Septins From Protists to People

Septin GTPases form nonpolar heteropolymers that play important roles in cytokinesis and other cellular processes. The ability to form heteropolymers appears to be critical to many septin functions and to have been a major driver of the high conservation of many septin domains. Septins fall into five orthologous groups. Members of Groups 1–4 interact with each other to form heterooligomers and are known as the “core septins.” Representative core septins are present in all fungi and animals so far examined and show positional orthology with monomer location in the heteropolymer conserved within groups. In contrast, members of Group 5 are not part of canonical heteropolymers and appear to interact only transiently, if at all, with core septins. Group 5 septins have a spotty distribution, having been identified in specific fungi, ciliates, chlorophyte algae, and brown algae. In this review we compare the septins from nine well-studied model organisms that span the tree of life (Homo sapiens, Drosophila melanogaster, Schistosoma mansoni, Caenorhabditis elegans, Saccharomyces cerevisiae, Aspergillus nidulans, Magnaporthe oryzae, Tetrahymena thermophila, and Chlamydomonas reinhardtii). We focus on classification, evolutionary relationships, conserved motifs, interfaces between monomers, and positional orthology within heteropolymers. Understanding the relationships of septins across kingdoms can give new insight into their functions.

ASPECTOS GENÉTICOS E BIOQUÍMICOS DE HTR1B NO TRANSTORNO DO DÉFICIT DE ATENÇÃO COM HIPERATIVIDADE

O transtorno de déficit de atenção e hiperatividade (TDAH) tem origem multifatorial, geralmente revelado na infância e, em alguns casos, acompanha o indivíduo por toda a vida, apresentando sintomas de desatenção, hiperatividade e impulsividade. Dada a sua importância para a saúde pública, diversos estudos vêm sendo realizados buscando sua correlação com a expressão de genes específicos, incluindo o receptor de 5-hidroxitriptamina 1B (HTR1B) que expressa um dos receptores de serotonina e é o alvo deste estudo. Dados levantados a partir de biologia computacional revelaram que o HTR1B está localizado no cromossomo 6, em 6q14.1, e está intimamente relacionado com transtornos mentais e comportamentais. Sua expressão ocorre em diversos tecidos humanos, com destaque no córtex cerebral que é a região mais afetada no TDAH. A correlação do gene HTR1B e o TDAH é explicada pela associação do C861G (polimorfismo de nucleotídeo único) com os sintomas característicos do transtorno, revelando a suscetibilidade dos portadores deste polimorfismo. O alinhamento da sequência de HTR1B de Homo sapiens revelou alta identidade com espécies de primatas, majoritariamente chimpanzés. Dada a importância do TDAH para os indivíduos acometidos e os prejuízos adquiridos, a continuidade de estudos que relacionem o transtorno e a expressão gênica e proteica de HTR1B se faz necessária, visando avanços no diagnóstico, tratamento e prevenção.

We are all migrants

Migration is the basis for development—economic, social, and psychological. In this paper I will examine borders on migration that entail the ambivalent relating by the societal context of migration to the act of movement of the people who become migrants, and their counterparts (“counter-migrants”) who do not. My focus on the issue stems from my theory of Cultural Psychology of Semiotic Dynamics that can deal with the process of becoming, being, and feeling as “migrant” or “counter-migrant”. A societal rule system is fortified by the system of social representations of the people who—by the act of moving from one place to another—are designated to become migrants by the rule systems of the non-migrants. Cultural psychology contributes to the study of the emerging prejudices and ways of their overcoming by the non-migrant local recipients as well as to the ambivalences of the persons who move to the relating with the social role “migrant” and its overcoming. Historically speaking—we as the species of Homo sapiens are all migrants—only at differing times and circumstances.

Synthetic Riboswitches for the Analysis of tRNA Processing by eukaryotic RNase P Enzymes

Removal of the 5' leader region is an essential step in the maturation of tRNA molecules in all domains of life. This reaction is catalyzed by various RNase P activities, ranging from ribonucleoproteins with ribozyme activity to protein-only forms. In Escherichia coli, the efficiency of RNase P mediated cleavage can be controlled by computationally designed riboswitch elements in a ligand-dependent way, where the 5' leader sequence of a tRNA precursor is either sequestered in a hairpin structure or presented as a single-stranded region accessible for maturation. In the presented work, the regulatory potential of such artificial constructs is tested on different forms of eukaryotic RNase P enzymes – two protein-only RNase P enzymes (PRORP1 and PRORP2) from Arabidopsis thaliana and the ribonucleoprotein of Homo sapiens. The PRORP enzymes were analyzed in vitro as well as in vivo in a bacterial RNase P complementation system. We also tested in HEK293T cells whether the riboswitches remain functional with human nuclear RNase P. While the regulatory principle of the synthetic riboswitches applies for all tested RNase P enzymes, the results also show differences in the substrate requirements of the individual enzyme versions. Hence, such designed RNase P riboswitches represent a novel tool to investigate the impact of the structural composition of the 5'-leader on substrate recognition by different types of RNase P enzymes.

Gene Function Prediction in Five Model Eukaryotes Exclusively Based on Gene Relative Location Through Machine Learning

The function of most genes is unknown. The best results in automated function prediction are obtained with machine learning-based methods that combine multiple data sources, typically sequence derived features, protein structure and interaction data. Even though there is ample evidence showing that a gene’s function is not independent of its location, the few available examples of gene function prediction based on gene location rely on sequence identity between genes of different organisms and are thus subjected to the limitations of the relationship between sequence and function. Here we predict thousands of gene functions in five model eukaryotes (Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, Mus musculus and Homo sapiens) using machine learning models exclusively trained with features derived from the location of genes in the genomes to which they belong. Our aim was not to obtain the best performing method to automated function prediction but to explore the extent to which a gene's location can predict its function in eukaryotes. We found that our models outperform BLAST when predicting terms from Biological Process and Cellular Component Ontologies, showing that, at least in some cases, gene location alone can be more useful than sequence to infer gene function.