Health effects of acid aerosols formed by atmospheric mixtures.

Under ambient conditions, sulfur and nitrogen oxides can react with photochemical products and airborne particles to form acidic vapors and aerosols. Inhalation toxicological studies were conducted, exposing laboratory animals, at rest and during exercise, to multicomponent atmospheric mixtures under conditions favorable to the formation of acidic reaction products. Effects of acid and ozone mixtures on early and late clearance of insoluble radioactive particles in the lungs of rats appeared to be dominated by the oxidant component (i.e., the mixture did cause effects that were significantly different from those of ozone alone). Histopathological evaluations showed that sulfuric acid particles alone did not cause inflammatory responses in centriacinar units of rat lung parenchyma (expressed in terms of percent lesion area) but did cause significant damage (cell killing followed by a wave of cell replication) in nasal respiratory epithelium, as measured by uptake of tritiated thymidine in the DNA of replicating cells. Mixtures of ozone and nitrogen dioxide, which form nitric acid, caused significant inflammatory responses in lung parenchyma (in excess of effects seen in rats exposed to ozone alone), but did not damage nasal epithelium. Mixtures containing acidic sulfate particles, ozone, and nitrogen dioxide damaged both lung parenchyma and nasal epithelia. In rats exposed at rest, the response of the lung appeared to be dominated by the oxidant gas-phase components, while responses in the nose were dominated by the acidic particles. In rats exposed at exercise, however, mixtures of ozone and sulfuric acid particles significantly (2.5-fold) elevated the degree of lung lesion formation over that seen in rats exposed to ozone alone under an identical exercise protocol

Structure-Based Prediction of Asparagine and Aspartate Degradation Sites in Antibody Variable Regions

Monoclonal antibodies (mAbs) and proteins containing antibody domains are the most prevalent class of biotherapeutics in diverse indication areas. Today, established techniques such as immunization or phage display allow for an efficient generation of new mAbs. Besides functional properties, the stability of future therapeutic mAbs is a key selection criterion which is essential for the development of a drug candidate into a marketed product. Therapeutic proteins may degrade via asparagine (Asn) deamidation and aspartate (Asp) isomerization, but the factors responsible for such degradation remain poorly understood. We studied the structural properties of a large, uniform dataset of Asn and Asp residues in the variable domains of antibodies. Their structural parameters were correlated with the degradation propensities measured by mass spectrometry. We show that degradation hotspots can be characterized by their conformational flexibility, the size of the C-terminally flanking amino acid residue, and secondary structural parameters. From these results we derive an accurate in silico prediction method for the degradation propensity of both Asn and Asp residues in the complementarity-determining regions (CDRs) of mAbs

Optimal diet selection by white-tailed deer: Balancing reproduction with starvation risk

Energy intake rates of wintering deer vary over time because of variation in the abundance and quality of their natural foods. Accordingly, there is a chance that energy requirements will not be satisfied in a feeding period. This is especially critical because deer are reproductive during winter; hence selecting diets to minimize the risk of starvation may not maximize fitnss. I examined diet selection by white-tailed deer ( Odocoileus virginianus ) using a risk-sensitive foraging model which predicts the optimal diet when foragers face starvation risks during a reproductive period. Optimal diets were estimated by quantifying the mean and variance in energy intake rate deer could obtain when selecting different potential diets and substituting these values into functions for estimating offspring production and starvation risk. I conducted a field experiment to ask whether deer selected deciduous and coniferous twigs according to model predictions. Starvation risk was manipulated by providing deer supplemental feed. When faced with starvation risks, deer appeared to select diets that balanced offspring production with starvation risk. When starvation risk was climinated, deer tended to select diets that simply maximized their mean energy intake rates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42743/1/10682_2005_Article_BF02270707.pd