55 research outputs found
Development and Remodeling of the Vertebrate Blood-Gas Barrier
During vertebrate development, the lung inaugurates as an endodermal bud from the primitive foregut. Dichotomous subdivision of the bud results in arborizing airways that form the prospective gas exchanging chambers, where a thin blood-gas barrier (BGB) is established. In the mammalian lung, this proceeds through conversion of type II cells to type I cells, thinning, and elongation of the cells as well as extrusion of the lamellar bodies. Subsequent diminution of interstitial tissue and apposition of capillaries to the alveolar epithelium establish a thin BGB. In the noncompliant avian lung, attenuation proceeds through cell-cutting processes that result in remarkable thinning of the epithelial layer. A host of morphoregulatory molecules, including transcription factors such as Nkx2.1, GATA, HNF-3, and WNT5a; signaling molecules including FGF, BMP-4, Shh, and TFG-ÎČand extracellular proteins and their receptors have been implicated. During normal physiological function, the BGB may be remodeled in response to alterations in transmural pressures in both blood capillaries and airspaces. Such changes are mitigated through rapid expression of the relevant genes for extracellular matrix proteins and growth factors. While an appreciable amount of information regarding molecular control has been documented in the mammalian lung, very little is available on the avian lung
Maturation of the gastric microvasculature in Xenopus laevis (Lissamphibia, Anura) occurs at the transition from the herbivorous to the carnivorous lifestyle, predominantly by intussuceptive microvascular growth (IMG): a scanning electron microscope study of microvascular corrosion casts and correlative light microscopy
The microvascular bed of the stomach of Xenopus laevis and the changes it undergoes when the herbivorous tadpole becomes a carnivorous adult were studied by scanning electron microscopy of vascular corrosion casts and light microscopy of stained tissue sections. In tadpoles an upper and a lower gastric artery supplied, and upper, middle and lower medial and lateral gastric veins drained the vertically extending stomach. During metamorphosis, the stomach gained a horizontal cranio-caudal extension and vessels accordingly become dorsal and ventral gastric arteries, and anterior, middle and posterior gastric veins, respectively. Up to stage 64 (late climax) mucosal capillaries formed a polygonal network of wide immature-looking capillaries ensheathing gastric glands in a basket-like manner. From stage 64 onwards, blood vessels of the stomach appeared mature, revealed a clear hierarchy and were correlated closely with the histomorphology of the stomach, which had also gained the adult pattern. Within the gastric mucosa, ascending arterioles branched in a fountain-like pattern into wide subepithelial capillaries establishing a centripetal blood flow along the gastric glands, which makes an ultrashort control loop of glandular cells within the branched tubular gastric glands very unlikely. Formation of the stomach external muscular layer started at stage 57 when smooth muscle cells locally formed a single longitudinal and one-to-two single circular layers. Abundant signs of intussusceptive microvascular growth and rare vascular sprouts in vascular corrosion casts indicated that the larval-to-adult microvascular pattern formation of the stomach of Xenopus laevis Daudin occurs predominantly by non-sprouting angiogenesis
Type IV collagen drives alveolar epithelial-endothelial association and the morphogenetic movements of septation
Background: Type IV collagen is the main component of the basement membrane that gives strength to the blood-gas barrier (BGB). In mammals, the formation of a mature BGB occurs primarily after birth during alveologenesis and requires the formation of septa from the walls of the saccule. In contrast, in avians, the formation of the BGB occurs rapidly and prior to hatching. Mutation in basement membrane components results in an abnormal alveolar phenotype; however, the specific role of type IV collagen in regulating alveologenesis remains unknown. Results: We have performed a microarray expression analysis in late chick lung development and found that COL4A1 and COL4A2 were among the most significantly upregulated genes during the formation of the avian BGB. Using mouse models, we discovered that mutations in murine Col4a1 and Col4a2 genes affected the balance between lung epithelial progenitors and differentiated cells. Mutations in Col4a1 derived from the vascular component were sufficient to cause defects in vascular development and the BGB. We also show that Col4a1 and Col4a2 mutants displayed disrupted myofibroblast proliferation, differentiation and migration. Lastly, we revealed that addition of type IV collagen protein induced myofibroblast proliferation and migration in monolayer culture and increased the formation of mesenchymal-epithelial septal-like structures in co-culture. Conclusions: Our study showed that type IV collagen and, therefore the basement membrane, play fundamental roles in coordinating alveolar morphogenesis. In addition to its role in the formation of epithelium and vasculature, type IV collagen appears to be key for alveolar myofibroblast development by inducing their proliferation, differentiation and migration throughout the developing septum
Wing pathology of white-nose syndrome in bats suggests life-threatening disruption of physiology
White-nose syndrome (WNS) is causing unprecedented declines in several species of North American bats. The characteristic lesions of WNS are caused by the fungus Geomyces destructans, which erodes and replaces the living skin of bats while they hibernate. It is unknown how this infection kills the bats. We review here the unique physiological importance of wings to hibernating bats in relation to the damage caused by G. destructans and propose that mortality is caused by catastrophic disruption of wing-dependent physiological functions. Mechanisms of disease associated with G. destructans seem specific to hibernating bats and are most analogous to disease caused by chytrid fungus in amphibians
Evidence and gap map of studies assessing the effectiveness of interventions for people with disabilities in lowâand middleâincome countries
Background: There are approximately 1 billion people in the world with some form of disability. This corresponds to approximately 15% of the world's population (World Report on Disability, 2011). The majority of people with disabilities (80%) live in low- and middle-income countries (LMICs), where disability has been shown to disproportionately affect the most disadvantaged sector of the population. Decision makers need to know what works, and what does not, to best invest limited resources aimed at improving the well-being of people with disabilities in LMICs. Systematic reviews and impact evaluations help answer this question. Improving the availability of existing evidence will help stakeholders to draw on current knowledge and to understand where new research investments can guide decision-making on appropriate use of resources. Evidence and gap maps (EGMs) contribute by showing what evidence there is, and supporting the prioritization of global evidence synthesis needs and primary data collection. Objectives: The aim of this EGM is to identify, map and describe existing evidence of effectiveness studies and highlight gaps in evidence base for people with disabilities in LMICs. The map helps identify priority evidence gaps for systematic reviews and impact evaluations. Methods: The EGM included impact evaluation and systematic reviews assessing the effect of interventions for people with disabilities and their families/carers. These interventions were categorized across the five components of community-based rehabilitation matrix; health, education, livelihood, social and empowerment. Included studies looked at outcomes such as, health, education, livelihoods, social inclusion and empowerment, and were published for LMICs from 2000 onwards until January 2018. The searches were conducted between February and March 2018. The EGM is presented as a matrix in which the rows are intervention categories (e.g., health) and subcategories (e.g., rehabilitation) and the column outcome domains (e.g., health) and subdomains (e.g., immunization). Each cell lists the studies for that intervention for those outcomes, with links to the available studies. Included studies were therefore mapped according to intervention and outcomes assessed and additional filters as region, population and study design were also coded. Critical appraisal of included systematic review was done using A Measurement Tool to Assess Systematic Reviewsâ rating scale. We also quality-rated the impact evaluation using a quality assessment tool based on various approaches to risk of bias assessment. Results: The map includes 166 studies, of which 59 are systematic reviews and 107 impact evaluation. The included impact evaluation are predominantly quasiexperimental studies (47%). The numbers of studies published each year have increased steadily from the year 2000, with the largest number published in 2017.The studies are unevenly distributed across intervention areas. Health is the most heavily populated area of the map. A total of 118 studies of the 166 studies concern health interventions. Education is next most heavily populated with 40 studies in the education intervention/outcome sector. There are relatively few studies for livelihoods and social, and virtually none for empowerment. The most frequent outcome measures are health-related, including mental health and cognitive development (n = 93), rehabilitation (n = 32), mortality and morbidity (n = 23) and health check-up (n = 15). Very few studies measured access to assistive devices, nutrition and immunization. Over half (n = 49) the impact evaluation come from upper-middle income countries. There are also geographic gaps, most notably for low income countries (n = 9) and lower-middle income countries (n = 34). There is a fair amount of evidence from South Asia (n = 73) and Sub-Saharan Africa (n = 51). There is a significant gap with respect to study quality, especially with respect to impact evaluation. There appears to be a gap between the framing of the research, which is mostly within the medical model and not using the social model of disability. Conclusion: Investing in interventions to improve well-being of people with disabilities will be critical to achieving the 2030 agenda for sustainable development goals. The EGM summarized here provides a starting point for researchers, decision makers and programme managers to access the available research evidence on the effectiveness of interventions for people with disabilities in LMICs in order to guide policy and programme activity, and encourage a more strategic, policy-oriented approach to setting the future research agenda
Visualisation and characterisation of mononuclear phagocytes in the chicken respiratory tract using CSF1R-transgenic chickens
Additional file 2. Location of B cells, T cells and follicular dendritic cells (FDC) in the lung of MacReporter chickens. The BALT region of 5 to 7 week old non-vaccination animals were analysed for B, T and FCD cells. Isotype controls were used to standardise the microscope and examine aspecific binding before acquiring images (A-B). The GC of MacReporter animals are tightly packed with Bu1-CSF1R-eGFP+ FDC cells and Bu1+CSF1R-eGFP- B cells (C) with few Bu1+ B cells found in the parabronchi (F). CD3+ T cells are disperse within and outside the GC (D) and parabronchi (G). CSF1R-eGFP+ FDC cells express Fc receptors and trap immunoglobulin by expressing IgY (E) and CSF1R-eGFP+ IgY+ FDC are rarely detected out with the GC, BALT region of the lung. GC are indicated by white dashed lines
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