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The quark structure of the f₀(980) hadron is still unknown after 50 years of its discovery. Here, the CMS Collaboration reports a measurement of the elliptic flow of the f₀(980) state in proton-lead collisions at a nucleon-nucleon centre-of-mass energy of 8.16 TeV, providing strong evidence that the state is an ordinary meson.

John et al. show that upon classical activation, macrophages undergo nitric oxide-driven reprogramming of nucleotide metabolism, which affects immune functions and responses.

The development of neuroprotective drugs has been hampered by the fact that many drugs interfere with normal brain functions. Stuart Lipton describes strategies for drug development that are based on the principle that drugs should interact with their target only during states of pathological activation.

Excessive glutamate receptor activity, principally of theN-methyl-D-aspartate (NMDA) subtype, contributes to neuronal damage in a large number of neurologic disorders, including dementia. Until recently, however, NMDA receptor antagonists had all failed in clinical trials. Stuart Lipton reviews the mechanism of action that led to the clinical approval of the first NMDA receptor antagonist, memantine, which has become the newest and one of the best-selling drugs for Alzheimer's disease.

The theory that haemoglobin evolved to carry oxygen around the body may need a rethink in light of another way in which molecules related to nitric oxide, released from haemoglobin, help the brain control respiration.

Aspirin may prevent neuronal cell death by inhibiting NF-κB, but what of NF-κB'S reported neuroprotective role?

This study introduces an in vivo protein footprinting method, revealing structural changes in proteome during progressing AD. It demonstrates these changes occur before expression alterations, advancing understanding of protein misfolding mechanisms.

Large genome-wide meta-analysis of clinically diagnosed late-onset Alzheimer’s disease (LOAD) from 94,437 individuals identifies new LOAD risk loci and implicates Aβ formation, tau protein binding, immune response and lipid metabolism.

Bacterial remineralization of algal organic matter promotes algal growth but is rarely quantified. Here, Mayali et al. quantify bacterial incorporation of algal-derived organic carbon and nitrogen, and algal incorporation of remineralized carbon and nitrogen, for 15 bacterial co-cultures growing with the diatom Phaeodactylum tricornutum to identify functional guilds of metabolic interactions.

Aminoadamantane compounds, delivered to cells via binding to viroporin channels, induce S-nitrosylation of the ACE2 protein, inhibiting binding to SARS-CoV-2 spike protein and viral infection.

Here the authors demonstrate that de novo DNA methylation mediated by DNMT3B is regulated by nitric oxide (NO). They also isolate a unique modulator (DBIC) that inhibits S-nitrosylation of DNMT3B, which mitigates cell proliferation and tumorigenic conversion in vivo.

Alzheimer's disease is linked to metabolic syndrome and Type-2 diabetes, but the mechanism behind this association is unclear. Here, the authors show that elevated glucose and amyloid ß work together to increase nitrosative stress, leading to aberrant mitochondrial activity and synaptic dysfunction.

Human MEF2C haploinsufficiency results in Autism Spectrum Disorder (ASD), but it is unclear if the same is true in mice. Here, the authors show that Mef2c ^+/− mice have behavioral defects and neuronal abnormalities similar to ASD, and symptoms can be ameliorated with the new drug, NitroSynapsin.

The most up-to-date combination of results on the properties of the Higgs boson is reported, which indicate that its properties are consistent with the standard model predictions, within the precision achieved to date.

The CMS Collaboration reports evidence for off-shell Higgs boson contributions in the production of Z boson pairs, and measures the width of the Higgs boson, which is inversely related to its lifetime.

The CMS Collaboration reports the study of three simultaneous hard interactions between quarks and gluons in proton–proton collisions. This manifests through the concurrent production of three J/ψ mesons, which consist of a charm-quark–antiquark pair.

Meta-analysis of genome-wide association studies on Alzheimer’s disease and related dementias identifies new loci and enables generation of a new genetic risk score associated with the risk of future Alzheimer’s disease and dementia.

In a mouse model of Huntington's disease, synaptic activation of NMDA receptors induces the formation of huntingtin-containing inclusions, rendering neurons more resistant to death in vivo and in vitro. In contrast, stimulation of extrasynaptic NMDA receptors increases neuronal vulnerability by preventing inclusion formation.

Cardiolipin is a phospholipid component of the inner mitochondrial membrane. Here the authors demonstrate that cardiolipin interacts with mutant α-synuclein, and that impaired cardiolipin function can lead to spread of α-synuclein between neurons.

Cerebrovascular changes and astrogliosis occur in Alzheimer’s disease (AD). Using an in vivo phage display technique, the authors identified a peptide that upon systematic administration, can home to brain endothelial cells and astrocytes in mouse models of AD at the early stages of the disease.

Huntington's disease is a neurodegenerative disorder associated with glutamate receptor dysfunction. Now Isabel Pérez-Otaño and colleagues report that the HTT protein that aggregates in the brains of individuals with the disease disrupts the ability of the adaptor protein PACSIN1 to keep the glutamate receptor subunit GluN3A away from the surface of neurons.

Larsen et al. find that presynaptic NMDA receptors at neocortical synapses are heteromeric receptors containing the developmentally expressed NR3A subunit. Their data also indicate that NR3A-containing presynaptic NMDARs mediate tonic presynaptic activity, synaptic transmission and spike timing–dependent plasticity.

Synaptic abnormalities and learning dysfunction are prominent characteristics of Down's syndrome. Now Huaxi Xu and colleagues show that expression of the protein SNX27 is reduced in Down's syndrome brains and that restoring its expression can ameliorate learning dysfunction in a mouse model of the disease.

The clot-busting drug tissue plasminogen activator (tPA) is currently the only FDA-approved therapy for acute stroke. However, increasing evidence suggests that tPA can also contribute to excitotoxic neuronal damage in animal models of stroke. (pages 59–64)

How neurons might protect themselves from free radical damage has been a mystery. A new study suggests that synaptic NMDA receptor activity affords neuroprotection by regulating oxidation-reduction (redox) pathways via transcription.

Neuroprotection requires a paradigm shift in drug development.