MpUL-multi: Software for Calculation of Amyloid Fibril Mass per Unit Length from TB-TEM Images.

Structure determination for amyloid fibrils presents many challenges due to the high variability exhibited by fibrils and heterogeneous morphologies present, even in single samples. Mass per unit length (MPL) estimates can be used to differentiate amyloid fibril morphologies and provide orthogonal evidence for helical symmetry parameters determined by other methods. In addition, MPL data can provide insight on the arrangement of subunits in a fibril, especially for more complex fibrils assembled with multiple parallel copies of the asymmetric unit or multiple twisted protofilaments. By detecting only scattered electrons, which serve as a relative measure of total scattering, and therefore protein mass, dark field imaging gives an approximation of the total mass of protein present in any given length of fibril. When compared with a standard of known MPL, such as Tobacco Mosaic Virus (TMV), MPL of the fibrils in question can be determined. The program suite MpUL-multi was written for rapid semi-automated processing of TB-TEM dark field data acquired using this method. A graphical user interface allows for simple designation of fibrils and standards. A second program averages intensities from multiple TMV molecules for accurate standard determination, makes multiple measurements along a given fibril, and calculates the MPL

Maternal Immunization with Pneumococcal Surface Protein A Protects against Pneumococcal Infections among Derived Offspring

Pathogen-specific antibody plays an important role in protection against pneumococcal carriage and infections. However, neonates and infants exhibit impaired innate and adaptive immune responses, which result in their high susceptibility to pneumococci. To protect neonates and infants against pneumococcal infection it is important to elicit specific protective immune responses at very young ages. In this study, we investigated the protective immunity against pneumococcal carriage, pneumonia, and sepsis induced by maternal immunization with pneumococcal surface protein A (PspA). Mother mice were intranasally immunized with recombinant PspA (rPspA) and cholera toxin B subunit (CTB) prior to being mated. Anti-PspA specific IgG, predominantly IgG1, was present at a high level in the serum and milk of immunized mothers and in the sera of their pups. The pneumococcal densities in washed nasal tissues and in lung homogenate were significantly reduced in pups delivered from and/or breast-fed by PspA-immunized mothers. Survival after fatal systemic infections with various types of pneumococci was significantly extended in the pups, which had received anti-PspA antibody via the placenta or through their milk. The current findings strongly suggest that maternal immunization with PspA is an attractive strategy against pneumococcal infections during early childhood. (191 words