Benthos

Currently, > 4,000 Arctic macro- and megabenthic species are known, representing the majority of Arctic marine faunal diversity. This estimate is expected to increase. • Benthic invertebrates are food to shes, marine mammals, seabirds and humans, and are commercially harvested. • Traditional Knowledge (TK) emphasizes the link between the benthic species and their predators, such as walrus, and their signi cance to culture. • Decadal changes in benthos biodiversity are observed in some well-studied regions, such as the Barents Sea and Chukchi Sea. • Drivers related to climate-change such as warming, ice decline and acidification are affecting the benthic community on a pan-Arctic scale, while drivers such as trawling, river/glacier discharge and invasive species have signficant impact on regional or local scales. • Increasing numbers of species are moving into, or shifting, their distributions in Arctic waters. These species will outcompete, prey on or offer less nutritious value as prey for Arctic species. • Current monitoring efforts have focused on macro- and megabenthic species, but have been confined to the Chukchi Sea and the Barents Sea. Efforts are increasing in waters of Greenland, Iceland, the Canadian Arctic, and in the Norwegian Sea. All other Arctic Marine Areas are lacking long-term benthic monitoring. • As a first step towards an international collaborative monitoring framework, we recommend to develop a time- and cost-effective, long-term and standardized monitoring of megabenthic communities in all Arctic regions with regular annual groundfish assessment surveys. Expanding monitoring on micro-, meio- and macrobenthic groups is encouraged

Immunohistochemical Evidence from APP-Transgenic Mice for Glutaminyl Cyclase as Drug Target to Diminish pE-Abeta Formation

Oligomeric assemblies of neurotoxic amyloid beta (Abeta) peptides generated by proteolytical processing of the amyloid precursor protein (APP) play a key role in the pathogenesis of Alzheimer's disease (AD). In recent years, a substantial heterogeneity of Abeta peptides with distinct biophysical and cell biological properties has been demonstrated. Among these, a particularly neurotoxic and disease-specific Abeta variant is N-terminally truncated and modified to pyroglutamate (pE-Abeta). Cell biological and animal experimental studies imply the catalysis of this modification by the enzyme glutaminyl cyclase (QC). However, direct histopathological evidence in transgenic animals from comparative brain region and cell type-specific expression of transgenic hAPP and QC, on the one hand, and on the formation of pE-Abeta aggregates, on the other, is lacking. Here, using single light microscopic, as well as triple immunofluorescent, labeling, we report the deposition of pE-Abeta only in the brain regions of APP-transgenic Tg2576 mice with detectable human APP and endogenous QC expression, such as the hippocampus, piriform cortex, and amygdala. Brain regions showing human APP expression without the concomitant presence of QC (the anterodorsal thalamic nucleus and perifornical nucleus) do not display pE-Abeta plaque formation. However, we also identified brain regions with substantial expression of human APP and QC in the absence of pE-Abeta deposition (the Edinger-Westphal nucleus and locus coeruleus). In these brain regions, the enzymes required to generate N-truncated Abeta peptides as substrates for QC might be lacking. Our observations provide additional evidence for an involvement of QC in AD pathogenesis via QC-catalyzed pE-Abeta formation

A glutaminyl cyclase-catalyzed α-synuclein modification identified in human synucleinopathies

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that is neuropathologically characterized by degeneration of dopaminergic neurons of the substantia nigra (SN) and formation of Lewy bodies and Lewy neurites composed of aggregated α-synuclein. Proteolysis of α-synuclein by matrix metalloproteinases was shown to facilitate its aggregation and to affect cell viability. One of the proteolysed fragments, Gln79-α-synuclein, possesses a glutamine residue at its N-terminus. We argue that glutaminyl cyclase (QC) may catalyze the pyroglutamate (pGlu)79-α-synuclein formation and, thereby, contribute to enhanced aggregation and compromised degradation of α-synuclein in human synucleinopathies. Here, the kinetic characteristics of Gln79-α-synuclein conversion into the pGlu-form by QC are shown using enzymatic assays and mass spectrometry. Thioflavin T assays and electron microscopy demonstrated a decreased potential of pGlu79-α-synuclein to form fibrils. However, size exclusion chromatography and cell viability assays revealed an increased propensity of pGlu79-α-synuclein to form oligomeric aggregates with high neurotoxicity. In brains of wild-type mice, QC and α-synuclein were co-expressed by dopaminergic SN neurons. Using a specific antibody against the pGlu-modified neo-epitope of α-synuclein, pGlu79-α-synuclein aggregates were detected in association with QC in brains of two transgenic mouse lines with human α-synuclein overexpression. In human brain samples of PD and dementia with Lewy body subjects, pGlu79-α-synuclein was shown to be present in SN neurons, in a number of Lewy bodies and in dystrophic neurites. Importantly, there was a spatial co-occurrence of pGlu79-α-synuclein with the enzyme QC in the human SN complex and a defined association of QC with neuropathological structures. We conclude that QC catalyzes the formation of oligomer-prone pGlu79-α-synuclein in human synucleinopathies, which may—in analogy to pGlu-Aβ peptides in Alzheimer’s disease—act as a seed for pathogenic protein aggregation

Growth and production of the brittle stars Ophiura sarsii and Ophiocten sericeum (Echinodermata: Ophiuroidea)

Dense brittle star assemblages dominate vast areas of the Arctic marine shelves, making them key components of Arctic ecosystem. This study is the first to determine the population dynamics of the dominant shelf brittle star species, Ophiura sarsii and Ophiocten sericeum, through age determination, individual production and total turnover rate (P:B). In the summer of 2013, O. sarsii were collected in the northeastern Chukchi Sea (depth 35–65 m), while O. sericeum were collected in the central Beaufort Sea (depth 37–200 m). Maximum age was higher for O. sarsii than for O. sericeum (27 and 20 years, respectively); however, both species live longer than temperate region congeners. Growth curves for both species had similar initial fast growth, with an inflection period followed by a second phase of fast growth. Predation avoidance in addition to changes in the allocation of energy may be the mechanisms responsible for the observed age dependent growth rates. Individual production was higher for O. sarsii than for O. sericeum by nearly an order of magnitude throughout the size spectra. The distinct distribution pattern of the two species in the Alaskan Arctic may be determined by environmental characteristics such as system productivity. Both species had equally low turnover rates (0.2 and 0.1, respectively), similar to Antarctic species, but lower than temperate species. Such characteristics suggest that the dense brittle star assemblages that characterize the Arctic shelf system could have a recovery time from disturbance on the order of decades

Biogeography of epibenthic assemblages in the central Beaufort Sea

Benthic communities change drastically in both biomass and community structure with increasing water depth on a global scale, attributed to a combination of food supply, environmental drivers, as well as physiological and competitive capacities. In the Arctic, benthic biogeographic patterns are additionally thought to be a result of the region’s glaciation history. Here, we investigate gross epibenthic biomass and assemblage structure turnover with water mass from coastal to bathyal depths from 136 beam trawl samples collected in the Beaufort Sea. We test whether Pacific Boreal Arctic species have their core distribution in shelf water masses while Atlantic Boreal Arctic species have wider depth ranges. Gross biomass estimates differed statistically among water masses, with high values mostly under the influences of the Polar Mixed Layer and Arctic Halocline (outer shelf and upper slope, respectively). Stations in the Coastal Zone and Canada Basin Deep Water had the lowest biomass. Epibenthic assemblages also differed significantly among water masses, with high taxon richness in shelf water masses that decreased considerably with depth. Biomass of benthic taxa with Pacific Boreal Arctic affinity was essentially limited to the shelf, while Atlantic Boreal Arctic taxa occurred across a broad depth range, though their biomass increased in deeper water masses for mollusks and echinoderms, but not for decapods/isopods. Our results confirm earlier evidence of a strong Atlantic-Arctic deep-water connectivity reaching into the Pacific Arctic region and suggest new arrivals of species from the boreal Pacific are likely to settle on Pacific Arctic shelves, but are unlikely to invade continental slope and basin waters in the foreseeable future

Proteolytic α-Synuclein Cleavage in Health and Disease

In Parkinson's disease, aggregates of α-synuclein within Lewy bodies and Lewy neurites represent neuropathological hallmarks. However, the cellular and molecular mechanisms triggering oligomeric and fibrillary α-synuclein aggregation are not fully understood. Recent evidence indicates that oxidative stress induced by metal ions and post-translational modifications such as phosphorylation, ubiquitination, nitration, glycation, and SUMOylation affect α-synuclein conformation along with its aggregation propensity and neurotoxic profiles. In addition, proteolytic cleavage of α-synuclein by specific proteases results in the formation of a broad spectrum of fragments with consecutively altered and not fully understood physiological and/or pathological properties. In the present review, we summarize the current knowledge on proteolytical α-synuclein cleavage by neurosin, calpain-1, cathepsin D, and matrix metalloproteinase-3 in health and disease. We also shed light on the contribution of the same enzymes to proteolytical processing of pathogenic proteins in Alzheimer's disease and report potential cross-disease mechanisms of pathogenic protein aggregation

Proteolytic α-Synuclein Cleavage in Health and Disease

In Parkinson’s disease, aggregates of α-synuclein within Lewy bodies and Lewy neurites represent neuropathological hallmarks. However, the cellular and molecular mechanisms triggering oligomeric and fibrillary α-synuclein aggregation are not fully understood. Recent evidence indicates that oxidative stress induced by metal ions and post-translational modifications such as phosphorylation, ubiquitination, nitration, glycation, and SUMOylation affect α-synuclein conformation along with its aggregation propensity and neurotoxic profiles. In addition, proteolytic cleavage of α-synuclein by specific proteases results in the formation of a broad spectrum of fragments with consecutively altered and not fully understood physiological and/or pathological properties. In the present review, we summarize the current knowledge on proteolytical α-synuclein cleavage by neurosin, calpain-1, cathepsin D, and matrix metalloproteinase-3 in health and disease. We also shed light on the contribution of the same enzymes to proteolytical processing of pathogenic proteins in Alzheimer’s disease and report potential cross-disease mechanisms of pathogenic protein aggregation

Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats

This find is registered at Portable Antiquities of the Netherlands with number PAN-0005330

Immunohistochemical Demonstration of the pGlu79 α-Synuclein Fragment in Alzheimer’s Disease and Its Tg2576 Mouse Model

The deposition of β-amyloid peptides and of α-synuclein proteins is a neuropathological hallmark in the brains of Alzheimer’s disease (AD) and Parkinson’s disease (PD) subjects, respectively. However, there is accumulative evidence that both proteins are not exclusive for their clinical entity but instead co-exist and interact with each other. Here, we investigated the presence of a newly identified, pyroglutamate79-modified α-synuclein variant (pGlu79-aSyn)—along with the enzyme matrix metalloproteinase-3 (MMP-3) and glutaminyl cyclase (QC) implicated in its formation—in AD and in the transgenic Tg2576 AD mouse model. In the human brain, pGlu79-aSyn was detected in cortical pyramidal neurons, with more distinct labeling in AD compared to control brain tissue. Using immunohistochemical double and triple labelings and confocal laser scanning microscopy, we demonstrate an association of pGlu79-aSyn, MMP-3 and QC with β-amyloid plaques. In addition, pGlu79-aSyn and QC were present in amyloid plaque-associated reactive astrocytes that were also immunoreactive for the chaperone heat shock protein 27 (HSP27). Our data are consistent for the transgenic mouse model and the human clinical condition. We conclude that pGlu79-aSyn can be generated extracellularly or within reactive astrocytes, accumulates in proximity to β-amyloid plaques and induces an astrocytic protein unfolding mechanism involving HSP27