Frog foams and natural protein surfactants

Foams and surfactants are relatively rare in biology because of their potential to harm cell membranes and other delicate tissues. However, in recent work we have identified and characterized a number of natural surfactant proteins found in the foam nests of tropical frogs and other unusual sources. These proteins, and their associated foams, are relatively stable and bio-compatible, but with intriguing molecular structures that reveal a new class of surfactant activity. Here we review the structures and functional mechanisms of some of these proteins as revealed by experiments involving a range of biophysical and biochemical techniques, with additional mechanistic support coming from more recent site-directed mutagenesis studies

Aqueous solubilization of C60 fullerene by natural protein surfactants, latherin and ranaspumin-2

C60 fullerene is not soluble in water and dispersion usually requires organic solvents, sonication or vigorous mechanical mixing. However, we show here that mixing of pristine C60 in water with natural surfactant proteins latherin and ranaspumin-2 (Rsn-2) at low concentrations yields stable aqueous dispersions with spectroscopic properties similar to those previously obtained by more vigorous methods. Particle sizes are significantly smaller than those achieved by mechanical dispersion alone, and concentrations are compatible with clusters approximating 1:1 protein:C60 stoichiometry. These proteins can also be adsorbed onto more intractable carbon nanotubes. This promises to be a convenient way to interface a range of hydrophobic nanoparticles and related materials with biological macromolecules, with potential to exploit the versatility of recombinant protein engineering in the development of nano-bio interface devices. It also has potential consequences for toxicological aspects of these and similar nanoparticles

Mean and Variance Modeling of Under-Dispersed and Over-Dispersed Grouped Binary Data

This article describes the R package BinaryEPPM and its use in determining maximum likelihood estimates of the parameters of extended Poisson process models for grouped binary data. These provide a Poisson process family of flexible models that can handle unlimited under-dispersion but limited over-dispersion in such data, with the binomial distribution being a special case. Within BinaryEPPM, models with the mean and variance related to covariates are constructed to match a generalized linear model formulation. Combining such under-dispersed models with standard over-dispersed models such as the beta binomial distribution provides a very general form of residual distribution for modeling grouped binary data. Use of the package is illustrated by application to several data-sets

Resonance assignments for latherin, a natural surfactant protein from horse sweat

Latherin is an intrinsically surfactant protein of ~23 kDa found in the sweat and saliva of horses. Its function is probably to enhance the translocation of sweat water from the skin to the surface of the pelt for evaporative cooling. Its role in saliva may be to enhance the wetting, softening and maceration of the dry, fibrous food for which equines are adapted. Latherin is unusual in its relatively high content of aliphatic amino acids (~25 % leucines) that might contribute to its surfactant properties. Latherin is related to the palate, lung, and nasal epithelium carcinoma-associated proteins (PLUNCs) of mammals, at least one of which is now known to exhibit similar surfactant activity to latherin. No structures of any PLUNC protein are currently available. 15N,13C-labelled recombinant latherin was produced in Escherichia coli, and essentially all of the resonances were assigned despite the signal overlap due to the preponderance of leucines. The most notable exceptions include a number of residues located in an apparently dynamic loop region between residues 145 and 154. The assignments have been deposited with BMRB accession number 19067

The structure of latherin, a surfactant allergen protein from horse sweat and saliva

Latherin is a highly surface-active allergen protein found in the sweat and saliva of horses and other equids. Its surfactant activity is intrinsic to the protein in its native form, and is manifest without associated lipids or glycosylation. Latherin probably functions as a wetting agent in evaporative cooling in horses, but it may also assist in mastication of fibrous food as well as inhibition of microbial biofilms. It is a member of the PLUNC family of proteins abundant in the oral cavity and saliva of mammals, one of which has also been shown to be a surfactant and capable of disrupting microbial biofilms. How these proteins work as surfactants while remaining soluble and cell membrane-compatible is not known. Nor have their structures previously been reported. We have used protein nuclear magnetic resonance spectroscopy to determine the conformation and dynamics of latherin in aqueous solution. The protein is a monomer in solution with a slightly curved cylindrical structure exhibiting a ‘super-roll’ motif comprising a four-stranded anti-parallel β-sheet and two opposing α-helices which twist along the long axis of the cylinder. One end of the molecule has prominent, flexible loops that contain a number of apolar amino acid side chains. This, together with previous biophysical observations, leads us to a plausible mechanism for surfactant activity in which the molecule is first localized to the non-polar interface via these loops, and then unfolds and flattens to expose its hydrophobic interior to the air or non-polar surface. Intrinsically surface-active proteins are relatively rare in nature, and this is the first structure of such a protein from mammals to be reported. Both its conformation and proposed method of action are different from other, non-mammalian surfactant proteins investigated so far

Extravehicular activities limitations study. Volume 1: Physiological limitations to extravehicular activity in space

This report contains the results of a comprehensive literature search on physiological aspects of EVA. Specifically, the topics covered are: (1) Oxygen levels; (2) Optimum EVA work; (3) Food and Water; (4) Carbon dioxide levels; (5) Repetitive decompressions; (6) Thermal, and (7) Urine collection. The literature was assessed on each of these topics, followed by statements on conclusions and recommended future research needs

Biologic Agents—A Panacea for Inflammatory Arthritis or Not?

Aim. To describe the retention rates for biological therapies in patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ankylosing spondylitis (AS) in a clinical setting. Methods. All patients managed in a dedicated biological therapy clinic in a teaching hospital in Australia were assessed for continuation on biological treatments and reasons for switching to an alternative biological agent or cessation of treatment. Results. There was a lower retention rate for RA patients on biological therapies compared to PsA and AS patients and the retention rate for RA patients was lower than that reported in RCTs. Conclusions. The retention rate on biological therapies for RA patients was lower in the clinic setting than what is reported in RCTs. The reasons for the lower retention rate in the clinical setting are discussed but no clear determinants for nonresponse to biological agents were identifiable. These agents have very limited steroid sparing effects