The accumulation of fibrillar amyloid-␤ protein (A␤) in cerebral blood vessels, a condition known as cerebral amyloid angiopathy (CAA), is a key pathological feature of Alzheimer's disease and certain related disorders and is intimately associated with cerebrovascular cell death both in vivo and in vitro. Moreover, severe CAA leads to loss of vessel wall integrity and cerebral hemorrhage. Although the basis for these latter pathological consequences in CAA remains unresolved alterations in local proteolytic mechanisms may be involved. Here we show that pathogenic forms of A␤ stimulate the expression of plasminogen activator activity in cultured human cerebrovascular smooth muscle (HCSM) cells, an in vitro model of CAA. RNase protection assays and plasminogen zymography showed that urokinase-type plasminogen activator (uPA) was responsible for this activity. There was preferential accumulation of uPA on the HCSM cell surface that was mediated through a concomitant increase in expression of the uPA receptor. In the presence of plasminogen there was robust degradation of A␤ that was added to the HCSM cells resulting in restoration of cell viability. This suggests that increased expression of uPA may initially serve as a protective mechanism leading to localized degradation and clearance of the pathogenic stimulus A␤. On the other hand, chronic expression of uPA and plasminogen activation led to a profound loss of HCSM cell attachment. This suggests that a similar prolonged effect in vivo in the cerebral vessel wall may contribute to loss of integrity and cerebral hemorrhage in CAA.A␤ 1 deposition in senile plaques in the neuropil and in the walls of cerebral blood vessels is a common pathological feature of patients with Alzheimer's disease and certain related disorders including Down's syndrome and hereditary cerebral hemorrhage with amyloidosis Dutch-type (1). A␤ is a 39 -43-amino acid peptide that has the propensity to self-assemble into insoluble, ␤-sheet-containing fibrils (1, 2). A␤ is proteolytically derived from a large type I integral membrane precursor protein, termed the amyloid ␤-protein precursor (A␤PP), encoded by a gene located on chromosome 21 (3-6). In this regard, full-length A␤PP is proteolytically processed by an enzyme, termed ␤-secretase, at the amino terminus of the A␤ domain. A membrane-associated aspartyl proteinase named BACE (for ␤ site A␤PP cleaving enzyme) has been identified as the ␤-secretase enzyme (7-10). Subsequent cleavage of the remaining amyloidogenic membrane-spanning A␤PP carboxyl-terminal fragment by an enzyme termed ␥-secretase liberates the 40-or 42-amino acid residue A␤ peptide. Although the precise identity of ␥-secretase remains unclear studies suggest that the presenilin proteins may function as this processing enzyme or as a required co-factor for ␥-secretase function (11-13). Alternatively, full-length A␤PP can be proteolytically processed by an enzyme termed ␣-secretase through the A␤ domain. This cleavage event generates a non-amyloidogenic membranespanning carboxyl...

Cerebrovascular deposition of the amyloid beta-protein (A beta) is a common pathologic event in patients with Alzheimer's disease (AD) and certain related disorders including hereditary cerebral hemorrhage with amyloidosis Dutch-type (HCHWA-D). A beta deposition occurs primarily in the medial layer of the cerebral vessel wall in an assembled fibrillar state. These deposits are associated with several pathological responses including degeneration of the smooth muscle cells in the cerebral vessel wall. Severe cases of cerebrovascular A beta deposition are also accompanied by loss of vessel wall integrity and hemorrhagic stroke. Although the reasons for this pathological consequence are unclear, altered proteolytic mechanisms within the cerebral vessel wall may be involved. Recent studies from our laboratory have shown that cell-surface assembly of A beta into fibrillar structures causes cellular degeneration via an apoptotic pathway and creates an altered proteolytic microenvironment on the cell surface of human cerebrovascular smooth muscle cells (HCSM cells). For example, HCSM cell-surface A beta fibrils serve as a site for tight binding of cell-secreted amyloid beta-precursor protein (A beta PP). Since A beta PP is a potent inhibitor of key proteinases of coagulation cascade, its enhanced localization on the A beta fibrils would provide an strong anticoagulant environment. In addition, HCSM cell-surface A beta fibrils are potent stimulators of tissue plasminogen activator (tPA) creating a profibrinolytic milieu. Our findings indicate that A beta fibril assembly on the HCSM cell surface causes cellular degeneration and results in both a strong anticoagulant and fibrinolytic environment. Together, these altered proteolytic events could create a setting that is conducive to loss of vessel wall integrity and hemorrhagic stroke.

Lesser (Chen caerulescens caerulescens, LSGO) and greater snow goose (Chen caerulescens atlantica, GSGO) populations have increased substantially in the past 50 years. The light goose conservation order established in 1998 (Canada) and 1999 (U.S.) aimed to increase snow goose harvest and stabilize populations because breeding ground abundance was thought to negatively impact arctic ecosystems. In the Atlantic flyway, where LSGO and GSGO are both available for harvest, techniques to differentiate sub‐species in the field using morphology may be helpful for harvest management because mid‐continent LSGO are ~16 times more abundant than GSGO (n < 1,000,000). We investigated percentages and spatial distribution of LSGO and GSGO in the spring harvest in NY as this information could be useful for snow goose population and harvest management decisions. We developed a discriminant function analysis (DFA) using heads from snow geese harvested during spring 2016 to 2018 and were able to differentiate between LSGO and GSGO with 95.5% accuracy. Based on the DFA results, we estimated that spring harvest in New York state was 80% GSGO and 20% LSGO. Using band recoveries from autumn and spring harvests, we also identified that GSGO harvest occurred farther west during spring than autumn and in the 2010s than prior two decades. Our results indicate that GSGO comprise most snow goose harvest in New York state and provide evidence for a shift in spring migration patterns of GSGO since the 1990s.

Conserving critical wildlife habitat at a regional scale can be challenging, especially when the region hosts a range of land uses, jurisdictions, and competing interests. Abundant opportunities exist for cooperation when vested conservation entities find common ground to use their unique strengths in a cooperative effort to protect and restore wetlands for wildlife and people. We present the Montezuma Wetlands Complex (MWC) Land Protection Partnership as a case study of regional conservation collaboration aimed at identifying areas in greatest need of wetland protection and restoration to support wetland wildlife and provide wildlife-based recreation. The MWC is among the most important wetland complexes in the Atlantic flyway of eastern North America for migratory birds because it provides critical migratory stopover habitat for millions of birds and regionally unique habitats for breeding birds and resident wildlife, including numerous endangered and threatened (E&T) species. This case study demonstrates how state, federal, and nonprofit entities with differing goals and objectives can partner to protect and restore critical wetland habitat for wildlife. Partners optimized efforts by developing an online survey that included physical, land cover, biological, and people/use attributes which were ranked by each partner to determine common priorities and applied these into a spatial mapping, decision-support tool. Within attribute categories, land protection (physical), emergent marshes (land use), E&T (biological), and recreational areas (people/use) were highest ranked by partners. The decision-support tool provided an objective method of ranking parcels of land for public outreach efforts by the partners to protect and restore wetland wildlife habitat.