Aquatic Invertebrate Community Structure, Biological Condition, Habitat, and Water Quality at Ozark National Scenic Riverways, Missouri, 2005-2014

Ozark National Scenic Riverways (OZAR) was established to protect the corridor of the Current River and its major tributary, the Jacks Fork. The Current River is one of the few remaining free-flowing rivers in the U.S., with much of its base flow coming from several large springs. To assess the biological condition of these rivers, aquatic invertebrate community structure was monitored from 2005 to 2014. Benthic invertebrate samples and associated habitat and water quality data were collected from each of nine sampling sites using a Slack-Surber sampler. The Stream Condition Index (SCI), a multimetric index that incorporates taxa richness, EPT (Ephemeroptera, Plecoptera, Trichoptera) richness, Shannon’s diversity index, and Hilsenhoff Biotic Index (HBI), was calculated. The benthic invertebrate fauna was diverse with 155 distinct taxa identified from all sites. Mean taxa richness was high, ranging from 22 to 30 among sites. The invertebrate taxa of the Current River and Jacks Fork are largely intolerant across all taxa represented (mean tolerance value= ~4.25). Mean HBI did not exceed 3.9 in the Current River or 4.4 for the Jacks Fork. Mean SCI scores across sampling sites generally were well above 16, indicating they are not impaired. Habitat and water quality data were summarized, but they were poorly correlated with individual invertebrate metrics. Sørenson’s similarity index was used to assess community similarity among sites, and similarity scores were then analyzed using ascendant hierarchical cluster analysis. Similarity among sites was 72% or greater. Cluster analysis showed that Current River and Jacks Fork sites clustered separately and in a downstream progression. The uppermost collection site on the Current River was most unlike the other sites, which probably relates to the distinct physical features of that site compared to the others. Nonmetric Multidimensional Scaling (NMDS) was used to evaluate the relationship of invertebrate metrics to habitat and water quality. The NMDS model was found to be a good fit (stress=0.04) and specific conductance, temperature, discharge, filamentous algae and aquatic vegetation were among the most important habitat variables in defining the relationship among sampling sites. The three lower Current River and Jacks Fork sites each were closely grouped in ordination space, but the three upper Current River sites were farther apart from each other. The influence of several large volume springs near those sites is suspected of producing such disparity through press type disturbances. Although the invertebrate communities and water quality in the Current River and Jacks Fork are largely sound and have high biological condition, ongoing and projected threats to these resources remain, and those threats largely originate outside park jurisdictional boundaries. Inherent variability of invertebrate community diversity across sites and years highlights the importance of using multi-metric assessments and multiyear monitoring to support management decisions

AQUATIC INVERTEBRATE COMMUNITY STRUCTURE IN THE NIOBRARA RIVER, AGATE FOSSIL BEDS NATIONAL MONUMENT, NEBRASKA, 1996-2009

Aquatic invertebrates were sampled annually in the Niobrara River, Nebraska, during the period 1996-2009 using Hester-Dendy multiplate samplers. Collections indicated the invertebrate community in the river has shifted from one dominated by Ephemeroptera, Plecoptera, and Trichoptera (EPT) taxa to one dominated by Chironomidae and Amphipoda. Generally, EPT richness and percentage abundance of EPT of the total community, as well as percentage abundance of Heptageniidae and Leptophlebiidae, has declined across the years. During that same period, percentage abundance of Amphipoda and Chironomidae, taxa evenness, Shannon\u27s Index, and the Hilsenhoff Biotic Index have increased. Stream discharge decreased significantly during the 15-year period when invertebrates were collected (Mann-Kendall trend test, P = 0.04). Water-surface elevation of the river measured with staff gages also gradually increased over time, although the trends were not significant (P \u3e/= 0.15). Although not analyzed statistically, water temperature (Degrees C), conductivity (uS/cm), and pH gradually increased over time while dissolved oxygen concentration (mg/liter) decreased over time. Although other factors cannot be ruled out, a proposed reason for the observed changes in invertebrate community structure may be related to changes in the physical habitat condition in the Niobrara River associated with encroachment of the nonnative and invasive emergent aquatic plant, yellow flag (Iris pseudacorus L.). This weed has expanded into the stream channel, where it blocks streamflow

Chronic Kidney Disease Increases Cerebral Microbleeds in Mouse and Man.

Brain microbleeds are increased in chronic kidney disease (CKD) and their presence increases risk of cognitive decline and stroke. We examined the interaction between CKD and brain microhemorrhages (the neuropathological substrate of microbleeds) in mouse and cell culture models and studied progression of microbleed burden on serial brain imaging from humans. Mouse studies: Two CKD models were investigated: adenine-induced tubulointerstitial nephritis and surgical 5/6 nephrectomy. Cell culture studies: bEnd.3 mouse brain endothelial cells were grown to confluence, and monolayer integrity was measured after exposure to 5-15% human uremic serum or increasing concentrations of urea. Human studies: Progression of brain microbleeds was evaluated on serial MRI from control, pre-dialysis CKD, and dialysis patients. Microhemorrhages were increased 2-2.5-fold in mice with CKD independent of higher blood pressure in the 5/6 nephrectomy model. IgG staining was increased in CKD animals, consistent with increased blood-brain barrier permeability. Incubation of bEnd.3 cells with uremic serum or elevated urea produced a dose-dependent drop in trans-endothelial electrical resistance. Elevated urea induced actin cytoskeleton derangements and decreased claudin-5 expression. In human subjects, prevalence of microbleeds was 50% in both CKD cohorts compared with 10% in age-matched controls. More patients in the dialysis cohort had increased microbleeds on follow-up MRI after 1.5 years. CKD disrupts the blood-brain barrier and increases brain microhemorrhages in mice and microbleeds in humans. Elevated urea alters the actin cytoskeleton and tight junction proteins in cultured endothelial cells, suggesting that these mechanisms explain (at least in part) the microhemorrhages and microbleeds observed in the animal and human studies

The Progression of β-amyloid Deposition in the Frontal Cortex of the Aged Canine

Brains from 41 aged canines (≥10 years of age) were examined immunohistochemically to characterize the laminar distribution and age-related progression of β-amyloid (Aβ) in frontal cortex. We classified the Aβ patterns into four distinct types. Type I was characterized by small, faint deposits of Aβ in deep cortical layers. Type II consisted of diffuse deposits of Aβ mainly in layers V and VI. Type III had both dense plaques in superficial layers, and diffuse deposits in deep layers. Finally, Type IV had solely dense plaques throughout all layers of cortex. We compared the Aβ distribution pattern between the Old canines (10–15 years, n=22) and the Very Old canines (\u3e15 years, n=19). The Old group primarily had negative staining, or Type I and Type II patterns of amyloid deposition (73%). Conversely, the Very Old group had predominantly Types II, III and IV deposits (89.5%), a difference that was significant (Pβ deposition in canine frontal cortex is a progressive age-related process beginning with diffuse deposits in the deep cortical layers followed by the development of deposits in outer layers. In support of this hypothesis, the deeper layer diffuse plaques in the Very Old group of dogs also contain the largest proportion of β-amyloid with an isomerized aspartic acid residue at position 7, indicating that these deposits had been present for some time. We also observed fiber-like Aβ immunoreactivity within regions of diffuse Aβ deposits. These fibers appeared to be degenerating neurites, which were negative for hyperphosphorylated tau. Therefore, these fibers may represent a very early form of neuritic change that precede tau hyperphosphorylation or develop by an alternative pathway

Long-term Aquatic Invertebrate Monitoring at Buffalo National River, Arkansas

Aquatic invertebrate community structure was used to assess long-term water quality integrity in the mainstem of the Buffalo National River, Arkansas from 2005 to 2013. Nine benthic invertebrate samples were collected from each of six sampling sites using a Slack-Surber sampler. The Stream Condition Index (SCI) developed for Ozark streams was used to assess integrity of the invertebrate communities. This index is calculated using taxa richness, EPT (Ephemeroptera, Plecoptera, Trichoptera) Richness, Shannon’s Diversity Index, and Hilsenhoff Biotic Index (HBI). Sørensen’s similarity index was used to assess community similarity among sites, and scores were then analyzed using ascendant hierarchical cluster analysis. The benthic invertebrate fauna was diverse with 167 distinct taxa identified from all sites, with similarities ranging from 70% to 83%. Cluster analysis showed that sites were clustered in a longitudinal progression, with those sites closest to one another in linear distance generally being the most closely related. Overall, the invertebrate taxa of the Buffalo River are largely intolerant (mean tolerance value= 4.38). Taxa richness was typically greater than 20 among samples, and EPT richness values consistently were greater than 12 for all sites in most years. Shannon’s diversity index values generally ranged from 2.0 to 2.5 among sites and years. Metric values tended to decrease in a downstream direction to Site 4, and then increase to levels observed upstream. The exception was for HBI, which did not show this response and values for this metric generally were below 5. SCI scores among sampling sites were variable but not generally impaired and were fully biologically-supporting. Water quality (temperature, dissolved oxygen, specific conductance, pH, turbidity) met state standards in all instances. Habitat data were summarized, but found to be poorly correlated with invertebrate metrics (\u3c30% significant). Although the condition of invertebrate communities and water quality in the Buffalo River are largely sound and have high integrity, numerous ongoing and projected threats to these resources remain, and those threats largely originate outside of the park’s jurisdictional boundaries. Inherent variability of invertebrate community diversity and density across sites and years highlights the importance of using multi-metric assessment and multiyear monitoring to support management decisions

Testing a MultiTEP-based combination vaccine to reduce Aβ and tau pathology in Tau22/5xFAD bigenic mice.

BackgroundAlzheimer disease (AD) is characterized by the accumulation of beta-amyloid (Aβ) plaques and neurofibrillary tangles composed of hyperphosphorylated tau, which together lead to neurodegeneration and cognitive decline. Current therapeutic approaches have primarily aimed to reduce pathological aggregates of either Aβ or tau, yet phase 3 clinical trials of these approaches have thus far failed to delay disease progression in humans. Strong preclinical evidence indicates that these two abnormally aggregated proteins interact synergistically to drive downstream neurodegeneration. Therefore, combinatorial therapies that concurrently target both Aβ and tau might be needed for effective disease modification.MethodsA combinatorial vaccination approach was designed to concurrently target both Aβ and tau pathologies. Tau22/5xFAD (T5x) bigenic mice that develop both pathological Aβ and tau aggregates were injected intramuscularly with a mixture of two MultiTEP epitope vaccines: AV-1959R and AV-1980R, targeting Aβ and tau, respectively, and formulated in AdvaxCpG, a potent polysaccharide adjuvant. Antibody responses of vaccinated animals were measured by ELISA, and neuropathological changes were determined in brain homogenates of vaccinated and control mice using ELISA and Meso Scale Discovery (MSD) multiplex assays.ResultsT5x mice immunized with a mixture of Aβ- and tau-targeting vaccines generated high Aβ- and tau-specific antibody titers that recognized senile plaques and neurofibrillary tangles/neuropil threads in human AD brain sections. Production of these antibodies in turn led to significant reductions in the levels of soluble and insoluble total tau, and hyperphosphorylated tau as well as insoluble Aβ42, within the brains of bigenic T5x mice.ConclusionsAV-1959R and AV-1980R formulated with AdvaxCpG adjuvant are immunogenic and therapeutically potent vaccines that in combination can effectively reduce both of the hallmark pathologies of AD in bigenic mice. Taken together, these findings warrant further development of this vaccine technology for ultimate testing in human AD

Exercise alters the immune profile in Tg2576 Alzheimer mice toward a response coincident with improved cognitive performance and decreased amyloid

Background: Inflammation is associated with A beta pathology in Alzheimer's disease (AD) and transgenic AD models. Previously, it has been demonstrated that chronic stimulation of the immune response induces pro-inflammatory cytokines IL-1 beta and TNF-alpha which contribute to neurodegeneration. However, recent evidence has shown that inducing the adaptive immune response reduces A beta pathology and is neuroprotective. Low concentrations of IFN-gamma modulate the adaptive immune response by directing microglia to differentiate to antigen presenting cells. Our objective was to determine if exercise could induce a shift from the immune profile in aged (17-19 months) Tg2576 mice to a response that reduces A beta pathology. Methods: TG (n = 29) and WT (n = 27) mice were divided into sedentary (SED) and exercised (RUN) groups. RUN animals were provided an in-cage running wheel for 3 weeks. Tissue was harvested and hippocampus and cortex dissected out. Quantitative data was analyzed using 2 x 2 ANOVA and student's t-tests. Results: IL-1 beta and TNF-alpha were significantly greater in hippocampi from sedentary Tg2576 (TG(SED)) mice than in wildtype (WT(SED)) (p = 0.04, p = 0.006). Immune response proteins IFN-gamma and MIP-1 alpha are lower in TG(SED) mice than in WT(SED) (p = 0.03, p = 0.07). Following three weeks of voluntary wheel running, IL-1 beta and TNF-alpha decreased to levels indistinguishable from WT. Concurrently, IFN-gamma. and MIP-1 alpha increased in TG(RUN). Increased CD40 and MHCII, markers of antigen presentation, were observed in TG(RUN) animals compared to TG(SED), as well as CD11c staining in and around plaques and vasculature. Additional vascular reactivity observed in TG(RUN) is consistent with an alternative activation immune pathway, involving perivascular macrophages. Significant decreases in soluble A beta(40) (p = 0.01) and soluble fibrillar A beta (p = 0.01) were observed in the exercised transgenic animals. Conclusion: Exercise shifts the immune response from innate to an adaptive or alternative response. This shift in immune response coincides with a decrease in A beta in advanced pathological states

Conceptual design of an Orbital Debris Defense System

Man made orbital debris has become a serious problem. Currently NORAD tracks over 7000 objects in orbit and less than 10 percent of these are active payloads. Common estimates are that the amount of debris will increase at a rate of 10 percent per year. Impacts of space debris with operational payloads or vehicles is a serious risk to human safety and mission success. For example, the impact of a 0.2 mm diameter paint fleck with the Space Shuttle Challenger window created a 2 mm wide by 0.6 mm deep pit. The cost to replace the window was over $50,000. A conceptual design for a Orbital Debris Defense System (ODDS) is presented which considers a wide range of debris sizes, orbits and velocities. Two vehicles were designed to collect and remove space debris. The first would attach a re-entry package to de-orbit very large debris, e.g. inactive satellites and spent upper stages that tend to break up and form small debris. This vehicle was designed to contain several re-entry packages, and be refueled and resupplied with more re-entry packages as needed. The second vehicle was designed to rendezvous with and capture debris ranging from 10 cm to 2 m. Due to tracking limitations, no technically feasible method for collecting debris below 10 cm in size could be devised; it must be accomplished through international regulations which reduce the accumulation of space debris

Comparative Analysis of H&E and Prussian Blue Staining in a Mouse Model of Cerebral Microbleeds

Cerebral microbleeds are microscopic hemorrhages with deposits of blood products in the brain, which can be visualized with MRI and are implicated in cerebrovascular diseases. Hematoxylin and eosin (H&E) and Perl’s Prussian blue are popular staining methods used to localize cerebral microbleeds in pathology. This paper compared these two staining techniques in a mouse model of cerebral microbleeds. We used lipopolysaccharide (LPS) to induce cerebral microhemorrhages. C57B6 mice were treated with LPS (5 mg/kg, i.p.) or vehicle at baseline and at 24 hr. The brains were extracted 48 hr after the first injection and adjacent coronal sections were stained with H&E and Prussian blue to compare the effectiveness of the two staining techniques. H&E-positive stains were increased with LPS treatment and were correlated with grossly visible microhemorrhages on the brain surface; Prussian blue-positive stains, by comparison, showed no significant increase with LPS treatment and did not correlate with either H&E-positive stains or surface microhemorrhages. H&E staining is thus a more reliable indicator of acute bleeding events induced by LPS in this model within a short time span