Summary
Mast cells (MCs) are innate immune cells that are scattered in tissues throughout the organism being particularly abundant at sites exposed to the environment such as the skin and mucosal ...surfaces. Generally known for their role in IgE‐mediated allergies, they have also important functions in the maintenance of tissue integrity by constantly sensing their microenvironment for signals by inflammatory triggers that can comprise infectious agents, toxins, hormones, alarmins, metabolic states, etc. When triggered their main function is to release a whole set of inflammatory mediators, cytokines, chemokines, and lipid products. This allows them to organize the ensuing innate immune and inflammatory response in tight coordination with resident tissue cells, other rapidly recruited immune effector cells as well as the endocrine and exocrine systems of the body. To complete these tasks, MCs are endowed with a large repertoire of receptors allowing them to respond to multiple stimuli or directly interact with other cells. Here we review some of the receptors expressed on MCs (ie, receptors for Immunoglobulins, pattern recognition receptors, nuclear receptors, receptors for alarmins, and a variety of other receptors) and discuss their functional implication in the immune and inflammatory response focusing on non‐IgE‐mediated activation mechanisms.
The vast majority of commodity plastics do not degrade and therefore they permanently pollute the environment. At present, less than 20% of post-consumer plastic waste in developed countries is ...recycled, predominately for energy recovery or repurposing as lower-value materials by mechanical recycling. Chemical recycling offers an opportunity to revert plastics back to monomers for repolymerization to virgin materials without altering the properties of the material or the economic value of the polymer. For plastic waste that is either cost prohibitive or infeasible to mechanically or chemically recycle, the nascent field of chemical upcycling promises to use chemical or engineering approaches to place plastic waste at the beginning of a new value chain. Here state-of-the-art methods are highlighted for upcycling plastic waste into value-added performance materials, fine chemicals and specialty polymers. By identifying common conceptual approaches, we critically discuss how the advantages and challenges of each approach contribute to the goal of realizing a sustainable plastics economy.
Early mast cell (MC) infiltration has been reported in a wide range of human and animal tumors particularly malignant melanoma and breast and colorectal cancer. The consequences of their presence in ...the tumor microenvironment (TME) or at their margins still remain unclear as it is associated with a good or poor prognosis based on the type and anatomical site of the tumor. Within the tumor, MC interactions occur with infiltrated immune cells, tumor cells, and extracellular matrix (ECM) through direct cell-to-cell interactions or release of a broad range of mediators capable of remodeling the TME. MCs actively contribute to angiogenesis and induce neovascularization by releasing the classical proangiogenic factors including VEGF, FGF-2, PDGF, and IL-6, and nonclassical proangiogenic factors mainly proteases including tryptase and chymase. MCs support tumor invasiveness by releasing a broad range of matrix metalloproteinases (MMPs). MC presence within the tumor gained additional significance when it was assumed that controlling its activation by tyrosine kinase inhibitors (imatinib and masitinib) and tryptase inhibitors (gabexate and nafamostat mesylate) or controlling their interactions with other cell types may have therapeutic benefit.
It is widely accepted that common diseases of the oral cavity, such as gingivitis and periodontitis, are preventable. Based on a large body of scientific evidence, a number of preventive strategies ...are known to prevent these diseases, but only if routinely implemented. Unfortunately, while most preventive strategies are theoretically simple to understand, they are often difficult to employ in practice at individual and public health levels. This volume of Periodontology 2000 provides the most current information on the state of the science and the evidence base supporting a preventive perspective for the management of periodontal disease, including evidence for proven interventions as well as cutting‐edge ideas for potential future interventions. In addition to well‐established and scientifically proven approaches (tooth and implant cleansing, topical chemotherapeutics, reduction in risk factors such as tobacco smoking), a number of new ideas are now under investigation, including antioxidant agents, probiotics, vaccines, and slow‐release alternative chemotherapeutics. Furthermore, there are new ideas to alter patient behaviors with the aim to improve adherence to preventive strategies. Finally, examples from implementation science and public health are provided that suggest novel approaches to bring new ideas into clinical practice.
The circadian system serves one of the most fundamental properties present in nearly all organisms: it generates 24-h rhythms in behavioral and physiological processes and enables anticipating and ...adapting to daily environmental changes. Recent studies indicate that the circadian system is important in regulating the daily rhythm in glucose metabolism. Disturbance of this circadian control or of its coordination relative to the environmental/behavioral cycle, such as in shift work, eating late, or due to genetic changes, results in disturbed glucose control and increased type 2 diabetes risk. Therefore, an in-depth understanding of the mechanisms underlying glucose regulation by the circadian system and its disturbance may help in the development of therapeutic interventions against the deleterious health consequences of circadian disruption.
Mountains, especially in the tropics, harbour a unique and large portion of the world's biodiversity. Their geographical isolation, limited range size and unique environmental adaptations make ...montane species potentially the most threatened under impeding climate change. Here, we provide a global baseline assessment of geographical range contractions and extinction risk of high-elevation specialists in a future warmer world. We consider three dispersal scenarios for simulated species and for the world's 1009 montane bird species. Under constrained vertical dispersal (VD), species with narrow vertical distributions are strongly impacted; at least a third of montane bird diversity is severely threatened. In a scenario of unconstrained VD, the location and structure of mountain systems emerge as a strong driver of extinction risk. Even unconstrained lateral movements offer little improvement to the fate of montane species in the Afrotropics, Australasia and Nearctic. Our results demonstrate the particular roles that the geography of species richness, the spatial structure of lateral and particularly vertical range extents and the specific geography of mountain systems have in determining the vulnerability of montane biodiversity to climate change. Our findings confirm the outstanding levels of biotic perturbation and extinction risk that mountain systems are likely to experience under global warming and highlight the need for additional knowledge on species' vertical distributions, dispersal and adaptive capacities.
It has recently been argued that corporate social responsibility (CSR) is ‘political’. It has been neglected however, that firms also operate politically in a traditional sense, in seeking to secure ...favourable political conditions for their businesses. We argue that there are potential synergies between CSR and corporate political activity (CPA) that are often overlooked by firms and that recognition of these synergies will stimulate firms to align their CSR and CPA. We develop a conceptual model that specifies how various configurations of a firm's CSR and CPA – alignment, misalignment, and non‐alignment – affect the firm's reputation beyond the separate reputation effects of CSR and CPA. This model has important implications for understanding how and why firms should pay attention to their CPA and CSR configurations, and thereby contributes to the broader issue of why firms should make sure that they are consistent in terms of responding to stakeholder concerns.
Opinion statement
TNM stage remains the key determinant of patient prognosis after surgical resection of colorectal cancer (CRC), and informs treatment decisions. However, there is considerable ...stage-independent variability in clinical outcome that is likely due to molecular heterogeneity. This variability underscores the need for robust prognostic and predictive biomarkers to guide therapeutic decision-making including the use of adjuvant chemotherapy. Although the majority of CRCs develop via a chromosomal instability pathway, approximately 12–15 % have deficient DNA mismatch repair (dMMR) which is characterized in the tumor by microsatellite instability (MSI). Tumors with the dMMR/MSI develop from a germline mutation in an MMR gene (MLH1, MSH2, MSH6, PMS2), i.e., Lynch syndrome, or more commonly from epigenetic inactivation of
MLH1
MMR gene. CRCs with dMMR/MSI status have a distinct phenotype that includes predilection for the proximal colon, poor differentiation, and abundant tumor-infiltrating lymphocytes. Consistent data indicate that these tumors have a better stage-adjusted survival compared to proficient MMR or microsatellite stable (MSS) tumors and may respond differently to 5-fluorouracil-based adjuvant chemotherapy. To increase the identification of dMMR/MSI patients in clinical practice that includes those with Lynch syndrome, it is recommended that all resected CRCs to be analyzed for MMR status. Available data indicate that patients with stage II dMMR CRCs have an excellent prognosis and do not benefit from 5-fluorouracil (FU)-based adjuvant chemotherapy which supports their recommended management by surgery alone. In contrast, the benefit of standard adjuvant chemotherapy with the FOLFOX regiment in stage III dMMR CRC patients awaits further study and therefore, all patients should be treated with standard adjuvant FOLFOX.
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