:1n-9 (oleic acid), and the radioactivity in tissues was evaluated at various time points. The 14C concentration decreased rapidly in gastrointestinal tract but gradually increased and peaked at 96 h in adipose tissue, muscle and skin in lean mice. The 14C concentration was constant in adipose tissue and muscle of obese mice from 4h to 168h. 14C-label content in adipose tissue was significantly affected by genotype, whereas muscle 14C-label content was affected by genotype, time and the interaction between genotype and time. There was higher total 14C retention (47.7%) in obese mice than in lean mice (9.0%) at 168 h (P<0.05). The 14C concentrations in the soleus and gastrocnemius muscle were higher in obese mice than in lean mice (P<0.05). Perirenal adipose tissue contained the highest 14C content in lean mice, whereas subcutaneous adipose tissue (SAT) had the highest 14C content and accounted for the largest proportion of total radioactivity among fat depots in obese mice. More lipid radioactivity was recovered as TAG in SAT from obese mice than from lean mice (P<0.05). Gene expression suggested acyl CoA binding protein and fatty acid binding protein are important for FA distribution in adipose tissue and muscle. The FA distribution in major tissues was altered in ob/ob mice, perhaps contributing to obesity. Understanding the disparity in FA disposal between lean and obese mice may reveal novel targets for the treatment and prevention of obesity. PMID:25826747

  17. Genetic and Environmental Influences on Adult Mental Health: Evidence for Gene-Environment Interplay as a Function of Maternal and Paternal Discipline and Affection.

    PubMed

    South, Susan C; Jarnecke, Amber M

    2015-07-01

    Researchers have long theorized that genetic influence on mental health may differ as a function of environmental risk factors. One likely moderator of genetic and environmental influences on psychopathological symptoms is parenting behavior, as phenotypic research shows that negative aspects of parent-child relationships are associated with greater likelihood of mental illness in adulthood. The current study examined whether levels of reported parental discipline and affection experienced in childhood act as a trigger, or buffer, for adult mental health problems. Results from a nationwide twin sample suggest level of father's discipline and affection, as reported by now-adult twins, moderated genetic and environmental influences on internalizing symptoms in adulthood, such that heritability was greatest at the highest levels of discipline and affection. Father's affection also moderated the etiological influences on alcohol use problems, with greater heritability at the lowest levels of affection. No moderating effect was found for mothers. Findings suggest relationships with fathers in childhood can have long-lasting effects on the etiological influences on adult mental health outcomes. PMID:25842345

  18. Reactive biomolecular divergence in genetically altered yeast cells and isolated mitochondria as measured by biocavity laser spectroscopy : a rapid diagnostic method for studying cellular responses to stress and disease.

    SciTech Connect

    Yaffe, Michael P. (University of California, San Diego, CA); Gourley, Paul Lee; Copeland, Robert Guild; McDonald, Anthony Eugene; Hendricks, Judy K.; Naviaux, Robert K. (Univesity of California, San Diego, CA)

    2006-12-01

    We report an analysis of four strains of baker's yeast (Saccharomyces cerevisiae) using biocavity laser spectroscopy. The four strains are grouped in two pairs (wild type and altered), in which one strain differs genetically at a single locus, affecting mitochondrial function. In one pair, the wild-type rho+ and a rho0 strain differ by complete removal of mitochondrial DNA (mtDNA). In the second pair, the wild-type rho+ and a rho- strain differ by knock-out of the nuclear gene encoding Cox4, an essential subunit of cytochrome c oxidase. The biocavity laser is used to measure the biophysical optic parameter Deltalambda, a laser wavelength shift relating to the optical density of cell or mitochondria that uniquely reflects its size and biomolecular composition. As such, Deltalambda is a powerful parameter that rapidly interrogates the biomolecular state of single cells and mitochondria. Wild-type cells and mitochondria produce Gaussian-like distributions with a single peak. In contrast, mutant cells and mitochondria produce leptokurtotic distributions that are asymmetric and highly skewed to the right. These distribution changes could be self-consistently modeled with a single, log-normal distribution undergoing a thousand-fold increase in variance of biomolecular composition. These features reflect a new state of stressed or diseased cells that we call a reactive biomolecular divergence (RBD) that reflects the vital interdependence of mitochondria and the nucleus.

  19. Genetically altered AMPA-type glutamate receptor kinetics in interneurons disrupt long-range synchrony of gamma oscillation.

    PubMed

    Fuchs, E C; Doheny, H; Faulkner, H; Caputi, A; Traub, R D; Bibbig, A; Kopell, N; Whittington, M A; Monyer, H

    2001-03-13

    Gamma oscillations synchronized between distant neuronal populations may be critical for binding together brain regions devoted to common processing tasks. Network modeling predicts that such synchrony depends in part on the fast time course of excitatory postsynaptic potentials (EPSPs) in interneurons, and that even moderate slowing of this time course will disrupt synchrony. We generated mice with slowed interneuron EPSPs by gene targeting, in which the gene encoding the 67-kDa form of glutamic acid decarboxylase (GAD67) was altered to drive expression of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subunit GluR-B. GluR-B is a determinant of the relatively slow EPSPs in excitatory neurons and is normally expressed at low levels in gamma-aminobutyric acid (GABA)ergic interneurons, but at high levels in the GAD-GluR-B mice. In both wild-type and GAD-GluR-B mice, tetanic stimuli evoked gamma oscillations that were indistinguishable in local field potential recordings. Remarkably, however, oscillation synchrony between spatially separated sites was severely disrupted in the mutant, in association with changes in interneuron firing patterns. The congruence between mouse and model suggests that the rapid time course of AMPA receptor-mediated EPSPs in interneurons might serve to allow gamma oscillations to synchronize over distance. PMID:11248119

  20. Genetic inhibition of hepatic acetyl-CoA carboxylase activity increases liver fat and alters global protein acetylationa

    PubMed Central

    Chow, Jenny D.Y.; Lawrence, Robert T.; Healy, Marin E.; Dominy, John E.; Liao, Jason A.; Breen, David S.; Byrne, Frances L.; Kenwood, Brandon M.; Lackner, Carolin; Okutsu, Saeko; Mas, Valeria R.; Caldwell, Stephen H.; Tomsig, Jose L.; Cooney, Gregory J.; Puigserver, Pere B.; Turner, Nigel; James, David E.; Villén, Judit; Hoehn, Kyle L.

    2014-01-01

    Lipid deposition in the liver is associated with metabolic disorders including fatty liver disease, type II diabetes, and hepatocellular cancer. The enzymes acetyl-CoA carboxylase 1 (ACC1) and ACC2 are powerful regulators of hepatic fat storage; therefore, their inhibition is expected to prevent the development of fatty liver. In this study we generated liver-specific ACC1 and ACC2 double knockout (LDKO) mice to determine how the loss of ACC activity affects liver fat metabolism and whole-body physiology. Characterization of LDKO mice revealed unexpected phenotypes of increased hepatic triglyceride and decreased fat oxidation. We also observed that chronic ACC inhibition led to hyper-acetylation of proteins in the extra-mitochondrial space. In sum, these data reveal the existence of a compensatory pathway that protects hepatic fat stores when ACC enzymes are inhibited. Furthermore, we identified an important role for ACC enzymes in the regulation of protein acetylation in the extra-mitochondrial space. PMID:24944901

  1. In vivo detection of exercised-induced ultrastructural changes in genetically-altered murine skeletal muscle using polarization-sensitive optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Boppart, Stephen

    2006-02-01

    Skeletal muscle fibers are a known source of form birefringence in biological tissue. The birefringence present in skeletal muscle is associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Certain structural proteins that prevent damage and maintain the structural and functional health of the muscle fiber preserve the organization of the Abands in skeletal muscle. Therefore, the level of birefringence detected can estimate the health of the muscle as well as the damage incurred during exercise. Murine skeletal muscle from both genetically-altered (mdx) and normal (wild-type) specimens were imaged in vivo with a fiber-based PSOCT imaging system to quantitatively determine the level of birefringence present in the tissue before and after exercise. The mdx muscle lacks dystrophin, a structural protein that is mutated in Duchenne muscular dystrophy in humans. Muscle from these mdx mice exhibited a marked decrease in birefringence after exercise, whereas the wild-type muscle was highly birefringent before and after exercise. The quantitative results from this tissue optics study suggest for the first time that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.

  2. Genetics

    NSDL National Science Digital Library

    The Tech Museum of Innovation

    2004-01-01

    This online tutorial from the TheTech Museum of Innovation focuses on genetics. The interactive topics will initially introduce the user to the DNA, chromosomes, and the make up of human genes. Further topics will examine forensic science, the history of forensics, fingerprinting, and cloning background research and community response to cloning. Finally, the resource provides connections to gallery exhibits, science labs, and a design challenge that engages the learner to write a persuasive letter to a group or organization responsible for cloning or DNA decision making. Copyright 2005 International Technology Education Association

  3. Ribosome-deficient plastids affect transcription of light-induced nuclear genes: genetic evidence for a plastid-derived signal

    Microsoft Academic Search

    Wolfgang R. Hess; Antje Müller; F. Nagy; T. BiJrner

    1994-01-01

    Transcription of ten nuclear genes was analysed in the albostrians mutant of barley (Hordeum vulgare L.). The lack of plastid ribosomes in white seedlings of this mutant results in a complex alteration of nuclear gene expression at the transcriptional level. We found a strong reduction in the accumulation of mRNAs transcribed from nuclear genes encoding chloroplast enzymes involved in the

  4. Transgenic tobacco plants expressing the maize Cat2 gene have altered catalase levels that affect plant-pathogen interactions and resistance to oxidative stress

    Microsoft Academic Search

    A. N. Polidoros; P. V. Mylona; J. G. Scandalios

    2001-01-01

    Transgenic tobacco genotypes expressing the maize Cat2 gene were developed with altered catalase (CAT) levels that resulted in a moderate increase of CAT activity in two transgenic lines. Bacterial infection, with a pathogen that does not share homology with the transgene, caused local and systemic down-regulation of the steady state mRNA levels of the 35S-driven transgene in a manner resembling

  5. Persistence of chromosomal alterations affecting the 1cen-q12 region in a human lymphoblastoid cell line exposed to diepoxybutane and mitomycin C

    Microsoft Academic Search

    M. N. Murg; M. Schuler; D. A. Eastmond

    1999-01-01

    Multicolor fluorescence in situ hybridization (FISH) with tandem-labeling probes for the 1cen-q12 region is a potential biomarker for the detection of structural chromosomal aberrations (CAs) in human cells. To determine the suitability of this technique for biomonitoring humans exposed to 1,3-butadiene (BD) and to characterize the alterations induced as well as their stability over time, the human lymphoblastoid cell line

  6. Grass-herbivore interactions altered by strains of a native endophyte

    Microsoft Academic Search

    Tammy Tintjer; Jennifer A. Rudgers

    2006-01-01

    Summary • Many plants support symbiotic microbes, such as endophytic fungi, that can alter interactions with herbivores. Most endophyte research has focused on agronomi- cally important species, with less known about the ecological roles of native endo- phytes in native plants. In particular, whether genetic variation among endophyte symbionts affects herbivores of plant hosts remains unresolved for most native endophytes.

  7. Altered genotypic and phenotypic frequencies of aphid populations under enriched CO2 and O3 atmospheres

    Microsoft Academic Search

    B. M ONDOR; M ICHELLE; N. T REMBLA; RICHARD L. L INDROTH

    2005-01-01

    Environmental change is anticipated to negatively affect both plant and animal popula- tions. As abiotic factors rapidly change habitat suitability, projections range from altered genetic diversity to wide-spread species loss. Here, we assess the degree to which changes in atmospheric composition associated with environmental change will influ- ence not only the abundance, but also the genotypic\\/phenotypic diversity, of herbivore populations.

  8. The Ketogenic Diet Alters the Hypoxic Response and Affects Expression of Proteins Associated with Angiogenesis, Invasive Potential and Vascular Permeability in a Mouse Glioma Model

    PubMed Central

    Woolf, Eric C.; Curley, Kara L.; Liu, Qingwei; Turner, Gregory H.; Charlton, Julie A.; Preul, Mark C.; Scheck, Adrienne C.

    2015-01-01

    Background The successful treatment of malignant gliomas remains a challenge despite the current standard of care, which consists of surgery, radiation and temozolomide. Advances in the survival of brain cancer patients require the design of new therapeutic approaches that take advantage of common phenotypes such as the altered metabolism found in cancer cells. It has therefore been postulated that the high-fat, low-carbohydrate, adequate protein ketogenic diet (KD) may be useful in the treatment of brain tumors. We have demonstrated that the KD enhances survival and potentiates standard therapy in a mouse model of malignant glioma, yet the mechanisms are not fully understood. Methods To explore the effects of the KD on various aspects of tumor growth and progression, we used the immunocompetent, syngeneic GL261-Luc2 mouse model of malignant glioma. Results Tumors from animals maintained on KD showed reduced expression of the hypoxia marker carbonic anhydrase 9, hypoxia inducible factor 1-alpha, and decreased activation of nuclear factor kappa B. Additionally, tumors from animals maintained on KD had reduced tumor microvasculature and decreased expression of vascular endothelial growth factor receptor 2, matrix metalloproteinase-2 and vimentin. Peritumoral edema was significantly reduced in animals fed the KD and protein analyses showed altered expression of zona occludens-1 and aquaporin-4. Conclusions The KD directly or indirectly alters the expression of several proteins involved in malignant progression and may be a useful tool for the treatment of gliomas. PMID:26083629

  9. Genetic variations in the SPP1 promoter affect gene expression and the level of osteopontin secretion into bovine milk.

    PubMed

    Dudemaine, P L; Thibault, C; Alain, K; Bissonnette, N

    2014-10-01

    Osteopontin (OPN) is now recognized as an important cytokine and extracellular integrin-binding protein at the crossroads of inflammation and homeostasis. In a previous study, we found that OPN gene (SPP1) polymorphisms are associated with milk performance traits and somatic cell score (SCS), a parameter used to estimate the genetic value of udder health in dairy cattle. In this study, we assessed whether the genetic variations had an impact on SPP1 promoter activity, immune response and the level of OPN secreted into milk. The influence of DNA polymorphisms on the promoter activity of SPP1 was confirmed in vitro. To measure the impact of the genetic variations on OPN secretion into milk, we measured OPN levels in both plasma and milk throughout lactation. Cows were grouped by the OPN haplotypes associated with a high (H2 × H3) or low (H1 × H4) SCS. For both H2 × H3 and H1 × H4, the OPN level in plasma remained low throughout lactation, although the concentration in the milk of H1 × H4 cows increased more in late lactation. Moreover, the macrophages of H1 × H4 cows expressed a lower SPP1 and proinflammatory IL6 in response to infection. Regarding the immune cell response, cows with the genetic potential to secrete higher OPN levels during late lactation had macrophages expressing fewer proinflammatory cytokines, a situation that might explain the genetic association with low somatic cells. Although OPN's favorable roles during late lactation remain to be elucidated, the tissue remodeling properties associated with OPN may be beneficial for reducing the incidence of infection during the transition period in lactating cows. PMID:24961487

  10. Alteration of the Alkaloid Profile in Genetically Modified Tobacco Reveals a Role of Methylenetetrahydrofolate Reductase in Nicotine N-Demethylation1[C][W][OA

    PubMed Central

    Hung, Chiu-Yueh; Fan, Longjiang; Kittur, Farooqahmed S.; Sun, Kehan; Qiu, Jie; Tang, She; Holliday, Bronwyn M.; Xiao, Bingguang; Burkey, Kent O.; Bush, Lowell P.; Conkling, Mark A.; Roje, Sanja; Xie, Jiahua

    2013-01-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme of the tetrahydrofolate (THF)-mediated one-carbon (C1) metabolic network. This enzyme catalyzes the reduction of 5,10-methylene-THF to 5-methyl-THF. The latter donates its methyl group to homocysteine, forming methionine, which is then used for the synthesis of S-adenosyl-methionine, a universal methyl donor for numerous methylation reactions, to produce primary and secondary metabolites. Here, we demonstrate that manipulating tobacco (Nicotiana tabacum) MTHFR gene (NtMTHFR1) expression dramatically alters the alkaloid profile in transgenic tobacco plants by negatively regulating the expression of a secondary metabolic pathway nicotine N-demethylase gene, CYP82E4. Quantitative real-time polymerase chain reaction and alkaloid analyses revealed that reducing NtMTHFR expression by RNA interference dramatically induced CYP82E4 expression, resulting in higher nicotine-to-nornicotine conversion rates. Conversely, overexpressing NtMTHFR1 suppressed CYP82E4 expression, leading to lower nicotine-to-nornicotine conversion rates. However, the reduced expression of NtMTHFR did not affect the methionine and S-adenosyl-methionine levels in the knockdown lines. Our finding reveals a new regulatory role of NtMTHFR1 in nicotine N-demethylation and suggests that the negative regulation of CYP82E4 expression may serve to recruit methyl groups from nicotine into the C1 pool under C1-deficient conditions. PMID:23221678

  11. Mutations that alter a repeated ACCA element located at the 5? end of the Potato virus X genome affect RNA accumulation

    Microsoft Academic Search

    Mi-Ri Park; Sun-Jung Kwon; Hong-Soo Choi; Cynthia L. Hemenway; Kook-Hyung Kim

    2008-01-01

    The repeated ACCA or AC-rich sequence and structural (SL1) elements in the 5? non-translated region (NTR) of the Potato virus X (PVX) RNA play vital roles in the PVX life cycle by controlling translation, RNA replication, movement, and assembly. It has already been shown that the repeated ACCA or AC-rich sequence affect both gRNA and sgRNA accumulation, while not affecting

  12. The Genetic and Epigenetic Contributions of Sperm to Early Embryogenesis

    Microsoft Academic Search

    Denny Sakkas; Maria Lalioti; Hasan M. El-Fakahany; Emre Seli

    \\u000a During fertilization, the sperm delivers a haploid set of chromosomes to the zygote. Genetic alterations, such as numerical\\u000a or structural chromosome defects, can affect the ability of the embryo to undergo normal development. Similarly, epigenetic\\u000a defects, such as abnormal methylation of gene promoters, may affect gene expression during embryogenesis and affect the viability\\u000a or health of the developing embryo. This

  13. Multiple genetic alterations in primary cutaneous large B-cell lymphoma, leg type support a common lymphomagenesis with activated B-cell-like diffuse large B-cell lymphoma.

    PubMed

    Pham-Ledard, Anne; Prochazkova-Carlotti, Martina; Andrique, Laetitia; Cappellen, David; Vergier, Béatrice; Martinez, Fabian; Grange, Florent; Petrella, Tony; Beylot-Barry, Marie; Merlio, Jean-Philippe

    2014-03-01

    Primary cutaneous large B-cell lymphoma, leg type has been individualized from nodal diffuse large B-cell lymphoma. The objective of this study was to screen primary cutaneous large B-cell lymphoma, leg type for genetic alterations recently described in nodal diffuse large B-cell lymphoma. Skin biopsies from 23 patients were analyzed for IRF4, BCL2, BCL6, and MYC expression. FISH testing was performed for BCL2, BCL6, MYC with separation probes and for CDKN2A and PRDM1/BLIMP1 deletion. Multiple sequential FISH analyses with up to six probes were performed to define samples with multiple cytogenetic alterations. MYD88 mutations were studied by Sanger sequencing. All cases but one displayed at least one genetic alteration (96%). Nine patients exhibited a single genetic mutation and 12 combined several alterations (52%). We observed a split for BCL2, BCL6, or MYC in 1/23, 6/23, and 3/23 of cases, respectively. No double-hit lymphoma was observed. CDKN2A deletion was detected by FISH in only 5/23 cases. BLIMP1 and/or 6q deletion was observed at a higher rate in 10/20 of cases. No correlation between rearrangement and immunohistochemical expression was found for BCL2 or MYC. FISH tracking of sequential hybridizations showed that several alterations were carried by the same nuclei. The p.L265P MYD88 mutation was found in 11/18 (61%) of cases. Contrary to most cutaneous lymphomas that rarely harbor primary genetic alteration of their nodal histological equivalent, primary cutaneous large B-cell lymphoma, leg type seems to be a 'cutaneous counterpart' of activated B-cell-like diffuse large B-cell lymphoma with a similar cytogenetic profile and a high rate of MYD88 oncogenic L265P mutation. This also suggests a common lymphomagenesis with NF-?B activation, strong IRF4 expression and terminal B-cell differentiation blockage. Our data support the use of therapies targeting NF-?B, as most patients displayed disease progression and resistance to conventional therapies. PMID:24030746

  14. The integration of mutant loci affecting maize endosperm development in a dense genetic map using an AFLP-based procedure

    Microsoft Academic Search

    Luca Pasini; Maria Rosaria Stile; Enrico Puja; Rita Valsecchi; Priscilla Francia; Giorgia Carletti; Francesco Salamini; Adriano Marocco

    2008-01-01

    In this paper, 10 mutations conditioning the appearance of defective, miniature or collapsed endosperm, but with normal sporophyte\\u000a development, were considered. Homozygous mutant kernels have reduced grain weight, kernel size, density and, in some of these,\\u000a higher than normal seed protein content. The mutant loci were integrated into a high-resolution genetic map in order to associate\\u000a them to specific genes.

  15. Impact of a Genetic Diagnosis of a Mitochondrial Disorder 5–17 Years After the Death of an Affected Child

    Microsoft Academic Search

    A. C. Sexton; M. Sahhar; D. R. Thorburn; S. A. Metcalfe

    2008-01-01

    This study used in-depth interviews to explore the experiences of parents who were re-contacted with new genetic results many\\u000a years after the death of a child with a mitochondrial disorder. At the time of their child’s illness, parents had consented\\u000a to a tissue sample being taken to help with diagnosis of a suspected mitochondrial disorder, and subsequently further DNA\\u000a testing

  16. Genetics, lighting environment, and heritable responses to lighting environment affect male color morph expression in bluefin killifish, Lucania goodei.

    PubMed

    Fuller, Rebecca C; Travis, Joseph

    2004-05-01

    Determining the degree to which variation in traits is controlled by genetics and/or environment is fundamental to understanding adaptation. In this study, we examine the genetic and environmental influences on color pattern expression in male bluefin killifish, Lucania goodei. This is a compelling system because both male color patterns and vision physiology are correlated with basic properties of the environment. Across populations, males with blue anal fins are more abundant in waters with low transmission of UV and blue wavelengths. Here, we present results from two paternal half-sib breeding experiments (one in the laboratory, one in the greenhouse) in which offspring were raised under light treatments that mimicked natural variation in the spectral composition of light. In both experiments, we found that red-versus-yellow expression is controlled by an autosomal locus of large effect where yellow (Y) is dominant over red (y). There was little blue expression in the laboratory. In the greenhouse, we found higher expression of blue anal fin morphs when males were raised in tea-stained water (low transmission UV/blue) than when raised in clear water (high transmission UV/blue). We also found genetic effects of sires and an interaction between sire and lighting environment (i.e. heritable plasticity). These results show that a relatively simple, environmentally dependent, epistatic interaction can produce a large amount of variation in male color patterns that presumably function in sexual selection. PMID:15212389

  17. Lack of evidence for increased genetic loading for autism among families of affected females: a replication from family history data in two large samples.

    PubMed

    Goin-Kochel, Robin P; Abbacchi, Anna; Constantino, John N

    2007-05-01

    Both the broad and narrow phenotypes of autism have been consistently observed in family members of affected individuals. Additionally, autism spectrum disorders (ASDs) present four times more often in males than in females, for reasons that are currently unknown. In this study, we examined whether there were differences in familial loading of ASD among families of male versus female probands. Analyses were conducted with existing data from two distinct samples. The first sample contained 417 individuals with autism and Asperger's disorder and included information on the ASD diagnoses of their first- and second-degree relatives. The second sample consisted of 405 sibships participating in the Autism Genetic Resource Exchange, of which one or more siblings had an ASD diagnosis. Results from both samples did not suggest significant differences in the prevalence of ASD among relatives of affected males versus females. PMID:17478580

  18. Transmissible Gastroenteritis Virus (TGEV) Infection Alters the Expression of Cellular MicroRNA Species That Affect Transcription of TGEV Gene 7

    PubMed Central

    Song, Xiangjun; Zhao, Xiaomin; Huang, Yong; Xiang, Hailing; Zhang, Wenlong; Tong, Dewen

    2015-01-01

    Transmissible gastroenteritis virus (TGEV) is a member of Coronaviridae family. TGEV infection has emerged as a major cause of severe gastroenteritis and leads to alterations of many cellular processes. Meanwhile, the pathogenic mechanism of TGEV is still unclear. microRNAs (miRNAs) are a novel class of small non-coding RNAs which are involved in the regulation of numerous biological processes such as viral infection and cell apoptosis. Accumulating data show that miRNAs are involved in the process of coronavirus infection such as replication of severe acute respiratory syndrome coronavirus (SARS-CoV). However, the link between miRNAs and TGEV infection is unknown. In this study, we performed microRNA microarray assay and predicted targets of altered miRNAs. The results showed TGEV infection caused the change of miRNAs profile. Then we selected miR-4331 for further analysis and subsequently identified cell division cycle-associated protein 7 (CDCA7) as the target of miR-4331. Moreover, miR-4331 showed the ability to inhibit transcription of TGEV gene 7 (a non-structure gene) via directly targeting CDCA7. In conclusion, differentially expressed miR-4331 that is caused by TGEV infection can suppress transcription of TGEV gene 7 via targeting cellular CDCA7. Our key finding is that TGEV selectively manipulates the expression of some cellular miRNAs to regulate its subgenomic transcription.

  19. Conformational altered p53 affects neuronal function: relevance for the response to toxic insult and growth-associated protein 43 expression

    PubMed Central

    Buizza, L; Prandelli, C; Bonini, S A; Delbarba, A; Cenini, G; Lanni, C; Buoso, E; Racchi, M; Govoni, S; Memo, M; Uberti, D

    2013-01-01

    The role of p53 in neurodegenerative diseases is essentially associated with neuronal death. Recently an alternative point of view is emerging, as altered p53 conformation and impaired protein function have been found in fibroblasts and blood cells derived from Alzheimer's disease patients. Here, using stable transfected SH-SY5Y cells overexpressing APP751wt (SY5Y-APP) we demonstrated that the expression of an unfolded p53 conformation compromised neuronal functionality. In particular, these cells showed (i) augmented expression of amyloid precursor protein (APP) and its metabolites, including the C-terminal fragments C99 and C83 and ?-amyloid peptide (ii) high levels of oxidative markers, such as 4-hydroxy-2-nonenal Michael-adducts and 3-nitro-tyrosine and (iii) altered p53 conformation, mainly due to nitration of its tyrosine residues. The consequences of high-unfolded p53 expression resulted in loss of p53 pro-apoptotic activity, and reduction of growth-associated protein 43 (GAP-43) mRNA and protein levels. The role of unfolded p53 in cell death resistance and lack of GAP-43 transcription was demonstrated by ZnCl2 treatment. Zinc supplementation reverted p53 wild-type tertiary structure, increased cells sensitivity to acute cytotoxic injury and GAP-43 levels in SY5Y-APP clone. PMID:23392172

  20. Genetic Studies of Unusual Loci That Affect Body Shape of the Nematode CAENORHABDITIS ELEGANS and May Code for Cuticle Structural Proteins

    PubMed Central

    Kusch, Meredith; Edgar, R. S.

    1986-01-01

    In Caenorhabditis elegans, four loci (sqt-1, sqt-2, sqt-3 and rol-8) in which mutations affect body shape and cuticle morphology have unusual genetic properties. (1) Mutant alleles of sqt-1 can interact to produce animals with a variety of mutant phenotypes: left roller, right roller, dumpy and long. At least three mutant phenotypes are specified by mutations in the sqt-3 locus. (2) Most alleles at these loci are either dominant or cryptic dominant (i.e., are dominant only in certain genetic backgrounds). (3) Most alleles of these loci exhibit codominance. (4) Two putative null alleles of the sqt-1 locus produce a wild-type phenotype. (5) Many alleles of these genes demonstrate unusual intergenic interactions that are not the result of simple epistasis: animals doubly heterozygous for mutations at two loci often display unexpected and unpredictable phenotypes. We suggest that these genetic properties might be expected of genes, such as the collagen genes, the products of which interact to form the animal's cuticle, and which are member genes of a gene family. PMID:3732788

  1. Proportion of circulating chicken heterophils and CXCLi2 expression in response to Salmonella enteritidis are affected by genetic line and immune modulating diet.

    PubMed

    Redmond, Sarah B; Chuammitri, Phongsakorn; Andreasen, Claire B; Pali?, Dušan; Lamont, Susan J

    2011-04-15

    Genetic line and diet affect chicken heterophil activity and gene expression, and the combination of these factors can enhance disease resistance. This study evaluated the effects of immune modulating diets on heterophil/lymphocyte (H/L) ratio and heterophil chemokine expression in distinct genetic lines. Fayoumi and Leghorn chickens were fed a basal diet or immune modulating diets enhanced with ?-glucans, ascorbic acid, or corticosterone. H/L ratios and heterophil gene expression in response to in vitro stimulation with Salmonella enteritidis (SE) were evaluated on days 1, 3, 7, and 21 of diet treatment. The stress-mimicking corticosterone diet influenced H/L ratio in the Leghorn line, but not the Fayoumi line, suggesting resistance to stress-induced immunosuppression in the Fayoumi line. Leghorn line H/L ratios were increased on days 1 and 3 of corticosterone diet treatment, but not days 7 or 21. Expression of CXCLi2 by SE stimulated heterophils was higher in the Leghorn line, suggesting that Leghorns rely more heavily on inflammatory response than do Fayoumis. Corticosterone diet was associated with reduced CXCLi2 expression in heterophils from both lines. Dietary ?-glucan or ascorbic acid did not affect H/L ratio or CXCLi2 expression, suggesting that benefits of these immunomodulators may not be evident in healthy birds. PMID:21295352

  2. Genetic polymorphism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase. Studies with human autoantibodies suggest a functionally altered cytochrome P-450 isozyme as cause of the genetic deficiency

    SciTech Connect

    Meier, U.T.; Meyer, U.A.

    1987-12-15

    The metabolism of the anticonvulsant mephenytoin is subject to a genetic polymorphism. In 2-5% of Caucasians and 18-23% of Japanese subjects a specific cytochrome P-450 isozyme, P-450 meph, is functionally deficient or missing. The authors have accumulated evidence that autoimmune antibodies observed in sera of patients with tienilic acid induced hepatitis (anti-liver kidney microsome 2 or anti-LKM2 antibodies) specifically recognize the cytochrome P-450 involved in the mephrenytoin hydroxylation polymorphism. This is demonstrated by immunoinhibition and immunoprecipitation of microsomal (S)-mephenytoin 4-hydroxylation activity and by the recognition by anti-LKM2 antibodies of a single (/sup 125/I)-protein band on immunoblots of human liver microsomes after sodium dodecyl sulfate-polyacrylamide gel electrophoresis or isoelectric focusing. The cytochrome P-450 recognized by anti-LKM2 antibodies was immunopurified from microsomes derived from livers of extensive (EM) or poor metabolizers (PM) of (S)-mephenytoin. Comparison of the EM-type cytochrome P-450 to that isolated from PM livers revealed no difference in regard to immuno-cross-reactivity, molecular weight, isoelectric point, relative content in microsomes, two-dimensional tryptic peptide maps, one-dimensional peptide maps with three proteases, amino acid composition, and amino-terminal protein sequence. Finally, the same protein was precipitated from microsomes prepared from the liver biopsy of a subject phenotyped in vivo as a poor metabolizer of mephenytoin. These data strongly suggest that the mephenytoin hydroxylation deficiency is caused by a minor structural change leading to a functionally altered cytochrome P-450 isozyme.

  3. Molecular genetics of growth and development in Populus (Salicaceae). V. Mapping quantitative trait loci affecting leaf variation

    SciTech Connect

    Wu, R.; Bradshaw, H.D. Jr.; Stettler, R.F. [Univ. of Washington, Seattle, WA (United States)

    1997-02-01

    The genetic variation of leaf morphology and development was studied in the 2-yr-old replicated plantation of an interspecific hybrid pedigree of Populus trichocarpa T. & G. and P. deltoides Marsh. via both molecular and quantitative genetic methods. Leaf traits chosen showed pronounced differences between the original parents, including leaf size, shape, orientation, color, structure, petiole size, and petiole cross section. In the F{sub 2} generation, leaf traits were all significantly different among genotypes, but with significant effects due to genotype X crown-position interaction. Variation in leaf pigmentation, petiole length, and petiole length proportion appeared to be under the control of few quantitative trait loci (QTLs). More QTLs were associated with single leaf area, leaf shape, lamina angle, abaxial color, and petiole flatness, and in these traits the number of QTLs varied among crown positions. In general the estimates of QTL numbers from Wright`s biometric method were close to those derived from molecular markers. For those traits with few underlying QTLs, a single marker interval could explain from 30-60% of the observed phenotypic variance. For multigenic traits, certain markers contributed more substantially to the observed variation than others. Genetic cluster analysis showed developmentally related traits to be more strongly associated with each other than with unrelated traits. This finding was also supported by the QTL mapping. For example, the same chromosomal segment of linkage group L seemed to account for 20% of the phenotypic variation of all dimension-related traits, leaf size, petiole length, and midrib angle. In both traits, the P. deltoides alleles had positive effects and were dominant to the P. trichocarpa alleles. Similar relationships were also found for lamina angle, abaxial greenness, and petiole flatness. 72 refs., 3 figs., 2 tabs.

  4. Surgical decision-making affected by clinical and genetic screening of a novel kindred with von Hippel-Lindau disease and pancreatic islet cell tumors.

    PubMed Central

    Curley, S A; Lott, S T; Luca, J W; Frazier, M L; Killary, A M

    1998-01-01

    OBJECTIVE: We report a unique, previously undescribed multigeneration kindred with von Hippel-Lindau (VHL) disease in whom clinical or genetic screening led to the detection of surgically resectable neoplastic disease in several family members. SUMMARY BACKGROUND DATA: Patients with VHL disease have a propensity to develop neoplasms of several different organ sites. Retinal angiomas, cerebellar and spinal hemangioblastomas, solid organ cysts, and renal carcinoma are common lesions; pheochromocytomas and pancreatic islet cell tumors occur less frequently but are important causes of morbidity and mortality. METHODS: A detailed pedigree was constructed based on clinical screening and family history that describes the development of pancreatic islet cell tumors in four of five female siblings. VHL mutation analysis was performed in an attempt to determine if genotype-phenotype correlations could be made in this interesting family. RESULTS: The age of onset of VHL-associated neoplasms for three affected siblings was in the third decade of life and in the fourth decade for the fourth sibling. The mother of the four siblings affected with pancreatic tumors developed bilateral pheochromocytomas in the seventh decade of life; she has no pancreatic or kidney tumors. We identified maternal transmission of a missense mutation in codon 238 in exon 3 of the VHL gene in the four affected siblings with pancreatic islet cell tumors. Mutation screening on unaffected family members showed no abnormalities in the VHL gene. Interestingly, one of the four affected siblings had no evidence of VHL on her initial clinical screening evaluation; however, she was followed closely because of her mutated VHL gene. Four years after initial screening, she developed two pancreatic islet cell tumors and a premalignant renal cyst. CONCLUSIONS: Clinical and genetic screening for VHL in this family had a significant impact on surgical management by detecting early-stage islet cell tumors or pheochromocytomas. Furthermore, we conclude that the preponderance of pancreatic islet cell tumors in this family cannot be explained by a strict genotype-phenotype correlation. This suggests that additional genetic abnormalities, possibly on chromosome 3p where the VHL gene is located, may be responsible for the variety of VHL-associated neoplasms. Images Figure 2. Figure 3. PMID:9488521

  5. Am. J. Hum. Genet. 77:365376, 2005 Genomewide Linkage Study in 1,176 Affected Sister Pair Families

    E-print Network

    Nyholt, Dale R.

    Families Identifies a Significant Susceptibility Locus for Endometriosis on Chromosome 10q26 Susan A of Medical Research and 5 Queensland Endometriosis Research Institute, Brisbane, Australia; 6 Oxagen, United Kingdom Endometriosis is a common gynecological disease that affects up to 10% of women

  6. Genetic variants that affect length/height in infancy/early childhood in Vietnamese-Korean families.

    PubMed

    Kim, Han-Na; Lee, Eun-Ju; Jung, Sung-Chul; Lee, Jong-Young; Chung, Hye Won; Kim, Hyung-Lae

    2010-10-01

    To identify genetic factors that influence height in infancy/early childhood, a family-based genome-wide association study was conducted using 269,888 single-nucleotide polymorphisms (SNPs) in 165 families composed of a Korean father, a Vietnamese mother and Vietnamese-Korean offspring in the International Marriage-based Immigrant Cohort in Korea. In a single-SNP-based analysis, the six SNPs in or near genes MAF, MAGI2, BMP4 and PTPN7 showed consistent suggestive associations at all height standard deviation scores using Korean, World Health Organization and Vietnamese growth references. Analyzing the haplotypes for the genes, haplotype blocks were found to be significantly associated with height. Similar to the results of a contiguous haplotype analysis using tag SNPs as above, noncontiguous haplotypes of variable length also showed a significant association near the suspected loci. Our result suggests that height during infancy/early childhood may be regulated by genetic variations that differ from those of adults. PMID:20668459

  7. Vector control measures failed to affect genetic structure of Aedes aegypti in a sentinel metropolitan area of Brazil.

    PubMed

    Souza, Kathleen R; Ribeiro, Gilmar; Silva dos Santos, Carlos Gustavo; de Lima, Eliaci Couto; Melo, Paulo R S; Reis, Mitermayer G; Blanton, Ronald E; Silva, Luciano K

    2013-12-01

    In order to evaluate subpopulation differentiation, effective population size (Ne) and evidence for population bottlenecks at various geographic levels, Aedes aegypti larvae were collected longitudinally from 2007 to 2009 from four areas in the city of Salvador, Brazil. The DNA from each larva was isolated and genotyped with five independent microsatellite markers. FST and Jost's D revealed significant population structuring (P<0.05) at the municipal and regional levels, while only RST was able to detect genetic differentiation at the level of strata within these areas. Ne analysis from longitudinal data did not show any evidence of significant change in population structure. The census population measured by the house index, however, showed a significant trend toward decrease in these areas. Active vector control measures did contribute to vector reduction, but this was not enough to decrease A. aegypti population genetic diversity in Salvador. The understanding of A. aegypti population dynamics may be helpful for planning and evaluation of control measures to make them more effective. PMID:24028791

  8. Agro-environmental effects due to altered cultivation practices with genetically modified herbicide-tolerant oilseed rape and implications for monitoring. A review

    Microsoft Academic Search

    F. Graef

    2009-01-01

    Genetically modified herbicide-tolerant oilseed rape or canola (Brassica napus L.) is at the forefront of being introduced into European agriculture. Concerns have been raised about how genetically modified\\u000a oilseed rape cultivation and the modified cropping practices might impair the agro-environment. The present review compiles\\u000a and categorises evidenced and potential agro-environmental effects of cultivating genetically modified oilseed rape and assesses\\u000a the

  9. Naphthenic acids affect plant water conductance but do not alter shoot Na + and Cl ? concentrations in jack pine ( Pinus banksiana ) seedlings

    Microsoft Academic Search

    Kent G. Apostol; Janusz J. Zwiazek; Michael D. MacKinnon

    2004-01-01

    Solution culture-grown, six-month old jack pine (Pinus banksiana Lamb.) seedlings were treated with naphthenic acids (NAs) (150 mg l-1) and sodium chloride (45 mM NaCl) which were applied together or separately to roots for four weeks. NAs aggravated the effects of NaCl in inhibiting stomatal conductance (gs) and root hydraulic conductance (Kr). Naphthenic acids did not affect needle and root electrolyte leakage in

  10. Genetic linkage of autosomal dominant juvenile glaucoma to 1q21-q31 in three affected pedigrees

    SciTech Connect

    Wiggs, J.L.; Paglinauan, C.; Fine, A.; Sporn, C.; Lou, D. (Tufts Univ. School of Medicine, Boston, MA (United States)); Haines, J.L. (Harvard Medical School, Boston, MA (United States))

    1994-05-15

    Glaucoma is a common disorder that results in irreversible damage to the optic nerve, causing absolute blindness. In most cases, the optic nerve is damaged by an elevation of the intraocular pressure that is the result of an abnormality in the normal drainage function of the trabecular meshwork. A family history of glaucoma is an important risk factor for the disease, suggesting that genetic defects predisposing to this condition are likely. Three pedigrees segregating an autosomal dominant juvenile glaucoma demonstrated significant linkage to a group of closely spaced markers on chromosome 1. These results confirm the initial mapping of this disease and suggest that this region on chromosome 1 contains an important locus for juvenile glaucoma. The authors describe recombination events that improve the localization of the responsible gene, reducing the size of the candidate region from 30 to 12 cM. 27 refs., 2 figs., 1 tab.

  11. Glycans Instructing Immunity: The Emerging Role of Altered Glycosylation in Clinical Immunology

    PubMed Central

    Lyons, Jonathan J.; Milner, Joshua D.; Rosenzweig, Sergio D.

    2015-01-01

    Protein glycosylation is an important epigenetic modifying process affecting expression, localization, and function of numerous proteins required for normal immune function. Recessive germline mutations in genes responsible for protein glycosylation processes result in congenital disorders of glycosylation and can have profound immunologic consequences. Genetic mutations in immune signaling pathways that affect glycosylation sites have also been shown to cause disease. Sugar supplementation and in vivo alteration of glycans by medication holds therapeutic promise for some of these disorders. Further understanding of how changes in glycosylation alter immunity may provide novel treatment approaches for allergic disease, immune dysregulation, and immunodeficiency in the future. PMID:26125015

  12. Genetics of methyl-accepting chemotaxis proteins in Escherichia coli: cheD mutations affect the structure and function of the Tsr transducer.

    PubMed Central

    Callahan, A M; Parkinson, J S

    1985-01-01

    The tsr gene specifies a methyl-accepting membrane protein involved in chemotaxis to serine and several repellent compounds. We have characterized a special class of tsr mutations designated cheD which alter the signaling properties of the Tsr transducer. Unlike tsr null mutants, cheD strains are generally nonchemotactic, dominant in complementation tests, and exhibit a pronounced counterclockwise bias in flagellar rotation. Several lines of evidence showed that cheD mutations were alleles of the tsr gene. First, cheD mutations were mapped into the same deletion segments as conventional tsr mutations. Second, restriction site analysis of the transducing phage deletions used to construct the genetic map demonstrated that the endpoints of the deletion segments fell within the tsr coding sequence. Third, a number of the cheD mutants synthesized Tsr proteins with slight changes in electrophoretic mobility, consistent with alterations in Tsr primary structure. These mutant proteins were able to undergo posttranslational deamidation and methylation reactions in the same manner as wild-type Tsr protein; however, the steady-state level of Tsr methylation in cheD strains was very high. The methylation state of the Tar protein, another species of methyl-accepting protein in Escherichia coli, was also higher than normal in cheD strains, suggesting that the aberrant Tsr transducer in cheD mutants has a generalized effect on the sensory adaptation system of the cell. These properties are consistent with the notion that the Tsr protein of cheD mutants is locked in an excitatory signaling mode that both activates the sensory adaptation system and drowns out chemotactic signals generated by other transducer species. Further study of cheD mutations thus promises to reveal valuable information about the functional architecture of the Tsr protein and how this transducer controls flagellar behavior. Images PMID:3155720

  13. Genetic variants in KDR transcriptional regulatory region affect promoter activity and intramuscular fat deposition in Erhualian pigs.

    PubMed

    Fu, Y; Sun, W; Xu, C; Gu, S; Li, Y; Liu, Z; Chen, J

    2014-06-01

    Kinase insert domain receptor (KDR), a vascular endothelial growth factor (VEGF) receptor, is widely regarded as having a principal role in mediating VEGF-induced responses in angiogenesis. As angiogenesis provides oxygen and nutrients for growth and deposition of adipose cells, our objective was to determine whether the promoter polymorphisms in the KDR gene have effects on intramuscular fat (IMF) deposition in the longissimus dorsi muscle. Three novel SNPs, c.-1316A>G, c.-1303C>T and c.-1108A>C, were revealed to have differential allele distribution between high- and low-IMF content groups by comparative sequencing of DNA pools. The three SNPs were completely linked, forming only ACA or GTC haplotypes when genotyped in 105 Erhualian purebred pigs and 98 Duroc × Large White × Yorkshire (D×L×Y) cross-bred pigs. It is interesting that the ACA haplotype is present exclusively in Erhualian pigs and not in D×L×Y pigs. The ACA promoter was found to have higher activity than GTC type for KDR transcription using either gene expression analysis or luciferase assay. Site-direct mutation analysis demonstrated that c.-1316A>G is the causation of promoter activity alteration. Furthermore, we detected that CD31 (also known as PECAM1) and CD34, two blood vessel endothelial markers, expressed higher in ACA/ACA individuals. We concluded that the ACA promoter might be a desirable form for improving IMF content by promoting higher KDR gene expression and more blood vessel network. PMID:24673468

  14. U s t a r r e s e a r c h How Genetic Disruptions Alter Brain Structures, Which Affects Behavior

    E-print Network

    Capecchi, Mario R.

    was becoming the new hub of medical research and would be critical for A charming 9-year-old girl with a rare BeautifulInterplaY: The girl has Williams syndrome, a disorder in which people are missing 25 to 28 genes for Biological Studies wrote about the unidentified girl in a study published in February. She has many

  15. Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells and alters the cytokine profile, but does not affect maturation or migration.

    PubMed

    Monrad, S U; Kojima, F; Kapoor, M; Kuan, E L; Sarkar, S; Randolph, G J; Crofford, L J

    2011-01-01

    We undertook this study to determine the role of Microsomal PGE Synthase-1 (mPGES-1), and mPGES-1-generated Prostaglandin (PG) E2 on Dendritic Cell (DC) phenotype and function. Using mPGES-1 KnockOut (KO) mice, we generated bone marrow derived DCs and determined their eicosanoid production profile, cell surface marker expression, and cytokine production. We also assessed DC migratory and functional capacity in vivo. Compared to wild-type, mPGES-1 deficient DCs exhibited a markedly attenuated increase in PGE2 production upon LPS stimulation, and displayed preferential shunting towards PGD2 production. mPGES-1 KO DCs did not display deficiencies in maturation, migration or ability to sensitize T cells. However, mPGES-1 deficient DCs generated reduced amounts of the Th1 cytokine IL-12, which may in part be due to increased PGD2 rather than decreased PGE2. These findings provide useful information on the effects of inducible PGE2 on the innate immune system, and have important implications regarding potential consequences of pharmacologic mPGES-1 inhibition. PMID:21190819

  16. Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells and alters the cytokine profile, but does not affect maturation or migration

    PubMed Central

    Monrad, S.U.; Kojima, F.; Kapoor, M.; Kuan, E.L.; Sarkar, S.; Randolph, G.J.; Crofford, L.J.

    2010-01-01

    SUMMARY We undertook this study to determine the role of microsomal PGE synthase-1 (mPGES-1) and mPGES-1-generated prostaglandin (PG) E2 on dendritic cell (DC) phenotype and function. Using mPGES-1 knockout (KO) mice, we generated bone marrow derived DCs and determined their eicosanoid production profile, cell surface marker expression, and cytokine production. We also assessed DC migratory and functional capacity in vivo. Compared to wild-type, mPGES-1 deficient DCs exhibited a markedly attenuated increase in PGE2 production upon LPS stimulation, and displayed preferential shunting towards PGD2 production. mPGES-1 KO DCs did not display deficiencies in maturation, migration or ability to sensitize T cells. However, mPGES-1 deficient DCs generated reduced amounts of the Th1 cytokine IL-12, which may in part be due to increased PGD2 rather than decreased PGE2. These findings provide useful information on the effects of inducible PGE2 on the innate immune system, and have important implications regarding potential consequences of pharmacologic mPGES-1 inhibition. PMID:21190819

  17. Term: Fall 2011 Course Number: GENET 290

    E-print Network

    alterations that contribute to genetic disease, how to identify the genetic components and alterationsTerm: Fall 2011 Course Number: GENET 290 Course Title: Genetics Journal Club Course Directors: Drs. Fern Tsien, Wanguo Liu and Udai Pandey Locations: CSRB, Genetics Conference Room Times of Class

  18. Overfeeding and genetics affect the composition of intestinal microbiota in Anas platyrhynchos (Pekin) and Cairina moschata (Muscovy) ducks.

    PubMed

    Vasaï, Florian; Brugirard Ricaud, Karine; Bernadet, Marie Dominique; Cauquil, Laurent; Bouchez, Olivier; Combes, Sylvie; Davail, Stéphane

    2014-01-01

    To investigate the effect of overfeeding on the ileal and cecal microbiota of two genotypes of ducks (Pekin and Muscovy), high-throughput 16S rRNA gene-based pyrosequencing was used. The ducks were overfed for 12 days with 58% maize flour and 42% maize grain. Samples were collected before the overfeeding period (at 12 weeks), at 13 weeks, at 14 weeks, and 3 h after feeding. In parallel, ducks fed ad libitum were killed at the same ages. Whatever the digestive segment, the genotype, and the level of intake, Firmicutes and Bacteroidetes are the dominant phyla in the bacterial community of ducks (at least 80%). Before overfeeding, ileal samples were dominated by Bacilli, Clostridia, and Bacteroidia classes (? 70%), and cecal samples, by Bacteroidia and Clostridia classes (around 90%) in both Pekin and Muscovy ducks. The richness and diversity decreased in the ileum and increased in the ceca after overfeeding. Overfeeding triggers major changes in the ileum, whereas the ceca are less affected. Overfeeding increased the relative abundance of Clostridiaceae, Lactobacillaceae, Streptococcaceae, and Enterococcaceae families in the ileum, whereas genotype affects particularly three families: Lachnospiraceae, Bacteroidaceae, and Desulfovibrionaceae in the ceca. PMID:24102552

  19. Deep Sequencing of the Nicastrin Gene in Pooled DNA, the Identification of Genetic Variants That Affect Risk of Alzheimer's Disease

    PubMed Central

    Lupton, Michelle K.; Proitsi, Petroula; Danillidou, Makrina; Tsolaki, Magda; Hamilton, Gillian; Wroe, Richard; Pritchard, Megan; Lord, Kathryn; Martin, Belinda M.; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Vellas, Bruno; Harold, Denise; Hollingworth, Paul; Lovestone, Simon; Powell, John F.

    2011-01-01

    Nicastrin is an obligatory component of the ?-secretase; the enzyme complex that leads to the production of A? fragments critically central to the pathogenesis of Alzheimer's disease (AD). Analyses of the effects of common variation in this gene on risk for late onset AD have been inconclusive. We investigated the effect of rare variation in the coding regions of the Nicastrin gene in a cohort of AD patients and matched controls using an innovative pooling approach and next generation sequencing. Five SNPs were identified and validated by individual genotyping from 311 cases and 360 controls. Association analysis identified a non-synonymous rare SNP (N417Y) with a statistically higher frequency in cases compared to controls in the Greek population (OR 3.994, CI 1.105–14.439, p?=?0.035). This finding warrants further investigation in a larger cohort and adds weight to the hypothesis that rare variation explains some of genetic heritability still to be identified in Alzheimer's disease. PMID:21364883

  20. The frequency of precocious segregation of sister chromatids in mouse female meiosis I is affected by genetic background.

    PubMed

    Danylevska, Anna; Kovacovicova, Kristina; Awadova, Thuraya; Anger, Martin

    2014-09-01

    Mammalian female gametes frequently suffer from numerical chromosomal aberrations, the main cause of miscarriages and severe developmental defects. The underlying mechanisms responsible for the development of aneuploidy in oocytes are still not completely understood and remain a subject of extensive research. From studies focused on prevalence of aneuploidy in mouse oocytes, it has become obvious that reported rates of aneuploidy are strongly dependent on the method used for chromosome counting. In addition, it seems likely that differences between mouse strains could influence the frequency of aneuploidy as well; however, up till now, such a comparison has not been available. Therefore, in our study, we measured the levels of aneuploidy which has resulted from missegregation in meiosis I, in oocytes of three commonly used mouse strains-CD-1, C3H/HeJ, and C57BL/6. Our results revealed that, although the overall chromosomal numerical aberration rates were similar in all three strains, a different number of oocytes in each strain contained prematurely segregated sister chromatids (PSSC). This indicates that a predisposition for this type of chromosome segregation error in oocyte meiosis I is dependent on genetic background. PMID:24935618

  1. Platelet CD36 surface expression levels affect functional responses to oxidized LDL and are associated with inheritance of specific genetic polymorphisms

    PubMed Central

    Ghosh, Arunima; Murugesan, Gurunathan; Chen, Kan; Zhang, Li; Wang, Qing; Febbraio, Maria; Anselmo, Rita Marie; Marchant, Kandice; Barnard, John

    2011-01-01

    CD36 modulates platelet function via binding to oxidized LDL (oxLDL), cell-derived microparticles, and thrombospondin-1. We hypothesized that the level of platelet CD36 expression may be associated with inheritance of specific genetic polymorphisms and that this would determine platelet reactivity to oxLDL. Analysis of more than 500 subjects revealed that CD36 expression levels were consistent in individual donors over time but varied widely among donors (200-14 000 molecules per platelet). Platelet aggregometry and flow cytometry in a subset of subjects with various CD36 expression levels revealed a high level of correlation (r2 = 0.87) between platelet activation responses to oxLDL and level of CD36 expression. A genome-wide association study of 374 white subjects from the Cleveland Clinic ASCLOGEN study showed strong associations of single nucleotide polymorphisms in CD36 with platelet surface CD36 expression. Most of these findings were replicated in a smaller subset of 25 black subjects. An innovative gene-based genome-wide scan provided further evidence that single nucleotide polymorphisms in CD36 were strongly associated with CD36 expression. These studies show that CD36 expression on platelets varies widely, correlates with functional responses to oxLDL, and is associated with inheritance of specific CD36 genetic polymorphisms, and suggest that inheritance of specific CD36 polymorphisms could affect thrombotic risk. PMID:21478428

  2. Genetic polymorphisms in the mevalonate pathway affect the therapeutic response to alendronate treatment in postmenopausal Chinese women with low bone mineral density.

    PubMed

    Wang, C; Zheng, H; He, J-W; Zhang, H; Yue, H; Hu, W-W; Gu, J-M; Shao, C; Fu, W-Z; Hu, Y-Q; Li, M; Liu, Y-J; Zhang, Z-L

    2015-04-01

    Alendronate is an antiosteoporotic drug that targets the mevalonate pathway. To investigate whether the genetic variations in this pathway affect the clinical efficacy of alendronate in postmenopausal Chinese women with osteopenia or osteoporosis, 23 single-nucleotide polymorphisms (SNPs) in 7 genes were genotyped in 500 patients treated with alendronate for 12 months. Bone mineral density (BMD) was measured at baseline and after 12 months. The rs10161126 SNP in the 3' flanking region of MVK and the GTCCA haplotype in FDFT1 were significantly associated with therapeutic response. A 6.6% increase in BMD in the lumbar spine was observed in the GG homozygotes of rs10161126; AG heterozygotes and AA homozygotes experienced a 4.4 and 4.5% increase, respectively. The odds ratio (95% confidence interval) of G allele carriers to be responders in lumbar spine BMD was 2.06 (1.08-6.41). GTCCA haplotype in FDFT1 was more frequently detected in the group of responders than in the group of non-responders at the total hip (2.6 vs 0.5%, P=0.009). Therefore, MVK and FDFT1 polymorphisms are genetic determinants for BMD response to alendronate therapy in postmenopausal Chinese women. PMID:25223561

  3. 28 CFR 36.402 - Alterations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...accommodation or a commercial facility that affects or could affect the usability of the building or facility or any part thereof. ...electrical systems are not alterations unless they affect the usability of the building or facility. (2) If existing...

  4. How Early Events Affect Growing Brains. An Interview with Neuroscientist Pat Levitt

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2006

    2006-01-01

    Recent advances in neuroscience show clearly how experience can change brain neurochemicals, and how this in turn affects the way the brain functions. As a result, early negative events actually get built into the growing brain's neurochemistry, altering the brain's architecture. Research is continuing to investigate how children with genetic

  5. Tissue-specific alterations in G protein expression in genetic versus diet-induced models of non-insulin-dependent diabetes mellitus in the mouse

    Microsoft Academic Search

    Thomas W. Gettys; Vickram Ramkumar; Richard S. Surwit; Ian L. Taylor

    1995-01-01

    Various tissues were obtained from the well-characterized genetic model (C57BL\\/6J-obob) of non-insulin-dependent diabetes mellitus (NIDDM) and from a diet-induced model of NIDDM produced in the same genetic background (C57BL\\/6J). The objectives were to determine whether the previously observed changes in guanine nucleotide-binding regulatory protein (G protein) expression in adipose tissue from obob mice were mirrored by concomitant changes in other

  6. Hypergravity-induced altered behavior in Drosophila

    NASA Astrophysics Data System (ADS)

    Hosamani, Ravikumar; Wan, Judy; Marcu, Oana; Bhattacharya, Sharmila

    2012-07-01

    Microgravity and mechanical stress are important factors of the spaceflight environment, and affect astronaut health and behavior. Structural, functional, and behavioral mechanisms of all cells and organisms are adapted to Earth's gravitational force, 1G, while altered gravity can pose challenges to their adaptability to this new environment. On ground, hypergravity paradigms have been used to predict and complement studies on microgravity. Even small changes that take place at a molecular and genetic level during altered gravity may result in changes in phenotypic behavior. Drosophila provides a robust and simple, yet very reliable model system to understand the complexity of hypergravity-induced altered behavior, due to availability of a plethora of genetic tools. Locomotor behavior is a sensitive parameter that reflects the array of molecular adaptive mechanisms recruited during exposure to altered gravity. Thus, understanding the genetic basis of this behavior in a hypergravity environment could potentially extend our understanding of mechanisms of adaptation in microgravity. In our laboratory we are trying to dissect out the cellular and molecular mechanisms underlying hypergravity-induced oxidative stress, and its potential consequences on behavioral alterations by using Drosophila as a model system. In the present study, we employed pan-neuronal and mushroom body specific knock-down adult flies by using Gal4/UAS system to express inverted repeat transgenes (RNAi) to monitor and quantify the hypergravity-induced behavior in Drosophila. We established that acute hypergravity (3G for 60 min) causes a significant and robust decrease in the locomotor behavior in adult Drosophila, and that this change is dependent on genes related to Parkinson's disease, such as DJ-1? , DJ-1? , and parkin. In addition, we also showed that anatomically the control of this behavior is significantly processed in the mushroom body region of the fly brain. This work links a molecular mechanism of response to changes in gravity with a phenotypical outcome. Characterizing the changes in altered gravity that are consequential for the overall physiology of organisms is crucial for assessing the risks of long-term space travel.

  7. Elongated phytoglycogen chain length in transgenic rice endosperm expressing active starch synthase IIa affects the altered solubility and crystallinity of the storage ?-glucan

    PubMed Central

    Fujita, Naoko; Toyosawa, Yoshiko; Utsumi, Yoshinori

    2012-01-01

    The relationship between the solubility, crystallinity, and length of the unit chains of plant storage ?-glucan was investigated by manipulating the chain length of ?-glucans accumulated in a rice mutant. Transgenic lines were produced by introducing a cDNA for starch synthase IIa (SSIIa) from an indica cultivar (SSIIa I, coding for active SSIIa) into an isoamylase1 (ISA1)-deficient mutant (isa1) that was derived from a japonica cultivar (bearing inactive SSIIa proteins). The water-soluble fraction accounted for >95% of the total ?-glucan in the isa1 mutant, whereas it was only 35–70% in the transgenic SSIIa I /isa1 lines. Thus, the ?-glucans from the SSIIa I /isa1 lines were fractionated into soluble and insoluble fractions prior to the following characterizations. X-ray diffraction analysis revealed a weak B-type crystallinity for the ?-glucans of the insoluble fraction, while no crystallinity was confirmed for ?-glucans in isa1. Concerning the degree of polymerization (DP) ?30, the chain lengths of these ?-glucans differed significantly in the order of SSIIa I /isa1 insoluble > SSIIa I /isa1 soluble > ?-glucans in isa1. The amount of long chains with DP ?33 was higher in the insoluble fraction ?-glucans than in the other two ?-glucans. No difference was observed in the chain length distributions of the ?-amylase limit dextrins among these ?-glucans. These results suggest that in the SSIIa I /isa1 transgenic lines, the unit chains of ?-glucans were elongated by SSIIaI, whereas the expression of SSIIaI did not affect the branch positions. Thus, the observed insolubility and crystallinity of the insoluble fraction can be attributed to the elongated length of the outer chains due to SSIIaI. PMID:23048127

  8. 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze

    PubMed Central

    Karabeg, Margherita M.; Grauthoff, Sandra; Kollert, Sina Y.; Weidner, Magdalena; Heiming, Rebecca S.; Jansen, Friederike; Popp, Sandy; Kaiser, Sylvia; Lesch, Klaus-Peter; Sachser, Norbert

    2013-01-01

    The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised alertness, possibly impeding optimal learning performance in the more stressful WM. PMID:24167611

  9. Assembly of the Genome of the Disease Vector Aedes aegypti onto a Genetic Linkage Map Allows Mapping of Genes Affecting Disease Transmission

    PubMed Central

    Juneja, Punita; Osei-Poku, Jewelna; Ho, Yung S.; Ariani, Cristina V.; Palmer, William J.; Pain, Arnab; Jiggins, Francis M.

    2014-01-01

    The mosquito Aedes aegypti transmits some of the most important human arboviruses, including dengue, yellow fever and chikungunya viruses. It has a large genome containing many repetitive sequences, which has resulted in the genome being poorly assembled — there are 4,758 scaffolds, few of which have been assigned to a chromosome. To allow the mapping of genes affecting disease transmission, we have improved the genome assembly by scoring a large number of SNPs in recombinant progeny from a cross between two strains of Ae. aegypti, and used these to generate a genetic map. This revealed a high rate of misassemblies in the current genome, where, for example, sequences from different chromosomes were found on the same scaffold. Once these were corrected, we were able to assign 60% of the genome sequence to chromosomes and approximately order the scaffolds along the chromosome. We found that there are very large regions of suppressed recombination around the centromeres, which can extend to as much as 47% of the chromosome. To illustrate the utility of this new genome assembly, we mapped a gene that makes Ae. aegypti resistant to the human parasite Brugia malayi, and generated a list of candidate genes that could be affecting the trait. PMID:24498447

  10. Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation.

    PubMed

    Kovacic, Peter; Somanathan, Ratnasamy

    2009-01-01

    Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action. The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and receptors in the central nervous system. The drug acts at the GABA(A) receptor benzodiazepine site, displaying high and intermediate affinities to various receptor regions. Structural features for tight binding were determined. The sedative and anticonvulsant activities are due to its action on the alpha-1-GABA(A) receptors. One of the common adverse responses to zolpidem is hallucinations. Proposed mechanisms comprise changes in the GABA(A) receptor, pharmacodynamic interactions involving serotonin and neuronal-weak photon emission processes entailing redox phenomena. Reports cite cases of abuse with cravings based on anxiolytic and stimulating actions. It is important to recognize that insight concerning processes at the fundamental, molecular level can translate into beneficial results involving both positive and adverse side effects. In order for this to occur, interdisciplinary interaction is necessary. Suggestions are made for future research aimed at testing the various hypotheses. PMID:20046645

  11. Genetic and hypoxic alterations of the microRNA-210-ISCU1/2 axis promote iron-sulfur deficiency and pulmonary hypertension

    E-print Network

    Dahlman, James E.

    Iron–sulfur (Fe?S) clusters are essential for mitochondrial metabolism, but their regulation in pulmonary hypertension (PH) remains enigmatic. We demonstrate that alterations of the miR?210?ISCU1/2 axis cause Fe?S deficiencies ...

  12. The Feeding Value of Soybeans Fed to Rats, Chickens, Catfish and Dairy Cattle Is Not Altered by Genetic Incorporation of Glyphosate Tolerance1'2

    Microsoft Academic Search

    BRUCE C. HAMMOND; JOHN L VICINI; CARY F. HARTNELL; MARK W. NAYLOR; CHRISTOPHER D. KNIGHT; EDWIN H. ROBINSON; ROY L. FUCHS; STEPHEN R. PADGETTE

    Animal feeding studies were conducted with rats, broiler chickens, catfish and dairy cows as part of a safety assessment program for a soybean variety genetically modified to tolerate in-season appli cation of glyphosate. These studies were designed to compare the feeding value (wholesomeness) of two lines of glyphosate-tolerant soybeans (GTS) to the feeding value of the parental cultivar from which

  13. Transcriptional Programs following Genetic Alterations in p53, INK4A, and H-Ras Genes along Defined Stages of Malignant Transformation

    Microsoft Academic Search

    Michael Milyavsky; Yuval Tabach; Igor Shats; Neta Erez; Yehudit Cohen; Xiaohu Tang; Marina Kalis; Ira Kogan; Yosef Buganim; Naomi Goldfinger; Doron Ginsberg; Curtis C. Harris; Eytan Domany; Varda Rotter

    2005-01-01

    The difficulty to dissect a complex phenotype of established malignant cells to several critical transcriptional programs greatly impends our understanding of the malignant trans- formation. The genetic elements required to transform some primary human cells to a tumorigenic state were described in several recent studies. We took the advantage of the global genomic profiling approach and tried to go one

  14. Japanese and North American\\/European patients with Beckwith–Wiedemann syndrome have different frequencies of some epigenetic and genetic alterations

    Microsoft Academic Search

    Kensaku Sasaki; Hidenobu Soejima; Ken Higashimoto; Hitomi Yatsuki; Hirofumi Ohashi; Shinya Yakabe; Keiichiro Joh; Norio Niikawa; Tsunehiro Mukai

    2007-01-01

    Beckwith–Wiedemann syndrome (BWS) is an imprinting-related human disease. The frequencies of causative alterations such as loss of methylation (LOM) of KvDMR1, hypermethylation of H19-DMR, paternal uniparental disomy, CDKN1C gene mutation, and chromosome abnormality have been described for North American and European patients, but the corresponding frequencies in Japanese patients have not been measured to date. Analysis of 47 Japanese cases

  15. Human genetics shape the gut microbiome.

    PubMed

    Goodrich, Julia K; Waters, Jillian L; Poole, Angela C; Sutter, Jessica L; Koren, Omry; Blekhman, Ran; Beaumont, Michelle; Van Treuren, William; Knight, Rob; Bell, Jordana T; Spector, Timothy D; Clark, Andrew G; Ley, Ruth E

    2014-11-01

    Host genetics and the gut microbiome can both influence metabolic phenotypes. However, whether host genetic variation shapes the gut microbiome and interacts with it to affect host phenotype is unclear. Here, we compared microbiotas across >1,000 fecal samples obtained from the TwinsUK population, including 416 twin pairs. We identified many microbial taxa whose abundances were influenced by host genetics. The most heritable taxon, the family Christensenellaceae, formed a co-occurrence network with other heritable Bacteria and with methanogenic Archaea. Furthermore, Christensenellaceae and its partners were enriched in individuals with low body mass index (BMI). An obese-associated microbiome was amended with Christensenella minuta, a cultured member of the Christensenellaceae, and transplanted to germ-free mice. C. minuta amendment reduced weight gain and altered the microbiome of recipient mice. Our findings indicate that host genetics influence the composition of the human gut microbiome and can do so in ways that impact host metabolism. PMID:25417156

  16. 14 CFR 77.13 - Construction or alteration requiring notice.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...2010-01-01 2010-01-01 false Construction or alteration requiring notice. 77...AFFECTING NAVIGABLE AIRSPACE Notice of Construction or Alteration § 77.13 Construction or alteration requiring notice....

  17. Glutamate receptor composition of the post-synaptic density is altered in genetic mouse models of NMDA receptor hypo- and hyperfunction

    Microsoft Academic Search

    Darrick T. Balu; Joseph T. Coyle

    2011-01-01

    The N-methyl-d-aspartate receptor (NMDAR) and ?-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) are ionotropic glutamate receptors responsible for excitatory neurotransmission in the brain. These excitatory synapses are found on dendritic spines, with the abundance of receptors concentrated at the postsynaptic density (PSD). We utilized two genetic mouse models, the serine racemase knockout (SR?\\/?) and the glycine transporter subtype 1 heterozygote mutant (GlyT1+\\/?), to determine

  18. The Genetics of CAENORHABDITIS ELEGANS

    PubMed Central

    Brenner, S.

    1974-01-01

    Methods are described for the isolation, complementation and mapping of mutants of Caenorhabditis elegans, a small free-living nematode worm. About 300 EMS-induced mutants affecting behavior and morphology have been characterized and about one hundred genes have been defined. Mutations in 77 of these alter the movement of the animal. Estimates of the induced mutation frequency of both the visible mutants and X chromosome lethals suggests that, just as in Drosophila, the genetic units in C. elegans are large. PMID:4366476

  19. No altered blood pressure and serum markers of oxidative stress after a long time dietary fish oil in the genetically 9 month-old type-2 diabetes Zucker rat.

    PubMed

    Tricot, Sompadthana; Mimouni, Virginie; Rompion, Sonia; Froger, Christelle; Lacroix, Pierre; Roux, Sylvain; Ulmann, Lionel

    2010-01-01

    In this study, we investigated the effect of a high n-3 fatty acid diet (eicosapentaenoic and docosahexaenoic acids) in Zucker obese and lean rats on blood pressure in association with physiological parameters, serum biochemistry and oxidative stress analysis. After 150 days of treatment, dietary fish oil supplementation in Zucker obese rats (9 months of age) reduces bodyweight gain and serum triglyceridemia and nitrite levels, increases serum glucose and angiotensin converting enzyme activity, but does not alter blood pressure, cholesterol levels and serum markers of oxidative stress (malondialdehyde, glutathione), compared to the Zucker rats fed control diet. According to these results, we can consider that after 150 days of treatment, fish oil is not enough to regulate parameters involved in the metabolic syndrome, such as cholesterolemia and blood pressure, in a 9 month-old genetically type-2 diabetes rat. PMID:20833009

  20. Genetically expressed HIV-1 viral proteins attenuate nicotine-induced behavioral sensitization and alter mesocorticolimbic ERK and CREB signaling in rats

    PubMed Central

    Midde, Narasimha M.; Gomez, Adrian M.; Harrod, Steven B.; Zhu, Jun

    2011-01-01

    The prevalence of tobacco smoking in HIV-1 positive individuals is 3-fold greater than that in the HIV-1 negative population; however, whether HIV-1 viral proteins and nicotine together produce molecular changes in mesolimbic structures that mediate psychomotor behavior has not been studied. This study determined whether HIV-1 viral proteins changed nicotine-induced behavioral sensitization in HIV-1 transgenic (HIV-1Tg) rats. Further, we examined cAMP response element binding protein (CREB) and extracellular regulated kinase (ERK1/2) signaling in the prefrontal cortex (PFC), nucleus accumbens (NAc) and ventral tegmental area (VTA). HIV-1Tg rats exhibited a transient decrease of activity during habituation, but showed attenuated nicotine (0.35 mg/kg, s.c.)-induced behavioral sensitization compared to Fisher 344 (F344) rats. The basal levels of phosphorylated CREB and ERK2 were lower in the PFC of HIV-1Tg rats, but not in the NAc and VTA, relative to the controls. In the nicotine-treated groups, the levels of phosphorylated CREB and ERK2 in the PFC were increased in HIV-1Tg rats, but decreased in F344 animals. Moreover, repeated nicotine administration reduced phosphorylated ERK2 in the VTA of HIV-1Tg rats and in the NAc of F344 rats, but had no effect on phosphorylated CREB, indicating a region-specific change of intracellular signaling. These results demonstrate that HIV-1 viral proteins produce differences in basal and nicotine-induced alterations in CREB and ERK signaling that may contribute to the alteration in psychomotor sensitization. Thus, HIV-1 positive smokers are possibly more vulnerable to alterations in CREB and ERK signaling and this has implications for motivated behavior, including tobacco smoking, in HIV-1 positive individuals who self-administer nicotine. PMID:21420997

  1. Highly aggressive behavior of malignant rhabdoid tumor: a special reference to SMARCB1\\/INI1 gene alterations using molecular genetic analysis including quantitative real-time PCR

    Microsoft Academic Search

    Kenichi Kohashi; Yoshinao Oda; Hidetaka Yamamoto; Sadafumi Tamiya; Teiyu Izumi; Shigeru Ohta; Tomoaki Taguchi; Sachiyo Suita; Masazumi Tsuneyoshi

    2007-01-01

    Purpose  \\u000a SMARCB1\\/INI1, which negatively regulates cell cycle progression from G0\\/G1 into the S-phase via the p16INK4a-RB-E2F pathway, has been\\u000a reported to be inactivated homozygously by deletion and\\/or mutations in malignant rhabdoid tumor (MRT). In the current study,\\u000a we investigated the alteration of the SMARCB1\\/INI1 gene using simple methods, and its gene product at the protein level. Moreover, we investigated the

  2. Genetics Home Reference: Genitopatellar syndrome

    MedlinePLUS

    ... may function differently than the full-length version, altering the regulation of various genes during early development. ... Center . Where can I find general information about genetic conditions? The Handbook provides basic information about genetics ...

  3. 2,3,7,8-Tetrachlorodibenzo-p-dioxin activates the aryl hydrocarbon receptor and alters sex steroid hormone secretion without affecting growth of mouse antral follicles in vitro

    SciTech Connect

    Karman, Bethany N., E-mail: bklement@illinois.edu; Basavarajappa, Mallikarjuna S., E-mail: mbshivapur@gmail.com; Craig, Zelieann R., E-mail: zelieann@illinois.edu; Flaws, Jodi A., E-mail: jflaws@illinois.edu

    2012-05-15

    The persistent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is an ovarian toxicant. These studies were designed to characterize the actions of TCDD on steroidogenesis and growth of intact mouse antral follicles in vitro. Specifically, these studies tested the hypothesis that TCDD exposure leads to decreased sex hormone production/secretion by antral follicles as well as decreased growth of antral follicles in vitro. Since TCDD acts through binding to the aryl hydrocarbon receptor (AHR), and the AHR has been identified as an important factor in ovarian function, we also conducted experiments to confirm the presence and activation of the AHR in our tissue culture system. To do so, we exposed mouse antral follicles for 96 h to a series of TCDD doses previously shown to have effects on ovarian tissues and cells in culture, which also encompass environmentally relevant and pharmacological exposures (0.1–100 nM), to determine a dose response for TCDD in our culture system for growth, hormone production, and expression of the Ahr and Cyp1b1. The results indicate that TCDD decreases progesterone, androstenedione, testosterone, and estradiol levels in a non-monotonic dose response manner without altering growth of antral follicles. The addition of pregnenolone substrate (10 ?M) restores hormone levels to control levels. Additionally, Cyp1b1 levels were increased by 3–4 fold regardless of the dose of TCDD exposure, evidence of AHR activation. Overall, these data indicate that TCDD may act prior to pregnenolone formation and through AHR transcriptional control of Cyp1b1, leading to decreased hormone levels without affecting growth of antral follicles. -- Highlights: ?TCDD disrupts sex steroid hormone levels, but not growth of antral follicles. ?Pregnenolone co-treatment by-passes TCDD-induced steroid hormone disruption. ?TCDD affects steroid hormone levels through an AHR pathway in antral follicles.

  4. [Molecular alterations in melanoma and targeted therapies].

    PubMed

    Mourah, Samia; Lebbé, Céleste

    2014-12-01

    Melanoma is a skin cancer whose incidence is increasing steadily. The recent discovery of frequent and recurrent genetic alterations in cutaneous melanoma allowed a molecular classification of tumors into distinct subgroups, and paved the way for targeted therapy. Several signaling pathways are involved in the progression of this disease with oncogenic mutations affecting signaling pathways: MAPK, PI3K, cAMP and cyclin D1/CDK4. In each of these pathways, several potential therapeutic targets have been identified and specific inhibitors have already been developed and have shown clinical efficacy. The use of these inhibitors is often conditioned by tumors genotyping. In France, melanomas genotyping is supported by the platforms of the National Cancer Institute (INCA), which implemented a national program ensuring access to innovation for personalized medicine. The identification of new targets in melanoma supplies a very active dynamic development of innovative molecules contributing to changing the therapeutic landscape of this pathology. PMID:25776766

  5. Oculoectodermal syndrome is a mosaic RASopathy associated with KRAS alterations.

    PubMed

    Peacock, Jacqueline D; Dykema, Karl J; Toriello, Helga V; Mooney, Marie R; Scholten, Donald J; Winn, Mary E; Borgman, Andrew; Duesbery, Nicholas S; Hiemenga, Judith A; Liu, Cong; Campbell, Stacey; Nickoloff, Brian P; Williams, Bart O; Steensma, Matthew

    2015-07-01

    Oculoectodermal syndrome (OES) is a rare disease characterized by a combination of congenital scalp lesions and ocular dermoids, with additional manifestations including non-ossifying fibromas and giant cell granulomas of the jaw occurring during the first decade of life. To identify the genetic etiology of OES, we conducted whole-genome sequencing of several tissues in an affected individual. Comparison of DNA from a non-ossifying fibroma to blood-derived DNA allowed identification of a somatic missense alteration in KRAS NM_033360.3(KRAS):c.38G>A, resulting in p.Gly13Asp. This alteration was also observed in the patient's other affected tissues including the skin and muscle. Targeted sequencing in a second, unrelated OES patient identified an NM_033360.3(KRAS):c.57G>C, p.Leu19Phe alteration. Allelic frequencies fell below 40% in all tissues examined in both patients, suggesting that OES is a mosaic RAS-related disorder, or RASopathy. The characteristic findings in OES, including scalp lesions, ocular dermoids, and benign tumors, are found in other mosaic and germline RASopathies. This discovery also broadens our understanding of the spectrum of phenotypes resulting from KRAS alterations. Future research into disease progression with regard to malignancy risk and investigation of RAS-targeted therapies in OES is warranted. KRAS sequencing is clinically available and may also now improve OES diagnostic criteria. © 2015 Wiley Periodicals, Inc. PMID:25808193

  6. Genetic and environmental factors impact age-related impairment of negative geotaxis in Drosophila by altering age-dependent climbing speed

    PubMed Central

    Rhodenizer, Devin; Martin, Ian; Bhandari, Poonam; Pletcher, Scott D.; Grotewiel, Mike

    2008-01-01

    Age-related locomotor impairment in humans is important clinically because it is associated with several co-morbidities and increased risk of death. One of the hallmarks of age-related locomotor impairment in humans is a decrease in walking speed with age. Genetically tractable model organisms such as Drosophila are essential for delineating mechanisms underlying age-related locomotor impairment and age-related decreases in locomotor speed. Negative geotaxis, the ability of flies to move vertically when startled, is a common measure of locomotor behavior that declines with age in Drosophila. Toward further developing Drosophila as a model for age-related locomotor impairment, we investigated whether negative geotaxis reflects climbing or a combination of climbing and other behaviors such as flying and jumping. Additionally, we investigated whether locomotor speed in negative geotaxis assays declines with age in flies as found for walking speed in humans. We find that the vast majority of flies climb during negative geotaxis assays and that removal of hind legs, but not wings, impairs the behavior. We also find that climbing speed decreases with age in four wild type genetic backgrounds, in flies housed at different temperatures, and in control and long-lived flies harboring a mutation in OR83b. The decreases in climbing speed correlate with the age-related impairments in the distance climbed. These studies establish negative geotaxis in Drosophila as a climbing behavior that declines with age due to a decrease in climbing speed. Age-related decreases in locomotor speed are common attributes of locomotor senescence in flies and humans. PMID:18515028

  7. Radiosensitivity profiles from a panel of ovarian cancer cell lines exhibiting genetic alterations in p53 and disparate DNA-dependent protein kinase activities

    SciTech Connect

    Langland, Gregory T.; Yannone, Steven M.; Langland, Rachel A.; Nakao, Aki; Guan, Yinghui; Long, Sydney B.T.; Vonguyen, Lien; Chen, David J.; Gray, Joe W; Chen, Fanqing

    2009-09-07

    The variability of radiation responses in ovarian tumors and tumor-derived cell lines is poorly understood. Since both DNA repair capacity and p53 status can significantly alter radiation sensitivity, we evaluated these factors along with radiation sensitivity in a panel of sporadic human ovarian carcinoma cell lines. We observed a gradation of radiation sensitivity among these sixteen lines, with a five-fold difference in the LD50 between the most radiosensitive and the most radioresistant cells. The DNA-dependent protein kinase (DNA-PK) is essential for the repair of radiation induced DNA double-strand breaks in human somatic cells. Therefore, we measured gene copy number, expression levels, protein abundance, genomic copy and kinase activity for DNA-PK in all of our cell lines. While there were detectable differences in DNA-PK between the cell lines, there was no clear correlation with any of these differences and radiation sensitivity. In contrast, p53 function as determined by two independent methods, correlated well with radiation sensitivity, indicating p53 mutant ovarian cancer cells are typically radioresistant relative to p53 wild-type lines. These data suggest that the activity of regulatory molecules such as p53 may be better indicators of radiation sensitivity than DNA repair enzymes such as DNAPK in ovarian cancer.

  8. Genetic Deficiency of Mtdh Gene in Mice Causes Male Infertility via Impaired Spermatogenesis and Alterations in the Expression of Small Non-coding RNAs.

    PubMed

    Meng, Xiangbing; Yang, Shujie; Zhang, Yuping; Wang, Xinjun; Goodfellow, Renee X; Jia, Yichen; Thiel, Kristina W; Reyes, Henry D; Yang, Baoli; Leslie, Kimberly K

    2015-05-01

    Increased expression of metadherin (MTDH, also known as AEG-1 and 3D3/LYRIC) has been associated with drug resistance, metastasis, and angiogenesis in a variety of cancers. However, the specific mechanisms through which MTDH is involved in these processes remain unclear. To uncover these mechanisms, we generated Mtdh knock-out mice via a targeted disruption of exon 3. Homozygous Mtdh knock-out mice are viable, but males are infertile. The homozygous male mice present with massive loss of spermatozoa as a consequence of meiotic failure. Accumulation of ?-H2AX in spermatocytes of homozygous Mtdh knock-out mice confirms an increase in unrepaired DNA breaks. We also examined expression of the DNA repair protein Rad18, which is regulated by MTDH at the post-transcriptional level. In testes from Mtdh exon 3-deficient mice, Rad18 foci were increased in the lumina of the seminiferous tubules. The Piwi-interacting RNA (piRNA)-interacting protein Mili was expressed at high levels in testes from Mtdh knock-out mice. Accordingly, genome-wide small RNA deep sequencing demonstrated altered expression of piRNAs in the testes of Mtdh knock-out mice as compared with wild type mice. In addition, we observed significantly reduced expression of microRNAs (miRNAs) including miR-16 and miR-19b, which are known to be significantly reduced in the semen of infertile men. In sum, our observations indicate a crucial role for MTDH in male fertility and the DNA repair mechanisms required for normal spermatogenesis. PMID:25787082

  9. Genetic variation in the functional ENG allele inherited from the non-affected parent associates with presence of pulmonary arteriovenous malformation in hereditary hemorrhagic telangiectasia 1 (HHT1) and may influence expression of PTPN14.

    PubMed

    Letteboer, Tom G W; Benzinou, Michael; Merrick, Christopher B; Quigley, David A; Zhau, Kechen; Kim, Il-Jin; To, Minh D; Jablons, David M; van Amstel, Johannes K P; Westermann, Cornelius J J; Giraud, Sophie; Dupuis-Girod, Sophie; Lesca, Gaetan; Berg, Jonathan H; Balmain, Allan; Akhurst, Rosemary J

    2015-01-01

    HHT shows clinical variability within and between families. Organ site and prevalence of arteriovenous malformations (AVMs) depend on the HHT causative gene and on environmental and genetic modifiers. We tested whether variation in the functional ENG allele, inherited from the unaffected parent, alters risk for pulmonary AVM in HHT1 mutation carriers who are ENG haploinsufficient. Genetic association was found between rs10987746 of the wild type ENG allele and presence of pulmonary AVM [relative risk = 1.3 (1.0018-1.7424)]. The rs10987746-C at-risk allele associated with lower expression of ENG RNA in a panel of human lymphoblastoid cell lines (P = 0.004). Moreover, in angiogenically active human lung adenocarcinoma tissue, but not in uninvolved quiescent lung, rs10987746-C was correlated with expression of PTPN14 (P = 0.004), another modifier of HHT. Quantitative TAQMAN expression analysis in a panel of normal lung tissues from 69 genetically heterogeneous inter-specific backcross mice, demonstrated strong correlation between expression levels of Eng, Acvrl1, and Ptpn14 (r2 = 0.75-0.9, P < 1 × 10(-12)), further suggesting a direct or indirect interaction between these three genes in lung in vivo. Our data indicate that genetic variation within the single functional ENG gene influences quantitative and/or qualitative differences in ENG expression that contribute to risk of pulmonary AVM in HHT1, and provide correlative support for PTPN14 involvement in endoglin/ALK1 lung biology in vivo. PTPN14 has been shown to be a negative regulator of Yap/Taz signaling, which is implicated in mechanotransduction, providing a possible molecular link between endoglin/ALK1 signaling and mechanical stress. EMILIN2, which showed suggestive genetic association with pulmonary AVM, is also reported to interact with Taz in angiogenesis. Elucidation of the molecular mechanisms regulating these interactions in endothelial cells may ultimately provide more rational choices for HHT therapy. PMID:25815003

  10. RNA-binding proteins in human genetic disease

    Microsoft Academic Search

    Kiven E. Lukong; Kai-wei Chang; Edouard W. Khandjian; Stéphane Richard

    2008-01-01

    RNA-binding proteins (RBPs) are key components in RNA metabolism, regulating the temporal, spatial and functional dynamics of RNAs. Altering the expression of RBPs has profound implications for cellular physiology, affecting RNA processes from pre-mRNA splicing to protein translation. Recent genetic and proteomic data and evidence from animal models reveal that RBPs are involved in many human diseases ranging from neuro-

  11. Stroke status evoked adhesion molecule genetic alterations in astrocytes isolated from stroke-prone spontaneously hypertensive rats and the apigenin inhibition of their expression.

    PubMed

    Yamagata, Kazuo; Kitazawa, Takuya; Shinoda, Masahiro; Tagawa, Chika; Chino, Makoto; Matsufuji, Hiroshi

    2010-01-01

    We examined the possibility that the expression of adhesion molecules is regulated differently in cultured astrocytes from stroke-prone spontaneously hypertensive rats (SHRSP/IZM) rats than in those from Wistar Kyoto rats (WKY/IZM) by tumor necrosis factor-alpha (TNF-alpha) or hypoxia and reoxygenation (H/R) and the inhibitory effects of apigenin. It was found that the expression of vascular cell adhesion molecule-1 (VCAM-1) by TNF-alpha in astrocytes isolated from SHRSP/IZM was increased compared with that in WKY/IZM. The expression of monocyte chemotactic protein-1 (MCP-1) mRNA induced by H/R in SHRSP/IZM astrocytes was increased compared with that in normal oxygen concentrations. Apigenin strongly attenuated TNF-alpha-induced VCAM-1 mRNA and protein expression and suppressed the adhesion of U937 cells and SHRSP/IZM astrocytes. These results suggest that the expression levels of adhesion molecules during H/R affect disease outcome and can drive SHRSP/IZM to stroke. It is suggested that apigenin regulates adhesion molecule expression in reactive astrocytes during ischemia. PMID:20700422

  12. Stroke Status Evoked Adhesion Molecule Genetic Alterations in Astrocytes Isolated from Stroke-Prone Spontaneously Hypertensive Rats and the Apigenin Inhibition of Their Expression

    PubMed Central

    Yamagata, Kazuo; Kitazawa, Takuya; Shinoda, Masahiro; Tagawa, Chika; Chino, Makoto; Matsufuji, Hiroshi

    2010-01-01

    We examined the possibility that the expression of adhesion molecules is regulated differently in cultured astrocytes from stroke-prone spontaneously hypertensive rats (SHRSP/IZM) rats than in those from Wistar Kyoto rats (WKY/IZM) by tumor necrosis factor-alpha (TNF-?) or hypoxia and reoxygenation (H/R) and the inhibitory effects of apigenin. It was found that the expression of vascular cell adhesion molecule-1 (VCAM-1) by TNF-? in astrocytes isolated from SHRSP/IZM was increased compared with that in WKY/IZM. The expression of monocyte chemotactic protein-1 (MCP-1) mRNA induced by H/R in SHRSP/IZM astrocytes was increased compared with that in normal oxygen concentrations. Apigenin strongly attenuated TNF-?-induced VCAM-1 mRNA and protein expression and suppressed the adhesion of U937 cells and SHRSP/IZM astrocytes. These results suggest that the expression levels of adhesion molecules during H/R affect disease outcome and can drive SHRSP/IZM to stroke. It is suggested that apigenin regulates adhesion molecule expression in reactive astrocytes during ischemia. PMID:20700422

  13. Molecular and Genomic Alterations in Glioblastoma Multiforme.

    PubMed

    Crespo, Ines; Vital, Ana Louisa; Gonzalez-Tablas, María; Patino, María Del Carmen; Otero, Alvaro; Lopes, María Celeste; de Oliveira, Catarina; Domingues, Patricia; Orfao, Alberto; Tabernero, Maria Dolores

    2015-07-01

    In recent years, important advances have been achieved in the understanding of the molecular biology of glioblastoma multiforme (GBM); thus, complex genetic alterations and genomic profiles, which recurrently involve multiple signaling pathways, have been defined, leading to the first molecular/genetic classification of the disease. In this regard, different genetic alterations and genetic pathways appear to distinguish primary (eg, EGFR amplification) versus secondary (eg, IDH1/2 or TP53 mutation) GBM. Such genetic alterations target distinct combinations of the growth factor receptor-ras signaling pathways, as well as the phosphatidylinositol 3-kinase/phosphatase and tensin homolog/AKT, retinoblastoma/cyclin-dependent kinase (CDK) N2A-p16(INK4A), and TP53/mouse double minute (MDM) 2/MDM4/CDKN2A-p14(ARF) pathways, in cells that present features associated with key stages of normal neurogenesis and (normal) central nervous system cell types. This translates into well-defined genomic profiles that have been recently classified by The Cancer Genome Atlas Consortium into four subtypes: classic, mesenchymal, proneural, and neural GBM. Herein, we review the most relevant genetic alterations of primary versus secondary GBM, the specific signaling pathways involved, and the overall genomic profile of this genetically heterogeneous group of malignant tumors. PMID:25976245

  14. Genetic Targeting of an Adenovirus Vector via Replacement of the Fiber Protein with the Phage T4 Fibritin

    Microsoft Academic Search

    VICTOR KRASNYKH; NATALYA BELOUSOVA; NIKOLAY KOROKHOV; GALINA MIKHEEVA; DAVID T. CURIEL

    2001-01-01

    The utility of adenovirus (Ad) vectors for gene therapy is restricted by their inability to selectively transduce disease-affected tissues. This limitation may be overcome by the derivation of vectors capable of interacting with receptors specifically expressed in the target tissue. Previous attempts to alter Ad tropism by genetic modification of the Ad fiber have had limited success due to structural

  15. Genetic Recombination

    ERIC Educational Resources Information Center

    Whitehouse, H. L. K.

    1973-01-01

    Discusses the mechanisms of genetic recombination with particular emphasis on the study of the fungus Sordaria brevicollis. The study of recombination is facilitated by the use of mutants of this fungus in which the color of the ascospores is affected. (JR)

  16. Understanding Genetics of Deafness

    E-print Network

    Goodrich, Lisa V.

    of their parents are affected. This deafness can also be passed on to future generations. Genetic tests canUnderstanding the Genetics of Deafness A Guide for Patients and Families Harvard Medical School Center For Hereditary Deafness #12;Understanding the Genetics of Deafness A Guide for Patients

  17. Genetic instability in human tumors

    Microsoft Academic Search

    Stavroula Raptis; Bharati Bapat

    Genetic, or genomic, instability refers to a series of observed spontaneous genetic changes occurring at an accelerated rate in cell populations derived from the same ancestral precursor. This is far from a new finding, but is one that has increasingly gained more attention in the last decade due to its plausible role(s) in tumorigenesis. The majority of genetic alterations contributing

  18. The Impact of Biotechnology, in Particular Genetically Modified Crops on International Agricultural Research, Production and Marketing and How this will Affect Agriculture in Western Australia

    Microsoft Academic Search

    Sandy Forbes

    2003-01-01

    In 2000 I was awarded a Nuffield Farming Scholarship to study the impact of biotechnology, in particular genetically modified crops, on international agricultural research, production and marketing. I studied this topic in 2001 in Canada, USA and United Kingdom in an attempt to gain an insight into the issues with GM crops and how this may impact on our decision

  19. Insulin-like growth factor-I treatment and genetic variation affect changes in indices of protein degradation in response to food deprivation in rainbow trout (Oncorhynchus mykiss)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study determined the effect of genetic variation, feed deprivation and IGF-I treatment on weight loss, plasma IGF-I and GH, and indices of protein degradation in eight full-sibling families of rainbow trout. After two weeks of feed deprivation, fish treated with IGF-I lost 16% less (P<0.05) wet...

  20. A genetic study of autism in Costa Rica: multiple variables affecting IQ scores observed in a preliminary sample of autistic cases

    Microsoft Academic Search

    L Alison McInnes; Patricia Jiménez González; Elina R Manghi; Marcela Esquivel; Silvia Monge; Marietha Fallas Delgado; Eduardo Fournier; Pamela Bondy; Kathryn Castelle

    2005-01-01

    BACKGROUND: Autism is a heritable developmental disorder of communication and socialization that has not been well studied in Hispanic populations. Therefore, we are collecting and evaluating all possible cases of autism from a population isolate in the Central Valley of Costa Rica (CVCR) for a clinical and genetic study. METHODS: We are assessing all subjects and parents, as appropriate, using

  1. SNPping away at the genetic basis of adolescent idiopathic scoliosis

    PubMed Central

    2015-01-01

    Adolescent idiopathic scoliosis (AIS) is a genetically complex disorder of spine development, defined by a lateral curvature of the spine of 10º or greater which affects children during their pubertal growth spurt. Prior linkage and candidate gene approaches to elucidating the genetic basis of AIS have been of limited use for identification of candidate genes for this condition. Genome wide association studies (GWAS) have recently identified single nucleotide polymorphisms (SNPs) in LBX1 and G protein-coupled receptor 126 (GPR126) that contribute to AIS occurrence. These discoveries support prior etiologic hypotheses regarding altered somatosensory function and skeletal growth in AIS. However, these loci account for a small percentage of the phenotypic variance associated with AIS, indicating the vast majority of the genetic causes of AIS remain to be delineated. A major translational application regarding understanding the genetic contributions to AIS relates to bracing efficacy. PMID:26046072

  2. SNPping away at the genetic basis of adolescent idiopathic scoliosis.

    PubMed

    Giampietro, Philip F

    2015-05-01

    Adolescent idiopathic scoliosis (AIS) is a genetically complex disorder of spine development, defined by a lateral curvature of the spine of 10º or greater which affects children during their pubertal growth spurt. Prior linkage and candidate gene approaches to elucidating the genetic basis of AIS have been of limited use for identification of candidate genes for this condition. Genome wide association studies (GWAS) have recently identified single nucleotide polymorphisms (SNPs) in LBX1 and G protein-coupled receptor 126 (GPR126) that contribute to AIS occurrence. These discoveries support prior etiologic hypotheses regarding altered somatosensory function and skeletal growth in AIS. However, these loci account for a small percentage of the phenotypic variance associated with AIS, indicating the vast majority of the genetic causes of AIS remain to be delineated. A major translational application regarding understanding the genetic contributions to AIS relates to bracing efficacy. PMID:26046072

  3. Genomic and transcriptomic alterations following hybridisation and genome doubling in trigenomic allohexaploid Brassica carinata?×?Brassica rapa.

    PubMed

    Xu, Y; Zhao, Q; Mei, S; Wang, J

    2012-02-01

    Allopolyploidisation is a prominent evolutionary force that involves two major events: interspecific hybridisation and genome doubling. Both events have important functional consequences in shaping the genomic architecture of the neo-allopolyploids. The respective effects of hybridisation and genome doubling upon genomic and transcriptomic changes in Brassica allopolyploids are unresolved. In this study, amplified fragment length polymorphism (AFLP), methylation-sensitive amplification polymorphism (MSAP) and cDNA-AFLP approaches were used to track genetic, epigenetic and transcriptional changes in both allohexaploid Brassica (ArArBcBcCcCc genome) and triploid hybrids (ArBcCc genome). Results from these groups were compared with each other and also to their parents Brassica carinata (BBCC genome) and Brassica rapa (AA genome). Rapid and dramatic genetic, DNA methylation and gene expression changes were detected in the triploid hybrids. During the shift from triploidy to allohexaploidy, some of the hybridisation-induced alterations underwent reversion. Additionally, novel genetic, epigenetic and transcriptional alterations were also detected. The proportions of A-genome-specific DNA methylation and gene expression alterations were significantly greater than those of BC-genome-specific alterations in the triploid hybrids. However, the two parental genomes were equally affected during the ploidy shift. Hemi-CCG methylation changes induced by hybridisation were recovered after genome doubling. Full-CG methylation changes were a more general process initiated in the hybrid and continued after genome doubling. These results indicate that genome doubling could ameliorate genomic and transcriptomic alterations induced by hybridisation and instigate additional alterations in trigenomic Brassica allohexaploids. Moreover, genome doubling also modified hybridisation-induced progenitor genome-biased alterations and epigenetic alteration characteristics. PMID:22309095

  4. Genetics and genomics of neuroblastoma.

    PubMed

    Capasso, Mario; Diskin, Sharon J

    2010-01-01

    Neuroblastoma is a pediatric cancer of the developing sympathetic nervous system that most often affects young children. It remains an important pediatric problem because it accounts for approximately 15% of childhood cancer mortality. The disease is clinically heterogeneous, with the likelihood of cure varying greatly according to age at diagnosis, extent of disease, and tumor biology. This extreme clinical heterogeneity reflects the complexity of genetic and genomic events associated with development and progression of disease. Inherited genetic variants and mutations that initiate tumorigenesis have been identified in neuroblastoma and multiple somatically acquired genomic alterations have been described that are relevant to disease progression. This chapter focuses on recent genome-wide studies that have utilized high-density single nucleotide polymorphism (SNP) genotyping arrays to discover genetic factors predisposing to tumor initiation such as rare mutations at locus 2p23 (in ALK gene) for familial neuroblastoma, common SNPs at 6p22 (FLJ22536 and FLJ44180) and 2q35 (BARD1), and a copy number polymorphism at 1q21.1 (NBPF23) for sporadic neuroblastoma. It also deals with well known and recently reported somatic changes in the tumor genome such as mutations, gain of alleles and activation of oncogenes, loss of alleles, or changes in tumor-cell ploidy leading to the diverse clinical behavior of neuroblastomas. Finally, this chapter reviews gene expression profiles of neuroblastoma associated with pathways of the signaling of neurotrophins and apoptotic factors that could have a role in neuroblastoma development and progression. Looking forward, a major challenge will be to understand how inherited genetic variation and acquired somatic alterations in the tumor genome interact to exact phenotypic differences in neuroblastoma, and cancer in general. PMID:20517688

  5. Altered Vision Near the Hands

    ERIC Educational Resources Information Center

    Abrams, Richard A.; Davoli, Christopher C.; Du, Feng; Knapp, William H., III; Paull, Daniel

    2008-01-01

    The present study explored the manner in which hand position may affect visual processing. We studied three classic visual attention tasks (visual search, inhibition of return, and attentional blink) during which the participants held their hands either near the stimulus display, or far from the display. Remarkably, the hands altered visual…

  6. Copyright 2011 by the Genetics Society of America DOI: 10.1534/genetics.110.125997

    E-print Network

    Plotkin, Joshua B.

    Copyright Ó 2011 by the Genetics Society of America DOI: 10.1534/genetics.110.125997 Epistasis an influential justification for the idea of a molecular clock and emphasized the importance of genetic drift that do not alter the fitness of the individual in which they arise, but that may alter the fitness

  7. Biotic interactions and sunlight affect persistence of fecal indicator bacteria and microbial source tracking genetic markers in the upper Mississippi river.

    PubMed

    Korajkic, Asja; McMinn, Brian R; Shanks, Orin C; Sivaganesan, Mano; Fout, G Shay; Ashbolt, Nicholas J

    2014-07-01

    The sanitary quality of recreational waters that may be impacted by sewage is assessed by enumerating fecal indicator bacteria (FIB) (Escherichia coli and enterococci); these organisms are found in the gastrointestinal tracts of humans and many other animals, and hence their presence provides no information about the pollution source. Microbial source tracking (MST) methods can discriminate between different pollution sources, providing critical information to water quality managers, but relatively little is known about factors influencing the decay of FIB and MST genetic markers following release into aquatic environments. An in situ mesocosm was deployed at a temperate recreational beach in the Mississippi River to evaluate the effects of ambient sunlight and biotic interactions (predation, competition, and viral lysis) on the decay of culture-based FIB, as well as molecularly based FIB (Entero1a and GenBac3) and human-associated MST genetic markers (HF183 and HumM2) measured by quantitative real-time PCR (qPCR). In general, culturable FIB decayed the fastest, while molecularly based FIB and human-associated genetic markers decayed more slowly. There was a strong correlation between the decay of molecularly based FIB and that of human-associated genetic markers (r(2), 0.96 to 0.98; P < 0.0001) but not between culturable FIB and any qPCR measurement. Overall, exposure to ambient sunlight may be an important factor in the early-stage decay dynamics but generally was not after continued exposure (i.e., after 120 h), when biotic interactions tended to be the only/major influential determinant of persistence. PMID:24747902

  8. Biotic Interactions and Sunlight Affect Persistence of Fecal Indicator Bacteria and Microbial Source Tracking Genetic Markers in the Upper Mississippi River

    PubMed Central

    McMinn, Brian R.; Shanks, Orin C.; Sivaganesan, Mano; Fout, G. Shay; Ashbolt, Nicholas J.

    2014-01-01

    The sanitary quality of recreational waters that may be impacted by sewage is assessed by enumerating fecal indicator bacteria (FIB) (Escherichia coli and enterococci); these organisms are found in the gastrointestinal tracts of humans and many other animals, and hence their presence provides no information about the pollution source. Microbial source tracking (MST) methods can discriminate between different pollution sources, providing critical information to water quality managers, but relatively little is known about factors influencing the decay of FIB and MST genetic markers following release into aquatic environments. An in situ mesocosm was deployed at a temperate recreational beach in the Mississippi River to evaluate the effects of ambient sunlight and biotic interactions (predation, competition, and viral lysis) on the decay of culture-based FIB, as well as molecularly based FIB (Entero1a and GenBac3) and human-associated MST genetic markers (HF183 and HumM2) measured by quantitative real-time PCR (qPCR). In general, culturable FIB decayed the fastest, while molecularly based FIB and human-associated genetic markers decayed more slowly. There was a strong correlation between the decay of molecularly based FIB and that of human-associated genetic markers (r2, 0.96 to 0.98; P < 0.0001) but not between culturable FIB and any qPCR measurement. Overall, exposure to ambient sunlight may be an important factor in the early-stage decay dynamics but generally was not after continued exposure (i.e., after 120 h), when biotic interactions tended to be the only/major influential determinant of persistence. PMID:24747902

  9. Factors affecting maternal participation in the genetic component of the National Birth Defects Prevention Study—United States, 1997–2007

    PubMed Central

    Glidewell, Jill; Reefhuis, Jennita; Rasmussen, Sonja A.; Woomert, Alison; Hobbs, Charlotte; Romitti, Paul A.; Crider, Krista S.

    2015-01-01

    Purpose As epidemiological studies expand to examine gene–environment interaction effects, it is important to identify factors associated with participation in genetic studies. The National Birth Defects Prevention Study is a multisite case–control study designed to investigate environmental and genetic risk factors for major birth defects. The National Birth Defects Prevention Study includes maternal telephone interviews and mailed buccal cell self-collection kits. Because subjects can participate in the interview, independent of buccal cell collection, detailed analysis of factors associated with participation in buccal cell collection was possible. Methods Multivariable logistic regression models were used to identify the factors associated with participation in the genetic component of the study. Results Buccal cell participation rates varied by race/ethnicity (non-Hispanic whites, 66.9%; Hispanics, 60.4%; and non-Hispanic blacks, 47.3%) and study site (50.2–74.2%). Additional monetary incentive following return of buccal cell kit and shorter interval between infant’s estimated date of delivery and interview were associated with increased participation across all racial/ethnic groups. Higher education and delivering an infant with a birth defect were associated with increased participation among non-Hispanic whites and Hispanics. Conclusion Factors associated with participation varied by race/ethnicity. Improved understanding of factors associated with participation may facilitate strategies to increase participation, thereby improving generalizability of study findings. PMID:24071796

  10. Genotyping-by-sequencing approach indicates geographic distance as the main factor affecting genetic structure and gene flow in Brazilian populations of Grapholita molesta (Lepidoptera, Tortricidae).

    PubMed

    Silva-Brandão, Karina Lucas; Silva, Oscar Arnaldo Batista Neto E; Brandão, Marcelo Mendes; Omoto, Celso; Sperling, Felix A H

    2015-06-01

    The oriental fruit moth Grapholita molesta is one of the major pests of stone and pome fruit species in Brazil. Here, we applied 1226 SNPs obtained by genotyping-by-sequencing to test whether host species associations or other factors such as geographic distance structured populations of this pest. Populations from the main areas of occurrence of G. molesta were sampled principally from peach and apple orchards. Three main clusters were recovered by neighbor-joining analysis, all defined by geographic proximity between sampling localities. Overall genetic structure inferred by a nonhierarchical amova resulted in a significant ?ST value = 0.19109. Here, we demonstrate for the first time that SNPs gathered by genotyping-by-sequencing can be used to infer genetic structure of a pest insect in Brazil; moreover, our results indicate that those markers are very informative even over a restricted geographic scale. We also demonstrate that host plant association has little effect on genetic structure among Brazilian populations of G. molesta; on the other hand, reduced gene flow promoted by geographic isolation has a stronger impact on population differentiation. PMID:26029261

  11. Genetic variation of lodgepole pine, Pinus contorta var. latifolia, chemical and physical defenses that affect mountain pine beetle, Dendroctonus ponderosae, attack and tree mortality.

    PubMed

    Ott, Daniel S; Yanchuk, Alvin D; Huber, Dezene P W; Wallin, Kimberly F

    2011-09-01

    Plant secondary chemistry is determined by both genetic and environmental factors, and while large intraspecific variation in secondary chemistry has been reported frequently, the levels of genetic variation of many secondary metabolites in forest trees in the context of potential resistance against pests have been rarely investigated. We examined the effect of tree genotype and environment/site on the variation in defensive secondary chemistry of lodgepole pine, Pinus contorta var. latifolia, against the fungus, Grosmannia clavigera (formerly known as Ophiostoma clavigerum), associated with the mountain pine beetle, Dendroctonus ponderosae. Terpenoids were analyzed in phloem samples from 887, 20-yr-old trees originating from 45 half-sibling families planted at two sites. Samples were collected both pre- and post-inoculation with G. clavigera. Significant variation in constitutive and induced terpenoid compounds was attributed to differences among families. The response to the challenge inoculation with G. clavigera was strong for some individual compounds, but primarily for monoterpenoids. Environment (site) also had a significant effect on the accumulation of some compounds, whereas for others, no significant environmental effect occurred. However, for a few compounds significant family x environment interactions were found. These results suggest that P. c. latifolia secondary chemistry is under strong genetic control, but the effects depend on the individual compounds and whether or not they are expressed constitutively or following induction. PMID:21845434

  12. Increased total number of genetic aberrations and changes affecting specific chromosomal regions may underlie prostate cancer recurrence and development of hormone-independent growth

    SciTech Connect

    Hyytinen, E.; Visakorpi, T.; Kallioniemi, A. [Tampere Univ. Hospital (Finland)] [and others

    1994-09-01

    At the time of diagnosis, prostate carcinomas are often rather slowly proliferating and shows a favorable response to anti-androgen treatment. However, often the tumors metastasize or recur locally and thereafter show an aggressive behavior and rapid growth despite of the endocrine therapy. In order to understand the genetic basis of this change in phenotype and clinical behavior, we used comparative genomic hybridization to analyze for losses and gains of DNA sequences along all human chromosomes in primary prostate carcinomas as well as in local recurrencies during hormonal therapy. The total number of genetic changes in 9 recurrences was almost three times higher than that observed in 31 primary prostate carcinomas. Whereas gains and amplifications were only seen in 6/31 primary tumors, all recurrences showed gains of at least one chromosomal site. Gain of 8q was seen at 89% of recurrences as compared to 6% in the primary tumors. Other prominent increases of prevalence were +X (56% vs. 0%), +7 (50% vs. 6%), and 8p- (78% vs. 32%). In one case where DNA was available from both the primary tumor and recurrence of the same patient, appearance of some of these gains during tumor progression was validated. Analysis of archival formalin-fixed paraffin-embedded tissues by CGH is in progress and will make it possible to extensively compare genetic changes between the primary tumor and its local recurrence or metastasis.

  13. Genotyping-by-sequencing approach indicates geographic distance as the main factor affecting genetic structure and gene flow in Brazilian populations of Grapholita molesta (Lepidoptera, Tortricidae)

    PubMed Central

    Silva-Brandão, Karina Lucas; Silva, Oscar Arnaldo Batista Neto e; Brandão, Marcelo Mendes; Omoto, Celso; Sperling, Felix A H

    2015-01-01

    The oriental fruit moth Grapholita molesta is one of the major pests of stone and pome fruit species in Brazil. Here, we applied 1226 SNPs obtained by genotyping-by-sequencing to test whether host species associations or other factors such as geographic distance structured populations of this pest. Populations from the main areas of occurrence of G. molesta were sampled principally from peach and apple orchards. Three main clusters were recovered by neighbor-joining analysis, all defined by geographic proximity between sampling localities. Overall genetic structure inferred by a nonhierarchical amova resulted in a significant ?ST value = 0.19109. Here, we demonstrate for the first time that SNPs gathered by genotyping-by-sequencing can be used to infer genetic structure of a pest insect in Brazil; moreover, our results indicate that those markers are very informative even over a restricted geographic scale. We also demonstrate that host plant association has little effect on genetic structure among Brazilian populations of G. molesta; on the other hand, reduced gene flow promoted by geographic isolation has a stronger impact on population differentiation. PMID:26029261

  14. The devil is in the details: genetic variation in introduced populations and its contributions to invasion.

    PubMed

    Dlugosch, Katrina M; Anderson, Samantha R; Braasch, Joseph; Cang, F Alice; Gillette, Heather D

    2015-05-01

    The influence of genetic variation on invasion success has captivated researchers since the start of the field of invasion genetics 50 years ago. We review the history of work on this question and conclude that genetic variation-as surveyed with molecular markers-appears to shape invasion rarely. Instead, there is a significant disconnect between marker assays and ecologically relevant genetic variation in introductions. We argue that the potential for adaptation to facilitate invasion will be shaped by the details of genotypes affecting phenotypes, and we highlight three areas in which we see opportunities to make powerful new insights. (i) The genetic architecture of adaptive variation. Traits shaped by large-effect alleles may be strongly impacted by founder events yet more likely to respond to selection when genetic drift is strong. Large-effect loci may be especially relevant for traits involved in biotic interactions. (ii) Cryptic genetic variation exposed during invasion. Introductions have strong potential to uncover masked variation due to alterations in genetic and ecological environments. (iii) Genetic interactions during admixture of multiple source populations. As divergence among sources increases, positive followed by increasingly negative effects of admixture should be expected. Although generally hypothesized to be beneficial during invasion, admixture is most often reported among sources of intermediate divergence, supporting the possibility that incompatibilities among divergent source populations might be limiting their introgression. Finally, we note that these details of invasion genetics can be coupled with comparative demographic analyses to link genetic changes to the evolution of invasiveness itself. PMID:25846825

  15. Genetics and the environment affect the relationship between depression and low back pain: a co-twin control study of Spanish twins.

    PubMed

    Pinheiro, Marina B; Ferreira, Manuela L; Refshauge, Kathryn; Colodro-Conde, Lucía; Carrillo, Eduvigis; Hopper, John L; Ordoñana, Juan R; Ferreira, Paulo H

    2015-03-01

    Although the co-occurrence of low back pain (LBP) and depression is common, the nature of this association remains unclear. We aimed to investigate whether symptoms of depression are associated with LBP after adjusting for various confounders, including genetics. We used cross-sectional data from 2148 twins from the Murcia Twin Registry, Spain. All twins answered questions about lifetime prevalence of LBP (outcome variable) and symptoms of depression, collected through two instruments, deriving 3 measures: (1) self-report feelings of depression and anxiety; (2) state depression, and (3) trait depression. First, associations were investigated using logistic regression analysis of the total sample. We performed subsequent matched within-pair twin case-control analyses with all complete twin pairs discordant for LBP regardless of zygosity, and separately for dizygotic and monozygotic pairs. This sequential analysis allows for more precise estimates of the relationship between variables, as in each step, the impact of early shared environment and genetics is further considered. Symptoms of depression and anxiety were associated with higher prevalence of LBP in the total sample analysis (odds ratio [OR], 1.64; 95% confidence interval [CI], 1.31-2.05), and this relationship was stronger in the subsequent case-control analysis (OR, 1.74; 95% CI, 1.13-2.69) and dizygotic case-control analysis (OR, 2.39; 95% CI, 1.39-4.08) but disappeared when the analysis was conducted for monozygotic twins (OR, 0.92; 95% CI, 0.42-2.05). A similar pattern was found for state and trait depression. The depression-LBP relationship disappears when high levels of control for confounding factors are applied and seems to be driven by genetic or environmental factors that influence both conditions. PMID:25679471

  16. Short Communication: Composition of Milk Protein and Milk Fatty Acids Is Stable for Cows Differing in Genetic Merit for Milk Production1

    Microsoft Academic Search

    G. Bobe; G. L. Lindberg; A. E. Freeman; D. C. Beitz

    2007-01-01

    Changing the composition of milk protein and of milk fatty acids alters nutritional and physical properties of dairy products and their consumer appeal. Genetic selection formilk yield decreases concentrationsof milk protein and of milk fat. Little is known, however, about how the decrease affects composition of milk protein and milk fatty acids. The objective of this study was to quantify

  17. Genetic and environmental factors affecting growth and reproductive performance of Santa Ines sheep in the semi-arid region of Brazil 

    E-print Network

    Sousa, Wandrick Hauss de

    1987-01-01

    GE?1ETIC AND ENVIRiONMENPAL FACTORS Ar FEC ING GROStTH AND REPRODUCTIVE PERFORYJ1jCE OF SAN A INES SHEEP IN THE SEMI-ARID REGIONi OF BRAZIL A T'ress s WANDRICX HAUSS DE SOUSA Submitted to the Graduate College of Tesas ARMi Unsversity... OF BRAZIL A Thesis by WANDRICK HAUSS DE SOUSA Approved as to style and content by: Thomas C. Cartwri t (Co-Chairman) (Co-Chairman) ( /'(' ~ t:. . \\ , Bo y J. Ragsdale (Member) Gary C. Smith (Head of Department) December 1987 ABSTRACT Genetic...

  18. Lack of Evidence for Increased Genetic Loading for Autism among Families of Affected Females: A Replication from Family History Data in Two Large Samples

    ERIC Educational Resources Information Center

    Goin-Kochel, Robin P.; Abbacchi, Anna; Constantino, John N.

    2007-01-01

    Both the broad and narrow phenotypes of autism have been consistently observed in family members of affected individuals. Additionally, autism spectrum disorders (ASDs) present four times more often in males than in females, for reasons that are currently unknown. In this study, we examined whether there were differences in familial loading of ASD…

  19. Genetic determinism of phenological traits highly affected by climate change in Prunus avium: flowering date dissected into chilling and heat requirements.

    PubMed

    Castède, Sophie; Campoy, José Antonio; García, José Quero; Le Dantec, Loïck; Lafargue, Maria; Barreneche, Teresa; Wenden, Bénédicte; Dirlewanger, Elisabeth

    2014-04-01

    The present study investigated the genetic determinism of flowering date (FD), dissected into chilling (CR) and heat (HR) requirements. Elucidation of the genetic determinism of flowering traits is crucial to anticipate the increasing of ecological misalignment of adaptative traits with novel climate conditions in most temperate-fruit species. CR and HR were evaluated over 3 yr and FD over 5 yr in an intraspecific sweet cherry (Prunus avium) F1 progeny, and FD over 6 yr in a different F1 progeny. One quantitative trait locus (QTL) with major effect and high stability between years of evaluation was detected for CR and FD in the same region of linkage group (LG) 4. For HR, no stable QTL was detected. Candidate genes underlying the major QTL on LG4 were investigated and key genes were identified for CR and FD. Phenotypic dissection of FD and year repetitions allowed us to identify CR as the high heritable component of FD and a high genotype × environment interaction for HR. QTLs for CR reported in this study are the first described in this species. Our results provide a foundation for the identification of genes involved in CR and FD in sweet cherry which could be used to develop ideotypes adapted to future climatic conditions. PMID:24417538

  20. Detection of QTL for metabolic and agronomic traits in wheat with adjustments for variation at genetic loci that affect plant phenology.

    PubMed

    Hill, Camilla B; Taylor, Julian D; Edwards, James; Mather, Diane; Langridge, Peter; Bacic, Antony; Roessner, Ute

    2015-04-01

    Mapping of quantitative trait loci associated with levels of individual metabolites (mQTL) was combined with the mapping of agronomic traits to investigate the genetic basis of variation and co-variation in metabolites, agronomic traits, and plant phenology in a field-grown bread wheat population. Metabolome analysis was performed using liquid chromatography-mass spectrometry resulting in identification of mainly polar compounds, including secondary metabolites. A total of 558 metabolic features were obtained from the flag leaves of 179 doubled haploid lines, of which 197 features were putatively identified, mostly as alkaloids, flavonoids and phenylpropanoids. Coordinated genetic control was observed for several groups of metabolites, such as organic acids influenced by two loci on chromosome 7A. Five major phenology-related loci, which were introduced as cofactors in the analyses, differed in their impact upon metabolic and agronomic traits with QZad-aww-7A having more impact on the expression of both metabolite and agronomic QTL than Ppd-B1, Vrn-A1, Eps, and QZad-aww-7D. This QTL study validates the utility of combining agronomic and metabolomic traits as an approach to identify potential trait enhancement targets for breeding selection and reinforces previous results that demonstrate the importance of including plant phenology in the assessment of useful traits in this wheat mapping population. PMID:25711822

  1. Genetics Home Reference: Congenital hypothyroidism

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Congenital hypothyroidism On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed May 2006 What is congenital hypothyroidism? Congenital hypothyroidism is a condition that affects infants ...

  2. Genetics Home Reference: Job syndrome

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Job syndrome On this page: Description Genetic changes Inheritance ... names Glossary definitions Reviewed February 2008 What is Job syndrome? Job syndrome is a condition that affects ...

  3. Genetics Home Reference: Systemic scleroderma

    MedlinePLUS

    ... Recent literature OMIM Genetic disorder catalog Conditions > Systemic scleroderma On this page: Description Genetic changes Inheritance Diagnosis ... Glossary definitions Reviewed April 2015 What is systemic scleroderma? Systemic scleroderma is an autoimmune disorder that affects ...

  4. The mineralization phenotype in Abcc6 ( -/- ) mice is affected by Ggcx gene deficiency and genetic background--a model for pseudoxanthoma elasticum.

    PubMed

    Li, Qiaoli; Uitto, Jouni

    2010-02-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive disorder characterized by ectopic mineralization of connective tissues and shows considerable intra- and inter-familial phenotypic variability. PXE is caused by mutations in the ABCC6 gene, and targeted ablation of Abcc6 in mouse recapitulates PXE. In this study, we examined the hypothesis that the GGCX gene encoding gamma-glutamyl carboxylase may interfere with the mineralization process in Abcc6 ( -/- ) mice. Thus, Abcc6 ( -/- ) and Ggcx (+/-) mice were generated on 129S1;C57 and 129S1;129X1;C57 genetic backgrounds, respectively, and backcrossed with C57BL/6J for five generations. Thus, these strains differ by the 129X1 contribution to the background of the mice. We then generated Abcc6 ( -/- ) ;Ggcx (+/+) and Abcc6 ( -/- ) ;Ggcx (+/-) mice by crossing Abcc6 ( -/- ) and Ggcx (+/-) mice. The degree of mineralization of connective capsule of vibrissae, a biomarker of the mineralization process in PXE, was evaluated by computerized morphometric analysis and quantified colorimetrically by calcium and phosphate levels in tissues. The mineralization of the vibrissae in Abcc6 ( -/- ) mice takes place at approximately 5-6 weeks of age and is significantly enhanced at 3 months of age in comparison to wild-type mice (>10-fold, p < 0.001). However, the onset of mineralization in Abcc6 ( -/- ) ;Ggcx (+/+) mice was delayed until between 3 and 4 months of age, suggesting that the genetic background plays a role in modifying the mineralization process. The mineralization in the Abcc6 ( -/- ) ;Ggcx (+/- ) mice was accelerated in comparison with age-matched Abcc6 ( -/- ) ;Ggcx (+/+) mice, with approximately 3-fold difference at 3, 4, and 9 months of age (p < 0.01). The mineralization process was also accelerated in these mice by a special custom-designed diet with mineral modifications. These findings suggest a role for both the GGCX gene and the genetic background as well as dietary factors in modulating the phenotypic severity of PXE caused by loss-of-function mutations in ABCC6. PMID:19784827

  5. Common Genetic Variants of Microsomal Epoxide Hydrolase Affect Warfarin Dose Requirements Beyond the Effect of Cytochrome P450 2C9

    Microsoft Academic Search

    Ronen Loebstein; Manuela Vecsler; Daniel Kurnik; Naomi Austerweil; Eva Gak; Hillel Halkin; Shlomo Almog

    2005-01-01

    Background: Warfarin dose response is partially explained by the polymorphisms in the cytochrome P450 (CYP) 2C9 gene, affecting S-warfarin clearance, as well as by age and body weight. We examined the influence on warfarin dose requirements of candidate genes encoding microsomal epoxide hydrolase (mEH), as well as glutathione S-transferase A1 (GSTA1) components of vitamin K epoxide reductase and the ?-glutamylcarboxylase

  6. Unifying Genetic Canalization, Genetic Constraint, and Genotype-by-Environment Interaction: QTL by Genomic Background by Environment Interaction of Flowering Time in Boechera stricta

    PubMed Central

    Lee, Cheng-Ruei; Anderson, Jill T.; Mitchell-Olds, Thomas

    2014-01-01

    Natural populations exhibit substantial variation in quantitative traits. A quantitative trait is typically defined by its mean and variance, and to date most genetic mapping studies focus on loci altering trait means but not (co)variances. For single traits, the control of trait variance across genetic backgrounds is referred to as genetic canalization. With multiple traits, the genetic covariance among different traits in the same environment indicates the magnitude of potential genetic constraint, while genotype-by-environment interaction (GxE) concerns the same trait across different environments. While some have suggested that these three attributes of quantitative traits are different views of similar concepts, it is not yet clear, however, whether they have the same underlying genetic mechanism. Here, we detect quantitative trait loci (QTL) influencing the (co)variance of phenological traits in six distinct environments in Boechera stricta, a close relative of Arabidopsis. We identified nFT as the QTL altering the magnitude of phenological trait canalization, genetic constraint, and GxE. Both the magnitude and direction of nFT's canalization effects depend on the environment, and to our knowledge, this reversibility of canalization across environments has not been reported previously. nFT's effects on trait covariance structure (genetic constraint and GxE) likely result from the variable and reversible canalization effects across different traits and environments, which can be explained by the interaction among nFT, genomic backgrounds, and environmental stimuli. This view is supported by experiments demonstrating significant nFT by genomic background epistatic interactions affecting phenological traits and expression of the candidate gene, FT. In contrast to the well-known canalization gene Hsp90, the case of nFT may exemplify an alternative mechanism: Our results suggest that (at least in traits with major signal integrators such as flowering time) genetic canalization, genetic constraint, and GxE may have related genetic mechanisms resulting from interactions among major QTL, genomic backgrounds, and environments. PMID:25340779

  7. Unifying genetic canalization, genetic constraint, and genotype-by-environment interaction: QTL by genomic background by environment interaction of flowering time in Boechera stricta.

    PubMed

    Lee, Cheng-Ruei; Anderson, Jill T; Mitchell-Olds, Thomas

    2014-10-01

    Natural populations exhibit substantial variation in quantitative traits. A quantitative trait is typically defined by its mean and variance, and to date most genetic mapping studies focus on loci altering trait means but not (co)variances. For single traits, the control of trait variance across genetic backgrounds is referred to as genetic canalization. With multiple traits, the genetic covariance among different traits in the same environment indicates the magnitude of potential genetic constraint, while genotype-by-environment interaction (GxE) concerns the same trait across different environments. While some have suggested that these three attributes of quantitative traits are different views of similar concepts, it is not yet clear, however, whether they have the same underlying genetic mechanism. Here, we detect quantitative trait loci (QTL) influencing the (co)variance of phenological traits in six distinct environments in Boechera stricta, a close relative of Arabidopsis. We identified nFT as the QTL altering the magnitude of phenological trait canalization, genetic constraint, and GxE. Both the magnitude and direction of nFT's canalization effects depend on the environment, and to our knowledge, this reversibility of canalization across environments has not been reported previously. nFT's effects on trait covariance structure (genetic constraint and GxE) likely result from the variable and reversible canalization effects across different traits and environments, which can be explained by the interaction among nFT, genomic backgrounds, and environmental stimuli. This view is supported by experiments demonstrating significant nFT by genomic background epistatic interactions affecting phenological traits and expression of the candidate gene, FT. In contrast to the well-known canalization gene Hsp90, the case of nFT may exemplify an alternative mechanism: Our results suggest that (at least in traits with major signal integrators such as flowering time) genetic canalization, genetic constraint, and GxE may have related genetic mechanisms resulting from interactions among major QTL, genomic backgrounds, and environments. PMID:25340779

  8. Genetics/genomics and drug effects.

    PubMed

    Heller, F

    2013-01-01

    Differences in response to medications both in terms of clinical activity and side-effects have long been recognised by physicians. Genetics has been recently considered as a potential factor to explain part of this variability. Pharmacogenetics focuses on the variants within one or more candidate genes while pharmacogenomics evaluates the entire genome for associations with pharmacologic phenotypes. Genetic variants can effect drug metabolism, drug transport or drug targets. Drug metabolism is responsible 1. for the conversion of prodrugs into active compounds or conversion of drug to toxic or inactive metabolites mostly through reactions mostly catalysed by cytochromes (CYP) P450 (phase reactions) and 2. for transforming drugs to compounds that are more water soluble and more easily excreted (phase type II reactions). Genetic polymorphisms can modify the activity of several CYPs such as CYPs, 2D6, 2C9, 2C19 with altered responses to codeine, tamoxifen, clopidogrel, warfarin, ... or of enzymes of the phase II reactions with abnormal responses to drugs like irinotecan, 5-fluorouracil, azathioprine, ... Proteins involved in the transport of drugs in or out the cells such as chemiotherapeutic agenrs, simvastatin, ... can also be affected by genetics. Genetics can also modify drug targets by mutations affecting tumour cells rending these later more or less responsive to drugs. Genetic tests have been launched for screening polymorphisms before giving drugs such as warfarin and several biomarkers are available in oncology. However, many challenges exist. For example, we need more prospective studies to have a better knowledge of the clinical impact and the cost-effectiveness of these tests. It remains that in the future pharmacogenetics/genomics will probably help to personalise medicine by conferring to the clinician the possibility of giving the right drug to the right patients and by this way improving efficacy and safety of medications. PMID:23967712

  9. Cyclin-Dependent Kinase 7 Controls mRNA Synthesis by Affecting Stability of Preinitiation Complexes, Leading to Altered Gene Expression, Cell Cycle Progression, and Survival of Tumor Cells

    PubMed Central

    Kelso, Timothy W. R.; Baumgart, Karen; Eickhoff, Jan; Albert, Thomas; Antrecht, Claudia; Lemcke, Sarah; Klebl, Bert

    2014-01-01

    Cyclin-dependent kinase 7 (CDK7) activates cell cycle CDKs and is a member of the general transcription factor TFIIH. Although there is substantial evidence for an active role of CDK7 in mRNA synthesis and associated processes, the degree of its influence on global and gene-specific transcription in mammalian species is unclear. In the current study, we utilize two novel inhibitors with high specificity for CDK7 to demonstrate a restricted but robust impact of CDK7 on gene transcription in vivo and in in vitro-reconstituted reactions. We distinguish between relative low- and high-dose responses and relate them to distinct molecular mechanisms and altered physiological responses. Low inhibitor doses cause rapid clearance of paused RNA polymerase II (RNAPII) molecules and sufficed to cause genome-wide alterations in gene expression, delays in cell cycle progression at both the G1/S and G2/M checkpoints, and diminished survival of human tumor cells. Higher doses and prolonged inhibition led to strong reductions in RNAPII carboxyl-terminal domain (CTD) phosphorylation, eventual activation of the p53 program, and increased cell death. Together, our data reason for a quantitative contribution of CDK7 to mRNA synthesis, which is critical for cellular homeostasis. PMID:25047832

  10. Cyclin-dependent kinase 7 controls mRNA synthesis by affecting stability of preinitiation complexes, leading to altered gene expression, cell cycle progression, and survival of tumor cells.

    PubMed

    Kelso, Timothy W R; Baumgart, Karen; Eickhoff, Jan; Albert, Thomas; Antrecht, Claudia; Lemcke, Sarah; Klebl, Bert; Meisterernst, Michael

    2014-10-01

    Cyclin-dependent kinase 7 (CDK7) activates cell cycle CDKs and is a member of the general transcription factor TFIIH. Although there is substantial evidence for an active role of CDK7 in mRNA synthesis and associated processes, the degree of its influence on global and gene-specific transcription in mammalian species is unclear. In the current study, we utilize two novel inhibitors with high specificity for CDK7 to demonstrate a restricted but robust impact of CDK7 on gene transcription in vivo and in in vitro-reconstituted reactions. We distinguish between relative low- and high-dose responses and relate them to distinct molecular mechanisms and altered physiological responses. Low inhibitor doses cause rapid clearance of paused RNA polymerase II (RNAPII) molecules and sufficed to cause genome-wide alterations in gene expression, delays in cell cycle progression at both the G1/S and G2/M checkpoints, and diminished survival of human tumor cells. Higher doses and prolonged inhibition led to strong reductions in RNAPII carboxyl-terminal domain (CTD) phosphorylation, eventual activation of the p53 program, and increased cell death. Together, our data reason for a quantitative contribution of CDK7 to mRNA synthesis, which is critical for cellular homeostasis. PMID:25047832

  11. Genetic and environmental factors affecting growth and reproductive performance of Santa Ines sheep in the semi-arid region of Brazil

    E-print Network

    Sousa, Wandrick Hauss de

    1987-01-01

    growth and reProductive performance of the Santa Ines breed of hair sheep. The characters studied were birth we'ght (BW), weight at 28 d of age (N28), weaning weight (WW), weight at 196 d of age (W196), average daily gain from birth to weaning (ADG1... parameters were obtained from paternal half-sib analyses. Q~e of birth was the most important source of variatior. for all growth traits except ADG2, and year of birth affected all growth traits and some reproductive traits (FR, LR, TWB, T(84 and SR...

  12. Genetic Variations Affecting Serum Carcinoembryonic Antigen Levels and Status of Regional Lymph Nodes in Patients with Sporadic Colorectal Cancer from Southern China

    PubMed Central

    Gao, Yong; Tan, Aihua; Yang, Xiaobo; Zhang, Haiying; Hu, Yanling; Qin, Xue; Li, Shan; Zhang, Shijun; Mo, Linjian; Liang, Zhenjia; Shi, Deyi; Huang, Zhang; Guan, Yingyong; Zhou, Jicheng; Winkler, Cheryl; O'Brien, Stephen J.; Xu, Jianfeng; Mo, Zengnan; Peng, Tao

    2014-01-01

    Background Serum carcinoembryonic antigen (sCEA) level might be an indicator of disease. Indeed, an elevated sCEA level is a prognostic factor in colorectal cancer (CRC) patients. However, the genetic determinants of sCEA level in healthy and CRC population remains unclear. Thus we investigated the genetic markers associated with elevated serum sCEA level in these two populations and its clinical implications. Methods and Findings Genome-wide association study (GWAS) was conducted in a cohort study with 4,346 healthy male adults using the Illumina Omni 1 M chip. Candidate SNPs associated with elevated sCEA levels were validated in 194 CRC patients on ABI Taqman platform. Eight candidate SNPs were validated in CRC patients. The rs1047781 (chr19- FUT2) (A/T) was associated with elevated sCEA levels, and rs8176746 (chr9- ABO) was associated with the regional lymph metastasis in the CRC patients. The preoperative sCEA level was a risk factor for tumor recurrence in 5 years after operation (OR?=?1.427, 95% CI: 1.005?1.843, P?=?0.006). It was also one of the risk factors for regional lymph node metastasis (OR?=?2.266, 95% CI: 1.196?4.293, P?=?0.012). The sCEA level in rs1047781-T carriers was higher than that in the A carriers in CRC patients without lymph node metastasis (P?=?0.006). The regional lymph node metastasis in patients with homozygote AA of rs8176746 was more common than that in the heterozygote AG carriers (P?=?0.022). In addition, rs1047781-AT and TT CRC patients exhibited a worse disease-free survival than AA genotype carriers (P?=?0.023). Conclusions We found candidate SNPs associated with elevated sCEA levels in both healthy males and CRC population. Rs1047781 (chr19- FUT2) may be the susceptible locus for recurrence of CRC in a population from Southern China. PMID:24941225

  13. Genetics of the Connectome

    PubMed Central

    Thompson, Paul M.; Ge, Tian; Glahn, David C.; Jahanshad, Neda; Nichols, Thomas E.

    2014-01-01

    Connectome genetics attempts to discover how genetic factors affect brain connectivity. Here we review a variety of genetic analysis methods – such as genome-wide association studies (GWAS), linkage and candidate gene studies – that have been fruitfully adapted to imaging data to implicate specific variants in the genome for brain-related traits. We then review studies of that emphasized the genetic influences on brain connectivity. Some of these perform genetic analysis of brain integrity and connectivity using diffusion MRI, and others have mapped genetic effects on functional networks using resting state functional MRI. Connectome-wide genome-wide scans have also been conducted, and we review the multivariate methods required to handle the extremely high dimension of genomic and the network data. We also review some consortium efforts, such as ENIGMA, that offer the power to detect robust common genetic associations using phenotypic harmonization procedures and meta-analysis. Current work on connectome genetics is advancing on many fronts and promises to shed light on how disease risk genes affect the brain. It is already discovering new genetic loci and even entire genetic networks that affect brain organization and connectivity. PMID:23707675

  14. Exclusion of PAX9 and MSX1 mutation in six families affected by tooth agenesis. A genetic study and literature review

    PubMed Central

    Manzanares-Céspedes, Maria C.; Carvalho-Lobato, Patricia; Valdivia-Gandur, Ivan; Arte, Sirpa; Nieminen, Pekka

    2014-01-01

    Objectives: In the present study, it is described the phenotypical analysis and the mutational screening, for genes PAX9 and MSX1, of six families affected by severe forms of tooth agenesis associated with other dental anomalies and systemic entities. Study Design: Six families affected by severe tooth agenesis associated with other dental anomalies and systemic entities were included. Oral exploration, radiological examination, medical antecedents consideration and mutational screening for PAX9 and MSX1 were carried out. Results: No mutations were discovered despite the fact that numerous teeth were missing. An important phenotypical variability was observed within the probands, not being possible to establish a parallelism with the patterns associated to previously described PAX9 and MSX1 mutations. Conclusions: These results bring us to conclude that probably other genes can determine phenotypical patterns of dental agenesis in the families studied, different than the ones described in the mutations of PAX9 and MSX1. Moreover, epigenetic factors can be involved, as those that can reduce gene dosage and other post-transcriptional modulation agents, causing dental agenesis associated or not with systemic anomalies. Key words:Maxillofacial development, tooth agenesis, PAX9 gene, MSX1 gene, gene mutation. PMID:24316698

  15. Genes affecting novel seed constituents in Limnanthes alba Benth: transcriptome analysis of developing embryos and a new genetic map of meadowfoam.

    PubMed

    Slabaugh, Mary B; Cooper, Laurel D; Kishore, Venkata K; Knapp, Steven J; Kling, Jennifer G

    2015-01-01

    The seed oil of meadowfoam, a new crop in the Limnanthaceae family, is highly enriched in very long chain fatty acids that are desaturated at the ?5 position. The unusual oil is desirable for cosmetics and innovative industrial applications and the seed meal remaining after oil extraction contains glucolimnanthin, a methoxylated benzylglucosinolate whose degradation products are herbicidal and anti-microbial. Here we describe EST analysis of the developing seed transcriptome that identified major genes involved in biosynthesis and assembly of the seed oil and in glucosinolate metabolic pathways. mRNAs encoding acyl-CoA ?5 desaturase were notably abundant. The library was searched for simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs). Fifty-four new SSR markers and eight candidate gene markers were developed and combined with previously developed SSRs to construct a new genetic map for Limnanthes alba. Mapped genes in the lipid biosynthetic pathway encode 3-ketoacyl-CoA synthase (KCS), ?5 desaturase (?5DS), lysophosphatidylacyl-acyl transferase (LPAT), and acyl-CoA diacylglycerol acyl transferase (DGAT). Mapped genes in glucosinolate biosynthetic and degradation pathways encode CYP79A, myrosinase (TGG), and epithiospecifier modifier protein (ESM). The resources developed in this study will further the domestication and improvement of meadowfoam as an oilseed crop. PMID:26038713

  16. Genetic variance in the HIV-1 founder virus Vpr affects its ability to induce cell cycle G?arrest and cell apoptosis.

    PubMed

    Jianyuan, Zhao; Jiwei, Ding; Zeyun, Mi; Jinming, Zhou; Tao, Wei; Shan, Cen

    2015-05-01

    In the event of acute infection, only a few HIV-1 viral variants can establish the initial productive clinical infection, and these viral variants are known as transmitted/founder viruses (T/F viruses). As one of the accessory proteins of HIV-1, viral protein R (Vpr) plays an important role in viral replication. Therefore, the characterization of T/F virus Vpr is beneficial to understand how virus replicates in a new host. In this study, flow cytometry was used to analyze the effect of G?arrest and cell apoptosis induced by the T/F virus Vpr and the chronic strain MJ4 Vpr. The results showed that the ability of T/F virus ZM246 Vpr and ZM247 Vpr inducing G?arrest and cell apoptosis are more potent than the MJ4 Vpr. The comparison of protein sequences indicated that the amino acids of 77, 85 and 94 contain high freqency mutations, suggesting that these sites may be involved in inducing G?arrest and cell apoptosis. Taken together, our work suggests that in acute infections, T/F viruses increase the capacity of G?arrest and cell apoptosis and promote viral replication and transmission in a new host by Vpr genetic mutation. PMID:25998437

  17. Genes affecting novel seed constituents in Limnanthes alba Benth: transcriptome analysis of developing embryos and a new genetic map of meadowfoam

    PubMed Central

    Cooper, Laurel D.; Kishore, Venkata K.; Knapp, Steven J.; Kling, Jennifer G.

    2015-01-01

    The seed oil of meadowfoam, a new crop in the Limnanthaceae family, is highly enriched in very long chain fatty acids that are desaturated at the ?5 position. The unusual oil is desirable for cosmetics and innovative industrial applications and the seed meal remaining after oil extraction contains glucolimnanthin, a methoxylated benzylglucosinolate whose degradation products are herbicidal and anti-microbial. Here we describe EST analysis of the developing seed transcriptome that identified major genes involved in biosynthesis and assembly of the seed oil and in glucosinolate metabolic pathways. mRNAs encoding acyl-CoA ?5 desaturase were notably abundant. The library was searched for simple sequence repeats (SSRs) and single nucleotide polymorphisms (SNPs). Fifty-four new SSR markers and eight candidate gene markers were developed and combined with previously developed SSRs to construct a new genetic map for Limnanthes alba. Mapped genes in the lipid biosynthetic pathway encode 3-ketoacyl-CoA synthase (KCS), ?5 desaturase (?5DS), lysophosphatidylacyl-acyl transferase (LPAT), and acyl-CoA diacylglycerol acyl transferase (DGAT). Mapped genes in glucosinolate biosynthetic and degradation pathways encode CYP79A, myrosinase (TGG), and epithiospecifier modifier protein (ESM). The resources developed in this study will further the domestication and improvement of meadowfoam as an oilseed crop. PMID:26038713

  18. Genetic structure and diversity of animal populations exposed to metal pollution.

    PubMed

    Mussali-Galante, Patricia; Tovar-Sánchez, Efraín; Valverde, Mahara; Rojas, Emilio

    2014-01-01

    Studying the genetic diversity of wild populations that are affected by pollution provides a basis for estimating the risks of environmental contamination to both wildlife, and indirectly to humans. Such research strives to produce both a better understanding of the underlying mechanisms by which genetic diversity is affected,and the long-term effects of the pollutants involved.In this review, we summarize key aspects of the field of genetic ecotoxicology that encompasses using genetic patterns to examine metal pollutants as environmental stressors of natural animal populations. We address genetic changes that result from xenobiotic exposure versus genetic alterations that result from natural ecological processes. We also describe the relationship between metal exposure and changes in the genetic diversity of chronically exposed populations, and how the affected populations respond to environmental stress. Further, we assess the genetic diversity of animal populations that were exposed to metals, focusing on the literature that has been published since the year 2000.Our review disclosed that the most common metals found in aquatic and terrestrial ecosystems were Cd, Zn, Cu and Pb; however, differences in the occurrence between aquatic (Cd=Zn>Cu>Pb>Hg) and terrestrial (Cu>Cd>Pb>Zn>Ni)environments were observed. Several molecular markers were used to assess genetic diversity in impacted populations, the order of the most common ones of which were SSR's > allozyme > RAPD's > mtDNA sequencing> other molecular markers.Genetic diversity was reduced for nearly all animal populations that were exposed to a single metal, or a mixture of metals in aquatic ecosystems (except in Hyalella azteca, Littorina littorea, Salmo trutta, and Gobio gobio); however, the pattern was less clear when terrestrial ecosystems were analyzed.We propose that future research in the topic area of this paper emphasizes seven key areas of activity that pertain to the methodological design of genetic ecotoxicological studies. Collectively, these points are designed to provide more accurate data and a deeper understanding of the relationship between alterations in genetic diversity of impacted populations and metal exposures. In particular, we believe that the exact nature of all tested chemical pollutants be clearly described, biomarkers be included, sentinel organisms be used, testing be performed at multiple experimental sites, reference populations be sampled in close geographical proximity to where pollution occurs, and genetic structure parameters and high-throughput technology be more actively employed. Furthermore, we propose a new class of biomarkers,termed "biomarkers of permanent effect," which may include measures of genetic variability in impacted populations. PMID:24158580

  19. Selection for low erucic acid and genetic mapping of loci affecting the accumulation of very long-chain fatty acids in meadowfoam seed storage lipids.

    PubMed

    Gandhi, S D; Kishore, V K; Crane, J M; Slabaugh, M B; Knapp, S J

    2009-06-01

    Erucic acid (22:1(13)) has been identified as an anti-nutritional compound in meadowfoam (Limnanthes alba) and other oilseeds in the Brassicales, a classification which has necessitated the development of low erucic acid cultivars for human consumption. The erucic acid concentrations of meadowfoam wild types (8%-24%) surpass industry standards for human consumption (affecting the accumulation of 22:1(13) and other very long-chain fatty acids (VLCFAs) in meadowfoam seed storage lipids. LE76, a low erucic acid line, was developed by 3 cycles of selection in an ethyl methanesulfonate-treated wildtype population. LE76 produced 3% 22:1(13), threefold less than the M0 population. Wildtype x LE76 F2 populations produced continuous, approximately normal erucic and dienoic acid distributions. Loss-of-function mutations apparently did not segregate and individuals with low 22:1(13) concentrations (affecting VLCFA profiles in seed storage lipids by genotyping and phenotyping wildtype x low erucic acid F2 progeny. Composite interval mapping identified 3 moderately large-effect erucic acid QTL. The low erucic acid parent transmitted favorable alleles for 2 of 3 QTL, suggesting low erucic acid cultivars can be developed by combining favorable alleles transmitted by wildtype and low erucic acid parents. PMID:19483773

  20. Combined genetic profiles of components and regulators of the vitamin K-dependent gamma-carboxylation system affect individual sensitivity to warfarin.

    PubMed

    Vecsler, Manuela; Loebstein, Ronen; Almog, Shlomo; Kurnik, Daniel; Goldman, Boleslav; Halkin, Hillel; Gak, Eva

    2006-02-01

    We examined the influence of combined genotypes on interindividual variability in warfarin dose-response. In 100 anticoagulated patients we quantified the effects of polymorphisms in: CYP2C9, VKORC1, calumenin (CALU), gamma-glutamyl carboxylase (GGCX) and microsomal epoxide hydrolase (EPHX1) on warfarin dose requirements. The G(1542)C VKORC1 polymorphism was associated with decreased warfarin doses in the hetero- and homozygous mutant patients (21% and 50% lower, respectively; p < 0.0001). Warfarin daily dose was predominantly determined by VKORC1 and CYP2C9 genotypes (partial r(2) = 0.21; 0.20, respectively). Together with age and body weight, these two genotypes explained 63% of the dose variance. A single patient, homozygous for G(11)A CALU mutant allele, required an exceptionally high warfarin dose (20 mg/day) and the prevalence of heterozygous (11)A allele carriers in the upper 10(th) dose percentile was significantly higher (0.27 vs. 0.18, p < 0.02). Combined genotype analysis revealed that CYP2C9 andVKORC1 wild type and CALU mutant patients required the highest warfarin doses (7.8 +/- 1.5mg/day; n = 9) as compared to the CYP2C9 and VKORC1 mutant and CALU wild type genotypes (2.8 +/- 0.3 mg/day; n = 18; p < 0.01). The odds ratio for doses <3mg/day was 5.9 (1.9-18.4) for this genotype. Compound genetic profiles comprising VKORC1, CALU and CYP2C9 improve categorization of individual warfarin dose requirements in more than 25% of patients at steady-state anticoagulation. PMID:16493479

  1. Epigenetics and Epigenetic Alterations in Pancreatic Cancer

    PubMed Central

    Omura, Noriyuki; Goggins, Michael

    2009-01-01

    Pancreatic cancer remains a major therapeutic challenge. In 2008, there will be approximately 37,680 new cases and 34,290 deaths attributable to pancreatic cancer in the United States (U.S.), making it the fourth leading cause of cancer-related death. Recent comprehensive pancreatic cancer genome project found that pancreatic adenocarcinomas harbored 63 intragenic mutations or amplifications/homozygous deletions and these alterations clustered in 12 signaling pathways. In addition to widespread genetic alterations, it is now apparent that epigenetic mechanisms are also central to the evolution and progression of human cancers. Since epigenetic silencing processes are mitotically heritable, they can drive neoplastic progression and undergo the same selective pressure as genetic alterations. This review will describe recent developments in cancer epigenetics and their importance in our understanding of pancreatic adenocarcinomas. PMID:19158989

  2. Genetic variability at promoters of IL-18 (pro-) and IL-10 (anti-) inflammatory gene affects susceptibility and their circulating serum levels: An explorative study of prostate cancer patients in North Indian populations.

    PubMed

    Dwivedi, Shailendra; Goel, Apul; Khattri, Sanjay; Mandhani, Anil; Sharma, Praveen; Misra, Sanjeev; Pant, Kamlesh Kumar

    2015-07-01

    Inflammation is an important hallmark of all types of cancers with a well-established role in carcinogenesis. The net inflammatory response is determined by the balance between pro- and anti-inflammatory cytokines, the levels of which may be affected by the genetic make-up. Interleukin (IL)-18, a pro-inflammatory cytokine expressed by various cells including those of the prostate, is a key mediator of anti-cancer immune response. IL-10, an anti-inflammatory cytokine associated with tumour malignancy, causes escape from immune surveillance. This study hypothesizes that genetic variants of IL-18 (-607 C/A and -137 G/T) and IL-10 (-819 C/T and -592 C/A) may influence the circulating levels of these interleukins, thereby generating susceptibility risk to prostate cancer. The study was conducted on 676 subjects (controls and patients of prostate cancer (PCa): 291 each; and 94 patients with benign prostate hypertrophy (BPH)). Genotyping was performed by PCR-RFLP and Real-Time PCR probe-based method. Circulating interleukin levels were obtained by ELISA. Circulating IL-18 levels were significantly elevated in cancer and BPH patients carrying GG genotypes for -137 of IL-18. The trend of circulating IL-18 levels was GG>GC>CC, observed in all groups. The -137 genetic variants of IL-18 significantly associated with PCa risk were GC, CC, and GC+CC, compared to GG (OR: 1.71, 95% CI: 1.20-2.46; OR: 3.35, 95% CI: 2.03-5.53; and OR: 2.05, 95% CI: 1.46-2.87, respectively). A significant association of AA and CA+AA against CC genotype was observed at -607 locus of IL-18 (OR: 0.46, 95%CI: 0.29-0.72; OR: 0.61, 95% CI: 0.41-0.90, respectively). Significantly elevated levels of IL-10 were observed with TT (wild) genotype at -819 of IL-10, compared to the CC (homozygous mutant) genotype in all three groups of subjects. However, no significant association was found between IL-10 promoter genotypes and PCa risk. We conclude that genetic variants of IL-18 and IL-10 promoters influence the circulating levels of these interleukins. Variations at -137 and -607 loci of IL-18 are associated with susceptibility to PCa. PMID:25892571

  3. Tobacco Exposure by Various Modes May Alter Proinflammatory (IL-12) and Anti-Inflammatory (IL-10) Levels and Affects the Survival of Prostate Carcinoma Patients: An Explorative Study in North Indian Population

    PubMed Central

    Khattri, Sanjay; Mandhani, Anil; Sharma, Praveen; Pant, Kamlesh Kumar

    2014-01-01

    Objective. Inflammation is an important hallmark of all cancers and net inflammatory response is determined by a delicate balance between pro- and anti-inflammatory cytokines, which may be affected by tobacco exposure, so the present study was designed to explore the effect of various modes of tobacco exposure on interleukin-12 (IL-12) and interleukin-10 (IL-10) inflammatory cytokine levels and survival in prostate carcinoma (PCa) patients. Methods. 285 cancer patients and equal controls with 94 BPH (benign prostatic hyperplasia) were recruited; baseline levels of serum IL-12 and IL-10 were measured and analyzed in various tobacco exposed groups by appropriate statistical tool. Five-year survivals of patients were analyzed by Log-rank (Mantel-Cox) test (graph pad version 5). Results. The expression of serum proinflammatory (IL-12) and anti-inflammatory (IL-10) cytokines was correlated with tobacco exposed group as smokers, chewers, and alcohol users have shown significantly higher levels (P < 0.001) with significantly lower median survivals (27.1 months, standard error = 2.86, and 95% CI: 21.4–32.62); than nonusers. Stages III and IV of tobacco addicted patients have also shown significantly increased levels of IL-12 and IL-10. Conclusions. IL-12 and IL-10 seem to be affected by various modes of tobacco exposure and inflammation also affects median survival of cancer patients. PMID:25177683

  4. Latest Research: Genetic Links

    MedlinePLUS

    ... Home Current Issue Past Issues Feature: Vision Latest Research: Genetic Links Past Issues / Summer 2008 Table of Contents ... Disease Genotyping Network (eyeGENE), the NEI is expanding genetic testing of ... of research labs that offers testing for affected individuals. EyeGENE ...

  5. Maternal Inflammation Contributes to Brain Overgrowth and Autism-Associated Behaviors through Altered Redox Signaling in Stem and Progenitor Cells

    PubMed Central

    Le Belle, Janel E.; Sperry, Jantzen; Ngo, Amy; Ghochani, Yasmin; Laks, Dan R.; López-Aranda, Manuel; Silva, Alcino J.; Kornblum, Harley I.

    2014-01-01

    Summary A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species. PMID:25418720

  6. Molecular genetic studies of schizophrenia

    Microsoft Academic Search

    Brien Riley; Kenneth S Kendler

    2006-01-01

    The study of schizophrenia genetics has confirmed the importance of genes in etiology, but has not so far identified the relationship between observed genetic risks and specific DNA variants, protein alterations or biological processes. In spite of many limitations, numerous regions of the human genome give consistent, although by no means unanimous, support for linkage, which is unlikely to occur

  7. Genetic analysis of regulatory mutants affecting synthesis of extracellular proteinases in the yeast Yarrowia lipolytica: identification of a RIM101/pacC homolog.

    PubMed Central

    Lambert, M; Blanchin-Roland, S; Le Louedec, F; Lepingle, A; Gaillardin, C

    1997-01-01

    Depending on the pH of the growth medium, the yeast Yarrowia lipolytica secretes both an acidic proteinase and an alkaline proteinase, the synthesis of which is also controlled by carbon, nitrogen, and sulfur availability, as well as by the presence of extracellular proteins. Recessive mutations at four unlinked loci, named PAL1 to PAL4, were isolated which prevent alkaline proteinase derepression under conditions of carbon and nitrogen limitation at pH 6.8. These mutations markedly affect mating and sporulation. A dominant suppressor of all four PAL mutations was isolated from a wild-type genomic library, which turned out to be a C-terminally truncated form of a 585-residue transcriptional factor of the His2Cys2 zinc finger family, which we propose to call YlRim101p. Another C-terminally truncated version of YlRim101p (419 residues) is encoded by the dominant RPH2 mutation previously isolated as expressing alkaline protease independently of the pH. YlRim101p is homologous to the transcriptional activators Rim101p of Saccharomyces cerevisiae, required for entry into meiosis, and PacC of Aspergillus nidulans and Penicillium chrysogenum, which were recently shown to mediate regulation by ambient pH. YlRim101p appears essential for mating and sporulation and for alkaline proteinase derepression. YlRIM101 expression is autoregulated, maximal at alkaline pH, and strongly impaired by PAL mutations. PMID:9199331

  8. 28 CFR 35.151 - New construction and alterations.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...part of a facility altered by, on behalf of, or for the use of a public entity in a manner that affects or could affect the usability of the facility or part of the facility shall, to the maximum extent feasible, be altered in such manner that the...

  9. Evolving the Architecture of a Multi-Part Program in Genetic Programming

    E-print Network

    Fernandez, Thomas

    Evolving the Architecture of a Multi- Part Program in Genetic Programming Using Architecture-Altering." This paper describes six new architecture-altering genetic operations for genetic programming Operations John R. Koza Abstract: This paper describes six new architecture-altering operations that provide

  10. Altering Public Opinion: The Role of Authorship Framing

    Microsoft Academic Search

    Laura Phillips

    2004-01-01

    In this paper I probe the role of authorship in public opinion, what shapes it, and how it is altered. The debate over genetically modified foods provides a prime example of a policy area where the public is distrustful and where strong preconceived attitudes exist. Because genetically modified (GM) foods may offer benefits not only to the developed world, but

  11. [Genetics and male infertility].

    PubMed

    Stouffs, K; Vandermaelen, D; Tournaye, H; Liebaers, I; Van Steirteghem, A; Lissens, W

    2009-01-01

    Infertility is a problem affecting many couples with a child wish. In about half of these couples a male factor is (co-) responsible for the fertility concern. For part of these patients a genetic factor will be the underlying cause of the problems. This paper gives an overview of the studies performed in the Department of Embryology and Genetics of the Vrije Universiteit Brussel and the Centre for Medical Genetics of UZ Brussel in order to gain more insight into the genetic causes of male infertility. The studies, focusing on men with fertility problems, can be subdivided into three groups: studies on deletions on the long arm of the Y chromosome, studies on X-linked genes and studies on autosomal genes. It is obvious that Yq microdeletions should be considered as a cause of male infertility. Only for patients with a complete AZFc deletion, a small number of spermatozoa can be retrieved. However, even for these patients assisted reproductive technologies are necessary. Complete AZF deletions are found in 4.6% of the patients visiting the centres for Reproductive Medicine and Medical Genetics of the UZ Brussel and for whom no other cause of the fertility problems have been detected. Taken into consideration this low prevalence of Yq microdeletions, it is obvious that also other factors, including genetic factors, must be causing fertility problems. Potentially, gr/gr deletions (partial deletions of the AZFc region) might influence the fertility status of the patients. It remains, however, unclear which of the genes located in the deleted regions are important for the progression of spermatogenesis, in case of partial or complete AZF deletions. In our studies we have also investigated mutations in genes located on the X chromosome. In analogy to the Y chromosome, the X chromosome is interesting in view of studying male infertility since men only have a single copy of the sex chromosomes. As a consequence, mutations in genes crucial for spermatogenesis will have an immediate impact on the sperm production. The genes NXF2, USP26 and TAF7L were investigated for the presence of mutations. All observed single nucleotide changes were also present in control samples, questioning their relationship with male infertility. We also studied five autosomal genes: SYCP3, MSH4, DNMT3L, STRA8 and ETV5. Only for the genes STRA8 and ETV5, changes were detected that were absent in a control population existing of men with normozoospermia. Functional analysis of the changes in ETV5 and the localization of the change observed in STRA8 showed that also these alterations were probably not the cause of the fertility problems in these men. It can be concluded that mutations are rarely detected in men with fertility problems. This low frequency of mutations has also been confirmed in several published studies. Therefore, further research is necessary to determine the impact of genetic causes on male infertility. PMID:20088251

  12. Alterations of Neocortical Pyramidal Neurons: Turning Points in the Genesis of Mental Retardation

    PubMed Central

    Granato, Alberto; De Giorgio, Andrea

    2014-01-01

    Pyramidal neurons (PNs) represent the majority of neocortical cells and their involvement in cognitive functions is decisive. Therefore, they are the most obvious target of developmental disorders characterized by mental retardation. Genetic and non-genetic forms of intellectual disability share a few basic pathogenetic signatures that result in the anomalous function of PNs. Here, we review the key mechanisms impairing these neurons and their participation in the cortical network, with special focus on experimental models of fetal exposure to alcohol. Due to the heterogeneity of PNs, some alterations affect selectively a given cell population, which may also differ depending on the considered pathology. These specific features open new possibilities for the interpretation of cognitive defects observed in mental retardation syndromes, as well as for novel therapeutic interventions. PMID:25157343

  13. [Altered states of consciousness].

    PubMed

    Gora, E P

    2005-01-01

    The review of modern ideas concerning the altered states of consciousness is presented in this article. Various methods of entry into the altered states of consciousness are looked over. It is shown that the altered states of consciousness are insufficiently known, but important aspects of human being existence. The role of investigation of the altered states of consciousness for the creation of integrative scientific conception base is discussed. PMID:15810684

  14. Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells

    PubMed Central

    Lee, Mark N.; Ye, Chun; Villani, Alexandra-Chloé; Raj, Towfique; Li, Weibo; Eisenhaure, Thomas M.; Imboywa, Selina H.; Chipendo, Portia I.; Ran, F. Ann; Slowikowski, Kamil; Ward, Lucas D.; Raddassi, Khadir; McCabe, Cristin; Lee, Michelle H.; Frohlich, Irene Y.; Hafler, David A.; Kellis, Manolis; Raychaudhuri, Soumya; Zhang, Feng; Stranger, Barbara E.; Benoist, Christophe O.; De Jager, Philip L.; Regev, Aviv; Hacohen, Nir

    2014-01-01

    Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to E. coli lipopolysaccharide, influenza or interferon-? (IFN?). We localized and validated causal variants to binding sites of pathogen-activated STAT and IRF transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I interferon induction in response to influenza infection. Our results reveal common alleles that explain inter-individual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases. PMID:24604203

  15. AQP1 expression alterations affect morphology and water transport in Schwann cells and hypoxia-induced up-regulation of AQP1 occurs in a HIF-1?-dependent manner.

    PubMed

    Zhang, J; Xiong, Y; Lu, L X; Wang, H; Zhang, Y F; Fang, F; Song, Y L; Jiang, H

    2013-11-12

    Aquaporin-1 (AQP1) is the principle water channel in the peripheral nervous system (PNS) and is specifically localized to Schwann cells in the PNS. However, the pathophysiological role of AQP1 in peripheral nerves is poorly understood. Here, we utilized RNA interference by lentiviral transduction to specifically down-regulate AQP1 expression and a lentiviral overexpression protocol to up-regulate AQP1 expression, in primary Schwann cell cultures. AQP1 gene silencing resulted in a cell shrinkage phenotype, while AQP1 gene overexpression caused a cell swelling phenotype, as validated by cell volume determinations. Secondly, we utilized an in vitro hypoxia model in Schwann cells to mimic in vivo facial nerve injury. We demonstrated that AQP1 expression was induced within 8h following hypoxia injury in vitro, and that AQP1 knockdown (KD) caused the cells to resist edema following hypoxia. Finally, we investigated the hypoxic regulation of the AQP1 gene, as well as the involvement of Hypoxia-inducible factor-1? (HIF-1?) in AQP1 modulation and we found that KD of HIF-1? decreased hypoxia-dependent induction of endogenous AQP1 expression at both the mRNA and protein levels. Taken together, these results indicate that (1) AQP1 is an important factor responsible for the fast water transport of cultured Schwann cells and is involved in cell plasticity; (2) AQP1 alterations may be a primary factor in hypoxia-induced peripheral nerve edema; (3) HIF-1? participates in the hypoxic induction of the AQP1 gene; (4) AQP1 inhibition might provide a new therapeutic alternative for the treatment of some forms of peripheral nerve edema. PMID:23948641

  16. Common genetic variants influence human subcortical brain structures

    PubMed Central

    Hibar, Derrek P.; Stein, Jason L.; Renteria, Miguel E.; Arias-Vasquez, Alejandro; Desrivières, Sylvane; Jahanshad, Neda; Toro, Roberto; Wittfeld, Katharina; Abramovic, Lucija; Andersson, Micael; Aribisala, Benjamin S.; Armstrong, Nicola J.; Bernard, Manon; Bohlken, Marc M.; Boks, Marco P.; Bralten, Janita; Brown, Andrew A.; Chakravarty, M. Mallar; Chen, Qiang; Ching, Christopher R. K.; Cuellar-Partida, Gabriel; den Braber, Anouk; Giddaluru, Sudheer; Goldman, Aaron L.; Grimm, Oliver; Guadalupe, Tulio; Hass, Johanna; Woldehawariat, Girma; Holmes, Avram J.; Hoogman, Martine; Janowitz, Deborah; Jia, Tianye; Kim, Sungeun; Klein, Marieke; Kraemer, Bernd; Lee, Phil H.; Olde Loohuis, Loes M.; Luciano, Michelle; Macare, Christine; Mather, Karen A.; Mattheisen, Manuel; Milaneschi, Yuri; Nho, Kwangsik; Papmeyer, Martina; Ramasamy, Adaikalavan; Risacher, Shannon L.; Roiz-Santiañez, Roberto; Rose, Emma J.; Salami, Alireza; Sämann, Philipp G.; Schmaal, Lianne; Schork, Andrew J.; Shin, Jean; Strike, Lachlan T.; Teumer, Alexander; van Donkelaar, Marjolein M. J.; van Eijk, Kristel R.; Walters, Raymond K.; Westlye, Lars T.; Whelan, Christopher D.; Winkler, Anderson M.; Zwiers, Marcel P.; Alhusaini, Saud; Athanasiu, Lavinia; Ehrlich, Stefan; Hakobjan, Marina M. H.; Hartberg, Cecilie B.; Haukvik, Unn K.; Heister, Angelien J. G. A. M.; Hoehn, David; Kasperaviciute, Dalia; Liewald, David C. M.; Lopez, Lorna M.; Makkinje, Remco R. R.; Matarin, Mar; Naber, Marlies A. M.; McKay, D. Reese; Needham, Margaret; Nugent, Allison C.; Pütz, Benno; Royle, Natalie A.; Shen, Li; Sprooten, Emma; Trabzuni, Daniah; van der Marel, Saskia S. L.; van Hulzen, Kimm J. E.; Walton, Esther; Wolf, Christiane; Almasy, Laura; Ames, David; Arepalli, Sampath; Assareh, Amelia A.; Bastin, Mark E.; Brodaty, Henry; Bulayeva, Kazima B.; Carless, Melanie A.; Cichon, Sven; Corvin, Aiden; Curran, Joanne E.; Czisch, Michael; de Zubicaray, Greig I.; Dillman, Allissa; Duggirala, Ravi; Dyer, Thomas D.; Erk, Susanne; Fedko, Iryna O.; Ferrucci, Luigi; Foroud, Tatiana M.; Fox, Peter T.; Fukunaga, Masaki; Gibbs, J. Raphael; Göring, Harald H. H.; Green, Robert C.; Guelfi, Sebastian; Hansell, Narelle K.; Hartman, Catharina A.; Hegenscheid, Katrin; Heinz, Andreas; Hernandez, Dena G.; Heslenfeld, Dirk J.; Hoekstra, Pieter J.; Holsboer, Florian; Homuth, Georg; Hottenga, Jouke-Jan; Ikeda, Masashi; Jack, Clifford R.; Jenkinson, Mark; Johnson, Robert; Kanai, Ryota; Keil, Maria; Kent, Jack W.; Kochunov, Peter; Kwok, John B.; Lawrie, Stephen M.; Liu, Xinmin; Longo, Dan L.; McMahon, Katie L.; Meisenzahl, Eva; Melle, Ingrid; Mohnke, Sebastian; Montgomery, Grant W.; Mostert, Jeanette C.; Mühleisen, Thomas W.; Nalls, Michael A.; Nichols, Thomas E.; Nilsson, Lars G.; Nöthen, Markus M.; Ohi, Kazutaka; Olvera, Rene L.; Perez-Iglesias, Rocio; Pike, G. Bruce; Potkin, Steven G.; Reinvang, Ivar; Reppermund, Simone; Rietschel, Marcella; Romanczuk-Seiferth, Nina; Rosen, Glenn D.; Rujescu, Dan; Schnell, Knut; Schofield, Peter R.; Smith, Colin; Steen, Vidar M.; Sussmann, Jessika E.; Thalamuthu, Anbupalam; Toga, Arthur W.; Traynor, Bryan J.; Troncoso, Juan; Turner, Jessica A.; Valdés Hernández, Maria C.; van ’t Ent, Dennis; van der Brug, Marcel; van der Wee, Nic J. A.; van Tol, Marie-Jose; Veltman, Dick J.; Wassink, Thomas H.; Westman, Eric; Zielke, Ronald H.; Zonderman, Alan B.; Ashbrook, David G.; Hager, Reinmar; Lu, Lu; McMahon, Francis J.; Morris, Derek W.; Williams, Robert W.; Brunner, Han G.; Buckner, Randy L.; Buitelaar, Jan K.; Cahn, Wiepke; Calhoun, Vince D.; Cavalleri, Gianpiero L.; Crespo-Facorro, Benedicto; Dale, Anders M.; Davies, Gareth E.; Delanty, Norman; Depondt, Chantal; Djurovic, Srdjan; Drevets, Wayne C.; Espeseth, Thomas; Gollub, Randy L.; Ho, Beng-Choon; Hoffmann, Wolfgang; Hosten, Norbert; Kahn, René S.; Le Hellard, Stephanie; Meyer-Lindenberg, Andreas; Müller-Myhsok, Bertram; Nauck, Matthias; Nyberg, Lars; Pandolfo, Massimo; Penninx, Brenda W. J. H.; Roffman, Joshua L.; Sisodiya, Sanjay M.; Smoller, Jordan W.; van Bokhoven, Hans; van Haren, Neeltje E. M.; Völzke, Henry; Walter, Henrik; Weiner, Michael W.; Wen, Wei; White, Tonya; Agartz, Ingrid; Andreassen, Ole A.; Blangero, John; Boomsma, Dorret I.; Brouwer, Rachel M.; Cannon, Dara M.; Cookson, Mark R.; de Geus, Eco J. C.; Deary, Ian J.; Donohoe, Gary; Fernández, Guillén; Fisher, Simon E.; Francks, Clyde; Glahn, David C.; Grabe, Hans J.; Gruber, Oliver; Hardy, John; Hashimoto, Ryota; Hulshoff Pol, Hilleke E.; Jönsson, Erik G.

    2015-01-01

    The highly complex structure of the human brain is strongly shaped by genetic influences1. Subcortical brain regions form circuits with cortical areas to coordinate movement2, learning, memory3 and motivation4, and altered circuits can lead to abnormal behaviour and disease2. To investigate how common genetic variants affect the structure of these brain regions, here we conduct genome-wide association studies of the volumes of seven subcortical regions and the intracranial volume derived from magnetic resonance images of 30,717 individuals from 50 cohorts. We identify five novel genetic variants influencing the volumes of the putamen and caudate nucleus. We also find stronger evidence for three loci with previously established influences on hippocampal volume5 and intracranial volume6. These variants show specific volumetric effects on brain structures rather than global effects across structures. The strongest effects were found for the putamen, where a novel intergenic locus with replicable influence on volume (rs945270; P = 1.08 × 10?33; 0.52% variance explained) showed evidence of altering the expression of the KTN1 gene in both brain and blood tissue. Variants influencing putamen volume clustered near developmental genes that regulate apoptosis, axon guidance and vesicle transport. Identification of these genetic variants provides insight into the causes of variability inhuman brain development, and may help to determine mechanisms of neuropsychiatric dysfunction. PMID:25607358

  17. Pattern Alteration: Principles of Pattern Alteration

    E-print Network

    2006-02-09

    or more inches larger than the high bust measurement. Fit across the upper chest is a wiser choice because of the difficulty of altering the upper chest, neck and shoulder areas. 2... in pinpointing areas usually needing alterations. To measure the pattern pieces Measure each pattern piece at points that correspond with body measurements. For example, if your full hip measurement was taken 10 inches below the waist, measure the pattern...

  18. Monitoring adaptive genetic responses to environmental change.

    PubMed

    Hansen, Michael M; Olivieri, Isabelle; Waller, Donald M; Nielsen, Einar E

    2012-03-01

    Widespread environmental changes including climate change, selective harvesting and landscape alterations now greatly affect selection regimes for most organisms. How animals and plants can adapt to these altered environments via contemporary evolution is thus of strong interest. We discuss how to use genetic monitoring to study adaptive responses via repeated analysis of the same populations over time, distinguishing between phenotypic and molecular genetics approaches. After describing monitoring designs, we develop explicit criteria for demonstrating adaptive responses, which include testing for selection and establishing clear links between genetic and environmental change. We then review a few exemplary studies that explore adaptive responses to climate change in Drosophila, selective responses to hunting and fishing, and contemporary evolution in Daphnia using resurrected resting eggs. We further review a broader set of 44 studies to assess how well they meet the proposed criteria, and conclude that only 23% fulfill all criteria. Approximately half (43%) of these studies failed to rule out the alternative hypothesis of replacement by a different, better-adapted population. Likewise, 34% of the studies based on phenotypic variation did not test for selection as opposed to drift. These shortcomings can be addressed via improved experimental designs and statistical testing. We foresee monitoring of adaptive responses as a future valuable tool in conservation biology, for identifying populations unable to evolve at sufficiently high rates and for identifying possible donor populations for genetic rescue. Technological advances will further augment the realization of this potential, especially next-generation sequencing technologies that allow for monitoring at the level of whole genomes. PMID:22269082

  19. During the Long Way to Mars: Effects of 520 Days of Confinement (Mars500) on the Assessment of Affective Stimuli and Stage Alteration in Mood and Plasma Hormone Levels

    PubMed Central

    Wang, Yue; Jing, Xiaolu; Lv, Ke; Wu, Bin; Bai, Yanqiang; Luo, Yuejia; Chen, Shanguang; Li, Yinghui

    2014-01-01

    For future interplanetary manned spaceflight, mental issues, as well as physiological problems, must inevitably be considered and solved. Mars500 is a high-fidelity ground simulation experiment that involved 520 days of confined isolation for six multinational crewmembers. This experiment provided a good opportunity to perform psycho-physiological and psycho-social researches on such missions. To investigate emotional responses and psychological adaptation over long-term confinement, the International Affective Pictures System (IAPS) was selected as the visual emotional stimuli in this study. Additional data collected and analyzed included the Profile of Mood States (POMS) questionnaire and the levels of four types of plasma hormones: cortisol, 5-hydroxy tryptamine, dopamine, and norepinephrine. The results demonstrated an obvious bias on valence rating for unpleasant stimuli with time (p<0.05), and the correlation between psychological and biochemical data was identified (p<0.05). Overall, we concluded that the confined crew tended to assign positive ratings to negative pictures with time, which might be driven by a defensive system. There was a stage-changing pattern of psychological adaptation of the Mars500 crew, which is similar to the third-quarter phenomenon. PMID:24695321

  20. Perturbations of Amino Acid Metabolism Associated with Glyphosate-Dependent Inhibition of Shikimic Acid Metabolism Affect Cellular Redox Homeostasis and Alter the Abundance of Proteins Involved in Photosynthesis and Photorespiration1[W][OA

    PubMed Central

    Vivancos, Pedro Diaz; Driscoll, Simon P.; Bulman, Christopher A.; Ying, Liu; Emami, Kaveh; Treumann, Achim; Mauve, Caroline; Noctor, Graham; Foyer, Christine H.

    2011-01-01

    The herbicide glyphosate inhibits the shikimate pathway of the synthesis of amino acids such as phenylalanine, tyrosine, and tryptophan. However, much uncertainty remains concerning precisely how glyphosate kills plants or affects cellular redox homeostasis and related processes in glyphosate-sensitive and glyphosate-resistant crop plants. To address this issue, we performed an integrated study of photosynthesis, leaf proteomes, amino acid profiles, and redox profiles in the glyphosate-sensitive soybean (Glycine max) genotype PAN809 and glyphosate-resistant Roundup Ready Soybean (RRS). RRS leaves accumulated much more glyphosate than the sensitive line but showed relatively few changes in amino acid metabolism. Photosynthesis was unaffected by glyphosate in RRS leaves, but decreased abundance of photosynthesis/photorespiratory pathway proteins was observed together with oxidation of major redox pools. While treatment of a sensitive genotype with glyphosate rapidly inhibited photosynthesis and triggered the appearance of a nitrogen-rich amino acid profile, there was no evidence of oxidation of the redox pools. There was, however, an increase in starvation-associated and defense proteins. We conclude that glyphosate-dependent inhibition of soybean leaf metabolism leads to the induction of defense proteins without sustained oxidation. Conversely, the accumulation of high levels of glyphosate in RRS enhances cellular oxidation, possibly through mechanisms involving stimulation of the photorespiratory pathway. PMID:21757634

  1. Genetic Counseling

    MedlinePLUS

    ... this page It's been added to your dashboard . Genetic counseling Genetic counseling is a service to help ... child care and genetic testing. Who should get genetic counseling? Anyone who has unanswered questions about origins ...

  2. Genetics Home Reference: X-linked intellectual disability, Siderius type

    MedlinePLUS

    ... of brain cells before birth prevents chromatin remodeling, altering the normal expression of genes involved in intellectual ... Center . Where can I find general information about genetic conditions? The Handbook provides basic information about genetics ...

  3. Factors affecting dystocia in cattle.

    PubMed

    Zaborski, D; Grzesiak, W; Szatkowska, I; Dybus, A; Muszynska, M; Jedrzejczak, M

    2009-06-01

    The paper reviews the various factors affecting dystocia in cattle. It is based mainly on the recent studies found in the literature of the subject but refers occasionally to some older papers as well. The factors are grouped into four main categories: direct factors, phenotypic factors related to calf and cow, non-genetic and genetic factors. The first group includes malpresentations and uterine torsion. The second one includes: calf birth weight, multiple calvings, perinatal mortality, cow pelvic area, cow body weight and body condition at calving, gestation length. The non-genetic factors are: cow age and parity, year and season of calving, place of calving, maintenance practises, disorders, calf sex and nutrition. Other non-genetic factors are the level of hormones in the periparturient period, in vitro production of embryos and embryo cloning. Finally, the genotypes of cow, bull and calf, inbreeding, muscular hypertrophy, selection and quantitative trait loci form the fourth group of genetic factors. PMID:19055561

  4. Medical genetics

    SciTech Connect

    Nora, J.J.; Fraser, F.C.

    1989-01-01

    This book presents a discussion of medical genetics for the practitioner treating or counseling patients with genetic disease. It includes a discussion of the relationship of heredity and diseases, the chromosomal basis for heredity, gene frequencies, and genetics of development and maldevelopment. The authors also focus on teratology, somatic cell genetics, genetics and cancer, genetics of behavior.

  5. Experience, Knowledge, and Opinions about Childhood Genetic Testing in Batten Disease

    PubMed Central

    Rose, Katherine; Augustine, Erika F.; Kwon, Jennifer M.; deBlieck, Elisabeth A.; Marshall, Frederick J.; Vierhile, Amy; Mink, Jonathan W.; Nance, Martha A.

    2013-01-01

    Background and Objectives Policies for genetic testing in children (GTIC) focus on medical or psychosocial benefit to the child, discouraging or prohibiting carrier testing, and advising caution regarding pre-symptomatic diagnosis if no treatment exists. This study sought to understand parents’ perspectives on these issues and determine their experiences and knowledge related to genetic testing for Batten disease – a set of inherited neurodegenerative diseases of childhood onset for which no disease modifying therapies yet exist. Methods Parents of children with Batten disease completed a survey of their knowledge of genetics, experience with genetic testing, and opinions regarding GTIC. Results 54% had sought genetic testing for non-affected family members, including predictive diagnosis of healthy, at-risk children. Participation in any genetic counseling was associated with greater knowledge on questions about genetics. The majority of parents felt it was better to know ahead of time that a child would develop Batten disease, believed that this knowledge would not alter how they related to their child, and that parents should have the final say in deciding whether to obtain GTIC. Conclusions Parents of children with an inherited disease are knowledgeable about genetics and wish to establish predictive or carrier status of at-risk children. PMID:24246680

  6. Nosology, epidemiology and genetics of schizophrenia

    SciTech Connect

    Tsuang, M.T.; Simpson, J.C. (Harvard Schools of Medicine and Public Health, Brockton, MA (US))

    1988-01-01

    This book contains 25 selections. Some of the titles are: The genetics of schizophrenia: An overview; The genetics of schizo-affective disorder and the schizophrenia spectrum; Mathematical models of genetic transmission; and Genetic studies of biochemical, pathophysiological and pharmacological factors in schizophrenia.

  7. SPECIAL FEATURE Community Genetics: New Insights into Community Ecology by

    E-print Network

    Agrawal, Anurag

    in multispecies commu- nities, and these changes can rapidly alter the genetics of community members. It is argued543 SPECIAL FEATURE Community Genetics: New Insights into Community Ecology by Integrating Population Genetics1 Community genetics is the study of the interaction between genes within a species

  8. The landscape of somatic copy-number alteration across human cancers

    E-print Network

    Raychaudhuri, Soumya

    ARTICLES The landscape of somatic copy-number alteration across human cancers Rameen Beroukhim1 in oncogenesis is to identify genomic regions that undergo frequent alteration in human cancers. Here we present by the acquisition of somatic genetic alterations, including single base substitutions, transloca- tions, infections

  9. Copyright 2010 by the Genetics Society of America DOI: 10.1534/genetics.109.113571

    E-print Network

    Sokolowski, Marla

    Copyright Ó 2010 by the Genetics Society of America DOI: 10.1534/genetics.109.113571 Genotype and Greg Gibson,§ *Department of Genetics, North Carolina State University, Raleigh, North Carolina 27695 for publication March 24, 2010 ABSTRACT The rising prevalence of complex disease suggests that alterations

  10. Altered mental status and fever

    PubMed Central

    Ajayi, Tokunbo; Bhatia, Ashmeet; Lambl, Barbara; Altamimi, Sarah

    2013-01-01

    West Nile virus (WNV) is still the most common cause of neuroinvasive arboviral disease in the USA with a case death of 10–30%. We are reporting a case of a 61-year-old woman with a history of Crohn's disease, fibromyalgia treated with chronic steroid therapy that presented with a day history of fever, confusion and lethargy. She had a lumbar puncture which was notable for lymphocytosis and was positive for WNV. She initially was treated with broad-spectrum antibiotics, which were subsequently discontinued when the diagnosis of WNV neuroinvasive disease (WNND) was made. A high index of suspicion is needed to diagnose WNND, and this should be suspected in elderly immunocompromised patient presenting with altered mental status and lumbar puncture suggestive of aseptic meningitis. Recent study has showed that there is genetic variation in the interferon response pathway which is associated with both risk for symptomatic WNV infection and disease progression. PMID:23813996

  11. Version 2 -June 25, 1996 for Handbook of Evolutionary Computation. Classifying Protein Segments as Transmembrane Domains Using Genetic Programming

    E-print Network

    Fernandez, Thomas

    as Transmembrane Domains Using Genetic Programming and Architecture-Altering Operations John R. Koza Computer-motivated approach using six new architecture- altering operations enables genetic programming to automatically. #12;Genetic programming with the architecture-altering operations was used to evolve a computer

  12. Genetics Home Reference: Atelosteogenesis type 1

    MedlinePLUS

    ... literature OMIM Genetic disorder catalog Conditions > Atelosteogenesis type 1 On this page: Description Genetic changes Inheritance Diagnosis ... definitions Reviewed September 2011 What is atelosteogenesis type 1? Atelosteogenesis type 1 is a disorder that affects ...

  13. Genes Contributing to Genetic Variation of Muscling in Sheep

    PubMed Central

    Tellam, Ross L.; Cockett, Noelle E.; Vuocolo, Tony; Bidwell, Christopher A.

    2012-01-01

    Selective breeding programs aiming to increase the productivity and profitability of the sheep meat industry use elite, progeny tested sires. The broad genetic traits of primary interest in the progeny of these sires include skeletal muscle yield, fat content, eating quality, and reproductive efficiency. Natural mutations in sheep that enhance muscling have been identified, while a number of genome scans have identified and confirmed quantitative trait loci (QTL) for skeletal muscle traits. The detailed phenotypic characteristics of sheep carrying these mutations or QTL affecting skeletal muscle show a number of common biological themes, particularly changes in developmental growth trajectories, alterations of whole animal morphology, and a shift toward fast twitch glycolytic fibers. The genetic, developmental, and biochemical mechanisms underpinning the actions of some of these genetic variants are described. This review critically assesses this research area, identifies gaps in knowledge, and highlights mechanistic linkages between genetic polymorphisms and skeletal muscle phenotypic changes. This knowledge may aid the discovery of new causal genetic variants and in some cases lead to the development of biochemical and immunological strategies aimed at enhancing skeletal muscle. PMID:22952470

  14. Expression of NR1, NR2A and NR2B NMDA receptor subunits is not altered in the genetically-inbred Balb\\/c mouse strain with heightened behavioral sensitivity to MK-801, a noncompetitive NMDA receptor antagonist

    Microsoft Academic Search

    Pin-Yu Perera; Jack H. Lichy; John Mastropaolo; Richard B. Rosse; Stephen I. Deutsch

    2008-01-01

    The genetically-inbred Balb\\/c mouse strain shows heightened sensitivity to the ability of MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, to raise the threshold voltage necessary to precipitate tonic hindlimb extension and elicit irregular episodes of intense jumping behavior (referred to as “popping”), relative to other inbred mouse strains and the outbred NIH Swiss mouse. Moreover, an allosteric modulatory effect of

  15. Amazing Altered Books

    ERIC Educational Resources Information Center

    Kieling, Linda W.

    2006-01-01

    Linda Kieling, an art teacher at Rosemont Ridge Middle school in West Linn, Oregon, describes an altered book art project she introduced to her students. Alteration of books is a form of recycling that started in the eleventh century when Italian monks recycled old manuscripts written on vellum by scraping off the ink and adding new text and…

  16. Genetics and genomics of melanoma

    PubMed Central

    Ghosh, Papia; Chin, Lynda

    2009-01-01

    The rapidly increasing incidence of melanoma, coupled with its highly aggressive metastatic nature, is of urgent concern. In order to design rational therapies, it is of critical importance to identify the genetic determinants that drive melanoma formation and progression. To date, signaling cascades emanating from the EGF receptor, c-MET and other receptors are known to be altered in melanoma. Important mutations in signaling molecules, such as BRAF and N-RAS, have been identified. In this review, some of the major genetic alterations and signaling pathways involved in melanoma will be discussed. Given the great deal of genetic heterogeneity observed in melanoma, it is likely that many more genetic determinants exist. Through the use of powerful genomic technologies, it is now possible to identify these additional genetic alterations in melanoma. A critical step in this analysis will be culling bystanders from functionally important drivers, as this will highlight genetic elements that will be promising therapeutic targets. Such technologies and the important points to consider in understanding the genetics of melanoma will be reviewed. PMID:20126509

  17. Medical genetics

    SciTech Connect

    Jorde, L.B.; Carey, J.C.; White, R.L.

    1995-10-01

    This book on the subject of medical genetics is a textbook aimed at a very broad audience: principally, medical students, nursing students, graduate, and undergraduate students. The book is actually a primer of general genetics as applied to humans and provides a well-balanced introduction to the scientific and clinical basis of human genetics. The twelve chapters include: Introduction, Basic Cell Biology, Genetic Variation, Autosomal Dominant and Recessive Inheritance, Sex-linked and Mitochondrial Inheritance, Clinical Cytogenetics, Gene Mapping, Immunogenetics, Cancer Genetics, Multifactorial Inheritance and Common Disease, Genetic Screening, Genetic Diagnosis and Gene Therapy, and Clinical Genetics and Genetic Counseling.

  18. Applications of graph theory to landscape genetics

    PubMed Central

    Garroway, Colin J; Bowman, Jeff; Carr, Denis; Wilson, Paul J

    2008-01-01

    We investigated the relationships among landscape quality, gene flow, and population genetic structure of fishers (Martes pennanti) in ON, Canada. We used graph theory as an analytical framework considering each landscape as a network node. The 34 nodes were connected by 93 edges. Network structure was characterized by a higher level of clustering than expected by chance, a short mean path length connecting all pairs of nodes, and a resiliency to the loss of highly connected nodes. This suggests that alleles can be efficiently spread through the system and that extirpations and conservative harvest are not likely to affect their spread. Two measures of node centrality were negatively related to both the proportion of immigrants in a node and node snow depth. This suggests that central nodes are producers of emigrants, contain high-quality habitat (i.e., deep snow can make locomotion energetically costly) and that fishers were migrating from high to low quality habitat. A method of community detection on networks delineated five genetic clusters of nodes suggesting cryptic population structure. Our analyses showed that network models can provide system-level insight into the process of gene flow with implications for understanding how landscape alterations might affect population fitness and evolutionary potential. PMID:25567802

  19. Applications of graph theory to landscape genetics.

    PubMed

    Garroway, Colin J; Bowman, Jeff; Carr, Denis; Wilson, Paul J

    2008-11-01

    We investigated the relationships among landscape quality, gene flow, and population genetic structure of fishers (Martes pennanti) in ON, Canada. We used graph theory as an analytical framework considering each landscape as a network node. The 34 nodes were connected by 93 edges. Network structure was characterized by a higher level of clustering than expected by chance, a short mean path length connecting all pairs of nodes, and a resiliency to the loss of highly connected nodes. This suggests that alleles can be efficiently spread through the system and that extirpations and conservative harvest are not likely to affect their spread. Two measures of node centrality were negatively related to both the proportion of immigrants in a node and node snow depth. This suggests that central nodes are producers of emigrants, contain high-quality habitat (i.e., deep snow can make locomotion energetically costly) and that fishers were migrating from high to low quality habitat. A method of community detection on networks delineated five genetic clusters of nodes suggesting cryptic population structure. Our analyses showed that network models can provide system-level insight into the process of gene flow with implications for understanding how landscape alterations might affect population fitness and evolutionary potential. PMID:25567802

  20. Genetic algorithms

    NASA Technical Reports Server (NTRS)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.