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Odgren P.R.,University of Massachusetts Medical School | Pratt C.H.,Institute for Molecular Biophysics | Pratt C.H.,The Jackson Laboratory | Mackay C.A.,University of Massachusetts Medical School | And 11 more authors.

Background: Investigations of naturally-occurring mutations in animal models provide important insights and valuable disease models. Lamins A and C, along with lamin B, are type V intermediate filament proteins which constitute the proteinaceous boundary of the nucleus. LMNA mutations in humans cause a wide range of phenotypes, collectively termed laminopathies. To identify the mutation and investigate the phenotype of a spontaneous, semi-dominant mutation that we have named Disheveled hair and ear (Dhe), which causes a sparse coat and small external ears in heterozygotes and lethality in homozygotes by postnatal day 10. Findings: Genetic mapping identified a point mutation in the Lmna gene, causing a single amino acid change, L52R, in the coiled coil rod domain of lamin A and C proteins. Cranial sutures in Dhe/+ mice failed to close. Gene expression for collagen types I and III in sutures was deficient. Skulls were small and disproportionate. Skeletons of Dhe/+ mice were hypomineralized and total body fat was deficient in males. In homozygotes, skin and oral mucosae were dysplastic and ulcerated. Nuclear morphometry of cultured cells revealed gene dose-dependent blebbing and wrinkling. Conclusion: Dhe mice should provide a useful new model for investigations of the pathogenesis of laminopathies © 2010 Odgren et al. Source

Allgeyer E.S.,University of Maine, United States | Sterling S.M.,University of Maine, United States | Neivandt D.J.,University of Maine, United States | Neivandt D.J.,Institute for Molecular Biophysics | And 2 more authors.
Review of Scientific Instruments

A recent iteration of fluorescence correlation spectroscopy (FCS), z-scan FCS, has drawn attention for its elegant solution to the problem of quantitative sample positioning when investigating two-dimensional systems while simultaneously providing an excellent method for extracting calibration-free diffusion coefficients. Unfortunately, the measurement of planar systems using (FCS and) z-scan FCS still requires extremely mechanically stable sample positioning, relative to a microscope objective. As axial sample position serves as the inherent length calibration, instabilities in sample position will affect measured diffusion coefficients. Here, we detail the design and function of a highly stable and mechanically simple inverted microscope stage that includes a temperature controlled liquid cell. The stage and sample cell are ideally suited to planar membrane investigations, but generally amenable to any quantitative microscopy that requires low drift and excellent axial and lateral stability. In the present work we evaluate the performance of our custom stage system and compare it with the stock microscope stage and typical sample sealing and holding methods. © 2011 American Institute of Physics. Source

Sterling S.M.,University of Maine, United States | Allgeyer E.S.,University of Maine, United States | Fick J.,University of Maine, United States | Prudovsky I.,University of Maine, United States | And 6 more authors.

Model cellular membranes enable the study of biological processes in a controlled environment and reduce the traditional challenges associated with live or fixed cell studies. However, model membrane systems based on the air/water or oil/solution interface do not allow for incorporation of transmembrane proteins or for the study of protein transport mechanisms. Conversely, a phospholipid bilayer deposited via the Langmuir-Blodgett/Langmuir- Schaefer method on a hydrogel layer is potentially an effective mimic of the cross section of a biological membrane and facilitates both protein incorporation and transport studies. Prior to application, however, such membranes must be fully characterized, particularly with respect to the phospholipid bilayer phase transition temperature. Here we present a detailed characterization of the phase transition temperature of the inner and outer leaflets of a chitosan supported model membrane system. Specifically, the lateral diffusion coefficient of each individual leaflet has been determined as a function of temperature. Measurements were performed utilizing z-scan fluorescence correlation spectroscopy (FCS), a technique that yields calibration-free diffusion information. Analysis via the method of Wawrezinieck and co-workers revealed that phospholipid diffusion changes from raftlike to free diffusion as the temperature is increased - an insight into the dynamic behavior of hydrogel supported membranes not previously reported. © 2013 American Chemical Society. Source

Meesters C.,Institute for Molecular Biophysics | Meesters C.,Institute for Medical Biometrics | Pairet B.,Institute for Molecular Biophysics | Rabenhorst A.,Institute for Molecular Biophysics | And 2 more authors.
Computational Biology and Chemistry

We present a modular, collaborative, open-source architecture for rigid body modelling based upon small angle scattering data, named sas-rigid. It is designed to provide a fast and extensible scripting interface using the easy-to-learn Python programming language. Features include rigid body modelling to result in static structures and three-dimensional probability densities using two different algorithms. © 2010 Elsevier Ltd. Source

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