Descriptive anatomy of the largest known specimen of Protoichthyosaurus prostaxalis (Reptilia: Ichthyosauria) including computed tomography and digital reconstruction of a three-dimensional skull

Ichthyosaur fossils are abundant in Lower Jurassic sediments with nine genera found in the UK. In this paper, we describe the partial skeleton of a large ichthyosaur from the Lower Jurassic (lower Sinemurian) of Warwickshire, England, which was conserved and rearticulated to form the centrepiece of a new permanent gallery at the Thinktank, Birmingham Science Museum in 2015. The unusual three-dimensional preservation of the specimen permitted computed tomography (CT) scanning of individual braincase elements as well as the entire reassembled skull. This represents one of the first times that medical imaging and three-dimensional reconstruction methods have been applied to a large skull of a marine reptile. Data from these scans provide new anatomical information, such as the presence of branching vascular canals within the premaxilla and dentary, and an undescribed dorsal (quadrate) wing of the pterygoid hidden within matrix. Scanning also revealed areas of the skull that had been modelled in wood, clay and other materials after the specimen’s initial discovery, highlighting the utility of applying advanced imaging techniques to historical specimens. Additionally, the CT data served as the basis for a new three-dimensional reconstruction of the skull, in which minor damage was repaired and the preserved bones digitally rearticulated. Thus, for the first time a digital reconstruction of the skull and mandible of a large marine reptile skull is available. Museum records show the specimen was originally identified as an example of Ichthyosaurus communis but we identify this specimen as Protoichthyosaurus prostaxalis. The specimen features a skull nearly twice as long as any previously described specimen of P. prostaxalis, representing an individual with an estimated total body length between 3.2 and 4 m

Excavating the 'Rutland Sea Dragon': The largest ichthyosaur skeleton ever found in the UK (Whitby Mudstone Formation, Toarcian, Lower Jurassic)

An almost complete ichthyosaur skeleton 10 m long was discovered in January 2021 at the Rutland Water Nature Reserve in the county of Rutland, UK. This was excavated by a small team of palaeontologists in the summer of the same year. Nicknamed ‘The Rutland Sea Dragon’, this almost fully articulated skeleton is an example of the large-bodied Early Jurassic ichthyosaur Temnodontosaurus. The specimen was analysed in situ, recorded (including a 3D scan using photogrammetry), excavated and removed from the site in a series of large plaster field jackets to preserve taphonomic information. Significantly, the specimen is the largest ichthyosaur skeleton to have been found in the UK and it may be the first recorded example of Temnodontosaurus trigonodon to be found in the country, extending its known geographic range significantly. It also represents the most complete skeleton of a large prehistoric reptile to have been found in the UK. We provide an account of the discovery and describe the methods used for excavating, recording and lifting the large skeleton which will aid palaeontologists facing similar challenges when collecting extensive remains of large and fragile fossil vertebrates. We also discuss the preliminary research findings and the global impact this discovery has had through public engagement

The State of the Region: Hampton Roads 2002

This is Old Dominion University\u27s third annual State of the Region report.While it represents the work of many individuals connected in various ways to the university, the report does not constitute an official viewpoint of the University, or it\u27s president, Dr. Roseann Runte. Our State of the Region reports maintain the modest goal of making Hampton Roads an even better place to live. We are proud of our region\u27s many successes, but realize that it is possible to improve the region\u27s performance. Yet, in order to improve our performance, we must have accurate information about where we are and a sound understanding of the policy options open to us. This year\u27s report places particular emphasis upon providing up-to-date information on how Hampton Roads compares to other regions nationally.https://digitalcommons.odu.edu/economics_books/1016/thumbnail.jp

Excitability and synaptic transmission in the enteric nervous system: Does diet play a role?

© Springer International Publishing Switzerland 2016. Changes in diet are a challenge to the gastrointestinal tract which needs to alter its processing mechanisms to continue to process nutrients and maintain health. In particular, the enteric nervous system (ENS) needs to adapt its motor and secretory programs to deal with changes in nutrient type and load in order to optimise nutrient absorption. The nerve circuits in the gut are complex, and the numbers and types of neurons make recordings of specific cell types difficult, time-consuming, and prone to sampling errors. Nonetheless, traditional research methods like intracellular electrophysiological approaches have provided the basis for our understanding of the ENS circuitry. In particular, animal models of intestinal inflammation have shown us that we can document changes to neuronal excitability and synaptic transmission. Recent studies examining diet-induced changes to ENS programming have opted to use fast imaging techniques to reveal changes in neuron function. Advances in imaging techniques using voltage- or calcium-sensitive dyes to record neuronal activity promise to overcome many limitations inherent to electrophysiological approaches. Imaging techniques allow access to a wide range of ENS phenotypes and to the changes they undergo during dietary challenges. These sorts of studies have shown that dietary variation or obesity can change how the ENS processes information-in effect reprogramming the ENS. In this review, the data gathered from intracellular recordings will be compared with measurements made using imaging techniques in an effort to determine if the lessons learnt from inflammatory changes are relevant to the understanding of diet-induced reprogramming

Differential modulatory effects of GSK-3β and HDM2 on sorafenib-induced AIF nuclear translocation (programmed necrosis) in melanoma

<p>Abstract</p> <p>Background</p> <p>GSK-3β phosphorylates numerous substrates that govern cell survival. It phosphorylates p53, for example, and induces its nuclear export, HDM2-dependent ubiquitination, and proteasomal degradation. GSK-3β can either enhance or inhibit programmed cell death, depending on the nature of the pro-apoptotic stimulus. We previously showed that the multikinase inhibitor sorafenib activated GSK-3β and that this activation attenuated the cytotoxic effects of the drug in various BRAF-mutant melanoma cell lines. In this report, we describe the results of studies exploring the effects of GSK-3β on the cytotoxicity and antitumor activity of sorafenib combined with the HDM2 antagonist MI-319.</p> <p>Results</p> <p>MI-319 alone increased p53 levels and p53-dependent gene expression in melanoma cells but did not induce programmed cell death. Its cytotoxicity, however, was augmented in some melanoma cell lines by the addition of sorafenib. In responsive cell lines, the MI-319/sorafenib combination induced the disappearance of p53 from the nucleus, the down modulation of Bcl-2 and Bcl-x_L, the translocation of p53 to the mitochondria and that of AIF to the nuclei. These events were all GSK-3β-dependent in that they were blocked with a GSK-3β shRNA and facilitated in otherwise unresponsive melanoma cell lines by the introduction of a constitutively active form of the kinase (GSK-3β-S9A). These modulatory effects of GSK-3β on the activities of the sorafenib/MI-319 combination were the exact reverse of its effects on the activities of sorafenib alone, which induced the down modulation of Bcl-2 and Bcl-x_Land the nuclear translocation of AIF only in cells in which GSK-3β activity was either down modulated or constitutively low. In A375 xenografts, the antitumor effects of sorafenib and MI-319 were additive and associated with the down modulation of Bcl-2 and Bcl-x_L, the nuclear translocation of AIF, and increased suppression of tumor angiogenesis.</p> <p>Conclusions</p> <p>Our data demonstrate a complex partnership between GSK-3β and HDM2 in the regulation of p53 function in the nucleus and mitochondria. The data suggest that the ability of sorafenib to activate GSK-3β and alter the intracellular distribution of p53 may be exploitable as an adjunct to agents that prevent the HDM2-dependent degradation of p53 in the treatment of melanoma.</p

Noncanonical DNA Motifs as Transactivation Targets by Wild Type and Mutant p53

Sequence-specific binding by the human p53 master regulator is critical to its tumor suppressor activity in response to environmental stresses. p53 binds as a tetramer to two decameric half-sites separated by 0–13 nucleotides (nt), originally defined by the consensus RRRCWWGYYY (n = 0–13) RRRCWWGYYY. To better understand the role of sequence, organization, and level of p53 on transactivation at target response elements (REs) by wild type (WT) and mutant p53, we deconstructed the functional p53 canonical consensus sequence using budding yeast and human cell systems. Contrary to early reports on binding in vitro, small increases in distance between decamer half-sites greatly reduces p53 transactivation, as demonstrated for the natural TIGER RE. This was confirmed with human cell extracts using a newly developed, semi–in vitro microsphere binding assay. These results contrast with the synergistic increase in transactivation from a pair of weak, full-site REs in the MDM2 promoter that are separated by an evolutionary conserved 17 bp spacer. Surprisingly, there can be substantial transactivation at noncanonical ½-(a single decamer) and ¾-sites, some of which were originally classified as biologically relevant canonical consensus sequences including PIDD and Apaf-1. p53 family members p63 and p73 yielded similar results. Efficient transactivation from noncanonical elements requires tetrameric p53, and the presence of the carboxy terminal, non-specific DNA binding domain enhanced transactivation from noncanonical sequences. Our findings demonstrate that RE sequence, organization, and level of p53 can strongly impact p53-mediated transactivation, thereby changing the view of what constitutes a functional p53 target. Importantly, inclusion of ½- and ¾-site REs greatly expands the p53 master regulatory network

An 8.5 m long ammonite drag mark from the Upper Jurassic Solnhofen Lithographic Limestones, Germany

Trackways and tracemakers preserved together in the fossil record are rare. However, the co-occurrence of a drag mark, together with the dead animal that produced it, is exceptional. Here, we describe an 8.5 m long ammonite drag mark complete with the preserved ammonite shell (Subplanites rueppellianus) at its end. Previously recorded examples preserve ammonites with drag marks of < 1 m. The specimen was recovered from a quarry near Solnhofen, southern Germany. The drag mark consists of continuous parallel ridges and furrows produced by the ribs of the ammonite shell as it drifted just above the sediment surface, and does not reflect behaviour of the living animal

The effects of Δ9-tetrahydrocannabinol on the dopamine system

Δ(9)-tetrahydrocannabinol (THC), the main psychoactive ingredient in cannabis, is a pressing concern to global mental health. Patterns of use are changing drastically due to legalisation, availability of synthetic analogues (‘spice’), cannavaping and aggrandizements in the purported therapeutic effects of cannabis. Many of THC’s reinforcing effects are mediated by the dopamine system. Due to complex cannabinoid-dopamine interactions there is conflicting evidence from human and animal research fields. Acute THC causes increased dopamine release and neuron activity, whilst long-term use is associated with blunting of the dopamine system. Future research must examine the long-term and developmental dopaminergic effects of the drug

Mid-Devensian climate and landscape in England : new data from Finningley, South Yorkshire

While there is extensive evidence for the Late Devensian, less is known about Early and Middle Devensian (approx. 110–30 ka) climates and environments in the UK. The Greenland ice-core record suggests the UK should have endured multiple changes, but the terrestrial palaeo-record lacks sufficient detail for confirmation from sites in the British Isles. Data from deposits at Finningley, South Yorkshire, can help redress this. A channel with organic silts, dated 40 314–39 552 cal a BP, contained plant macrofossil and insect remains showing tundra with dwarf-shrub heath and bare ground. Soil moisture conditions varied from free draining to riparian, with ponds and wetter vegetated areas. The climate was probably low arctic with snow cover during the winter. Mutual climatic range (MCR), based on Coleoptera, shows the mean monthly winter temperatures of −22 to −2°C and summer ones of 8–14°C. Periglacial structures within the basal gravel deposits and beyond the glacial limits indicate cold-climate conditions, including permafrost. A compilation of MCR reconstructions for other Middle Devensian English sites shows that marine isotope stage 3—between 59 and 28 ka—experienced substantial variation in climate consistent with the Greenland ice-core record. The exact correlation is hampered by temporal resolution, but the Finningley site stadial at approximately 40 ka may correlate with the one of the Greenland stadials 7–11