The early pathogenesis of bovine mastitis due to Escherichia coli

The pathogenesis of coliform mastitis was studied after infusing each of ten lactating quarters of three dairy cows with a large dose (ca. 1 x 10(9) colony-forming units) of virulent Escherichia coli strain B117. This approach was adopted first to maximize the chance of observing microscopic lesions in the tissues of a gland and secondly to overwhelm the differences that might be shown between animals in their response to the infection. The infected glands were examined at intervals of up to 4 h after infection by scanning and transmission electron microscopy and by light microscopy. The earliest lesions were seen after 1 h and consisted of necrosis and sloughing of the epithelial cells of the teat and lactiferous sinuses. After 2 h this was more severe, and was followed by an intense neutrophil response. Neutrophils migrated through the epithelial lesions and at first remained attached to the epithelial surface, forming large mounds. This resulted in gross underestimation of the number of cells in the lumen of the gland when neutrophils in the secretion were counted. At no stage was there evidence of attachment of organisms to the epithelial cells. Tissue damage did not extent beyond the basement membrane, which helps to explain the rapid clinical resolution seen in most field cases of the disease. There was considerable variation in the degree of response shown by the three cows, and also within the infected glands, where the damage was most severe in the lactiferous and teat sinuses. It seems unlikely that all aspects of the disease could be attributed to endotoxin.     

From monomer to fibril: Abeta-amyloid binding to Aducanumab antibody studied by molecular dynamics simulation

Alzheimer's disease is one of the most common causes of dementia. It is believed that the aggregation of short Aβ -peptides to form oligomeric and protofibrillar amyloid assemblies plays a central role for disease-relevant neurotoxicity. In recent years, passive immunotherapy has been introduced as a potential treatment strategy with anti-amyloid antibodies binding to Aβ -amyloids and inducing their subsequent degradation by the immune system. Although so far mostly unsuccessful in clinical studies, the high-dosed application of the monoclonal antibody Aducanumab has shown therapeutic potential that might be attributed to its much greater affinity to Aβ -aggregates vs monomeric Aβ -peptides. In order to better understand how Aducanumab interacts with aggregated Aβ -forms compared to monomers, we have generated structural model complexes based on the known structure of Aducanumab in complex with an Aβ_{2 − 7} -eptitope. Structural models of Aducanumab bound to full-sequence Aβ_{1 − 40} -monomers, oligomers, protofilaments and mature fibrils were generated and investigated using extensive molecular dynamics simulations to characterize the flexibility and possible additional interactions. Indeed, an aggregate-specific N-terminal binding motif was found in case of Aducanumab binding to oligomers, protofilaments and fibrils that is located next to but not overlapping with the epitope binding site found in the crystal structure with Aβ_{2 − 7} . Analysis of binding energetics indicates that this motif binds weaker than the epitope but likely contributes to Aducanumab's preference for aggregated Aβ -species. The predicted aggregate-specific binding motif could potentially serve as a basis to reengineer Aducanumab for further enhanced preference to bind Aβ -aggregates vs monomers.     

Changing Views of the Interconnections Between the Oceans and Human Health in Europe

Early steps in the emergence of the discipline of “Oceans and Human Health” are charted in the USA and discussed in relation to past and present marine environment and human health research activities in Europe. Differences in terminology are considered, as well as differences in circumstances related to the various seas of Europe and the intensity of human coastal activity and impact. Opportunities to progress interdisciplinary research are described, and the value of horizon scanning for the early identification of emerging issues is highlighted. The challenges facing researchers and policymakers addressing oceans and human health issues are outlined and some suggestions offered regarding how further progress in research and training into both the risks and benefits of Oceans and Human Health might be made on both sides of the Atlantic.     

Bacterial feeding by the rotifer Brachionus calyciflorus: Clearance and ingestion rates,behavior and population dynamics

Summary The rotifer Brachionus calyciflorus is capable of collecting and ingesting cells or short chains of a laboratory-grown bacterium Aerobacter aerogenes. Clearance rate, the volume of water effectively processed animal ^-1h^-1, does not vary systematically with bacterial density between 0.01 and 100 g dry weight ml^-1. Consequently, ingestion rates are strongly density-dependent, reaching maximal values at the highest food densities tested. Bacterial feeding rates are consistently lower than those determined with larger food types, except in very dense cell suspensions. A. aerogenes in high concentration (100 g ml^-1) induces Brachionus to orient their pseudotrochal cirri to form screens over the buccal funnel; this behavior is at least four times less frequently observed at low (10 g ml^-1) food density. Despite its occurrence, pseudotrochal screening appears ineffective in regulating bacterial ingestion rate. B. calyciflorus can be cultured xenically for greater than 40 generations fed A. aerogenes alone, with no diminution in net reproductive rate or intrinsic rate of natural increase, and no lengthening in cohort generation time.