Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.

Apolipoprotein E (ApoE) polymorphisms modify the risk of Alzheimer's disease with ApoE4 strongly increasing and ApoE2 modestly decreasing risk relative to the control ApoE3. To investigate how ApoE isoforms alter risk, we measured changes in proteome homeostasis in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). The regulation of each protein's homeostasis is observed by measuring turnover rate and abundance for that protein.

Do very young oocyte donors negatively impact live birth rates in their recipients?

To understand whether there was an association between very young oocyte donors and adverse outcomes, this was a single centre retrospective study (Lister Fertility Clinic, London) examining data collected between 1st January 2010 and 31st December 2021. A total of 1,182 oocyte donors were included in the final analysis. Data was categorised by donor age in years; ≤22, 23-25, 26-28, 29-31, 32-34.

Permafrost thaw subsidence, sea-level rise, and erosion are transforming Alaska's Arctic coastal zone.

Arctic shorelines are vulnerable to climate change impacts as sea level rises, permafrost thaws, storms intensify, and sea ice thins. Seventy-five years of aerial and satellite observations have established coastal erosion as an increasing Arctic hazard. However, other hazards at play-for instance, the cumulative impact that sea-level rise and permafrost thaw subsidence will have on permafrost shorelines-have received less attention, preventing assessments of these processes' impacts compared to and combined with coastal erosion.

Supramolecular chemistry in solution and solid-gas interfaces: synthesis and photophysical properties of monocolor and bicolor fluorescent sensors for barium tagging in neutrinoless double beta decay.

Translation of photophysical properties of fluorescent sensors from solution to solid-gas environments functionalized surfaces constitutes a challenge in chemistry. In this work, we report on the chemical synthesis, barium capture ability and photophysical properties of two families of monocolor and bicolor fluorescent sensors. These sensors were prepared to capture barium cations that can be produced in neutrinoless double beta decay of Xe-136.

Identifying CNS infections in transplantation and immunomodulatory therapy.

Opportunistic central nervous system (CNS) infections are a significant cause of morbidity and mortality in immunocompromized patients, including those undergoing transplantation and receiving immunomodulatory therapy. Particularly in these individuals, the clinical presentation of these infections may have atypical patterns, emphasizing the need to consider various diagnostic possibilities, including noninfectious conditions. Quick and accurate identification, along with prompt treatment, is crucial for improving patient outcomes.

Ligand-centred phenotype-driven development of potent kinase inhibitors against oesophageal cancer.

Oesophageal cancer (OC) is one of the leading causes of cancer-related deaths worldwide. Due in part to its high heterogeneity, OC prognosis remains poor despite the introduction of targeted and immunotherapy drugs. Although numerous kinases play a significant role in the oncogenesis and progression of OC, targeting kinases have shown so far limited therapeutic success.

NEARER SCAN (LENO BESIK) evaluation of a task-sharing echocardiographic active case finding programme for rheumatic heart disease in Australia and Timor-Leste: protocol for a hybrid type II effectiveness-implementation study.

Introduction: Rheumatic heart disease (RHD) is underdiagnosed globally resulting in missed treatment opportunities and adverse clinical outcomes. We describe the protocol for a study which aims to co-design, implement and conduct an evaluation of a task-sharing approach to echocardiographic active case finding for early detection and management of RHD in high-risk settings in Australia and Timor-Leste.

Methods And Analysis: Echocardiograms will be obtained by trained local staff using hand-held echocardiographic devices employing the 'Single Parasternal Long Axis view with a Sweep of the Heart' (SPLASH) technique and interpreted by experts remote from the site of acquisition.

Evaluating an early social communication intervention for young children with Down syndrome (ASCEND): results from a feasibility randomised control trial.

Background: This paper reports the results from a feasibility trial of an early parent-delivered social communication intervention for young children with Down syndrome ('ASCEND'). The intervention focuses on developing children's early social communication skills, in particular responding to shared attention. The aim was to inform the feasibility of running a full-scale trial through National Health Service (NHS) Speech and Language Therapy (SaLT) services, to assess whether the intervention is effective in improving language skills before children with Down syndrome start school.

Singlet oxygen-mediated photochemical cross-linking of an engineered fluorescent flavoprotein iLOV.

Genetically encoded photoactive proteins are integral tools in modern biochemical and molecular biological research. Within this tool box, truncated variants of the phototropin two light-oxygen-voltage flavoprotein have been developed to photochemically generate singlet oxygen (O) in vitro and in vivo, yet the effect of O on these genetically encoded photosensitizers remains underexplored. In this study, we demonstrate that the "improved" light-oxygen-voltage flavoprotein is capable of photochemical O generation.

Hydride Shuttle Catalysis: From Conventional to Inverse Mode.

Hydride shuttle catalysis has emerged as a powerful synthetic platform, enabling the selective formation of C-C bonds to yield sp-rich structures. By virtue of the compelling reactivity of sterically encumbered Lewis acids from the frustrated Lewis pair regime, hydride shuttle catalysis enables the regioselective functionalization of alkyl amines at either the α- or β-position. In contrast to classical Lewis acid reactivity, the increased steric hindrance prevents interaction with the Lewis basic amine itself, instead leading to reversible abstraction of a hydride from the amine α-carbon.

The impact of surfaces on indoor air chemistry following cooking and cleaning.

Cooking and cleaning are common sources of indoor air pollutants, including volatile organic compounds (VOCs). The chemical fate of VOCs indoors is determined by both gas-phase and multi-phase chemistry, and can result in the formation of potentially hazardous secondary pollutants. Chemical interactions at the gas-surface boundary play an important role in indoor environments due to the characteristically high surface area to volume ratios (SAVs).

Quantitative and Kinetic Proteomics Reveal ApoE Isoform-dependent Proteostasis Adaptations in Mouse Brain.

Apolipoprotein E (ApoE) polymorphisms modify the risk of neurodegenerative disease with the ApoE4 isoform increasing and ApoE2 isoform decreasing risk relative to the 'wild-type control' ApoE3 isoform. To elucidate how ApoE isoforms alter the proteome, we measured relative protein abundance and turnover in transgenic mice expressing a human ApoE gene (isoform 2, 3, or 4). This data provides insight into how ApoE isoforms affect the synthesis and degradation of a wide variety of proteins.

Deletions in the MAL gene result in loss of Mal protein, defining the rare inherited AnWj-negative blood group phenotype.

The genetic background of the high prevalence red blood cell antigen AnWj has remained unresolved since its identification in 1972, despite reported associations with both CD44 and Smyd1 histone methyltransferase. Development of anti-AnWj, which may be clinically significant, is usually due to transient suppression of antigen expression, but a small number of individuals with persistent, autosomally-recessive inherited AnWj-negative phenotype have been reported. Whole exome sequencing of individuals with the rare inherited AnWj-negative phenotype revealed no shared mutations in CD44H or SMYD1, but instead we discovered homozygosity for the same large exonic deletion in MAL, which was confirmed in additional unrelated AnWj-negative individuals.

Behavioural compatibility, not fear, best predicts the looking patterns of chacma baboons.

Animal vigilance is often investigated under a narrow set of scenarios, but this approach may overestimate its contribution to animal lives. A solution may be to sample all looking behaviours and investigate numerous competing hypotheses in a single analysis. In this study, using a wild group of habituated chacma baboons (Papio ursinus griseipes) as a model system, we implemented a framework for predicting the key drivers of looking by comparing the strength of a full array of biological hypotheses.

A Cross-Sectional Survey of Healthcare Professionals' Knowledge, Attitude and Current Behaviours towards Female Fertility Preservation Services within the UK.

(1) Background: This study aims to establish the knowledge, attitudes and current behaviours towards female fertility preservation (FP) services amongst healthcare professionals (HCPs) in the UK. (2) Methods: An online survey was advertised publicly on the social media platform between 25 February 2021 and 11 March 2021. (3) Results: In total, 415 participants fulfilled the inclusion criteria and completed the survey.

Cardioneural ablation-the first case series without the use of fluoroscopy.

Introduction: Cardioneural ablation (CNA) and fluoroless ablation (FA) are emerging procedures and movements in contemporary in electrophysiology. Ablation of ganglionated plexus (GP) inputs in the atrium has been successfully targeted as a treatment for symptomatic bradyarrhythmias due to increased parasympathetic tone. As most of these patients are young, avoidance of ionizing radiation is of critical importance to limit potential long term deleterious effects.

LarvaTagger: manual and automatic tagging of Drosophila larval behaviour.

Motivation: As more behavioural assays are carried out in large-scale experiments on Drosophila larvae, the definitions of the archetypal actions of a larva are regularly refined. In addition, video recording and tracking technologies constantly evolve. Consequently, automatic tagging tools for Drosophila larval behaviour must be retrained to learn new representations from new data.

Challenges in clinical diagnosis of Clade I Mpox: Highlighting the need for enhanced diagnostic approaches.

Background: Due to limited diagnostic capacity and availability of point-of-care tests, diagnosis of Clade I mpox in the geographical regions most affected is usually on clinical grounds. This may be complicated due to the similarity between mpox and varicella (chickenpox) lesions. Visual assessment of lesions is also used for determining clinical progress and to assess patient outcomes in clinical trials.

Chimpanzees () recognize that their guesses could be wrong and can pass a two-cup disjunctive syllogism task.

When chimpanzees search for hidden food, do they realize that their guesses may not be correct? We applied a post-decision wagering paradigm to a simple two-cup search task, varying whether we gave participants visual access to the baiting and then asking after they had chosen one of the cups whether they would prefer a smaller but certain reward instead of their original choice (experiment 1). Results showed that chimpanzees were more likely to accept the smaller reward in occluded than visible conditions. Experiment 2 found the same effect when we blocked visual access but manipulated the number of hiding locations for the food piece, showing that the effect is not owing to representation type.

Biochemical and structural insights into a 5' to 3' RNA ligase reveal a potential role in tRNA ligation.

ATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here we identify C12orf29 as an atypical ATP-grasp enzyme that ligates RNA.