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Antibiotic use (ABU) in animals is postulated to be a major contributor to selection of antibiotic resistance (ABR) which subsequently causes infections in human populations. However, there are few quantifications of the size of this association. Denmark, as a country with high levels of pig production and strong ABR surveillance data, is an ideal case study for exploring this association.This study compiles a dataset on ABU across several animal species and antibiotic classes, and data on the rate of antibiotic resistance (ABR) in humans across key pathogens, in Denmark over time (2010−2020). Panel data regressions (fixed effects, random effects, first difference and pooled ordinary least squares) were used to test the association between the level of ABR in human isolates and the level of ABU in animals.A positive relationship was identified between ABR in humans and ABU in cattle, with some evidence of a positive relationship for poultry and companion animals, and a negative relationship for fish, although the latter is likely driven by confounding factors. When lagging ABU by one year, the effect of ABU in cattle and companion animals remained similar, the effect of ABU in poultry fell in size, and ABU in fish was no longer significant, perhaps due to differences in life cycle length among animal species. Additional covariates were explored, including pet populations, agricultural production and GDP per capita (at purchasing power parity), but these results were limited by the statistical power of the dataset. Under all models, animal ABU determined only a minority of the change in human ABR levels in this context with adjusted R2 ranging from 0.19 to 0.44.This paper supports the role of animal ABU in determining human ABR levels but suggests that, despite comprising a large portion of systemwide ABU, it only explains a minority of the variation. This is likely driven in part by data limitations, and could also be due to a persistence of ABR once resistance has emerged, suggesting a significant role for socioeconomic and transmission factors in bringing ABR down to desirable levels.

Prostate cancer (PCa) is the second most common cancer diagnosed in men. While radical prostatectomy and radiotherapy are often successful in treating localised disease, post-treatment recurrence is common. As the androgen receptor (AR) and androgen hormones play an essential role in prostate carcinogenesis and progression, androgen deprivation therapy (ADT) is often used to deprive PCa cells of the pro-proliferative effect of androgens. ADTs act by either blocking androgen biosynthesis (e.g. abiraterone) or blocking AR function (e.g. bicalutamide, enzalutamide, apalutamide, darolutamide). ADT is often effective in initially suppressing PCa growth and progression, yet emergence of castrate-resistant PCa and progression to neuroendocrine-like PCa following ADT are major clinical challenges. For this reason, there is an urgent need to identify novel approaches to modulate androgen signalling to impede PCa progression whilst also preventing or delaying therapy resistance.The mechanistic convergence of androgen and epitranscriptomic signalling offers a potential novel approach to treat PCa. The epitranscriptome involves covalent modifications of mRNA, notably, in the context of this review, the N(6)-methyladenosine (m6A) modification. m6A is involved in the regulation of mRNA splicing, stability, and translation, and has recently been shown to play a role in PCa and androgen signalling. The m6A modification is dynamically regulated by the METTL3-containing methyltransferase complex, and the FTO and ALKBH5 RNA demethylases.Given the need for novel approaches to treat PCa, there is significant interest in new therapies that target m6A that modulate AR expression and androgen signalling. This review critically summarises the potential benefit of such epitranscriptomic therapies for PCa patients.

The design of heliostats throughout a concentrated solar power (CSP) plant are currently of uniform design, however, research into the variation in heliostat wind loading within a radially staggered field array can provide insight into potential material cost savings in heliostat field design. Experimental investigation was carried out on a field array model in the University of Adelaide large wind tunnel. A total of 64 heliostat models of size 0.1 × 0.1 m were radially arranged over four surround rows. Four 3-axis load cells were utilized to analyze field array cases of morning (0700 hours), noon (1200 hours), and evening (1700 hours) configurations. Angle calculations for beam reflection were made for the 21st March (equinox). Results show mean and peak drag force coefficients reduce with distance into the field for a 1700 hour case due to high upstream blockage. Comparing the downstream drag and lift force coefficients against each test configuration, when heliostats are at steep elevation angles, high flow blockage leads to a reduction of coefficients downstream (0700 hour and 1700 hour cases). When elevation angles are reduced (1200 hours), drag and lift coefficients increase with distance from the central tower in the downstream direction. Results also show the central tower increases load coefficients on downstream heliostats, and therefore should be considered in heliostat wind loading and field design.

This study analyses the turbulent wind properties in the lower 10 m of the atmospheric surface layer close to the ground where heliostats are located. Power spectral densities of streamwise and vertical components of wind are analysed, and the frequencies associated with the peak of the spectra are determined using field data collected at two open-country terrains in addition to spectral models of ESDU85020. Variations of the peak frequencies with height from the ground, terrain type and average wind speed are discussed and the impact on heliostat wind loads are described. It is found that while the peak frequency of the streamwise turbulence is between 0.01–0.1 Hz, the peak of the vertical turbulence occurs at frequencies in the range of 0.1–1 Hz. It is shown that smaller heliostats that are located closer to the ground are exposed to turbulent wind fluctuations at a higher frequency and are thus expected to experience wind loads with a higher dominant frequency compared to larger heliostats located higher above the ground. These frequencies need to be considered in design of heliostat drives and structural components

The paper explores the potential of big data analytics for researching anti-immigrant discourse. We emphasize contextualization as an essential element of research and follow a hybrid approach inspired by best practices of computational content analysis, combining human hermeneutic expertise with supervised machine learning to classify a corpus of comments in online news communities in Singapore over 6 months ( N = 399,225). The paper highlights how big data analytics can provide a nuanced and critical apprehension of immigrant-related discourse in large social media datasets.

IntroductionThe discourse on immigration and immigrants is central to contemporary political and public discussions. Analyzing online conversations about immigrants provides valuable insights into public opinion, complemented by data from questionnaires on how attitudes are formed.MethodsThe research includes two studies examining the expressive and informational use of social media. Study 1 conducted a computational text analysis of comments on Singaporean Facebook pages and forums, focusing on how social media is used to discuss immigrants. Study 2 utilized survey data to examine the use of social media at the individual level, testing the relationships between cognitive ability, perceptions of threat, negative emotions towards immigrants, and social media usage within the Integrated Threat Theory framework.ResultsStudy 1 found that discussions about immigrants on social media often involved negative emotions and concerns about economic impact, such as competition for jobs and crime. Complementing these findings about perceived economic threats, Study 2 showed that individuals with higher social media usage and greater perceptions of threat were more likely to have negative emotions towards immigrants. These relationships were mediated by perceptions of threat and were stronger in individuals with lower cognitive abilities.DiscussionThe findings from both studies demonstrate the role of social media in shaping public attitudes towards immigrants, highlighting how perceived threats influence these attitudes. This research suggests the importance of considering how digital platforms contribute to public opinion on immigration, with implications for understanding the dynamics of attitude formation in the digital age.

IntroductionReducing nontherapeutic antibiotic use (ABU) in livestock animals has been identified as an important way of curbing the growth of antimicrobial resistance (AMR). However, nontherapeutic ABU may be important for managing animal disease. In order to reduce nontherapeutic ABU, farmers may need to implement other complementary interventions to safeguard animal health and minimize risk. We should therefore investigate if nontherapeutic ABU is associated with better animal health outcomes before advocating to reduce it. We should also investigate non-antibiotic factors which protect animal health and can make nontherapeutic use less necessary, as well as factors which can encourage farmers to improve their antibiotic stewardship.MethodsThe study investigated these questions using data from the AMUSE survey, which is designed to evaluate knowledge, attitudes and practices relating to AMR in smallholder livestock farms. The sample included 320 animal herds from 216 smallholder livestock farms in Burkina Faso, with livestock species including poultry, small ruminants, and cattle. The determinants of the occurrence of animal disease and nontherapeutic ABU were investigated using binary logistic regression.ResultsResults revealed that nontherapeutic ABU was positively associated with animal disease, although the potential reverse causality of this relationship should be investigated further. Going primarily to a public veterinarian for animal health services, and having a higher level of formal education, were negatively associated with the occurrence of disease. Going primarily to a community animal health worker was positively associated with using antibiotics nontherapeutically, whereas going primarily to a public veterinarian was negatively associated with this outcome. Having an animal health professional (of any kind) provide diagnosis and treatment was positively associated with nontherapeutic antibiotic use for goats and sheep.DiscussionThese findings support the expansion of education access and public veterinary services as a way to encourage better antibiotic stewardship while guarding against any animal health risks associated with doing so. They also highlight that animal health professionals other than public veterinarians may prioritize animal health outcomes over antibiotic stewardship goals.

This study investigated high-frequency load fluctuations on a rectangular heliostat model in a boundary layer wind tunnel experiment. Statistical methods for peak wind load predictions were compared with load distributions through load cell and surface pressure measurements on the heliostat model placed in two simulated atmospheric boundary layers (ABLs) representing a flat desert terrain and open country terrain. It was found that statistical peak predictions based on horizontal wind gust velocity amplitude underestimates the load coefficients in stow and at oblique azimuth angles for maximum azimuth moments. In addition, it was shown that the distributions of the centre of pressure position and the hinge moment in stow position are non-Gaussian. It is therefore recommended that the frequency and amplitude of the vertical wind velocity component must be considered for peak load predictions of hinge moments and azimuth moments.

The Heliostat Consortium (HelioCon) Wind Load Subtask was initiated with the aim of bringing research work pertaining to wind load measurement, characterization, and prediction taking place across several tasks, including Advanced Manufacturing, Components and Controls, and Field Deployment. The cross-cutting wind load subtopic in the HelioCon roadmap report [1] highlighted standardized methods and tools that are needed for a more detailed understanding of the static and dynamic loads on a heliostat. This will enable cost reduction of wind-dependent heliostat components to avoid unnecessarily conservative, overly constrained designs and increase field efficiency/reliability, to reduce the risk of component failures due to high-wind events (>15 m/s). Gaps related to heliostat wind load include site characterization for wind measurements, critical load cases for heliostat design, turbulence impacts on heliostat tracking error, testing of heliostat array configurations, understanding spatial variation of maximum loads across the solar field, and heliostat field layout and operating strategies. The recommended highest-priority pathway as first steps taken by HelioCon to address these gaps are to develop site characterization guidelines for heliostat design and field load measurements.

Migration from one location to another often comes with a change in environmental conditions. Here, we analysed features of DNA methylation in young, adult British-Bangladeshi women who experienced different environments during their childhoods: a) migrants, who grew up in Bangladesh with exposure to comparatively higher pathogen loads and poorer health care, and b) second-generation British-Bangladeshis, born to Bangladeshi parents, who grew up in the UK. We used buccal DNA to estimate DNA methylation-based age (DNAm age) from 14 migrants and 11 second-generation migrants, aged 18–35 years. ‘AgeAccel,’ a measure of DNAm age, independent of chronological age, showed that the group of women who spent their childhood in Bangladesh had higher AgeAccel (P = 0.028), compared to their UK peers. Since epigenetic clocks have been proposed to be associated with maintenance processes of epigenetic systems, we evaluated the preference for concordant DNA methylation at the luteinizing hormone/choriogonadotropin receptor (LHCGR/LHR) locus, which harbours one of the CpGs contributing to Horvath’s epigenetic clock. Measurements on both strands of individual, double-stranded DNA molecules indicate higher stability of DNA methylation states at this LHCGR/LHR locus in samples of women who grew up in Bangladesh. Together, our two independent analytical approaches imply that childhood environments may induce subtle changes that are detectable long after exposure occurred, which might reflect altered activity of the epigenetic maintenance system or a difference in the proportion of cell types in buccal tissue. This exploratory work supports our earlier findings that adverse childhood environments lead to phenotypic life history trade-offs.

The University of Adelaide has recently commissioned a facility dedicated to investigating the atmospheric boundary layer (ABL) for the analysis of wind loads on full-scale heliostats. Wind tunnel testing is an affordable way to analyse loads on a scaled structure before committing to a full-scale design. Scale testing however has its challenges as most cases in literature fail to correctly scale the ABL when scaling a model due to the differences between the ratio of the heliostat chord to the boundary layer depth in a wind tunnel and ABL. There is a lack of direct comparison between wind tunnel and full-scale heliostat wind loads. The Atmospheric Boundary Layer Research Facility (ABLRF) consists of arrays of ultrasonic anemometers and a 1.5 aspect ratio heliostat, mounted on a 6-axis load cell, for the comparison of loads measured in the wind tunnel with a full-scale model. Preliminary results categorise the site to have a roughness of 0.01 m to 0.03 m indicating open country farmland, when compared to standards. Comparison between coefficients of lift force, drag force, and hinge moment on the heliostat model at a single elevation angle at the ABLRF and wind tunnel models in literature verify the commissioning of the site, allowing for further in-depth analysis of wind load coefficients at varying elevation and azimuth angles.

BackgroundIn vitro maturation (IVM) of germinal vesicle intact oocytes prior to in vitro fertilization (IVF) is practiced widely in animals. In human assisted reproduction it is generally reserved for fertility preservation or where ovarian stimulation is contraindicated. Standard practice incorporates complex proteins (CP), in the form of serum and/or albumin, into IVM media to mimic the ovarian follicle environment. However, the undefined nature of CP, together with batch variation and ethical concerns regarding their origin, necessitate the development of more defined formulations. A known component of follicular fluid, melatonin, has multifaceted roles including that of a metabolic regulator and antioxidant. In certain circumstances it can enhance oocyte maturation. At this stage in development, the germinal-vesicle intact oocyte is prone to aneuploidy and epigenetic dysregulation.ObjectivesTo determine the developmental, cytogenetic and epigenetic consequences of removing CP and including melatonin during bovine IVM.Materials and methodsThe study comprised a 2 x 2 factorial arrangement comparing (i) the inclusion or exclusion of CP, and (ii) the addition (100 nM) or omission of melatonin, during IVM. Cumulus-oocyte complexes (COCs) were retrieved from stimulated cycles. Following IVM and IVF, putative zygotes were cultured to Day 8 in standard media. RNAseq was performed on isolated cumulus cells, cytogenetic analyses (SNP-based algorithms) on isolated trophectoderm cells, and DNA methylation analysis (reduced representation bisulfite sequencing) on isolated cells of the inner-cell mass.ResultsRemoval of CP during IVM led to modest reductions in blastocyst development, whilst added melatonin was beneficial in the presence but detrimental in the absence of CP. The composition of IVM media did not affect the nature or incidence of chromosomal abnormalities but cumulus-cell transcript expression indicated altered metabolism (primarily lipid) in COCs. These effects preceded the establishment of distinct metabolic and epigenetic signatures several days later in expanded and hatching blastocysts.ConclusionsThese findings highlight the importance of lipid, particularly sterol, metabolism by the COC during IVM. They lay the foundation for future studies that seek to develop chemically defined systems of IVM for the generation of transferrable embryos that are both cytogenetically and epigenetically normal.

The impact of antimicrobial resistance (AMR) extends beyond the farm-level to other stakeholders warranting the need for a collaborative approach to combat AMR while optimising production objectives and safeguarding human health. This study maps out the effect of AMR originating from poultry production in Senegal and highlights the entry points for interventions from stakeholders’ perspectives. A causal loop diagram (CLD) was developed following a group model building procedure with 20 stakeholders and integrated with network analysis by translating the CLD into an unweighted directed network. Results indicate that with an eigenvector centrality of 1, 0.85, and 0.74, the production cost, on-farm profit, and on-farm productivity, respectively are the most ranked influential variables driving the complexity of AMR in the poultry production system. Two reinforcing feedback loops highlight the dual benefits of improving on-farm productivity and increasing on-farm profit. However, one balancing feedback loop that revolves around the causal link between producers’ investment in qualified human resource personnel to ensure good farm management practices underline the financial implication of producers’ investment decisions. The findings provide precursory groundings for the development of a quantitative SD model, the formulation of intervention scenarios and ex-ante impact assessment of the cost-effectiveness of the interventions.

Abstract Background Women facing increased energetic demands in childhood commonly have altered adult ovarian activity and shorter reproductive lifespan, possibly comprising a strategy to optimize reproductive success. Here, we sought to understand the mechanisms of early-life programming of reproductive function, by integrating analysis of reproductive tissues in an appropriate mouse model with methylation analysis of proxy tissue DNA in a well-characterized population of Bangladeshi migrants in the UK. Bangladeshi women whose childhood was in Bangladesh were found to have later pubertal onset and lower age-matched ovarian reserve than Bangladeshi women who grew-up in England. Subsequently, we aimed to explore the potential relevance to the altered reproductive phenotype of one of the genes that emerged from the screens. Results Of the genes associated with differential methylation in the Bangladeshi women whose childhood was in Bangladesh as compared to Bangladeshi women who grew up in the UK, 13 correlated with altered expression of the orthologous gene in the mouse model ovaries. These mice had delayed pubertal onset and a smaller ovarian reserve compared to controls. The most relevant of these genes for reproductive function appeared to be SRD5A1, which encodes the steroidogenic enzyme 5α reductase-1. SRD5A1 was more methylated at the same transcriptional enhancer in mice ovaries as in the women’s buccal DNA, and its expression was lower in the hypothalamus of the mice as well, suggesting a possible role in the central control of reproduction. The expression of Kiss1 and Gnrh was also lower in these mice compared to controls, and inhibition of 5α reductase-1 reduced Kiss1 and Gnrh mRNA levels and blocked GnRH release in GnRH neuronal cell cultures. Crucially, we show that inhibition of this enzyme in female mice in vivo delayed pubertal onset. Conclusions SRD5A1/5α reductase-1 responds epigenetically to the environment and its downregulation appears to alter the reproductive phenotype. These findings help to explain diversity in reproductive characteristics and how they are shaped by early-life environment and reveal novel pathways that might be targeted to mitigate health issues caused by life-history trade-offs.

N6-methyladenosine (m6A) is the most abundant internal mRNA modification and is dynamically regulated through distinct protein complexes that methylate, demethylate, and/or interpret the m6A modification. These proteins, and the m6A modification, are involved in the regulation of gene expression, RNA stability, splicing and translation. Given its role in these crucial processes, m6A has been implicated in many diseases, including in cancer development and progression. Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer in men and recent studies support a role for m6A in PCa. Despite this, the literature currently lacks an integrated analysis of the expression of key components of the m6A RNA methyltransferase complex, both in PCa patients and in well-established cell line models. For this reason, this study used immunohistochemistry and functional studies to investigate the mechanistic and clinical significance of the METTL3, METTL14, WTAP and CBLL1 components of the m6A methyltransferase complex in PCa specimens and cell lines. Expression of METTL3 and CBLL1, but not METTL14 and WTAP, was associated with poorer PCa patient outcomes. Expression of METTL3, METTL14, WTAP and CBLL1 was higher in PCa cells compared with non-malignant prostate cells, with the highest expression seen in castrate-sensitive, androgen-responsive PCa cells. Moreover, in PCa cell lines, expression of METTL3 and WTAP was found to be androgen-regulated. To investigate the mechanistic role(s) of the m6A methyltransferase complex in PCa cells, short hairpin RNA (shRNA)-mediated knockdown coupled with next generation sequencing was used to determine the transcriptome-wide roles of METTL3, the catalytic subunit of the m6A methyltransferase complex. Functional depletion of METTL3 resulted in upregulation of the androgen receptor (AR), together with 134 AR-regulated genes. METTL3 knockdown also resulted in altered splicing, and enrichment of cell cycle, DNA repair and metabolic pathways. Collectively, this study identified the functional and clinical significance of four essential m6A complex components in PCa patient specimens and cell lines for the first time. Further studies are now warranted to determine the potential therapeutic relevance of METTL3 inhibitors in development to treat leukaemia to benefit patients with PCa.

We describe improvements in CCD performance that have been achieved on 4k×4k, (15 μm)2-pixel, fully depleted CCDs for the Dark Energy Spectroscopic Instrument (DESI) [1]. With respect to our previous work on CCDs for the Dark Energy Camera and the Baryon Oscillation Spectroscopic Survey, our goals for the DESI CCD development were to improve read noise and quantum efficiency, improve the astrometric precision, and decrease pixel-size variations. We report experimental results on recently fabricated CCDs to be used in DESI.

Weaning represents one of the most critical periods in pig production associated with increase in disease risk, reduction in performance and economic loss. Physiological changes faced by piglets during the weaning period have been well characterised, however little is currently known about the underlying molecular pathways involved in these processes. As pig meat remains one of the most consumed sources of protein worldwide, understanding how these changes are mediated is critical to improve pig production and consequently sustainable food production globally. In this study, we evaluated the effect of weaning on transcriptomic changes in the colon of healthy piglets over time using an RNA-sequencing approach. The findings revealed a complex and coordinated response to weaning with the majority of genes found to be rapidly differentially expressed within 1 day post weaning. Multiple genes and pathways affected by weaning in the colon were associated with immune regulation, cell signalling and bacterial defence. NOD-like receptors, Toll-like receptor and JAK-STAT signalling pathways were amongst the pathways significantly enriched. Immune activation was evidenced by the enrichment of pathways involved in interferon response, cytokines interactions, oxidoreductase activities and response to microbial invasion. Biosynthesis of amino acids, in particular arginine, was also amongst the most enriched KEGG pathways in weaned pigs, reinforcing the critical role of arginine in gut homeostasis under stress conditions. Overall, transcriptomic and physiological results suggest that pigs going through the weaning transition undergo a transient period of inflammatory state with a temporary breakdown of barrier functions in the gut. These findings could provide valuable tools to monitor host response post weaning, and may be of particular relevance for the investigation and development of intervention strategies aimed to reduce antibiotic use and improve pig health and performance.

Identifying associations between phenotype and genotype is the fundamental basis of genetic analyses. Inspired by frequentist probability and the work of R. A. Fisher, genome-wide association studies (GWAS) extract information using averages and variances from genotype-phenotype datasets. Averages and variances are legitimated upon creating distribution density functions obtained through the grouping of data into categories. However, as data from within a given category cannot be differentiated, the investigative power of such methodologies is limited. Genomic informational field theory (GIFT) is a method specifically designed to circumvent this issue. The way GIFT proceeds is opposite to that of GWAS. Although GWAS determines the extent to which genes are involved in phenotype formation (bottom-up approach), GIFT determines the degree to which the phenotype can select microstates (genes) for its subsistence (top-down approach). Doing so requires dealing with new genetic concepts, a.k.a. genetic paths, upon which significance levels for genotype-phenotype associations can be determined. By using different datasets obtained in Ovis aries related to bone growth (dataset 1) and to a series of linked metabolic and epigenetic pathways (dataset 2), we demonstrate that removing the informational barrier linked to categories enhances the investigative and discriminative powers of GIFT, namely that GIFT extracts more information than GWAS. We conclude by suggesting that GIFT is an adequate tool to study how phenotypic plasticity and genetic assimilation are linked. NEW & NOTEWORTHY: The genetic basis of complex traits remains challenging to investigate using classic genome-wide association studies (GWASs). Given the success of gene editing technologies, this point needs to be addressed urgently since there can only be useful editing technologies whether precise genotype-phenotype mapping information is available initially. Genomic informational field theory (GIFT) is a new mapping method designed to increase the investigative power of biological/medical datasets suggesting, in turn, the need to rethink the conceptual bases of quantitative genetics. [ABSTRACT FROM AUTHOR]

The growing amount of space debris in the low Earth orbit poses a danger to manned as well as uncrewed missions. Additionally, the new business model of providing internet from space is emerging among new space players, making low Earth orbit more crowded. These factors have encouraged the space community to focus on sustainability in space. Satellite manufacturers typically have the capability to perform complete life cycle analysis (LCA) on their own products based on the manufacturing data. However, there is a lack of a method for non-manufacturers such as environmentalists and the general public to predict the carbon footprint of satellite manufacturing using a subsystem-level mass budget. Hence, this paper presents a method to quantify environmental pollution caused by the production of satellite constellations. Starlink is taken as a case study in this paper, and mass budget is predicted based on space systems engineering budget estimation techniques, the parametric method, and Federal Communication Commission orbital data. With the budget table used as an input, space-specific life cycle assessment is performed based on European Space Agency's life cycle inventory database. Finally, the single score for Starlink constellation version 1 was found to be 76 kilo points. This signifies the annual environmental load. These results could be helpful in obtaining an overview of the environmental effects of the production phase of satellite constellations. Further, the results could act as a foundation for further research on implementing more circular approach practices on Earth as well as in space. [ABSTRACT FROM AUTHOR]

Blythe et al investigate the patterns of oxidized forms of the 5-methylcytosine DNA modification during spermatogenesis. They find that open reading frames of evolutionarily young and transcriptionally active LINE-1 retrotransposons are enriched in 5-carboxylcytosine (5caC) during spermatid maturation, suggesting a link between 5cac and LINE-1 activity.