Molecular organization of vomeronasal chemoreception

The vomeronasal organ (VNO) has a key role in mediating the social and defensive responses of many terrestrial vertebrates to species- and sex-specific chemosignals. More than 250 putative pheromone receptors have been identified in the mouse VNO, but the nature of the signals detected by individual VNO receptors has not yet been elucidated. To gain insight into the molecular logic of VNO detection leading to mating, aggression or defensive responses, we sought to uncover the response profiles of individual vomeronasal receptors to a wide range of animal cues. Here we describe the repertoire of behaviourally and physiologically relevant stimuli detected by a large number of individual vomeronasal receptors in mice, and define a global map of vomeronasal signal detection. We demonstrate that the two classes (V1R and V2R) of vomeronasal receptors use fundamentally different strategies to encode chemosensory information, and that distinct receptor subfamilies have evolved towards the specific recognition of certain animal groups or chemical structures. The association of large subsets of vomeronasal receptors with cognate, ethologically and physiologically relevant stimuli establishes the molecular foundation of vomeronasal information coding, and opens new avenues for further investigating the neural mechanisms underlying behaviour specificity.     

Diet composition of an invasive population of Lithobates catesbeianus (American Bullfrog) from Argentina

The American bullfrog Lithobates catesbeianus has been introduced around the world, with invasive populations reported from almost all South American countries. A population of this species was introduced in the Calingasta department of San Juan province, which is an arid environment in western Argentina. This work provides information on the dietary composition of an invasive population of L. catesbeianus, and compares the degree of dietary overlap between adults and juveniles. Stomach contents of 169 bullfrogs (82 adults and 87 juveniles) were analysed. Adults consumed 40 prey taxa and Hymenoptera (Insecta) was the most numerous prey item (41.8%), followed by Araneae (13.6%) and Aeglidae (13.4%). Juveniles consumed 29 prey taxa and Hymenoptera constituted the highest percentage in prey number (77.2%). The trophic overlap niche index at the same level shows a value of 0.64 overlap in dietary community between adults and juveniles of this bullfrog. Aeglidae was volumetrically the most important trophic item (25.4%), followed by Anura (25.02%). Our results showed that cannibalism in bullfrogs is more common than the consumption of native anurans, coinciding with that reported in other populations of introduced bullfrogs. The high similarity in the diets of both size classes and the association between the size of the predator and prey suggest that the impact caused by bullfrogs throughout their ontogeny is high and probably has an impact on their prey. Freshwater crabs are the main items in the diet of Lithobates catesbeianus in other introduced populations and are usually the most conspicuous at our study site. The crabs in freshwater ecosystems are part of the lowest trophic level in the food chain. The major threats to the southern region’s freshwater crabs include deforestation, farming and exotic species. Lithobates catesbeianus has a generalist diet and high overlap between adults and juveniles.     

Arithmetization and Rigor as Beliefs in the Development of Mathematics

With the arrival of the nineteenth century, a process of change guided the treatment of three basic elements in the development of mathematics: rigour, the arithmetization and the clarification of the concept of function, categorised as the most important tool in the development of the mathematical analysis. In this paper we will show how several prominent mathematicians contributed greatly to the development of these basic elements that allowed the solid underpinning of mathematics and the consideration of mathematics as an axiomatic way of thinking in which anyone can deduce valid conclusions from certain types of premises. This nineteenth century stage shares, possibly with the Heroic Age of Ancient Greece, the most revolutionary period in all history of mathematics.     

Tetrapyrrole biosynthesis from 4,5-dioxovaleric acid in rhodopseudomonas spheroides.

Prophyrin biosynthesis from 4,5-dioxovaleric acid was studied in cell suspensions of R. spheroides. The experiments show that 4,5-dioxovaleric acid is a far precursor of porphyrins through delta amino laevulinic acid formation in a transmination reaction involving also l-alanine. It differs radically from the classical delta aminolaevulinic acid synthesis using glycine and succinyl CoA as substrates.     

Tetrapyrrole biosynthesis from 4,5-dioxovaleric acid inRhodopseudomonas spheroides

Summary Porphyrin biosynthesis from 4,5-dioxovaleric acid was studied in cell suspensions ofR. spheroides. The experiments show that 4,5-dioxovaleric acid is a far precursor of porphyrins through amino laevulinic acid formation in a transamination reaction involving also 1-alanine. It differs radically from the classical aminolaevulinic acid synthesis using glycine and succinyl CoA as substrates.Acknowledgments: The authors are indebted to Dr Rodolfo García for helpful discussions and criticisms. Special thanks are given to Dr Aldo Mitta and other members of the Comisión Nacional de la Energía Atómica for their continuous help and support and for using their facilities in order to synthetise DVA.     

Reaction path of protein farnesyltransferase at atomic resolution

Protein farnesyltransferase (FTase) catalyses the attachment of a farnesyl lipid group to numerous essential signal transduction proteins, including members of the Ras superfamily. The farnesylation of Ras oncoproteins, which are associated with 30% of human cancers, is essential for their transforming activity. FTase inhibitors are currently in clinical trials for the treatment of cancer. Here we present a complete series of structures representing the major steps along the reaction coordinate of this enzyme. From these observations can be deduced the determinants of substrate specificity and an unusual mechanism in which product release requires binding of substrate, analogous to classically processive enzymes. A structural model for the transition state consistent with previous mechanistic studies was also constructed. The processive nature of the reaction suggests the structural basis for the successive addition of two prenyl groups to Rab proteins by the homologous enzyme geranylgeranyltransferase type-II. Finally, known FTase inhibitors seem to differ in their mechanism of inhibiting the enzyme.     

ALCAM/CD166 adhesive function is regulated by the tetraspanin CD9

ALCAM/CD166 is a member of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAMs) which mediates intercellular adhesion through either homophilic (ALCAM–ALCAM) or heterophilic (ALCAM–CD6) interactions. ALCAM-mediated adhesion is crucial in different physiological and pathological phenomena, with particular relevance in leukocyte extravasation, stabilization of the immunological synapse, T cell activation and proliferation and tumor growth and metastasis. Although the functional implications of ALCAM in these processes is well established, the mechanisms regulating its adhesive capacity remain obscure. Using confocal microscopy colocalization, and biochemical and functional analyses, we found that ALCAM directly associates with the tetraspanin CD9 on the leukocyte surface in protein complexes that also include the metalloproteinase ADAM17/TACE. The functional relevance of these interactions is evidenced by the CD9-induced upregulation of both homophilic and heterophilic ALCAM interactions, as reflected by increased ALCAM-mediated cell adhesion and T cell migration, activation and proliferation. The enhancement of ALCAM function induced by CD9 is mediated by a dual mechanism involving (1) augmented clustering of ALCAM molecules, and (2) upregulation of ALCAM surface expression due to inhibition of ADAM17 sheddase activity.     

Tegmina-size variation in a Neotropical cricket with implications on spectral song properties

This study evaluates the relationship between shape and size of tegmen, harp, mirror, and spectral range of calling song frequency of a Neotropical cricket subpopulation (Lerneca inalata beripocone. In addition, we compare intraspecific morphological divergence and calling song properties between individuals from different sites of the Pantanal of Poconé, Mato Grosso, Brazil. Regression analysis showed that the dominant and maximum calling song frequencies were negatively correlated with tegmen size, i.e. frequencies are either lower or higher depending on the corresponding size variation in resonance structures of the forewings. Canonical variable analysis demonstrated marked intraspecific differences in morphometric characters between localities of a L. inalata subpopulation c. 35 km apart (SESC-Pantanal Advanced Research Base and Pouso Alegre Farm, Mato Grosso, Brazil). Lerneca inalata beripocone at SESC had larger forewings than conspecifics from Pouso Alegre Farm. These morphological variations of wing properties related to reproductive behaviours were interpreted as fitness parameters, likely shaped by restricted gene flow during temporal habitat isolation episodes. Such isolation patterns occur in the Pantanal wetlands for several months during the annual hydrological cycle.     

Nestin-expressing progenitor cells: function,identity and therapeutic implications

The neuroepithelial stem cell protein, or Nestin, is a cytoskeletal intermediate filament initially characterized in neural stem cells. However, current extensive evidence obtained in in vivo models and humans shows presence of Nestin⁺ cells with progenitor and/or regulatory functions in a number of additional tissues, remarkably bone marrow. This review presents the current knowledge on the role of Nestin in essential stem cell functions, including self-renewal/proliferation, differentiation and migration, in the context of the cytoskeleton. We further discuss the available in vivo models for the study of Nestin⁺ cells and their progeny, their function and elusive nature in nervous system and bone marrow, and their potential mechanistic role and promising therapeutic value in preclinical models of disease. Future improved in vivo models and detection methods will allow to determine the true essence of Nestin⁺ cells and confirm their potential application as therapeutic target in a range of diseases.     

Financial density forecasts: A comprehensive comparison of risk‐neutral and historical schemes

We investigate the forecasting ability of the most commonly used benchmarks in financial economics. We approach the usual caveats of probabilistic forecasts studies—small samples, limited models, and nonholistic validations—by performing a comprehensive comparison of 15 predictive schemes during a time period of over 21 years. All densities are evaluated in terms of their statistical consistency, local accuracy and forecasting errors. Using a new composite indicator, the integrated forecast score, we show that risk‐neutral densities outperform historical‐based predictions in terms of information content. We find that the variance gamma model generates the highest out‐of‐sample likelihood of observed prices and the lowest predictive errors, whereas the GARCH‐based GJR‐FHS delivers the most consistent forecasts across the entire density range. In contrast, lognormal densities, the Heston model, or the nonparametric Breeden–Litzenberger formula yield biased predictions and are rejected in statistical tests.