Predisposition footprints in the somatic genome of Wilms tumours.

Ten percent of children with cancer harbour a mutation in a predisposition gene. In children with the kidney cancer, Wilms tumour, the prevalence is as high as 30%. Certain predispositions are associated with defined histological and clinical features, suggesting differences in tumourigenesis.

Behavioral activity patterns but not hair cortisol concentrations explain steers' transition-related stress in the first 6 wk in the feedlot.

Stress during the transition of beef steers from ranch to feedlot may depend on steer source and preconditioning. The interplay between physiological and behavioral patterns of preconditioned (PC) and auction-derived (AD) steers, particularly after commingling, is poorly understood. Our objective was to evaluate whether hair cortisol (HC) concentrations were related to the health and performance of PC and AD steers and study behavioral activities after commingling over 6 wk in a feedlot.

Educational and psychological interventions for managing atopic dermatitis (eczema).

Background: Atopic dermatitis (eczema), can have a significant impact on well-being and quality of life for affected people and their families. Standard treatment is avoidance of triggers or irritants and regular application of emollients and topical steroids or calcineurin inhibitors. Thorough physical and psychological assessment is central to good-quality treatment.

Flp/-mediated disruption of and in sporozoites inhibits liver-stage development.

causes severe malaria and assembles a protein translocon (PTEX) complex at the parasitophorous vacuole membrane (PVM) of infected erythrocytes, through which several hundred proteins are exported to facilitate growth. The preceding liver stage of infection involves growth in a hepatocyte-derived PVM; however, the importance of protein export during liver infection remains unexplored. Here, we use the FlpL/ system to conditionally excise genes in sporozoites for functional liver-stage studies.

Examining the recent strike wave in the UK: The problem with official statistics.

In the UK, there has been a significant increase in strike activity since the summer of 2022. Due to these increased levels of strike activity, it is logical for academics and policy makers to turn to the official data on labour disputes to help us understand what has been happening. Strikes remain of core sociological interest, yet are under researched in this journal.

Blinatumomab for First-Line Treatment of Children and Young Persons With B-ALL.

Purpose: We tested whether blinatumomab (Blina) is effective as a toxicity-sparing alternative to first-line intensive chemotherapy in children and young persons (CYP) with B-ALL who were chemotherapy-intolerant or chemotherapy-resistant.

Methods: Data were collected for consecutive CYP (age 1-24 years) with Philadelphia chromosome-positive or Philadelphia chromosome-negative B-ALL who received Blina as first-line therapy. Blina was given as replacement for postremission intensive chemotherapy to patients with chemotherapy intolerance or resistance.

The Effect of a Mental Task Versus Unilateral Physical Fatigue on Non-Local Muscle Fatigue in Recreationally Active Young Adults.

Non-local muscle fatigue (NLMF) has been attributed to both physical and mental fatigue. The purpose of this study was to investigate the effects of mental exertion versus unilateral physical fatigue on NLMF. Sixteen recreationally active participants completed a physical task (2-sets of 100-s unilateral knee extension (KE) maximal voluntary isometric contractions (MVIC) with the dominant leg with 40-s recovery between sets, mental task (4-minute Stroop task), and control condition.

Establishing SARS-CoV-2 membrane protein-specific antibodies as a valuable serological target via high-content microscopy.

The prevalence and strength of serological responses mounted toward SARS-CoV-2 proteins other than nucleocapsid (N) and spike (S), which may be of use as additional serological markers, remains underexplored. Using high-content microscopy to assess antibody responses against full-length StrepTagged SARS-CoV-2 proteins, we found that 85% (166/196) of unvaccinated individuals with RT-PCR confirmed SARS-CoV-2 infections and 74% (31/42) of individuals infected after being vaccinated developed detectable IgG against the structural protein M, which is higher than previous estimates. Compared with N antibodies, M IgG displayed a shallower time-dependent decay and greater specificity.

Impacts of commingling preconditioned and auction-derived beef calves on bovine respiratory disease related morbidity, mortality, and weight gain.

Introduction: Stressors predisposing to bovine respiratory disease (BRD) upon arrival in the feedlot, include the ranch to feedlot transition and mixing cattle from multiple sources. Preconditioning (PC) reduces multiple stressors, but commingling PC and auction-derived (AD) calves in a feedlot may increase BRD risk. Our objective was to evaluate PC calf performance over the first 40 days in the feedlot and determine impacts of commingling with varying proportions of AD calves (25, 50, and 75%).

Can Ponies (Equus Caballus) Distinguish Human Facial Expressions?

Communication within a species is essential for access to resources, alerting to dangers, group facilitation and social bonding; human facial expressions are considered to be an important factor in one’s ability to communicate with others. Evidence has shown that dogs and horses are able to distinguish positive and negative facial expressions by observing photographs of humans, however there is currently no research on how facial expressions from a live human are perceived by horses. This study investigated how ponies distinguish facial expressions presented by live actors.

Substrate Peptidomimetic Inhibitors of P. falciparum Plasmepsin X with Potent Antimalarial Activity.

Plasmepsin X (PMX) is an aspartyl protease that processes proteins essential for Plasmodium parasites to invade and egress from host erythrocytes during the symptomatic asexual stage of malaria. PMX substrates possess a conserved cleavage region denoted by the consensus motif, SFhE (h=hydrophobic amino acid). Peptidomimetics reflecting the P -P positions of the consensus motif were designed and showed potent and selective inhibition of PMX.

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms.

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human protein-protein interaction and viral protein localization analyses for all three viruses.

Structure of the Plasmodium falciparum PfSERA5 pseudo-zymogen.

PfSERA5, a significantly abundant protein present within the parasitophorous vacuole (PV) and essential for normal growth during the blood-stage life cycle of the malaria parasite Plasmodium falciparum, displays structural similarity to many other cysteine proteases. However, PfSERA5 does not exhibit any detectable protease activity and therefore the role of the PfSERA5 papain-like domain (PfSERA5E), thought to remain bound to its cognate prodomain, remains unknown. In this study, we present a revised structure of the central PfSERA5E domain at a resolution of 1.

New Technology, Work and Employment in the era of COVID-19: reflecting on legacies of research.

The outbreak of COVID-19 is having a drastic impact on work and employment. This review piece outlines the relevance of existing research into new technology, work and employment in the era of COVID-19. It is important to be retrospective and undertake both a historically and theoretically informed position on the impact of new technologies in the current crisis and beyond.

Eye Blink Rates and Eyelid Twitches as a Non-Invasive Measure of Stress in the Domestic Horse.

Physiological changes provide indices of stress responses, however, behavioural measures may be easier to determine. Spontaneous eye blink rate has potential as a non-invasive indicator of stress. Eyelid movements, along with heart rate (HR) and behaviour, from 33 horses were evaluated over four treatments: (1) control-horse in its normal paddock environment; (2) feed restriction-feed was withheld at regular feeding time; (3) separation-horse was removed from visual contact with their paddock mates; and (4) startle test-a ball was suddenly thrown on the ground in front of the horse.

Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex.

Plasmodium falciparum causes the severe form of malaria that has high levels of mortality in humans. Blood-stage merozoites of P. falciparum invade erythrocytes, and this requires interactions between multiple ligands from the parasite and receptors in hosts.

Enhanced antimalarial activity of plasmepsin V inhibitors by modification of the P position of PEXEL peptidomimetics.

Plasmepsin V is an aspartyl protease that plays a critical role in the export of proteins bearing the Plasmodium export element (PEXEL) motif (RxLxQ/E/D) to the infected host erythrocyte, and thus the survival of the malaria parasite. Previously, development of transition state PEXEL mimetic inhibitors of plasmepsin V have primarily focused on demonstrating the importance of the P Arg and P Leu in binding affinity and selectivity. Here, we investigate the importance of the P position by incorporating both natural and non-natural amino acids into this position and show disubstituted beta-carbon amino acids convey the greatest potency.

Differing rates of antibody acquisition to merozoite antigens in malaria: implications for immunity and surveillance.

Antibodies play a key role in acquired human immunity to (Pf) malaria and target merozoites to reduce or prevent blood-stage replication and the development of disease. Merozoites present a complex array of antigens to the immune system, and currently, there is only a partial understanding of the targets of protective antibodies and how responses to different antigens are acquired and boosted. We hypothesized that there would be differences in the rate of acquisition of antibodies to different antigens and how well they are boosted by infection, which impacts the acquisition of immunity.