Host-derived O-glycans inhibit toxigenic conversion by a virulence-encoding phage in Vibrio cholerae.

Pandemic and endemic strains of Vibrio cholerae arise from toxigenic conversion by the CTXφ bacteriophage, a process by which CTXφ infects nontoxigenic strains of V. cholerae. CTXφ encodes the cholera toxin, an enterotoxin responsible for the watery diarrhea associated with cholera infections. Despite the critical role of CTXφ during infections, signals that affect CTXφ-driven toxigenic conversion or expression of the CTXφ-encoded cholera toxin remain poorly characterized, particularly in the context of the gut mucosa. Here, we identify mucin polymers as potent regulators of CTXφ-driven pathogenicity in V. cholerae. Our results indicate that mucin-associated O-glycans block toxigenic conversion by CTXφ and suppress the expression of CTXφ-related virulence factors, including the toxin co-regulated pilus and cholera toxin, by interfering with the TcpP/ToxR/ToxT virulence pathway. By synthesizing individual mucin glycan structures de novo, we identify the Core 2 motif as the critical structure governing this virulence attenuation. Overall, our results highlight a novel mechanism by which mucins and their associated O-glycan structures affect CTXφ-mediated evolution and pathogenicity of V. cholerae, underscoring the potential regulatory power housed within mucus.

Natural variation and dosage of the HEI10 meiotic E3 ligase control Arabidopsis crossover recombination.

During meiosis, homologous chromosomes undergo crossover recombination, which creates genetic diversity and balances homolog segregation. Despite these critical functions, crossover frequency varies extensively within and between species. Although natural crossover recombination modifier loci have been detected in plants, causal genes have remained elusive. Using natural Arabidopsis thaliana accessions, we identified two major recombination quantitative trait loci (rQTLs) that explain 56.9% of crossover variation in Col×Ler F2 populations. We mapped rQTL1 to semidominant polymorphisms in HEI10, which encodes a conserved ubiquitin E3 ligase that regulates crossovers. Null hei10 mutants are haploinsufficient, and, using genome-wide mapping and immunocytology, we show that transformation of additional HEI10 copies is sufficient to more than double euchromatic crossovers. However, heterochromatic centromeres remained recombination-suppressed. The strongest HEI10-mediated crossover increases occur in subtelomeric euchromatin, which is reminiscent of sex differences in Arabidopsis recombination. Our work reveals that HEI10 naturally limits Arabidopsis crossovers and has the potential to influence the response to selection.

Massive crossover elevation via combination of HEI10 and recq4a recq4b during Arabidopsis meiosis.

During meiosis, homologous chromosomes undergo reciprocal crossovers, which generate genetic diversity and underpin classical crop improvement. Meiotic recombination initiates from DNA double-strand breaks (DSBs), which are processed into single-stranded DNA that can invade a homologous chromosome. The resulting joint molecules can ultimately be resolved as crossovers. In Arabidopsis, competing pathways balance the repair of ∼100-200 meiotic DSBs into ∼10 crossovers per meiosis, with the excess DSBs repaired as noncrossovers. To bias DSB repair toward crossovers, we simultaneously increased dosage of the procrossover E3 ligase gene HEI10 and introduced mutations in the anticrossovers helicase genes RECQ4A and RECQ4B As HEI10 and recq4a recq4b increase interfering and noninterfering crossover pathways, respectively, they combine additively to yield a massive meiotic recombination increase. Interestingly, we also show that increased HEI10 dosage increases crossover coincidence, which indicates an effect on interference. We also show that patterns of interhomolog polymorphism and heterochromatin drive recombination increases distally towards the subtelomeres in both HEI10 and recq4a recq4b backgrounds, while the centromeres remain crossover suppressed. These results provide a genetic framework for engineering meiotic recombination landscapes in plant genomes.

Recombination Rate Heterogeneity within Arabidopsis Disease Resistance Genes.

Meiotic crossover frequency varies extensively along chromosomes and is typically concentrated in hotspots. As recombination increases genetic diversity, hotspots are predicted to occur at immunity genes, where variation may be beneficial. A major component of plant immunity is recognition of pathogen Avirulence (Avr) effectors by resistance (R) genes that encode NBS-LRR domain proteins. Therefore, we sought to test whether NBS-LRR genes would overlap with meiotic crossover hotspots using experimental genetics in Arabidopsis thaliana. NBS-LRR genes tend to physically cluster in plant genomes; for example, in Arabidopsis most are located in large clusters on the south arms of chromosomes 1 and 5. We experimentally mapped 1,439 crossovers within these clusters and observed NBS-LRR gene associated hotspots, which were also detected as historical hotspots via analysis of linkage disequilibrium. However, we also observed NBS-LRR gene coldspots, which in some cases correlate with structural heterozygosity. To study recombination at the fine-scale we used high-throughput sequencing to analyze ~1,000 crossovers within the RESISTANCE TO ALBUGO CANDIDA1 (RAC1) R gene hotspot. This revealed elevated intragenic crossovers, overlapping nucleosome-occupied exons that encode the TIR, NBS and LRR domains. The highest RAC1 recombination frequency was promoter-proximal and overlapped CTT-repeat DNA sequence motifs, which have previously been associated with plant crossover hotspots. Additionally, we show a significant influence of natural genetic variation on NBS-LRR cluster recombination rates, using crosses between Arabidopsis ecotypes. In conclusion, we show that a subset of NBS-LRR genes are strong hotspots, whereas others are coldspots. This reveals a complex recombination landscape in Arabidopsis NBS-LRR genes, which we propose results from varying coevolutionary pressures exerted by host-pathogen relationships, and is influenced by structural heterozygosity.

Discourses Reproducing Gender Inequities in Hospice Palliative Home Care.

BACKGROUND: As home is a site where gendered attitudes, beliefs, and practices are reproduced, it is imperative that policies and practices promote gender equity in end-of-life care at home. PURPOSE: The purpose of this study was to critically analyze gender relations in the sociopolitical context of hospice palliative home care. METHODS: Using a critical feminist perspective, we examined gender relations between and among clients with cancer, their family caregivers, and nurses in hospice palliative home care. Ethnographic methods of in-depth interviews (n = 25), observations of home visits (n = 9), and review of documents (n = 12) were employed to expose gender (in)equities. FINDINGS: This critical analysis sheds light on institutional discourses that reproduce gender inequities: discourses of difference and denial; discourses of individuality, autonomy, and choice; and discourses of efficiency, objectivity, and rationality. Although gender was discounted, these neoliberal discourses reinforced traditional gender relations. DISCUSSION: Neoliberal discourses frame health and health-care experiences as resulting primarily from individual behaviors and biomedical factors, permitting health-care providers and policy makers to overlook power relations and the sociopolitical forces that obscure gender inequities. A critical perspective is needed to consider how social structures significantly shape everyday gendered experiences in hospice palliative home care.

Modification of meiotic recombination by natural variation in plants.

Meiosis is a specialized cell division that produces haploid gametes required for sexual reproduction. During the first meiotic division, homologous chromosomes pair and undergo reciprocal crossing over, which recombines linked sequence variation. Meiotic recombination frequency varies extensively both within and between species. In this review, we will examine the molecular basis of meiotic recombination rate variation, with an emphasis on plant genomes. We first consider cis modification caused by polymorphisms at the site of recombination, or elsewhere on the same chromosome. We review cis effects caused by mismatches within recombining joint molecules, the effect of structural hemizygosity, and the role of specific DNA sequence motifs. In contrast, trans modification of recombination is exerted by polymorphic loci encoding diffusible molecules, which are able to modulate recombination on the same and/or other chromosomes. We consider trans modifiers that act to change total recombination levels, hotspot locations, or interactions between homologous and homeologous chromosomes in polyploid species. Finally, we consider the significance of genetic variation that modifies meiotic recombination for adaptation and evolution of plant species.

Structural impact on gendered expectations and exemptions for family caregivers in hospice palliative home care.

Evidence of gender differences in the amount and type of care provided by family caregivers in hospice palliative home care suggests potential inequities in health and health care experiences. As part of a larger critical ethnographic study examining gender relations among clients with cancer, their family caregivers and primary nurses, this article describes gendered expectations and exemptions for family caregivers within the sociopolitical context of end-of-life at home. Data were collected from in-depth interviews (n = 25), observations of agency home care visits (n = 9) and analyses of policy and home care agency documents (n = 12). Employing a critical feminist lens, a gender-based analysis revealed that structural discourses emphasizing an artificial divide between public and private spheres constructed end-of-life at home as private and apolitical. Associated with care of home and family, women were most impacted by these public/private discourses underpinning neoliberal values of cost-efficiency. Findings suggest that a critical perspective is needed to assist policy makers and healthcare providers to view how caregiver experiences are shaped by structures that control the availability of resources. Thus, instead of focusing on caregivers' deficits, interventions should be directed at the social, political and economic conditions that shape gendered experiences.

Gendered Processes in Hospice Palliative Home Care for Seniors With Cancer and Their Family Caregivers.

There has been limited investigation into the processes that shape gender (in)equities in hospice palliative home care. As part of a larger critical ethnographic study, we examined how and why gender relations occur in this context. Using a critical feminist lens, we conducted in-depth interviews with clients living with terminal cancer, their family caregivers and primary nurses; observations of agency home visits; and review of institutional documents. A gender-based analysis revealed that gender enactments of Regulating Gender Relations were legitimized through ideological processes of Normalizing Gender Relations and Equalizing Gender Relations (Re)produced through institutional discourses of individualism and egalitarianism, these gendered processes both advantaged and disadvantaged men and women in hospice palliative home care. Findings suggest that to promote equity, health care providers and policy makers must attend to gender as a prevalent social determinant of health and health care. Implications for policy, practice, education, and research are discussed.

Ontario's Poverty Reduction Strategy: A Critical Discourse Analysis.

This article overviews the second phase of a two-phase study which examined experiences of health and social exclusion among mothers experiencing homelessness in Ontario, Canada. A critical discourse analysis was employed to analyze the policy document, Realizing Our Potential: Ontario's Poverty Reduction Strategy, 2014-2019. In nursing, analysis of policy is an emerging form of scholarship, one that draws attention to the macro levels influencing health and health promotion, such as the social determinants of health, and the policies that impact them. The clear neo-liberal underpinnings, within the strategy, with a focus on productivity and labor market participation leave little room for an understanding of poverty reduction from a human rights perspective. Further, gender-neutrality rendered the poverty experienced by women, and mothers, invisible. Notably, there were a lack of deadlines, target dates, and thorough action and evaluation plans. Such absence troubles whether poverty reduction is truly a priority for the government, and society as a whole.

Creating an Ethnodrama to Catalyze Dialogue in Home-Based Dementia Care.

This article describes the development of a theater script derived from a critical ethnographic study that followed people living with dementia--and their family and professional caregivers--over an 18-month period. Analysis of the ethnographic data yielded four themes that characterized home-based dementia care relationships: managing care resources, making care decisions, evaluating care practices, and reifying care norms. The research team expanded to include a colleague with playwright experience, who used these themes to write a script. A theater director was included to cast and direct the play, and finally, a videography company filmed the actors on a realistic set. To contribute to the qualitative health research and the research-based theater knowledge translation literatures, this article describes and explains the creative decisions taken as part of our effort to disseminate research focused on home-based dementia care in a way that catalyzes and fosters critical (actionable) dialogue.

Social Exclusion and Health: The Development of Nursing Knowledge.

The concept of social exclusion has been proposed as an important social determinant of health. However, use of the concept in health and health promotion research is in its infancy. In nursing discourse, in particular, exploration and application of the concept of social exclusion is minimal. The purpose of this article is to explore the relevance of the concept of social exclusion in the development of nursing knowledge. Current knowledge regarding social exclusion is examined and its use in health-related research is explored. To conclude, a conceptualization of social exclusion for the development of nursing knowledge is proposed.

Il a été proposé que le concept d'exclusion sociale soit considéré comme un important déterminant social de la santé. Cependant, le recours à ce concept dans la recherche en santé et en promotion de la santé en est encore à ses balbutiements. Dans le discours des sciences infirmières en particulier, l'étude et l'application du concept d'exclusion sociale sont toujours minimes. L'objectif du présent article est d'explorer la pertinence du concept d'exclusion sociale dans le développement du savoir en sciences infirmières. Les auteures y examinent les connaissances actuelles relatives à l'exclusion sociale et leur utilisation dans la recherche liée à la santé. L'article propose en conclusion une conceptualisation de l'exclusion sociale adaptée au développement des connaissances en sciences infirmières.

Nurses negotiating professional-familial care boundaries: striving for balance within double duty caregiving.

The purpose of this sequential, two-phase mixed-methods study was to examine the health of male and female nurses who provided care to older relatives (i.e., double duty caregivers). We explored the experiences of 32 double duty caregivers, which led to the development of an emergent grounded theory, Negotiating Professional-Familial Care Boundaries with two broad dialectical processes: professionalizing familial care and striving for balance. This article examines striving for balance, which is the process that responds to familial care expectations in the midst of available resources and reflects the health experiences of double duty caregivers. Two subprocesses of striving for balance, reaping the benefits and taking a toll, are presented in three composite vignettes, each representing specific double duty caregiving (DDC) prototypes (making it work, working to manage, living on the edge). This emergent theory extends current thinking of family caregiving that will inform the development and refinement of practices and policies relevant to DDC.

Engineering plant-microbe communication for plant nutrient use efficiency.

Nutrient availability and efficient use are critical for crop productivity. Current agricultural practices rely on excessive chemical fertilizers, contributing to greenhouse gas emissions and environmental pollution. Rhizosphere microbes facilitate plant nutrient acquisition and contribute to nutrient use efficiency. Thus, engineering plant-microbe communication within the rhizosphere emerges as a promising and sustainable strategy to enhance agricultural productivity. Recent advances in plant engineering have enabled the development of plants capable of selectively enriching beneficial microbes through root exudates. At the same time, synthetic biology techniques have produced microbes capable of improving nutrient availability and uptake by plants. By engineering plant-microbe communication, researchers aim to harness beneficial soil microbes, thereby offering a targeted and efficient approach to optimizing plant nutrient use efficiency.

Double-Duty Carers' Health and Wellbeing during COVID-19: Exploring the Role of Mobility of the Care Economy in Southern Ontario, Canada.

Double-Duty Carers (DDCs) refer to people who work in the healthcare industry while also providing unpaid care to relatives, friends, or neighbours. The expectations placed on DDCs is expected to grow, and these employees already experience a high caring burden. As such it is important to understand how best to support their health and wellbeing. This paper explores DDCs' wellbeing during the COVID-19 pandemic, focusing an understudied factor: their mobility constraints. Following the Mobility of the Care Economy framework and a qualitative research design, it does so through a thematic analysis of 16 semi-structured interviews with female DDCs in Southern Ontario, Canada. Once data saturation was reached, three mobility pathways during the pandemic were identified, all of which negatively affected DDCs wellbeing. First, some COVID-19 policies (e.g., testing requirements) resulted in increased mobility demands and increased spatiotemporal constraints. Second, the closure of institutions that care for dependents (schools, daycares, day centres) resulted in forced reduced mobility, which increased financial stress. Finally, indirect mobility effects were identified: the reduced mobility of other informal carers increased the workload and emotional strain on DDCs. The paper concludes with a discussion of mobility-related policies that could improve DDC wellbeing.

Double-duty caregivers enduring COVID-19 pandemic to endemic: "It's just wearing me down".

The COVID-19 pandemic has considerably strained health care providers and family caregivers. Double-duty caregivers give unpaid care at home and are employed as care providers. This sequential mixed-method study, a survey followed by qualitative interviews, aimed to comprehensively understand the experiences of these Canadian double-duty caregivers amidst the pandemic and the transition to the endemic phase. The multi-section survey included standardized assessments such as the Double-duty Caregiver Scale and the State Anxiety Scale, along with demographic, employment-related, and care work questions. Data analysis employed descriptive and linear regression modeling statistics, and content analysis of the qualitative data. Out of the 415 respondents, the majority were female (92.5%) and married (77.3%), with 54.9% aged 35 to 54 years and 29.2% 55 to 64 years. 68.9% reported mental health decline over the past year, while 60.7% noted physical health deteriorated. 75.9% of participants self-rated their anxiety as moderate to high. The final regression model explained 36.8% of the variance in participants' anxiety levels. Factors contributing to lower anxiety included more personal supports, awareness of limits, younger age, and fewer weekly employment hours. Increased anxiety was linked to poorer self-rated health, and both perceptions and consequences of blurred boundaries. The eighteen interviewees highlighted the stress of managing additional work and home care during the pandemic. They highlighted the difficulty navigating systems and coordinating care. Double-duty caregivers form a significant portion of the healthcare workforce. Despite the spotlight on care and caregiving during the COVID-19 pandemic, the vital contributions and well-being of double-duty caregivers and family caregivers have remained unnoticed. Prioritizing their welfare is crucial for health systems as they make up the largest care workforce, particularly evident during the ongoing healthcare workforce shortage.

Client-provider relationships in a community health clinic for people who are experiencing homelessness.

Recognizing the importance of health-promoting relationships in engaging people who are experiencing homelessness in care, most research on health clinics for homeless persons has involved some recognition of client-provider relationships. However, what has been lacking is the inclusion of a critical analysis of the policy context in which relationships are enacted. In this paper, we question how client-provider relationships are enacted within the culture of community care with people who are experiencing homelessness and how clinic-level and broader social and health policies shape relationships in this context. We explore these questions within a critical theoretical perspective utilizing a critical ethnographic methodology. Data were collected using multiple methods of document review, participant observation, in-depth interviews and focus groups. The participants include both clients at a community health clinic, and all clinic service providers. We explore how clients and providers characterized each other as 'good' or 'bad'. For providers, this served as a means by which they policed behaviours and enforced social norms. The means by which both providers' and clients' negotiated relationships are explored, but this is couched within both local and system-level policies. This study highlights the importance of healthcare providers and clients being involved in broader policy and systemic change.

Community health promotion with people who are experiencing homelessness.

Homelessness is an experience of being displaced. Once removed from their personal places, homeless people are barred access to healthy places in which to be. Health clinics for people who are experiencing homelessness offer an opportunity to create health-promoting places. In this study, we explore how place is experienced within a community health clinic for people who are experiencing homelessness. A critical ethnographic methodology was used. Results illustrate how clients and providers contested the space of the clinic. Discourses of safety, health promotion, and privacy were enacted, altered, and resisted in a constant practice of culture-making. Physical components of the space became conceptual components of how place and power in place were understood by clients and providers. Results point to the importance of conceptualizing service users as the key stakeholders in their care, considering how places may be more or less health promoting, and rethinking how safety is conceptualized.

Social Isolation of Older Adults, Family, and Formal Caregivers During the COVID-19 Pandemic: Stories and Solutions Through Participatory Action Research.

This participatory action research (PAR) aimed to understand the health implications of guidelines impacting social isolation among frail community-dwelling older adults and their family and formal caregivers during the coronavirus disease (COVID-19) pandemic. Reflexive thematic analysis (RTA) of data collected from 10 policy/procedural documents revealed four themes: valuing principles, identifying problem(s), setting priorities, and making recommendations. Interviews with 31 participants from Peterborough, Ontario, also revealed four themes: sacrificing social health, diminishing physical health, draining mental health, and defining supports. Recommendations to decision makers were finalized at a knowledge exchange event involving participants and members of Age-friendly Peterborough. Key findings demonstrate the need for Canadian governments and health and social service agencies to enhance access to technology-based interventions, and educational and financial resources for caregivers. Meaningful communication and collaboration between older adults, caregivers, and decision makers are also needed to reduce the gap between policy and practice when addressing social isolation.

Delayed boosting improves human antigen-specific Ig and B cell responses to the RH5.1/AS01B malaria vaccine.

Modifications to vaccine delivery that increase serum antibody longevity are of great interest for maximizing efficacy. We have previously shown that a delayed fractional (DFx) dosing schedule (0-1-6 month) - using AS01B-adjuvanted RH5.1 malaria antigen - substantially improves serum IgG durability as compared with monthly dosing (0-1-2 month; NCT02927145). However, the underlying mechanism and whether there are wider immunological changes with DFx dosing were unclear. Here, PfRH5-specific Ig and B cell responses were analyzed in depth through standardized ELISAs, flow cytometry, systems serology, and single-cell RNA-Seq (scRNA-Seq). Data indicate that DFx dosing increases the magnitude and durability of circulating PfRH5-specific B cells and serum IgG1. At the peak antibody magnitude, DFx dosing was distinguished by a systems serology feature set comprising increased FcRn binding, IgG avidity, and proportion of G2B and G2S2F IgG Fc glycans, alongside decreased IgG3, antibody-dependent complement deposition, and proportion of G1S1F IgG Fc glycan. Concomitantly, scRNA-Seq data show a higher CDR3 percentage of mutation from germline and decreased plasma cell gene expression in circulating PfRH5-specific B cells. Our data, therefore, reveal a profound impact of DFx dosing on the humoral response and suggest plausible mechanisms that could enhance antibody longevity, including improved FcRn binding by serum Ig and a potential shift in the underlying cellular response from circulating short-lived plasma cells to nonperipheral long-lived plasma cells.

Negotiating relational practice patterns in palliative home care.

Providing palliative care in the home presents a variety of challenges for nurses and other care providers. As part of a focused ethnographic study examining client/caregiver/care-provider relationships within the socio-cultural context of home-based palliative care, this paper describes the provision of palliative care to Canadian seniors with advanced cancer from the perspective of nurses. Data were collected through in-depth interviews (n=19) with three palliative care nurses and participant observations in four households over a six-to-eight-month period. Home-based palliative care nursing was depicted in this study as a dialectical experience, revealing three relational practice patterns: making time-forfeiting time, connecting-withdrawing, and enabling-disabling. Nurses attempted to negotiate the tensions between these opposing approaches to palliative care. Study findings suggest that the sociocultural context of palliative care is not conducive to high-quality palliative care and provide several insights related to future directions for practice, policy, and research.