The first skeletal record of the Cretaceous Enigmatic Sawfish genus Ptychotrygon (Chondrichthyes: Batoidea) from the Turonian (Cretaceous) of Morocco

A new fossil batoid (ray) Ptychotrygon rostrispatula sp. nov. is described from five exceptionally well-preserved, three-dimensional skeletal remains from the Turonian (Late Cretaceous) of Morocco. These specimens represent the first known skeletal remains for the genus Ptychotrygon and allow an almost complete description of the genus providing a new insight to its phylogenetic relations and validate its taxonomic status as a member of the Sclerorhynchoidei. Mechanical preparation of the fossil remains revealed a relatively large batoid species (estimated total length beyond 1 meter). Overall morphology resembles that of sclerorhynchoids with a robust hypertrophied rostrum that lacks enlarged rostral denticles with enlarged paddle-like pectoral proximal elements (propterygium, mesopterygium and metapterygium). Never seen before details of the branchial skeleton are presented (large second hypobranchial without anterior process which was probably fused to the basibranchial and no evidence of articulation with other branchial element). To assess the phylogenetic relations of these specimens within the sclerorhynchoids a parsimonious analysis using TNT and PAUP software packages was performed. These analyses included Asflapristis cristadentis that along with Ptychotrygon rostrispatula sp. nov. were used as representatives of Ptychotrygonidae and also includes six other genera of sclerorhynchoids with relatively good skeletal remains. Both analyses recovered two monophyletic groups within sclerorhynchoids: the first contains Ischyrhiza, Onchopristis and Schizorhiza and a second that includes Micropristis, Sclerorhynchus, Libanopristis and Ptychotrygonidae

Genetic Background and Sex: Impact on Generalizability of Research Findings in Pharmacology Studies

Animal models consisting of inbred laboratory rodent strains have been a powerful tool for decades, helping to unravel the underpinnings of biological problems and employed to evaluate potential therapeutic treatments in drug discovery. While inbred strains demonstrate relatively reliable and predictable responses, using a single inbred strain alone or as a background to a mutation is analogous to running a clinical trial in a single individual and their identical twins. Indeed, complex etiologies drive the most common human diseases, and a single inbred strain that is a surrogate of a single genome, or data generated from a single sex, is not representative of the genetically diverse patient populations. Further, pharmacological and toxicology data generated in otherwise healthy animals may not translate to disease states where physiology, metabolism, and general health are compromised. The purpose of this chapter is to provide guidance for improving generalizability of preclinical studies by providing insight into necessary considerations for introducing systematic variation within the study design, such as genetic diversity, the use of both sexes, and selection of appropriate age and disease model. The outcome of implementing these considerations should be that reproducibility and generalizability of significant results are significantly enhanced leading to improved clinical translation

Long-term treatment with valproic acid does not alleviate the condition of HAM/TSP

Long-Term Treatment with Valproic Acid Does Not Alleviate the Condition of HAM/TSP Olindo, S.,1 Belrose, G.,2 Lezin, A.,2 Gillet, N.,3 Defoiche, J.,4 Rodriguez, S.,4 Signaté, A.,1 Verlaeten, O.,4 Smadja, D.,1 Césaire, R.,2 Willems, L.4 1Service de Neurologie and JE 2503, Centre Hospitalier Universitaire de Fort-de-France, 97200 Fort-de-France, Martinique, France; 2Laboratoire de Virologie-Immunologie and JE 2503, Centre Hospitalier Universitaire de Fort-de-France, 97200 Fort-de-France, Martinique, France; 3Department of Immunology, Imperial College, London, UK; 4Molecular and Cellular Biology, University Academia ‘‘Wallonie-Europe’’, 5030 Gembloux, Belgium. LW is Research Director of the FNRS. We previously proposed to interfere with proviral loads in HAM/TSP patients by modulating lysine deacetylase activity using valproic acid (VPA). The strategy aims at activating viral gene expression in order to expose virus-positive cells to the host immune response. We conducted a single-center, two-year open-label trial, with 19 HAM/TSP volunteers treated with oral doses of VPA (20mg/Kg/day). Objectives were to assess biological response and clinical safety to VPA treatment in HAM/TSP patients. By microarray analysis, we show that VPA treatment moderately stimulated expression of cyclinD2 and Rho GTPase activating protein 18 in CD4-T cells. CD8-mediated lysis efficiency of Tax-expressing cells was unaltered by VPA treatment. The CD4-T cell turnover rate was calculated by GC/MS analysis from quantitative incorporation of deuterium into DNA. Transient increase in proviral loads correlated with accelerated proliferation. After 2 years, the proviral loads reached levels similar to those before treatment. The main clinical side effects were drowsiness (52%), tremor (47%), digestive symptoms (37%), vertigo (26%), and alopecia (10%). The frequency of side symptoms tended to decrease over the trial course. The neurological status over the study constituted the primary clinical safety measures. Disability Status Scale, muscle testing score, Ashworth score, and urinary dysfunction score showed no significant changes. Walking Time Test (WTT) slightly varied over the study except in 3 patients in whom the WTT variation rates were>20%. These 3 patients experienced drowsiness and tremor and improved rapidly after treatment discontinuation. Together, these observations indicated that long term treatment with VPA is safe but does not alleviate the condition of HAM/TSP

Drake Passage gateway opening and Antarctic Circumpolar Current onset 31 Ma ago: The message of foraminifera and reconsideration of the Neodymium isotope record

International audienceThe establishment of the Antarctic Circumpolar Current (ACC) is one of the most important events of the Cenozoic for both global oceanic circulation and climate. The onset of this major current hinges on the opening of two major oceanic passages, the Drake Passage and the Tasmanian gateways that connect Pacific, Atlantic and Indian oceans, allowing a modern-like thermohaline circulation. For decades, the ACC onset has been considered as the trigger of the Oligocene glaciation at 33.7 Ma, which marks the beginning of the modern icehouse climate. Today, this scenario is debated. The main obstacle to evaluate the ACC influence on the Oligocene glaciation remains the ill-constrained timing of the Drake Passage gateway opening. Here, we analyse the geochemical composition and Sr isotope ratio of dated planktonic and benthic foraminifera from two IODP and ODP legs in the Southern Atlantic and Pacific oceans (SAO and PO, respectively) to assess the variability of seawater masses' chemical composition through time and to better constrain the timing of the Drake Passage gateway opening along the Eocene-Oligocene interval. These results, based on seawater paleo temperature (Mg/Ca molar ratios), redox (Ce/Ce* anomaly) and provenance (87Sr/86Sr) proxies, highlight a gradual seawater mass mixing between the SAO and PO from 31 Ma to 26 Ma. Combined with a reconsideration of the fossil fish teeth Neodymium isotope records, these geochemical tracers evidencing the SAO-PO interconnection depicts the Drake Passage gateway opening and deepening during this 31–26 Ma interval and thus, the timing of the ACC onset. Hence, antecedence of the Oligocene glaciation onset (at 33.7 Ma) relative to the ACC onset (31–26 Ma) implies that the ACC did not trigger the Oligocene glaciation and that the role of atmospheric pCO2 should be further considered

Eocene-Oligocene southwest Pacific Ocean paleoceanography new insights from foraminifera chemistry (DSDP site 277, Campbell Plateau)

International audienceDespite its major role in the Earth’s climate regulation, the evolution of high-latitude ocean dynamics through geological time remains unclear. Around Antarctica, changes in the Southern Ocean (SO) circulation are inferred to be responsible for cooling from the late Eocene and glaciation in the early Oligocene. Here, we present a geochemical study of foraminifera from DSDP Site 277 (Campbell Plateau), to better constrain thermal and redox evolution of the high latitude southwest Pacific Ocean during this time interval. From 56 to 48 Ma, Mg/Ca- and δ 18 O-paleothermometers indicate high surface and bottom water temperatures (24–26°C and 12–14°C, respectively), while weak negative Ce anomalies indicate poorly oxygenated bottom waters. This is followed by a cooling of ∼4° between 48 and 42 Ma, possibly resulting from a weakening of a proto-EAC (East Australian Current) and concomitant strengthening of a proto-Ross gyre. This paleoceanographic change is associated with better ventilation at Site 277, recorded by an increasing negative Ce anomaly. Once this proto-Ross gyre was fully active, increasing biogenic sedimentation rates and decreasing Subbotina sp. δ 13 C values indicate enhanced productivity. This resulted in a shoaling of the oxygen penetration in the sediment pile recorded by increasing the foraminiferal U/Ca ratio. The negative Ce anomaly sharply increased two times at ∼35 and ∼31 Ma, indicating enhanced seawater ventilation synchronously with the opening of the Tasmanian and Drake Passage gateways, respectively. The Oligocene glaciation is recorded by a major increase of bottom seawater δ 18 O during the EOT (Eocene-Oligocene Transition) while Mg/Ca-temperatures remain rather constant. This indicates a significant ice control on the δ 18 O record