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Early Host Defense Against Virus Infections
Get PDFEarly host defense eliminates many viruses before infections are established while clearing others so they remain subclinical or cause only mild disease. The field of immunology has been shaped by broad concepts, including the pattern recognition theory that currently dominates innate immunology. Focusing on early host responses to virus infections, we analyze the literature to build a working hypothesis for the principles that govern the early line of cellular antiviral defense. Aiming to ultimately arrive at a criteria-based theory with strong explanatory power, we propose that both controlling infection and limiting inflammation are key drivers for the early cellular antiviral response. This response, which we suggest is exerted by a set of “microbe- and inflammation-restricting mechanisms,” directly restrict viral replication while also counteracting inflammation. Exploring the mechanisms and physiological importance of the early layer of cellular antiviral defense may open further lines of research in immunology
AlphaFold2-Based Characterization of Apo and Holo Protein Structures and Conformational Ensembles Using Randomized Alanine Sequence Scanning Adaptation: Capturing Shared Signature Dynamics and Ligand-Induced Conformational Changes
Get PDFProteins often exist in multiple conformational states, influenced by the binding of ligands or substrates. The study of these states, particularly the apo (unbound) and holo (ligand-bound) forms, is crucial for understanding protein function, dynamics, and interactions. In the current study, we use AlphaFold2, which combines randomized alanine sequence masking with shallow multiple sequence alignment subsampling to expand the conformational diversity of the predicted structural ensembles and capture conformational changes between apo and holo protein forms. Using several well-established datasets of structurally diverse apo-holo protein pairs, the proposed approach enables robust predictions of apo and holo structures and conformational ensembles, while also displaying notably similar dynamics distributions. These observations are consistent with the view that the intrinsic dynamics of allosteric proteins are defined by the structural topology of the fold and favor conserved conformational motions driven by soft modes. Our findings provide evidence that AlphaFold2 combined with randomized alanine sequence masking can yield accurate and consistent results in predicting moderate conformational adjustments between apo and holo states, especially for proteins with localized changes upon ligand binding. For large hinge-like domain movements, the proposed approach can predict functional conformations characteristic of both apo and ligand-bound holo ensembles in the absence of ligand information. These results are relevant for using this AlphaFold adaptation for probing conformational selection mechanisms according to which proteins can adopt multiple conformations, including those that are competent for ligand binding. The results of this study indicate that robust modeling of functional protein states may require more accurate characterization of flexible regions in functional conformations and the detection of high-energy conformations. By incorporating a wider variety of protein structures in training datasets, including both apo and holo forms, the model can learn to recognize and predict the structural changes that occur upon ligand binding
Hyperglycemia Causes Differential Change in Macrophage Population in the Lacrimal Gland, Conjunctiva and Cornea
Get PDFBackground: Due to its location, the ocular surface is exposed to environmental microbes. Innate immune cells including macrophages are first line defense against infections. In vitro exposure to high glucose as well as diabetes-associated hyperglycemia has been shown to affect innate immune cell function and population. The present study was designed to examine the effect of diabetes-associated hyperglycemia on the lacrimal gland, conjunctiva and cornea macrophage population, phenotypic changes and cytokines/chemokines.
Methods: Mouse model of Streptozotocin-induced diabetes was used to induce hyperglycemia. Immunostaining for CD11b and F4/80 was performed to stain macrophages in whole mount cornea, conjunctiva and 50 µm lacrimal gland sections. Flowcytometry was performed on single cell suspension to identify macrophage phenotypes and activation using CD11b, F4/80, CD80, CD206 and MHCII staining. Real time PCR was performed to quantify gene expression for macrophage-associated cytokines (IL-1β, TNF-α, IFN-γ) and chemokine (CCL2).
Results: Our data demonstrates the diabetes-associated hyperglycemia caused a rapid onset and significant decrease in macrophage population in lacrimal gland, conjunctiva and cornea. The onset of this noted decrease was as early as 7 days after hyperglycemia in lacrimal gland and conjunctiva followed by a notable increase towards recovery only in conjunctiva but not in the lacrimal gland. The cornea tissue showed a steady decline up to the tested time point of 28 days. Further, hyperglycemia did not cause any notable changes in macrophage phenotypes, their activation status or the expression of IL-1β, TNF-α, IFN-γ, CCL2 except in the cornea where an increase in the cytokine levels was noted after 7 days of hyperglycemia
Conclusion: Our data shows that diabetes-associated hyperglycemia can cause a significant decrease in microphage population with changing their plasticity or activation status in lacrimal gland, conjunctiva and cornea but the kinetics of decrease and recovery show differential pattern specific for each tissue
Identifying Opportunities for Nature-Based Solutions with Geospatialized Life Cycle Assessments and Fine-scale Socioecological Data
Get PDFAs we increasingly understand the impact that land management intensification has on local and global climate, the call for nature-based solutions (NbS) in agroecosystems has expanded. Moreover, the pressing need to determine when and where NbS should be used raises challenges to socioecological data integration as we overcome spatiotemporal resolutions. Natural and working lands is an effort promoting NbS, particularly emissions reduction and carbon stock maintenance in forests. To overcome the spatiotemporal limitation, we integrated life cycle assessments (LCA), an ecological carbon stock model, and a land cover land use change model to synthesize rates of global warming potential (GWP) within a fine-scale geographic area (30 m). We scaled National Agricultural Statistic Survey land management data to National Land Cover Data cropland extents to assess GWP of cropland management over time and among management units (i.e. counties and production systems). We found that cropland extent alone was not indicative of GWP emissions; rather, rates of management intensity, such as energy and fertilizer use, are greater indicators of anthropogenic GWP. We found production processes for fuel and fertilizers contributed 51.93% of GWP, where 33.58% GWP was estimated from N2O emissions after fertilization, and only 13.31% GWP was due to energy consumption by field equipment. This demonstrates that upstream processes in LCA should be considered in NbS with the relative contribution of fertilization to GWP. Additionally, while land cover change had minimal GWP effect, urbanization will replace croplands and forests where NbS are implemented. Fine-scale landscape variations are essential for NbS to identify, as they accumulate within regional and global estimates. As such, this study demonstrates the capability to harness both LCA and fine-resolution imagery for applications in spatiotemporal and socioecological research towards identifying and monitoring NbS
\u3cem\u3eEtherealBreathing\u3c/em\u3e: A Holographic Biofeedback Game to Support Relaxation in Autistic Children
Get PDFBiofeedback training for box breathing is becoming increasingly accessible due to advancements in consumer-grade breathing sensors. However, there is limited research on their design and applications for specialized populations. This study evaluates a novel biofeedback holographic game, EtherealBreathing, designed to support autistic children. In EtherealBreathing, children practice box breathing to collect virtual elements to maintain the Earth\u27s balance, using a wearable sensor to measure chest expansion for breath detection. A deployment study with 20 autistic children revealed that EtherealBreathing effectively promotes box breathing, leading to better health-related outcomes, such as lowering participants’ heart and respiratory rates than traditional practices. Biofeedback games can be effective in the healthcare domain, reducing stress-related physiological variables like heart and respiratory rate
Addressing Social Risks to Accelerate Health Equity in Cancer Prevention and Control
No full textAddressing social risks in cancer prevention and control presents a new opportunity for accelerating cancer health equity. As members of the American Society of Preventive Oncology (ASPO) Cancer Health Disparities Special Interest Group, we describe the current state of science on social risks in oncology research and practice. To reduce and eliminate the unjust burden of cancer, we also provide recommendations for multilevel research examining social risks as contributors to inequities and the development of social risks-focused interventions. Suggestions for research and practice are provided within levels of the socio-ecological model, including the interpersonal, organizational, community, and policy levels
Investigating the Experiences of Evangelical Couples Coping with Painful Intercourse During Early Marriage
Get PDFWomen who internalize evangelical purity messages face heightened risk for persistent pain or difficulty with penile-vaginal intercourse. Drawing on research in communication, psychology, and sexual medicine, the aim of this multilevel qualitative study is to increase understanding of how evangelical couples communicatively cope with painful intercourse and the memorable messages they believe contribute to their experiences of coping. This study involved conducting qualitative interviews with 20 evangelical married couples (40 total spouses) who currently or recently experienced a wife’s persistent pain during (attempted) penile-vaginal intercourse and 16 female clinicians (pelvic floor physical therapists and mental health professionals) who regularly work with women or couples affected by painful intercourse. Interview data were abductively analyzed at the individual level, couple-level, and across data points using the flexible coding method and assisted by thematic analysis. Guided by the Theory of Memorable Messages, the findings of this study illuminate how sexual socializing messages received in and outside of religious contexts may set the stage for delayed support and subsequent emotional and communicative challenges, whereas other messages may intervene in the trajectory, facilitating couples’ ability to work as a team, seek support, and reframe their individual and shared experiences. This study supports and extends extant interdisciplinary literature by revealing the social context of female sexual pain, utilizing multiple data points to provide in-depth insight into the phenomenon of coping with painful intercourse, and illuminating timing and co-occurrence of memorable messages as important aspects of their function and memorability. Practically, the findings offer couples, practitioners, and evangelical Christian leaders possible points of communicative intervention that may empower couples and facilitate the coping process
Exploring the Impact of Subject Placement on Exam Questions
Get PDFQuizzes and exams are crucial elements of undergraduate biology courses; however, little research has been done exploring the importance of the phrasing used in the questions on these assessments. Question framing has the potential to impact student performance and sense of belonging greatly. In this study, we conducted an experiment where we created three versions of the exact same question except for the framing for the experimental scenarios. One version was written with self-referential framing using the term “you,” simulating the student conducting the experiment; another version used classmate-referential framing, placing one of their peers in the experiment; the third version, referred to as authentic framing, included names from a diverse variety of scientists. All students and sections received the exact same questions for each assessment, with the phrasing varying between the assessments given throughout the semester (the first quiz used self-referential, the second quiz used classmate referential, etc.). This study is the second iteration of a similar study that used the same framework but instead gave each section a different assessment framing (Hsu, Clark, Hill, & Rowland-Goldsmith, 2023). Across all sections, our results indicate no significant change in students’ grades, self-reported stress, or sense of belonging. Students reported a strong preference for the self-referential version of the assessment question, followed by classmate-referential framing and authentic framing as the least preferred version. When we asked students why they preferred certain versions, we received a variety of responses that were similar to the first iteration of this study, indicating that question framing can affect a student’s attitude towards questions
The Gender Divide: Exploring Gender Patterns of Perceived and Realistic Risks of Murder by Unknown and Known Perpetrators
Get PDFIn a society where vulnerability is often associated with femininity, women are depicted as helpless victims, which in turn underscores the gendered challenges faced by both men and women. It is thought that gender disparities among women increase the likelihood of fear and risk of murder victimization. Rather, both men and women face homicide at significant rates where gender vulnerability is correlated to different types of violence. In this paper, I examine the complexities of gendered perceptions of perceived and realistic risks behind the fear of being murdered by someone you know and murdered by a stranger. Relying on the Chapman Survey of American Fears, a representative national sample of U.S. adults, I find a strong relationship between the fear of being murdered by someone you know and murder by a stranger to be significantly higher among women respondents, compared to male respondents. However, I find that men are more likely to be victims of stranger homicide, while women are more likely to be victims of intimate homicide. Based on the vulnerability theory, potential intimate partner violence perceives a higher risk of vulnerability among women than men. Along with this, the media covers cases of violence against women disproportionately, emphasizing perceptions of vulnerability to be higher among women compared to men. While women are perceived to have higher risks of murder victimization due to gender disparities and media influence, the differentiation I find is that while the majority of intimate-related homicides are women, the majority of homicide victims are male. Understanding the disconnect between gender dimensions related to fear of being murdered by someone you know and by a stranger enables a nuanced understanding to develop gender-sensitive approaches to differential violence prevention