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Professional phagocytes like neutrophils and macrophages tightly control what they consume, how much they consume, and when they move after cargo uptake. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G protein subunit Gβ4 exhibited profound plasma membrane expansion, accompanied by marked reduction in plasma membrane tension. These biophysical changes promoted the phagocytosis of bacteria, fungus, apoptotic corpses, and cancer cells. We also found that Gβ4-deficient neutrophils are defective in the normal inhibition of migration following cargo uptake. Sphingolipid synthesis played a central role in these phenotypes by driving plasma membrane accumulation in cells lacking Gβ4. In Gβ4 knockout mice, neutrophils not only exhibited enhanced phagocytosis of inhaled fungal conidia in the lung but also increased trafficking of engulfed pathogens to other organs. Together, these results reveal an unexpected, biophysical control mechanism central to myeloid functional decision-making.

The college and career readiness movement figures prominently in the nation's educational reform and policies, including strategies to increase graduation rates among disadvantaged students in urban schools. As part of a multi-pronged approach to help youth transition to post-secondary education and the workforce, the present study evaluated a new career intervention, Making My Future Work, designed to serve as a comprehensive, flexible career curriculum. Based on a quasi-experimental design among a sample of urban youth (N = 429), multilevel modeling revealed promising evidence for its impact across a range of outcomes, including grade point average, school engagement, career preparation, self-determination, and self-awareness. The implications of the findings, limitations, and future directions for research are discussed.

Self-regulation is a well-known construct in educational and psychological research, as it is often related to academic success and well-being. Drawing from criticisms of a lack of context applied to the investigation of this construct, the current study examined the multi-dimensional role of social support (teachers, parents, peers) and coping skills as predictors of self-regulated learning among a diverse sample of urban youth (N = 229). Based on a cross-sectional and longitudinal design, structural equation modeling was used to test two models. Social support predicted self-regulated learning at Time 1 and Time 2 after controlling for grades. Results further indicated that coping skills did not predict self-regulated learning in either model. The implications for practice, limitations of the study, and future directions for research are discussed.

This article details the development and validation of a measure of critical consciousness, defined as the capacity of oppressed or marginalized people to critically analyze their social and political conditions, endorsement of societal equality, and action to change perceived inequities. In Study 1, an exploratory factor analysis (EFA) was conducted with a diverse sample of youth, resulting in three internally consistent factors: (a) Critical Reflection: Perceived Inequality, (b) Critical Reflection: Egalitarianism, and (c) Critical Action: Sociopolitical Participation. In Study 2, a confirmatory factor analysis (CFA) was completed with a new sample of youth. Strong model fit estimates in Study 2 confirmed the factor structure of Study 1 and resulted in a final 22-item measure called the "Critical Consciousness Scale" (CCS). The CCS has the potential to unite and advance the fragmented conceptualization and measurement of critical consciousness, the primary motivation for the development of the scale.

Managing feral water buffalo in the Northern Territory is a formidable challenge. As an introduced species, buffalo are associated with a myriad of biosecurity, economic, cultural and environmental issues ranging from overgrazing, decreased water quality, disease vectors to the destruction of cultural assets. Nevertheless, the buffalo are also a harvestable resource that can support economic development of the region. To mitigate some of the biosecurity, economic, cultural and environmental risks they pose and manage buffalo effectively, we need a detailed understanding of their spatial and behavioural ecology. However, several factors make understanding how best to manage the dense populations of wild individuals challenging as buffalo inhabit remote areas with limited infrastructure and accessibility and their large size and often aggressive nature can make them difficult to observe in otherwise inaccessible areas. GPS tracking allows for high‐frequency data collection and surveillance of individual buffalo. Here, we investigated how the different seasonal periods of a Northern Territory floodplain area shaped patterns of habitat use for 17 buffalo tracked over 16 months. We found in the dry season, buffalo space use is restricted, and the size of home ranges are significantly smaller than in the wet season. During the wet season, buffalo expand their home range area as well as their social encounter area with other buffalo. These differences in their space use and social patterns suggest that increased disease surveillance may be needed for the wet season when buffalo are more likely to share space and interact. During the dry season, however, buffalo movement is more predictable and restricted, suggesting greater optimisation opportunities for buffalo management. Results from these models can be used by land holders, Traditional Owners and wildlife managers to make evidence‐based decisions to improve buffalo management with respect to disease risk, sustainable harvest and damage to environmental and cultural assets. [ABSTRACT FROM AUTHOR]

Therapeutic antibodies targeting ovarian cancer (OvCa)-enriched receptors have largely been disappointing due to limited tumor-specific antibody-dependent cellular cytotoxicity. Here we report a symbiotic approach that is highly selective and superior compared with investigational clinical antibodies. This bispecific-anchored cytotoxicity activator antibody is rationally designed to instigate "cis" and "trans" cytotoxicity by combining specificities against folate receptor alpha-1 (FOLR1) and death receptor 5 (DR5). Whereas the in vivo agonist DR5 signaling requires FcγRIIB interaction, the FOLR1 anchor functions as a primary clustering point to retain and maintain a high level of tumor-specific apoptosis. The presented proof of concept study strategically makes use of a tumor cell-enriched anchor receptor for agonist death receptor targeting to potentially generate a clinically viable strategy for OvCa.

The development of T cell tolerance in the thymus requires the presentation of host proteins by multiple antigen-presenting cell (APC) types. However, the importance of transferring host antigens from transcription factor AIRE-dependent medullary thymic epithelial cells (mTECs) to bone marrow (BM) APCs is unknown. We report that antigen was primarily transferred from mTECs to CD8α+ dendritic cells (DCs) and showed that CD36, a scavenger receptor selectively expressed on CD8α+ DCs, mediated the transfer of cell-surface, but not cytoplasmic, antigens. The absence of CD8α+ DCs or CD36 altered thymic T cell selection, as evidenced by TCR repertoire analysis and the loss of allo-tolerance in murine allogeneic BM transplantation (allo-BMT) studies. Decreases in these DCs and CD36 expression in peripheral blood of human allo-BMT patients correlated with graft-versus-host disease. Our findings suggest that CD36 facilitates transfer of mTEC-derived cell-surface antigen on CD8α+ DCs to promote tolerance to host antigens during homeostasis and allo-BMT.

Dendritic cells (DCs) produce major histocompatibility complex II (MHCII) in large amounts to function as professional antigen presenting cells. Paradoxically, DCs also ubiquitinate and degrade MHCII in a constitutive manner. Mice deficient in the MHCII-ubiquitinating enzyme membrane-anchored RING-CH1, or the ubiquitin-acceptor lysine of MHCII, exhibit a substantial reduction in the number of regulatory T (Treg) cells, but the underlying mechanism was unclear. Here we report that ubiquitin-dependent MHCII turnover is critical to maintain homeostasis of lipid rafts and the tetraspanin web in DCs. Lack of MHCII ubiquitination results in the accumulation of excessive quantities of MHCII in the plasma membrane, and the resulting disruption to lipid rafts and the tetraspanin web leads to significant impairment in the ability of DCs to engage and activate thymocytes for Treg cell differentiation. Thus, ubiquitin-dependent MHCII turnover represents a novel quality-control mechanism by which DCs maintain homeostasis of membrane domains that support DC's Treg cell-selecting function.

Regulated cell death is an integral part of life, and has broad effects on organism development and homeostasis.sup.1. Malfunctions within the regulated cell death process, including the clearance of dying cells, can manifest in diverse pathologies throughout various tissues including the gastrointestinal tract.sup.2. A long appreciated, yet elusively defined relationship exists between cell death and gastrointestinal pathologies with an underlying microbial component.sup.3-6, but the direct effect of dying mammalian cells on bacterial growth is unclear. Here we advance a concept that several Enterobacteriaceae, including patient-derived clinical isolates, have an efficient growth strategy to exploit soluble factors that are released from dying gut epithelial cells. Mammalian nutrients released after caspase-3/7-dependent apoptosis boosts the growth of multiple Enterobacteriaceae and is observed using primary mouse colonic tissue, mouse and human cell lines, several apoptotic triggers, and in conventional as well as germ-free mice in vivo. The mammalian cell death nutrients induce a core transcriptional response in pathogenic Salmonella, and we identify the pyruvate formate-lyase-encoding pflB gene as a key driver of bacterial colonization in three contexts: a foodborne infection model, a TNF- and A20-dependent cell death model, and a chemotherapy-induced mucositis model. These findings introduce a new layer to the complex host-pathogen interaction, in which death-induced nutrient release acts as a source of fuel for intestinal bacteria, with implications for gut inflammation and cytotoxic chemotherapy treatment. Intestinal microorganisms exploit nutrients released by apoptotic gut epithelial cells for growth., Author(s): Christopher J. Anderson [sup.1] [sup.2] , Christopher B. Medina [sup.3] , Brady J. Barron [sup.3] , Laura Karvelyte [sup.1] , Tania Løve Aaes [sup.1] [sup.2] , Irina Lambertz [sup.1] [...]

Phagocytes express multiple phosphatidylserine (PtdSer) receptors that recognize apoptotic cells. It is unknown whether these receptors are interchangeable or if they play unique roles during cell clearance. Loss of the PtdSer receptor Mertk is associated with apoptotic corpse accumulation in the testes and degeneration of photoreceptors in the eye. Both phenotypes are linked to impaired phagocytosis by specialized phagocytes: Sertoli cells and the retinal pigmented epithelium (RPE). Here, we overexpressed the PtdSer receptor BAI1 in mice lacking MerTK (Mertk -/- Bai1 Tg ) to evaluate PtdSer receptor compensation in vivo. While Bai1 overexpression rescues clearance of apoptotic germ cells in the testes of Mertk -/- mice it fails to enhance RPE phagocytosis or prevent photoreceptor degeneration. To determine why MerTK is critical to RPE function, we examined visual cycle intermediates and performed unbiased RNAseq analysis of RPE from Mertk +/+ and Mertk -/- mice. Prior to the onset of photoreceptor degeneration, Mertk -/- mice had less accumulation of retinyl esters and dysregulation of a striking array of genes, including genes related to phagocytosis, metabolism, and retinal disease in humans. Collectively, these experiments establish that not all phagocytic receptors are functionally equal, and that compensation among specific engulfment receptors is context and tissue dependent.

Caspase-dependent apoptosis accounts for approximately 90% of homeostatic cell turnover in the body.sup.1, and regulates inflammation, cell proliferation, and tissue regeneration.sup.2-4. How apoptotic cells mediate such diverse effects is not fully understood. Here we profiled the apoptotic metabolite secretome and determined its effects on the tissue neighbourhood. We show that apoptotic lymphocytes and macrophages release specific metabolites, while retaining their membrane integrity. A subset of these metabolites is also shared across different primary cells and cell lines after the induction of apoptosis by different stimuli. Mechanistically, the apoptotic metabolite secretome is not simply due to passive emptying of cellular contents and instead is a regulated process. Caspase-mediated opening of pannexin 1 channels at the plasma membrane facilitated the release of a select subset of metabolites. In addition, certain metabolic pathways continued to remain active during apoptosis, with the release of only select metabolites from a given pathway. Functionally, the apoptotic metabolite secretome induced specific gene programs in healthy neighbouring cells, including suppression of inflammation, cell proliferation, and wound healing. Furthermore, a cocktail of apoptotic metabolites reduced disease severity in mouse models of inflammatory arthritis and lung-graft rejection. These data advance the concept that apoptotic cells are not inert cells waiting for removal, but instead release metabolites as 'good-bye' signals to actively modulate outcomes in tissues. Apoptotic cells communicate with neighbouring cells by the regulated release of specific metabolites, and a cocktail of select apoptotic metabolites reduces disease severity in mouse models of inflammatory arthritis and lung transplant rejection., Author(s): Christopher B. Medina [sup.1] [sup.2] , Parul Mehrotra [sup.3] , Sanja Arandjelovic [sup.1] [sup.2] , Justin S. A. Perry [sup.1] [sup.2] , Yizhan Guo [sup.4] , Sho Morioka [sup.1] [...]

The present study explored the causal relationship between self-esteem and school belongingness among a sample of urban youth. Based on a longitudinal cross-lagged panel design, the results offered initial support for the personal agency perspective of growth in self-esteem leading to growth in school belongingness. We discuss the implications for school counselors and the study's limitations and directions for future research.

The present study investigated developmental differences and stability in possible selves within the educational and occupational domain among a diverse sample of urban youth (N = 319). A secondary aim was to test the "aspiration-expectation gap" while exploring the role of subjective social class and gender differences. Results did not indicate any significant differences among possible selves between different grades in high school. Seniors evidenced the lowest levels of subjective social class, whereas freshmen had the highest levels. Subjective social class was significantly associated with the expected levels of education. In addition, girls aspired toward significantly higher levels of prestige than boys in terms of occupations they hoped to attain, while a substantial gap was found between hoped-for and expected education. Implications for practice, limitations, and directions for research are discussed.

Study Design: Retrospective cohort study using PearlDiver database. Objectives: To evaluate the effect of prior thyroidectomy on complications of Anterior Cervical Discectomy and Fusion (ACDF) surgery. Methods: PearlDiver was used to identify patients without prior dysphagia or dysphonia undergoing ACDF between the years 2010-2020Q1. Patients with and without prior thyroidectomy were matched by levels of fusion, alcohol use, and gastroesophageal reflux disease in a 1:5 ratio. Postoperative outcomes were assessed for each cohort with multivariable logistic regression, controlling for age, sex, and Elixhauser Comorbidity Index. Results: Between 2010 and 2019, matched cohorts of 792 ACDF patients with prior thyroidectomy and 3960 ACDF only patients were included in the study. Of patients with previous thyroidectomy undergoing ACDF, 16.3% experienced dysphagia at 1-year compared with 10.6% for patients undergoing ACDF only (aOR=1.39, P=.004). Patients with previous thyroidectomy also had higher odds of dysphonia at 1-year following ACDF, as compared to patients with ACDF alone (2.7% vs 1.2%, aOR=1.74, P=.048). Patients undergoing ACDF with prior thyroidectomy did not have increased risk of revision at 1 year (aOR=1.10, P=.698), 2 years (aOR=1.16, P=.457), or 5 years (aOR=1.20, P=.255) following surgery. There were no differences in postoperative opioid utilization rates at 1 month (aOR=2.07, P=.138), 3 months (aOR=2.45, P=.095), 6 months (aOR=1.34, P=.520), and 12 months (aOR=1.69, P=.202). Prior thyroidectomy was not associated with reintubation following ACDF (P=.995). Conclusions: Patients with prior thyroidectomy undergoing ACDF surgery experience increased odds of dysphagia and dysphonia at 1-year follow-up compared to those without prior thyroidectomy. [ABSTRACT FROM AUTHOR]

In general, vocational psychologists have not been engaged in applied research that demonstrates how career interventions can improve educational problems that matter to relevant decision-makers and stakeholders. This article describes how vocational psychology can make a difference in K-12 education by embracing an interdisciplinary community-based approach. To illustrate this approach, a quasi-experimental evaluation of multiple after-school programs provided to a sample of Hispanic Americans is presented. This study offers a realistic example of how researchers in the field can induce change through the development of meaningful partnerships within the community.

We report, for the first time, a multimodal investigation of current crude oil reprocessing and storage sites to assess their impact on the environment after 50 years of continuous operation. We have adopted a dual approach to investigate potential soil contamination. The first approach uses conventional analytical techniques i.e. energy dispersive X-ray fluorescence (ED-XRF) for metal analysis, and a complementary metabolomic investigation using hydrophilic liquid interaction chromatography hi-resolution mass spectrometry (HILIC-MS) for organic contaminants. Secondly, the deployment of an unmanned aerial vehicle (UAV) with a multispectral image (MSI) camera, for the remote sensing of vegetation stress, as a proxy for sub-surface soil contamination. The results identified high concentrations of barium (mean 21 017 ± 5950 μg g−1, n = 36) as well as metabolites derived from crude oil (polycyclic aromatic hydrocarbons), cleaning processes (surfactants) and other organic pollutants (e.g. pesticides, plasticizers and pharmaceuticals) in the reprocessing site. This data has then been correlated, with post-flight data analysis derived vegetation indices (NDVI, GNDVI, SAVI and Cl green VI), to assess the potential to identify soil contamination because of vegetation stress. It was found that strong correlations exist (an average R2 of >0.68) between the level of soil contamination and the ground cover vegetation. The potential to deploy aerial remote sensing techniques to provide an initial survey, to inform decision-making, on suspected contaminated land sites can have global implications. [ABSTRACT FROM AUTHOR]

Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional phagocytes via efferocytosis.sup.1. How a phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood.sup.1,2. Here, using RNA sequencing to characterize the transcriptional program of phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis.sup.2--that is, 'smell' ('find-me' signals or sensing factors released by apoptotic cells), 'taste' (phagocyte-apoptotic cell contact) and 'ingestion' (corpse internalization)--activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis.sup.3. Whereas glycolysis within phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells.Distinct transcriptional programs are activated during different stages of apoptotic cell engulfment, including a unique program of genes coding for solute carrier proteins and enzymes in the glycolytic pathway., Author(s): Sho Morioka [sup.1] [sup.2] , Justin S. A. Perry [sup.1] [sup.2] , Michael H. Raymond [sup.1] [sup.3] , Christopher B. Medina [sup.1] [sup.2] , Yunlu Zhu [sup.4] , Liyang [...]

The present study investigated the impact of a Science, Technology, Engineering, Mathematics and Health (STEM+H) university-based pipeline program, the Careers in Health and Medical Professions Program, over the course of two summers among predominantly African-American high school students recruited from urban school districts (N = 155). Based on a mixed methods approach, results indicated that youth made significant gains in both academic and career knowledge. Furthermore, youth generally rated the program's sessions favorably, but also rated sessions with varying levels of satisfaction. The limitations and implications for program delivery and evaluation methods among pipeline programs are discussed.