Seeding activity of human superoxide dismutase 1 aggregates in familial and sporadic amyotrophic lateral sclerosis postmortem neural tissues by real-time quaking-induced conversion.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disease with average lifespan of 2-5 years after diagnosis. The identification of novel prognostic and pharmacodynamic biomarkers are needed to facilitate therapeutic development. Metalloprotein human superoxide dismutase 1 (SOD1) is known to accumulate and form aggregates in patient neural tissue with familial ALS linked to mutations in their SOD1 gene. Aggregates of SOD1 have also been detected in other forms of ALS, including the sporadic form and the most common familial form linked to abnormal hexanucleotide repeat expansions in the Chromosome 9 open reading frame 72 (C9ORF72) gene. Here, we report the development of a real-time quaking-induced conversion (RT-QuIC) seed amplification assay using a recombinant human SOD1 substrate to measure SOD1 seeding activity in postmortem spinal cord and motor cortex tissue from persons with different ALS etiologies. Our SOD1 RT-QuIC assay detected SOD1 seeds in motor cortex and spinal cord dilutions down to 10-5. Importantly, we detected SOD1 seeding activity in specimens from both sporadic and familial ALS cases, with the latter having mutations in either their SOD1 or C9ORF72 genes. Analyses of RT-QuIC parameters indicated similar lag phases in spinal cords of sporadic and familial ALS patients, but higher ThT fluorescence maxima by SOD1 familial ALS specimens and sporadic ALS thoracic cord specimens. For a subset of sporadic ALS patients, motor cortex and spinal cords were examined, with seeding activity in both anatomical regions. Our results suggest SOD1 seeds are in ALS patient neural tissues not linked to SOD1 mutation, suggesting that SOD1 seeding activity may be a promising biomarker, particularly in sporadic ALS cases for whom genetic testing is uninformative.

Trends of Diverse POPs in Air and Water Across the Western Atlantic Ocean: Strong Gradients in the Ocean but Not in the Air.

Oceans have remained the least well-researched reservoirs of persistent organic pollutants (POPs) globally, due to their vast scale, difficulty of access, and challenging (trace) analysis. Little data on POPs exists along South America and the effect of different currents and river plumes on aqueous concentrations. Research cruise KN210-04 (R/V Knorr) offered a unique opportunity to determine POP gradients in air, water, and their air-water exchange along South America, covering both hemispheres. Compounds of interest included polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), polybrominated diphenylethers (PBDEs), and polycyclic aromatic hydrocarbons (PAHs). Remote tropical Atlantic Ocean atmospheric concentrations varied little between both hemispheres; for HCB, BDEs 47 and 99, they were ∼5 pg/m3, PCBs were ∼1 pg/m3, α-HCH was ∼0.2 pg/m3, and phenanthrene and other PAHs were in the low 100s pg/m3. Aqueous concentrations were dominated by PCB 52 (mean 4.1 pg/L), HCB (1.6 pg/L), and ß-HCH (1.9 pg/L), with other compounds <1 pg/L. Target PCBs tended to undergo net volatilization from the surface ocean, while gradients indicated net deposition for a-HCH. In contrast to atmospheric concentrations, which were basically unchanged between hemispheres, we detected strong gradients in aqueous POPs, with mostly nondetects in the tropical western South Atlantic. These results highlight the importance of currents and loss processes on ocean scales for the distribution of POPs.

Carbon stable isotopes as indicators of coastal eutrophication.

Coastal ecologists and managers have frequently used nitrogen stable isotopes (delta15N) to trace and monitor sources of anthropogenic nitrogen (N) in coastal ecosystems. However, the interpretation of delta15N data can often be challenging, as the isotope values fractionate substantially due to preferential retention and uptake by biota. There is a growing body of evidence that carbon isotopes may be a useful alternative indicator for eutrophication, as they may be sensitive to changes in primary production that result from anthropogenic nutrient inputs. We provide three examples of systems where delta13C values sensitively track phytoplankton production. First, earlier (1980s) mesocosm work established positive relationships between delta13C and dissolved inorganic nitrogen and dissolved silica concentrations. Consistent with these findings, a contemporary mesocosm experiment designed to replicate a temperate intertidal salt marsh environment also demonstrated that the system receiving supplementary nutrient additions had higher nutrient concentrations, higher chlorophyll concentrations, and higher delta13C values. This trend was particularly pronounced during the growing season, with differences less evident during senescence. And finally, these results were replicated in the open waters of Narragansett Bay, Rhode Island, USA, during a spring phytoplankton bloom. These three examples, taken together with the pre-existing body of literature, suggest that, at least in autotrophic, phytoplankton-dominated systems, delta13C values can be a useful and sensitive indicator of eutrophication.

Time Trends of Polybrominated Diphenyl Ethers (PBDEs) in Antarctic Biota.

Polybrominated diphenyl ethers (PBDEs) are "emerged" contaminants that were produced and used as flame retardants in numerous consumer and industrial applications for decades until banned. They remain ubiquitously present in the environment today. Here, a unique set of >200 biotic samples from the Antarctic was analyzed for PBDEs, including phytoplankton, krill, fish, and fur seal milk, spanning several sampling seasons over 14 years. PBDE-47 and -99 were the dominant congeners determined in all samples, constituting >60% of total PBDEs. A temporal trend was observed for ∑7PBDE concentrations in fur seal milk, where concentrations significantly increased (R2 = 0.57, p < 0.05) over time (2000-2014). Results for krill and phytoplankton also suggested increasing PBDE concentrations over time. Trends of PBDEs in fur seal milk of individual seals sampled 1 or more years apart showed no clear temporal trends. Overall, there was no indication of PBDEs decreasing in Antarctic biota yet, whereas numerous studies have reported decreasing trends in the northern hemisphere. Similar PBDE concentrations in perinatal versus nonperinatal milk implied the importance of local PBDE sources for bioaccumulation. These results indicate the need for continued assessment of contaminant trends, such as PBDEs, and their replacements, in Antarctica.

Preliminary Evidence for the Amplification of Global Warming in Shallow, Intertidal Estuarine Waters.

Over the past 50 years, mean annual water temperature in northeastern U.S. estuaries has increased by approximately 1.2°C, with most of the warming recorded in the winter and early spring. A recent survey and synthesis of data from four locations in Southern Rhode Island has led us to hypothesize that this warming may be amplified in the shallow (<1 m), nearshore portions of these estuaries. While intertidal areas are not typically selected as locations for long-term monitoring, we compiled data from published literature, theses, and reports that suggest that enhanced warming may be occurring, perhaps at rates three times higher than deeper estuarine waters. Warmer spring waters may be one of the factors influencing biota residing in intertidal regions both in general as well as at our specific sites. We observed greater abundance of fish, and size of Menidia sp., in recent (2010-2012) seine surveys compared to similar collections in 1962. While any linkages are speculative and data are preliminary, taken together they suggest that shallow intertidal portions of estuaries may be important places to look for the effects of climate change.