Precisely measured protein lifetimes in the mouse brain reveal differences across tissues and subcellular fractions DOI Creative Commons
Eugenio F. Fornasiero, Sunit Mandad,

Hanna Wildhagen

et al.

Nature Communications, Journal Year: 2018, Volume and Issue: 9(1)

Published: Oct. 8, 2018

The turnover of brain proteins is critical for organism survival, and its perturbations are linked to pathology. Nevertheless, protein lifetimes have been difficult obtain in vivo. They readily measured vitro by feeding cells with isotopically labeled amino acids, followed mass spectrometry analyses. In vivo generated from at least two sources: acids the diet, non-labeled degradation pre-existing proteins. This renders measurements difficult. Here we solved this problem rigorously a workflow that combines mouse isotopic labeling, spectrometry, mathematical modeling. We also established several independent approaches test validate results. enabled us measure accurate ~3500 high precision our data provided large set biologically significant observations, including pathway-, organelle-, organ-, or cell-specific effects, along comprehensive catalog extremely long-lived (ELLPs).

Language: Английский

Nanoscale Memristor Device as Synapse in Neuromorphic Systems DOI

Sung Hyun Jo,

Ting‐Chang Chang,

Idongesit E. Ebong

et al.

Nano Letters, Journal Year: 2010, Volume and Issue: 10(4), P. 1297 - 1301

Published: March 1, 2010

A memristor is a two-terminal electronic device whose conductance can be precisely modulated by charge or flux through it. Here we experimentally demonstrate nanoscale silicon-based and show that hybrid system composed of complementary metal−oxide semiconductor neurons synapses support important synaptic functions such as spike timing dependent plasticity. Using memristors in neuromorphic circuits potentially offer both high connectivity density required for efficient computing.

Language: Английский

Citations

3901

Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function DOI Open Access
Monika Piwecka, Petar Glažar, Luis R. Hernández-Miranda

et al.

Science, Journal Year: 2017, Volume and Issue: 357(6357)

Published: Aug. 11, 2017

Hundreds of circular RNAs (circRNAs) are highly abundant in the mammalian brain, often with conserved expression. Here we show that circRNA Cdr1as is massively bound by microRNAs (miRNAs) miR-7 and miR-671 human mouse brains. When locus was removed from genome, knockout animals displayed impaired sensorimotor gating-a deficit ability to filter out unnecessary information-which associated neuropsychiatric disorders. Electrophysiological recordings revealed dysfunctional synaptic transmission. Expression specifically posttranscriptionally misregulated all brain regions analyzed. immediate early genes such as Fos, a direct target, enhanced Cdr1as-deficient brains, providing possible molecular link behavioral phenotype. Our data indicate an vivo loss-of-function phenotype suggest interactions between miRNAs important for normal function.

Language: Английский

Citations

1109

Memory effects in complex materials and nanoscale systems DOI
Yuriy V. Pershin, Massimiliano Di Ventra

Advances In Physics, Journal Year: 2011, Volume and Issue: 60(2), P. 145 - 227

Published: Feb. 10, 2011

Memory effects are ubiquitous in nature and particularly relevant at the nanoscale where dynamical properties of electrons ions strongly depend on history system, least within certain time scales. We review here memory various materials systems which appear most strikingly their non-trivial time-dependent resistive, capacitative inductive characteristics. describe these characteristics framework memristors, memcapacitors meminductors, namely circuit elements whose state system. examine basic issues related to such critically report both theoretical experimental progress understanding functionalities. also discuss possible applications areas science technology ranging from digital analog electronics, biologically-inspired circuits, learning. finally future research opportunities field.

Language: Английский

Citations

727

A trans-synaptic nanocolumn aligns neurotransmitter release to receptors DOI
Ai‐Hui Tang, Haiwen Chen, Tuo Peter Li

et al.

Nature, Journal Year: 2016, Volume and Issue: 536(7615), P. 210 - 214

Published: July 26, 2016

Language: Английский

Citations

621

Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex DOI
Gerard M. J. Beaudoin,

Seung-Hye Lee,

Dipika Singh

et al.

Nature Protocols, Journal Year: 2012, Volume and Issue: 7(9), P. 1741 - 1754

Published: Aug. 30, 2012

Language: Английский

Citations

604

Axonal Transport of TDP-43 mRNA Granules Is Impaired by ALS-Causing Mutations DOI Creative Commons
Nael H. Alami, Rebecca B. Smith, Mónica A. Carrasco

et al.

Neuron, Journal Year: 2014, Volume and Issue: 81(3), P. 536 - 543

Published: Feb. 1, 2014

Language: Английский

Citations

593

Prions hijack tunnelling nanotubes for intercellular spread DOI
Karine Gousset,

Edwin Schiff,

Christelle Langevin

et al.

Nature Cell Biology, Journal Year: 2009, Volume and Issue: 11(3), P. 328 - 336

Published: Feb. 8, 2009

Language: Английский

Citations

575

Super-Resolution Imaging Reveals That AMPA Receptors Inside Synapses Are Dynamically Organized in Nanodomains Regulated by PSD95 DOI Open Access
Deepak Nair, Eric Hosy, Jennifer D. Petersen

et al.

Journal of Neuroscience, Journal Year: 2013, Volume and Issue: 33(32), P. 13204 - 13224

Published: Aug. 7, 2013

The spatiotemporal organization of neurotransmitter receptors in postsynaptic membranes is a fundamental determinant synaptic transmission and information processing by the brain. Using four independent super-resolution light imaging methods EM genetically tagged endogenous receptors, we show that, rat hippocampal neurons, AMPARs are often highly concentrated inside synapses into few clusters ∼70 nm that contain ∼20 receptors. stabilized reversibly these nanodomains diffuse freely outside them. Nanodomains dynamic their shape position within can form or disappear minutes, although they mostly stable for up to 1 h. AMPAR often, but not systematically, colocalized with scaffold protein PSD95, which generally larger size than nanoclusters. PSD95 expression level regulates nanodomain compactness parallel miniature EPSC amplitude. Monte Carlo simulations further indicate impact concentration on efficacy transmission. observation nanodomains, instead diffusively distributed PSD as thought, has important consequences our understanding excitatory neurotransmission. Furthermore, results glutamatergic controlled nanometer-scale regulation nanodomains.

Language: Английский

Citations

567

A simple, versatile method for GFP-based super-resolution microscopy via nanobodies DOI
Jonas Ries, Charlotte Kaplan,

Evgenia Platonova

et al.

Nature Methods, Journal Year: 2012, Volume and Issue: 9(6), P. 582 - 584

Published: April 29, 2012

Language: Английский

Citations

554

Vertical silicon nanowires as a universal platform for delivering biomolecules into living cells DOI
Alex K. Shalek, Jacob T. Robinson,

Ethan S. Karp

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2010, Volume and Issue: 107(5), P. 1870 - 1875

Published: Jan. 11, 2010

A generalized platform for introducing a diverse range of biomolecules into living cells in high-throughput could transform how complex cellular processes are probed and analyzed. Here, we demonstrate spatially localized, efficient, universal delivery immortalized primary mammalian using surface-modified vertical silicon nanowires. The method relies on the ability nanowires to penetrate cell’s membrane subsequently release surface-bound molecules directly cytosol, thus allowing highly efficient without chemical modification or viral packaging. This modality enables one assess phenotypic consequences broad biological effectors (DNAs, RNAs, peptides, proteins, small molecules) almost any cell type. We show that this can be used guide neuronal progenitor growth with molecules, knock down transcript levels by delivering siRNAs, inhibit apoptosis introduce targeted proteins specific organelles. further codelivery siRNAs single substrate microarray format, highlighting technology’s potential as robust, monolithic high-throughput, miniaturized bioassays.

Language: Английский

Citations

545