RESUMEN
Circular RNAs (circRNAs) are a large class of noncoding RNAs. Despite the identification of thousands of circular transcripts, the biological significance of most of them remains unexplored, partly because of the lack of effective methods for generating loss-of-function animal models. In this study, we focused on circTulp4, an abundant circRNA derived from the Tulp4 gene that is enriched in the brain and synaptic compartments. By creating a circTulp4-deficient mouse model, in which we mutated the splice acceptor site responsible for generating circTulp4 without affecting the linear mRNA or protein levels, we were able to conduct a comprehensive phenotypic analysis. Our results demonstrate that circTulp4 is critical in regulating neuronal and brain physiology, modulating the strength of excitatory neurotransmission and sensitivity to aversive stimuli. This study provides evidence that circRNAs can regulate biologically relevant functions in neurons, with modulatory effects at multiple levels of the phenotype, establishing a proof of principle for the regulatory role of circRNAs in neural processes.
Asunto(s)
Encéfalo , ARN Circular , Transmisión Sináptica , ARN Circular/genética , Animales , Ratones , Encéfalo/metabolismo , Encéfalo/fisiología , Ratones Noqueados , Neuronas/metabolismo , Neuronas/fisiologíaRESUMEN
Computer-assisted species recognition facilitates the analysis of relevant biological information in continuous audio recordings. In the present study, we assess the suitability of this approach for determining distinct life-cycle phases of the Southern Lapwing Vanellus chilensis lampronotus based on adult vocal activity. For this purpose we use passive 14-min and 30-min soundscape recordings (n = 33 201) collected in 24/7 mode between November 2012 and October 2013 in Brazil's Pantanal wetlands. Time-stamped detections of V. chilensis call events (n = 62 292) were obtained with a species-specific sound recognizer. We demonstrate that the breeding season fell in a three-month period from mid-May to early August 2013, between the end of the flood cycle and the height of the dry season. Several phases of the lapwing's life history were identified with presumed error margins of a few days: pre-breeding, territory establishment and egg-laying, incubation, hatching, parental defense of chicks, and post-breeding. Diurnal time budgets confirm high acoustic activity levels during midday hours in June and July, indicative of adults defending young. By August, activity patterns had reverted to nonbreeding mode, with peaks around dawn and dusk and low call frequency during midday heat. We assess the current technological limitations of the V. chilensis recognizer through a comprehensive performance assessment and scrutinize the usefulness of automated acoustic recognizers in studies on the distribution pattern, ecology, life history, and conservation status of sound-producing animal species.
Asunto(s)
Acústica , Conducta Animal/fisiología , Reconocimiento de Normas Patrones Automatizadas/métodos , Sonido , Vocalización Animal , Animales , Aves , Procesamiento de Señales Asistido por ComputadorRESUMEN
The first record of the Orthoptera species Lerneca inalata for Brazil is presented here. The taxon is represented by a new subspecies Lerneca inalata beripocone subsp. nov. (Phalangopsidae, Luzarinae), collected in the Pantanal of Poconé, Mato Grosso, Brazil. This work includes morphological and morphometric data as well as descriptions of female genitalia and calling song. The new subspecies has as diagnostic features the male genitalia with six ventral spines on the B sclerite, the first spine having a subtle bifurcation; the mid-region of the strongly sclerotized pseudepiphallus; inclination of C sclerite with slightly concave curvature; tegmina-length ratio and the speculum (syn. mirror) width approximately three times the length of the apical area. The description of the female genitalia and the calling song is presented for the first time for the species Lerneca inalata. A distribution map covers the local occurrence of its subspecies.
Asunto(s)
Ortópteros/clasificación , Animales , Brasil , Femenino , Genitales/anatomía & histología , Masculino , Ortópteros/anatomía & histologíaRESUMEN
The molecular basis of bipolar disorder (BD) is still unknown as is the mechanism through which lithium, the therapy of choice, exerts its effects in treatment of BD. So far, no biomarkers exist to facilitate diagnosis of BD or treatment evaluation. To investigate whether BD and its treatment with lithium leaves a characteristic signature in the serum proteome, we used SELDI-TOF MS to analyze individual serum samples from BD patients treated with lithium (BD-plus-Li, n=15) or other drugs (BD-minus-Li, n=10) and from healthy controls (n=15). Interestingly, features of 28 kDa (one peak) and 14 kDa (three peaks) showed a decreased level in the BD-minus-Li group and a level restored to that of the control group in the BD-plus-Li group. To reveal the identity of these features, we subjected pooled serum samples from both BD groups to the 2-D DIGE technology and identified 28 kDa apolipoprotein A-I (apo A-I) and three 14 kDa fragments thereof as upregulated in the BD-plus-Li group. Immunoturbidimetry, a routine clinical assay, verified the characteristic apo A-I signature in individual serum samples. In conclusion, we propose apo A-I as a candidate marker that can visualize response to lithium treatment at the serum protein level.
Asunto(s)
Antipsicóticos/uso terapéutico , Apolipoproteína A-I/sangre , Trastorno Bipolar/diagnóstico , Trastorno Bipolar/tratamiento farmacológico , Compuestos de Litio/uso terapéutico , Adulto , Secuencia de Aminoácidos , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Proteoma/metabolismo , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
In the present work, metallomics studies using biomolecular (matrix-assisted laser desorption ionization time-of-flight tandem mass spectrometry, MALDI-TOF MS/MS) and elemental mass spectrometry (laser ablation inductively coupled plasma mass spectrometry, LA-ICPMS) of human blood serum samples from bipolar disorder (BD) patients compared to controls were performed. The serum samples from three different groups: control (n = 25), BD patients treated with Li (n = 15), and BD patients not treated with Li (n = 10), were pooled according to their groups and separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE). Then, in order to determine the metals bound to the protein spots and search for differences among the studied groups, the 2-D gels were analyzed by LA-ICPMS in three distinct modes: bioimaging of metals in gel sections, line scan through the protein spots, and microlocal analysis of selected protein spots. MALDI-TOF MS/MS characterized 32 serum proteins, and they were associated with the metals previously detected. When comparing control and treated BD patient groups, a differentiation in terms of metals bound to proteins was possible to observe. The main metals bound to proteins found in all groups were Na, Mg, Zn, Ca, and Fe. Mn was only detected in the control group; Co was only observed in the control and BD patients treated with Li group. K and Ti were only found in the BD patient groups, and P was only observed in control and BD patients not treated with Li drugs. This exploratory work shows that the association of LA-ICPMS with MALDI-TOF MS/MS is a powerful strategy in metallomics studies applied to determine differences in metal-containing proteins, being able to play an important role on the discovery of potential markers for BD and its treatment with Li in serum samples.