Endocast of the Late Triassic (Carnian) dinosaur Saturnalia tupiniquim: implications for the evolution of brain tissue in Sauropodomorpha

The evolutionary history of dinosaurs might date back to the first stages of the Triassic (c. 250-240 Ma), but the oldest unequivocal records of the group come from Late Triassic (Carnian -c. 230 Ma) rocks of South America. Here, we present the first braincase endocast of a Carnian dinosaur, the sauropodomorph Saturnalia tupiniquim, and provide new data regarding the evolution of the floccular and parafloccular lobe of the cerebellum (FFL), which has been extensively discussed in the field of palaeoneurology. Previous studies proposed that the development of a permanent quadrupedal stance was one of the factors leading to the volume reduction of the FFL of sauropods. However, based on the new data for S. tupiniquim we identified a first moment of FFL volume reduction in non-sauropodan Sauropodomorpha, preceding the acquisition of a fully quadrupedal stance. Analysing variations in FFL volume alongside other morphological changes in the group, we suggest that this reduction is potentially related to the adoption of a more restricted herbivore diet. In this context, the FFL of sauropods might represent a vestigial trait, retained in a reduced version from the bipedal and predatory early sauropodomorphs

Focal, remote-controlled, chronic chemical modulation of brain microstructures

Direct delivery of fluid to brain parenchyma is critical in both research and clinical settings. This is usually accomplished through acutely inserted cannulas. This technique, however, results in backflow and significant dispersion away from the infusion site, offering little spatial or temporal control in delivering fluid. We present an implantable, MRI-compatible, remotely controlled drug delivery system for minimally invasive interfacing with brain microstructures in freely moving animals. We show that infusions through acutely inserted needles target a region more than twofold larger than that of identical infusions through chronically implanted probes due to reflux and backflow. We characterize the dynamics of in vivo infusions using positron emission tomography techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled agents are quantified. We further demonstrate the importance of precise drug volume dosing to neural structures to elicit behavioral effects reliably. Selective modulation of the substantia nigra, a critical node in basal ganglia circuitry, via muscimol infusion induces behavioral changes in a volume-dependent manner, even when the total dose remains constant. Chronic device viability is confirmed up to 1-y implantation in rats. This technology could potentially enable precise investigation of neurological disease pathology in preclinical models, and more efficacious treatment in human patients. Keywords: brain; drug delivery; substantia nigra; neural implant; PETNational Institutes of Health (U.S.) (Grant R01 EB016101)National Institute of Biomedical Imaging and Bioengineering (U.S.) (Grant R01 EB016101)National Cancer Institute (U.S.) (Grant P30-CA14051

The Late Triassic Ischigualasto Formation at Cerro Las Lajas (La Rioja, Argentina): fossil tetrapods, high-resolution chronostratigraphy, and faunal correlations

Present knowledge of Late Triassic tetrapod evolution, including the rise of dinosaurs, relies heavily on the fossil-rich continental deposits of South America, their precise depositional histories and correlations. We report on an extended succession of the Ischigualasto Formation exposed in the Hoyada del Cerro Las Lajas (La Rioja, Argentina), where more than 100 tetrapod fossils were newly collected, augmented by historical finds such as the ornithosuchid Venaticosuchus rusconii and the putative ornithischian Pisanosaurus mertii. Detailed lithostratigraphy combined with high-precision U–Pb geochronology from three intercalated tuffs are used to construct a robust Bayesian age model for the formation, constraining its deposition between 230.2 ± 1.9 Ma and 221.4 ± 1.2 Ma, and its fossil-bearing interval to 229.20 + 0.11/− 0.15–226.85 + 1.45/− 2.01 Ma. The latter is divided into a lower Hyperodapedon and an upper Teyumbaita biozones, based on the ranges of the eponymous rhynchosaurs, allowing biostratigraphic correlations to elsewhere in the Ischigualasto-Villa Unión Basin, as well as to the Paraná Basin in Brazil. The temporally calibrated Ischigualasto biostratigraphy suggests the persistence of rhynchosaur-dominated faunas into the earliest Norian. Our ca. 229 Ma age assignment to Pi. mertii partially fills the ghost lineage between younger ornithischian records and the oldest known saurischians at ca. 233 Ma.Fil: Desojo, Julia Brenda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Fiorelli, Lucas Ernesto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Universidad Nacional de Catamarca. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Secretaría de Industria y Minería. Servicio Geológico Minero Argentino. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja. - Provincia de La Rioja. Centro Regional de Investigaciones Científicas y Transferencia Tecnológica de La Rioja; ArgentinaFil: Ezcurra, Martin Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Martinelli, Agustín Guillermo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Ramezani, Jahandar. Massachusetts Institute of Technology; Estados UnidosFil: Da Rosa, Átila. A. S.. Universidade Federal de Santa Maria; BrasilFil: von Baczko, Maria Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: 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: Montefeltro, Felipe C.. Universidade Estadual Paulista Julio de Mesquita Filho; BrasilFil: Ezpeleta, Miguel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Centro de Investigaciones en Ciencias de la Tierra. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Centro de Investigaciones en Ciencias de la Tierra; ArgentinaFil: Langer, Max C.. Universidade de Sao Paulo; Brasi

New sauropodomorph and cynodont remains from the Late Triassic Sacisaurus site in southern Brazil and its stratigraphic position in the Norian Caturrita Formation

Sacisaurus agudoensis is the only silesaurid known from the Triassic beds of the Santa Maria Supersequence and the correlation of its type locality to the other Triassic deposits of south Brazil has always been controversial. In an attempt to improve this, a handful of dinosaur and cynodont remains found associated to S. agudoensis are here described and compared. The anatomy of the sauropodomorph is more similar to that of Norian forms such as Pantydraco caducus and Unaysaurus tolentinoi than to that of Carnian taxa such as Saturnalia tupiniquim and Pampadromaeus barberenai. The cynodonts recovered based on isolated teeth include a brasilodontid and a Riograndia-like form. This assemblage is consistent with a Norian age, as is also suggested by local stratigraphic correlation, which positions the site in the Caturrita Formation

A Late Cretaceous mammal from Brazil and the first radioisotopic age for the Bauru Group

In the last three decades, records of tribosphenidan mammals from India, continental Africa, Madagascar and South America have challenged the notion of a strictly Laurasian distribution of the group during the Cretaceous. Here, we describe a lower premolar from the Late Cretaceous Adamantina Formation, São Paulo State, Brazil. It differs from all known fossil mammals, except for a putative eutherian from the same geologic unity and Deccanolestes hislopi, from the Maastrichtian of India. The incompleteness of the material precludes narrowing down its taxonomic attribution further than Tribosphenida, but it is larger than most coeval mammals and shows a thin layer of parallel crystallite enamel. The new taxon helps filling two major gaps in the fossil record: the paucity of Mesozoic mammals in more northern parts of South America and of tribosphenidans in the Cretaceous of that continent. In addition, high-precision U-Pb geochronology provided a post-Turonian maximal age (≤87.8 Ma) for the type stratum, which is overlain by the dinosaur-bearing Marília Formation, constraining the age of the Adamantina Formation at the site to late Coniacian–late Maastrichtian. This represents the first radioisotopic age for the Bauru Group, a key stratigraphic unit for the study of Cretaceous tetrapods in Gondwana.Facultad de Ciencias Naturales y Muse

Untangling the dinosaur family tree

For over a century, the standard classification scheme has split dinosaurs into two fundamental groups: ‘lizard-hipped’ saurischians (including meat-eating theropods and long-necked sauropodomorphs) and ‘bird-hipped’ ornithischians (including a variety of herbivorous species).In a recent paper, Baron et al. challenged this paradigm with a new phylogenetic analysis that places theropods and ornithischians together in a group called Ornithoscelida, to the exclusion of sauropodomorphs, and used their phylogeny to argue that dinosaurs may have originated in northern Pangaea, not in the southern part of the supercontinent, as has more commonly been considered. Here we evaluate and reanalyse the morphological dataset underpinning the proposal by Baron et al. and provide quantitative biogeographic analyses, which challenge the key results of their study by recovering a classical monophyletic Saurischia and a Gondwanan origin for dinosaurs. This shows that the Ornithoscelida hypothesis is not the final word, and that there is still great uncertainty around the basic structure of the dinosaur family tree.Fil: Langer, Max C.. Universidade de Sao Paulo; BrasilFil: Ezcurra, Martin Daniel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Rauhut, Oliver Walter Mischa. Ludwig Maximilians Universitat; AlemaniaFil: Benton, Michael J.. University of Bristol; Reino UnidoFil: Knoll, Fabien. University of Manchester; Reino UnidoFil: McPhee, Blair W.. Universidade de Sao Paulo; BrasilFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales “Bernardino Rivadavia”; ArgentinaFil: Pol, Diego. Museo Paleontológico Egidio Feruglio; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Brusatte, Stephen L.. University of Edinburgh; Reino Unid

The Bauru Basin in São Paulo and its tetrapods

Funding Information: The authors thank the editors of Derbyana, especially its Editor-in-Chief Silvio T. Hiruma, for the invitation to participate in this volume dedicated to “Advances in Paleontology”. This contribution results from FAPESP grant 2020/07997-4, to which most of the authors are affiliated. We also thank the Derbyana ad-hoc reviewers, Drs. Agustin Martinelli and Fabiano Iori, for their helpful comments to the manuscript. FIGURE 6 – Cumulative chronological distribution of the tetrapod fossil record in the Bauru Basin of São Paulo (1913-2022) compared to science and technology funding metrics and events: A – For all tetrapods; grey bars indicate total records of tables 1-5; green line indicates taxonomic richness (grey lines in Tables 1-5); pink line indicates FAPESP budget in billions of reais between 1976 and 2021 (FAPESP 2022); blue line indicates CNPq, CAPES, and FINEP budget in millions of reais between 1996 and 2018 (ESCOBAR 2019). Events indicated by arrows correspond, in chronological sequence, to the foundations of USP, “Instituto Geográfico e Geológico”, FAPESP, Unicamp, UNESP, “Instituto Geológico”, and Monte Alto Museum of Paleontology, the implementations of the Qualis list, the Lattes curriculum, the CAPES Portal de Periódicos, and the CNPq “grant”, the foundation of the Marília Museum of Paleontology, the release of the first MCT/CNPq public call for “Strengthening National Paleontology”, and the foundation of “Pedro Candolo” Museum of Paleontology. B – Separately for each recorded tetrapod group, coloured lines indicate total of records in tables 1-5 of Anura = light blue, Crocodyliformes = red, Mammalia = purple, Sauropoda = green, Squamata = yellow, Testudines = orange, and Theropoda = dark blue. Publisher Copyright: Copyright © 2022 The Institute of Electronics, Information and Communication Engineers.The Bauru Basin bears one of the best sampled tetrapod paleofaunas of Brazil, with about 70% of this diversity collected from its deposits in São Paulo. Its fossils are known since the beginning of the 20th century, coming from all stratigraphic units of the Basin cropping-out in the state, i.e., Santo Anastácio, Araçatuba, Adamantina (alternatively divided into Vale do Rio do Peixe, Presidente Prudente, and São José do Rio Preto formations), and Marília formations. Identified taxa include rare anurans, mammals, and squamates, an important set of testudines, theropods (including birds), and sauropods, in addition to one of the most diverse crocodyliform faunas known worldwide. This congregates more than fifty unique taxonomic entities, including 42 formally described species. Based on biostratigraphic correlations (including tetrapods), on few absolute ages, and other sources of evidence, the Bauru Basin deposits in São Paulo seem to be chronologically restricted to the Late Cretaceous, but further investigation is much needed. Finally, the history of research with such fossils highlights the importance of public funding for research and decentralization of university education for the advancement of science.publishersversionpublishe

Whispering to the Deaf: Communication by a Frog without External Vocal Sac or Tympanum in Noisy Environments

Atelopus franciscus is a diurnal bufonid frog that lives in South-American tropical rain forests. As in many other frogs, males produce calls to defend their territories and attract females. However, this species is a so-called “earless” frog lacking an external tympanum and is thus anatomically deaf. Moreover, A. franciscus has no external vocal sac and lives in a sound constraining environment along river banks where it competes with other calling frogs. Despite these constraints, male A. franciscus reply acoustically to the calls of conspecifics in the field. To resolve this apparent paradox, we studied the vocal apparatus and middle-ear, analysed signal content of the calls, examined sound and signal content propagation in its natural habitat, and performed playback experiments. We show that A. franciscus males can produce only low intensity calls that propagate a short distance (<8 m) as a result of the lack of an external vocal sac. The species-specific coding of the signal is based on the pulse duration, providing a simple coding that is efficient as it allows discrimination from calls of sympatric frogs. Moreover, the signal is redundant and consequently adapted to noisy environments. As such a coding system can be efficient only at short-range, territory holders established themselves at short distances from each other. Finally, we show that the middle-ear of A. franciscus does not present any particular adaptations to compensate for the lack of an external tympanum, suggesting the existence of extra-tympanic pathways for sound propagation

Prediction of Promiscuous P-Glycoprotein Inhibition Using a Novel Machine Learning Scheme

BACKGROUND: P-glycoprotein (P-gp) is an ATP-dependent membrane transporter that plays a pivotal role in eliminating xenobiotics by active extrusion of xenobiotics from the cell. Multidrug resistance (MDR) is highly associated with the over-expression of P-gp by cells, resulting in increased efflux of chemotherapeutical agents and reduction of intracellular drug accumulation. It is of clinical importance to develop a P-gp inhibition predictive model in the process of drug discovery and development. METHODOLOGY/PRINCIPAL FINDINGS: An in silico model was derived to predict the inhibition of P-gp using the newly invented pharmacophore ensemble/support vector machine (PhE/SVM) scheme based on the data compiled from the literature. The predictions by the PhE/SVM model were found to be in good agreement with the observed values for those structurally diverse molecules in the training set (n = 31, r(2) = 0.89, q(2) = 0.86, RMSE = 0.40, s = 0.28), the test set (n = 88, r(2) = 0.87, RMSE = 0.39, s = 0.25) and the outlier set (n = 11, r(2) = 0.96, RMSE = 0.10, s = 0.05). The generated PhE/SVM model also showed high accuracy when subjected to those validation criteria generally adopted to gauge the predictivity of a theoretical model. CONCLUSIONS/SIGNIFICANCE: This accurate, fast and robust PhE/SVM model that can take into account the promiscuous nature of P-gp can be applied to predict the P-gp inhibition of structurally diverse compounds that otherwise cannot be done by any other methods in a high-throughput fashion to facilitate drug discovery and development by designing drug candidates with better metabolism profile