Faculty Bibliography

The cytoskeletal regulators that mediate the change in the neuronal cytoskeletal machinery from one that promotes oriented motility to one that facilitates differentiation at the appropriate locations in the developing neocortex remain unknown. We found that Nck-associated protein 1 (Nap1), an adaptor protein thought to modulate actin nucleation, is selectively expressed in the developing cortical plate, where neurons terminate their migration and initiate laminar-specific differentiation. Loss of Nap1 function disrupts neuronal differentiation. Premature expression of Nap1 in migrating neurons retards migration and promotes postmigratory differentiation. Nap1 gene mutation in mice leads to neural tube and neuronal differentiation defects. Disruption of Nap1 retards the ability to localize key actin cytoskeletal regulators such as WAVE1 to the protrusive edges where they are needed to elaborate process outgrowth. Thus, Nap1 plays an essential role in facilitating neuronal cytoskeletal changes underlying the postmigratory differentiation of cortical neurons, a critical step in functional wiring of the cortex.

Although three-dimensional electron microscopy (3D-EM) permits structural characterization of macromolecular assemblies in distinct functional states, the inability to classify projections from structurally heterogeneous samples has severely limited its application. We present a maximum likelihood-based classification method that does not depend on prior knowledge about the structural variability, and demonstrate its effectiveness for two macromolecular assemblies with different types of conformational variability: the Escherichia coli ribosome and Simian virus 40 (SV40) large T-antigen.

OBJECTIVE:To determine how memory-encoding tasks elicit functional perfusion change in subjects with amnestic mild cognitive impairment (aMCI). METHODS:Twelve subjects with aMCI and 14 age-matched cognitively normal (CN) subjects were recruited for this study. Arterial spin-labeling perfusion MRI (ASL-MRI) was employed to measure regional cerebral blood flow (CBF) during both control and encoding task conditions. RESULTS:Experimental results demonstrated that hypoperfusion occurred in the right precuneus and cuneus in the aMCI group, and not the CN group, during the control state. During the memory-task performance, the difference in these regional hypoperfusion areas extended to the posterior cingulate. These regional perfusion rates correlated with the Mini-Mental State Examination and the Rey Auditory Verbal Learning Test scores. In addition, a CBF percentage increase (22.7%) occurred in the right parahippocampus region during the memory-encoding task performance in the CN group, with approximately no change in the aMCI group. CONCLUSION/CONCLUSIONS:Subjects with amnestic mild cognitive impairment had significant regional cerebral hypoperfusion and lacked the dynamic capability to modulate their regional cerebral blood flow responses to the challenge of the functional tasks.

Cryo-electron microscopy can provide high-resolution structural information about cells and organelles in the nearly native, frozen-hydrated state. Applicability, however, is limited by difficulties encountered in preparing suitably thin, vitreously frozen biological specimens. We demonstrate, by cryo-electron tomography of Escherichia coli cells, that a focused ion beam (FIB) can be used to thin whole frozen-hydrated cells in a convenient and essentially artifact-free way.

The demand for bone grafts in orthopaedic and craniofacial surgery is steadily increasing. Estimations suggest that about 500,000 are performed annually in the United States that include bone grafting as a component of the surgery, and the majority of these surgeries employ autografts. This perspective focuses on the biological events that occur during osseointegration of such bone grafts. Here, three key factors of graft osseointegration--the embryonic origin, the inclusion of skeletal progenitor cells, and the integrity of the recipient site--are discussed. Altogether, they form the foundation for survival of the bone graft and eventually for a positive clinical outcome of the procedure.

A newly designed Gemini-shaped hexabenzocoronene amphiphile (1), carrying an isothiouronium ion-appended side chain, self-assembles in CH2Cl2 to form a nanotubular object, whose graphitic wall is densely covered by a positively charged molecular layer of isothiouronium ion pendants. The graphitic nanotube can be dispersed uniformly in aqueous media owing to effective hydration as well as electrostatic repulsion. Post-supramolecular functionalization of the nanotube surface is possible, without disruption of the tubular morphology, by taking advantage of a specific interaction of the isothiouronium ion pendants with oxoanion guests. Mixing with sodium poly(4-styrenesulfonate) results in wrapping of the nanotube, while complexation with an electron-accepting oxoanion such as anthraquinone carboxylate allows photoinduced electron transfer from the graphitic wall to the bound guest molecules.