Evolutionary responses by native species to major anthropogenic changes to their ecosystems: Pacific salmon in the Columbia River hydropower system

The human footprint is now large in all the Earth’s ecosystems, and construction of large dams in major river basins is among the anthropogenic changes that have had the most profound ecological consequences, particularly for migratory fishes. In the Columbia River basin of the western USA, considerable effort has been directed toward evaluating demographic effects of dams, yet little attention has been paid to evolutionary responses of migratory salmon to altered selective regimes. Here we make a first attempt to address this information gap. Transformation of the free-flowing Columbia River into a series of slackwater reservoirs has relaxed selection for adults capable of migrating long distances upstream against strong flows; conditions now favour fish capable of migrating through lakes and finding and navigating fish ladders. Juveniles must now be capable of surviving passage through multiple dams or collection and transportation around the dams. River flow patterns deliver some groups of juvenile salmon to the estuary later than is optimal for ocean survival, but countervailing selective pressures might constrain an evolutionary response toward earlier migration timing. Dams have increased the cost of migration, which reduces energy available for sexual selection and favours a nonmigratory life history. Reservoirs are a benign environment for many non-native species that are competitors with or predators on salmon, and evolutionary responses are likely (but undocumented). More research is needed to tease apart the relative importance of evolutionary vs. plastic responses of salmon to these environmental changes; this research is logistically challenging for species with life histories like Pacific salmon, but results should substantially improve our understanding of key processes. If the Columbia River is ever returned to a quasinatural, free-flowing state, remaining populations might face a Darwinian debt (and temporarily reduced fitness) as they struggle to re-evolve historical adaptations

Detection of CWD Prions in Urine and Saliva of Deer by Transgenic Mouse Bioassay

Chronic wasting disease (CWD) is a prion disease affecting captive and free-ranging cervids (e.g. deer, elk, and moose). The mechanisms of CWD transmission are poorly understood, though bodily fluids are thought to play an important role. Here we report the presence of infectious prions in the urine and saliva of deer with chronic wasting disease (CWD). Prion infectivity was detected by bioassay of concentrated, dialyzed urine and saliva in transgenic mice expressing the cervid PrP gene (Tg[CerPrP] mice). In addition, PrP(CWD) was detected in pooled and concentrated urine by protein misfolding cyclic amplification (PMCA). The concentration of abnormal prion protein in bodily fluids was very low, as indicated by: undetectable PrP(CWD) levels by traditional assays (western blot, ELISA) and prolonged incubation periods and incomplete TSE attack rates in inoculated Tg(CerPrP) mice (373(+/-)3 days in 2 of 9 urine-inoculated mice and 342(+/-)109 days in 8 of 9 saliva-inoculated mice). These findings help extend our understanding of CWD prion shedding and transmission and portend the detection of infectious prions in body fluids in other prion infections

Detection of Sub-Clinical CWD Infection in Conventional Test-Negative Deer Long after Oral Exposure to Urine and Feces from CWD+ Deer

Chronic wasting disease (CWD) of cervids is a prion disease distinguished by high levels of transmissibility, wherein bodily fluids and excretions are thought to play an important role. Using cervid bioassay and established CWD detection methods, we have previously identified infectious prions in saliva and blood but not urine or feces of CWD+ donors. More recently, we identified very low concentrations of CWD prions in urine of deer by cervid PrP transgenic (Tg[CerPrP]) mouse bioassay and serial protein misfolding cyclic amplification (sPMCA). This finding led us to examine further our initial cervid bioassay experiments using sPMCA. distribution in these animals.Various neural and lymphoid tissues from conventional test-negative deer were reanalyzed for CWD prions by sPMCA and cervid transgenic mouse bioassay in parallel with appropriate tissue-matched positive and negative controls. was amplified from both lymphoid and neural tissues of positive control deer but not from identical tissues of negative control deer.Detection of subclinical infection in deer orally exposed to urine and feces (1) suggests that a prolonged subclinical state can exist, necessitating observation periods in excess of two years to detect CWD infection, and (2) illustrates the sensitive and specific application of sPMCA in the diagnosis of low-level prion infection. Based on these results, it is possible that low doses of prions, e.g. following oral exposure to urine and saliva of CWD-infected deer, bypass significant amplification in the LRS, perhaps utilizing a neural conduit between the alimentary tract and CNS, as has been demonstrated in some other prion diseases

Detection of prion protein in the cerebrospinal fluid of elk (\u3ci\u3eCervus canadensis nelsoni\u3c/i\u3e) with chronic wasting disease using protein misfolding cyclic amplification

Cerebrospinal fluid (CSF) has been examined as a possible source for preclinical diagnosis of prion diseases in hamsters and sheep. The present report describes the detection of chronic wasting disease (CWD) in the CSF of elk and evaluates its usefulness as an antemortem test for CWD. The CSF from 6 captive and 31 free-ranging adult elk was collected at necropsy and evaluated for the presence of the abnormal isoform of the prion protein that has been associated with CWD (PrPCWD) via protein misfolding cyclic amplification. Additionally, the obex from each animal was examined by immunohistochemistry (IHC). Four out of 6 captive animals were CWD-positive and euthanized due to signs of terminal CWD. The remaining 2 were CWD negative. None of the 31 free-range animals showed overt signs of CWD, but 12 out of 31 tested positive for CWD by IHC. Protein misfolding cyclic amplification detected PrPCWD from 3 of the 4 captive animals showing clinical signs of CWD and none of the nonclinical animals that were CWD positive by IHC. The data suggests that CWD prions can be detected in the CSF of elk, but only relatively late in the course of the disease

Dietary magnesium and copper affect survival time and neuroinflammation in chronic wasting disease

Chronic wasting disease (CWD), the only known wildlife prion disease, affects deer, elk and moose. The disease is an ongoing and expanding problem in both wild and captive North American cervid populations and is difficult to control in part due to the extreme environmental persistence of prions, which can transmit disease years after initial contamination. The role of exogenous factors in CWD transmission and progression is largely unexplored. In an effort to understand the influence of environmental and dietary constituents on CWD, we collected and analyzed water and soil samples from CWD-negative and positive captive cervid facilities, as well as from wild CWD-endozootic areas. Our analysis revealed that, when compared with CWD-positive sites, CWD-negative sites had a significantly higher concentration of magnesium, and a higher magnesium/copper (Mg/Cu) ratio in the water than that from CWD-positive sites. When cevidized transgenic mice were fed a custom diet devoid of Mg and Cu and drinking water with varied Mg/Cu ratios, we found that higher Mg/Cu ratio resulted in significantly longer survival times after intracerebral CWD inoculation. We also detected reduced levels of inflammatory cytokine gene expression in mice fed a modified diet with a higher Mg/Cu ratio compared to those on a standard rodent diet. These findings indicate a role for dietary Mg and Cu in CWD pathogenesis through modulating inflammation in the brain

Kti12, a PSTK-like tRNA dependent ATPase essential for tRNA modification by Elongator

Posttranscriptional RNA modifications occur in all domains of life. Modifications of anticodon bases are of particular importance for ribosomal decoding and proteome homeostasis. The Elongator complex modifies uridines in the wobble position and is highly conserved in eukaryotes. Despite recent insights into Elongator's architecture, the structure and function of its regulatory factor Kti12 have remained elusive. Here, we present the crystal structure of Kti12's nucleotide hydrolase domain trapped in a transition state of ATP hydrolysis. The structure reveals striking similarities to an O-phosphoseryl-tRNA kinase involved in the selenocysteine pathway. Both proteins employ similar mechanisms of tRNA binding and show tRNASec-dependent ATPase activity. In addition, we demonstrate that Kti12 binds directly to Elongator and that ATP hydrolysis is crucial for Elongator to maintain proper tRNA anticodon modification levels in vivo. In summary, our data reveal a hitherto uncharacterized link between two translational control pathways that regulate selenocysteine incorporation and affect ribosomal tRNA selection via specific tRNA modifications.</p

Superconductivity in the Intercalated Graphite Compounds C6Yb and C6Ca

In this letter we report the discovery of superconductivity in the isostructural graphite intercalation compounds C6Yb and C6Ca, with transition temperatures of 6.5K and 11.5K respectively. A structural characterisation of these compounds shows them to be hexagonal layered systems in the same class as other graphite intercalates. If we assume that all the outer s-electrons are transferred from the intercalant to the graphite sheets, then the charge transfer in these compounds is comparable to other superconducting graphite intercalants such as C8K 1,2 . However, the superconducting transition temperatures of C6Yb and C6Ca are up to two orders of magnitude greater. Interestingly, superconducting upper critical field studies and resistivity measurements suggest that these compounds are significantly more isotropic than pure graphite. This is unexpected as the effect of introducing the intercalant is to move the graphite layer further apart.Comment: 2 Figures. Please see accompanying theoretical manuscript, "Electronic Structure of the Superconducting Graphite Intercalates" by Csanyi et al., cond-mat/050356

Analysis of the putative role of CR1 in Alzheimer’s disease: Genetic association, expression and function

Chronic activation of the complement system and induced inflammation are associated with neuropathology in Alzheimer's disease (AD). Recent large genome wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) in the C3b/C4b receptor (CR1 or CD35) that are associated with late onset AD. Here, anti-CR1 antibodies (Abs) directed against different epitopes of the receptor, were used to localize CR1 in brain, and relative binding affinities of the CR1 ligands, C1q and C3b, were assessed by ELISA. Most Abs tested stained red blood cells in blood vessels but showed no staining in brain parenchyma. However, two monoclonal anti-CR1 Abs labeled astrocytes in all of the cases tested, and this reactivity was preabsorbed by purified recombinant human CR1. Human brain-derived astrocyte cultures were also reactive with both mAbs. The amount of astrocyte staining varied among the samples, but no consistent difference was conferred by diagnosis or the GWAS-identified SNPs rs4844609 or rs6656401. Plasma levels of soluble CR1 did not correlate with diagnosis but a slight increase was observed with rs4844609 and rs6656401 SNP. There was also a modest but statistically significant increase in relative binding activity of C1q to CR1 with the rs4844609 SNP compared to CR1 without the SNP, and of C3b to CR1 in the CR1 genotypes containing the rs6656401 SNP (also associated with the larger isoform of CR1) regardless of clinical diagnosis. These results suggest that it is unlikely that astrocyte CR1 expression levels or C1q or C3b binding activity are the cause of the GWAS identified association of CR1 variants with AD. Further careful functional studies are needed to determine if the variant-dictated number of CR1 expressed on red blood cells contributes to the role of this receptor in the progression of AD, or if another mechanism is involved