Browse Articles
Discover research articles across all indexed journals
Advancing the genetic engineering toolbox by combining AsCas12a knock-in mice with ultra-compact screening
Abstract Cas12a is a next-generation gene editing tool that enables multiplexed gene targeting. Here, we present a mouse model that constitutively expresses enhanced Acidaminococcus sp. Cas12a (enAsCas12a) linked to an mCherry fluorescent reporter. We demonstrate efficient single and multiplexed gene editing in vitro, using primary and transformed cells from enAsCas12a mice. We further demonstrate successful in vivo gene editing, using normal and cancer-prone enAsCas12a stem cells to reconstitute the haematopoietic system of wild-type mice. We also present compact, genome-wide Cas12a knockout libraries, with four crRNAs per gene encoded across one (Scherzo) or two (Menuetto) vectors, and demonstrate the utility of these libraries across methodologies: in vitro enrichment and drop-out screening in lymphoma cells and immortalised fibroblasts, respectively, and in vivo screens to identify lymphoma-driving events. Finally, we demonstrate CRISPR multiplexing via simultaneous gene knockout (via Cas12a) and activation (via dCas9-SAM) using primary T cells and fibroblasts. Our enAsCas12a mouse and accompanying crRNA libraries enhance genome engineering capabilities and complement current CRISPR technologies.
Prevalence and antimicrobial resistant Campylobacter spp. in broiler chicken carcasses and hygiene practises in informal urban markets in a low-income setting
Campylobacteriosis is one of the most commonly reported foodborne diseases and is of particular importance in low-income countries. More data is needed to better understand the epidemiology of Campylobacter spp. in food sold at informal markets, where most people in low-income countries buy their food. This study aimed to determine the prevalence and antimicrobial resistance (AMR) of Campylobacter spp. among broiler chicken carcasses sold at informal urban markets in Uganda and to gain more knowledge about hygienic handling practices and awareness of foodborne bacterial diseases among the market vendors. In total, 120 broiler chicken carcasses from 30 different markets were analysed using ISO 10272 and confirmed by PCR. AMR analyses were performed using the disc diffusion test. Epidemiological data on food safety practices and awareness was collected from the vendors using a questionnaire. Campylobacter spp. was isolated from 66% (79/120) of the carcasses; 32% were C. jejuni, 14% were C. coli and 54% comprised of a mixture of both species. All C. jejuni isolates showed resistance to tetracycline, 88% to ciprofloxacin and 28% to erythromycin. Of the C. coli isolates, 82% showed resistance to tetracycline, 73% to erythromycin and the quinolones ciprofloxacin and nalidixic acid. More than half of the vendors had heard about food-borne illnesses, but none knew about Campylobacter spp., and the knowledge regarding hygienic practices was low. These data calls for urgent interventions to improve food safety, protect the public from foodborne illness, and prevent the spreading of AMR.
Effectiveness of iNTS vaccination in sub-Saharan Africa
Abstract Invasive non-Typhoidal Salmonella (iNTS) is one of the leading causes of blood stream infections in Sub-Saharan Africa, especially among children. iNTS can be difficult to diagnose, particularly in areas where malaria is endemic, and difficult to treat, partly because of the emergence of antibiotic resistance. We developed a mathematical model to evaluate the impact of a vaccine for iNTS in 49 countries of sub-Saharan Africa. Without vaccination we estimate 9.2 million new iNTS cases among children below 5 years old in these 49 countries from 2022 to 2038, 6.2 million of which between 2028 and 2038. The introduction of a $$85\%$$ ( $$95\%$$ ) efficacy vaccine in 2028 would prevent 2.6 (2.9) million of these new infections. We provide the country-specific impact of a iNTS vaccine considering the different age structures and vaccine coverage levels.
Observation of ultraviolet photothermoelectric bipolar impulse in gallium-based heterostructure nanowires
New information on Bonapartenykus (Alvarezsauridae: Theropoda) from the Allen Formation (middle Campanian-lower Maastrichtian) of Río Negro Province, Patagonia, Argentina clarifies the Patagonykinae body plan
Alvarezsauria is a group of morphologically distinctive, medium- to small-sized later-diverging coelurosaurian theropod dinosaurs, whose record ranges from the Late Jurassic to the Late Cretaceous. This clade had a widespread distribution in Laurasia in what is now Europe, Asia, and North America, although there are also several Cretaceous taxa from Gondwana in what is now Argentina that all belong to the family Alvarezsauridae. Although alvarezsaurid taxonomic diversity and anatomical knowledge has expanded over the last decade, alvarezsaurid internal phylogenetic relationships remain highly debated. In this contribution, we describe new alvarezsaurid material and review previously reported alvarezsaurid specimens from the middle Campanian—lower Maastrichtian Allen Formation discovered at the Salitral Ojo de Agua locality in Río Negro province, Patagonia, Argentina. Although these specimens were collected at different times without precise original provenance information, here we gathered X-ray diffraction data of the associated sediments that now suggests that all of these specimens come from the same site and stratigraphic level as the holotype of the alvarezsaurid Bonapartenykus ultimus. Based on this new provenance information and the morphological similarity of the considered specimens, here we tentatively refer them to the genus Bonapartenykus. These newly referred specimens add to the record of this genus and shed light on the body plan of the alvarezsaurid clade Patagonykinae by permitting a more complete reconstruction of the neck, pectoral girdle, hindlimb, and tail.
Non-targeted metabolomics reveals fatty acid and associated pathways driving resistance to whitefly and tomato leafminer in wild tomato accessions
A shout-out for AI studies that don’t make the headlines
GNSS spoofing in conflict zones disrupts wildlife tracking and hampers research and conservation efforts
Examining the mediating role of motivation in the relationships between teacher-created motivational climates and quality of engagement in secondary school physical education
Grounded in Duda’s integrated model of the motivational climate, the current study examined the hypothesized mediating role of motivation quality in the relationships between empowering and disempowering teacher-created motivational climates and indicators of quality engagement in secondary school physical education (PE). The hypothesised model was tested cross-sectionally and longitudinally in two separate samples of students. Data were collected via questionnaires measuring the motivational climate, autonomous and controlled motivation and indicators of engagement (enjoyment, concentration and boredom). Cross sectional data collected from 832 students (439 males and 386 females) while longitudinal data stemmed 299 students (166 males and 163 females). All students were from schools in Wales aged between 12 and 15 years. Structural equation modelling was used to test the hypothesised model and the mediating role of autonomous and controlled motivation. The hypothesised model was supported cross-sectionally and longitudinally, indicating that empowering climates positively predicted students’ autonomous motivation for PE, whereas disempowering motivational climates positively predicted controlled motivation. In turn, autonomous and controlled motivation positively and negatively predicted indictors of students’ engagement in PE in the hypothesised directions. Analyses revealed relationships between empowering and disempowering climates with enjoyment, concentration and boredom were indirect via autonomous and controlled motivation. In summary, results support the role of autonomous and controlled motivation in the differential relationships between empowering and disempowering motivational climates and indicators of the quality of student engagement. The findings suggest that targeted professional learning opportunities for PE teachers are needed which facilitate more empowering climates and reducing disempowering strategies.
An optimized lightweight real-time detection network model for IoT embedded devices
Pasteurisation temperatures effectively inactivate influenza A viruses in milk
Abstract In late 2023 an H5N1 lineage of high pathogenicity avian influenza virus (HPAIV) began circulating in American dairy cattle Concerningly, high titres of virus were detected in cows’ milk, raising the concern that milk could be a route of human infection. Cows’ milk is typically pasteurised to render it safe for human consumption, but the effectiveness of pasteurisation on influenza viruses in milk was uncertain. To assess this, here we evaluate heat inactivation in milk for a panel of different influenza viruses. This includes human and avian influenza A viruses (IAVs), an influenza D virus that naturally infects cattle, and recombinant IAVs carrying contemporary avian or bovine H5N1 glycoproteins. At pasteurisation temperatures of 63 °C and 72 °C, we find that viral infectivity is rapidly lost and becomes undetectable before the times recommended for pasteurisation (30 minutes and 15 seconds, respectively). We then show that an H5N1 HPAIV in milk is effectively inactivated by a comparable treatment, even though its genetic material remains detectable. We conclude that pasteurisation conditions should effectively inactivate H5N1 HPAIV in cows’ milk, but that unpasteurised milk could carry infectious influenza viruses.
Acquired hypothyroidism, iodine status and hearing impairment in adults: A pilot study
Objectives Hearing impairment can have major impacts on behavior, educational attainment, social status, and quality of life. In congenital hypothyroidism, the incidence of hearing impairment reaches 35–50%, while in acquired hypothyroidism there is a reported incidence of 25%. Despite this, knowledge of the pathogenesis, incidence and severity of hearing impairment remains greatly lacking. The aim of our study was to evaluate hearing in patients with acquired hypothyroidism. Methods 30 patients with untreated and newly diagnosed peripheral hypothyroidism (H) and a control group of 30 healthy probands (C) were enrolled in the study. Biochemical markers were measured, including median iodine urine concentrations (IUC) µg/L. The hearing examination included a subjective complaint assessment, otomicroscopy, tympanometry, transitory otoacoustic emission (TOAE), tone audiometry, and brainstem auditory evoked potential (BERA) examinations. The Mann-Whitney U test, Fisher’s Exact test and multivariate regression were used for statistical analysis. Results The H and C groups had significantly different thyroid hormone levels (medians with 95% CI) TSH mU/L 13.3 (8.1, 19.3) vs. 1.97 (1.21, 2.25) p = 0 and fT4 pmol/L 10.4 (9.51, 11.1) vs. 15 (13.8, 16.7) p = 0. The groups did not significantly differ in age 39 (34, 43) vs. 41 (36,44) p = 0.767 and IUC 142 (113, 159) vs. 123 (101, 157) p = 0.814. None of the hearing examinations showed differences between the H and C groups: otomicroscopy (p = 1), tympanometry (p = 1), TOAE (p = 1), audiometry (p = 0.179), and BERA (p = 0.505). Conclusions We did not observe any hearing impairment in adults with acquired hypothyroidism, and there were no associations found between hearing impairment and the severity of hypothyroidism or iodine status. However, some forms of hearing impairment, mostly mild, were very common in both studied groups.
Changes in lake sturgeon spawning periodicity is associated with prior reproductive effort
Site-specific substitution in atomically precise carboranethiol-protected nanoclusters and concomitant changes in electronic properties
Generating context-specific sports training plans by combining generative adversarial networks
Personalized sports training plans are essential for addressing individual athlete needs, but traditional methods often need to integrate diverse data types, limiting adaptability and effectiveness. Existing machine learning (ML) and rule-based approaches cannot dynamically generate context-specific training programs, reducing their applicability in real-world scenarios. This study aims to develop a Generative Adversarial Network (GAN)- based framework to create context-specific training plans by integrating numeric attributes (e.g., age, heart rate) and motion features from video data. The research focuses on improving context-specific efficiency and real-time adaptability while addressing the limitations of traditional methods. The proposed GAN framework combines numeric and motion features using a generator-discriminator architecture to produce tailored training plans. The model is evaluated quantitatively through metrics like mean square error (MSE) and generation time and qualitatively through subjective ratings from athletes and coaches using a five-point Likert scale for context-specific, scientificity, applicability, and feasibility. Statistical significance is analyzed using ANOVA testing. The proposed GAN model outperforms traditional ML and rule-based methods, achieving a 22% reduction in MSE and a 45% improvement in generation time. Subjective evaluations reveal significant improvements in context-specific and applicability, with ratings averaging 4.8/5 compared to 3.9/5 for baseline models. The GAN framework effectively integrates multimodal data, demonstrating dynamic adaptability and high efficiency suitable for real-world applications. The proposed GAN-based framework advances the generation of personalized sports training plans by integrating numeric and motion data, achieving superior adaptability and efficiency. These results highlight the model’s potential for practical deployment in athletic coaching systems, addressing critical gaps in existing methodologies and offering scalable solutions for individualized training.
Muscarinic acetylcholine receptor 3 localized to primary endothelial cilia regulates blood pressure and cognition
Deep mutational scanning of the Trypanosoma brucei developmental regulator RBP6 reveals an essential disordered region influenced by positive residues
Long-term engagement in smoking cessation campaign: A mixed methods randomized trial
Introduction A long-term engagement (LTE) intervention was embedded in a social marketing campaign aimed at motivating quit attempts among Canadian adult commercial tobacco users 35 to 64 years of age. The purpose of this study was to examine the effectiveness and appeal of LTE within a marketing campaign. Methods 3,199 Canadians who smoked cigarettes aged 35–64 recruited using Facebook and Instagram advertisements were randomized into Intervention and Control groups. Over the course of two years, Intervention Group participants received monthly emails connecting them to campaign news and activities, Mini Surveys to inform campaign refinement, feedback opportunities via focus groups and interviews, financial incentives, and proactive knowledge exchange presenting study findings. Both groups responded to a baseline and follow-up surveys every six months. Results LTE Intervention Group participants engaged frequently with emails (unique opens, open rates, click rates, and total clicks). Compared with Control Group members, they had significantly higher rates of: unaided and aided campaign awareness; engagement with the social marketing campaign (website visits, social media visits, likes/shares); actions towards making quit attempts; quit attempts. Many participants expressed feelings of motivation, support, and a sense of belonging. Conclusions When embedded in a social marketing campaign, meaningful long-term engagement of adults who smoke cigarettes shows promise as an intervention to promote quitting behaviors. Implications Active long-term engagement can significantly amplify the effects of social marketing campaigns aimed at promoting quit smoking behaviours among adults. The active engagement approach applied indicates that frequent long-term engagement is more effective when done in a more holistic, empathetic manner. The intervention also allows for real-time learning to support campaign development. Trial registration ISRCTN94797633.