Bounds on Heavy Axions with an X-Ray Free Electron Laser.

We present new exclusion bounds obtained at the European X-Ray Free Electron Laser facility (EuXFEL) on axionlike particles in the mass range 10^{-3}  eV≲m_{a}≲10^{4}  eV. Our experiment exploits the Primakoff effect via which photons can, in the presence of a strong external electric field, decay into axions, which then convert back into photons after passing through an opaque wall. While similar searches have been performed previously at a third-generation synchrotron [Yamaji et al.

Heroin Regulates the Voltage-Gated Sodium Channel Auxiliary Subunit, SCN1b, to Modulate Nucleus Accumbens Medium Spiny Neuron Intrinsic Excitability and Cue-Induced Heroin Seeking.

Self-administration of addictive substances like heroin can couple the rewarding/euphoric effects of the drug with drug-associated cues, and opioid cue reactivity contributes to relapse vulnerability in abstinent individuals recovering from an opioid use disorder (OUD). Opioids are reported to alter the intrinsic excitability of medium spiny neurons (MSNs) in the nucleus accumbens (NAc), a key brain reward region linked to drug seeking, but how opioids alter NAc MSN neuronal excitability and the impact of altered MSN excitability on relapse-like opioid seeking remain unclear. Here, we discovered that self-administered, but not experimenter-administered, heroin reduced NAc protein levels of the voltage-gated sodium channel auxiliary subunit, SCN1b, in male and female rats.

Epigenetic control of an auxiliary subunit of voltage-gated sodium channels regulates the strength of drug-cue associations and relapse-like cocaine seeking.

Background: Repeated use of illicit drugs produces long-lasting and prepotent drug-cue associations that increase vulnerability for relapse in individuals with a substance use disorder. Epigenetic factors, like histone deacetylase 5 (HDAC5), play a key role in regulating the formation of drug-cue associations, but the underlying mechanisms remain unclear.

Methods: We used a combination of molecular biology, cultured cells, tandem mass spectrometry, deacetylase activity measurements, co-immunoprecipitation, and molecular dynamics simulations to assess HDAC5 structure-activity relationships.

Plastic responses to past environments shape adaptation to novel selection pressures.

Phenotypic plasticity may pave the way for rapid adaptation to newly encountered environments. Although it is often contested, there is growing evidence that initial plastic responses of ancestral populations to new environmental cues may promote subsequent adaptation. However, we do not know whether plasticity to cues present in the ancestral habitat (past-cue plasticity) can facilitate adaptation to novel cues.

A long noncoding eRNA forms R-loops to shape emotional experience-induced behavioral adaptation.

Emotional experiences often evoke neural plasticity that supports adaptive changes in behavior, including maladaptive plasticity associated with mood and substance use disorders. These adaptations are supported in part by experience-dependent activation of immediate-early response genes, such as (neuronal PAS domain protein 4). Here we show that a conserved long noncoding enhancer RNA (lnc-eRNA), transcribed from an activity-sensitive enhancer, produces DNA:RNA hybrid R-loop structures that support three-dimensional chromatin looping between enhancer and proximal promoter and rapid gene induction.

The activity-regulated cytoskeleton-associated protein (Arc) functions in a cell type- and sex-specific manner in the adult nucleus accumbens to regulate non-contingent cocaine behaviors.

Repeated cocaine use produces adaptations in brain function that contribute to long-lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity-regulated cytoskeleton-associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)-a brain region linked to CUD-related behavior. We show here that repeated, non-contingent cocaine administration in global Arc KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience-dependent sensitization of conditioned place preference (CPP).

NPAS4 supports cocaine-conditioned cues in rodents by controlling the cell type-specific activation balance in the nucleus accumbens.

Powerful associations that link drugs of abuse with cues in the drug-paired environment often serve as prepotent relapse triggers. Drug-associated contexts and cues activate ensembles of nucleus accumbens (NAc) neurons, including D1-class medium spiny neurons (MSNs) that typically promote, and D2-class MSNs that typically oppose, drug seeking. We found that in mice, cocaine conditioning upregulated transiently the activity-regulated transcription factor, Neuronal PAS Domain Protein 4 (NPAS4), in a small subset of NAc neurons.

Prolonged HPA axis dysregulation in postpartum depression associated with adverse early life experiences: A cross-species translational study.

Childhood and adolescent stress increase the risk of postpartum depression (PPD), often providing an increased probability of treatment refractoriness. Nevertheless, the mechanisms linking childhood/adolescent stress to PPD remain unclear. Our study investigated the longitudinal effects of adolescent stress on the hypothalamic-pituitary-adrenal (HPA) axis and postpartum behaviors in mice and humans.

Bone biochemistry in children with fractures presenting with non-accidental injury.

Background: In cases of fractures in children with suspicion of non-accidental injury (NAI), biochemical markers of calcium homeostasis should be performed.

Objectives: To describe the pattern of biochemistry in children with fractures NAI is suspected.

Participants And Setting: Children ≤2 years of age who had undergone a skeletal survey as part of a child protection investigation where 1/+ fracture was identified over a ten-year period (2012-2021) at the Royal Hospital for Children, Glasgow.

A Change in Scope: Endoscopic Retrograde Cholangiopancreatography via a Gastroscope in Billroth II Gastrojejunostomy.

Previous gastric procedures often make endoscopic interventions challenging. Our case study focuses specifically on performing an endoscopic retrograde cholangiopancreatography (ERCP) through a gastroscope (EVIS EXERA III GIF-HQ190, Olympus, Center Valley, USA) in a patient with a history of Billroth II gastrojejunostomy. Successful ERCP in Billroth II using a gastroscope with traditional ERCP instrumentation has been very rarely reported in case reports in the literature review.

Redox Triggers Guest Release and Uptake Across a Series of Azopyridine-Based Metal-Organic Capsules.

Precise control over guest release and recapture using external stimuli is a valuable goal, potentially enabling new modes of chemical purification. Including redox moieties within the ligand cores of molecular capsules to trigger the release and uptake of guests has proved effective, but this technique is limited to certain capsules and guests. Herein, the construction of a series of novel metal-organic capsules from ditopic, tritopic, and tetratopic ligands is demonstrated, all of which contain redox-active azo groups coordinated to Fe centers.

Examination of New York City Transit's Bus and Subway Ridership Trends During the COVID-19 Pandemic.

The New York City metropolitan area was hard hit by COVID-19, and the pandemic brought with it unprecedented challenges for New York City Transit. This paper addresses the techniques used to estimate dramatically changing ridership, at a time when previously dependable sources suddenly became unavailable (e.g.

Finding and treating early-stage HIV infections: A cost-effectiveness analysis of the study in Lima, Peru.

Background: , a treatment-as-prevention intervention among men who have sex with men and transgender women in Lima, Peru, was developed to identify HIV during early primary infection (<3 months from acquisition) through monthly serologic assays and HIV RNA tests. Newly diagnosed individuals were rapidly linked to care and offered to initiate ART. In this study we sought to study the cost-effectiveness of compared to the standard of care (SOC) for HIV testing and initiation of treatment.

Genetic assimilation of ancestral plasticity during parallel adaptation to zinc contamination in Silene uniflora.

Phenotypic plasticity in ancestral populations is hypothesized to facilitate adaptation, but evidence is piecemeal and often contradictory. Further, whether ancestral plasticity increases the probability of parallel adaptive changes has not been explored. The most general finding is that ancestral responses to a new environment are reversed following adaptation (known as reversion).

Ion Microscope Imaging Mass Spectrometry Using a Timepix3-Based Optical Camera.

Ion microscopy allows for high-throughput mass spectrometry imaging. In order to resolve congested mass spectra, a high degree of timing precision is required from the microscope detector. In this paper we present an ion microscope mass spectrometer that uses a Timepix3 hybrid pixel readout with an optimal 1.

Mapping Ligand Interactions of Bromodomains BRD4 and ATAD2 with FragLites and PepLites─Halogenated Probes of Druglike and Peptide-like Molecular Interactions.

The development of ligands for biological targets is critically dependent on the identification of sites on proteins that bind molecules with high affinity. A set of compounds, called FragLites, can identify such sites, along with the interactions required to gain affinity, by X-ray crystallography. We demonstrate the utility of FragLites in mapping the binding sites of bromodomain proteins BRD4 and ATAD2 and demonstrate that FragLite mapping is comparable to a full fragment screen in identifying ligand binding sites and key interactions.

Impact of a prescriber and patient educational intervention on discharge analgesia prescribing and hospital readmission rates following elective unilateral total hip and knee arthroplasty.

Introduction: Pain management after elective, unilateral total hip and knee arthroplasty (THA and TKA) should use a multimodal approach. At discharge, challenges include ensuring correct prescribing practices to optimise analgesia and rationalise opioid use as well as ensuring patients are adequately educated to take these medications safely and effectively in the community. This audit cycle reports on a prescriber and patient education intervention using printed guidelines, educational outreach and prescription standardisation along with a patient information sheet to address the high unplanned readmission rate following THA and TKA at our institution.

Rapid Parallel Adaptation to Anthropogenic Heavy Metal Pollution.

The impact of human-mediated environmental change on the evolutionary trajectories of wild organisms is poorly understood. In particular, capacity of species to adapt rapidly (in hundreds of generations or less), reproducibly and predictably to extreme environmental change is unclear. Silene uniflora is predominantly a coastal species, but it has also colonized isolated, disused mines with phytotoxic, zinc-contaminated soils.

Fast track dialysis: Improving emergency department and hospital throughput for patients requiring hemodialysis.

Objective: To describe the impact of a novel communication and triage pathway called fast track dialysis (FTD) on the length of stay (LOS), resource utilization, and charges for unscheduled hemodialysis for end stage renal disease (ESRD) patients presenting to the emergency department (ED).

Methods: Prospective and retrospective cohorts of ESRD patients meeting requirements of routine or urgent hemodialysis at a tertiary academic hospital from September 25th, 2016 to September 25th, 2018 in 1 year cohorts. Two sample t-tests were used to compare most outcomes of the cohorts with a Mann-Whitney U test used for skewed data.

Discriminative SKP2 Interactions with CDK-Cyclin Complexes Support a Cyclin A-Specific Role in p27KIP1 Degradation.

The SCF ubiquitin ligase relieves G1 checkpoint control of CDK-cyclin complexes by promoting p27KIP1 degradation. We describe reconstitution of stable complexes containing SKP1-SKP2 and CDK1-cyclin B or CDK2-cyclin A/E, mediated by the CDK regulatory subunit CKS1. We further show that a direct interaction between a SKP2 N-terminal motif and cyclin A can stabilize SKP1-SKP2-CDK2-cyclin A complexes in the absence of CKS1.