Mitochondrial polymorphisms in rat genetic models of hypertension

Hypertension is a complex trait that has been studied extensively for genetic contributions of the nuclear genome. We examined mitochondrial genomes of the hypertensive strains: the Dahl Salt-Sensitive (S) rat, the Spontaneously Hypertensive Rat (SHR), and the Albino Surgery (AS) rat, and the relatively normotensive strains: the Dahl Salt-Resistant (R) rat, the Milan Normotensive Strain (MNS), and the Lewis rat (LEW). These strains were used previously for linkage analysis for blood pressure (BP) in our laboratory. The results provide evidence to suggest that variations in the mitochondrial genome do not account for observed differences in blood pressure between the S and R rats. However, variants were detected among the mitochondrial genomes of the various hypertensive strains, S, SHR, and AS, and also among the normotensive strains R, MNS, and LEW. A total of 115, 114, 106, 106, and 16 variations in mtDNA were observed between the comparisons S versus LEW, S versus MNS, S versus SHR, S versus AS, and SHR versus AS, respectively. Among the 13 genes coding for proteins of the electron transport chain, 8 genes had nonsynonymous variations between S, LEW, MNS, SHR, and AS. The lack of any sequence variants between the mitochondrial genomes of S and R rats provides conclusive evidence that divergence in blood pressure between these two inbred strains is exclusively programmed through their nuclear genomes. The variations detected among the various hypertensive strains provides the basis to construct conplastic strains and further evaluate the effects of these variants on hypertension and associated phenotypes

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

The upper Cenomanian-lower Turonian of the Preafrican Trough (Morocco): Platform configuration and palaeoenvironmental conditions

International audienceA synthetic study was carried out based on sedimentological, palaeontological, geochemical and mineralogical data of the upper Cenomanian lower Turonian carbonate platform of the Preafrican Trough (eastern Morocco) in order to (1) propose a 3D representation of the platform and constrain the temporal framework of the dysoxic/anoxic episodes recorded during the OAE2, (2) define and discuss the prevailing climate on the platform during this period, and (3) make comparisons with other Cenomanian Turonian platforms. During the late Cenomanian, both before and during the CCIE (Cenomanian Carbon Isotope Excursion), the platform displayed an east west polarity. Three third-order sequences of transgression regression can be defined. Dysoxic conditions were developed in the sediments and the bottom waters of the deepest environment (mid- to outer-ramp setting), in the western part of the platform. Well-oxygenated waters were present in the eastern part of the platform (peritidal zone to mid-ramp environment). The climate was arid before the CCIE, becoming warm with contrasted seasons during the CCIE. This climate is associated with a low palaeoproductivity over the entire platform, along with the presence of photozoan followed by heterozoan carbonate-producers, as found also in other parts of the Saharan platform. However, such conditions are not in accordance with many studies which suggest a wet climate during the CCIE, leading to intense chemical weathering of the continent favouring the appearance of high palaeoproductivity at a global scale and the establishment of dysoxic/anoxic conditions. In the Preafrican Trough, poorly-oxygenated waters spread outwards from the deep basins and covered the platform in response to sea-level rise. Many disturbances are recorded in the platform succession during the early Turonian, after the CCIE. Indeed, just after the C/T boundary, the development of an outer-ramp environment over the entire Preafrican Trough reflects flooding of the platform, linked to the end of the major Cenomanian transgression and the presence of eutrophic conditions which disrupted carbonate-producing organisms. This high palaeoproductivity, due to considerable nutrient input, led to the establishment of highly dysoxic/conditions in the bottom and intermediate waters, causing the disappearance of the majority of the Cenomanian palaeontological groups, except for the opportunist benthic and planktonic foraminifera which proliferated. Part of the nutrient input could be due to the presence of a hot and wet climate that may have led a slight increase in the degree of chemical weathering of the continent. Nevertheless, many lines of evidence, such as the decrease of the detrital influx during the early Turonian and the reduction of the weatherable continental areas after the Cenomanian transgression, suggest the existence of another source of nutrient inputs. Combined with the presence of dysoxic/anoxic conditions during the lower Turonian in several regions of the tropical Central Atlantic, the occurrence of these nutrient inputs may be linked to the volcanism/hydrothermalism of the Caribbean LIP and the mid-ocean ridges