Search

Especially in the wake of the recent pandemic, asynchronous consulting has become increasingly central to writing center work. Yet writing center scholarship has little attended to the significant impact writer input can have on asynchronous writer-consultant exchanges. Drawing on asynchronous consultation data collected before and after our 2019 redesign of our writing center's asynchronous system, this comparative study examines the specific effect of the writer appointment form on the nature of both writers' requests for feedback (RFFs) and consultants' resulting comments. Our findings suggest that differently designed appointments forms can scaffold significantly different kinds of asynchronous writer-consultant exchanges, especially visible in the different emphases writers and consultants put on issues of correctness, clarity, organization, and the writer's rhetorical situation. We argue that, particularly in the case of asynchronous consulting--which can easily devolve to a "fix-it" model of consulting--it is important for writing center administrators to design asynchronous platforms that encourage both writers and consultants to more explicitly consider how the specific rhetorical features of a writing task can shape revising goals.

Immersive learning practices (ILPs) in higher education are multidisciplinary in nature and varied in levels of integration into the student learning process. They appear in a variety of higher education programs such as teacher education, social work, law, and health sciences, and in practices such as service-learning, study away, internships, and foreign-language instruction. Based on observations of teaching and data from an open-ended survey and semi-structured interviews with post-secondary educators from three different countries, this study theorizes that immersive learning practices are composed of six distinct underlying theoretical components that work in combination. These six components can be used to describe, define, compare, and design different types of structured ILPs. This study suggests that ILPs are pedagogically distinct from other forms of engaged and experiential learning.

ABSTRACT Nitrogen is an essential element for all living organisms, including Escherichia coli. Potential nitrogen sources are abundant in the intestine, but knowledge of those used specifically by E. coli to colonize remains limited. Here, we sought to determine the specific nitrogen sources used by E. coli to colonize the streptomycin-treated mouse intestine. We began by investigating whether nitrogen is limiting in the intestine. The NtrBC two-component system upregulates approximately 100 genes in response to nitrogen limitation. We showed that NtrBC is crucial for E. coli colonization, although most genes of the NtrBC regulon are not induced, which indicates that nitrogen is not limiting in the intestine. RNA-seq identified upregulated genes in colonized E. coli involved in transport and catabolism of seven amino acids, dipeptides and tripeptides, purines, pyrimidines, urea, and ethanolamine. Competitive colonization experiments revealed that L-serine, N-acetylneuraminic acid, N-acetylglucosamine, and di- and tripeptides serve as nitrogen sources for E. coli in the intestine. Furthermore, the colonization defect of a L-serine deaminase mutant was rescued by excess nitrogen in the drinking water but not by an excess of carbon and energy, demonstrating that L-serine serves primarily as a nitrogen source. Similar rescue experiments showed that N-acetylneuraminic acid serves as both a carbon and nitrogen source. To a minor extent, aspartate and ammonia also serve as nitrogen sources. Overall, these findings demonstrate that E. coli utilizes multiple nitrogen sources for successful colonization of the mouse intestine, the most important of which is L-serine.IMPORTANCEWhile much is known about the carbon and energy sources that are used by E. coli to colonize the mammalian intestine, very little is known about the sources of nitrogen. Interrogation of colonized E. coli by RNA-seq revealed that nitrogen is not limiting, indicating an abundance of nitrogen sources in the intestine. Pathways for assimilation of nitrogen from several amino acids, dipeptides and tripeptides, purines, pyrimidines, urea, and ethanolamine were induced in mice. Competitive colonization assays confirmed that mutants lacking catabolic pathways for L-serine, N-acetylneuraminic acid, N-acetylglucosamine, and di- and tripeptides had colonization defects. Rescue experiments in mice showed that L-serine serves primarily as a nitrogen source, whereas N-acetylneuraminic acid provides both carbon and nitrogen. Of the many nitrogen assimilation mutants tested, the largest colonization defect was for an L-serine deaminase mutant, which demonstrates L-serine is the most important nitrogen source for colonized E. coli.

Digital tools and online presence have become a cornerstone in public engagement and involvement strategy and delivery. We here describe the co-production process behind launching a new multilingual resource for schools in the United Kingdom and beyond, jointly between university scientists, engagement professionals, primary and secondary teachers, and web designers. The ‘Superbugs’ website aims at raising awareness and increasing the public understanding of the microbial world in, on, and around us—with a focus on infection, hygiene, and antimicrobial resistance—and attracted >19,000 online visitors, >33,500 page views, and > 775,000 Twitter impressions over the past 24 months. Superbugs.online is available in English, Welsh, Irish, and Scottish Gaelic, thus making it accessible to everyone in the United Kingdom and Ireland, regardless of the language in which they receive and deliver their science education. The website is easy to navigate and features background information, quizzes, animations, videos, illustrated stories, interactive timelines, games, and protocols for home experiments. All materials are presented in a non-prescriptive way, aimed at allowing flexibility for the materials to be adapted to the individual needs of teachers and pupils alike. Our study has led to a demonstrable impact on the co-production team and on pupils and teachers as key stakeholders, based on a comprehensive evaluation of the co-production process itself, the impact of the end product, and the creation of lasting relationships with stakeholders and co-producers, for the mutual benefit of everyone involved.

Trinidad and Tobago are important islands to Neotropical woody bamboo taxonomy. Trinidad is a type locality for two widely applied names with poorly defined species concepts: Arthrostylidium pubescens and A. excelsum, and two potentially endemic species: Chusquea cylindrica and Rhipidocladum prestoei. Few resources exist for the islands to adequately identify all the woody bamboo species that putatively grow there. The serialized vascular flora of Trinidad and Tobago (1928–1992), for instance, lacks a treatment for Poaceae. Moreover, the most speciose native genus, Arthrostylidium, is only partially revised, with the emphasis on the South American species and not those of the West Indies. Our objective is to critically review the woody bamboos of Trinidad and Tobago, clarify which species are or have been known from the islands, and provide an identification key, species accounts and distribution maps for the revised list of taxa. We conducted fieldwork campaigns in 2021–2023, and reviewed herbarium specimens and human observation records of woody bamboos from the islands. Newly collected specimens were vouchered and all woody bamboo records were georeferenced and plotted using QGIS. We confirmed two species of native woody bamboo and four species of introduced woody bamboo were extant on Trinidad. An additional three Western Hemisphere species have historic records of occurrence on the islands. Native species diversity correlated well with previously identified floristic hotspots. One introduced species, Bambusa vulgaris, is common on both islands. To the best of our knowledge, there are currently no native woody bamboo species present on Tobago, however, A. pubescens appears to have been growing along the Main Ridge in the past. The historic presence of some species not currently found may be the result of dynamic and/or stochastic colonization events among the islands and mainland South America.

With the scaling of lateral dimensions in advanced transistors, an increased gate capacitance is desirable both to retain the control of the gate electrode over the channel and to reduce the operating voltage1. This led to a fundamental change in the gate stack in 2008, the incorporation of high-dielectric-constant HfO2 (ref. 2), which remains the material of choice to date. Here we report HfO2-ZrO2 superlattice heterostructures as a gate stack, stabilized with mixed ferroelectric-antiferroelectric order, directly integrated onto Si transistors, and scaled down to approximately 20 ångströms, the same gate oxide thickness required for high-performance transistors. The overall equivalent oxide thickness in metal-oxide-semiconductor capacitors is equivalent to an effective SiO2 thickness of approximately 6.5 ångströms. Such a low effective oxide thickness and the resulting large capacitance cannot be achieved in conventional HfO2-based high-dielectric-constant gate stacks without scavenging the interfacial SiO2, which has adverse effects on the electron transport and gate leakage current3. Accordingly, our gate stacks, which do not require such scavenging, provide substantially lower leakage current and no mobility degradation. This work demonstrates that ultrathin ferroic HfO2-ZrO2 multilayers, stabilized with competing ferroelectric-antiferroelectric order in the two-nanometre-thickness regime, provide a path towards advanced gate oxide stacks in electronic devices beyond conventional HfO2-based high-dielectric-constant materials.

Aegilops tauschii, the diploid wild progenitor of the D subgenome of bread wheat, is a reservoir of genetic diversity for improving bread wheat performance and environmental resilience. Here we sequenced 242 Ae. tauschii accessions and compared them to the wheat D subgenome to characterize genomic diversity. We found that a rare lineage of Ae. tauschii geographically restricted to present-day Georgia contributed to the wheat D subgenome in the independent hybridizations that gave rise to modern bread wheat. Through k-mer-based association mapping, we identified discrete genomic regions with candidate genes for disease and pest resistance and demonstrated their functional transfer into wheat by transgenesis and wide crossing, including the generation of a library of hexaploids incorporating diverse Ae. tauschii genomes. Exploiting the genomic diversity of the Ae. tauschii ancestral diploid genome permits rapid trait discovery and functional genetic validation in a hexaploid background amenable to breeding.

Doctoral researchers and early career researchers (ECRs) are crucial to producing scientific advancements and represent the future of academic leadership. Their research endeavours were changed radically by lockdowns in response to the COVID-19 pandemic. The aim of this study was to explore the perceived benefits and challenges of the national lockdown in the UK from the perspective of doctoral researchers and ECRs. We present analysis of qualitative survey data from 1,142 doctoral researchers and ECRs on their experiences of the first UK lockdown collected from April 16, 2020-May 14, 2020. Our findings suggest considerable heterogeneity in how the pandemic impacted this key group of academic workers. Challenges arising from the lockdown largely cohered around a poor work environment, limited access to resources, perceptions of pressure, and negative psychological outcomes. Conversely, respondents also highlighted several benefits in the early stages of the pandemic, with the change to working from home creating more time, resulting in greater productivity and a better work-life balance. Collectively, findings indicate the importance of considering the personal circumstances and needs of individual researchers. We discuss the implications for support these researchers require to rebuild their careers in the wake of the initial disruption.

Neuroimaging has a key role in identifying small-vessel vasculitis from common diseases it mimics, such as multiple sclerosis. Oftentimes, a multitude of these conditions present similarly, and thus diagnosis is difficult. To date, there is no standardized method to differentiate between these diseases. This review identifies and presents existing scoring tools that could serve as a starting point for integrating artificial intelligence/machine learning (AI/ML) into the clinical decision-making process for these rare diseases. A scoping literature review of EMBASE and MEDLINE included 114 articles to evaluate what criteria exist to diagnose small-vessel vasculitis and common mimics. This paper presents the existing criteria of small-vessel vasculitis conditions and mimics them to guide the future integration of AI/ML algorithms to aid in diagnosing these conditions, which present similarly and non-specifically.

Abstract Background Vasomotor symptoms (VMS) can often significantly impact women’s quality of life at menopause. In vivo studies have shown that increased neurokinin B (NKB) / neurokinin 3 receptor (NK3R) signalling contributes to VMS, with previous genetic studies implicating the TACR3 gene locus that encodes NK3R. Large-scale genomic analyses offer the possibility of biological insights but few such studies have collected data on VMS, while proxy phenotypes such as hormone replacement therapy (HRT) use are likely to be affected by changes in clinical practice. We investigated the genetic basis of VMS by analysing routinely-collected health records. Methods We performed a GWAS of VMS derived from linked primary-care records and cross-sectional self-reported HRT use in up to 153,152 women from UK Biobank, a population-based cohort. In a subset of this cohort (n = 39,356), we analysed exome-sequencing data to test the association with VMS of rare deleterious genetic variants. Finally, we used Mendelian randomisation analysis to investigate the reasons for HRT use over time. Results Our GWAS of health-records derived VMS identified a genetic signal near TACR3 associated with a lower risk of VMS (OR=0.76 (95% CI 0.72,0.80) per A allele, P=3.7x10-27), which was consistent with previous studies, validating this approach. Conditional analyses demonstrated independence of genetic signals for puberty timing and VMS at the TACR3 locus, including a rare variant predicted to reduce functional NK3R levels that was associated with later menarche (P = 5 × 10–9) but showed no association with VMS (P = 0.6). Younger menopause age was causally-associated with greater HRT use before 2002 but not after. Conclusions We provide support for TACR3 in the genetic basis of VMS but unexpectedly find that rare genomic variants predicted to lower NK3R levels did not modify VMS, despite the proven efficacy of NK3R antagonists. Using genomics we demonstrate changes in genetic associations with HRT use over time, arising from a change in clinical practice since the early 2000s, which is likely to reflect a switch from preventing post-menopausal complications in women with earlier menopause to primarily treating VMS. Our study demonstrates that integrating routinely-collected primary care health records and genomic data offers great potential for exploring the genetic basis of symptoms.

Abstract Background Major depressive disorder (MDD) has a significant impact on global burden of disease. Complications in clinical management can occur when response to pharmacological modalities is considered inadequate and symptoms persist (treatment-resistant depression (TRD)). We aim to investigate inflammation, proxied by C-reactive protein (CRP) levels, and body mass index (BMI) as putative causal risk factors for depression and subsequent treatment resistance, leveraging genetic information to avoid confounding via Mendelian randomisation (MR). Methods We used the European UK Biobank subcohort ( $$n=451,025$$ n = 451 , 025 ), the mental health questionnaire (MHQ) and clinical records. For treatment resistance, a previously curated phenotype based on general practitioner (GP) records and prescription data was employed. We applied univariable and multivariable MR models to genetically predict the exposures and assess their causal contribution to a range of depression outcomes. We used a range of univariable, multivariable and mediation MR models techniques to address our research question with maximum rigour. In addition, we developed a novel statistical procedure to apply pleiotropy-robust multivariable MR to one sample data and employed a Bayesian bootstrap procedure to accurately quantify estimate uncertainty in mediation analysis which outperforms standard approaches in sparse binary outcomes. Given the flexibility of the one-sample design, we evaluated age and sex as moderators of the effects. Results In univariable MR models, genetically predicted BMI was positively associated with depression outcomes, including MDD ( $$\beta$$ β ( $$95\%$$ 95 % CI): 0.133(0.072, 0.205)) and TRD (0.347(0.002, 0.682)), with a larger magnitude in females and with age acting as a moderator of the effect of BMI on severity of depression (0.22(0.050, 0.389)). Multivariable MR analyses suggested an independent causal effect of BMI on TRD not through CRP (0.395(0.004, 0.732)). Our mediation analyses suggested that the effect of CRP on severity of depression was partly mediated by BMI. Individuals with TRD ( $$n=2199$$ n = 2199 ) observationally had higher CRP and BMI compared with individuals with MDD alone and healthy controls. Discussion Our work supports the assertion that BMI exerts a causal effect on a range of clinical and questionnaire-based depression phenotypes, with the effect being stronger in females and in younger individuals. We show that this effect is independent of inflammation proxied by CRP levels as the effects of CRP do not persist when jointly estimated with BMI. This is consistent with previous evidence suggesting that overweight contributed to depression even in the absence of any metabolic consequences. It appears that BMI exerts an effect on TRD that persists when we account for BMI influencing MDD.

Abstract Background We sought to determine the extent to which cortisol suppressed innate and T cell-mediated cytokine production and whether it could be involved in reducing peripheral cytokine production following subarachnoid haemorrhage (SAH). Methods Whole blood from healthy controls, patients with SAH and healthy volunteers was stimulated with lipopolysaccharide (LPS), to stimulate innate immunity, or phytohaemagglutinin (PHA), to stimulate T cell-mediated immunity. Varying concentrations of cortisol were included, with or without the cortisol antagonist RU486. Concentration of interleukin-6 (IL-6), IL-1β and tumour necrosis factor-alpha) TNFα were determined as a measure of innate immunity. IL-6, IL-17 (interferon gamma) IFNƔ and IL-17 were determined as an indicator of T cell-mediated immunity. Results Suppression of innate responses to LPS was apparent in whole blood from SAH patients, relative to healthy controls, and TNFα production was inversely correlated with plasma cortisol concentration. Cytokine production in whole blood from healthy volunteers was inhibited by cortisol concentrations from 0.33 µM, or 1 µM and above, and these responses were effectively reversed by the cortisol antagonist RU-486. In SAH patients, RU-486 reversed suppression of innate TNF-α and IL-6 responses, but not IL-1ß or T cell-mediated responses. Conclusion These data suggest that cortisol may play a role in reducing innate, but not T cell-mediated immune responses in patients with injuries such as SAH and that cortisol antagonists could be effective in boosting early innate responses.

Abstract Lions are one of the world’s most iconic species but are threatened with extinction. Developing effective range-wide conservation plans are crucial but hampered by the relative lack of knowledge on specific threats facing each population and the socio-political context for conservation. Here, we present a range-wide examination of the relative fragility of lion populations, examining socio-political factors alongside ecological ones. We found Ethiopia’s Maze National Park had the most ecologically fragile geographic population while Kavango-Zambezi was the least. At a country level, lion populations had highest ecological fragility in Cameroon and Malawi. When we examined socio-political fragility, Somalia was the most fragile lion range country, followed by South Sudan. When socio-political and ecological fragility were combined, lion populations in Maze National Park and Bush-Bush (Somalia) and more broadly, Somalian and Malawian lion populations were the most fragile. These insights should help inform more nuanced and appropriately targeted lion conservation plans.

Abstract Aim To describe community healthcare professionals' experiences of preventing malnutrition among children in rural Bangladesh. Methods A descriptive qualitative study with a total of seven healthcare professionals were recruited from a non‐governmental organisation in rural Bangladesh. Individual in‐depth interviews were conducted in November 2018 using a semi‐structured interview guide. The audio‐recorded interviews were transcribed verbatim and analysed manually using content analysis. Results The data analysis resulted in two main categories: Implementation and practices in preventing malnutrition and Challenges in working with prevention of malnutrition. Education was considered an important and essential preventative intervention. Healthcare professionals faced challenges in their work in relation to socio‐cultural and climate factors. The findings indicate how healthcare professional identified the need for increased knowledge and resources in the community to promote nutritional health in children.

Itaconate has emerged as a critical immunoregulatory metabolite. Here, we examined the therapeutic potential of itaconate in atherosclerosis. We found that both itaconate and the enzyme that synthesizes it, aconitate decarboxylase 1 (Acod1, also known as immune-responsive gene 1 [IRG1]), are upregulated during atherogenesis in mice. Deletion of Acodl in myeloid cells exacerbated inflammation and atherosclerosis in vivo and resulted in an elevated frequency of a specific subset of M1-polarized proinflammatory macrophages in the atherosclerotic aorta. Importantly, Acod1 levels were inversely correlated with clinical occlusion in atherosclerotic human aorta specimens. Treating mice with the itaconate derivative 4- octyl itaconate attenuated inflammation and atherosclerosis induced by high cholesterol. Mechanistically, we found that the antioxidant transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), was required for itaconate to suppress macrophage activation induced by oxidized lipids in vitro and to decrease atherosclerotic lesion areas in vivo. Overall, our work shows that itaconate suppresses atherogenesis by inducing Nrf2-dependent inhibition of proinflammatory responses in macrophages. Activation of the itaconate pathway may represent an important approach to treat atherosclerosis., Introduction Itaconate has emerged as a compelling immunomodulatory metabolite produced in the tricarboxylic acid (TCA) cycle (1, 2). The enzyme cis-aconitate decarboxylase 1 (Acod1, also named Irg1) is responsible for [...]