Strategies to mitigate climate change often center on clean technologies, such as electric vehicles and solar panels, while the mitigation potential of a quality educational experience is rarely ...discussed. In this paper, we investigate the long-term impact that an intensive one-year university course had on individual carbon emissions by surveying students at least five years after having taken the course. A majority of course graduates reported pro-environmental decisions (i.e., type of car to buy, food choices) that they attributed at least in part to experiences gained in the course. Furthermore, our carbon footprint analysis suggests that for the average course graduate, these decisions reduced their individual carbon emissions by 2.86 tons of CO2 per year. Surveys and focus group interviews identify that course graduates have developed a strong personal connection to climate change solutions, and this is realized in their daily behaviors and through their professional careers. The paper discusses in more detail the specific components of the course that are believed to be most impactful, and the uncertainties associated with this type of research design. Our analysis also demonstrates that if similar education programs were applied at scale, the potential reductions in carbon emissions would be of similar magnitude to other large-scale mitigation strategies, such as rooftop solar or electric vehicles.
This review provides a practical overview of the excess cancer risks related to radiation from medical imaging. Primary care physicians should have a basic understanding of these risks. Because of ...recent attention to this issue, patients are more likely to express concerns over radiation risk. In addition, physicians can play a role in reducing radiation risk to their patients by considering these risks when making imaging referrals. This review provides a brief overview of the evidence pertaining to low-level radiation and excess cancer risks and addresses the radiation doses and risks from common medical imaging studies. Specific subsets of patients may be at greater risk from radiation exposure, and radiation risk should be considered carefully in these patients. Recent technical innovations have contributed to lowering the radiation dose from computed tomography, and the referring physician should be aware of these innovations in making imaging referrals.
Staphylococcus aureus is a skin- and respiratory tract-colonizing bacterium and is the leading cause of community-acquired skin infections. Dissemination of these bacteria into systemic circulation ...causes bacteremia, which has a high mortality rate. Therefore, understanding the immunologic barriers that prevent dissemination is critical to developing novel treatments. In this study, we demonstrate that an S. aureus breach across skin leads to some migration of the pathogen to the draining lymph node, but no further. While subcapsular sinus (SCS) macrophage in lymph nodes were important in detaining S. aureus, a rapid complement-dependent neutrophil recruitment (independent of the SCS macrophage) via high endothelial venules (HEVs) resulted in high numbers of neutrophils that intercepted the bacteria in the lymph nodes. Peripheral Node Addressin together with its two ligands, L-selectin and platelet P-selectin, are critical for recruiting neutrophils via the HEVs. Almost no neutrophils entered the lymph nodes via lymphatics. Neutrophils actively phagocytosed S. aureus and helped sterilize the lymph nodes and prevent dissemination to blood and other organs.
Central tolerance can be mediated by peripheral dendritic cells (DCs) that transport innocuous antigens (Ags) to the thymus for presentation to developing T cells, but the responsible DC subsets ...remained poorly defined. Immature plasmacytoid DCs (pDCs) express CCR9, a chemokine receptor involved in migration of T cell precursors to the thymus. We show here that CCR9 mediated efficient thymic entry of endogenous or i.v. transfused pDCs. pDCs activated by Toll-like receptor (TLR) ligands downregulated CCR9 and lost their ability to home to the thymus. Moreover, endogenous pDCs took up subcutaneously injected fluorescent Ag and, in the absence of TLR signals, transported Ag to the thymus in a CCR9-dependent fashion. Injected, Ag-loaded pDCs effectively deleted Ag-specific thymocytes, and this thymic clonal deletion required CCR9-mediated homing and was prevented by infectious signals. Thus, peripheral pDCs can contribute to immune tolerance through CCR9-dependent transport of peripheral Ags and subsequent deletion of Ag-reactive thymocytes.
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► CCR9 controls pDCs numbers in the thymus ► CCR9 is a marker and thymic homing receptor on immature pDCs ► TLR activation or lack of CCR9 prevents thymic clonal deletion by peripheral pDCs ► Peripheral Ag transport to the thymus by endogenous unactivated pDC is CCR9 dependent
Leukocyte trafficking to the small and large intestines is tightly controlled to maintain intestinal immune homeostasis, mediate immune responses, and regulate inflammation. A wide array of ...chemoattractants, chemoattractant receptors, and adhesion molecules expressed by leukocytes, mucosal endothelium, epithelium, and stromal cells controls leukocyte recruitment and microenvironmental localization in intestine and in the gut-associated lymphoid tissues (GALTs). Naive lymphocytes traffic to the gut-draining mesenteric lymph nodes where they undergo antigen-induced activation and priming; these processes determine their memory/effector phenotypes and imprint them with the capacity to migrate via the lymph and blood to the intestines. Mechanisms of T-cell recruitment to GALT and of T cells and plasmablasts to the small intestine are well described. Recent advances include the discovery of an unexpected role for lectin CD22 as a B-cell homing receptor GALT, and identification of the orphan G-protein–coupled receptor 15 (GPR15) as a T-cell chemoattractant/trafficking receptor for the colon. GPR15 decorates distinct subsets of T cells in mice and humans, a difference in species that could affect translation of the results of mouse colitis models to humans. Clinical studies with antibodies to integrin α4β7 and its vascular ligand mucosal vascular addressin cell adhesion molecule 1 are proving the value of lymphocyte trafficking mechanisms as therapeutic targets for inflammatory bowel diseases. In contrast to lymphocytes, cells of the innate immune system express adhesion and chemoattractant receptors that allow them to migrate directly to effector tissue sites during inflammation. We review the mechanisms for innate and adaptive leukocyte localization to the intestinal tract and GALT, and discuss their relevance to human intestinal homeostasis and inflammation.
Scores of tools to measure outcomes that matter to patients have been developed over the past 30 years but few are used routinely at the point of care. Nelson and colleagues describe examples where ...they are used in primary and secondary care and argue for their wider uptake to improve quality of care
Summary
Vitamin D (VD3) has been linked to immunological processes, and its supplementation may have a role in treatment or prevention of diseases with underlying autoimmune or pro‐inflammatory ...states. As initiators of the immune responses, dendritic cells (DC) are a potential target of VD3 to dampen autoimmunity and inflammation, but the role of DC in VD3‐mediated immunomodulation in vivo is not understood. In addition to being targets of VD3, DC can provide a local source of bioactive VD3 for regulation of T‐cell responses. Here we review existing studies that describe the tolerogenic potential of VD3 on DC, and discuss them in the context of current understanding of DC development and function. We speculate on mechanisms that might account for the potent but poorly understood tolerogenic activities of VD3 and the role of DC as both targets and sources of this hormone.
Islands rimming Pacific atolls typically form narrow, low‐lying lands that are commonly perceived to be particularly vulnerable to global changes such as sea‐level rise. As these, low islands form ...the only habitable land for many island nations, understanding the character of shorelines, and the rates and controls that operate to bring about changes, is an issue of central importance. The purpose of this study is to unravel the characteristics of coastal change on atoll islands of the Gilbert Island chain of the equatorial Pacific nation of Kiribati, especially as they relate to autogenic shoreline processes and El Niño/Southern Oscillation variability. Integration of field observations, differential global positioning system data, historical aerial photographs and ultra‐high resolution remote sensing images demonstrates the nature, spatial patterns and rates of change from 17 islands on Maiana and Aranuka atolls. The results illustrate that, between 2005 and 2009, ca 50% of the shorelines on these islands displayed a discernable shift in position; some shorelines were accretionary (at net rates up to ca 8 m year−1) and others were erosional (up to ca 18 m year−1). Long‐term net rates of change on Maiana between 1969 and 2009 were lower than short‐term net rates measured between 2005 and 2009. Both short‐term and long‐term observations illustrate some of the greatest change occur near terminations of the largest, north–south oriented islands, associated with longshore movement of coarse sand and gravel. Direct hits by tropical depressions and marked seasonality, factors interpreted as being essential in island growth and shoreline dynamics elsewhere, do not directly impact these equatorial atolls and can be eliminated as fundamental controls on shoreline dynamics. Similarly, observations over four years suggested that shoreline variability probably is not influenced directly by marked sea‐level change, although a recent increase in the rates of shoreline change could reflect instability related to the cumulative effect of a long‐term increase in the rate of sea‐level rise. Within this framework of global change, local anthropogenic effects, autogenic shoreline processes and El Niño/Southern Oscillation‐influenced wind and wave variability control many aspects of these dynamic shorelines. These results provide quantitative insights into the character and variability of rates of shoreline change, information essential for evaluating and mitigating the vulnerability of island nations such as Kiribati.
An aged circulatory environment can activate microglia, reduce neural precursor cell activity and impair cognition in mice. We hypothesized that brain endothelial cells (BECs) mediate at least some ...of these effects. We observe that BECs in the aged mouse hippocampus express an inflammatory transcriptional profile with focal upregulation of vascular cell adhesion molecule 1 (VCAM1), a protein that facilitates vascular-immune cell interactions. Concomitantly, levels of the shed, soluble form of VCAM1 are prominently increased in the plasma of aged humans and mice, and their plasma is sufficient to increase VCAM1 expression in cultured BECs and the hippocampi of young mice. Systemic administration of anti-VCAM1 antibody or genetic ablation of Vcam1 in BECs counteracts the detrimental effects of plasma from aged individuals on young brains and reverses aging aspects, including microglial reactivity and cognitive deficits, in the brains of aged mice. Together, these findings establish brain endothelial VCAM1 at the blood-brain barrier as a possible target to treat age-related neurodegeneration.
Ag-presenting dendritic cells (DCs) interpret environmental signals to orchestrate local and systemic immune responses. They govern the balance between tolerance and inflammation at epithelial ...surfaces, where the immune system must provide robust pathogen responses while maintaining tolerance to commensal flora and food Ags. The Wnt family of secreted proteins, which control epithelial and hematopoietic development and homeostasis, is emerging as an important regulator of inflammation. In this study, we show that canonical and noncanonical Wnts directly stimulate murine DC production of anti-inflammatory cytokines. Wnt3A triggers canonical β-catenin signaling and preferentially induces DC TGF-β and VEGF production, whereas Wnt5A induces IL-10 through alternative pathways. The Wnts also alter DC responses to microbe- or pathogen-associated molecular patterns, inhibiting proinflammatory cytokine induction in response to TLR ligands and promoting DC generation of Foxp3(+) regulatory T cells. Moreover, although both Wnts suppress proinflammatory responses to bacterial endotoxin and to TLR1/2, TLR7, and TLR9 ligands, Wnt5A, but not Wnt3A, inhibits IL-6 production in response to the viral mimic, polyinosinic:polycytidylic acid. Thus, Wnt family members directly and differentially regulate DC functions, an ability that may contribute to the balance between tolerance and inflammation at epithelial sites of exposure to microbes and environmental Ags.
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