Chromatin modifications, especially histone-tail acetylation, have been implicated in memory formation. Increased histone-tail acetylation induced by inhibitors of histone deacetylases (HDACis) facilitates learning and memory in wildtype mice as well as in mouse models of neurodegeneration. Harnessing the therapeutic potential of HDACi requires knowledge of the specific HDAC family member(s) linked to cognitive enhancement. Here we show that neuron-specific overexpression of HDAC2, but not HDAC1, reduced dendritic spine density, synapse number, synaptic plasticity, and memory formation. Conversely, HDAC2 deficiency resulted in increased synapse number and memory facilitation, similar to chronic HDACi treatment in mice. Notably, reduced synapse number and learning impairment of HDAC2-overexpressing mice were ameliorated by chronic HDACi treatment. Correspondingly, HDACi treatment failed to further facilitate memory formation in HDAC2-deficient mice. Furthermore, analysis of promoter occupancy revealed association of HDAC2 with the promoters of genes implicated in synaptic plasticity and memory formation. Together, our results suggest that HDAC2 plays a role in modulating synaptic plasticity and long-lasting changes of neural circuits, which in turn negatively regulates learning and memory. These observations encourage the development and testing of HDAC2-selective inhibitors for human diseases associated with memory impairment.
Rechargeable aqueous zinc-ion batteries are promising energy storage devices due to their high safety and low cost. However, they remain in their infancy because of the limited choice of positive electrodes with high capacity and satisfactory cycling performance. Furthermore, their energy storage mechanisms are not well established yet. Here we report a highly reversible zinc/sodium vanadate system, where sodium vanadate hydrate nanobelts serve as positive electrode and zinc sulfate aqueous solution with sodium sulfate additive is used as electrolyte. Different from conventional energy release/storage in zinc-ion batteries with only zinc-ion insertion/extraction, zinc/sodium vanadate hydrate batteries possess a simultaneous proton, and zinc-ion insertion/extraction process that is mainly responsible for their excellent performance, such as a high reversible capacity of 380 mAh g–1 and capacity retention of 82% over 1000 cycles. Moreover, the quasi-solid-state zinc/sodium vanadate hydrate battery is also a good candidate for flexible energy storage device.
Neurodegenerative diseases of the central nervous system are often associated with impaired learning and memory, eventually leading to dementia. An important aspect in pre-clinical research is the exploration of strategies to re-establish learning ability and access to long-term memories. By using a mouse model that allows temporally and spatially restricted induction of neuronal loss, we show here that environmental enrichment reinstated learning behaviour and re-established access to long-term memories after significant brain atrophy and neuronal loss had already occurred. Environmental enrichment correlated with chromatin modifications (increased histone-tail acetylation). Moreover, increased histone acetylation by inhibitors of histone deacetylases induced sprouting of dendrites, an increased number of synapses, and reinstated learning behaviour and access to long-term memories. These data suggest that inhibition of histone deacetylases might be a suitable therapeutic avenue for neurodegenerative diseases associated with learning and memory impairment, and raises the possibility of recovery of long-term memories in patients with dementia.
To the Editors-Electrochemical conversion of dinitrogen to ammonia in aqueous electrolyte solutions at high selectivity and rate requires a catalyst with unique properties. In particular, the surface of such a catalyst should exhibit higher affinity for nitrogen, as opposed to hydrogen, to facilitate the nitrogen reduction reaction (NRR) and suppress the hydrogen evolution reaction (HER). Detailed density functional theory (DFT) studies by Skúlason and co-workers 3 suggest that this is hardly possible with most metals traditionally considered in electrocatalytic research. One metal not included in the analysis in ref. 3 and long known to be a very poor HER catalyst 4 is bismuth, which was very recently introduced by Hao et al. 1 as an efficient NRR catalyst in their report in Nature Catalysis. However, DFT data reported in the same paper clearly indicate that N2 adsorption on various bismuth surfaces is highly thermodynamically unfavourable with an essentially insurmountable energy barrier of more than 2.7 eV. Nevertheless, despite this contradiction, the highly impressive experimental data on the Bicatalysed NRR reported by Hao et al. 1 present the best performances reported to date and therefore would represent important progress in this field. This prompted us to attempt to reproduce these experimental results. Details of our materials and equipment are provided
Graphical Abstract Highlights d Super-resolution live-cell imaging up to 266 fps at 97-nm resolution d Hitchhiking interactions among organelles remodel ER and mitochondrial networks d ER-mitochondrion contacts promote coalescence of mitochondrial membranes d Collision of late endosomes or lysosomes carried along microtubules split ER tubules
Aqueous zinc‐ion batteries have been considered as potential energy storage devices owing to their high safety and low cost. Traditional zinc‐ion batteries often implement a typical Zn2+ insertion/extraction mechanism. Compared with traditional Zn2+ insertion/extraction mechanism, supercapacitor‐liked dual‐ion mechanism often endow the batteries with higher operating voltage, better rate capability, and longer cycle life. Herein, aqueous Zn/polyaniline batteries are developed, which can combine the Zn2+ insertion/extraction and dual‐ion mechanisms. The Zn/polyaniline batteries deliver excellent electrochemical performance, especially a long cycle life up to 3000 cycles with high‐capacity retention of 92%. This hybrid mechanism provides a promising battery chemistry. Furthermore, Zn/polyaniline batteries can be assembled into quasi‐solid‐state soft‐packaged and cable‐type configurations and display stable electrochemical performance even under different bending states, showing potential applications for flexible electronics.
Substrate specificity of SARS-CoV and SARS-CoV-2 M pro s. To determine the SARS-CoV M pro and SARS-CoV-2 M pro substrate preferences, we applied a HyCoSuL approach. The library consists of
Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.
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