A novel mutation and variable phenotypic expression in a large consanguineous pedigree with Jalili syndrome.

PurposeJalili syndrome is an autosomal recessive disorder characterized by simultaneous appearance of cone-rod dystrophy (CRD) and amelogenesis imperfecta (AI). Mutations in CNNM4 gene have been identified as the underlying cause of the syndrome. In this study, we investigated a large affected family to identify the causative mutation.Patients and MethodsA seven-generation family with 24 members affected with Jalili syndrome were enrolled in the study. Comprehensive ophthalmologic and dental examinations were performed on them. The entire coding region of CNNM4 gene was sequenced for detection of potential mutations.ResultsOcular examinations showed nystagmus and photophobia along with early onset visual impairment. Fundoscopic exams revealed a spectrum of macular dystrophies in different family members, from macular coloboma and advanced form of beaten bronze macular dystrophy (bull's eye) to milder form of macular thinning along with a range of pigmentary changes and vascular attenuation in the posterior pole and periphery. Scotopic and photopic electro-retinographic responses (ERGs) were extinguished or significantly depressed. Mutation analysis revealed a novel mutation (c.1091delG) in homozygous form in the patients and as a heterozygous form in the normal carrier subjects.ConclusionWe identified a novel homozygous deleterious mutation in CNNM4 gene which causes Jalili syndrome.

Physical inactivity and risk of hospitalisation for chronic obstructive pulmonary disease.

The association between physical activity and risk of hospitalisation for chronic obstructive pulmonary disease (COPD) is not yet clear. We conducted a systematic review of the literature to fill this gap in knowledge. Eight electronic databases were searched using a selection of controlled vocabulary and keywords. The search resulted in more than 1000 initial hits, of which four met the inclusion criteria. For each identified study, relevant data were extracted and appraised. The results indicate that less physically active patients with COPD were more likely to be admitted to hospital. Consistent with a lower level of physical activity, the patients tended to have shorter walking times as well as spend fewer hours outdoors. In multivariate regression analysis, self-reported physical activity predicted hospitalisation in patients from the general population and re-hospitalisation in patients admitted for an acute exacerbation. The evidence for an association between physical activity and risk of hospitalisation for COPD is limited to a few prospective cohort studies. More research is needed to quantify the degree of physical activity associated with reduced risk of hospitalisation.

Short-time inertial response of viscoelastic fluids measured with Brownian motion and with active probes.

We have directly observed short-time stress propagation in viscoelastic fluids using two optically trapped particles and a fast interferometric particle-tracking technique. We have done this both by recording correlations in the thermal motion of the particles and by measuring the response of one particle to the actively oscillated second particle. Both methods detect the vortexlike flow patterns associated with stress propagation in fluids. This inertial vortex flow propagates diffusively for simple liquids, while for viscoelastic solutions the pattern spreads superdiffusively, depending on the shear modulus of the medium.

Twin optical traps for two-particle cross-correlation measurements: eliminating cross-talk.

The correlated motions of two micron-sized particles reflect the (micro-) rheological properties of a fluid and can be conveniently detected using two optical traps in combination with interferometric displacement detection. When the correlations become small, cross-talk between the two beams becomes important. We have used dual optical traps created by either two orthogonally polarized laser beams derived from one laser source, or by two independent lasers of different wavelengths for microrheology experiments. High numerical aperture lenses (objective and condenser) in the optical path can introduce depolarization, and polarizing beam splitters are not perfect, both of which can lead to optical cross-talk. We have characterized the cross-talk in our setup and demonstrate that the use of two independent laser eliminates cross-talk entirely.

High-bandwidth viscoelastic properties of aging colloidal glasses and gels.

We report measurements of the frequency-dependent shear moduli of aging colloidal systems that evolve from a purely low-viscosity liquid to a predominantly elastic glass or gel. Using microrheology, we measure the local complex shear modulus G;{*}(omega) over a very wide range of frequencies (from 1Hzto100kHz ). The combined use of one- and two-particle microrheology allows us to differentiate between colloidal glasses and gels-the glass is homogenous, whereas the colloidal gel shows a considerable degree of heterogeneity on length scales larger than 0.5microm . Despite this characteristic difference, both systems exhibit similar rheological behaviors which evolve in time with aging, showing a crossover from a single-power-law frequency dependence of the viscoelastic modulus to a sum of two power laws. The crossover occurs at a time t_{0} , which defines a mechanical transition point. We found that the data acquired during the aging of different samples can be collapsed onto a single master curve by scaling the aging time with t_{0} . This raises questions about the prior interpretation of two power laws in terms of a superposition of an elastic network embedded in a viscoelastic background.

Correlated fluctuations of microparticles in viscoelastic solutions: quantitative measurement of material properties by microrheology in the presence of optical traps.

The Brownian motions of microscopic particles in viscous or viscoelastic fluids can be used to measure rheological properties. This is the basis of recently developed one- and two-particle microrheology techniques. For increased temporal and spatial resolution, some microrheology techniques employ optical traps, which introduce additional forces on the particles. We have systematically studied the effect that confinement of particles by optical traps has on their auto- and cross-correlated fluctuations. We show that trapping causes anticorrelations in the motion of two particles at low frequencies. We demonstrate how these anticorrelations depend on trap strength and the shear modulus of viscoelastic media. We present a method to account for the effects of optical traps, which permits the quantitative measurement of viscoelastic properties in one- and two-particle microrheology over an extended frequency range in a variety of viscous and viscoelastic media.

High-frequency stress relaxation in semiflexible polymer solutions and networks.

We measure the linear viscoelasticity of sterically entangled and chemically cross-linked networks of actin filaments over more than five decades of frequency. The high-frequency response reveals rich dynamics unique to semiflexible polymers, including a previously unobserved relaxation due to rapid axial tension propagation. For high molecular weight, and for cross-linked gels, we obtain quantitative agreement with predicted shear moduli in both amplitude and frequency dependence.

Short-time inertial response of viscoelastic fluids: observation of vortex propagation.

We probe the response of viscous and viscoelastic fluids on micrometer and microsecond length and time scales using two optically trapped beads. In this way we resolve the flow field, which exhibits clear effects of fluid inertia. Specifically, we resolve the short-time vortex flow and the corresponding evolution of this vortex, which propagates diffusively for simple liquids. For viscoelastic fluids, this propagation is shown to be faster than diffusive and the displacement correlations reflect the frequency-dependent shear modulus of the medium.

High-frequency microrheology of wormlike micelles.

We have measured the frequency-dependent shear modulus of entangled solutions of wormlike micelles by high-frequency microrheology and have compared the results with those from macrorheology experiments done on the same samples. Using optical microrheology based on laser interferometry we have measured loss and storage moduli over six decades in frequency up to about 100 kHz. We present data over a decade in concentration in the entangled regime and find good agreement between micro- and macrorheology, thus validating recently developed microrheology techniques. By collapsing data for different concentrations, we furthermore determine both the concentration scaling of the plateau modulus and a power-law exponent of the complex shear modulus at high frequencies.