The Early Evolution of Rhynchosaurs

The rhynchosaurian archosauromorphs are an important and diverse group of fossil tetrapods that first appeared during the Early Triassic and probably became extinct during the early Late Triassic (early Norian). Here, the early evolution of rhynchosaurs during the Early and early Middle Triassic (Induan-Anisian: 252.2-242 Mya) is reviewed based on new anatomical observations and their implications for the taxonomy, phylogenetic relationships and macroevolutionary history of the group. A quantitative phylogenetic analysis recovered a paraphyletic genus Rhynchosaurus, with “Rhynchosaurus” brodiei more closely related to hyperodapedontines than to Rhynchosaurus articeps. Therefore, a new genus is erected, resulting in the new combination Langeronyx brodiei. A body size analysis found two independent increases in size in the evolutionary history of rhynchosaurs, one among stenaulorhynchines and the other in the hyperodapedontine lineage. Maximum likelihood fitting of phenotypic evolution models to body size data found ambiguous results, with body size evolution potentially interpreted as fitting either a non-directional Brownian motion model or a stasis model. A Dispersal-ExtinctionCladogenesis analysis reconstructed the areas that are now South Africa and Europe as the ancestral areas of Rhynchosauria and Rhynchosauridae, respectively. The reconstruction of dispersal events between geographic areas that are broadly separated paleolatitudinally implies that barriers to the dispersal of rhynchosaurs from either side of the paleo-Equator during the Middle Triassic were either absent or permeable.Fil: Ezcurra, Martin Daniel. University of Birmingham; Reino Unido. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Montefeltro, Felipe C.. University of Birmingham; Reino Unido. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Butler, Richard J.. University of Birmingham; Reino Unid

A new species of basal rhynchosaur (Diapsida: Archosauromorpha) from the early Middle Triassic of South Africa, and the early evolution of Rhynchosauria

Made available in DSpace on 2018-12-11T16:38:39Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-07-01Rhynchosauria was an important clade of herbivorous archosauromorph reptiles during the Triassic, with a worldwide distribution. We describe a new genus and species of early rhynchosaur, Eohyosaurus wolvaardti gen. et sp. nov., from the early Middle Triassic (early Anisian) CynognathusAssemblage Zone (Subzone B) of the Karoo Supergroup, South Africa. Eohyosaurus wolvaardti is known from a single skull, and is recovered as the sister taxon of Rhynchosauridae in a new phylogenetic analysis. CynognathusSubzone B has previously yielded the stratigraphically oldest well-understood rhynchosaur species, Mesosuchus browni and Howesia browni. Eohyosaurus wolvaardti increases the rhynchosaur diversity within this stratigraphical horizon to three species. Intriguingly, all currently confirmed rhynchosaur occurrences from the Early Triassic to earliest Middle Triassic are from South Africa. This may suggest a relatively restricted palaeogeographical distribution for early rhynchosaurs, followed by a global dispersal of rhynchosaurids during the Middle Triassic.School of Geography Earth and Environmental Sciences University of BirminghamGeoBio-Center Ludwig-Maximilians-Universität München, Richard-Wagner-Str. 10Departamento de Biologia e Zootecnia UNESP, Rua Monção 226Division of Paleontology Steinmann Institute University of Bonn, Nussallee 8Museum für Naturkunde Berlin Leibniz-Institut für Evolutions- und Biodiversitätsforschung, Invalidenstraße 43Departamento de Biologia e Zootecnia UNESP, Rua Monção 22

The stem-archosaur evolutionary radiation in South America

The oldest archosauromorphs (dinosaurs, birds, crocodiles, and their stem-taxa) arerecorded in middle−upper Permian rocks, but it was not after the Permo−Triassic massextinction that the group shows a substantially high taxonomic richness andecomorphological disparity. The early evolutionary history of the Archosauromorphaduring the Early and Middle Triassic is mainly based on fossils recovered from rocks insouthern Africa, Europe and Asia, whereas South America possesses a morecomplete fossil record of the group only in the Late Triassic. Here we revisit, discuss,and reanalyse the non-archosaurian archosauromorph fossil record of the current-daySouth America. The Early Triassic archosauromorph record in this continent is stillscarce, but it documents the early evolution of the group in western Pangaea and iscrucial to understand more globally the biotic recovery after the Permo−Triassic massextinction. The Middle Triassic record is extremely scarce, but the Late Triassicarchosauromorph assemblage of South America is among the most diverse andabundant worldwide. The last decade has witnessed a considerable improvement inour knowledge of the record, taxonomy, phylogeny, and macroevolution of the groupwith the input from the South American fossils. Nevertheless, a considerable amount ofresearch is needed and ideally should be focused on some particular aspects of theTriassic evolutionary radiation of Archosauromorpha. Among them, the Early Triassicrecord should be expanded, more numerous and more complete Middle Triassicarchosauromorph specimens are crucial to have a more complete picture of theevolution of the group, and the taxonomy of groups like proterochampsids andhyperodapedontine rhynchosaurs should be clarified through detailed anatomical work.Fil: Ezcurra, Martin Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Argentino de Ciencias Naturales ‘Bernardino Rivadavia’; ArgentinaFil: Montefeltro, Felipe C.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Pinheiro, Felipe L.. Universidade Federal do Pampa; BrasilFil: Trotteyn, Maria Jimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Juan. Centro de Investigaciones de la Geosfera y Biosfera. Universidad Nacional de San Juan. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones de la Geosfera y Biosfera; ArgentinaFil: Gentil, Adriel Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Argentino de Ciencias Naturales ‘Bernardino Rivadavia’; ArgentinaFil: Lehmann, Oscar Emilio Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Argentino de Ciencias Naturales ‘Bernardino Rivadavia’; ArgentinaFil: Pradelli, Luciano Agustín. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Museo Argentino de Ciencias Naturales ‘Bernardino Rivadavia’; Argentin

Fine tune control of dopamine neurotransmission by alpha-synuclein: down- and over-expression models

Póster presentado en el IX Simposi de Neurobiologia Experimental, celebrado los días 22 y 23 de octubre de 2014 en Barcelona y organizado por la Societat Catalana de Biologia del Institut d'Estudis CatalansAlpha-synuclein protein (α-syn) accumulates in the brain of patients with Parkinson´s disease (PD) and leaves a degeneration of midbrain dopamine (DA) neurons. However, the normal function of α-syn on DA neurotransmission in vivo remains poorly understood. Here, we used two mouse models with a) reduced α-syn expression in the substantia nigra compacta (SNc) and ventral tegmental area (VTA) induced by antisense oligonucleotide molecule (ASO) and, b) modest α-syn over-expression in tyrosine hydroxylase (TH)-positive neurons in the absence of overt toxicity. ASO sequence against α-syn was conjugated to a cell-specific ligand, indatraline (monoamine transporter inhibitor), to promote its selective delivery into monoamine neurons after intranasal administration. Indatraline-α-syn-ASO conjugate (1233ASO) entered into midbrain DA cells followed by trafficking to deep endomembrane vesicles associated with Rab7 resulting in an efficient α-syn knockdown. Indeed, 4-day 1233ASO treatment (30µg/day) decreased α-syn mRNA and protein levels in SNc/VTA (84.1±1.7% and 57.7±7.8% of PBS-treated animals, respectively). Alpha-synuclein suppression displayed an enhancement striatal DA tone using intracerebral microdialysis. Local veratridine (50 µM) perfusion increased extracellular DA levels more efficient in 1233ASO-treated than PBS-treated mice. Similarly, nomifensine (1-10-50 µM) or amphetamine (1-10-100 µM) showed a marked doseeffect which phenotypic differences. Tetrabenazine (VMAT2 inhibitor, 100 µM) reduced striatal DA levels in 1233ASO-treated mice. This effect was lower than in control mice. Conversely, we found that over-expressed α-syn inhibits striatal DA release. Together, this evidence indicates a physiological role for a-syn as a >fine tune> modulator of nigroestriatal DA release and the effects depend on the a-syn expression levelsSpanish Ministery of Economy and Competitiveness, INNPACTO Subprogram IPT-2012-1208-300000; Instituto de Salud Carlos III (ISCIII) Grant PI13/01390. Some of these grants are co-financed by the European Regional Development Fund “A way to build Europe”Peer Reviewe

Therapeutic antidepressant potential of a conjugated siRNA silencing the serotonin transporter after intranasal administration

A Ferrés-Coy et al.Major depression brings about a heavy socio-economic burden worldwide due to its high prevalence and the low efficacy of antidepressant drugs, mostly inhibiting the serotonin transporter (SERT). As a result, similar to 80% of patients show recurrent or chronic depression, resulting in a poor quality of life and increased suicide risk. RNA interference (RNAi) strategies have been preliminarily used to evoke antidepressant-like responses in experimental animals. However, the main limitation for the medical use of RNAi is the extreme difficulty to deliver oligonucleotides to selected neurons/systems in the mammalian brain. Here we show that the intranasal administration of a sertraline-conjugated small interfering RNA (C-SERT-siRNA) silenced SERT expression/function and evoked fast antidepressant-like responses in mice. After crossing the permeable olfactory epithelium, the sertraline-conjugated-siRNA was internalized and transported to serotonin cell bodies by deep Rab-7-associated endomembrane vesicles. Seven-day C-SERT-siRNA evoked similar or more marked responses than 28-day fluoxetine treatment. Hence, C-SERT-siRNA (i) downregulated 5-HT1A-autoreceptors and facilitated forebrain serotonin neurotransmission, (ii) accelerated the proliferation of neuronal precursors and (iii) increased hippocampal complexity and plasticity. Further, short-term C-SERT-siRNA reversed depressive -like behaviors in corticosterone-treated mice. The present results show the feasibility of evoking antidepressant -like responses by selectively targeting neuronal populations with appropriate siRNA strategies, opening a way for further translational studies.This work was supported by grants from CDTI—Spanish Ministry of Science and Innovation—DENDRIA contribution, 'nLife all rights reserved' (to AB and FA); Instituto de Salud Carlos III PI10/00290 and PI13/01390 (to AB), PI/10/0123 (to JCL) and Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM); NARSAD Independent Investigator Grant from the Brain & Behavior Research Foundation Grant 20003 (to AB); Ministry of Economy and Competitiveness SAF2012-35183 (to FA) and SAF2011-25020 (to AP); and Generalitat de Catalunya, Secretaria d’Universitat i Recerca del Departament d’Economia i Coneixement (SGR2014) Catalan Government Grant 2009SGR220 (to FA). Some of these grants are co-financed by the European Regional Development Fund 'A way to build Europe'. AF-C is a recipient of a fellowship from Spanish Ministry of Education, Culture and Sport.Peer Reviewe

RNAi-mediated serotonin transporter suppression rapidly increases serotonergic neurotransmission and hippocampal neurogenesis

Current antidepressants, which inhibit the serotonin transporter (SERT), display limited efficacy and slow onset of action. Here, we show that partial reduction of SERT expression by small interference RNA (SERT-siRNA) decreased immobility in the tail suspension test, displaying an antidepressant potential. Moreover, short-term SERT-siRNA treatment modified mouse brain variables considered to be key markers of antidepressant action: reduced expression and function of 5-HT(1A)-autoreceptors, elevated extracellular serotonin in forebrain and increased neurogenesis and expression of plasticity-related genes (BDNF, VEGF, Arc) in hippocampus. Remarkably, these effects occurred much earlier and were of greater magnitude than those evoked by long-term fluoxetine treatment. These findings highlight the critical role of SERT in serotonergic function and show that the reduction of SERT expression regulates serotonergic neurotransmission more potently than pharmacological blockade of SERT. The use of siRNA-targeting genes in serotonin neurons (SERT, 5-HT(1A)-autoreceptor) may be a novel therapeutic strategy to develop fast-acting antidepressants

Digital photogrammetry applied to footprints of medium and large mammalfrom two forest fragments in the area influence of the Ilha Solteira Hydroelectric Complex, Brazil / Fotogrametria digital aplicada a pegadas de mamíferos médios e grandes de dois fragmentos de floresta na área de influência do Complexo Hidroeléctrico da Ilha Solteira, Brasil

Medium and large neotropical mammals are usually nocturnal, shy animals, which challenge direct observations, and compromising the study these animals in the field. One solution to this problem is the analysis of vestiges, which include tracks and footprints, as a way to assess the community of medium and large terrestrial mammals. Species identification can be based on the observation of key characters of footprints, which is commonly evaluated through comparisons with photographs and linear drawings in specialized guides. However, since the quality of each footprint depends on the environment factors, including substrate and climate conditions, the guides represent ideal footprints that do not necessarily reflect the conditions most common seen in the field. We carried out an inventory of medium and large mammals through footprint analysis in two fragments in the region under the influence of the Ilha Solteira HPP, Brazil, between February and April 2019. We recorded a total of 16 mammals, of seven orders. We rendered three-dimensional footprint models of four of the recorded species using digital photogrammetry. We argue that this technique allows the reconstruction of the footprints in a faithful way for medium and large neotropical mammals, posing as a viable, and inexpensive alternative to the two-dimensional images of field guides, with the advantage that the 3D models can be analysed from different angles and be produced from footprints on different substrates

Selective suppression of α-Synuclein in monoaminergic neurons of mice by intranasal delivery of targeted small interfering RNA or antisense oligonucleotides: Potential therapy for Parkinson's disease

Póster presentado en: ACNP (American College of Neuropsychopharmacology) 52nd Annual Conference, celebrada del 8 al 12 de diciembre de 2013 en Hollywood, Florida (Estados Unidos)Abstract publicado en: Neuropsychopharmacology 38:S419-S420 (2013). ISSN: 0893-133X. eISSN: 1740-634X. DOI:10.1038/npp.2013.280α-Synuclein (α-Syn) appears to play a crucial role in the pathogenesis of several neurodegenerative disorders including Parkinson's disease (PD). The brains of Parkinson patients typically contain insoluble intracellular protein inclusions called Lewy bodies. Increased neuronal α-Syn levels represent a major component of Lewy bodies and therefore, the suppression of α-Syn expression provides a valid therapeutic target for PD. The goal of this study was to assess the ability of various small interfering RNA (siRNA) and antisense oligonucleotide (ASO) sequences directed against α-Syn to downregulate endogenous or overexpressed α-Syn mRNA levels in BE-M17 neuroblastoma cells. Moreover, we evaluated the feasibility of reducing α-Syn expression selectively in PD-vulnerable brain areas including substantia nigra pars compacta (SNc), ventral tegmental area (VTA), locus coeruleus (LC) and dorsal raphe nucleus (DR) of mice after the internalization of conjugated siRNA/ASO molecules into monoamine neurons following intranasal administration. Conclusions: These results set the stage for the testing of these molecules as potential disease-modifying agents in neurotoxin-based and genetic models of PD linked to pathogenic increases in α-Syn. In this study we have characterized conjugated siRNA and ASO molecules that actively reduce endogenous α-Syn expression in vivo using the intranasal route to deliver directly siRNA/ASO into the brainPeer Reviewe

Intracerebral Administration of a Ligand-ASO Conjugate Selectively Reduces α-Synuclein Accumulation in Monoamine Neurons of Double Mutant Human A30P*A53T*α-Synuclein Transgenic Mice

α-Synuclein (α-Syn) protein is involved in the pathogenesis of Parkinson’s disease (PD). Point mutations and multiplications of the α-Syn, which encodes the SNCA gene, are correlated with early-onset PD, therefore the reduction in a-Syn synthesis could be a potential therapy for PD if delivered to the key affected neurons. Several experimental strategies for PD have been developed in recent years using oligonucleotide therapeutics. However, some of them have failed or even caused neuronal toxicity. One limiting step in the success of oligonucleotide-based therapeutics is their delivery to the brain compartment, and once there, to selected neuronal populations. Previously, we developed an indatraline-conjugated antisense oligonucleotide (IND-1233-ASO), that selectively reduces α-Syn synthesis in midbrain monoamine neurons of mice, and nonhuman primates. Here, we extended these observations using a transgenic male mouse strain carrying both A30P and A53T mutant human α-Syn (A30P*A53T*α-Syn). We found that A30P*A53T*α-Syn mice at 4–5 months of age showed 3.5-fold increases in human α-Syn expression in dopamine (DA) and norepinephrine (NE) neurons of the substantia nigra pars compacta (SNc) and locus coeruleus (LC), respectively, compared with mouse α-Syn levels. In parallel, transgenic mice exhibited altered nigrostriatal DA neurotransmission, motor alterations, and an anxiety-like phenotype. Intracerebroventricular IND-1233-ASO administration (100 µg/day, 28 days) prevented the α-Syn synthesis and accumulation in the SNc and LC, and recovered DA neurotransmission, although it did not reverse the behavioral phenotype. Therefore, the present therapeutic strategy based on a conjugated ASO could be used for the selective inhibition of α-Syn expression in PD-vulnerable monoamine neurons, showing the benefit of the optimization of ASO molecules as a disease modifying therapy for PD and related α-synucleinopathies.This study was supported by grants SAF2016-75797-R, PID2019-105136RB-100, Retos- Colaboración Subprogram RTC-2015-3309-1, Ministry of Economy and Competitiveness (MINECO) and European Regional Development Fund (ERDF), UE; and CB/07/09/0034 Center for Networked Biomedical Research on Mental Health (CIBERSAM)