Exceptional skull of huayqueriana (mammalia, litopterna, macraucheniidae) from the late miocene of Argentina: Anatomy, systematics, and peleobiological implications

The Huayquerías Formation (Late Miocene, Huayquerian SALMA) is broadly exposed in westcentral Argentina (Mendoza). The target of several major paleontological expeditions in the first half of the 20th century, the Mendozan Huayquerías (badlands) have recently yielded a significant number of new fossil finds. In this contribution we describe a complete skull (IANIGLA-PV 29) and place it systematically as Huayqueriana cf. H. cristata (Rovereto, 1914) (Litopterna, Macraucheniidae). The specimen shares some nonexclusive features with H. cristata (similar size, rostral border of the orbit almost level with distal border of M3, convergence of maxillary bones at the level of the P3/P4 embrasure, flat snout, very protruding orbits, round outline of premaxillary area in palatal view, and small diastemata between I3/C and C/P1). Other differences (e.g., lack of sagittal crest) may or may not represent intraspecific variation. In addition to other features described here, endocast reconstruction utilizing computer tomography (CT) revealed the presence of a derived position of the orbitotemporal canal running below the rhinal fissure along the lateroventral aspect of the piriform lobe. CT scanning also established that the maxillary nerve (CN V2) leaves the skull through the sphenoorbital fissure, as in all other litopterns, a point previously contested for macraucheniids. The angle between the lateral semicircular canal and the plane of the base of the skull is about 26°, indicating that in life the head was oriented much as in modern horses. Depending on the variables used, estimates of the body mass of IANIGLA-PV 29 produced somewhat conflicting results. Our preferred body mass estimate is 250 kg, based on the centroid size of 36 3D cranial landmarks and accompanying low prediction error. The advanced degree of tooth wear in IANIGLA-PV 29 implies that the individual died well into old age. However, a count of cementum lines on the sectioned left M2 is consistent with an age at death of 10 or 11 years, younger than expected given its body mass. This suggests that the animal had a very abrasive diet. Phylogenetic analysis failed to resolve the position of IANIGLA-PV 29 satisfactorily, a result possibly influenced by intraspecific variation. There is no decisive evidence for the proposition that Huayqueriana, or any other litoptern, were foregut fermenters.Fil: Forasiepi, Analia Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: MacPhee, Ross D. E.. American Museum Of Natural History; Estados UnidosFil: Hernández del Pino, Santiago Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Provincia de Mendoza. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales. Universidad Nacional de Cuyo. Instituto Argentino de Nivología, Glaciología y Ciencias Ambientales; ArgentinaFil: Schmidt, Gabriela Ines. Provincia de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Universidad Autónoma de Entre Ríos. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Centro de Investigaciones Científicas y Transferencia de Tecnología a la Producción; ArgentinaFil: Amson, Eli. Universitat Zurich; SuizaFil: Grohé, Camille. American Museum Of Natural History; Estados Unido

Deep-sequencing reveals broad subtype-specific HCV resistance mutations associated with treatment failure

A percentage of hepatitis C virus (HCV)-infected patients fail direct acting antiviral (DAA)-based treatment regimens, often because of drug resistance-associated substitutions (RAS). The aim of this study was to characterize the resistance profile of a large cohort of patients failing DAA-based treatments, and investigate the relationship between HCV subtype and failure, as an aid to optimizing management of these patients. A new, standardized HCV-RAS testing protocol based on deep sequencing was designed and applied to 220 previously subtyped samples from patients failing DAA treatment, collected in 39 Spanish hospitals. The majority had received DAA-based interferon (IFN) a-free regimens; 79% had failed sofosbuvir-containing therapy. Genomic regions encoding the nonstructural protein (NS) 3, NS5A, and NS5B (DAA target regions) were analyzed using subtype-specific primers. Viral subtype distribution was as follows: genotype (G) 1, 62.7%; G3a, 21.4%; G4d, 12.3%; G2, 1.8%; and mixed infections 1.8%. Overall, 88.6% of patients carried at least 1 RAS, and 19% carried RAS at frequencies below 20% in the mutant spectrum. There were no differences in RAS selection between treatments with and without ribavirin. Regardless of the treatment received, each HCV subtype showed specific types of RAS. Of note, no RAS were detected in the target proteins of 18.6% of patients failing treatment, and 30.4% of patients had RAS in proteins that were not targets of the inhibitors they received. HCV patients failing DAA therapy showed a high diversity of RAS. Ribavirin use did not influence the type or number of RAS at failure. The subtype-specific pattern of RAS emergence underscores the importance of accurate HCV subtyping. The frequency of “extra-target” RAS suggests the need for RAS screening in all three DAA target regions

Assessment of perfluoroalkyl substances in placenta by coupling salt assisted liquid-liquid extraction with dispersive liquid-liquid microextraction prior to liquid chromatography-tandem mass spectrometry

The widespread use of perfluoroalkyl substances (PFAS) is resulting in a broad human exposure to these endocrine disrupting chemicals (EDCs), prompting biomonitoring research to evaluate its magnitude and impact, especially during critical windows of exposure such as fetal and perinatal periods. This study was focused on developing a method to determine 10 PFAS in placental tissue by combining salt-assisted liquid-liquid extraction with dispersive liquid-liquid microextraction and using liquid chromatography-tandem mass spectrometry. Chemometric strategies were applied to optimize the experimental parameters. The limit of quantification was 0.02 ng g− 1 for all analytes, and the inter-day variability (as relative standard deviation) ranged from 7.9% to 13.8%. Recoveries ranged from 88.2% to 113.9%. The suitableness of the procedure was demonstrated by assessing the targeted compounds in 20 placenta samples. The highest concentrations were recorded for perfluorooctanoic acid and perfluorooctane sulfonate, with maximum concentrations of 0.62 and 1.02 ng g− 1 and median concentrations of 0.13 and 0.53 ng g− 1 , respectively. Median concentrations of the other PFAS ranged from detected values to 0.08 ng g− 1 . This analytical procedure yields useful data on fetal exposure to PFAS.European Union's Horizon 2020 research and innovation programme 733032Instituto de Salud Carlos III FIS-PI16/01820 FIS-PI16/01812 FIS-PI16/01858Instituto de Salud Carlos III"Fondo Europeo de Desarrollo Regional" (ISCIII/FEDER) CD17/0021