Slit2-Robo Signaling Promotes Glomerular Vascularization and Nephron Development

2021 ◽  
pp. ASN.2020111640
Author(s):  
Jinyu Li ◽  
Luiz Henrique Geraldo ◽  
Alexandre Dubrac ◽  
Georgia Zarkada ◽  
Anne Eichmann

BackgroundKidney function requires continuous blood filtration by glomerular capillaries. Disruption of glomerular vascular development or maintenance contributes to the pathogenesis of kidney diseases, but the signaling events regulating renal endothelium development remain incompletely understood. Here, we discovered a novel role of Slit2-Robo signaling in glomerular vascularization. Slit2 is a secreted polypeptide that binds to transmembrane Robo receptors and regulates axon guidance as well as ureteric bud branching and angiogenesis.MethodsWe performed Slit2-alkaline phosphatase binding to kidney cryosections from mice with or without tamoxifen-inducible Slit2 or Robo1 and -2 deletions, and we characterized the phenotypes using immunohistochemistry, electron microscopy, and functional intravenous dye perfusion analysis.ResultsOnly the glomerular endothelium, but no other renal endothelial compartment, responded to Slit2 in the developing kidney vasculature. Induced Slit2 gene deletion or Slit2 ligand trap at birth affected nephrogenesis and inhibited vascularization of developing glomeruli by reducing endothelial proliferation and migration, leading to defective cortical glomerular perfusion and abnormal podocyte differentiation. Global and endothelial-specific Robo deletion showed that both endothelial and epithelial Robo receptors contributed to glomerular vascularization.ConclusionsOur study provides new insights into the signaling pathways involved in glomerular vascular development and identifies Slit2 as a potential tool to enhance glomerular angiogenesis.

2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Ali Mohamad Mouazen ◽  
Ana Beatriz Hernández-Lara

Purpose Smart cities attract efficient and profitable economic activities, contribute to the societal welfare of their citizens and foster the efficient use and conservation of natural resources. Developing smart cities has become a priority for many developed countries, but as they are preferred destinations for migrants, this raises sustainability issues. They attract people who are seeking a better quality of life, smart services and solutions, a better environment and business activities. The purpose of this paper is to review the state of the art on the relationship between smart cities and migration, with a view to determining sustainability. Design/methodology/approach A bibliometric review and text mining analyses were conducted on publications between 2000 and 2019. Findings The results determined the main parameters of this research topic in terms of its growth, top journals and articles. The role of sustainability in the relationship between smart cities and migration is also identified, highlighting the special interest of its social dimension. Originality/value A bibliometric approach has not been used previously to investigate the link between smart cities and migration. However, given the current relevance of both phenomena, their emergence and growth, this approach is appropriate in determining the state of the art and its main descriptors, with special emphasis on the sustainability implications.


2020 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Chinedu Obi ◽  
Fabio Bartolini ◽  
Marijke D’Haese

Purpose This paper aims to explore the connectivity between social media use, access to migrant networks, information asymmetry and migration intentions. Design/methodology/approach The study was conducted using data from individuals living in Nigeria and analysed with a generalized structural equation model, which is rare for this kind of research. Findings The authors find a dual mediating role of the social media and the migrant networks in facilitating migration, i.e. reducing the threshold cost required to migrate and introducing a bias in terms of information asymmetry. While social media and access to migrant networks directly increase migration intentions, this changes when incomplete information is provided. People who use social media and their migrant networks for information are more likely to have information about destination countries than information on the transit risk. Social implications The study adds valuable insights for designing awareness campaigns aimed at reducing irregular migration. Originality/value This study contributes to the understanding of the intersection of migration and digitalization


1998 ◽  
Vol 89 (4) ◽  
pp. 559-567 ◽  
Author(s):  
Richard S. Polin ◽  
Murad Bavbek ◽  
Mark E. Shaffrey ◽  
Kevin Billups ◽  
Christopher A. Bogaev ◽  
...  

Object. The goal of this study was to explore whether the levels of soluble adhesion molecules were elevated in cerebrospinal fluid (CSF) after subarachnoid hemorrhage (SAH). This association was suggested by the known inflammatory response in vasospasm and the role of vascular adhesion molecules in regulating leukocytic adhesion to, and migration across, vascular endothelium. Methods. A prospective analysis was performed on CSF samples obtained in 17 patients who had suffered a recent aneurysmal SAH and in 16 control patients by using quantitative enzyme-linked immunosorbent assays for E-selectin, intercellular adhesion molecule—1 (ICAM—1), vascular adhesion molecule—1 (VCAM-1), and L-selectin. Levels of soluble forms of E-selectin (p = 0.0013), ICAM-1 (p = 0.0001), and VCAM-1 (p = 0.048) were found to be elevated in the CSF of patients after SAH compared with levels in the CSF of normal controls, patients with unruptured aneurysms, and patients tested months after SAH occurred. In addition, individual patients tested at the time of their initial ictus demonstrated a fall in adhesion molecule levels over time. Levels of E-selectin (p = 0.044) were highest in patients who later developed moderate or severe vasospasm. Conclusions. Adhesion molecules are known to be involved in white cell adherence to the endothelium and subsequent diapedesis and migration in which a role in initiation of tissue damage is postulated. The authors have demonstrated the elevation of three adhesion molecules, with severely elevated levels of E-selectin seen in patients who later develop vasospasm. A correlation with a role of vascular adhesion molecules in the pathogenesis of cerebral vasospasm is suggested.


2001 ◽  
Vol 220 (1) ◽  
pp. 1-17 ◽  
Author(s):  
Thomas J. Poole ◽  
Eric B. Finkelstein ◽  
Christopher M. Cox

foresight ◽  
2020 ◽  
Vol 22 (4) ◽  
pp. 437-468 ◽  
Author(s):  
Luigi Aldieri ◽  
Maxim Kotsemir ◽  
Concetto Paolo Vinci

Purpose What is the effect of an increase of migration inflows on the R&D and innovative performance of developing countries? The purpose of this paper is to investigate the impact of migration inflows on the R&D and innovation activity (measured as expenditures on R&D and technological innovations) in Russian regions. Design/methodology/approach To this end, the authors use data on 85 Russian regions for the period 2010-2016 through a multi-region economic geography model. In particular, the authors test the hypothesis about the importance of migration inflows on R&D and technological innovation activity (H1) and the hypothesis about the importance of immigrants’ (incoming migrants) human capital (measured by the education level of incoming migrants) on R&D and innovation activity (H2). Findings Empirical findings support the evidence in favour of a positive causal link between innovation and migration inflows. Results of our investigation are important because they suggest useful insights for formulating science and innovation policies in Russia, which is a developing country where the recent policies favouring the technological innovation as the transition period have not yet achieved a satisfying outcome. Originality/value This paper increases the knowledge in the field with respect to the existing literature, shedding further light on the migration inflows effects, which is a political topic to manage very relevant in all countries.


2005 ◽  
Vol 169 (6) ◽  
pp. 941-952 ◽  
Author(s):  
Tang-Long Shen ◽  
Ann Y.-J. Park ◽  
Ana Alcaraz ◽  
Xu Peng ◽  
Ihnkyung Jang ◽  
...  

Focal adhesion kinase (FAK) is a critical mediator of signal transduction by integrins and growth factor receptors in a variety of cells including endothelial cells (ECs). Here, we describe EC-specific knockout of FAK using a Cre-loxP approach. In contrast to the total FAK knockout, deletion of FAK specifically in ECs did not affect early embryonic development including normal vasculogenesis. However, in late embryogenesis, FAK deletion in the ECs led to defective angiogenesis in the embryos, yolk sac, and placenta, impaired vasculature and associated hemorrhage, edema, and developmental delay, and late embryonic lethal phenotype. Histologically, ECs and blood vessels in the mutant embryos present a disorganized, detached, and apoptotic appearance. Consistent with these phenotypes, deletion of FAK in ECs isolated from the floxed FAK mice led to reduced tubulogenesis, cell survival, proliferation, and migration in vitro. Together, these results strongly suggest a role of FAK in angiogenesis and vascular development due to its essential function in the regulation of multiple EC activities.


2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Marina Latukha ◽  
Mariia Shagalkina ◽  
Ekaterina Kalinina ◽  
Daria Khasieva

PurposeThe growing trends in talent migration, which in the extreme lead to brain drain, in step with an increasing female participation in labor markets and migration flows, set challenges for both business and governments managing these processes. In this vein, it is proposed that macro talent management (MTM) is effective in managing the above-mentioned macro-level issues. The purpose of this paper is to identify and compare the determinants of talent migration with respect to gender and to analyze the role that talent management (TM) practices may play in the migration of diverse talent groups (male and female) within the Russian context.Design/methodology/approachAnticipating the possible differences in talent migration determinants between men and women and using data from 557 Russian graduates, considered to be high-potential talents, the authors found that these determinants converge.FindingsMale and female talent migration intentions in Russia are influenced by the same industry and individual push factors as well as family reasons, confirming that women are acting as independent economic migrants rather than tied movers. Moreover, the authors identified that talents in our sample evaluate highly the possibility of TM practices to change their migration intentions, and that female talents are more sensitive and responsive in this regard. Therefore, the TM system in the emerging economies' context, in particular Russia, is important for increasing the share of women in the workforce, in particular in leadership positions.Originality/valueThe study's results are important as they provide evidence on the gendered dimension of talent migration in particular in terms of the gendered assessment of talent migration determinants. Moreover, the study shows the positive role of TM in managing talent flows at the country level, in particular the ability of TM practices to attract talents to local organizations and, hence, retain them in a country.


2017 ◽  
Vol 51 (4) ◽  
pp. 772-794 ◽  
Author(s):  
Angela Gracia B. Cruz ◽  
Margo Buchanan-Oliver

Purpose The purpose of this paper is to explore the capital-based benefits which arise when acculturating immigrants perform touristic practices, and how these shape their tourism and migration experiences. Design/methodology/approach Grounded in consumer culture theory, this paper draws on theories of capital consumption to inform a hermeneutic analysis of multi-modal depth interviews with Southeast Asian skilled migrants in New Zealand. Findings Domestic touristic practices offer three types of capital-based benefits, enabling consumers to index economic capital, accrue social capital and index cultural capital. Additionally, the quest for capital emphasises iconic forms of tourism and supersedes concerns about commodification. Research limitations/implications This paper demonstrates the important role of touristic practices not only in short-term mobility, but also for long-term migrants. Further research should investigate how capital shapes the touristic practices of other types of mobile consumers. Practical implications Understanding the capital-based benefits of touristic practices in acculturation informs the design of migrant settlement policy and the managerial staging of touristic experiences. Originality/value While theorists of liquid modernity have largely treated tourism as a discrete type of mobility, this paper reframes tourism as a key acculturation practice. In contrast to dominant conceptualisations of tourism as a quest for cultural authenticity, this paper reconceptualises tourism as a quest for capital. Finally, while previous studies have focused on how capital constrains acculturation outcomes, this paper explores how a consumption practice enables the expression and accumulation of capital.


2020 ◽  
pp. 11-15
Author(s):  
A. S. Krutova ◽  
V. N. Luchaninova ◽  
O. V. Semeshina ◽  
A. Nee ◽  
O. G. Bykova

The review of studies of international and national researchers on the impact of matrix metalloproteinases (matrix metalloproteinases, ММРs) and their inhibitors (tissue inhibitors of metalloproteinases, TIMPs) on physiological and pathological processes in children with kidney diseases. It is shown that MMPs play a significant role in organogenesis, i.e. nephrogenesis. Thus, MMP-2, MMP-9 and TIMPs play a large role in basal membranes remodeling associated with epithelial structures in a developing kidney. Immunohistochemistry assay showed that MMP-2 was localized in structures of immature nephrons undergoing epithelial differentiation, MMP-9 – only in vascular structures included in immature glomeruli. Decreased activity of MMP and /or increased synthesis of TIMPs in nephrocytes contribute to the reduction of intercellular substance components catabolism and serve as a basis for glomerular fibrosis and renal interstitium. MMPs are the major group of proteases which regulate metabolism in extracellular matrix and serve as the most important parameters in tissue remodeling observed in acute and chronic inflammatory processes in kidneys. The literature review gives an opportunity to assess the importance of drug design preventing and delaying the progression of nephrosclerosis.


2015 ◽  
Vol 308 (6) ◽  
pp. F602-F613 ◽  
Author(s):  
A. Blumenthal ◽  
J. Giebel ◽  
G. Warsow ◽  
L. Li ◽  
R. Ummanni ◽  
...  

Elevated glomerular pressure represents a high risk for the development of severe kidney diseases and causes an increase in mechanical load to podocytes. In this study, we investigated whether mechanical stress alters gene expression in cultured podocytes using gene arrays. We found that tetraspanin CD9 is significantly upregulated in cultured podocytes after mechanical stress. The differential expression of CD9 was confirmed by RT-PCR and Western blotting under stretched and unstretched conditions. Furthermore, mechanical stress resulted in a relocalization of CD9. To get an insight into the functional role of CD9, podocytes were transfected with pEGFP-CD9. The expression of CD9 induced the formation of substratum-attached thin arborized protrusions. Ca2+ depletion revealed that podocytes overexpressing CD9 possess altered adhesive properties in contrast to the control transfected cells. Finally, elevated CD9 expression increased migration of podocytes in a wound assay. In summary, our results suggest that upregulation of CD9 may play an important role in podocyte morphology, adhesion, and migration.


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