Influence of Divalent Metal Ions on the Precipitation of the Plasma Protein Fibrinogen.

Fibrinogen nanofibers are very attractive biomaterials to mimic the native blood clot architecture. Previously, we reported the self-assembly of fibrinogen nanofibers in the presence of monovalent salts and have now studied how divalent salts influence fibrinogen precipitation. Although the secondary fibrinogen structure was significantly altered with divalent metal ions, morphological analysis revealed exclusively smooth fibrinogen precipitates. In situ monitoring of the surface roughness facilitated predicting the tendency of various salts to form fibrinogen fibers or smooth films. Analysis of the chemical composition revealed that divalent salts were removed from smooth fibrinogen films upon rinsing while monovalent Na+ species were still present in fibrinogen fibers. Therefore, we assume that the decisive factor controlling the morphology of fibrinogen precipitates is direct ion-protein contact, which requires disruption of the ion-surrounding hydration shells. We conclude that in fibrinogen aggregates, this mechanism is effective only for monovalent ions, whereas divalent ions are limited to indirect fibrinogen adsorption.

Resolving the life cycle alters expected impacts of climate change.

Recent models predict contrasting impacts of climate change on tropical and temperate species, but these models ignore how environmental stress and organismal tolerance change during the life cycle. For example, geographical ranges and extinction risks have been inferred from thermal constraints on activity during the adult stage. Yet, most animals pass through a sessile embryonic stage before reaching adulthood, making them more susceptible to warming climates than current models would suggest. By projecting microclimates at high spatio-temporal resolution and measuring thermal tolerances of embryos, we developed a life cycle model of population dynamics for North American lizards. Our analyses show that previous models dramatically underestimate the demographic impacts of climate change. A predicted loss of fitness in 2% of the USA by 2100 became 35% when considering embryonic performance in response to hourly fluctuations in soil temperature. Most lethal events would have been overlooked if we had ignored thermal stress during embryonic development or had averaged temperatures over time. Therefore, accurate forecasts require detailed knowledge of environmental conditions and thermal tolerances throughout the life cycle.

Monitoring the quality of medicines: results from Africa, Asia, and South America.

Monitoring the quality of medicines plays a crucial role in an integrated medicines quality assurance system. In a publicly available medicines quality database (MQDB), the U.S. Pharmacopeial Convention (USP) reports results of data collected from medicines quality monitoring (MQM) activities spanning the period of 2003-2013 in 17 countries of Africa, Asia, and South America. The MQDB contains information on 15,063 samples collected and tested using Minilab® screening methods and/or pharmacopeial methods. Approximately 71% of the samples reported came from Asia, 23% from Africa, and 6% from South America. The samples collected and tested include mainly antibiotic, antimalarial, and antituberculosis medicines. A total of 848 samples, representing 5.6% of total samples, failed the quality test. The failure proportion per region was 11.5%, 10.4%, and 2.9% for South America, Africa, and Asia, respectively. Eighty-one counterfeit medicines were reported, 86.4% of which were found in Asia and 13.6% in Africa. Additional analysis of the data shows the distribution of poor-quality medicines per region and by therapeutic indication as well as possible trends of counterfeit medicines.