A divergent approach to the preparation of cysteine and serine analogs

Malonate diesters containing a prochiral quaternary carbon have been successfully transformed into analogs of cysteine and serine. The chiral half‐esters are obtained in good yield, and enantioselectivity by selective hydrolysis using Pig‐Liver Esterase (PLE) as the catalyst. The resulting half‐ester intermediates are transformed into α^{2, 2}‐, β^{2, 2}‐, and β^{3, 3}‐analogs of cysteine and serine. The methodology described here allows for the preparation of both enantiomers of the amino‐acid analogs by selective manipulation of the ester and acid functionalities. This divergent strategy allows a common synthetic strategy to be used to prepare a variety of unnatural amino‐acid classes from a common intermediate which should prove useful in the design of novel peptide libraries. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.     

Critical roles for multiple formins during cardiac myofibril development and repair

Cardiac and skeletal muscle function depends on the proper formation of myofibrils, which are tandem arrays of highly organized actomyosin contractile units called sarcomeres. How the architecture of these colossal molecular assemblages is established during development and maintained over the lifetime of an animal is poorly understood. We investigate the potential roles in myofibril formation and repair of formin proteins, which are encoded by 15 different genes in mammals. Using quantitative real-time PCR analysis, we find that 13 formins are differentially expressed in mouse hearts during postnatal development. Seven formins immunolocalize to sarcomeres in diverse patterns, suggesting that they have a variety of functional roles. Using RNA interference silencing, we find that the formins mDia2, DAAM1, FMNL1, and FMNL2 are required nonredundantly for myofibrillogenesis. Knockdown phenotypes include global loss of myofibril organization and defective sarcomeric ultrastructure. Finally, our analysis reveals an unanticipated requirement specifically for FMNL1 and FMNL2 in the repair of damaged myofibrils. Together our data reveal an unexpectedly large number of formins, with diverse localization patterns and nonredundant roles, functioning in myofibril development and maintenance, and provide the first evidence of actin assembly factors being required to repair myofibrils.     

Acclimation or stress symptom? An integrated study of intraspecific variation in the clonal plant Aechmea bromeliifolia,a widespread CAM tank‐bromeliad

The clonal tank-bromeliad Aechmea bromeliifolia (Rudge) Baker was found in four different habitats in a restinga (vegetation mosaic on sandy coastal plains), of south-eastern Brazil. These habitats (swamp forest, dry forest, dry shrubland and herbaceous marsh) lie within a few hundred metres of each other along a gradient extending inland from the coast, and differ markedly in terms of light and flood regime. We compared ramet morphology, leaf anatomy and physiology, and population parameters to examine the amplitude of trait variation of this widespread species in the studied restinga. This integrated approach allowed us to examine which variation conferred acclimation and which was merely a stress symptom. A . bromeliifolia showed site-specific differences in abundance, distribution, rosette size and shape, leaf anatomical arrangement and photochemical efficiency (potential quantum yield; F _v/ F _m) during the day. Most of the variation found seemed to be related to the interaction of light and flooding. The lowest number and size of ramets at the exposed, dry shrubland was matched by a marked leaf photoinhibition, which suggested poor acclimation to local levels of light intensity and limited water supply. In the other habitats, the morpho-physiological parameters measured suggested adequate foraging behaviour and site acclimation.  © 2002 The Linnean Society of London, Botanical Journal of the Linnean Society, 2002, 140 , 391-401.