Although it has been known for over 50 years that abnormal concentrations of iron are associated with virtually all neurodegenerative diseases, including Alzheimer's disease, its origin, nature and role have remained a mystery. Here, we use high-resolution transmission electron microscopy (HR-TEM), energy dispersive X-ray (EDX) spectroscopy and electron energy-loss spectroscopy (EELS), electron tomography, and electron diffraction to image and characterize iron-rich plaque core material-a hallmark of Alzheimer's disease pathology-in three dimensions. In these cores, we unequivocally identify biogenic magnetite and/or maghemite as the dominant iron compound. Our results provide an indication that abnormal iron biomineralization processes are likely occurring within the plaque or the surrounding diseased tissue and may play a role in aberrant peptide aggregation. The size distribution of the magnetite cores implies formation from a ferritin precursor, implicating a malfunction of the primary iron storage protein in the brain.

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Compartmentalization of cellular signaling forms the molecular basis of cellular behavior. The primary cilium constitutes a subcellular compartment that orchestrates signal transduction independent from the cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary signaling has been challenging due to the lack of tools to investigate ciliary signaling. Here, we describe a nanobody-based targeting approach for optogenetic tools in mammalian cells and in vivo in zebrafish to specifically analyze ciliary signaling and function. Thereby, we overcome the loss of protein function observed after fusion to ciliary targeting sequences. We functionally localized modifiers of cAMP signaling, the photo-activated adenylyl cyclase bPAC and the light-activated phosphodiesterase LAPD, and the cAMP biosensor mlCNBD-FRET to the cilium. Using this approach, we studied the contribution of spatial cAMP signaling in controlling cilia length. Combining optogenetics with nanobody-based targeting will pave the way to the molecular understanding of ciliary function in health and disease.

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Epitaxial layers of CoSi 2 have been grown on Si͑100͒ by the technique of nitride-mediated epitaxy. An ultrathin layer of silicon nitride was formed on the Si͑001͒ surface by exposure to ammonia gas at 900°C, followed by the deposition of a layer of Co ϳ20 Å in thickness at room temperature. The sample was then annealed at 600°C and the microstructure monitored by in situ transmission electron microscopy and diffraction. The formation of epitaxial islands of CoSi 2 was observed directly, with no evidence of the formation of intermediate phases. The CoSi 2 islands were found to be elongated along the in-plane Si͗110͘ directions, consistent with reports of the deposition of Co by molecular beam epitaxy on clean Si͑100͒ at low deposition rates and elevated temperature. This technique of silicidation may be of particular interest in the fabrication of advanced devices incorporating multilayer oxide/nitride gate stacks.

Compartmentalization of cellular signaling forms the molecular basis of cellular behavior. Primary cilia constitute a subcellular compartment that orchestrates signal transduction independent from the cell body. Ciliary dysfunction causes severe diseases, termed ciliopathies. Analyzing ciliary signaling and function has been challenging due to the lack of tools to manipulate and analyze ciliary signaling in living cells. Here, we describe a nanobodybased targeting approach for optogenetic tools that allows to specifically analyze ciliary signaling and function, and that is applicable in vitro and in vivo. We overcome the loss of protein function observed after direct fusion to a ciliary targeting sequence, and functionally localize the photo-activated adenylate cyclase bPAC, the light-activated phosphodiesterase LAPD, and the cAMP biosensor mlCNBD-FRET to the cilium. Using this approach, we unravel the contribution of spatial cAMP signaling in controlling cilia length. Combining optogenetics with nanobody-based targeting will pave the way to the molecular understanding of ciliary function in health and disease.

bstractTran mi ion electron micro copy, off-axi electron holography and energy-elected imaging were u ed to tudy the crystallography, morphology, and magnetic micro tructure of nano cale greigite (Fe3S4) magnetosome in magnetotactic bacteria from a ulfidic habitat. The greigite magnetosomes were organized in chains but were less ordered than magnetite magnetosomes in other bacteria.evertheles , the magneto ome comprise a permanent magnetic dipole, sufficient for magnelotaxi .

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