The Braincase of the Basal Sauropod Dinosaur Spinophorosaurus and 3D Reconstructions of the Cranial Endocast and Inner Ear

Background: Sauropod dinosaurs were the largest animals ever to walk on land, and, as a result, the evolution of their remarkable adaptations has been of great interest. The braincase is of particular interest because it houses the brain and inner ear. However, only a few studies of these structures in sauropods are available to date. Because of the phylogenetic position of Spinophorosaurus nigerensis as a basal eusauropod, the braincase has the potential to provide key evidence on the evolutionary transition relative to other dinosaurs. Methodology/Principal Findings: The only known braincase of Spinophorosaurus (‘Argiles de l'Irhazer’, Irhazer Group; Agadez region, Niger) differs significantly from those of the Jurassic sauropods examined, except potentially for Atlasaurus imelakei (Tilougguit Formation, Morocco). The basisphenoids of Spinophorosaurus and Atlasaurus bear basipterygoid processes that are comparable in being directed strongly caudally. The Spinophorosaurus specimen was CT scanned, and 3D renderings of the cranial endocast and inner-ear system were generated. The endocast resembles that of most other sauropods in having well-marked pontine and cerebral flexures, a large and oblong pituitary fossa, and in having the brain structure obscured by the former existence of relatively thick meninges and dural venous sinuses. The labyrinth is characterized by long and proportionally slender semicircular canals. This condition recalls, in particular, that of the basal non-sauropod sauropodomorph Massospondylus and the basal titanosauriform Giraffatitan. Conclusions/Significance: Spinophorosaurus has a moderately derived paleoneuroanatomical pattern. In contrast to what might be expected early within a lineage leading to plant-eating graviportal quadrupeds, Spinophorosaurus and other (but not all) sauropodomorphs show no reduction of the vestibular apparatus of the inner ear. This character-state is possibly a primitive retention in Spinophorosaurus, but due the scarcity of data it remains unclear whether it is also the case in the various later sauropods in which it is present or whether it has developed homoplastically in these taxa. Any interpretations remain tentative pending the more comprehensive quantitative analysis underway, but the size and morphology of the labyrinth of sauropodomorphs may be related to neck length and mobility, among other factors.The sojourns of Dr. Knoll in the Museum für Naturkunde (Berlin) were partly funded by the Alexander von Humboldt Foundation through a sponsorship of renewed research stay in Germany and by the European Community Research Infrastructure Action under the FP7 “Capacities” Program through a Synthesys grant (http://www.synthesys.info/). Dr. Knoll is currently supported by the Ramón y Cajal Program. This is a contribution to the research project CGL2009-12143, from the Ministerio de Ciencia e Innovación (Madrid), conducted by Dr. Knoll (PI), Dr. Witmer, and Dr. Schwarz-Wings. Dr. Witmer and Dr. Ridgely acknowledge funding support from the United States National Science Foundation (IBN-9601174, IBN-0343744, IOB-0517257) and the Ohio University Heritage College of Osteopathic Medicine. The Ohio Supercomputing Center also provided support.Peer reviewe

A basal lithostrotian titanosaur (Dinosauria: Sauropoda) with a complete skull: Implications for the evolution and paleobiology of titanosauria

We describe Sarmientosaurus musacchioi gen. et sp. nov., a titanosaurian sauropod dinosaur from the Upper Cretaceous (Cenomanian - Turonian) Lower Member of the Bajo Barreal Formation of southern Chubut Province in central Patagonia, Argentina. The holotypic and only known specimen consists of an articulated, virtually complete skull and part of the cranial and middle cervical series. Sarmientosaurus exhibits the following distinctive features that we interpret as autapomorphies: (1) maximum diameter of orbit nearly 40% rostrocaudal length of cranium; (2) complex maxilla - lacrimal articulation, in which the lacrimal clasps the ascending ramus of the maxilla; (3) medial edge of caudal sector of maxillary ascending ramus bordering bony nasal aperture with low but distinct ridge; (4) ´tongue-like´ ventral process of quadratojugal that overlaps quadrate caudally; (5) separate foramina for all three branches of the trigeminal nerve; (6) absence of median venous canal connecting infundibular region to ventral part of brainstem; (7) subvertical premaxillary, procumbent maxillary, and recumbent dentary teeth; (8) cervical vertebrae with ´strut-like´ centroprezygapophyseal laminae; (9) extremely elongate and slender ossified tendon positioned ventrolateral to cervical vertebrae and ribs. The cranial endocast of Sarmientosaurus preserves some of the most complete information obtained to date regarding the brain and sensory systems of sauropods. Phylogenetic analysis recovers the new taxon as a basal member of Lithostrotia, as the most plesiomorphic titanosaurian to be preserved with a complete skull. Sarmientosaurus provides a wealth of new cranial evidence that reaffirms the close relationship of titanosaurs to Brachiosauridae. Moreover, the presence of the relatively derived lithostrotian Tapuiasaurus in Aptian deposits indicates that the new Patagonian genus represents a ´ghost lineage´ with a comparatively plesiomorphic craniodental form, the evolutionary history of which is missing for at least 13 million years of the Cretaceous. The skull anatomy of Sarmientosaurus suggests that multiple titanosaurian species with dissimilar cranial structures coexisted in the early Late Cretaceous of southern South America. Furthermore, the new taxon possesses a number of distinctive morphologies - such as the ossified cervical tendon, extremely pneumatized cervical vertebrae, and a habitually downward- facing snout - that have rarely, if ever, been documented in other titanosaurs, thus broadening our understanding of the anatomical diversity of this remarkable sauropod clade. The latter two features were convergently acquired by at least one penecontemporaneous diplodocoid, and may represent mutual specializations for consuming low-growing vegetation.Fil: Martínez, Rubén Darío. Universidad Nacional de la Patagonia; ArgentinaFil: Lamanna, Matthew C.. Carnegie Museum Of Natural History; Estados UnidosFil: Novas, Fernando Emilio. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "bernardino Rivadavia"; ArgentinaFil: Ridgely, Ryan C.. Ohio University College Of Osteopathic Medicine; Estados UnidosFil: Casal, Gabriel. Universidad Nacional de la Patagonia; ArgentinaFil: Martínez, Javier E.. Hospital Regional de Comodoro Rivadavia; ArgentinaFil: Vita, Javier R.. Resonancia Magnética Borelli; ArgentinaFil: Witmer, Lawrence M.. Ohio University College Of Osteopathic Medicine; Estados Unido

CpG-creating mutations are costly in many human viruses.

Mutations can occur throughout the virus genome and may be beneficial, neutral or deleterious. We are interested in mutations that yield a C next to a G, producing CpG sites. CpG sites are rare in eukaryotic and viral genomes. For the eukaryotes, it is thought that CpG sites are rare because they are prone to mutation when methylated. In viruses, we know less about why CpG sites are rare. A previous study in HIV suggested that CpG-creating transition mutations are more costly than similar non-CpG-creating mutations. To determine if this is the case in other viruses, we analyzed the allele frequencies of CpG-creating and non-CpG-creating mutations across various strains, subtypes, and genes of viruses using existing data obtained from Genbank, HIV Databases, and Virus Pathogen Resource. Our results suggest that CpG sites are indeed costly for most viruses. By understanding the cost of CpG sites, we can obtain further insights into the evolution and adaptation of viruses

Acute and long-term outcomes in a Drosophila melanogaster model of classic galactosemia occur independently of galactose-1-phosphate accumulation

Classic galactosemia (CG) is a potentially lethal inborn error of metabolism that results from the profound loss of galactose-1-phosphate uridylyltransferase (GALT), the second enzyme in the Leloir pathway of galactose metabolism. Neonatal detection and dietary restriction of galactose minimizes or resolves the acute sequelae of CG, but fails to prevent the long-term complications experienced by a majority of patients. One of the substrates of GALT, galactose-1-phosphate (Gal-1P), accumulates to high levels in affected infants, especially following milk exposure, and has been proposed as the key mediator of acute and long-term pathophysiology in CG. However, studies of treated patients demonstrate no association between red blood cell Gal-1P level and long-term outcome severity. Here, we used genetic, epigenetic and environmental manipulations of a Drosophila melanogaster model of CG to test the role of Gal-1P as a candidate mediator of outcome in GALT deficiency. Specifically, we both deleted and knocked down the gene encoding galactokinase (GALK) in control and GALT-null Drosophila, and assessed the acute and long-term outcomes of the resulting animals in the presence and absence of dietary galactose. GALK is the first enzyme in the Leloir pathway of galactose metabolism and is responsible for generating Gal-1P in humans and Drosophila. Our data confirmed that, as expected, loss of GALK lowered or eliminated Gal-1P accumulation in GALT-null animals. However, we saw no concomitant rescue of larval survival or adult climbing or fecundity phenotypes. Instead, we saw that loss of GALK itself was not benign and in some cases phenocopied or exacerbated the outcome seen in GALT-null animals. These findings strongly contradict the long-standing hypothesis that Gal-1P alone underlies pathophysiology of acute and long-term outcomes in GALT-null Drosophila and suggests that other metabolite(s) of galactose, and/or other pathogenic factors, might be involved

Staffing Patterns of Non-ACGME Fellowships with 4-Year Residency Programs: A National Survey

Introduction: Emergency medicine (EM) is one of few specialties with variable training lengths. Hiring a three-year graduate to continue fellowship training in a department that supports a four-year residency program can lead to conflicts around resident supervision. We sought to understand hiring and clinical supervision, or staffing, patterns of non-Accreditation Council for Graduate Medical Education (ACGME) fellowships hosted at institutions supporting four-year residency programs.Methods: We performed a web-based, cross-sectional survey of non-ACGME fellowship directors (FD) hosted at institutions supporting four-year EM residency programs. We calculated descriptive statistics. Our primary outcome was the proportion of programs with four-year EM residencies that hire non-ACGME fellows graduating from three-year EM residencies.Results: Of 119 eligible FDs, 88 (74%) completed the survey. Seventy FDs (80%) indicated that they hire graduates of three-year residencies. Fifty-six (80%) indicated that three-year graduates supervise residents. Most FDs (74%) indicated no additional requirements exist to supervise residents outside of being hired as faculty. The FDs cited department policy, concerns about quality and length of training, and resident complaints as reasons for not hiring three-year graduates. A majority (10/18, 56%) noted that not hiring fellows from three-year programs negatively impacts recruitment and gives them access to a smaller applicant pool.Conclusion: Most non-ACGME fellowships at institutions with four-year EM programs recruit three-year graduates and allow them to supervise residents. This survey provides programs information on how comparable fellowships recruit and staff their departments, which may inform policies that fit the needs of their learners, the fellowship, and the department

Nicotine withdrawal alters neural responses to psychosocial stress

IntroductionPsychosocial stress is considered to be an important mechanism underlying smoking behavior and relapse. Thus, understanding the effects of acute nicotine withdrawal on responses to stress is important to intervene to prevent stress-induced relapse. The current study investigated the neural correlates of psychosocial stress during acute nicotine withdrawal in chronic smokers.MethodsThirty-nine treatment-seeking smokers were randomized to one of two conditions (abstinent 24 h (n = 21) or smoking as usual (n = 18)). They were then exposed to the Montreal Imaging Stress Task (MIST), a psychosocial stress task consisting of difficult mental arithmetic problems while receiving negative performance feedback while undergoing functional magnetic resonance imaging (fMRI).ResultsSubjective measures of stress increased following the MIST, compared to baseline. Whole brain between-group analysis identified significant activation clusters in four regions for the stress induction minus control contrast: inferior frontal gyrus (IFG), anterior/para cingulate cortex (ACC), precuneus, and supramarginal gyrus (SMG). In all regions, the deprived group showed significantly greater activation compared to the non-deprived group. No significant correlations were found between subjective stress and BOLD signal activation (ps > 0.07).ConclusionsThis study provides new evidence that brain regions previously shown to be predictive of relapse, such as the precuneus and IFG, display heightened neural responses to stress during nicotine deprivation. These data identify the brain regions that may be associated with withdrawal-related stress responses. Increased stress-related activation during nicotine withdrawal may identify those most vulnerable to relapse and represent a target for novel pharmacological intervention.publishe

Neuroimaging of the Philadelphia Neurodevelopmental Cohort

The Philadelphia Neurodevelopmental Cohort (PNC) is a large-scale, NIMH funded initiative to understand how brain maturation mediates cognitive development and vulnerability to psychiatric illness, and understand how genetics impacts this process. As part of this study, 1445 adolescents ages 8–21 at enrollment underwent multimodal neuroimaging. Here, we highlight the conceptual basis for the effort, the study design, and the measures available in the dataset. We focus on neuroimaging measures obtained, including T1-weighted structural neuroimaging, diffusion tensor imaging, perfusion neuroimaging using arterial spin labeling, functional imaging tasks of working memory and emotion identification, and resting state imaging of functional connectivity. Furthermore, we provide characteristics regarding the final sample acquired. Finally, we describe mechanisms in place for data sharing that will allow the PNC to become a freely available public resource to advance our understanding of normal and pathological brain development