Human Pleural Fluid Elicits Pyruvate and Phenylalanine Metabolism in Acinetobacter baumannii to Enhance Cytotoxicity and Immune Evasion

The CCAAT box-harboring proteins represent a family of heterotrimeric transcription factors which is highly conserved in eukaryotes. In fungi, one of the particularly important homologs of this family is the Hap complex that separates the DNA-binding domain from the activation domain and imposes essential impacts on regulation of a wide range of cellular functions. So far, a comprehensive summary of this complex has been described in filamentous fungi but not in the yeast. In this review, we summarize a number of studies related to the structure and assembly mode of the Hap complex in a list of representative yeasts. Furthermore, we emphasize recent advances in understanding the regulatory functions of this complex, with a special focus on its role in regulating respiration, production of reactive oxygen species (ROS) and iron homeostasis.Fil: Nyah, Rodman. California State University; Estados UnidosFil: Martinez, Jasmine. California State University; Estados UnidosFil: Fung, Sammie. California State University; Estados UnidosFil: Nakanouchi, Jun. California State University; Estados UnidosFil: Myers, Amber L.. California State University; Estados UnidosFil: Harris, Caitlin M.. California State University; Estados UnidosFil: Dang, Emily. California State University; Estados UnidosFil: Fernandez, Jennifer. California State University; Estados UnidosFil: Liu, Christine. California State University; Estados UnidosFil: Mendoza, Anthony M.. California State University; Estados UnidosFil: Jimenez, Verónica. California State University; Estados UnidosFil: Nikolaidis, Nikolas. California State University; Estados UnidosFil: Brennan, Catherine A.. California State University; Estados UnidosFil: Bonomo, Robert A.. Louis Stokes Cleveland Department of Veterans Affairs Medical Cente; Estados Unidos. Center for Antimicrobial Resistance and Epidemiology; Estados Unidos. Case Western Reserve University School of Medicine; Estados UnidosFil: Sieira, Rodrigo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; ArgentinaFil: Ramirez, Maria Soledad. California State University; Estados Unido

Gut microbiota induce IGF-1 and promote bone formation and growth

New interventions are needed to improve bone health and reduce the risk for osteoporosis and fracture. Dysbiosis is increasingly linked to metabolic abnormalities, although the effect of the microbiota on skeletal health is poorly understood. Previous studies suggest microbiota are detrimental to bone by increasing resorption. In this report, we show that the gut resident microbiota promote bone formation, as well as resorption, with long-term exposure to microbiota resulting in net skeletal growth. Microbiota induce the hormone insulin-like growth factor 1 (IGF-1), which promotes bone growth and remodeling. Short-chain fatty acids (SCFAs), produced when microbiota ferment fiber, also induce IGF-1, suggesting a mechanism by which microbiota affect bone health. Manipulating the microbiome or its metabolites may afford opportunities to optimize bone health and growth

Diverse high-torque bacterial flagellar motors assemble wider stator rings using a conserved protein scaffold

Although it is known that diverse bacterial flagellar motors produce different torques, the mechanism underlying torque variation is unknown. To understand this difference better, we combined genetic analyses with electron cryo-tomography subtomogram averaging to determine in situ structures of flagellar motors that produce different torques, from Campylobacter and Vibrio species. For the first time, to our knowledge, our results unambiguously locate the torque-generating stator complexes and show that diverse high-torque motors use variants of an ancestrally related family of structures to scaffold incorporation of additional stator complexes at wider radii from the axial driveshaft than in the model enteric motor. We identify the protein components of these additional scaffold structures and elucidate their sequential assembly, demonstrating that they are required for stator-complex incorporation. These proteins are widespread, suggesting that different bacteria have tailored torques to specific environments by scaffolding alternative stator placement and number. Our results quantitatively account for different motor torques, complete the assignment of the locations of the major flagellar components, and provide crucial constraints for understanding mechanisms of torque generation and the evolution of multiprotein complexes

The Use of Theories, Models, and Frameworks to Inform the Uptake of Evidence-based Practices in Veterinary Medicine–A Scoping Review

Evidence based practices (EBPs) provide strategies to improve the health, welfare and productivity of animal species. However, ensuring implementation and uptake into routine practice of these EBPs is often challenging. In human health research, one approach used to improve uptake of EBPs is the use of theories, models and/or frameworks (TMFs), however the extent of the use of this approach in veterinary medicine is unknown. The aim of this scoping review was to identify existing veterinary uses of TMFs to inform the uptake of EBPs, and to understand the focus of these applications. Searches were conducted in CAB Abstracts, MEDLINE, Embase and Scopus, alongside grey literature, and ProQuest Dissertations & Theses. The search strategy consisted of a list of known existing TMFs that have been used to improve uptake of EBPs in human health, alongside more generic terminology for implementation and terminology relevant to veterinary medicine. Peer reviewed journal articles and grey literature detailing the use of a TMF to inform uptake of EBP(s) in a veterinary context were included. The search identified 68 studies that met the eligibility criteria. Included studies represented a diverse spread of countries, areas of veterinary concern and EBP. A range of 28 different TMFs were used, although the Theory of Planned Behaviour (TPB) predominated, featuring in 46% of included studies (n = 31). The majority of studies (n = 65, 96%) utilised a TMF with the aim to understand and/or explain what influences implementation outcomes. Only 8 studies (12%) reported the use of a TMF alongside/in conjunction with the actual implementation of an intervention. It is clear there has been some use to date of TMFs to inform uptake of EBPs in veterinary medicine, however it has been sporadic. There has been a heavy reliance on usage of the TPB and other similar classic theories. This has typically been to inform the understanding of factors, such as barriers and facilitators, that may influence the outcome of an implementation effort without then applying this knowledge to the actual implementation of an intervention. Furthermore, there has been a lack of acknowledgement of wider contextual factors and consideration of sustainability of interventions. There is clear potential to increase and expand the usage of TMFs to improve uptake of EBPs in veterinary medicine, including utilising a wider range of TMFs and developing interdisciplinary collaborations with human implementation experts

Environmental DNA reveals links between abundance and composition of airborne grass pollen and respiratory health

This is the final version. Available on open access from Elsevier via the DOI in this recordData and Code Availability Statement: Data collected using qPCR is archived and on NERC EIDC [https://doi.org/10.5285/28208be4-0163-45e6-912c-2db205126925]. Standard pollen monitoring ‘count’ data were sourced from the MEDMI database, with the exception of data from Bangor which were produced as part of the present study and are available on request. Prescribing datasets are publicly available, as are weather, air pollution, deprivation (IMD) and rural-urban category data. Hospital episode statistics (HES) datasets are sensitive, individual-level health data, which are subject to strict privacy regulations and are not publicly available. The study did not generate any unique codeGrass (Poaceae) pollen is the most important outdoor aeroallergen, exacerbating a range of respiratory conditions, including allergic asthma and rhinitis (‘hay fever’). Understanding the relationships between respiratory diseases and airborne grass pollen with view to improving forecasting has broad public health and socioeconomic relevance. It is estimated that there are over 400 million people with allergic rhinitis and over 300 million with asthma, globally, often comorbidly . In the UK, allergic asthma has an annual cost of around US$ 2.8 billion (2017). The relative contributions of the >11,000 (worldwide) grass species to respiratory health have been unresolved, as grass pollen cannot be readily discriminated using standard microscopy. Instead, here we used novel environmental DNA (eDNA) sampling and quantitative PCR (qPCR) , to measure the relative abundances of airborne pollen from common grass species, during two grass pollen seasons (2016 and 2017), across the UK. We quantitatively demonstrate discrete spatiotemporal patterns in airborne grass pollen assemblages. Using a series of generalised additive models (GAMs), we explore the relationship between the incidences of airborne pollen and severe asthma exacerbations (sub-weekly) and prescribing rates of drugs for respiratory allergies (monthly). Our results indicate that a subset of grass species may have disproportionate influence on these population-scale respiratory health responses during peak grass pollen concentrations. The work demonstrates the need for sensitive and detailed biomonitoring of harmful aeroallergens in order to investigate and mitigate their impacts on human health.Natural Environment Research Council (NERC)National Institute for Health Research (NIHR)Public Health EnglandUniversity of ExeterUniversity College LondonMet Offic

Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe

Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season

Reimagining the language of engagement in a post-stakeholder world

Language matters in shaping perceptions and guiding behaviour. The term stakeholder is widely used, yet little attention is paid to the possibility that its use may inadvertently perpetuate colonial narratives and reinforce systemic inequities. In this article, we critically examine the limitations of the stakeholder concept and its ambiguity, normativity, and exclusionary implications. We emphasise the importance of using language that gives a voice to marginalised groups, promotes inclusion and equity, and fosters meaningful and reflexive participation in decision-making processes. In critiquing the use of the term and calling for alternative practices, we aim to contribute to the decolonisation of research norms and the creation of more inclusive and equitable societies. Therefore, rather than advocating a single alternative term, we suggest a focus on the people, places, and species affected by decisions, interventions, projects, and issues

Identifying models of HIV care and treatment service delivery in Tanzania, Uganda, and Zambia using cluster analysis and Delphi survey.

BACKGROUND: Organization of HIV care and treatment services, including clinic staffing and services, may shape clinical and financial outcomes, yet there has been little attempt to describe different models of HIV care in sub-Saharan Africa (SSA). Information about the relative benefits and drawbacks of different models could inform the scale-up of antiretroviral therapy (ART) and associated services in resource-limited settings (RLS), especially in light of expanded client populations with country adoption of WHO's test and treat recommendation. METHODS: We characterized task-shifting/task-sharing practices in 19 diverse ART clinics in Tanzania, Uganda, and Zambia and used cluster analysis to identify unique models of service provision. We ran descriptive statistics to explore how the clusters varied by environmental factors and programmatic characteristics. Finally, we employed the Delphi Method to make systematic use of expert opinions to ensure that the cluster variables were meaningful in the context of actual task-shifting of ART services in SSA. RESULTS: The cluster analysis identified three task-shifting/task-sharing models. The main differences across models were the availability of medical doctors, the scope of clinical responsibility assigned to nurses, and the use of lay health care workers. Patterns of healthcare staffing in HIV service delivery were associated with different environmental factors (e.g., health facility levels, urban vs. rural settings) and programme characteristics (e.g., community ART distribution or integrated tuberculosis treatment on-site). CONCLUSIONS: Understanding the relative advantages and disadvantages of different models of care can help national programmes adapt to increased client load, select optimal adherence strategies within decentralized models of care, and identify differentiated models of care for clients to meet the growing needs of long-term ART patients who require more complicated treatment management

Airborne DNA reveals predictable spatial and seasonal dynamics of fungi.

Fungi are among the most diverse and ecologically important kingdoms in life. However, the distributional ranges of fungi remain largely unknown as do the ecological mechanisms that shape their distributions1,2. To provide an integrated view of the spatial and seasonal dynamics of fungi, we implemented a globally distributed standardized aerial sampling of fungal spores3. The vast majority of operational taxonomic units were detected within only one climatic zone, and the spatiotemporal patterns of species richness and community composition were mostly explained by annual mean air temperature. Tropical regions hosted the highest fungal diversity except for lichenized, ericoid mycorrhizal and ectomycorrhizal fungi, which reached their peak diversity in temperate regions. The sensitivity in climatic responses was associated with phylogenetic relatedness, suggesting that large-scale distributions of some fungal groups are partially constrained by their ancestral niche. There was a strong phylogenetic signal in seasonal sensitivity, suggesting that some groups of fungi have retained their ancestral trait of sporulating for only a short period. Overall, our results show that the hyperdiverse kingdom of fungi follows globally highly predictable spatial and temporal dynamics, with seasonality in both species richness and community composition increasing with latitude. Our study reports patterns resembling those described for other major groups of organisms, thus making a major contribution to the long-standing debate on whether organisms with a microbial lifestyle follow the global biodiversity paradigms known for macroorganisms4,5

Reimagining the language of engagement in a post-stakeholder world

Language matters in shaping perceptions and guiding behaviour. The term stakeholder is widely used, yet little attention is paid to the possibility that its use may inadvertently perpetuate colonial narratives and reinforce systemic inequities. In this article, we critically examine the limitations of the stakeholder concept and its ambiguity, normativity, and exclusionary implications. We emphasise the importance of using language that gives a voice to marginalised groups, promotes inclusion and equity, and fosters meaningful and reflexive participation in decision-making processes. In critiquing the use of the term and calling for alternative practices, we aim to contribute to the decolonisation of research norms and the creation of more inclusive and equitable societies. Therefore, rather than advocating a single alternative term, we suggest a focus on the people, places, and species affected by decisions, interventions, projects, and issues