Pericytes:The lung-forgotten cell type

Pericytes are a heterogeneous population of mesenchymal cells located on the abluminal surface of microvessels, where they provide structural and biochemical support. Pericytes have been implicated in numerous lung diseases including pulmonary arterial hypertension (PAH) and allergic asthma due to their ability to differentiate into scar-forming myofibroblasts, leading to collagen deposition and matrix remodelling and thus driving tissue fibrosis. Pericyte-extracellular matrix interactions as well as other biochemical cues play crucial roles in these processes. In this review, we give an overview of lung pericytes, the key pro-fibrotic mediators they interact with, and detail recent advances in preclinical studies on how pericytes are disrupted and contribute to lung diseases including PAH, allergic asthma, and chronic obstructive pulmonary disease (COPD). Several recent studies using mouse models of PAH have demonstrated that pericytes contribute to these pathological events; efforts are currently underway to mitigate pericyte dysfunction in PAH by targeting the TGF-β, CXCR7, and CXCR4 signalling pathways. In allergic asthma, the dissociation of pericytes from the endothelium of blood vessels and their migration towards inflamed areas of the airway contribute to the characteristic airway remodelling observed in allergic asthma. Although several factors have been suggested to influence this migration such as TGF-β, IL-4, IL-13, and periostin, recent evidence points to the CXCL12/CXCR4 pathway as a potential therapeutic target. Pericytes might also play an essential role in lung dysfunction in response to ageing, as they are responsive to environmental risk factors such as cigarette smoke and air pollutants, which are the main drivers of COPD. However, there is currently no direct evidence delineating the contribution of pericytes to COPD pathology. Although there is a lack of human clinical data, the recent available evidence derived from in vitro and animal-based models shows that pericytes play important roles in the initiation and maintenance of chronic lung diseases and are amenable to pharmacological interventions. Therefore, further studies in this field are required to elucidate if targeting pericytes can treat lung diseases.</p

Effects of cytokine signaling inhibition on inflammation-driven tissue remodeling

Fibrosis is a common condition that can affect all body tissues, driven by unresolved tissue inflammation and resulting in tissue dysfunction and organ failure that could ultimately lead to death. A myriad of factors are thought to contribute to fibrosis and, although it is relatively common, treatments focusing on reversing fibrosis are few and far between. The process of fibrosis involves a variety of cell types, including epithelial, endothelial, and mesenchymal cells, as well as immune cells, which have been shown to produce pro-fibrotic cytokines. Advances in our understanding of the molecular mechanisms of inflammation-driven tissue fibrosis and scar formation have led to the development of targeted therapeutics aiming to prevent, delay, or even reverse tissue fibrosis. In this review, we describe promising targets and agents in development, with a specific focus on cytokines that have been well-described to play a role in fibrosis: IL-1, TNF-α, IL-6, and TGF-β. An array of small molecule inhibitors, natural compounds, and biologics have been assessed in vivo, in vivo, and in the clinic, demonstrating the capacity to either directly interfere with pro-fibrotic pathways or to block intracellular enzymes that control fibrosis-related signaling pathways. Targeting pro-fibrotic cytokines, potentially via a multi-pronged approach, holds promise for the treatment of inflammation-driven fibrotic diseases in numerous organs. Despite the complexity of the interplay of cytokines in fibrotic tissues, the breadth of the currently ongoing research targeting cytokines suggests that these may hold the key to mitigating tissue fibrosis and reducing organ damage in the future

Matricellular Protein Periostin Promotes Pericyte Migration in Fibrotic Airways

Introduction: Periostin is a matricellular protein that is currently used as a biomarker for asthma. However, its contribution to tissue remodeling in allergic asthma is currently unknown. We have previously demonstrated that tissue-resident mesenchymal stem cells known as pericytes are a key cell type involved in airway remodeling. This is thought to be caused the uncoupling of pericytes from the microvasculature supporting the large airways, facilitated by inflammatory growth factors and cytokines. It is hypothesized that periostin may be produced by profibrotic pericytes and contribute to the remodeling observed in allergic asthma. Methods: Lung sections from mice with allergic airway disease driven by exposure to house dust mite (HDM) were stained using an anti-periostin antibody to explore its involvement in fibrotic lung disease. Human pericytes were cultured in vitro and stained for periostin to assess periostin expression. Migration assays were performed using human pericytes that were pretreated with TGF-β or periostin. ELISAs were also carried out to assess periostin expression levels in bronchoalveolar lavage fluid as well as the induction of periostin production by IL-13. Results: Immunostaining indicated that pericytes robustly express periostin, with increased expression following treatment with TGF-β. Migration assays demonstrated that pericytes treated with periostin were more migratory. Periostin production was also increased in HDM exposed mice as well as in cultured pericytes treated with IL-13. Conclusion: Periostin is produced by pericytes in response to TGF-β or IL-13, and periostin plays a key role in inducing pericyte migration. The increase in periostin expression in TGF-β or IL-13 treated pericytes suggests that IL-13 may trigger periostin production in pericytes whilst TGF-β modulates periostin expression to promote pericyte migration in the context of tissue fibrosis

Determining a Core Curriculum in Surgical Infections for Fellowship Training in Acute Care Surgery Using the Delphi Technique

Background: Recent data highlight the educational, financial, and healthcare benefits of acute care surgery (ACS). These data serve as the impetus to create ACS fellowships, which now are accredited by the American Association for the Surgery of Trauma. However, the core components of a curriculum fundamental for ACS training and that yield competence and proficiency have yet to be determined. Methods: Experts in ACS from the United States (n=86) were asked to propose topics in surgical infectious diseases of potential importance in developing a core curriculum for ACS fellowship training. They were then required to rank these topics in order of importance to identify those considered most fundamental. Results: Thirty-one filters ranking in the highest tertile are proposed as topics of surgical infectious diseases that are fundamental to any curriculum of ACS fellowship training. The majority pertains to aspects of thoracic infections (n=8), although topics of soft tissue infections (n=5) comprised four of the top 10 (40%) filters. Abdominal infections (n=6), the biology of sepsis (n=6), and risk, prevention, and prophylaxis (n=6) completed the list. Conclusion: This study identifies the most important topics of surgical infectious disease that merit consideration for incorporation into a core curriculum of ACS training. Hopefully, this information will assist in the development of ACS fellowships that optimize the training of future ACS surgeons.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140213/1/sur.2012.202.pd

EFFECTS OF MANAGEMENT PRACTICES ON GRASSLAND BIRDS: LESSER PRAIRIE-CHICKEN

Information on the habitat requirements and effects of habitat management on grassland birds were summarized from information in more than 4,000 published and unpublished papers. A range map is provided to indicate the breeding distribution of Lesser Prairie-Chicken in the United States and southern Canada. Although birds frequently are observed outside the breeding range indicated, the maps are intended to show areas where managers might concentrate their attention. It may be ineffectual to manage habitat at a site for a species that rarely occurs in an area. The species account begins with a brief capsule statement, which provides the fundamental components or keys to management for the species. A section on breeding range outlines the current breeding distribution of the species in North America. The suitable habitat section describes the breeding habitat and occasionally microhabitat characteristics of the species, especially those habitats that occur in the Great Plains. Details on habitat and microhabitat requirements often provide clues to how a species will respond to a particular management practice. A table near the end of the account complements the section on suitable habitat, and lists the specific habitat characteristics for the species by individual studies. A special section on prey habitat is included for those predatory species that have more specific prey requirements. The area requirements section provides details on territory and home range sizes, minimum area requirements, and the effects of patch size, edges, and other landscape and habitat features on abundance and productivity. It may be futile to manage a small block of suitable habitat for a species that has minimum area requirements that are larger than the area being managed. The Brown-headed Cowbird (Molothrus ater) is an obligate brood parasite of many grassland birds. The section on cowbird brood parasitism summarizes rates of cowbird parasitism, host responses to parasitism, and factors that influence parasitism, such as nest concealment and host density. The impact of management depends, in part, upon a species’ nesting phenology and biology. The section on breeding-season phenology and site fidelity includes details on spring arrival and fall departure for migratory populations in the Great Plains, peak breeding periods, the tendency to renest after nest failure or success, and the propensity to return to a previous breeding site. The duration and timing of breeding varies among regions and years. Species’ response to management summarizes the current knowledge and major findings in the literature on the effects of different management practices on the species. The section on management recommendations complements the previous section and summarizes specific recommendations for habitat management provided in the literature. If management recommendations differ in different portions of the species’ breeding range, recommendations are given separately by region. The literature cited contains references to published and unpublished literature on the management effects and habitat requirements of the species. This section is not meant to be a complete bibliography; a searchable, annotated bibliography of published and unpublished papers dealing with habitat needs of grassland birds and their responses to habitat management is posted at the Web site mentioned below

Pericytes::The lung-forgotten cell type

Pericytes are a heterogeneous population of mesenchymal cells located on the abluminal surface of microvessels, where they provide structural and biochemical support. Pericytes have been implicated in numerous lung diseases including pulmonary arterial hypertension (PAH) and allergic asthma due to their ability to differentiate into scar-forming myofibroblasts, leading to collagen deposition and matrix remodelling and thus driving tissue fibrosis. Pericyte-extracellular matrix interactions as well as other biochemical cues play crucial roles in these processes. In this review, we give an overview of lung pericytes, the key pro-fibrotic mediators they interact with, and detail recent advances in preclinical studies on how pericytes are disrupted and contribute to lung diseases including PAH, allergic asthma, and chronic obstructive pulmonary disease (COPD). Several recent studies using mouse models of PAH have demonstrated that pericytes contribute to these pathological events; efforts are currently underway to mitigate pericyte dysfunction in PAH by targeting the TGF-β, CXCR7, and CXCR4 signalling pathways. In allergic asthma, the dissociation of pericytes from the endothelium of blood vessels and their migration towards inflamed areas of the airway contribute to the characteristic airway remodelling observed in allergic asthma. Although several factors have been suggested to influence this migration such as TGF-β, IL-4, IL-13, and periostin, recent evidence points to the CXCL12/CXCR4 pathway as a potential therapeutic target. Pericytes might also play an essential role in lung dysfunction in response to ageing, as they are responsive to environmental risk factors such as cigarette smoke and air pollutants, which are the main drivers of COPD. However, there is currently no direct evidence delineating the contribution of pericytes to COPD pathology. Although there is a lack of human clinical data, the recent available evidence derived from in vitro and animal-based models shows that pericytes play important roles in the initiation and maintenance of chronic lung diseases and are amenable to pharmacological interventions. Therefore, further studies in this field are required to elucidate if targeting pericytes can treat lung diseases

Effects of Management Practices on Grassland Birds: Sprague’s Pipit

Sprague’s Pipit (Anthus spragueii): Breeding range Suitable habitat Area requirements Brown-headed Cowbird brood parasitism Breeding-season phenology and site fidelity Species’ response to management Management Recommendations Habitat Characteristic

Effects of Management Practices on Grassland Birds: Sprague’s Pipit

Sprague’s Pipit (Anthus spragueii): Breeding range Suitable habitat Area requirements Brown-headed Cowbird brood parasitism Breeding-season phenology and site fidelity Species’ response to management Management Recommendations Habitat Characteristic

Effects of Management Practices on Grassland Birds: Grasshopper Sparrow

Grasshopper Sparrow (Ammodramus savannarum): Breeding range Suitable habitat Area requirements Brown-headed Cowbird brood parasitism Breeding-season phenology and site fidelity Species’ response to management Management Recommendations Habitat Characteristic

Effects of Management Practices on Grassland Birds: Grasshopper Sparrow

Grasshopper Sparrow (Ammodramus savannarum): Breeding range Suitable habitat Area requirements Brown-headed Cowbird brood parasitism Breeding-season phenology and site fidelity Species’ response to management Management Recommendations Habitat Characteristic