Timing of reproduction modifies transgenerational effects of chronic exposure to stressors in an annual vertebrate.

Stressful environmental conditions can shape both an individual's phenotype and that of its offspring. However, little is known about transgenerational effects of chronic (as opposed to acute) stressors, nor whether these vary across the breeding lifespan of the parent. We exposed adult female (F0 generation) three-spined sticklebacks () to chronic environmental stressors and compared their reproductive allocation with that of non-exposed controls across early, middle and late clutches produced within the single breeding season of this annual population.

Solitary symbolic play, object substitution and peer role play skills at age 3 predict different aspects of age 7 structural language abilities in a matched sample of autistic and non-autistic children.

Backgrounds And Aims: Early symbolic play abilities are closely related to long-term language development for both autistic and non-autistic children, but few studies have explored these relations for different dimensions of pretence and of language. The current study explores carer-reported measures of solitary symbolic play, object substitution and peer role play abilities at age 3, and their respective relations with parent-reported semantics, syntax and narrative abilities at age 7 for both autistic and non-autistic children.

Methods: We conducted secondary data analyses exploring links between different aspects of pretence and of language on the Longitudinal Study of Australian Children population cohort.

Effect of current density on the solid electrolyte interphase formation at the lithium∣LiPSCl interface.

Understanding the chemical composition and morphological evolution of the solid electrolyte interphase (SEI) formed at the interface between the lithium metal electrode and an inorganic solid-state electrolyte is crucial for developing reliable all-solid-state lithium batteries. To better understand the interaction between these cell components, we carry out X-ray photoemission spectroscopy (XPS) measurements during lithium plating on the surface of a LiPSCl solid-state electrolyte pellet using an electron beam. The analyses of the XPS data highlight the role of Li plating current density on the evolution of a uniform and ionically conductive (i.

Potential impacts of prolonged absence of influenza virus circulation on subsequent epidemics.

Background: During the first two years of the COVID-19 pandemic, the circulation of seasonal influenza viruses was unprecedentedly low. This led to concerns that the lack of immune stimulation to influenza viruses combined with waning antibody titres could lead to increased susceptibility to influenza in subsequent seasons, resulting in larger and more severe epidemics.

Methods: We analyzed historical influenza virus epidemiological data from 2003-2019 to assess the historical frequency of near-absence of seasonal influenza virus circulation and its impact on the size and severity of subsequent epidemics.

Antimicrobials in dog-to-dog bite wounds: A retrospective study of 1526 dog bite events (1999-2019).

Background: Although dog-to-dog bite wounds (DBW) are common, few studies worldwide have evaluated antimicrobial usage patterns or appropriateness of use.

Objectives: Report frequency and results of DBW cultures, including antimicrobial susceptibility patterns. Determine the most commonly prescribed antimicrobials and their appropriateness for the treatment of DBW, and if antimicrobial importance is associated with wound severity, clinic type or year.

Feedforward growth rate control mitigates gene activation burden.

Heterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here, we introduce a feedforward controller that actuates growth rate upon activation of a gene of interest (GOI) to compensate for such a burden. The controller achieves this by activating a modified SpoT enzyme (SpoTH) with sole hydrolysis activity, which lowers ppGpp level and thus increases growth rate.

Proline-Rich Region II (PRR2) Plays an Important Role in Tau-Glycan Interaction: An NMR Study.

(1) Background: Prion-like transcellular spreading of tau pathology in Alzheimer's disease (AD) is mediated by tau binding to the cell-surface glycan heparan sulfate (HS). However, the structural determinants for tau-HS interaction are not well understood. (2) Methods and Results: Binding-site mapping using NMR showed two major binding regions in full-length tau responsible for heparin interaction.

Sequestration of a dual function DNA-binding protein by CRP.

Although the mechanism by which the cyclic AMP receptor protein (CRP) regulates global gene transcription has been intensively studied for decades, new discoveries remain to be made. Here, we report that, during rapid growth, CRP associates with both the well-conserved, dual-function DNA-binding protein peptidase A (PepA) and the cell membrane. These interactions are not present under nutrient-limited growth conditions, due to post-translational modification of three lysines on a single face of CRP.

Whole-genome sequencing of chronic lymphocytic leukemia identifies subgroups with distinct biological and clinical features.

The value of genome-wide over targeted driver analyses for predicting clinical outcomes of cancer patients is debated. Here, we report the whole-genome sequencing of 485 chronic lymphocytic leukemia patients enrolled in clinical trials as part of the United Kingdom's 100,000 Genomes Project. We identify an extended catalog of recurrent coding and noncoding genetic mutations that represents a source for future studies and provide the most complete high-resolution map of structural variants, copy number changes and global genome features including telomere length, mutational signatures and genomic complexity.

Social withdrawal in Parkinson's disease: A scoping review.

Background: Parkinson's disease (PD) can interfere with individuals' social functioning and lead to social withdrawal. Social withdrawal may result in negative outcomes for persons with PD and their caregivers, such as decreased quality of life. It is necessary to understand the nature of social withdrawal in PD in order to develop strategies to address this issue and prevent negative outcomes.

On the Relative Importance of Li Bulk Diffusivity and Interface Morphology in Determining the Stripped Capacity of Metallic Anodes in Solid-State Batteries.

Lithium metal self-diffusion is too slow to sustain large current densities at the interface with a solid electrolyte, and the resulting formation of voids on stripping is a major limiting factor for the power density of solid-state cells. The enhanced morphological stability of some lithium alloy electrodes has prompted questions on the role of lithium diffusivity in these materials. Here, the lithium diffusivity in Li-Mg alloys is investigated by an isotope tracer method, revealing that the presence of magnesium slows down the diffusion of lithium.

Dinuclear Complexes of Uranyl, Neptunyl, and Plutonyl: Structures and Oxidation States Revealed by Experiment and Theory.

Dinuclear perchlorate complexes of uranium, neptunium, and plutonium were characterized by reactivity and DFT, with results revealing structures containing pentavalent, hexavalent, and heptavalent actinyls, and actinyl-actinyl interactions (AAIs). Electrospray ionization produced native complexes [(AnO)(ClO)] for An:An = U:U, Np:Np, Pu:Pu, and Np:Pu, which are intuitively formulated as actinyl(V) perchlorates. However, DFT identified lower-energy structures [(AnO)(AnO)(ClO)(ClO)] comprising a perchlorate fragmented to ClO, actinyl(VI) cation AnO, and neutral AnO.

Posterior Quadrant Disconnection Procedure for Intractable Epilepsy: A Case Series of 5 Young Pediatric Patients.

Background: Posterior quadrant disconnection (PQD) has been described as a treatment for patients with refractory posterior quadrant subhemispheric epilepsy. Surgical outcomes are difficult to interpret because of limited literature.

Objective: To provide insight regarding the operative technique and postsurgical seizure freedom in young pediatric patients who underwent surgical disconnection for the treatment of posterior quadrant subhemispheric epilepsy at our institution.

Predictors of anxiety in Parkinson's disease: results from a 3-year longitudinal cohort study.

Introduction: Anxiety symptoms are the most common neuropsychiatric manifestation of Parkinson's disease (PD), contributing to decreased quality of life. Few longitudinal studies in PD samples have examined correlates of anxiety symptoms over time. Understanding predictor variables may help to identify novel targets for reducing anxiety in PD.

Motor Responses in Pediatric Pompe Disease in the ADVANCE Participant Cohort.

Background: ADVANCE (NCT01526785) presented an opportunity to obtain a more nuanced understanding of motor function changes in treatment-experienced children with Pompe disease receiving 4000L-production-scale alglucosidase alfa for 52 weeks.

Objective: To estimate minimal detectable change (MDC) and effect size on Gross Motor Function Measure-88 (GMFM-88) after 52 weeks of 4000L alglucosidase alfa (complete data N =  90).

Methods: The GMFM-88 mean total % score changes, MDC, and effect size were analyzed post hoc by Pompe Motor Function Level at enrollment, age groups at enrollment, and fraction of life on pre-study 160L-production-scale alglucosidase alfa.

Challenges associated with test dose pharmacokinetic predictions of high dose melphalan exposure in patients with multiple myeloma.

Aim: To evaluate the accuracy of melphalan test dose pharmacokinetic (PK) predictions of the subsequent high dose (HDM) area under the concentration-versus-time curve (AUC) and to identify sources of prediction error (PE).

Methods: A prospective multicentre PK study was conducted in 40 myeloma patients of median age 60 (range:35-71) years using a 20 mg/m test dose administered 1-3 days prior to HDM (predominantly 180 mg/m). PK data were collected post the test and high doses to compare predicted versus actual AUCs determined using the trapezoidal rule.

A review of levator ani avulsion after childbirth: Incidence, imaging and management.

Key Content • Levator ani muscle (LAM) avulsion injury occurs occultly during childbirth, most commonly during operative vaginal deliveries. • Injuries of levator ani have long term sequelae for pelvic floor health. As life expectancy increases the burden of disease upon urogynaecology services will need to be considered.

Covalent fragment inhibits intramembrane proteolysis.

Alzheimer's disease (AD) is a serious public health crisis with only one current modifying treatment. The reduction of amyloid load by targeting γ-secretase (GS) has been a leading approach in AD drug discovery and development. Despite the focus on GS inhibition, multiple GS inhibitors (GSIs) have failed in clinical trials as a result of side effects including exacerbated cognitive decline.

Vibrio cholerae high cell density quorum sensing activates the host intestinal innate immune response.

Quorum sensing fundamentally alters the interaction of Vibrio cholerae with aquatic environments, environmental hosts, and the human intestine. At high cell density, the quorum-sensing regulator HapR represses not only expression of cholera toxin and the toxin co-regulated pilus, virulence factors essential in human infection, but also synthesis of the Vibrio polysaccharide (VPS) exopolysaccharide-based matrix required for abiotic and biotic surface attachment. Here, we describe a feature of V.

Complete Genome Sequence of Microbacterium foliorum Bacteriophage Librie.

Bacteriophage Librie was isolated from a soil sample from Clarksville, TN, using the bacterium Microbacterium foliorum. Librie has a 39,941 bp genome with 62 predicted protein-coding genes and 1 predicted gene for tRNA. Based on its gene content similarity to actinobacteriophages, Librie is grouped with phages in cluster EA5.

Systems approach to enhance Lynch syndrome diagnosis through tumour testing.

Background: Guidelines recommend universal mismatch repair (MMR) tumour testing of colorectal adenocarcinomas (CRCs) to screen for Lynch syndrome (LS). However, its implementation remains disjointed and referral for genetic testing dismal, particularly among minorities. We aimed to increase referral, cancer genetic testing and eventually LS diagnosis by developing the CLEAR LS (Closed Loop Enhanced Assessment and Referral for Lynch Syndrome) intervention, a systems approach which in the second phase was automated.

A study protocol for a double-blind randomised placebo-controlled trial evaluating the efficacy of carrageenan nasal and throat spray for COVID-19 prophylaxis-ICE-COVID.

Introduction: At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors.

Evidence informed generalist palliative care content for undergraduate nursing curriculum: An integrative review.

Background: Clinicians delivering palliative care require the specific knowledge, skill and understanding to meet the needs of the dying. Research shows that undergraduate nursing students report feeling inadequately prepared to provide safe and effective palliative care.

Objectives: To identify existing empirical evidence on generalist palliative care content within international undergraduate nursing curricula and to synthesize existing generalist palliative care topics.

KDM6B cooperates with Tau and regulates synaptic plasticity and cognition via inducing VGLUT1/2.

The excitatory neurotransmitter glutamate shapes learning and memory, but the underlying epigenetic mechanism of glutamate regulation in neuron remains poorly understood. Here, we showed that lysine demethylase KDM6B was expressed in excitatory neurons and declined in hippocampus with age. Conditional knockout of KDM6B in excitatory neurons reduced spine density, synaptic vesicle number and synaptic activity, and impaired learning and memory without obvious effect on brain morphology in mice.