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.     

Current Therapies and Technological Advances in Aqueous Aerosol Drug Delivery

Recent advances in aerosolization technology have led to renewed interest in pulmonary delivery of a variety of drugs. Pressurized metered dose inhalers (pMDIs) and dry powder inhalers (DPIs) have experienced success in recent years; however, many limitations are presented by formulation difficulties, inefficient delivery, and complex device designs. Simplification of the formulation process as well as adaptability of new devices has led many in the pharmaceutical industry to reconsider aerosolization in an aqueous carrier. In the acute care setting, breath-enhanced air-jet nebulizers are controlling and minimizing the amount of wasted medication, while producing a high percentage of respirable droplets. Vibrating mesh nebulizers offer advantages in higher respirable fractions (RFs) and slower velocity aerosols when compared with air-jet nebulizers. Vibrating mesh nebulizers incorporating formulation and patient adaptive components provide improvements to continuous nebulization technology by generating aerosol only when it is most likely to reach the deep lung. Novel innovations in generation of liquid aerosols are now being adapted for propellant-free pulmonary drug delivery to achieve unprecedented control over dose delivered and are leading the way for the adaptation of systemic drugs for delivery via the pulmonary route. Devices designed for the metered dose delivery of insulin, morphine, sildenafil, triptans, and various peptides are all currently under investigation for pulmonary delivery to treat nonrespiratory diseases. Although these devices are currently still in clinical testing (with the exception of the Respimat®), metered dose liquid inhalers (MDLIs) have already shown superior outcomes to current pulmonary and systemic delivery methods.     

Portraits portrayed

Abstract

The coffee-table is where Faces looks as if it belongs. A weighty package of 540 expensively produced pages, with 380 duo-tone reproductions, the book exudes a familiar slickness. But, as often with photographs themselves, the surface impression misleads. Ben Maddow's text is no mere accompaniment to the pictures. Winding among the landmarks of photographic history, the text vies in interest with the images; the text too is an artful performance. This alone gives this otherwise overproduced book high marks. Intelligent and interesting (let alone artful) writing about photographs, especially in the presence of images powerful enough to threaten speech with the charge of impertinence, is rare indeed. Novelist, poet, film maker, Maddow here undertakes ‘a narrative history’ of faces in photography, and while the history itself holds no surprises, the sheer facility and alertness of the writing keeps the text always slightly ahead of the pictures The writing dominates the book, all appearances to the contrary notwithstanding, and that is a welcome change in photography publications.     

A Modified Bandwidth K Factor Relationship Due to Parasitic Effects in Semiconductor Lasers

Abstract

A novel relationship between the maximum bandwidth and the bandwidth K factor has been obtained to describe the frequency response of laser diodes under the influence of parasitic effects. The relationship is applicable to the evaluation of the intrinsic bandwidth of quantum well lasers subject to carrier transport effects.