Introduction of d-Glutamate at a Critical Residue of Aβ42 Stabilizes a Prefibrillary Aggregate with Enhanced Toxicity.

Published in Chemistry (Weinheim an der Bergstrasse, Germany)

The amyloid beta peptide 42 (Aβ42) is an aggregation-prone peptide that plays a pivotal role in Alzheimer's disease. We report that a subtle perturbation to the peptide through a single chirality change at glutamate 22 leads to a pronounced delay in the β-sheet adoption of the peptide. This was accompanied by an attenuated propensity of the peptide...

Phosphono Bisbenzguanidines as Irreversible Dipeptidomimetic Inhibitors and Activity-Based Probes of Matriptase-2.

Published in Chemistry (Weinheim an der Bergstrasse, Germany)

Matriptase-2, a type II transmembrane serine protease, plays a key role in human iron homeostasis. Inhibition of matriptase-2 is considered as an attractive strategy for the treatment of iron-overload diseases, such as hemochromatosis and β-thalassemia. In the present study, synthetic routes to nine dipeptidomimetic inactivators were developed. Fiv...

Corticothalamic Axons Are Essential for Retinal Ganglion Cell Axon Targeting to the Mouse Dorsal Lateral Geniculate Nucl...

Published in The Journal of neuroscience : the official journal of the Society for Neuroscience

The dorsal lateral geniculate nucleus (dLGN) is a sensory thalamic relay area that receives feedforward inputs from retinal ganglion cells (RGCs) in the retina, and feed back inputs from layer 6 neurons in the visual cortex. In this study we examined genetically manipulated mice that develop without a cortex or without cortical layer 6 axonal proje...

Facilitating a culture of responsible and effective sharing of cancer genome data.

Published in Nature medicine

Rapid and affordable tumor molecular profiling has led to an explosion of clinical and genomic data poised to enhance the diagnosis, prognostication and treatment of cancer. A critical point has now been reached at which the analysis and storage of annotated clinical and genomic information in unconnected silos will stall the advancement of precisi...

Kinesin-1 tail autoregulation and microtubule-binding regions function in saltatory transport but not ooplasmic streamin...

Published in Development (Cambridge, England)

Bidirectional radial Ca(2+) activity regulates neurogenesis and migration during early cortical column formation.

Published in Science advances

Cortical columns are basic cellular and functional units of the cerebral cortex that are malformed in many brain disorders, but how they initially develop is not well understood. Using an optogenetic sensor in the mouse embryonic forebrain, we demonstrate that Ca(2+) fluxes propagate bidirectionally within the elongated fibers of radial glial cells...

Common Polymorphisms in the Solute Carrier SLC30A10 are Associated With Blood Manganese and Neurological Function.

Published in Toxicological sciences : an official journal of the Society of Toxicology

Manganese (Mn) is an essential nutrient in humans, but excessive exposure to Mn may cause neurotoxicity. Despite homeostatic regulation, Mn concentrations in blood vary considerably among individuals. We evaluated if common single-nucleotide polymorphisms (SNPs) in SLC30A10, which likely encodes an Mn transporter, influence blood Mn concentrations ...

Electrostatic Similarity Analysis of Human β-Defensin Binding in the Melanocortin System.

Published in Biophysical journal

The β-defensins are a class of small cationic proteins that serve as components of numerous systems in vertebrate biology, including the immune and melanocortin systems. Human β-defensin 3 (HBD3), which is produced in the skin, has been found to bind to melanocortin receptors 1 and 4 through complementary electrostatics, a unique mechanism of ligan...

Prenatal and postnatal manganese teeth levels and neurodevelopment at 7, 9, and 10.5 years in the CHAMACOS cohort.

Published in Environment international

We observed that higher prenatal and early postnatal Mn levels measured in dentine of deciduous teeth, a novel biomarker that provides reliable information on the developmental timing of exposures to Mn, were associated with poorer behavioral outcomes in school-age boys and girls and better motor function, memory, and/or cognitive abilities in scho...

Contrast Sensitivity With a Subretinal Prosthesis and Implications for Efficient Delivery of Visual Information.

Published in Investigative ophthalmology & visual science

To evaluate the contrast sensitivity of a degenerate retina stimulated by a photovoltaic subretinal prosthesis, and assess the impact of low contrast sensitivity on transmission of visual information. We measure ex vivo the full-field contrast sensitivity of healthy rat retina stimulated with white light, and the contrast sensitivity of degenerate ...