New TRP Channels in Hearing and Mechanosensation

AbstractDespite extensive biophysical characterization and the superb example of the bacterial MscL channel, molecular identification of eukaryotic mechanosensitive channels has been slow. New members of the TRP superfamily have emerged as candidate channels to mediate touch, hearing, fluid flow, and osmosensation in sensory and nonsensory cells. Distinguishing between direct mechanical activation and indirect second messenger activation is still a challenge

Differential effects of Alzheimer\u27s disease and Huntington\u27s disease on the performance of mental rotation

he ability to spatially rotate a mental image was compared in patients with Alzheimer\u27s disease (AD; n = 18) and patients with Huntington\u27s disease (HD; n = 18). Compared to their respective age-matched normal control (NC) group, the speed, but not the accuracy, of mental rotation abnormally decreased with increasing angle of orientation for patients with HD. In contrast, the accuracy, but not the speed, of rotation abnormally decreased with increasing angle of orientation for patients with AD. Additional analyses showed that these unique patterns of performance were not attributable to different speed/accuracy trade-off sensitivities. This double dissociation suggests that the distinct brain regions affected in the two diseases differentially contribute to speed and accuracy of mental rotation. Specifically, the slowing exhibited by HD patients may be mediated by damage to the basal ganglia, whereas the spatial manipulation deficit of AD patients may reflect pathology in parietal and temporal lobe association cortices important for visuospatial processing. (JINS, 2005, 11, 30–39.

C-MYC Transcriptionally Amplifies SOX2 Target Genes to Regulate Self-Renewal in Multipotent Otic Progenitor Cells

Summary Sensorineural hearing loss is caused by the loss of sensory hair cells and neurons of the inner ear. Once lost, these cell types are not replaced. Two genes expressed in the developing inner ear are c-Myc and Sox2. We created immortalized multipotent otic progenitor (iMOP) cells, a fate-restricted cell type, by transient expression of C-MYC in SOX2-expressing otic progenitor cells. This activated the endogenous C-MYC and amplified existing SOX2-dependent transcripts to promote self-renewal. RNA-seq and ChIP-seq analyses revealed that C-MYC and SOX2 occupy over 85% of the same promoters. C-MYC and SOX2 target genes include cyclin-dependent kinases that regulate cell-cycle progression. iMOP cells continually divide but retain the ability to differentiate into functional hair cells and neurons. We propose that SOX2 and C-MYC regulate cell-cycle progression of these cells and that downregulation of C-MYC expression after growth factor withdrawal serves as a molecular switch for differentiation

From Biological Cilia to Artificial Flow Sensors: Biomimetic Soft Polymer Nanosensors with High Sensing Performance

We report the development of a new class of miniature all-polymer flow sensors that closely mimic the intricate morphology of the mechanosensory ciliary bundles in biological hair cells. An artificial ciliary bundle is achieved by fabricating bundled polydimethylsiloxane (PDMS) micro-pillars with graded heights and electrospinning polyvinylidenefluoride (PVDF) piezoelectric nanofiber tip links. The piezoelectric nature of a single nanofiber tip link is confirmed by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Rheology and nanoindentation experiments are used to ensure that the viscous properties of the hyaluronic acid (HA)-based hydrogel are close to the biological cupula. A dome-shaped HA hydrogel cupula that encapsulates the artificial hair cell bundle is formed through precision drop-casting and swelling processes. Fluid drag force actuates the hydrogel cupula and deflects the micro-pillar bundle, stretching the nanofibers and generating electric charges. Functioning with principles analogous to the hair bundles, the sensors achieve a sensitivity and threshold detection limit of 300 mV/(m/s) and 8 μm/s, respectively. These self-powered, sensitive, flexible, biocompatibale and miniaturized sensors can find extensive applications in navigation and maneuvering of underwater robots, artificial hearing systems, biomedical and microfluidic devices.Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology)Singapore-MIT Alliance for Research and Technology (SMART) (Innovation Grants ING148079- ENG

Three Recombinant Engineered Antibodies against Recombinant Tags with High Affinity and Specificity

We describe three recombinant engineered antibodies against three recombinant epitope tags, constructed with divalent binding arms to recognize divalent epitopes and so achieve high affinity and specificity. In two versions, an epitope is inserted in tandem into a protein of interest, and a homodimeric antibody is constructed by fusing a high-affinity epitope-binding domain to a human or mouse Fc domain. In a third, a heterodimeric antibody is constructed by fusing two different epitope-binding domains which target two different binding sites in GFP, to polarized Fc fragments. These antibody/epitope pairs have affinities in the low picomolar range and are useful tools for many antibody-based applications

Microextensive Chaos of a Spatially Extended System

By analyzing chaotic states of the one-dimensional Kuramoto-Sivashinsky equation for system sizes L in the range 79 <= L <= 93, we show that the Lyapunov fractal dimension D scales microextensively, increasing linearly with L even for increments Delta{L} that are small compared to the average cell size of 9 and to various correlation lengths. This suggests that a spatially homogeneous chaotic system does not have to increase its size by some characteristic amount to increase its dynamical complexity, nor is the increase in dimension related to the increase in the number of linearly unstable modes.Comment: 5 pages including 4 figures. Submitted to PR