A membrane-targeted photoswitch restores physiological ON/OFF responses to light in the degenerate retina.

The lack of effective therapies for visual restoration in Retinitis pigmentosa and macular degeneration has led to the development of new strategies, such as optogenetics and retinal prostheses. However, visual restoration is poor due to the massive light-evoked activation of retinal neurons, regardless of the segregation of visual information in ON and OFF channels, which is essential for contrast sensitivity and spatial resolution. Here, we show that Ziapin2, a membrane photoswitch that modulates neuronal capacitance and excitability in a light-dependent manner, is capable of reinstating, in mouse and rat genetic models of photoreceptor degeneration, brisk and sluggish ON, OFF, and ON-OFF responses in retinal ganglion cells evoked by full-field stimuli, with reactivation of their excitatory and inhibitory conductances.

A claudin5-binding peptide enhances the permeability of the blood-brain barrier in vitro.

The blood-brain barrier (BBB) maintains brain homeostasis but also prevents most drugs from entering the brain. No paracellular diffusion of solutes is allowed because of tight junctions that are made impermeable by the expression of claudin5 (CLDN5) by brain endothelial cells. The possibility of regulating the BBB permeability in a transient and reversible fashion is in strong demand for the pharmacological treatment of brain diseases.

TBC1D24 interacts with the v-ATPase and regulates intraorganellar pH in neurons.

The vacuolar ATPase (v-ATPase) is essential for acidification of intracellular organelles, including synaptic vesicles. Its activity is controlled by cycles of association and dissociation of the ATP hydrolysis (V) and proton transport (V) multi-protein subunits. Mutations in genes coding for both v-ATPase subunits and TBC1D24 cause neurodevelopmental disorders with overlapping syndromes; therefore, it is important to investigate their potentially interrelated functions.

Membrane-targeted push-pull azobenzenes for the optical modulation of membrane potential.

We introduce a family of membrane-targeted azobenzenes (MTs) with a push-pull character as a new tool for cell stimulation. These molecules are water soluble and spontaneously partition in the cell membrane. Upon light irradiation, they isomerize from trans to cis, changing the local charge distribution and thus stimulating the cell response.

Ion and water permeation through claudin-10b and claudin-15 paracellular channels.

The structural scaffold of epithelial and endothelial tight junctions (TJs) comprises multimeric strands of claudin (Cldn) proteins that anchor adjacent cells and control the paracellular flux of water and solutes. Based on the permeability properties they confer to the TJs, Cldns are classified as channel- or barrier-forming. For instance, Cldn10b, expressed in kidneys, lungs, and other tissues, displays high permeability for cations and low permeability for water.

Constitutive opening of the Kv7.2 pore activation gate causes -developmental encephalopathy.

Pathogenic variants in encoding Kv7.2 voltage-gated potassium channel subunits cause developmental encephalopathies (-encephalopathies), both with and without epilepsy. We herein describe the clinical, in vitro, and in silico features of two encephalopathy-causing variants (A317T, L318V) in Kv7.

Solid-State Nanopores for Spatially Resolved Chemical Neuromodulation.

Most neural prosthetic devices are based on electrical stimulation, although the modulation of neuronal activity by a localized chemical delivery would better mimic physiological synaptic machinery. In the past decade, various drug delivery approaches attempted to emulate synaptic transmission, although they were hampered by poor retention of their cargo while reaching the target destination, low spatial resolution, and poor biocompatibility and stability of the materials involved. Here, we propose a planar solid-state device for multisite neurotransmitter translocation at the nanoscale consisting of a nanopatterned ceramic membrane connected to a reservoir designed to store neurotransmitters.

Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role.

Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A.

Biomimetic Plasmonic Nanophages by Head/Tail Self-Assembling: Gold Nanoparticle/Virus Interactions.

Gold nanoparticles (AuNPs), because of their dual plasmonic and catalytic functionalities, are among the most promising nanomaterials for the development of therapeutic and diagnostic tools for severe diseases such as cancer and neurodegeneration. Bacteriophages, massively present in human biofluids, are emerging as revolutionary biotechnological tools as they can be engineered to display multiple specific binding moieties, providing effective targeting ability, high stability, low cost, and sustainable production. Coupling AuNPs with phages can lead to an advanced generation of nanotools with great potential for biomedical applications.

Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.

Purpose: Spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising 8 with SINO and 4 with an autosomal recessive condition attributed to biallelic KIDINS220 variants.

Methods: In our international cohort, we have included 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form.

A pH-sensitive closed-loop nanomachine to control hyperexcitability at the single neuron level.

Epilepsy affects 1% of the general population and 30% of patients are resistant to antiepileptic drugs. Although optogenetics is an efficient antiepileptic strategy, the difficulty of illuminating deep brain areas poses translational challenges. Thus, the search of alternative light sources is strongly needed.

The Lack of Synapsin Alters Presynaptic Plasticity at Hippocampal Mossy Fibers in Male Mice.

Synapsins are highly abundant presynaptic proteins that play a crucial role in neurotransmission and plasticity via the clustering of synaptic vesicles. The synapsin III isoform is usually downregulated after development, but in hippocampal mossy fiber boutons, it persists in adulthood. Mossy fiber boutons express presynaptic forms of short- and long-term plasticity, which are thought to underlie different forms of learning.

ATP6V1A is required for synaptic rearrangements and plasticity in murine hippocampal neurons.

Aim: Understanding the physiological role of ATP6V1A, a component of the cytosolic V domain of the proton pump vacuolar ATPase, in regulating neuronal development and function.

Methods: Modeling loss of function of Atp6v1a in primary murine hippocampal neurons and studying neuronal morphology and function by immunoimaging, electrophysiological recordings and electron microscopy.

Results: Atp6v1a depletion affects neurite elongation, stabilization, and function of excitatory synapses and prevents synaptic rearrangement upon induction of plasticity.

Nanoactuator for Neuronal Optoporation.

Light-driven modulation of neuronal activity at high spatial-temporal resolution is becoming of high interest in neuroscience. In addition to optogenetics, nongenetic membrane-targeted nanomachines that alter the electrical state of the neuronal membranes are in demand. Here, we engineered and characterized a photoswitchable conjugated compound (BV-1) that spontaneously partitions into the neuronal membrane and undergoes a charge transfer upon light stimulation.

The homeostatic effects of the RE-1 silencing transcription factor on cortical networks are altered under ictogenic conditions in the mouse.

Aim: The Repressor Element-1 Silencing Transcription Factor (REST) is an epigenetic master regulator playing a crucial role in the nervous system. In early developmental stages, REST downregulation promotes neuronal differentiation and the acquisition of the neuronal phenotype. In addition, postnatal fluctuations in REST expression contribute to shaping neuronal networks and maintaining network homeostasis.

Restoring vision in adult amblyopia by enhancing plasticity through deletion of the transcriptional repressor REST.

Visual cortical plasticity is high during early life, but gradually decreases with development. This is due to the Otx2-driven maturation of intracortical inhibition that parallels the condensation of extracellular matrix components into perineuronal nets mainly around parvalbumin-positive GABAergic neurons. Repressor Element 1 Silencing Transcription (REST) epigenetically controls the expression of a plethora of neuron-specific genes.

Self-assembly of an amino acid derivative as an anode interface layer for advanced alkaline Al-air batteries.

Alkaline Al-air batteries (AABs) are gaining increasing attention for large-scale energy storage systems due to their attractive intrinsic safety and cost-effectiveness. Nonetheless, the future development of AABs is substantially hampered by water-induced self-corrosion processes on the Al anode. In this work, we introduce an amino acid derivative, namely α-Boc-1-formyl-L-tryptophan (NBLT), into a 4 M NaOH electrolyte to construct a unique layer that can effectively regulate the surface microstructure of the Al anode.

Unlocking mechanosensitivity: integrins in neural adaptation.

Mechanosensitivity extends beyond sensory cells to encompass most neurons in the brain. Here, we explore recent research on the role of integrins, a diverse family of adhesion molecules, as crucial biomechanical sensors translating mechanical forces into biochemical and electrical signals in the brain. The varied biomechanical properties of neuronal integrins, including their force-dependent conformational states and ligand interactions, dictate their specific functions.

Alterations in KIDINS220/ARMS Expression Impact Sensory Processing and Social Behavior in Adult Mice.

Kinase D-interacting substrate of 220 kDa (Kidins220) is a transmembrane protein that participates in neural cell survival, maturation, and plasticity. Mutations in the human gene are associated with a neurodevelopmental disorder ('SINO' syndrome) characterized by spastic paraplegia, intellectual disability, and in some cases, autism spectrum disorder. To better understand the pathophysiology of KIDINS220-linked pathologies, in this study, we assessed the sensory processing and social behavior of transgenic mouse lines with reduced Kidins220 expression: the CaMKII-driven conditional knockout (cKO) line, lacking Kidins220 in adult forebrain excitatory neurons, and the Kidins220floxed line, expressing constitutively lower protein levels.

Environmental and Health Impacts of Graphene and Other Two-Dimensional Materials: A Graphene Flagship Perspective.

Two-dimensional (2D) materials have attracted tremendous interest ever since the isolation of atomically thin sheets of graphene in 2004 due to the specific and versatile properties of these materials. However, the increasing production and use of 2D materials necessitate a thorough evaluation of the potential impact on human health and the environment. Furthermore, harmonized test protocols are needed with which to assess the safety of 2D materials.