Congenital Nystagmus Gene FRMD7 Is Necessary for Establishing a Neuronal Circuit Asymmetry for Direction Selectivity.

Neuronal circuit asymmetries are important components of brain circuits, but the molecular pathways leading to their establishment remain unknown. Here we found that the mutation of FRMD7, a gene that is defective in human congenital nystagmus, leads to the selective loss of the horizontal optokinetic reflex in mice, as it does in humans. This is accompanied by the selective loss of horizontal direction selectivity in retinal ganglion cells and the transition from asymmetric to symmetric inhibitory input to horizontal direction-selective ganglion cells. In wild-type retinas, we found FRMD7 specifically expressed in starburst amacrine cells, the interneuron type that provides asymmetric inhibition to direction-selective retinal ganglion cells. This work identifies FRMD7 as a key regulator in establishing a neuronal circuit asymmetry, and it suggests the involvement of a specific inhibitory neuron type in the pathophysiology of a neurological disease. VIDEO ABSTRACT.

Consequences of lineage-specific gene loss on functional evolution of surviving paralogs: ALDH1A and retinoic acid signaling in vertebrate genomes

Genome duplications increase genetic diversity and may facilitate the evolution of gene subfunctions. Little attention, however, has focused on the evolutionary impact of lineage-specific gene loss. Here, we show that identifying lineage-specific gene loss after genome duplication is important for understanding the evolution of gene subfunctions in surviving paralogs and for improving functional connectivity among human and model organism genomes. We examine the general principles of gene loss following duplication, coupled with expression analysis of the retinaldehyde dehydrogenase Aldh1a gene family during retinoic acid signaling in eye development as a case study. Humans have three ALDH1A genes, but teleosts have just one or two. We used comparative genomics and conserved syntenies to identify loss of ohnologs (paralogs derived from genome duplication) and to clarify uncertain phylogenies. Analysis showed that Aldh1a1 and Aldh1a2 form a clade that is sister to Aldh1a3-related genes. Genome comparisons showed secondarily loss of aldh1a1 in teleosts, revealing that Aldh1a1 is not a tetrapod innovation and that aldh1a3 was recently lost in medaka, making it the first known vertebrate with a single aldh1a gene. Interestingly, results revealed asymmetric distribution of surviving ohnologs between co-orthologous teleost chromosome segments, suggesting that local genome architecture can influence ohnolog survival. We propose a model that reconstructs the chromosomal history of the Aldh1a family in the ancestral vertebrate genome, coupled with the evolution of gene functions in surviving Aldh1a ohnologs after R1, R2, and R3 genome duplications. Results provide evidence for early subfunctionalization and late subfunction-partitioning and suggest a mechanistic model based on altered regulation leading to heterochronic gene expression to explain the acquisition or modification of subfunctions by surviving ohnologs that preserve unaltered ancestral developmental programs in the face of gene loss.

Experimental Cournot oligopoly and inequity aversion

This paper explores the role of inequity aversion as an explanation for observed behavior in experimental Cournot oligopolies. We show that inequity aversion can change the nature of the strategic interaction: quantities are strategic substitutes for sufficiently asymmetric output levels but strategic complements otherwise. We find that inequity aversion can explain why: (i) some experiments result in higher than Cournot-Nash production levels while others result in lower, (ii) collusion often occurs with only two players whereas with three or more players market outcomes are very close to Cournot-Nash, and (iii) players often achieve equal profits in asymmetric Cournot oligopoly.

Total synthesis of (-)-isoavenaciolide

An enantioselective approach to (-)-isoavenaciolide was achieved starting from 1- undecyn-3-ol. The synthesis relied upon the preparation of a chiral 4-silyloxy-2-alkenylborane by hydroboration of a protected 2,3-allenol and subsequent stereoselective addition to 2- thiophenecarboxaldehyde

Mode of interaction of the Gαo subunit of heterotrimeric G proteins with the GoLoco1 motif of Drosophila Pins is determined by guanine nucleotides.

Drosophila GoLoco motif-containing protein Pins is unusual in its highly efficient interaction with both GDP- and the GTP-loaded forms of the α-subunit of the heterotrimeric Go protein. We analysed the interactions of Gαo in its two nucleotide forms with GoLoco1-the first of the three GoLoco domains of Pins-and the possible structures of the resulting complexes, through combination of conventional fluorescence and FRET measurements as well as through molecular modelling. Our data suggest that the orientation of the GoLoco1 motif on Gαo significantly differs between the two nucleotide states of the latter. In other words, a rotation of the GoLoco1 peptide in respect with Gαo must accompany the nucleotide exchange in Gαo. The sterical hindrance requiring such a rotation probably contributes to the guanine nucleotide exchange inhibitor activity of GoLoco1 and Pins as a whole. Our data have important implications for the mechanisms of Pins regulation in the process of asymmetric cell divisions.

Complex patterns of global spread in invasive insects: eco-evolutionary and management consequences

The advent of simple and affordable tools for molecular identification of novel insect invaders and assessment of population diversity has changed the face of invasion biology in recent years. The widespread application of these tools has brought with it an emerging understanding that patterns in biogeography, introduction history and subsequent movement and spread of many invasive alien insects are far more complex than previously thought. We reviewed the literature and found that for a number of invasive insects, there is strong and growing evidence that multiple introductions, complex global movement, and population admixture in the invaded range are commonplace. Additionally, historical paradigms related to species and strain identities and origins of common invaders are in many cases being challenged. This has major consequences for our understanding of basic biology and ecology of invasive insects and impacts quarantine, management and biocontrol programs. In addition, we found that founder effects rarely limit fitness in invasive insects and may benefit populations (by purging harmful alleles or increasing additive genetic variance). Also, while phenotypic plasticity appears important post-establishment, genetic diversity in invasive insects is often higher than expected and increases over time via multiple introductions. Further, connectivity among disjunct regions of global invasive ranges is generally far higher than expected and is often asymmetric, with some populations contributing disproportionately to global spread. We argue that the role of connectivity in driving the ecology and evolution of introduced species with multiple invasive ranges has been historically underestimated and that such species are often best understood in a global context.

Contribuições recentes da reação de hidroformilação na síntese de produtos farmacêuticos: parte II

The hydroformylation reaction represents one of the most important C1-chemistry area in the chemical industry. This catalytic process, which has been developed up to now mainly to the production of commodities chemicals, has shown a remarkable potential for the preparation of several categories of specialty chemicals and in particular pharmaceutical compounds. Arylpropanoic acids, various amines containing aryl groups, and intermediates for the preparation of vitamins, carbocyclic and heterocyclic compounds and many other classes of organic molecules endowed with pharmacological activity are currently accessible in good-to-high yields through hydroformylation of selected olefinic substrates. The asymmetric hydroformylation is going to reach the stage of maturity and hence to contribute in solving many troublesome synthetic problems connected with the preparation of pharmacologically active compounds with very high enantiomeric purity. The present survey emphasizes the usefulness of synthesis gas as a starting material in fine chemistry, which is expected to be important for industry.

Estereosseletividade em reações eletródicas

This review discusses the present state of the art of the stereochemistry of electrochemical reactions. The extent of asymmetric induction is progressing, but in general diastereoselectivities and enantioselectivities remain behind those from chemical synthesis. In recent years, new methodological developments have been successful. Effects that play important roles in homogeneous chemistry have been used with success. Lack of expressive enantiomeric excess (ee) could be related to the absence of tightly organized structures during the reaction of interest. The highest ee might be expected for redox reactions where conformational preference in transition state plays the important role or for the ones performed while adsorbed on the electrode, and where the chiral element is also at the surface, either adsorbed or chemically bound to the surface and interacting directly with the substrate. Electroenzymatic synthesis has a promising future.

Paleontological research on late Triassic radiolarians from Oman and Sicily

Les radiolaires sont des unicellulaires planctoniques qui peuplent nos océans depuis plus de 500 millions d'années. Ces microorganismes développent un squelette en silice ayant des géométries extrêmement diversifiées et sophistiqués qui varient rapidement à l'échelle géologique et permettent de construire des échelles biochronologiques basées sur les différents assemblages qui se succèdent dans le temps. On retrouve ces organismes à l'état fossile dans les roches ma¬rines siliceuse desquelles on peut les extraire avec de l'acide. Des échantillons provenant du sultanat d'Oman et de Sicile ont été étudiés afin de mieux com¬prendre les relations de parenté entre les groupes et de comparer les faunes avec celles du même âge venant de Colombie britannique, du Japon et de Turquie, qui sont représentatives de divers domaines océaniques de l'époque. Certains radiolaires possèdent un anneau autour de leur coque centrale sphérique et ont ainsi été baptisés Saturnalides. Il y a 215 millions d'années, au Norien moyen, ce groupe se diversifie soudainement et donne naissance à une multitude d'espèces qui évoluent rapidement ce qui a permis d'établir des subdivisions temporelles supplémentaires et d'affiner les zonations exis¬tantes. L'étude détaillée de formes intermédiaires entre les espèces a permis d'établir de nouveaux liens de parenté et de considérer le genre Praehexasaturnalis comme l'ancêtre probable de nom¬breuses formes dans le Norien moyen et supérieur. Grâce à l'étude comparative des espèces de Saturnalidae allant du Mésozoïque au Cénozoïque, un certain type d'asymétrie de l'anneau a pu être identifiée comme étant propre à cette famille et plus précisément liée à la disposition de la coque la plus interne (microsphère). Deux nouveaux genres, Blechschmidtia et Tjerkium, s'inscrivent dans une lignée parallèle au Saturnalidae. Cette lignée met en évidence la formation au cours du temps d'un anneau à partir de la fusion de deux épines opposées. -- Late Triassic marine deposits of the Tethyan realm have been investigated in the Sultanate of Oman and in Sicily in order to contribute to the knowledge of radiolarian taxonomy and bio- stratigraphy of this key period preceding the Triassic-Jurassic boundary. In the middle Norian, the saturnalid radiolarians display intense diversification. This blooming of fast evolving spe¬cies has been used to establish a new zonation based on evolutionary successions that refine the existing zonal schemes. One new genus and 16 new species are described. The chronologic distribution of 172 species belonging to 72 genera is established from five sections in the Umar and Al Aridh units of the Hawasina Basin. Many Late Triassic saturnalid species are interpreted to originate from the genus Praehexasaturnalis Kozur & Mostler, which shows strong morpho¬logical diversification patterns. Detailed comparative studies of different types of asymmetric ring morphologies of Mesozoic to Cainozoic saturnalid species permitted to relate the origin of the asymmetry to the disposition of the initial skeletal structure and to gain new insight on the internal and external geometrical transformations of this group trough time and how the emergence of new families is induced by environmental stress. RÉSUMÉ Les formations marines du Trias supérieur du domaine téthysien ont été étudiées dans le Sultanat d'Oman et en Sicile afin de contribuer à la connaissance et au développement de la taxonomie et de la biostratigraphie des radiolaires de cette période clé qui précède la crise de la limite Trias-Jurassique. Au Norien moyen, les radiolaires Saturnalides montrent une intense diversi¬fication. Ce véritable "bloom" d'espèces qui évoluent rapidement a été utilisé pour l'établisse¬ment d'une nouvelle zonation basée sur les successions évolutives de ce groupe qui permettent d'affiner les subdivisions biochronologiques existantes. Un nouveau genre et seize nouvelles espèces sont décrits. La distribution stratigraphique de 172 espèces appartenant à 72 genres est établie pour 5 sections dans les unités d'Umar et d'Al Aridh du bassin de Hawasina. Un essai d'établissement d'une phylogénèse des Saturnalidae du Trias supérieur mène à proposer que le genre Praehexasaturnalis Kozur & Mostler est l'ancêtre de beaucoup d'espèces de Saturnalidae du Trias supérieur. L'étude comparative détaillée des différents types d'asymétrie de l'anneau chez les Saturnali¬dae du Mésozoïque au Cénozoïque a permis de lier l'origine de ce phénomène à la disposition de la structure initiale de leur squelette et par ce fait d'avoir une meilleure compréhension des transformations géométriques internes et externes subies par ce groupe au cours du temps et de concevoir comment l'émergence de nouvelles familles est induite lors de périodes de stress environnemental.

Projeto e construção de um bioreator para síntese orgânica assimétrica catalisada por saccharomyces cerevisiae (fermento biológico de padaria)

A model for the construction of a simple and cheap apparatus to be used as bioreactor for reactions catalyzed by baker's yeast (Saccharomyces cerevisiae) is described. The bioconversion and separation of cells from products and residual substrates are obtained at the same time. The reactions carried out in this type of reactor are faster than those catalyzed by immobilized cells. Yeast cells can be cultivated in this bioreactor operating with cell recycling at appropriated conditions using glucose and other nutrients.

Substâncias enantiomericamente puras (SEP): a questão dos fármacos quirais

The thalidomide disaster, in the 60,s, is the most painful reminder of the importance of chirality for biological activity. After this episode, much attention has been devoted to study the correlations between toxicological and pharmacological properties and chirality. Actualy, to get a licence for a new chiral drug in EUA, European community and Japan, it is necessary to study the biological properties of each enatiomer independently. This article presents an overview about the importance of the chirality of organic compounds and its relationships with biological activity, asymmetric synthetic methodologies and market.

Unsaturated Oxazolopiperidone Lactams: an Unexpected Domino-type Double Conjugate Additioncyclization Process

Reactions of 2-acetylindole enolate with unsaturated oxazolopiperidones 3, 4 and 10 unexpectedly gives pentacyclic dilactams 6, 7 and 11, respectively, resulting from a domino-type process involving two successive conjugate additions and a final cyclization.

Abordagens em síntese assimétrica

The approaches in asymmetric synthesis as the chiron approach, chiral auxiliaries, chiral reagents and asymmetric catalysis are described in a simplified way.

Ilmaan johdettavien epäpuhtauksien päästökartoitus Porvoon öljynjalostamolla

Työn tarkoituksena oli laatia suunnitelma ilmaan johdettavien epäpuhtauksien päästökartoitukselle Porvoon öljynjalostamolla. Raskasmetallien, metaanin, fluorivetyhapon, rikkivedyn ja ammoniakin merkittävät päästöpaikat ja -tarkkailumenetelmät kartoitettaisiin tulevaa päästöraportointia varten. Tarkkailun alaisten komponenttien muodostuminen, kulkeutuminen ja merkittävät päästöpaikat Porvoon jalostamolla selvitettiin kirjallisuuslähteiden, jalostamon toimintajärjestelmän ohjeiden sekä työntekijöiden haastattelujen perusteella. Merkittäviä häiriöpäästötilanteita kartoitettiin ja arvioitiin jalostamon poikkeamatilastojen ja haastattelujen avulla. Normaalitoiminnan aikana tarkkailun alaisista epäpuhtauksista vapautuu ilmaan merkittäviä määriä ainoastaan metaania ja raskasmetalleja. Metaania vapautuu ilmaan polttoprosesseissa sekä hajapäästönä. Raskasmetallipäästöjä syntyy pohjaöljyn poltossa energialaitoksella sekä leijukatalyyttisessä krakkauksessa. Rikkilaitosten häiriötilanteista aiheutuu rikkivety- ja ammoniakkipäästöjä pääasiassa soihtujärjestelmän kautta. Alkylointiyksikön vuodoissa voi vapautua fluorivetyhappoa ilmaan. Päästömääriä arvioidaan pääosin laskennallisesti. Päästökartoitussuunnitelma on kokonaisuudessaan tämän työn liitteenä. Näyttäisi siltä, että TRS-yhdisteiden, ammoniakin ja fluorivetyhapon ilmapäästöt eivät ole merkittäviä Porvoon öljynjalostamolla. Uuden pohjaöljy-yksikön käyttöönotto on vähentänyt myös raskasmetallipäästöjä energialaitoksella. Metaanipäästö vaikuttaa kartoitukseen sisällytettävistä epäpuhtauksista merkityksellisimmältä Porvoon öljynjalostamolla.

Time-varying Risk Premiums and Conditional Market Risk: Empirical Evidence from European Stock Markets

This study investigates the relationship between the time-varying risk premiums and conditional market risk in the stock markets of the ten member countries of Economy and Monetary Union. Second, it examines whether the conditional second moments change over time and are there asymmetric effects in the conditional covariance matrix. Third, it analyzes the possible effects of the chosen testing framework. Empirical analysis is conducted using asymmetric univariate and multivariate GARCH-in-mean models and assuming three different degrees of market integration. For a daily sample period from 1999 to 2007, the study shows that the time-varying market risk alone is not enough to explain the dynamics of risk premiums and indications are found that the market risk is detected only when its price is allowed to change over time. Also asymmetric effects in the conditional covariance matrix, which is found to be time-varying, are clearly present and should be recognized in empirical asset pricing analyses.