Genètica avui, etologia demà

Genetics today, ethology tomorrow: Neurobiology of the futureThe History of Science has witnessed few cases in which the confrontation of two concepts has stirred up such passion as the issue of «genes and behaviour». Perhaps this is because, often, confrontation is interpreted as if it were, in reality, between«determinism and randomness». Even when this interpretation is wrongly rooted, its emotional effects in any ambit of discussion tend to abort any attempt to apply a rational method to the topic. Although we are aware of this reality, we will try to do so once more

Un experimento de cuarenta años

La democracia trajo a España un caudal de esperanza único en toda su historia. La investigación científica podría haber transformado la economía y la educación de todo el país permitiendo su equiparación con otros de su dimensión poblacional. Los primeros pasos fueron en la dirección correcta pero pronto resultó evidente que había una inercia interna, al tiempo que una falta de voluntad para llegar hasta el final del camino, que frustraron todo el proyecto. No hay que buscar causas externas para este fracaso. La ciencia importa muy poco a nuestra sociedad y, por tanto, a los gestores que nos han representado. Ahora podría haber una nueva oportunidad. ¿Querrán aprovecharla

Monoclonal Antibodies against the Drosophila Nervous System

A panel of 148 monoclonal antibodies directed against Drosophila neural antigens has been prepared by using mice immunized with homogenates of Drosophila tissue. Antibodies were screened immunohistochemically on cryostat sections of fly heads. A large diversity of staining patterns was observed. Some antigens were broadly distributed among tissues; others were highly specific to nerve fibers, neuropil, muscle, the tracheal system, cell nuclei, photoreceptors, or other structures. The antigens for many of the antibodies have been identified on immunoblots. Monoclonal antibodies that identify specific molecules within the nervous system should prove useful in the study of the molecular genetics of neural development

Two Frequenins in Drosophila: unveiling the evolutionary history of an unusual Neuronal Calcium Sensor (NCS) duplication

13 pages, 4 figures, 1 table, 5 additional files.[Background] Drosophila Frequenin (Frq), the homolog of the mammalian Neuronal Calcium Sensor-1 (NCS-1), is a high affinity calcium-binding protein with ubiquitous expression in the nervous system. This protein has an important role in the regulation of neurotransmitter release per synapse, axonal growth and bouton formation. In D. melanogaster, Frequenin is encoded by two genes (frq1 and frq2), a very unexpected feature in the Frq/NCS-1 subfamily. These genes are located in tandem in the same genomic region, and their products are 95% identical in their amino acid sequence, clearly indicating their recent origin by gene duplication. Here, we have investigated the factors involved in this unusual feature by examining the molecular evolution of the two frq genes in Drosophila and the evolutionary dynamics of NCS family in a large set of bilaterian species.[Results] Surprisingly, we have found no amino acid replacements fixed across the twelve Drosophila species surveyed. In contrast, synonymous substitutions have been prevalent in the evolution of the coding region of frq1 and frq2, indicating the presence of strong functional constraints following gene duplication. Despite that, we have detected that significant evolutionary rate acceleration had occurred in Frq1 in early times from the duplication, in which positive selection (likely promoting functional diversification) had probably an important role. The analysis of sequence conservation and DNA topology at the non-coding regions of both genes has allowed the identification of DNA regions candidates to be cis-regulatory elements. The results reveal a possible mechanism of regulatory diversification between frq1 and frq2.[Conclusions] The presence of two Frequenins in Drosophila and the rapid accumulation of amino acid substitutions after gene duplication are very unusual features in the evolution of the Frq/NCS-1 subfamily. Here we show that the action of positive selection in concordance with some extent of regulatory diversification might explain these findings. Selected amino acid substitutions in Frq1 likely contributed to the functional divergence between the two duplicates, which, in turn, should have diverged in their regulation by Ecdysone-induced early genes.Research was funded by grants BFU 2006-10180 and the European Research Network of Excellence MYORES ref.: CE-511978.Peer reviewe

Synapse Loss in Olfactory Local Interneurons Modifies Perception

Synapse loss correlates with cognitive decline in aging and most neurological pathologies. Sensory perception changes often represent subtle dysfunctions that precede the onset of a neurodegenerative disease. However, a cause–effect relationship between synapse loss and sensory perception deficits is difficult to prove and quantify due to functional and structural adaptation of neural systems. Here we modified a PI3K/AKT/GSK3 signaling pathway to reduce the number of synapses—without affecting the number of cells—in five subsets of local interneurons of the Drosophila olfactory glomeruli and measured the behavioral effects on olfactory perception. The neuron subsets were chosen under the criteria of GABA or ChAT expression. The reduction of one subset of synapses, mostly inhibitory, converted the responses to all odorants and concentrations tested as repulsive, while the reduction of another subset, mostly excitatory, led to a shift toward attraction. However, the simultaneous reduction of both synapse subsets restored normal perception. One group of local interneurons proved unaffected by the induced synapse loss in the perception of some odorants, indicating a functional specialization of these cells. Using genetic tools for space and temporal control of synapse number decrease, we show that the perception effects are specific to the local interneurons, rather than the mushroom bodies, and are not based on major structural changes elicited during development. These findings demonstrate that synapse loss cause sensory perception changes and suggest that normal perception is based on a balance between excitation and inhibition.Peer reviewe

Study of biological properties of gold nanoparticles: Low toxicity, no proliferative activity, no ability to induce cell gene expression and no antiviral activity

Gold nanoparticles (AuNPs) are a fundamental building block of many applications across nanotechnology as they have excellent biosafety which make them promising for a broad range of biomedical applications. Here we explore their in vivo toxicity, cytotoxicity and proliferative capacity in human keratinocyte HaCaT cells, their ability to induce gene expression and their antiviral properties against a surrogate of SARS-CoV-2. These nanoparticles were characterized by transmission electron microscopy, dynamic light scattering and zeta potential. The results showed that these AuNPs with sizes ranging from 10 to 60 nm are non-toxic in vivo at any concentration up to 800 μg/mL. However, AuNP cytotoxicity in human HaCaT cells is time-dependent, so that concentrations of up to 300 μg/mL did not show any in vitro toxic effect at 3, 12 and 24 h, although higher concentrations were found to have some significant toxic activity, especially at 24 h. No significant proliferative activity was observed when using low AuNP concentrations (10, 20 and 40 μg/mL), while the AuNP antiviral tests indicated low or insignificant antiviral activity. Surprisingly, none of the 13 analyzed genes had their expressions modified after 24 h's exposure to AuNPs. Therefore, the results show that AuNPs are highly stable inactive materials and thus very promising for biomedical and clinical applications demanding this type of materials

Microbial Succession in the Gut: Directional Trends of Taxonomic and Functional Change in a Birth Cohort of Spanish Infants

In spite of its major impact on life-long health, the process of microbial succession in the gut of infants remains poorly understood. Here, we analyze the patterns of taxonomic and functional change in the gut microbiota during the first year of life for a birth cohort of 13 infants. We detect that individual instances of gut colonization vary in the temporal dynamics of microbiota richness, diversity, and composition at both functional and taxonomic levels. Nevertheless, trends discernible in a majority of infants indicate that gut colonization occurs in two distinct phases of succession, separated by the introduction of solid foods to the diet. This change in resource availability causes a sharp decrease in the taxonomic richness of the microbiota due to the loss of rare taxa (p = 2.06e-9), although the number of core genera shared by all infants increases substantially. Moreover, although the gut microbial succession is not strictly deterministic, we detect an overarching directionality of change through time towards the taxonomic and functional composition of the maternal microbiota. Succession is however not complete by the one year mark, as significant differences remain between one-year-olds and their mothers in terms of taxonomic (p = 0.009) and functional (p = 0.004) microbiota composition, and in taxonomic richness (p = 2.76e-37) and diversity (p = 0.016). Our results also indicate that the taxonomic composition of the microbiota shapes its functional capacities. Therefore, the observed inter-individual variability in taxonomic composition during succession is not fully compensated by functional equivalence among bacterial genera and may have important physiological consequences. Finally, network analyses suggest that positive interactions among core genera during community assembly contribute to ensure their permanence within the gut, and highlight an expansion of complexity in the interactions network as the core of taxa shared by all infants grows following the introduction of solid foods. © 2014 Vallès et al.This work has been supported by the Spanish MICINN (project SAF2009-13032-C02-02 and project CSD2009-00006 of the CONSOLIDER program). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer Reviewe