858 resultados para amyloidosis (AMY)


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Accumulating evidence suggests that deposition of neurotoxic a-synuclein aggregates in the brain during the development of neurodegenerative diseases like Parkinson's disease can be curbed by anti-aggregation strategies that either disrupt or eliminate toxic aggregates. Curcumin, a dietary polyphenol exhibits anti-amyloid activity but the use of this polyphenol is limited owing to its instability. As chemical modifications in curcumin confiscate this limitation, such efforts are intensively performed to discover molecules with similar but enhanced stability and superior properties. This study focuses on the inhibitory effect of two stable analogs of curcumin viz. curcumin pyrazole and curcumin isoxazole and their derivatives against a-synuclein aggregation, fibrillization and toxicity. Employing biochemical, biophysical and cell based assays we discovered that curcumin pyrazole (3) and its derivative N-(3-Nitrophenylpyrazole) curcumin (15) exhibit remarkable potency in not only arresting fibrillization and disrupting preformed fibrils but also preventing formation of A11 conformation in the protein that imparts toxic effects. Compounds 3 and 15 also decreased neurotoxicity associated with fast aggregating A53T mutant form of a-synuclein. These two analogues of curcumin described here may therefore be useful therapeutic inhibitors for the treatment of a-synuclein amyloidosis and toxicity in Parkinson's disease and other synucleinopathies.

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The propensity of protein molecules to self-assemble into highly ordered, fibrillar aggregates lies at the heart of understanding many disorders ranging from Alzheimer's disease to systemic lysozyme amyloidosis. In this paper we use highly accurate kinetic measurements of amyloid fibril growth in combination with spectroscopic tools to quantify the effect of modifications in solution conditions and in the amino acid sequence of human lysozyme on its propensity to form amyloid fibrils under acidic conditions. We elucidate and quantify the correlation between the rate of amyloid growth and the population of nonnative states, and we show that changes in amyloidogenicity are almost entirely due to alterations in the stability of the native state, while other regions of the global free-energy surface remain largely unmodified. These results provide insight into the complex dynamics of a macromolecule on a multidimensional energy landscape and point the way for a better understanding of amyloid diseases.

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The objective of the study described here was to determine the effect on variable-leaf watermilfoil of various combinations of triclopyr concentrations and exposure times using dosage rates that controlled Eurasian watermilfoil under laboratory and field conditions (Netherland and Getsinger 1992, Getsinger et al. 1997, Petty et al. 1998).

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Navassa is a small, undeveloped island in the Windward Passage between Jamaica and Haiti. It was designated a National Wildlife Refuge under the jurisdiction of the U.S. Fish and Wildlife Service in 1999, but the remote location makes management and enforcement challenging, and the area is regularly fished by artisanal fishermen from Haiti. In April 2006, the NOAA Center for Coastal Fisheries and Habitat Research conducted a research cruise to Navassa. The cruise produced the first high-resolution multibeam bathymetry for the area, which will facilitate habitat mapping and assist in refuge management. A major emphasis of the cruise was to study the impact of Haitian fishing gear on benthic habitats and fish communities; however, in 10 days on station only one small boat was observed with five fishermen and seven traps. Fifteen monitoring stations were established to characterize fish and benthic communities along the deep (28-34 m) shelf, as these areas have been largely unstudied by previous cruises. The fish communities included numerous squirrelfishes, triggerfishes, and parrotfishes. Snappers and grouper were also present but no small individuals were observed. Similarly, conch surveys indicated the population was in low abundance and was heavily skewed towards adults. Analysis of the benthic photoquadrats is currently underway. Other cruise activities included installation of a temperature logger network, sample collection for stable isotope analyses to examine trophic structure, and drop camera surveys to ground-truth habitat maps and overhead imagery. (PDF contains 58 pages)

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Over the past five years, a biogeographic characterization of Tortugas Ecological Reserve(TER) has been carried out to measure the post-implementation effects of TER as a refuge for exploited species. Our results demonstrate that there is substantial microalgal biomass at depths between 10 and 30 m in the soft sediments at the coral reef interface, and that this community may play an important role in the food web supporting reef organisms. In addition, preliminary stable isotope data, in conjunction with prior results from the west Florida shelf, suggest that the shallow water benthic habitats surrounding the coral reefs of TER will prove to be an important source of the primary production ultimately fueling fish production throughout TER. The majority of the fish analyzed so far have exhibited a C isotope signature consistent with a food web which relies heavily on benthic primary production. Fish counts indicate a marked increase in the abundance of large fish (>20 cm) within the Reserve relative to the Out and Park strata, across years. Faunal collections from open and protected soft bottom habitat near the northern boundary of Tortugas North strongly suggest that relaxation of trawling pressure has increased benthic biomass and diversity in this area of TER. These data, employing an integrated Before - After Control Impact (BACI) design at multiple spatial scales, will allow us to continue to document and quantify the post-implementation effects of TER. (PDF contains 58 pages)

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Executive Summary: The Estuary Restoration Act of 2000 (ERA), Title I of the Estuaries and Clean Waters Act of 2000, was created to promote the restoration of habitats along the coast of the United States (including the US protectorates and the Great Lakes). The NOAA National Centers for Coastal Ocean Science was charged with the development of a guidance manual for monitoring plans under this Act. This guidance manual, titled Science-Based Restoration Monitoring of Coastal Habitats, is written in two volumes. It provides technical assistance, outlines necessary steps, and provides useful tools for the development and implementation of sound scientific monitoring of coastal restoration efforts. In addition, this manual offers a means to detect early warnings that the restoration is on track or not, to gauge how well a restoration site is functioning, to coordinate projects and efforts for consistent and successful restoration, and to evaluate the ecological health of specific coastal habitats both before and after project completion (Galatowitsch et al. 1998). The following habitats have been selected for discussion in this manual: water column, rock bottom, coral reefs, oyster reefs, soft bottom, kelp and other macroalgae, rocky shoreline, soft shoreline, submerged aquatic vegetation, marshes, mangrove swamps, deepwater swamps, and riverine forests. The classification of habitats used in this document is generally based on that of Cowardin et al. (1979) in their Classification of Wetlands and Deepwater Habitats of the United States, as called for in the ERA Estuary Habitat Restoration Strategy. This manual is not intended to be a restoration monitoring “cookbook” that provides templates of monitoring plans for specific habitats. The interdependence of a large number of site-specific factors causes habitat types to vary in physical and biological structure within and between regions and geographic locations (Kusler and Kentula 1990). Monitoring approaches used should be tailored to these differences. However, even with the diversity of habitats that may need to be restored and the extreme geographic range across which these habitats occur, there are consistent principles and approaches that form a common basis for effective monitoring. Volume One, titled A Framework for Monitoring Plans under the Estuaries and Clean Waters Act of 2000, begins with definitions and background information. Topics such as restoration, restoration monitoring, estuaries, and the role of socioeconomics in restoration are discussed. In addition, the habitats selected for discussion in this manual are briefly described. (PDF contains 116 pages)

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Almost 120 days at sea aboard three NOAA research vessels and one fishing vessel over the past three years have supported biogeographic characterization of Tortugas Ecological Reserve (TER). This work initiated measurement of post-implementation effects of TER as a refuge for exploited species. In Tortugas South, seafloor transect surveys were conducted using divers, towed operated vehicles (TOV), remotely operated vehicles (ROV), various sonar platforms, and the Deepworker manned submersible. ARGOS drifter releases, satellite imagery, ichthyoplankton surveys, sea surface temperature, and diver census were combined to elucidate potential dispersal of fish spawning in this environment. Surveys are being compiled into a GIS to allow resource managers to gauge benthic resource status and distribution. Drifter studies have determined that within the ~ 30 days of larval life stage for fishes spawning at Tortugas South, larvae could reach as far downstream as Tampa Bay on the west Florida coast and Cape Canaveral on the east coast. Together with actual fish surveys and water mass delineation, this work demonstrates that the refuge status of this area endows it with tremendous downstream spillover and larval export potential for Florida reef habitats and promotes the maintenance of their fish communities. In Tortugas North, 30 randomly selected, permanent stations were established. Five stations were assigned to each of the following six areas: within Dry Tortugas National Park, falling north of the prevailing currents (Park North); within Dry Tortugas National Park, falling south of the prevailing currents (Park South); within the Ecological Reserve falling north of the prevailing currents (Reserve North); within the Ecological Reserve falling south of the prevailing currents (Reserve South); within areas immediately adjacent to these two strata, falling north of the prevailing currents (Out North); and within areas immediately adjacent to these two strata, falling south of the prevailing currents (Out South). Intensive characterization of these sites was conducted using multiple sonar techniques, TOV, ROV, diver-based digital video collection, diver-based fish census, towed fish capture, sediment particle-size, benthic chlorophyll analyses, and stable isotope analyses of primary producers, fish, and, shellfish. In order to complement and extend information from studies focused on the coral reef, we have targeted the ecotone between the reef and adjacent, non-reef habitats as these areas are well-known in ecology for indicating changes in trophic relationships at the ecosystem scale. Such trophic changes are hypothesized to occur as top-down control of the system grows with protection of piscivorous fishes. Preliminary isotope data, in conjunction with our prior results from the west Florida shelf, suggest that the shallow water benthic habitats surrounding the coral reefs of TER will prove to be the source of a significant amount of the primary production ultimately fueling fish production throughout TER and downstream throughout the range of larval fish dispersal. Therefore, the status and influence of the previously neglected, non-reef habitat within the refuge (comprising ~70% of TER) appears to be intimately tied to the health of the coral reef community proper. These data, collected in a biogeographic context, employing an integrated Before-After Control Impact design at multiple spatial scales, leave us poised to document and quantify the postimplementation effects of TER. Combined with the work at Tortugas South, this project represents a multi-disciplinary effort of sometimes disparate disciplines (fishery oceanography, benthic ecology, food web analysis, remote sensing/geography/landscape ecology, and resource management) and approaches (physical, biological, ecological). We expect the continuation of this effort to yield critical information for the management of TER and the evaluation of protected areas as a refuge for exploited species. (PDF contains 32 pages.)

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Each year, more than 500 motorized vessel groundings cause widespread damage to seagrasses in Florida Keys National Marine Sanctuary (FKNMS). Under Section 312 of the National Marine Sanctuaries Act (NMSA), any party responsible for the loss, injury, or destruction of any Sanctuary resource, including seagrass, is liable to the United States for response costs and resulting damages. As part of the damage assessment process, a cellular automata model is utilized to forecast seagrass recovery rates. Field validation of these forecasts was accomplished by comparing model-predicted percent recovery to that which was observed to be occurring naturally for 30 documented vessel grounding sites. Model recovery forecasts for both Thalassia testudinum and Syringodium filiforme exceeded natural recovery estimates for 93.1% and 89.5% of the sites, respectively. For Halodule wrightii, the number of over- and under-predictions by the model was similar. However, where under-estimation occurred, it was often severe, reflecting the well-known extraordinary growth potential of this opportunistic species. These preliminary findings indicate that the recovery model is consistently generous to Responsible Parties in that the model forecasts a much faster recovery than was observed to occur naturally, particularly for T. testudinum, the dominant seagrass species in the region and the species most often affected. Environmental setting (i.e., location, wave exposure) influences local seagrass landscape pattern and may also play a role in the recovery dynamics for a particular injury site. An examination of the relationship between selected environmental factors and injury recovery dynamics is currently underway. (PDF file contains 20 pages.)

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The population of eastern oyster, C. virginica, has declined over the last century on most areas of the east and gulf coasts. North Carolina’s restoration efforts depend on the construction of subtidal oyster reefs to be used as broodstock sanctuaries in Pamlico Sound, NC. Successful restoration of the oyster population requires several thriving reefs connected as a meta-population. C. virginica has a 2-3 week larval stage, during which it gradually settles through the water column. Larvae that can travel from one reef to another during that stage form the basis of a meta-population. (PDF contains 3 pages)

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Barrier islands are ecosystems that border coastal shorelines and form a protective barrier between continental shorelines and the wave action originating offshore. In addition to forming and maintaining an array of coastal and estuarine habitats of ecological and economic importance, barrier island coastlines also include some of the greatest concentrations of human populations and accompanying anthropogenic development in the world. These islands have an extremely dynamic nature whereby major changes in geomorphology and hydrology can occur over short time periods (i.e. days, hours) in response to extreme episodic storm events such as hurricanes and northeasters. The native vegetation and geological stability of these ecosystems are tightly coupled with one another and are vulnerable to storm-related erosion events, particularly when also disturbed by anthropogenic development. (PDF contains 4 pages)

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Due to the universal lack of donor tissue, there has been emerging interest in engineering materials to stimulate living cells to restore the features and functions of injured organs. We are particularly interested in developing materials for corneal use, where the necessity to maintain the tissue’s transparency presents an additional challenge. Every year, there are 1.5 – 2 million new cases of monocular blindness due to irregular healing of corneal injuries, dwarfing the approximately 150,000 corneal transplants performed. The large gap between the need and availability of cornea transplantation motivates us to develop a wound-healing scaffold that can prevent corneal blindness.

To develop such a scaffold, it is necessary to regulate the cells responsible for repairing the damaged cornea, namely myofibroblasts, which are responsible for the disordered and non-refractive index matched scar that leads to corneal blindness. Using in vitro assays, we identified that protein nanofibers of certain orientation can promote cell migration and modulate the myofibroblast phenotype. The nanofibers are also transparent, easy to handle and non-cytotoxic. To adhere the nanofibers to a wound bed, we examined the use of two different in situ forming hydrogels: an artificial extracellular matrix protein (aECM)-based gel and a photo-crosslinkable heparin-based gel. Both hydrogels can be formed within minutes, are transparent upon gelation and are easily tunable.

Using an in vivo mouse model for epithelial defects, we show that our corneal scaffolds (nanofibers together with hydrogel) are well-tolerated (no inflammatory response or turbidity) and support epithelium regrowth. We developed an ex vivo corneal tissue culture model where corneas that are wounded and treated with our scaffold can be cultured while retaining their ability to repair wounds for up to 21 days. Using this technique, we found that the aECM-based treatment induced a more favorable wound response than the heparin-based treatment, prompting us to further examine the efficacy of the aECM-based treatment in vivo using a rabbit model for stromal wounds. Results show that treated corneas have fewer myofibroblasts and immune cells than untreated ones, indicating that our corneal scaffold shows promise in promoting a calmer wound response and preventing corneal haze formation.

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Zostera marina is a member of a widely distributed genus of seagrasses, all commonly called eelgrass. The reported distribution of eelgrass along the east coast of the United States is from Maine to North Carolina. Eelgrass inhabits a variety of coastal habitats, due in part to its ability to tolerate a wide range of environmental parameters. Eelgrass meadows provide habitat, nurseries, and feeding grounds for a number of commercially and ecologically important species, including the bay scallop, Argopecten irradians. In the early 1930’s, a marine event, termed the “wasting disease,” was responsible for catastrophic declines in eelgrass beds of the coastal waters of North America and Europe, with the virtual elimination of Z. marina meadows in the Atlantic basin. Following eelgrass declines, disastrous losses were documented for bay scallop populations, evidence of the importance of eelgrass in supporting healthy scallop stocks. Today, increased turbidity arising from point and non-point source nutrient loading and sediment runoff are the primary threats to eelgrass along the Atlantic coast and, along with recruitment limitation, are likely reasons for the lack of recovery by eelgrass to pre-1930’s levels. Eelgrass is at a historical low for most of the western Atlantic with uncertain prospects for systematic improvement. However, of all the North American seagrasses, eelgrass has a growth rate and strategy that makes it especially conducive to restoration and several states maintain ongoing mapping, monitoring, and restoration programs to enhance and improve this critical resource. The lack of eelgrass recovery in some areas, coupled with increasing anthropogenic impacts to seagrasses over the last century and heavy fishing pressure on scallops which naturally have erratic annual quantities, all point to a fishery with profound challenges for survival.

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Pelagic pair trawling for tuna, Thunnus spp., and swordfish, Xiphias gladius, was introduced in U.S. Northwest Atlantic waters in 1991. During autumn (October-November) of 1992 under the authority oft he Federal Atlantic Swordfish Regulations, the National Marine Fisheries Service placed observers aboard pelagic pair trawl vessels to document the catch, bycatch, discard, and gear used in this new fishery. The fishery is conducted primarily at night along shelf-edge waters from June to November. In late 1991, revised regulations restricted swordfish to bycatch in this fishery resulting in pelagic pair trawl vessels targeting tuna throughout 1992. Analyses of 1992 data indicate that albacore, T. alalunga, was the predominant species caught, although yellowfin tuna, T. albaeares, and bigeye tuna, T. obesus, were the preferred target species. Bycatch also included swordfish, large sharks, pelagic rays and other pelagic fishes, other tunas, and marine mammals.

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Ecologic researchers are modeling the impact of vessel grounding to seagrass beds using GIS in the Florida Keys National Marine Sanctuary. The surface creation tools in the ArcGIS 3D Analyst extension help assess both the damage and recovery of these seagrass beds.