Role of Left-Hand Cut Contributions on Pole Extractions from Lattice Data: Case Study for T_{cc}(3875)^{+}.

We discuss recent lattice data for the T_{cc}(3875)^{+} state to stress, for the first time, a potentially strong impact of left-hand cuts from the one-pion exchange on the pole extraction for near-threshold exotic states. In particular, if the left-hand cut is located close to the two-particle threshold, which happens naturally in the DD^{*} system for the pion mass exceeding its physical value, the effective-range expansion is valid only in a very limited energy range up to the cut and as such is of little use to reliably extract the poles. Then, an accurate extraction of the pole locations requires the one-pion exchange to be implemented explicitly into the scattering amplitudes.

Developing antisense oligonucleotides for a mutation-induced, ultra-rare neurological disorder using patient-derived cellular models.

Mutations in the gene are the cause of an ultra-rare neurological disorder characterized by intellectual disability, impaired speech, motor delay, and hypotonia evolving to spasticity, central sleep apnea, and premature death (SPG49 or HSAN9; OMIM: 615031). Little is known about the biological function of TECPR2, and there are currently no available disease-modifying therapies for this disease. Here we describe implementation of an antisense oligonucleotide (ASO) exon-skipping strategy targeting c.

Is the existence of a J/ψJ/ψ bound state plausible?

In a recent measurement LHCb reported pronounced structures in the J/ψJ/ψ spectrum. One of the various possible explanations of those is that they emerge from non-perturbative interactions of vector charmonia. It is thus important to understand whether it is possible to form a bound state of two charmonia interacting through the exchange of gluons, which hadronise into two pions at the longest distance.

Erratum: Coupled-Channel Interpretation of the LHCb Double-J/ψ Spectrum and Hints of a New State Near the J/ψJ/ψ Threshold [Phys. Rev. Lett. 126, 132001 (2021)].

This corrects the article DOI: 10.1103/PhysRevLett.126.

Coupled-Channel Interpretation of the LHCb Double-J/ψ Spectrum and Hints of a New State Near the J/ψJ/ψ Threshold.

Recently, the LHCb Collaboration reported pronounced structures in the invariant mass spectrum of J/ψ pairs produced in proton-proton collisions at the Large Hadron Collider. In this Letter, we argue that the data can be very well described within two variants of a coupled-channel approach employing T matrices consistent with unitarity: (i) with just two channels, J/ψJ/ψ and ψ(2S)J/ψ, as long as energy-dependent interactions in these channels are allowed, or (ii) with three channels J/ψJ/ψ, ψ(2S)J/ψ, and ψ(3770)J/ψ with just constant contact interactions. Both formulations hint at the existence of a near-threshold state in the J/ψJ/ψ system with the quantum numbers J^{PC}=0^{++} or 2^{++}, which we refer to as X(6200).

disrupts intracellular lipid homeostasis in human iPSC-derived glia.

The allele of the apolipoprotein E gene () has been established as a genetic risk factor for many diseases including cardiovascular diseases and Alzheimer's disease (AD), yet its mechanism of action remains poorly understood. APOE is a lipid transport protein, and the dysregulation of lipids has recently emerged as a key feature of several neurodegenerative diseases including AD. However, it is unclear how APOE4 perturbs the intracellular lipid state.

PICALM Rescues Endocytic Defects Caused by the Alzheimer's Disease Risk Factor APOE4.

The ε4 allele of apolipoprotein E (APOE4) is a genetic risk factor for many diseases, including late-onset Alzheimer's disease (AD). We investigate the cellular consequences of APOE4 in human iPSC-derived astrocytes, observing an endocytic defect in APOE4 astrocytes compared with their isogenic APOE3 counterparts. Given the evolutionarily conserved nature of endocytosis, we built a yeast model to identify genetic modifiers of the endocytic defect associated with APOE4.

Probing Synaptic Signaling with Optogenetic Stimulation and Genetically Encoded Calcium Reporters.

Optogenetics provides a powerful approach for investigating neuronal electrophysiology at the scale required for drug discovery applications. Probing synaptic function with high throughput using optogenetics requires robust tools that enable both precise stimulation of and facile readout of synaptic activity. Here we describe two functional assays to achieve this end: (1) a pre-synaptic calcium assay that utilizes the channelrhodopsin, CheRiff, patterned optogenetic stimulus, and the pre-synaptically targeted calcium reporter jRGECO1a to monitor pre-synaptic changes in calcium influx and (2) a synaptic transmission assay in which CheRiff and cytosolic jRGECO1a are expressed in non-overlapping sets of neurons, enabling pre-synaptic stimulation and post-synaptic readout of activity.

Extraction of the Neutron Charge Radius from a Precision Calculation of the Deuteron Structure Radius.

We present a high-accuracy calculation of the deuteron structure radius in chiral effective field theory. Our analysis employs the state-of-the-art semilocal two-nucleon potentials and takes into account two-body contributions to the charge density operators up to fifth order in the chiral expansion. The strength of the fifth-order short-range two-body contribution to the charge density operator is adjusted to the experimental data on the deuteron charge form factor.

Interpretation of the LHCb P_{c} States as Hadronic Molecules and Hints of a Narrow P_{c}(4380).

Three hidden-charm pentaquark P_{c} states, P_{c}(4312), P_{c}(4440), and P_{c}(4457) were revealed in the Λ_{b}^{0}→J/ψpK^{-} process measured by LHCb using both run I and run II data. Their nature is under lively discussion, and their quantum numbers have not been determined. We analyze the J/ψp invariant mass distributions under the assumption that the crossed-channel effects provide a smooth background.

Lipidomic Analysis of α-Synuclein Neurotoxicity Identifies Stearoyl CoA Desaturase as a Target for Parkinson Treatment.

In Parkinson's disease (PD), α-synuclein (αS) pathologically impacts the brain, a highly lipid-rich organ. We investigated how alterations in αS or lipid/fatty acid homeostasis affect each other. Lipidomic profiling of human αS-expressing yeast revealed increases in oleic acid (OA, 18:1), diglycerides, and triglycerides.

FKBP12 contributes to α-synuclein toxicity by regulating the calcineurin-dependent phosphoproteome.

Calcineurin is an essential Ca-dependent phosphatase. Increased calcineurin activity is associated with α-synuclein (α-syn) toxicity, a protein implicated in Parkinson's Disease (PD) and other neurodegenerative diseases. Calcineurin can be inhibited with Tacrolimus through the recruitment and inhibition of the 12-kDa proline isomerase FK506-binding protein (FKBP12).

In Situ Peroxidase Labeling and Mass-Spectrometry Connects Alpha-Synuclein Directly to Endocytic Trafficking and mRNA Metabolism in Neurons.

Synucleinopathies, including Parkinson's disease (PD), are associated with the misfolding and mistrafficking of alpha-synuclein (α-syn). Here, using an ascorbate peroxidase (APEX)-based labeling method combined with mass spectrometry, we defined a network of proteins in the immediate vicinity of α-syn in living neurons to shed light on α-syn function. This approach identified 225 proteins, including synaptic proteins, proteins involved in endocytic vesicle trafficking, the retromer complex, phosphatases and mRNA binding proteins.

Genome-Scale Networks Link Neurodegenerative Disease Genes to α-Synuclein through Specific Molecular Pathways.

Numerous genes and molecular pathways are implicated in neurodegenerative proteinopathies, but their inter-relationships are poorly understood. We systematically mapped molecular pathways underlying the toxicity of alpha-synuclein (α-syn), a protein central to Parkinson's disease. Genome-wide screens in yeast identified 332 genes that impact α-syn toxicity.

Calcineurin determines toxic versus beneficial responses to α-synuclein.

Calcineurin (CN) is a highly conserved Ca(2+)-calmodulin (CaM)-dependent phosphatase that senses Ca(2+) concentrations and transduces that information into cellular responses. Ca(2+) homeostasis is disrupted by α-synuclein (α-syn), a small lipid binding protein whose misfolding and accumulation is a pathological hallmark of several neurodegenerative diseases. We report that α-syn, from yeast to neurons, leads to sustained highly elevated levels of cytoplasmic Ca(2+), thereby activating a CaM-CN cascade that engages substrates that result in toxicity.

Identification and rescue of α-synuclein toxicity in Parkinson patient-derived neurons.

The induced pluripotent stem (iPS) cell field holds promise for in vitro disease modeling. However, identifying innate cellular pathologies, particularly for age-related neurodegenerative diseases, has been challenging. Here, we exploited mutation correction of iPS cells and conserved proteotoxic mechanisms from yeast to humans to discover and reverse phenotypic responses to α-synuclein (αsyn), a key protein involved in Parkinson's disease (PD).

Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast.

Aβ (beta-amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown.

Abashian-Booth-Crowe effect in basic double-pionic fusion: a new resonance?

We report on an exclusive and kinematically complete high-statistics measurement of the basic double-pionic fusion reaction pn→dπ(0)π(0) over the full energy region of the ABC effect, a pronounced low-mass enhancement in the ππ-invariant mass spectrum. The measurements, which cover also the transition region to the conventional t-channel ΔΔ process, were performed with the upgraded WASA detector setup at COSY. The data reveal the Abashian-Booth-Crowe effect to be uniquely correlated with a Lorentzian energy dependence in the integral cross section.

Clubbed thiazoles by MAOS: a novel approach to cyclin-dependent kinase 5/p25 inhibitors as a potential treatment for Alzheimer's disease.

A novel clubbed triazolyl thiazole series of cdk5/p25 inhibitors, potentially useful for the treatment of Alzheimer's disease, is disclosed. Evaluation of the SAR of substitution within these series has allowed the identification of a range of compounds which significantly reduce brain cdk5/p25 and thus have potential as possible treatments for Alzheimer's disease.

[Transport of RNA from rat liver cell nuclei in vitro. Effect of superoxide dismutase on the release of rapidly labeled RNA from isolated nuclei].

Purified superoxide dismutase from beaf and rat liver cytosol was found to inhibit in vitro a release of the newly synthesized poly(A)-containing RNA from isolated hepatocyte nuclei in a cell-free system. The inhibition was concentration-dependent. Similar effect was observed with Cu2+ and coppertyrosine complex, which possess SOD-like type catalytic activity.