University of Notre Dame

About: University of Notre Dame is a education organization based out in Notre Dame, Indiana, United States. It is known for research contribution in the topics: Population & Context (language use). The organization has 22238 authors who have published 55201 publications receiving 2032925 citations. The organization is also known as: University of Notre Dame du Lac & University of Notre Dame, South Bend.

A Highly Specific Inhibitor of Matrix Metalloproteinase-9 Rescues Laminin from Proteolysis and Neurons from Apoptosis in Transient Focal Cerebral Ischemia

Abstract: Neuronal cell death occurs during many neurodegenerative disorders and stroke. The aberrant, excessive activity of matrix metalloproteinases (MMPs), especially MMP-9, contributes directly to neuron apoptosis and brain damage (Rosenberg et al., 1996; Asahi et al., 2001; Gu et al., 2002; Horstmann et al., 2003). We determined that MMP-9 degrades the extracellular matrix protein laminin and that this degradation induces neuronal apoptosis in a transient focal cerebral ischemia model in mice. We also determined that the highly specific thiirane gelatinase inhibitor SB-3CT blocks MMP-9 activity, including MMP-9-mediated laminin cleavage, thus rescuing neurons from apoptosis. We conclude that MMP-9 is a highly promising drug target and that SB-3CT derivatives have significant therapeutic potential in stroke patients.

Genomic insights into the Ixodes scapularis tick vector of Lyme disease

Abstract: Ticks transmit more pathogens to humans and animals than any other arthropod. We describe the 2.1 Gbp nuclear genome of the tick, Ixodes scapularis (Say), which vectors pathogens that cause Lyme disease, human granulocytic anaplasmosis, babesiosis and other diseases. The large genome reflects accumulation of repetitive DNA, new lineages of retro-transposons, and gene architecture patterns resembling ancient metazoans rather than pancrustaceans. Annotation of scaffolds representing ∼57% of the genome, reveals 20,486 protein-coding genes and expansions of gene families associated with tick-host interactions. We report insights from genome analyses into parasitic processes unique to ticks, including host 'questing', prolonged feeding, cuticle synthesis, blood meal concentration, novel methods of haemoglobin digestion, haem detoxification, vitellogenesis and prolonged off-host survival. We identify proteins associated with the agent of human granulocytic anaplasmosis, an emerging disease, and the encephalitis-causing Langat virus, and a population structure correlated to life-history traits and transmission of the Lyme disease agent.

Structure and function of the plasminogen/plasmin system.

Abstract: Activation of the fibrinolytic system is dependent on the conversion of the plasma zymogen, plasminogen (Pg), to the serine protease plasmin (Pm) by the physiological activators urokinase-type Pg activator (uPA) or tissue-type plasminogen activator (tPA). The primary in vivo function of Pm is to regulate vascular patency by degrading fibrin-containing thrombi. However, the identification of Pg/Pm receptors and the ability of Pm to degrade other matrix proteins have implicated Pm in other functions involving degradation of protein barriers, thereby mediating cell migration, an important event in a number of normal e.g., embryogenesis, wound healing, angiogenesis, and pathological, e.g., tumor growth and dissemination, processes. Prior to the development of Pg-deficient mice, much of the evidence for its role in other biological events was based on indirect studies. With the development and characterization of these mice, and ability to apply challenges utilizing a number of animal models that mimic the human condition, a clearer delineation of Pg/Pm function has evolved and has contributed to an understanding of mechanisms associated with a number of pathophysiological events.

Ecological stoichiometry in freshwater benthic systems: recent progress and perspectives

Abstract: SUMMARY 1. Ecological stoichiometry deals with the mass balance of multiple key elements [e.g. carbon (C), nitrogen (N), phosphorus (P)] in ecological systems. This conceptual framework, largely developed in the pelagic zone of lakes, has been successfully applied to topics ranging from population dynamics to biogeochemical cycling. More recently, an explicit stoichiometric approach has also been used in many other environments, including freshwater benthic ecosystems. 2. Description of elemental patterns among benthic resources and consumers provides a useful starting point for understanding causes of variation and stoichiometric imbalance in feeding interactions. Although there is considerable overlap among categories, terrestrially-derived resources, such as wood, leaf litter and green leaves have substantially higher C : nutrient ratios than other resources of both terrestrial and aquatic origin, such as periphyton and fine particulate organic matter. The elemental composition of these resources for benthic consumers is modulated by a range of factors and processes, including nutrient availability and ratios, particle size and microbial colonisation. 3. Among consumers in benthic systems, bacteria are the most nutrient-rich, followed (in descending order) by fishes, invertebrate predators, invertebrate primary consumers, and fungi. Differences in consumer C : nutrient ratios appear to be related to broad-scale phylogenetic differences which determine body size, growth rate and resource allocation to structural body constituents (e.g. P-rich bone). 4. Benthic consumers can influence the stoichiometry of dissolved nutrients and basal resources in multiple ways. Direct consumption alters the stoichiometry of food resources by increasing nutrient availability (e.g. reduced boundary layer thickness on substrata) or through removal of nutrient-rich patches (e.g. selective feeding on fungal patches within leaf litter). In addition, consumers alter the stoichiometry of resources and dissolved nutrient pools through the return of egested or excreted nutrients. In some cases, consumer excretion supplies a large proportion of the nutrients required by algae and heterotrophic microbes and alters elemental ratios of dissolved nutrient pools. 5. Organic matter decomposition in benthic systems is accompanied by significant changes in the elemental composition of organic matter. Microbial colonisation of leaf litter influences C : nutrient ratios, and patterns of microbial succession (e.g. fungi followed by bacteria) may be under some degree of stoichiometric control. Large elemental imbalances