Michael J. Hynes

Bio: Michael J. Hynes is an academic researcher from National University of Ireland, Galway. The author has contributed to research in topics: Aspergillus nidulans & Gene. The author has an hindex of 55, co-authored 265 publications receiving 10695 citations. Previous affiliations of Michael J. Hynes include University of Melbourne & National University of Ireland.

Sequencing of Aspergillus nidulans and comparative analysis with A. fumigatus and A. oryzae

Abstract: The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.

EQNMR : a computer program for the calculation of stability constants from nuclear magnetic resonance chemical shift data

Abstract: A computer program has been elaborated which uses the complexation-induced displacements of NMR chemical shifts to calculate the stability constants for the general reaction (i) which gives the generalised stability constant (ii). The program can deal with data from a wide variety of reactions including proton mM +nL +jH ⇌ MmHjLn(i), βmjn=[MmHjLn]/[M]m[H]j[L]n(ii) equilibria, metal-ion hydrolysis and metal–ligand interactions. It can also deal with situations where both ligand proton equilibria and complex-formation reactions must be considered.

A Versatile and Efficient Gene-Targeting System for Aspergillus nidulans

Abstract: Aspergillus nidulans is an important experimental organism, and it is a model organism for the genus Aspergillus that includes serious pathogens as well as commercially important organisms. Gene targeting by homologous recombination during transformation is possible in A. nidulans, but the frequency of correct gene targeting is variable and often low. We have identified the A. nidulans homolog (nkuA) of the human KU70 gene that is essential for nonhomologous end joining of DNA in double-strand break repair. Deletion of nkuA (nkuAΔ) greatly reduces the frequency of nonhomologous integration of transforming DNA fragments, leading to dramatically improved gene targeting. We have also developed heterologous markers that are selectable in A. nidulans but do not direct integration at any site in the A. nidulans genome. In combination, nkuAΔ and the heterologous selectable markers make up a very efficient gene-targeting system. In experiments involving scores of genes, 90% or more of the transformants carried a single insertion of the transforming DNA at the correct site. The system works with linear and circular transforming molecules and it works for tagging genes with fluorescent moieties, replacing genes, and replacing promoters. This system is efficient enough to make genomewide gene-targeting projects feasible.

Transformation of Aspergillus niger by the amdS gene of Aspergillus nidulans.

Abstract: Aspergillus niger grows poorly on acetamide as a nitrogen or carbon source and lacks sequences detectably homologous to the amdS gene encoding the acetamidase of Aspergillus nidulans. We have taken advantage of these observations to develop a transformation system for A. niger using the amdS gene as a dominant heterologous marker for selecting transformants on the basis of acetamide utilization. Transformants varied in their ability to grow on amide media and the number of integrated copies of the amdS plasmid ranged from 1 or 2 to greater than 100. Southern analysis of transformants revealed that the multiple copies were integrated into the chromosome in tandem arrays. This result indicates that transformation of A. niger is more similar to mammalian cells than to yeast. Analysis of enzyme activity levels and RNA levels showed that most of the copies of amdS were expressed. Mitotic stabilities of transformants were found to be high. A transformant containing greater than 100 copies of the amdS gene was impaired in omega-amino acid utilization, a result that has also been found in A. nidulans. Since, in A. nidulans, omega-amino acids induce acetamidase via a characterizied regulatory gene (amdR/intA) this observation implies that titration of an analogous A. niger regulatory gene product by multiple amdS copies has occurred. Additional evidence suggested that the amdS gene is regulated in A. niger. It has also been shown that an unselected plasmid can be co-transformed with the amdS plasmid into A. niger.

Isolation of genomic clones containing the amdS gene of Aspergillus nidulans and their use in the analysis of structural and regulatory mutations.

Abstract: Previous analysis of the amdS gene of Aspergillus nidulans has identified multiple regulatory circuits mediated by trans-acting regulatory genes, cis-acting mutations have been identified and shown to specifically affect individual regulatory circuits. Fine-structure genetic mapping of the amdS regions showed that these cis-acting mutations occur in a complex controlling region adjacent to the amdS structural gene. The amdS gene was cloned by differential hybridization, using cDNA probes derived from a high-level-producing strain and from a strain with a large amdS deletion mutation. RNA blotting experiments showed that a single RNA species of 1,600 to 1,700 base pairs is transcribed from the amdS gene. DNA blotting experiments on a large number of amdS mutant strains, including deletions and translocations, allowed the genetic and physical maps of the gene to be correlated. The controlling region of the gene is situated at the 5' end of the gene and the direction of transcription is toward the centromere of chromosome III. The regulatory mutations in the controlling region were found to be due to small-scale alterations in the DNA rather than to large-scale rearrangements resulting in gene fusions.

Bowling alone: The collapse and revival of American community

Abstract: The present historical moment may seem a particularly inopportune time to review Bowling Alone, Robert Putnam's latest exploration of civic decline in America. After all, the outpouring of volunteerism, solidarity, patriotism, and self-sacrifice displayed by Americans in the wake of the September 11 terrorist attacks appears to fly in the face of Putnam's central argument: that \"social capital\" -defined as \"social networks and the norms of reciprocity and trustworthiness that arise from them\" (p. 19)'has declined to dangerously low levels in America over the last three decades. However, Putnam is not fazed in the least by the recent effusion of solidarity. Quite the contrary, he sees in it the potential to \"reverse what has been a 30to 40-year steady decline in most measures of connectedness or community.\"' As an example of how the current \"war on terrorism\" could generate a durable civic renewal, Putnam points to the burst in civic practices that occurred during and after World War II, which he says \"permanently marked\" the generation that lived through it and had a \"terrific effect on American public life over the last half-century.\" 3 If Americans can follow this example and channel their current civic

Social Media and Fake News in the 2016 Election

Abstract: Following the 2016 U.S. presidential election, many have expressed concern about the effects of false stories (“fake news”), circulated largely through social media. We discuss the economics of fake news and present new data on its consumption prior to the election. Drawing on web browsing data, archives of fact-checking websites, and results from a new online survey, we find: (i) social media was an important but not dominant source of election news, with 14 percent of Americans calling social media their “most important” source; (ii) of the known false news stories that appeared in the three months before the election, those favoring Trump were shared a total of 30 million times on Facebook, while those favoring Clinton were shared 8 million times; (iii) the average American adult saw on the order of one or perhaps several fake news stories in the months around the election, with just over half of those who recalled seeing them believing them; and (iv) people are much more likely to believe stories that favor their preferred candidate, especially if they have ideologically segregated social media networks.

Climate change 2014 - Mitigation of climate change

Abstract: The talk with present the key results of the IPCC Working Group III 5th assessment report. Concluding four years of intense scientific collaboration by hundreds of authors from around the world, the report responds to the request of the world's governments for a comprehensive, objective and policy neutral assessment of the current scientific knowledge on mitigating climate change. The report has been extensively reviewed by experts and governments to ensure quality and comprehensiveness.

Molecular characterization of an enzyme that degrades neuromodulatory fatty-acid amides

Abstract: Endogenous neuromodulatory molecules are commonly coupled to specific metabolic enzymes to ensure rapid signal inactivation. Thus, acetylcholine is hydrolysed by acetylcholine esterase and tryptamine neurotransmitters like serotonin are degraded by monoamine oxidases. Previously, we reported the structure and sleep-inducing properties of cis-9-octadecenamide, a lipid isolated from the cerebrospinal fluid of sleep-deprived cats. cis-9-Octadecenamide, or oleamide, has since been shown to affect serotonergic systems and block gap-junction communication in glial cells (our unpublished results). We also identified a membrane-bound enzyme activity that hydrolyses oleamide to its inactive acid, oleic acid. We now report the mechanism-based isolation, cloning and expression of this enzyme activity, originally named oleamide hydrolase, from rat liver plasma membranes. We also show that oleamide hydrolase converts anandamide, a fatty-acid amide identified as the endogenous ligand for the cannabinoid receptor, to arachidonic acid, indicating that oleamide hydrolase may serve as the general inactivating enzyme for a growing family of bioactive signalling molecules, the fatty-acid amides. Therefore we will hereafter refer to oleamide hydrolase as fatty-acid amide hydrolase, in recognition of the plurality of fatty-acid amides that the enzyme can accept as substrates.