Analysis of the fluvial stratigraphic response to the Paleocene–Eocene Thermal Maximum in the Bighorn Basin, U.S.A.

The appendix contains five sections, each of which shows the summarized raw sedimentary logs for all locations studies. Section A1.1: Sedimentary logs from the Beartooth systems. Section A1.2: Sedimentary logs from the Absoraka systems. Section A1.3: sedimentary logs from Washakie sedimentary systems. Section A1.4: sedimentary logs from the Owl Creek systems. Section A1.5: sedimentary logs from the Axial system.Geological deposits can reveal how environments of the past have responded to climate change, enabling important insights into how environments may respond to our current anthropogenically induced warming. The Paleocene–Eocene Thermal Maximum (PETM) occurred ca. 56 Ma and was a short-lived (approximately 200,000 years) global warming event (5–8°C rise). The PETM has been investigated at several terrestrial and marine localities across the globe. However, many studies are based on single successions, with very few sites being placed within a well-defined spatial and temporal context and with comparisons limited to deposits that lie immediately above and below the event. Due to the inherent variability of sedimentary systems, it is imperative that the appropriate context is provided to fully understand the impacts of climate change on landscapes and subsequent deposits. This study examines 28 locations, totaling over 4 km of recorded stratigraphy, within a newly defined quantified sedimentary basin context (Bighorn Basin, USA) to evaluate variability of fluvial response to the PETM. We show that channel-body and story thicknesses across the PETM are not statistically significantly different from deposits outside the climate event, implying that there is not a consistent sedimentary response to the climate event across the basin. Based on our large dataset we calculate that precipitation would have had to double for statistically significant changes in deposit thickness to be generated. We discuss how climatic signals may be lost due to the self-organization, spatial–temporal varied response and preservation potential in large fluvial systems. This study gives a new quantified perspective to climate events in the geologic record.AO, AH, and GW thanks FSRG 2 sponsors for funding field campaigns. AE thanks University of Aberdeen for funding field work. We thank all residents in the Bighorn Basin who allowed access to private land to study the Paleogene fill, which greatly enhanced the size and quality of this dataset. Isobel Buchanon, Alistair Swan, and Mauricio Santos are thanked for their assistance in the field

Propagation of RML Prions in Mice Expressing PrP Devoid of GPI Anchor Leads to Formation of a Novel, Stable Prion Strain

PrPC, a host protein which in prion-infected animals is converted to PrPSc, is linked to the cell membrane by a GPI anchor. Mice expressing PrPC without GPI anchor (tgGPI- mice), are susceptible to prion infection but accumulate anchorless PrPSc extra-, rather than intracellularly. We investigated whether tgGPI− mice could faithfully propagate prion strains despite the deviant structure and location of anchorless PrPSc. We found that RML and ME7, but not 22L prions propagated in tgGPI− brain developed novel cell tropisms, as determined by the Cell Panel Assay (CPA). Surprisingly, the levels of proteinase K-resistant PrPSc (PrPres) in RML- or ME7-infected tgGPI− brain were 25–50 times higher than in wild-type brain. When returned to wild-type brain, ME7 prions recovered their original properties, however RML prions had given rise to a novel prion strain, designated SFL, which remained unchanged even after three passages in wild-type mice. Because both RML PrPSc and SFL PrPSc are stably propagated in wild-type mice we propose that the two conformations are separated by a high activation energy barrier which is abrogated in tgGPI− mice

A Simple, Versatile and Sensitive Cell-Based Assay for Prions from Various Species

Detection and quantification of prion infectivity is a crucial step for various fundamental and applied aspects of prion research. Identification of cell lines highly sensitive to prion infection led to the development of cell-based titration procedures aiming at replacing animal bioassays, usually performed in mice or hamsters. However, most of these cell lines are only permissive to mouse-adapted prions strains and do not allow titration of prions from other species. In this study, we show that epithelial RK13, a cell line permissive to mouse and bank vole prion strains and to natural prion agents from sheep and cervids, enables a robust and sensitive detection of mouse and ovine-derived prions. Importantly, the cell culture work is strongly reduced as the RK13 cell assay procedure designed here does not require subcultivation of the inoculated cultures. We also show that prions effectively bind to culture plastic vessel and are quantitatively detected by the cell assay. The possibility to easily quantify a wider range of prions, including rodent experimental strains but also natural agents from sheep and cervids, should prompt the spread of cell assays for routine prion titration and lead to valuable information in fundamental and applied studies

Resistance of Bovine Spongiform Encephalopathy (BSE) Prions to Inactivation

Distinct prion strains often exhibit different incubation periods and patterns of neuropathological lesions. Strain characteristics are generally retained upon intraspecies transmission, but may change on transmission to another species. We investigated the inactivation of two related prions strains: BSE prions from cattle and mouse-passaged BSE prions, termed 301V. Inactivation was manipulated by exposure to sodium dodecyl sulfate (SDS), variations in pH, and different temperatures. Infectivity was measured using transgenic mouse lines that are highly susceptible to either BSE or 301V prions. Bioassays demonstrated that BSE prions are up to 1,000-fold more resistant to inactivation than 301V prions while Western immunoblotting showed that short acidic SDS treatments reduced protease-resistant PrPSc from BSE prions and 301V prions at similar rates. Our findings argue that despite being derived from BSE prions, mouse 301V prions are not necessarily a reliable model for cattle BSE prions. Extending these comparisons to human sporadic Creutzfeldt-Jakob disease and hamster Sc237 prions, we found that BSE prions were 10- and 106-fold more resistant to inactivation, respectively. Our studies contend that any prion inactivation procedures must be validated by bioassay against the prion strain for which they are intended to be used

Serotonin synthesis, release and reuptake in terminals: a mathematical model

<p>Abstract</p> <p>Background</p> <p>Serotonin is a neurotransmitter that has been linked to a wide variety of behaviors including feeding and body-weight regulation, social hierarchies, aggression and suicidality, obsessive compulsive disorder, alcoholism, anxiety, and affective disorders. Full understanding of serotonergic systems in the central nervous system involves genomics, neurochemistry, electrophysiology, and behavior. Though associations have been found between functions at these different levels, in most cases the causal mechanisms are unknown. The scientific issues are daunting but important for human health because of the use of selective serotonin reuptake inhibitors and other pharmacological agents to treat disorders in the serotonergic signaling system.</p> <p>Methods</p> <p>We construct a mathematical model of serotonin synthesis, release, and reuptake in a single serotonergic neuron terminal. The model includes the effects of autoreceptors, the transport of tryptophan into the terminal, and the metabolism of serotonin, as well as the dependence of release on the firing rate. The model is based on real physiology determined experimentally and is compared to experimental data.</p> <p>Results</p> <p>We compare the variations in serotonin and dopamine synthesis due to meals and find that dopamine synthesis is insensitive to the availability of tyrosine but serotonin synthesis is sensitive to the availability of tryptophan. We conduct <it>in silico </it>experiments on the clearance of extracellular serotonin, normally and in the presence of fluoxetine, and compare to experimental data. We study the effects of various polymorphisms in the genes for the serotonin transporter and for tryptophan hydroxylase on synthesis, release, and reuptake. We find that, because of the homeostatic feedback mechanisms of the autoreceptors, the polymorphisms have smaller effects than one expects. We compute the expected steady concentrations of serotonin transporter knockout mice and compare to experimental data. Finally, we study how the properties of the the serotonin transporter and the autoreceptors give rise to the time courses of extracellular serotonin in various projection regions after a dose of fluoxetine.</p> <p>Conclusions</p> <p>Serotonergic systems must respond robustly to important biological signals, while at the same time maintaining homeostasis in the face of normal biological fluctuations in inputs, expression levels, and firing rates. This is accomplished through the cooperative effect of many different homeostatic mechanisms including special properties of the serotonin transporters and the serotonin autoreceptors. Many difficult questions remain in order to fully understand how serotonin biochemistry affects serotonin electrophysiology and vice versa, and how both are changed in the presence of selective serotonin reuptake inhibitors. Mathematical models are useful tools for investigating some of these questions.</p

Groundwater vulnerability assessment: Hydrogeologie perspective and example from salinas valley, california

Vulnerability of groundwater to contamination has typically been addressed by analysis or inference of near-surface hydrologic processes. Yet, in many basins like the Salinas Valley, California, shallow groundwater quality has already been degraded over large areas by nitrates, pesticides, salinity from irrigation, or other contaminants. The ultimate impact of this contamination on deeper groundwater quality during the decades, centuries or millennia to come is a highly relevant issue. We demonstrate an approach to groundwater vulnerability assessment that emphasizes important geologic features in a stochastic-geostatistical framework and incorporates information on both shallow and deep groundwater flow and contaminant transport in the context of a circulating groundwater system. The approach complements more common, shallow investigative approaches, which emphasize source inventory, soil characteristics, and vadose-zone flow and transport. Results from an assessment of groundwater vulnerability to nitrate contamination in the Salinas Valley agree with observed regional patterns in groundwater nitrate concentrations