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

Survival and Selection of Migrating Salmon from Capture-Recapture Models with Individual Traits

Capture–recapture studies are powerful tools for studying animal population dynamics, providing information on population abundance, survival rates, population growth rates, and selection for phenotypic traits. In these studies, the probability of observing a tagged individual reflects both the probability of the individual surviving to the time of recapture and the probability of recapturing an animal, given that it is alive. If both of these probabilities are related to the same phenotypic trait, it can be difficult to distinguish effects on survival probabilities from effects on recapture probabilities. However, when animals are individually tagged and have multiple opportunities for recapture, we can properly partition observed trait-related variability into survival and recapture components. We present an overview of capture–recapture models that incorporate individual variability and develop methods to incorporate results from these models into estimates of population survival and selection for phenotypic traits. We conducted a series of simulations to understand the performance of these estimators and to assess the consequences of ignoring individual variability when it exists. In addition, we analyzed a large data set of .153 000 juvenile chinook salmon (Oncorhynchus tshawytscha) and steelhead (O. mykiss) of known length that were PIT-tagged during their seaward migration. Both our simulations and the case study indicated that the ability to precisely estimate selection for phenotypic traits was greatly compromised when differential recapture probabilities were ignored. Estimates of population survival, however, were far more robust. In the chinook salmon and steelhead study, we consistently found that smaller fish had a greater probability of recapture. We also uncovered length-related survival relationships in over half of the release group/river segment combinations that we observed, but we found both positive and negative relationships between length and survival probability. These results have important implications for the management of salmonid populations

Synaptic Localization of Nitric Oxide Synthase and Soluble Guanylyl Cyclase in the Hippocampus

Functional evidence suggests that nitric oxide released from CA1 pyramidal cells can act as a retrograde messenger to mediate hippocampal long-term potentiation, but the failure to find neuronal nitric oxide synthase (NOS-I) in the dendritic spines of these cells has cast doubt on this suggestion. We hypothesized that NOS-I may be in spines but in a form inaccessible to antibody when using standard histological fixation procedures. Supporting this hypothesis, we found that after a weak fixation protocol shown previously to enhance staining of synaptic proteins, CA1 pyramidal cells exhibit clear immunoreactivity for NOS-I. Confocal microscopy revealed that numerous dendritic spines in the stratum radiatum contained the NR2 subunit of the NMDA receptor and the adaptor protein postsynaptic density-95, and a subset of these spines also contained NOS-I. Quantitative studies showed that only approximately 8% of synaptic puncta (identified by synaptophysin staining) were associated with NOS-I, and approximately 9% contained the beta subunit of soluble guanylyl cyclase (sGC), a major target of NO. However, the majority of NOS-I-positive synaptic puncta was associated with sGC and vice versa. Postembedding immunogold electron microscopy showed that NOS-I concentrates just inside the postsynaptic plasma membrane of asymmetric axospinous synapses in the stratum radiatum of CA1, whereas sGCbeta concentrates just inside the presynaptic membrane. Together, these findings support the possibility that NO may act as a retrograde messenger to help mediate homosynaptic plasticity in a subpopulation of synapses in the stratum radiatum of CA1

Benzotriazolate cage complexes of tin(II) and lithium: halide-influenced serendipitous assembly

The one-pot reactions of the tin(II) halides SnX2 (X = F, Cl, Br, I) with lithium hexamethyldisilazide, [Li(hmds)], and benzotriazole, (bta)H, produce contrasting outcomes. Tin(II) fluoride does not react with [Li(hmds)] and (bta)H, the outcome being the formation of insoluble [Li(bta)]∞. Tin(II) chloride and tin(II) bromide react with [Li(hmds)] and (bta)H in toluene to produce the hexadecametallic tin(II)-lithium cages [(hmds)8Sn8(bta)12Li8X4]·(ntoluene) [X = Cl, 3·(8 toluene); X = Br, 4·(3 toluene)]. The reaction of tin(II) iodide with [Li(hmds)] and (bta)H in thf solvent produces the ion-separated species [{(thf)2Li(bta)}3{Li(thf)}]2[SnI4]·(thf), [5]2[SnI4]·(thf), the structure of which contains a cyclic trimeric unit of lithium benzotriazolate and a rare example of the tetraiodostannate(II) dianion

Preclinical development of a vaccine against oligomeric alpha-synuclein based on virus-like particles

Parkinson's disease (PD) is a progressive and currently incurable neurological disorder characterised by the loss of midbrain dopaminergic neurons and the accumulation of aggregated alpha-synuclein (a-syn). Oligomeric a-syn is proposed to play a central role in spreading protein aggregation in the brain with associated cellular toxicity contributing to a progressive neurological decline. For this reason, a-syn oligomers have attracted interest as therapeutic targets for neurodegenerative conditions such as PD and other alpha-synucleinopathies. In addition to strategies using small molecules, neutralisation of the toxic oligomers by antibodies represents an attractive and highly specific strategy for reducing disease progression. Emerging active immunisation approaches using vaccines are already being trialled to induce such antibodies. Here we propose a novel vaccine based on the RNA bacteriophage (Qbeta) virus-like particle conjugated with short peptides of human a-syn. High titres of antibodies were successfully and safely generated in wild-type and human a-syn over-expressing (SNCA-OVX) transgenic mice following vaccination. Antibodies from vaccine candidates targeting the C-terminal regions of a-syn were able to recognise Lewy bodies, the hallmark aggregates in human PD brains. Furthermore, antibodies specifically targeted oligomeric and aggregated a-syn as they exhibited 100 times greater affinity for oligomeric species over monomer a-syn proteins in solution. In the SNCA-OVX transgenic mice used, vaccination was, however, unable to confer significant changes to oligomeric a-syn bioburden. Similarly, there was no discernible effect of vaccine treatment on behavioural phenotype as compared to control groups. Thus, antibodies specific for oligomeric a-syn induced by vaccination were unable to treat symptoms of PD in this particular mouse model.</p

Columbia River plume fronts. II. Distribution, abundance, and feeding ecology of juvenile salmon

Well-defined fronts develop at the seaward edge of riverine plumes where suspended materials and planktonic organisms are concentrated by convergent water flows. Riverine plume fronts have been hypothesized to be favorable fish habitats because they can lead to localized prey aggregations. We examined the spatial distribution of juvenile Pacific salmonids Oncorhynchus spp. in and around plankton-rich frontal regions of the Columbia River plume to test the hypothesis that juvenile salmonids aggregate at riverine plume fronts to feed. Juvenile salmonids tended to be abundant in the frontal and plume regions compared to the more marine shelf waters, but this pattern differed among species and was not consistent across the 2 study years. Stomach fullness tended to be higher in the more marine shelf waters than either the front or plume areas, which does not support the hypothesis that salmonids consistently ingest more prey at frontal regions. Many prey organisms were disproportionately abundant at these fronts, but salmon stomach-content analysis did not reveal higher stomach contents at fronts or identify prey groups indicative of feeding in the frontal areas. Although our results indicate that the Columbia River plume influences the distributions of juvenile salmon, our observations do not support the hypothesis that juvenile salmonids congregate to feed at fronts at the leading edge of the Columbia River plume. The short persistence time of these fronts may prevent juvenile salmon from exploiting these food-rich, but ephemeral, features.Keywords: Feeding habits, Distribution, Juvenile salmon, Frontal regions, Columbia River plumeKeywords: Feeding habits, Distribution, Juvenile salmon, Frontal regions, Columbia River plum

The association of spatial T wave axis deviation with incident coronary events. The ARIC cohort

BACKGROUND: Although current evidence suggests that the spatial T wave axis captures important information about ventricular repolarization abnormalities, there are only a few and discordant epidemiologic studies addressing the ability of the spatial T wave axis to predict coronary heart disease (CHD) occurrence. METHODS: This prospective study analyzed data from 12,256 middle-aged African American and white men and women, from the Atherosclerosis Risk in Communities Study (ARIC). Following a standardized protocol, resting standard 12-lead, 10-second electrocardiograms were digitized and analyzed with the Marquette GE program. The median follow-up time was 12.1 years; incident coronary heart disease comprised fatal and non-fatal CHD events. RESULTS: The incidence rate of CHD was 4.26, 4.18, 4.28 and 5.62 per 1000 person-years respectively, across the spatial T wave axis quartiles. Among women for every 10 degrees increase in the spatial T wave axis deviation, there was an estimated increase in the risk of CHD of 1.16 (95% CI 1.04–1.28). After adjustment for age, height, weight, smoking, hypertension, diabetes, QRS axis and minor T wave abnormalities, this hazard rate ratio for women fell to 1.03 (0.92–1.14). The corresponding crude and adjusted hazard ratios for men were 1.05 (95% CI 0.96–1.15) and 0.95 (0.86–1.04) respectively. CONCLUSIONS: In conclusion, this prospective, population-based, bi-ethnic study of men and women free of coronary heart disease at baseline shows that spatial T wave axis deviation is not associated with incident coronary events during long-term follow up. It is doubtful that spatial T wave axis deviation would add benefit in the prediction of CHD events above and beyond the current traditional risk factors

Effect of low tidal volume ventilation on lung function and inflammation in mice

<p>Abstract</p> <p>Background</p> <p>A large number of studies have investigated the effects of high tidal volume ventilation in mouse models. In contrast data on very short term effects of low tidal volume ventilation are sparse. Therefore we investigated the functional and structural effects of low tidal volume ventilation in mice.</p> <p>Methods</p> <p>38 Male C57/Bl6 mice were ventilated with different tidal volumes (Vt 5, 7, and 10 ml/kg) without or with application of PEEP (2 cm H₂O). Four spontaneously breathing animals served as controls. Oxygen saturation and pulse rate were monitored. Lung function was measured every 5 min for at least 30 min. Afterwards lungs were removed and histological sections were stained for measurement of infiltration with polymorphonuclear leukocytes (PMN). Moreover, mRNA expression of macrophage inflammatory protein (MIP)-2 and tumor necrosis factor (TNF)α in the lungs was quantified using real time PCR.</p> <p>Results</p> <p>Oxygen saturation did not change significantly over time of ventilation in all groups (P > 0.05). Pulse rate dropped in all groups without PEEP during mechanical ventilation. In contrast, in the groups with PEEP pulse rate increased over time. These effects were not statistically significant (P > 0.05). Tissue damping (G) and tissue elastance (H) were significantly increased in all groups after 30 min of ventilation (P < 0.05). Only the group with a Vt of 10 ml/kg and PEEP did not show a significant increase in H (P > 0.05). Mechanical ventilation significantly increased infiltration of the lungs with PMN (P < 0.05). Expression of MIP-2 was significantly induced by mechanical ventilation in all groups (P < 0.05). MIP-2 mRNA expression was lowest in the group with a Vt of 10 ml/kg + PEEP.</p> <p>Conclusions</p> <p>Our data show that very short term mechanical ventilation with lower tidal volumes than 10 ml/kg did not reduce inflammation additionally. Formation of atelectasis and inadequate oxygenation with very low tidal volumes may be important factors. Application of PEEP attenuated inflammation.</p