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Can cognitive function tests discriminate between patients with glioma and healthy controls prior to treatment? A systematic review
Get PDFTissue-specific consequences of tag fusions on protein expression in transgenic mice
Get PDFGenetic fusion of protein tags is widely used to study protein functions in vivo. It is well known that tag fusion can cause unwanted changes in protein stability, but whether this is an inherent property of the tagged protein, or can be influenced by the cell and tissue environment, is unclear. Using a series of genome edited mouse models, we show that tag-dependent changes in protein expression can vary across different primary cell and tissue contexts. In one case (Ncaph2), a C-terminal auxin inducible degron fusion strongly increased protein stability in some tissues but decreased it in others. Destabilisation resulted from tissue-specific ‘leakage’ of the auxin-inducible degron, which depended on TIR1 expression, and occurred selectively in the small intestine where basal concentrations of auxin / indole-3-acetic acid can reach levels that are sufficient to trigger protein degradation in cultured cells. Stabilisation occurred in post-mitotic cells via an endogenous degradation signal situated at the Ncaph2 C-terminus, which normally undergoes activation upon cell cycle exit, but is inactivated by C-terminal tag fusion. Our results highlight the underappreciated importance of cell and tissue environment in determining the consequences of tag fusions on protein expression, which may be particularly important in animal models that contain diverse cell types
Content of visual–mental imagery in mood and anxiety disorders:A qualitative systematic literature review
Get PDFMental imagery is an internal representation of perceptual experiences without external sensory input. Mental imagery plays a recognized role in the development and maintenance of anxiety and mood disorders. In this systematic literature review, we explored the type of mental imagery content, its emotional impact, and possible recurrent mental imagery patterns (i.e., specific theme/content type) in individuals with mood and anxiety disorders. The mood disorders included in the review were Major Depressive Disorder (MDD), bipolar disorder, suicidal behavior (attempts) and ideation, or non-suicidal injury (NSSI).according to DSM-V. Anxiety disorders included post-traumatic stress disorder (PTSD) and social anxiety (SA) according to DSM-IV and DSM-V. Electronic searches of five databases between January 2000 and April 2024 were undertaken to identify relevant publications, including qualitative, qualitative, and mixed-methods studies, with a final list of 17 studies eligible for review. The studies were synthesized using thematic synthesis. The results suggest that recurrent visual imagery content patterns across different mental health conditions include visualizing interpersonal interactions such as fighting with a spouse or another family member, suicide or self-harm-based imagery, and crossing one’s boundaries by another. In addition, although individuals with anxiety and mood disorders are more prone to experience negative mental imagery, they can also experience positive mental imagery. In conclusion, the content of mental imagery can be objectively positive and negative, but ultimately, an individual's appraisal is the driving factor behind the emotional impact of mental imagery
Multiple Equilibria Enables Tunable Wetting of Droplets on Patterned Liquid Surfaces
Get PDFPatterning solid surfaces with varying wettability is important to manage droplets in microfluidics, heat transfer, and printing. Solid surface roughness poses fundamental limitations including contact-line pinning and solid friction. Here, we report an experimental strategy and theoretical design principles for patterned liquid surfaces (PaLS) that combine the controlled wettability from patterning with the ultrasmoothness of a lubricant-infused surface. In contrast to a solid, on PaLS, a droplet can be in 10 different wetting states. This richness arises from the adaptation of the liquid lubricants and can be harnessed to control the apparent contact angle of the droplet over the full range of wettability while removing contact-line pinning effects induced by the solid surface. In the limit of thin liquid films, we derive surface-averaged laws for the apparent contact angle for each wetting state, which capture both experimental and simulation data. Our results provide a distinct approach to surface patterning that exploits the interaction of fluids with lubricant-impregnated surfaces.</p
Barking up the right tree: Immune checkpoint signatures of human and dog cancers
Get PDFIn the quest for improved therapeutics targeting immune checkpoints (ICs), we turn to spontaneously developing dog (canine) cancers, some of which genetically and clinically mirror the human counterparts. Despite its potential, canine cancer immunology remains largely unexplored. Here, we examine the RNA-seq-based expression of 44 ICs across 14 canine cancer types and an extensive human dataset. We unveil diverse canine IC expression patterns and unique human IC signatures that reflect the histological type and primary site of cancer. We uncover a striking similarity between canine brain cancers, osteosarcoma, and their human counterparts, identifying them as prospective immunotherapy models. Four ICs - CD160, A2AR, NKG2A, and OX40 - are key to the differences observed between species. We also find that individual human IC signatures vary in how well they align with their respective cancer types, a pattern that may influence future approaches to personalized therapy. This exploration highlights aspects of canine and human cancer immunology that warrant further study, setting the stage for discoveries at their crossroads.</p
‘It's healthy. It's good for you’:Children's perspectives on utilising their autonomy in the writing classroom
Get PDFGrowing concern about children's writing motivation highlights the need for more research that foregrounds pupil autonomy and examines how classroom practices influence students' sense of agency and control in their writing. This study adopts a self-determination theory (SDT) perspective to explore the role of autonomy and locus of control in shaping writing motivation among primary-aged students. Specifically, it reports on a qualitative interview study with 24 children (aged 9–11, 50% female) from three primary schools in England, focusing on their feelings and experiences of autonomy in relation to school-based writing. Thematic analysis, illustrated within Graham's (2018) production strategies for writing, identified three key themes relating to children's perceptions of the locus of control for their writing and the extent to which this was held by, or shared between, the teachers or themselves, with (a) teacher-controlled writing, (b) student-controlled writing and (c) collaboratively-controlled writing themes identified. Children's perceptions of the advantages and disadvantages of teacher and student-controlled writing are discussed, before their thoughts on a ‘collaboratively-controlled writing’ approach are shared. This research provides novel and important insights for educators, researchers and policy-makers into how collaboratively-controlled writing projects could enhance primary students' writing motivation, and contributes to current discourse on effective and affecting writing pedagogy.</p
Characterizing typologies of overlapping IPV & VAC in the home:Findings from DRC, Ethiopia, and South Africa
Get PDFBackgroundWhile intimate partner violence (IPV) and caregiver-perpetrated violence against children (VAC) are recognized as global epidemics, gaps persist in understanding the nature of co-occurring violence within the home.ObjectiveThis study seeks to characterize the nature and overlap of concurrent IPV and caregiver-perpetrated VAC in families across three African contexts.Participants and settingA sample of adult women and children was obtained from the [study name redacted] Wave 1 (2018–2019), [study name redacted] DRC baseline (2019–2020), and [study name redacted] South Africa Wave 3 (2022–2024) studies.MethodsLatent class analysis (LCA) distinguished groups of families by nature and overlap of IPV and VAC. Violence was conceptualized as one construct in DRC and South Africa and two constructs in Ethiopia.ResultsCo-occurring IPV and VAC affected 18.3 % of families in South Africa, 34.3 % in Ethiopia, and 56.1 % in DRC. Twenty percent of Ethiopian families, 15.3 % in DRC, and 4.5 % in South Africa, were characterized by emotional IPV alongside both physical and psychological VAC. In Ethiopia, two classes were distinguished by presence of economic abuse related to either women's earnings (4.1 %) or men's earnings (4.3 %). Systematic violence, characterized by overlap of multiple domains of IPV alongside VAC, affected 15.5 % of families in DRC, 8.2 % in South Africa, and 3.2 % in Ethiopia.ConclusionsEfforts to measure and address IPV and VAC should include emotional and economic IPV, and consider variation of types and intensity across families. More substantial investment in GBV and VAC services are needed to address shared drivers and ensure coordinated response
Continuous Evolution of Eurasian avian-like H1N1 Swine Influenza Viruses with pdm/09-derived Internal Genes Enhances Pathogenicity in Mice
Get PDFSwine influenza A virus (swIAV) is an important zoonotic pathogen with the potential to cause human influenza pandemics. Swine are considered "mixing vessels" for generating novel reassortant influenza A viruses. In 2009, a swine-origin reassortant virus (2009 pandemic H1N1, pdm/09 H1N1) spilled over to humans, causing a global influenza pandemic. This virus soon spread back into swine herds and reassorted with the circulating swIAVs. We previously reported that the genotype 4 (G4) reassortant Eurasian avian-like (EA) H1N1 virus, which bore pdm/09- and triple reassortant (TR)-derived internal genes, had been predominant in swine populations of China since 2016, posing a threat to both the swine industry and public health. Here, our ongoing surveillance confirmed that G4 EA H1N1 viruses remained the predominant swIAVs in China from 2019 to 2023 and had reassorted with the co-circulating swIAVs, such as the H3N2 virus, to generate novel reassortant EA H1N2 viruses. Genetic analyses revealed that the pdm/09-derived internal genes of G4 EA H1N1 viruses originated from reassortments between pdm/09 H1N1 and EA H1N1 viruses in 2009-2010 and underwent independent and continuous evolution in the swine host, exhibiting higher evolutionary rates than those of the pdm/09 H1N1 virus circulating in humans. The accelerated evolution of internal genes enhanced the polymerase activity of G4 EA H1N1 viruses in mammalian cells, resulting in increased viral replication and pathogenicity in mice. This study provides evidence for swine in promoting the genetic evolution of influenza A virus and highlights the need for increased attention to novel reassortant viruses in swine.IMPORTANCEThe emergence of pdm/09 H1N1 virus highlights the role of swine influenza A viruses (swIAVs) in generating novel influenza viruses with pandemic potential. Since 2009, the pdm/09 H1N1 virus has been frequently transmitted to swine and reassorted with the circulating swIAVs, generating many new reassortant viruses bearing pdm/09-derived genes globally. The G4 EA H1N1 viruses, which bore pdm/09-derived internal genes and acquired increased human infectivity, remained the predominant swIAVs in China from 2019 to 2023 and reassorted with the co-circulating swIAVs to generate novel subtype viruses. The internal genes of G4 EA H1N1 viruses originated from the human pdm/09 H1N1 viruses during 2009-2010 and exhibited higher evolutionary rates and greater genetic diversity than those in the human host. This has contributed to increased viral adaptation and pathogenicity in mammals. Therefore, sustained surveillance and immunization efforts are essential to control emerging reassortant swIAVs and protect public health.</p
Antibiotic use in the commercial poultry sector of Uganda and its public health implications: A cross-sectional survey
Get PDFIntroduction: Rising poultry demand is driving shifts towards intensive farming in the Global South, raising concerns about antibiotic use and food chain risks. This study examines the nature and extent of antibiotic use in Uganda's commercial poultry sector and quantifies antibiotic use at bird, farm, and national levels. Further the study estimates antibiotic residues in broiler, layer and duo purpose poultry meat at slaughter to evaluate food chain risks. Methods: This cross-sectional survey used the World Organisation for Animal Health standards for monitoring quantities of antimicrobial agents used in food producing animals, on 374 commercial poultry farms with 187,798 birds randomly selected from the Northern, West Nile, Eastern and Southwestern sub regions of Uganda.Results: The overall antibiotic use was 82kg per farm per cycle, with variability by poultry type, farm size and at regional level i.e., ~ 170mg more were used in broiler than dual-purpose birds, ~ 220mg more were used on broiler than layer farms, ~180g more used in the Southwestern than the Eastern region. Smaller farms (<=200 birds) use 1050mg more than larger farms (>=800 birds). Drug formulation (whether powdered or liquid) and access to veterinary extension services were associated with higher and lower antibiotic use respectively. 24.7 tons (~ 63% of the poultry annual antibiotic imports) are used by the commercial sector. Tetracycline and colistin sulphate are the most used, and we estimated 14% and 54% of broiler farms with non-adherence to their withdrawal periods, respectively, exceeding maximum residue levels of 150 ng/kg and 200 ng/kg of meat. Conclusions: We estimate that the commercial poultry sector, that makes 30% of the national poultry population, uses 63% of imported antibiotics, with potential public health implications such as residues in the food chain. Interventions should be tailored to poultry production types hinged on robust veterinary extension services
Historical and experimental evidence that inherent properties are overweighted in early scientific explanation
No full textScientific explanation is one of the most sophisticated forms of human reasoning. Nevertheless, here we hypothesize that scientific explanation is susceptible to some of the same biases that influence everyday thinking—particularly during the initial stages of theory building, when scientists are first grappling with complex phenomena and are thus more likely to rely on explanatory “guesses.” Specifically, we investigated whether scientific explanation exhibits an inherence bias—a tendency to explain phenomena through inherent or intrinsic features rather than extrinsic factors such as context or relations. Consistent with this hypothesis, a comprehensive analysis of major explanatory transitions across the history of Western science revealed that initial scientific explanations systematically favored inherent properties, while subsequent explanations incorporated extrinsic factors more consistently. Seven experiments with lay participants (both adults and children; N = 1,673) and two experiments with practicing scientists from top departments worldwide (N = 275) provided converging evidence for this bias and identified the psychological mechanisms involved. When explaining unfamiliar phenomena, even leading scientists showed a robust tendency to overweight inherent properties and underweight extrinsic factors relative to established scientific understanding. This bias appears rooted in basic cognitive constraints on attention and memory that excessively narrow the space of hypotheses initially considered. These findings advance our understanding of both the psychology of explanation and the development of scientific knowledge, while suggesting specific ways to improve scientific training and education
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