To see the other types of publications on this topic, follow the link: Regulations BBC.
Journal articles on the topic 'Regulations BBC'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Regulations BBC.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Yudhiasta, Sheidy, and Leily Suci Rahmatin. "Netnographic Analysis of Youtube Users Comments on Conservation Threats." Jurnal Spektrum Komunikasi 10, no. 1 (2022): 62–77. http://dx.doi.org/10.37826/spektrum.v10i1.276.
Full textAbstract:
Conservation and mining are considered as two contradictory aspects of an activity. Conservation activities will be lost if mining development does not match the area analysis. Ecosystems are threatened, and endemic species in an area will become extinct. Mining activities are often two sharp blades. On the one hand, it will increase the economy. However, on the other hand, the more significant damage will make it difficult for the ecosystem to return to its original condition. This is what is currently happening in the Sangihe Islands. Gold mining has become an issue in online discussions on the internet; objections and protests are conveyed to preserve the ecosystem of the region, not only from endemic animal and plant species but also from human existence. This research was conducted by exploring public comments, especially YouTube users in the comments column of the BBC News Indonesia YouTube video: Tambang Emas Pulau Sangihe Mengancam Hutan dan Burung Endemik yang Hampir Punah. A qualitative approach is used in this study with netnographic analysis to analyze netizen comments on BBC News Indonesia YouTube videos. Data retrieval using the botster.io website and analyzed using NVivo 12 software as a qualitative research management tool. The data obtained is 1.000 comments in the comments column. The analysis results show that the majority of internet residents in comments on YouTube videos uploaded by BBC News Indonesia gave a negative response to the Sangihe Island gold mine because it was considered a threat to the conservation and extinction of Sangihe's endemic species, namely the Sangihe Seriwang bird. People on the internet also respond that policy makers' participation in making regulations is important to cancel decisions related to the mining area.
2
Hayati, Shohwunni. "Desacralization in Dressing as a Political Identity for World Peace in the Millennial Era." International Journal Ihya' 'Ulum al-Din 22, no. 1 (2020): 53. http://dx.doi.org/10.21580/ihya.22.1.5607.
Full textAbstract:
When someone dress, other people easily judges about the culture or religion that others have. It invites differences of opinion in enforcing rules within an institution such as schools, campuses, and offices. On March 06, 2018 BBC News reported there was a ban on wearing the face mask (cadar) at a state Islamic university because the threat of radicalism which always gave birth to new people especially in the millennial era now.This is because for some people the face mask (cadar) is seen as a sign of the development of conservative Islam and shows one's identity. But it creates public unrest and some people feel uneasy about the sacralization in the dress. Researcher used library research methods by using descriptive-qualitative type by using primary sources, literature on the theory of desacralization and politic of identity and secondary sources is from several supporting literature. The results, desacralization in dressing is that a person does not contain sacred in clothes except when worship this is at a profane time that dressing has a good meaning with applicable state regulations. Desacralization in dress as politics of identity will be able to position his own identity without disturbing the identity of others.
3
Saleh, Alamira Samah. "Foreign Correspondents between the Hammer and the Anvil." Contemporary Arab Affairs 13, no. 3 (2020): 98–122. http://dx.doi.org/10.1525/caa.2020.13.3.98.
Full textAbstract:
For many decades, Egypt has been considered a distinctive society in which individuals from different nations with different backgrounds and ideologies can live. However, it seems that the Egyptian political, social, and media landscape has witnessed considerable shifts in the dimensions of such diversity. This study examines the contemporary Egyptian perspective on the presence of foreign correspondents and the radical change in Egypt’s regulations toward their work, and moreover, the repercussions of such policies that might be affecting the safety, level of freedom, and sometimes the whole identity of foreign correspondents in Egypt. Moreover, it examines the tactics with which the government seeks to accentuate the discourses of “Othering” in Egyptian public perceptions via whipping up hype in the media. Undoubtedly, the events experienced by Egypt between 25 January 2011 and the present have changed the idea the state and society have of foreigners, in general, and foreign correspondents, in particular. Some indicators confirmed that a state of “xenophobia” has been escalating over the past nine years. Foreign correspondents and journalists have been among the groups harmed by this sentiment, to the detriment of their working conditions. Results show that the transitional period that followed Hosni Mubarak’s toppling in 2011 until today has witnessed many transformations in the handling of foreign correspondents’ work in Egypt. There have been attacks on and expulsions of journalists from Al Arabiya, Al Jazeera, The Associated Press, the BBC, CBS, CNN, Danish television, and others.
4
Seco-Cervera, M., C. Bauset, C. Santana-Plata, et al. "P094 Transcriptomic and small RNA sequencing profile in ileal resections from complicated Crohn′s Disease patients." Journal of Crohn's and Colitis 16, Supplement_1 (2022): i191—i192. http://dx.doi.org/10.1093/ecco-jcc/jjab232.223.
Full textAbstract:
Abstract Background Crohn′s disease is a chronic inflammatory disorder of gastrointestinal tract that is classified into three different behaviours: the inflammatory (B1), the stenotic (B2) or the penetrating (B3). We pretend to identify differences in transcriptomic and non-long coding RNA expression profiles associated to damaged and no-damaged surgical ileal resections from complicated CD patients. Methods We conducted both RNA and small RNA sequencing profiling on ileal surgical resections from CD patients with structuring (n=10) or penetrating (n=10) behaviour; from each patient we obtained a sample from affected tissue (B2A and B3A, respectively) and the paired non-affected ileum (B2C and B3C, respectively). Ten ileal resections (control samples) were obtained from non-affected ileum of patients with right colorectal cancer (IL). Enrichment scores of the GO terms and KEGG pathways were used to functional analysis investigated in this study. Gene expression and miRNA profiles were validated by RT-qPCR. Results Our comparative bioinformatic analysis of RNA sequencing showed that the comparation of IL and the non-affected ileum from CD patients (B2C+B3C) revealed that only 11 genes were significantly altered and any miRNA with significative expression. The comparative analysis between B2A+B3A vs B2C+B3C showed: a) 2562 genes differentially regulated and the GO enrichment analysis determined that inflammation, cell activation, and regulation of the extracellular matrix (EM) were the main biological processes altered (Figure 1a). KEGG analysis showed that cytokine-receptor interaction and MAPK and Ras signalling were the most affected pathways (Figure 1b). Among the top ten up-regulated genes we found several immunoglobulins (such as IGHG4, IGHG3, and IGHG1), proteins of the extracellular matrix EM (such as EPYC, COMP, and CHI3L1), and transcription factors (such as PRRX1). When the analysis was performed by CD behaviour, results revealed that most of these genes were significantly increased in both, B2 and B3 CD; b) 103 miRNAs with differential expression, 56 were up-regulated and 47 were down-regulated. Negative and significant correlations were detected between the RNA expression of ECM components and some miRNA expression. Figure 1. Bar plot of enrichment analysis with differential expressed genes between B2A+B3A vs B2C+B3C. A) Biological Process (BP), Cellular Component (CC), and Molecular Function (MF) of Gene Ontology (GO) enrichment analysis. B) Enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Conclusion The correlation detected between extracellular matrix components and some miRNA suggest an epigenetic regulation in the affected ileum of complicated CD patients.
5
Jayachandran, J., and S. Malathi. "Improved power quality buck boost converter for SMPS." International Journal of Electrical and Computer Engineering (IJECE) 9, no. 2 (2019): 789. http://dx.doi.org/10.11591/ijece.v9i2.pp789-801.
Full textAbstract:
In this paper, a Neural Network (NN) controlled Buck-Boost Converter (BBC) based Switched Mode Power Supply (SMPS) for a PC application is proposed. The proposed BBC is analyzed, modeled and designed for the rated load. Generally, the utilization of Multiple Output SMPS (MOSMPS) for PC application introduces Power Quality (PQ) issues in the power system network. Unlike conventional SMPS the proposed NN controlled BBC can accomplish improvement of power quality. The NN controller reduces the Total Harmonic Distortion (THD) of source current below 5%, maintains input side Power Factor (PF) to be nearly unity and improves the output voltage regulation. In the proposed system, NN controller replaces the conventional PI controller and overcomes the drawbacks of the conventional system. The proposed BBC is validated adopting MATLAB/SIMULINK software. The simulation analysis validate that the proposed NN controlled BBC performs better than conventional converter in terms of PQ indices under fluctuating conditions.
6
Budd, Alan. "The peacock committee and the BBC: Liberal values versus regulation." Chartered Institute of Public Finance and Accountancy. Public Money 6, no. 3 (1986): 29–33. http://dx.doi.org/10.1080/09540968609387395.
Full text
7
BAADE, CHRISTINA. "‘The dancing front’: dance music, dancing, and the BBC in World War II." Popular Music 25, no. 3 (2006): 347–68. http://dx.doi.org/10.1017/s0261143006000973.
Full textAbstract:
This paper offers a case history of the BBC's ambivalent engagement with dance music during the Second World War. It examines what ‘dance music’ meant to the BBC, musicians, and the public, and how they contested and performed those meanings in the context of new social dance practices and the growing popularity of what became known as ‘swing’ in Britain. Although broadcasting in effect disembodied music closely associated with the physical, the BBC was a primary way for people to access dance music which supported their bodily acts of leisure and regimentation. The BBC's study and regulation of dance music centred around two goals: pleasing important groups in national service and broadcasting morale-boosting music. The problem of whether these goals were congruent lay at the heart of the issue, for the youth active in national service emerged as the primary audience for the two genres – ‘swing’ and ‘sentimentality’ – about which the BBC felt most dubious.
8
Fernández Vivas, Yolanda. "El régimen jurídico de los medios de comunicación en el Reino Unido." Teoría y Realidad Constitucional, no. 36 (July 1, 2015): 497. http://dx.doi.org/10.5944/trc.36.2015.16075.
Full textAbstract:
El trabajo que aquí presentamos tiene por objeto el análisis del régimen jurídico de los medios de comunicación en el Reino Unido —prensa, radio y televisión, pública y privada, así como las autoridades de supervisión y control—, que se caracteriza por ser un sistema basado en los principios de independencia, imparcialidad y autorregulación, y cuyo modelo de radiotelevisión pública (la BBC) constituye una referencia en la prestación del servicio público de radiodifusión.This essay analyzes the legal framework for the media in the UK — press, radio and television both public and private, as well as the supervisory authorities — which is based on the principles of independence, impartiality and self-regulation, and whose model of public broadcasting (BBC) is the most relevant reference in public service broadcasting.
9
Sexton, Max. "The Tripods: Distinction, Science Fiction and the BBC." Journal of British Cinema and Television 13, no. 3 (2016): 469–83. http://dx.doi.org/10.3366/jbctv.2016.0330.
Full textAbstract:
This article focuses on how mode and genre shaped the formal and narrative possibilities in The Tripods (BBC, 1984–5). It explores how the first and second series are substantially different from each other and offers an approach that attempts to explain the complex ways in which generic boundaries are made to operate within television. Such an approach can offer insight into how modifications in mode were a desire to replace an existing but ailing show, Doctor Who (BBC, 1963–) with one that would be successful because it fitted the existing industrial model of televisual flow. However, The Tripods ultimately failed because it deployed a strategy of visual distinction in contravention of the prevailing industrial televisual model. The regulation of form can be shown to be historically specific on British television, and the article examines assumptions regarding the fluidity of genre in this particular medium. The modification of The Tripods from an adventure show that addressed a general television audience to one that specifically addressed fans of science fiction demonstrates how shifts in genre can be linked to wider arguments about the increased complexity of the television image and a strategy of visual distinction as an example of the ‘era of availability’ on British television. Finally, a discussion of genre demonstrates the tensions between stability and uncertainty in an extensive cultural form such as television, and how the modality of genre is made complex by bringing together the social and the technological.
10
Zha, Daojun, Qingsong Wang, Ming Cheng, Fujin Deng, and Giuseppe Buja. "Regulation Performance of Multiple DC Electric Springs Controlled by Distributed Cooperative System." Energies 12, no. 18 (2019): 3422. http://dx.doi.org/10.3390/en12183422.
Full textAbstract:
DC electric springs (DCESs) have been recently developed to improve the voltage stability of a DC microgrid. A lately proposed DCES topology is comprised of a DC/DC three port converter (TPC), a bi-directional buck-boost converter (BBC) and a battery, and is arranged as follows: The TPC input port is fed by a renewable energy source (RES) whilst the two TPC output ports supply a non-critical load (NCL) and a critical load (CL) separately; in turn, BBC together with the battery constitutes the DCES energy storage unit (ESU) and is connected in parallel to CL. In this paper, a set of DCESs with such a topology and with their CLs connected to a common DC bus is considered. The control of the DCESs is built up around a distributed cooperative system having two control levels, namely primary and secondary, each of them endowed with algorithms committed to specific tasks. The structure of the control levels is explicated and their parameters are designed. The control system is applied to a DCES set taken as a study-case and tested by simulation. The results of the tests show the excellent performance of the control system in both regulating the CL DC bus voltage and keeping the state-of-charge of the battery within predefined limits.
11
Li, Xiaolong, Yan Cai, Zuo Zhang, and Jiyin Zhou. "Glial and Vascular Cell Regulation of the Blood-Brain Barrier in Diabetes." Diabetes & Metabolism Journal 46, no. 2 (2022): 222–38. http://dx.doi.org/10.4093/dmj.2021.0146.
Full textAbstract:
As a structural barrier, the blood-brain barrier (BBB) is located at the interface between the brain parenchyma and blood, and modulates communication between the brain and blood microenvironment to maintain homeostasis. The BBB is composed of endothelial cells, basement membrane, pericytes, and astrocytic end feet. BBB impairment is a distinguishing and pathogenic factor in diabetic encephalopathy. Diabetes causes leakage of the BBB through downregulation of tight junction proteins, resulting in impaired functioning of endothelial cells, pericytes, astrocytes, microglia, nerve/glial antigen 2-glia, and oligodendrocytes. However, the temporal regulation, mechanisms of molecular and signaling pathways, and consequences of BBB impairment in diabetes are not well understood. Consequently, the efficacy of therapies diabetes targeting BBB leakage still lags behind the requirements. This review summarizes the recent research on the effects of diabetes on BBB composition and the potential roles of glial and vascular cells as therapeutic targets for BBB disruption in diabetic encephalopathy.
12
Savidge, Tor C. "MIND the gap: an astroglial perspective on barrier regulation." Neuron Glia Biology 3, no. 3 (2007): 191–97. http://dx.doi.org/10.1017/s1740925x08000124.
Full textAbstract:
AbstractThe blood–brain barrier (BBB) is a specialized tissue interface that provides an important homeostatic and immunosurveillance role in the CNS. Unlike most microvascular tissues, which readily promote paracellular passage of solutes and macromolecules, the BBB is more analogous to polarized mucosal epithelia that restrict such permeability in order to prevent disease onset. Recent transgenic ablation studies have demonstrated that the BBB and mucosal tissues also share a requirement for astroglial-regulated barrier integrity. This review highlights the emerging concept that astroglia regulate barrier function at markedly different tissue interfaces. It also explores possible lessons that might be learnt by adopting epithelial model paradigms of the BBB. For example, novel glial-derived S-nitrosylation signals that regulate intestinal permeability in the digestive tract might provide new mechanistic insights into the function of the BBB. A better understanding of such universal mechanisms for barrier regulation will facilitate novel therapeutic strategies that target permeability disorders at CNS and mucosal tissue interfaces.
13
Stamatovic, Svetlana M., Parvin Shakui, Richard F. Keep, et al. "Monocyte Chemoattractant Protein-1 Regulation of Blood–Brain Barrier Permeability." Journal of Cerebral Blood Flow & Metabolism 25, no. 5 (2005): 593–606. http://dx.doi.org/10.1038/sj.jcbfm.9600055.
Full textAbstract:
The present study was designed to elucidate the effects of the chemokine monocyte chemoattractant protein (MCP-1) on blood–brain barrier (BBB) permeability. Experiments were conducted under in vitro conditions (coculture of brain endothelial cells and astrocytes) to study the cellular effects of MCP-1 and under in vivo conditions (intracerebral and intracerebroventricular administration of MCP-1) to study the potential contribution of MCP-1 to BBB disruption in vivo. Our results showed that MCP-1 induces a significant increase in the BBB permeability surface area product for fluorescein isothiocyanate (FITC)-albumin under in vivo conditions, particularly during prolonged (3 or 7 days) exposure (0.096±0.008 versus 0.031±0.005 μL/g min in controls at 3 days, P<0.001). Monocyte chemoattractant protein-1 also enhanced (17-fold compared with control) the permeability of the in vitro BBB (coculture) model. At the cellular level, MCP-1 causes alteration of tight junction (TJ) proteins in endothelial cells (redistribution of TJ proteins determined by Western blotting and loss of immunostaining for occludin, claudin-5, ZO-1, ZO-2). Monocyte chemoattractant protein-1-induced alterations in BBB permeability are mostly realized through the CCR2 receptor. Absence of CCR2 diminishes any effect of MCP-1 on BBB permeability in vitro and in vivo. The permeability surface area product for FITC-albumin after 3 days exposure to MCP-1 was 0.096±0.006 and 0.032±0.007 μL/g min, in CCR2+/+ and CCR2−/− mice, respectively ( P<0.001). Monocytes/macrophages also participate in MCP-1-induced alterations in BBB permeability in vivo. Monocytes/macrophages depletion (by clodronate liposomes) reduced the effect of MCP-1 on BBB permeability in vivo ∼2 fold. Our results suggest that, besides its main function of recruiting leukocytes at sites of inflammation, MCP-1 also plays a role in ‘opening’ the BBB.
14
Kim, Cheol-Ho. "A Study on the Laws and Regulations related B2C Cross-border e-Commerce." Journal of Korea Research Association of International Commerce 18, no. 4 (2018): 17–36. http://dx.doi.org/10.29331/jkraic.2018.08.18.4.17.
Full text
15
Langen, Urs H., Swathi Ayloo, and Chenghua Gu. "Development and Cell Biology of the Blood-Brain Barrier." Annual Review of Cell and Developmental Biology 35, no. 1 (2019): 591–613. http://dx.doi.org/10.1146/annurev-cellbio-100617-062608.
Full textAbstract:
The vertebrate vasculature displays high organotypic specialization, with the structure and function of blood vessels catering to the specific needs of each tissue. A unique feature of the central nervous system (CNS) vasculature is the blood-brain barrier (BBB). The BBB regulates substance influx and efflux to maintain a homeostatic environment for proper brain function. Here, we review the development and cell biology of the BBB, focusing on the cellular and molecular regulation of barrier formation and the maintenance of the BBB through adulthood. We summarize unique features of CNS endothelial cells and highlight recent progress in and general principles of barrier regulation. Finally, we illustrate why a mechanistic understanding of the development and maintenance of the BBB could provide novel therapeutic opportunities for CNS drug delivery.
16
Moats-Staats, B. M., H. W. Jarvis, A. J. D'Ercole, and A. D. Stiles. "Cloning and characterization of a novel RNA involved in cellular growth regulation." Molecular and Cellular Biology 14, no. 5 (1994): 2936–45. http://dx.doi.org/10.1128/mcb.14.5.2936.
Full textAbstract:
During the course of antisense oligodeoxynucleotide (oligo) inhibition experiments investigating the role of insulin-like growth factor I (IGF-I) in the WI-38 cell cycle, we found that a sense-strand oligo (S oligo), used as a control, inhibited DNA synthesis 90 to 95%. S1 nuclease protection assays demonstrated that this S oligo formed intracellular duplexes with WI-38 RNA, and Northern (RNA) hybridization analyses demonstrated specific hybridization of this 32P-labeled S oligo to 1.8-, 2.3-, and 3.2-kb RNAs. We have cloned and sequenced a 2,251-bp cDNA, designated BB1, corresponding to the 2.3-kb RNA. Decoding of the BB1 cDNA sequence reveals several open reading frames arranged in a motif similar to that seen in proteins subject to translational control mechanisms. Homology searches of nucleic acid and protein data bases reveal no significant homology of BB1 with known sequences other than a 234-bp region in the BB1 5' untranslated region that shared 97% homology with a region in the 3' untranslated region of the human cdc42 mRNA. S1 nuclease protection analyses performed with IGF-I gene fragments and computer homology searches demonstrated that the BB1 RNA does not derive from transcription from the opposite strand of the IGF-I gene. Northern hybridization analyses of RNA extracted from serum-starved HeLa S3 cells demonstrated that steady-state BB1 RNA levels increased upon serum growth stimulation, with steady-state levels peaking 4 h after release from the block induced by serum starvation. Antisense oligo inhibition experiments using specific BB1 antisense oligos targeted to the putative open reading frames of the BB1 RNA reduce DNA synthesis of HeLa S3 cells to 15% of control levels, indicating that the BB1 RNA is essential for cell cycle traversal and, as such, encodes a growth-reguLating gene product.
17
Moats-Staats, B. M., H. W. Jarvis, A. J. D'Ercole, and A. D. Stiles. "Cloning and characterization of a novel RNA involved in cellular growth regulation." Molecular and Cellular Biology 14, no. 5 (1994): 2936–45. http://dx.doi.org/10.1128/mcb.14.5.2936-2945.1994.
Full textAbstract:
During the course of antisense oligodeoxynucleotide (oligo) inhibition experiments investigating the role of insulin-like growth factor I (IGF-I) in the WI-38 cell cycle, we found that a sense-strand oligo (S oligo), used as a control, inhibited DNA synthesis 90 to 95%. S1 nuclease protection assays demonstrated that this S oligo formed intracellular duplexes with WI-38 RNA, and Northern (RNA) hybridization analyses demonstrated specific hybridization of this 32P-labeled S oligo to 1.8-, 2.3-, and 3.2-kb RNAs. We have cloned and sequenced a 2,251-bp cDNA, designated BB1, corresponding to the 2.3-kb RNA. Decoding of the BB1 cDNA sequence reveals several open reading frames arranged in a motif similar to that seen in proteins subject to translational control mechanisms. Homology searches of nucleic acid and protein data bases reveal no significant homology of BB1 with known sequences other than a 234-bp region in the BB1 5' untranslated region that shared 97% homology with a region in the 3' untranslated region of the human cdc42 mRNA. S1 nuclease protection analyses performed with IGF-I gene fragments and computer homology searches demonstrated that the BB1 RNA does not derive from transcription from the opposite strand of the IGF-I gene. Northern hybridization analyses of RNA extracted from serum-starved HeLa S3 cells demonstrated that steady-state BB1 RNA levels increased upon serum growth stimulation, with steady-state levels peaking 4 h after release from the block induced by serum starvation. Antisense oligo inhibition experiments using specific BB1 antisense oligos targeted to the putative open reading frames of the BB1 RNA reduce DNA synthesis of HeLa S3 cells to 15% of control levels, indicating that the BB1 RNA is essential for cell cycle traversal and, as such, encodes a growth-reguLating gene product.
18
Hardy, Jonathan. "UK Television Policy and Regulation, 2000–10." Journal of British Cinema and Television 9, no. 4 (2012): 521–47. http://dx.doi.org/10.3366/jbctv.2012.0104.
Full textAbstract:
Between 2000 and 2010, new institutional arrangements were created for UK broadcasting regulation, built upon a radical rethinking of communications policy. This article examines key changes arising from Labour's media policy, the Communications Act 2003 and the work of Ofcom. It argues that changes within broadcasting were less radical than the accompanying rhetoric, and that contradictory tendencies set limits to dominant trends of marketisation and liberalisation. The article explores these tendencies by reviewing the key broadcasting policy issues of the decade including policies on the BBC, commercial public service and commercial broadcasting, spectrum and digital switchover, and new digital services. It assesses changes in the structural regulation of media ownership, the shift towards behavioural competition regulation, and the regulation of media content and commercial communications. In doing so, it explores policy rationales and arguments, and examines tensions and contradictions in the promotion of marketisation, the discourses of market failure, political interventions, and the professionalisation of policy-making.
19
Michinaga, Shotaro, and Yutaka Koyama. "Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage." International Journal of Molecular Sciences 20, no. 3 (2019): 571. http://dx.doi.org/10.3390/ijms20030571.
Full textAbstract:
The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage. Emerging evidence suggests key roles of astrocyte-derived factors in BBB disruption and recovery after brain damage. The astrocyte-derived vascular permeability factors include vascular endothelial growth factors, matrix metalloproteinases, nitric oxide, glutamate and endothelin-1, which enhance BBB permeability leading to BBB disruption. By contrast, the astrocyte-derived protective factors include angiopoietin-1, sonic hedgehog, glial-derived neurotrophic factor, retinoic acid and insulin-like growth factor-1 and apolipoprotein E which attenuate BBB permeability resulting in recovery of BBB function. In this review, the roles of these astrocyte-derived factors in BBB function are summarized, and their significance as therapeutic targets for BBB protection and recovery after brain damage are discussed.
20
Löscher, Wolfgang, and Birthe Gericke. "Novel Intrinsic Mechanisms of Active Drug Extrusion at the Blood-Brain Barrier: Potential Targets for Enhancing Drug Delivery to the Brain?" Pharmaceutics 12, no. 10 (2020): 966. http://dx.doi.org/10.3390/pharmaceutics12100966.
Full textAbstract:
The blood-brain barrier (BBB) limits the pharmacotherapy of several brain disorders. In addition to the structural and metabolic characteristics of the BBB, the ATP-driven, drug efflux transporter P-glycoprotein (Pgp) is a selective gatekeeper of the BBB; thus, it is a primary hindrance to drug delivery into the brain. Here, we review the complex regulation of Pgp expression and functional activity at the BBB with an emphasis on recent studies from our laboratory. In addition to traditional processes such as transcriptional regulation and posttranscriptional or posttranslational modification of Pgp expression and functionality, novel mechanisms such as intra- and intercellular Pgp trafficking and intracellular Pgp-mediated lysosomal sequestration in BBB endothelial cells with subsequent disposal by blood neutrophils are discussed. These intrinsic mechanisms of active drug extrusion at the BBB are potential therapeutic targets that could be used to modulate P-glycoprotein activity in the treatment of brain diseases and enhance drug delivery to the brain.
21
Liebner, Stefan, Monica Corada, Thorsten Bangsow та ін. "Wnt/β-catenin signaling controls development of the blood–brain barrier". Journal of Cell Biology 183, № 3 (2008): 409–17. http://dx.doi.org/10.1083/jcb.200806024.
Full textAbstract:
The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.
22
Ionescu, Cezar Valentin. "Predictors of performance at the Baccalaureate in Romania. A Pilot Study." Studia Doctoralia 9, no. 2 (2018): 77–86. http://dx.doi.org/10.47040/sd/sdpsych.v9i2.79.
Full textAbstract:
The aim of the present study is to examine the predictors of performance on the Romanian Bacalaureat (BAC). The study analyses the relationship between the composite BAC score as the criterion and several psychological attributes as the predictors: general cognitive ability, emotional intelligence, learning motivation, grit, conscientiousness, self-regulation, and the hours spent on exam preparation. Data analysis reveals the fact that intelligence does not predict BAC performance at all. The same result also holds for the association between BAC performance and emotional intelligence or motivation. Self-regulation, conscientiousness and grit are trivially, yet not statistically significant associated with BAC performance. Even the number of hours spent on exam preparation donot predict BAC performance.Taking these results into account, it is crucial to explain why no statistically significant association was obtained between the predictors and criterion. In the author’s mind, the findings should sound a warning with regard to the exam held in Romania when one graduates high school.
23
Ionescu, Cezar Valentin. "Predictors of performance at the Baccalaureate in Romania. A Pilot Study." Studia Doctoralia 9, no. 2 (2018): 77–86. http://dx.doi.org/10.47040/sd0000060.
Full textAbstract:
The aim of the present study is to examine the predictors of performance on the Romanian Bacalaureat (BAC). The study analyses the relationship between the composite BAC score as the criterion and several psychological attributes as the predictors: general cognitive ability, emotional intelligence, learning motivation, grit, conscientiousness, self-regulation, and the hours spent on exam preparation. Data analysis reveals the fact that intelligence does not predict BAC performance at all. The same result also holds for the association between BAC performance and emotional intelligence or motivation. Self-regulation, conscientiousness and grit are trivially, yet not statistically significant associated with BAC performance. Even the number of hours spent on exam preparation donot predict BAC performance.Taking these results into account, it is crucial to explain why no statistically significant association was obtained between the predictors and criterion. In the author’s mind, the findings should sound a warning with regard to the exam held in Romania when one graduates high school.
24
Wei, Xin, and Timothy Phoenix. "HGG-22. EVALUATING THE REGULATION OF BLOOD-BRAIN BARRIER INTEGRITY IN DIPG MOUSE MODELS." Neuro-Oncology 23, Supplement_1 (2021): i21. http://dx.doi.org/10.1093/neuonc/noab090.086.
Full textAbstract:
Abstract Diffuse intrinsic pontine gliomas (DIPGs) are considered to maintain a fairly intact blood-brain barrier (BBB) based on patient imaging tumor histology. In characterizing recently developed DIPG and HGG mouse models, we identified differences in BBB function and increased Angiopoietin1 (Angpt1) in H3 K27M DIPG models. We hypothesize that H3 K27M mutations promote the maintenance of DIPG BBB integrity through upregulation of Angpt1. To determine DIPG and HGG BBB phenotypes we performed an intergrative analysis of vascular histology and endothelial transcriptomes Ongoing studies using electroporation based DIPG mouse models are being performed examine the regulation and function of Angpt1 in DIPG BBB integrity. We have initiated studies comparing H3 K27M DIPG mouse models to H3 WT and G34R cortical HGG mouse models, demonstrating that DIPG models show minimal changes in vascular phenotype, including vessel density, branching, and diameter compared to cortical HGG models. Comparing DIPG and HGG purified endothelial transcriptomes, HGG ECs displayed enrichments of inflammatory signals and proliferation gene sets, and increased expression of tip cell identity genes. We identified Angpt1 as selectively upregulated in H3 K27M mouse models and derived cell lines. Preliminary data suggests Angpt1 supports the maintenance of BBB integrity in DIPG models. BBB phenotype differences are present in DIPG and HGG mouse models. Uncovering mutation specific mechanisms that regulate BBB function in brain tumors will be critical to advance our understanding of brain tumor pathogenesis and treatment response.
25
Kalani, Anuradha, Pradip K. Kamat, Anastasia Familtseva, et al. "Role of MicroRNA29b in Blood–Brain Barrier Dysfunction during Hyperhomocysteinemia: An Epigenetic Mechanism." Journal of Cerebral Blood Flow & Metabolism 34, no. 7 (2014): 1212–22. http://dx.doi.org/10.1038/jcbfm.2014.74.
Full textAbstract:
Although blood–brain barrier (BBB) integrity is maintained by the cross-talk of endothelial cells, junction proteins, and neurogliovascular network, the epigenetic mechanisms behind BBB permeability are largely unknown. We are reporting for the first time miR29b-mediated regulation of BBB, which is a novel mechanism underlying BBB integrity. We hypothesize that miR29b regulates BBB dysfunction by regulating DNMT3b, which consequently regulates the levels of metalloproteinases, that can eat up the membrane and junction proteins leading to leaky vasculature. In addition, 5′-azacytidine (5′-aza) was used to test its efficacy on BBB permeability. Blood–brain barrier disruption model was created by using homocysteine, and in the models miR29b was identified to be most affected, by using microRNA RT 2 -qPCR array. MiR29b mimics and inhibitors also confirmed that miR29b regulates the levels DNMT3b and MMP9. In hyperhomocysteinemic cystathionine-β-synthase deficient (CBS+/−) mice with high brain vessel permeability, miR29b levels were also high as compared with wild-type (WT) mice. Interestingly, 5′-aza improved BBB permeability by decreasing the expression of miR29b. In conclusion, our data suggested miR29b-mediated regulation of BBB dysfunction through DNMT3b and MMP9. It also potentiates the use of microRNAs as candidates for future epigenetic therapies in the improvement of BBB integrity.
26
Pan, Weihong, and Abba J. Kastin. "The Blood-Brain Barrier." Neuroscientist 23, no. 2 (2016): 124–36. http://dx.doi.org/10.1177/1073858416639005.
Full textAbstract:
Sleep and its disorders are known to affect the functions of essential organs and systems in the body. However, very little is known about how the blood-brain barrier (BBB) is regulated. A few years ago, we launched a project to determine the impact of sleep fragmentation and chronic sleep restriction on BBB functions, including permeability to fluorescent tracers, tight junction protein expression and distribution, glucose and other solute transporter activities, and mediation of cellular mechanisms. Recent publications and relevant literature allow us to summarize here the sleep-BBB interactions in five sections: (1) the structural basis enabling the BBB to serve as a huge regulatory interface; (2) BBB transport and permeation of substances participating in sleep-wake regulation; (3) the circadian rhythm of BBB function; (4) the effect of experimental sleep disruption maneuvers on BBB activities, including regional heterogeneity, possible threshold effect, and reversibility; and (5) implications of sleep disruption-induced BBB dysfunction in neurodegeneration and CNS autoimmune diseases. After reading the review, the general audience should be convinced that the BBB is an important mediating interface for sleep-wake regulation and a crucial relay station of mind-body crosstalk. The pharmaceutical industry should take into consideration that sleep disruption alters the pharmacokinetics of BBB permeation and CNS drug delivery, being attentive to the chrono timing and activation of co-transporters in subjects with sleep disorders.
27
Santa-Maria, Ana R., Fruzsina R. Walter, Ricardo Figueiredo, et al. "Flow induces barrier and glycocalyx-related genes and negative surface charge in a lab-on-a-chip human blood-brain barrier model." Journal of Cerebral Blood Flow & Metabolism 41, no. 9 (2021): 2201–15. http://dx.doi.org/10.1177/0271678x21992638.
Full textAbstract:
Microfluidic lab-on-a-chip (LOC) devices allow the study of blood-brain barrier (BBB) properties in dynamic conditions. We studied a BBB model, consisting of human endothelial cells derived from hematopoietic stem cells in co-culture with brain pericytes, in an LOC device to study fluid flow in the regulation of endothelial, BBB and glycocalyx-related genes and surface charge. The highly negatively charged endothelial surface glycocalyx functions as mechano-sensor detecting shear forces generated by blood flow on the luminal side of brain endothelial cells and contributes to the physical barrier of the BBB. Despite the importance of glycocalyx in the regulation of BBB permeability in physiological conditions and in diseases, the underlying mechanisms remained unclear. The MACE-seq gene expression profiling analysis showed differentially expressed endothelial, BBB and glycocalyx core protein genes after fluid flow, as well as enriched pathways for the extracellular matrix molecules. We observed increased barrier properties, a higher intensity glycocalyx staining and a more negative surface charge of human brain-like endothelial cells (BLECs) in dynamic conditions. Our work is the first study to provide data on BBB properties and glycocalyx of BLECs in an LOC device under dynamic conditions and confirms the importance of fluid flow for BBB culture models.
28
Gregory, Mark A. "Impending Media Review." Journal of Telecommunications and the Digital Economy 4, no. 1 (2016): ii—iv. http://dx.doi.org/10.18080/jtde.v4n1.51.
Full textAbstract:
In the March 2016 issue papers cover a range of topics that include the UK BBC charter review, film and television being affected by Internet clichés and an interesting look at digital currencies. Two historical articles on the bombing of Darwin and radio telephone surveying provide interesting reading about past telecommunications challenges. In Australia the government appears to be taking concerns raised by media organisations seriously and recent reductions in television licence fees point to the government’s impending media regulation review being more than just window dressing.
29
Brown, Caitlin, Sarah Pemberton, Alice Babin, et al. "Insulin blood-brain barrier transport and interactions are greater following exercise in mice." Journal of Applied Physiology 132, no. 3 (2022): 824–34. http://dx.doi.org/10.1152/japplphysiol.00866.2021.
Full textAbstract:
Central nervous system (CNS) insulin and exercise are beneficial for cognition. CNS insulin resistance is present in Alzheimer’s disease. CNS insulin levels are regulated by transport across the blood-brain barrier (BBB). We show that exercise can enhance insulin BBB transport and binding of insulin to the brain’s vasculature in mice. There were no changes in serum factors known to alter insulin BBB pharmacokinetics. We conclude exercise could impact cognition through regulation of insulin BBB transport.
30
Ronaldson, Patrick T., and Thomas P. Davis. "Regulation of blood–brain barrier integrity by microglia in health and disease: A therapeutic opportunity." Journal of Cerebral Blood Flow & Metabolism 40, no. 1_suppl (2020): S6—S24. http://dx.doi.org/10.1177/0271678x20951995.
Full textAbstract:
The blood–brain barrier (BBB) is a critical regulator of CNS homeostasis. It possesses physical and biochemical characteristics (i.e. tight junction protein complexes, transporters) that are necessary for the BBB to perform this physiological role. Microvascular endothelial cells require support from astrocytes, pericytes, microglia, neurons, and constituents of the extracellular matrix. This intricate relationship implies the existence of a neurovascular unit (NVU). NVU cellular components can be activated in disease and contribute to dynamic remodeling of the BBB. This is especially true of microglia, the resident immune cells of the brain, which polarize into distinct proinflammatory (M1) or anti-inflammatory (M2) phenotypes. Current data indicate that M1 pro-inflammatory microglia contribute to BBB dysfunction and vascular “leak”, while M2 anti-inflammatory microglia play a protective role at the BBB. Understanding biological mechanisms involved in microglia activation provides a unique opportunity to develop novel treatment approaches for neurological diseases. In this review, we highlight characteristics of M1 proinflammatory and M2 anti-inflammatory microglia and describe how these distinct phenotypes modulate BBB physiology. Additionally, we outline the role of other NVU cell types in regulating microglial activation and highlight how microglia can be targeted for treatment of disease with a focus on ischemic stroke and Alzheimer’s disease.
31
Lama, Chamala, Cameron R. Love, Hoa Nhu Le, et al. "The nuclear receptor Hr46/Hr3 is required in the blood brain barrier of mature males for courtship." PLOS Genetics 18, no. 1 (2022): e1009519. http://dx.doi.org/10.1371/journal.pgen.1009519.
Full textAbstract:
The blood brain barrier (BBB) forms a stringent barrier that protects the brain from components in the circulation that could interfere with neuronal function. At the same time, the BBB enables selective transport of critical nutrients and other chemicals to the brain. Beyond these functions, another recently recognized function is even less characterized, specifically the role of the BBB in modulating behavior by affecting neuronal function in a sex-dependent manner. Notably, signaling in the adult Drosophila BBB is required for normal male courtship behavior. Courtship regulation also relies on male-specific molecules in the BBB. Our previous studies have demonstrated that adult feminization of these cells in males significantly lowered courtship. Here, we conducted microarray analysis of BBB cells isolated from males and females. Findings revealed that these cells contain male- and female-enriched transcripts, respectively. Among these transcripts, nuclear receptor Hr46/Hr3 was identified as a male-enriched BBB transcript. Hr46/Hr3 is best known for its essential roles in the ecdysone response during development and metamorphosis. In this study, we demonstrate that Hr46/Hr3 is specifically required in the BBB cells for courtship behavior in mature males. The protein is localized in the nuclei of sub-perineurial glial cells (SPG), indicating that it might act as a transcriptional regulator. These data provide a catalogue of sexually dimorphic BBB transcripts and demonstrate a physiological adult role for the nuclear receptor Hr46/Hr3 in the regulation of male courtship, a novel function that is independent of its developmental role.
32
Atallah, Afnan, Sakina Mhaouty-Kodja, and Valérie Grange-Messent. "Chronic depletion of gonadal testosterone leads to blood–brain barrier dysfunction and inflammation in male mice." Journal of Cerebral Blood Flow & Metabolism 37, no. 9 (2016): 3161–75. http://dx.doi.org/10.1177/0271678x16683961.
Full textAbstract:
A dysfunction in the blood–brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.
33
Ahmad, Abraham Al, Carole Bürgi Taboada, Max Gassmann, and Omolara O. Ogunshola. "Astrocytes and Pericytes Differentially Modulate Blood—Brain Barrier Characteristics during Development and Hypoxic Insult." Journal of Cerebral Blood Flow & Metabolism 31, no. 2 (2010): 693–705. http://dx.doi.org/10.1038/jcbfm.2010.148.
Full textAbstract:
Understanding regulation of blood–brain barrier (BBB) is crucial to reduce/prevent its disruption during injury. As high brain complexity makes interpretation of in vivo data challenging, BBB studies are frequently performed using simplified in vitro models. However, many models fail to address the three-dimensional (3D) cellular interactions that occur in vivo, an important feature that may explain discrepancies in translation of in vitro data to the in vivo situation. We have designed and characterized an innovative 3D model that reproduces morphological and functional characteristics of the BBB in vivo and used it to investigate cellular interactions and contribution of astrocytes and pericytes to BBB development. Our model shows that both astrocytes and pericytes significantly suppress endothelial proliferation. In contrast, differential effects on tubulogenesis were observed with astrocytes reducing the number of tubes formed but increasing diameters and length, whereas pericytes had the opposite effect. Pericytes also induce proper localization of barrier proteins, lumen polarization, and functional activity of ATP-binding cassette (ABC) transporters similar to astrocytes, but the presence of both cells is required to maintain optimal barrier characteristics during hypoxic exposure. This model is simple, dynamic, and convenient to study many aspects of BBB function and represents an exciting new tool to address open questions of BBB regulation.
34
Miura, Shigenori, Yuya Morimoto, Tomomi Furihata, and Shoji Takeuchi. "Functional analysis of human brain endothelium using a microfluidic device integrating a cell culture insert." APL Bioengineering 6, no. 1 (2022): 016103. http://dx.doi.org/10.1063/5.0085564.
Full textAbstract:
The blood-brain barrier (BBB) is a specialized brain endothelial barrier structure that regulates the highly selective transport of molecules under continuous blood flow. Recently, various types of BBB-on-chip models have been developed to mimic the microenvironmental cues that regulate the human BBB drug transport. However, technical difficulties in complex microfluidic systems limit their accessibility. Here, we propose a simple and easy-to-handle microfluidic device integrated with a cell culture insert to investigate the functional regulation of the human BBB endothelium in response to fluid shear stress (FSS). Using currently established immortalized human brain microvascular endothelial cells (HBMEC/ci18), we formed a BBB endothelial barrier without the substantial loss of barrier tightness under the relatively low range of FSS (0.1–1 dyn/cm2). Expression levels of key BBB transporters and receptors in the HBMEC/ci18 cells were dynamically changed in response to the FSS, and the effect of FSS reached a plateau around 1 dyn/cm2. Similar responses were observed in the primary HBMECs. Taking advantage of the detachable cell culture insert from the device, the drug efflux activity of P-glycoprotein (P-gp) was analyzed by the bidirectional permeability assay after the perfusion culture of cells. The data revealed that the FSS-stimulated BBB endothelium exhibited the 1.9-fold higher P-gp activity than that of the static culture control. Our microfluidic system coupling with the transwell model provides a functional human BBB endothelium with secured transporter activity, which is useful to investigate the bidirectional transport of drugs and its regulation by FSS.
35
Wacker, Bradley K., Angela B. Freie, Jennifer L. Perfater, and Jeffrey M. Gidday. "Junctional Protein Regulation by Sphingosine Kinase 2 Contributes to Blood–Brain Barrier Protection in Hypoxic Preconditioning-Induced Cerebral Ischemic Tolerance." Journal of Cerebral Blood Flow & Metabolism 32, no. 6 (2012): 1014–23. http://dx.doi.org/10.1038/jcbfm.2012.3.
Full textAbstract:
Protection of the blood–brain barrier (BBB) is correlated with improved outcome in stroke. Sphingosine kinase (SphK)-directed production of sphingosine-1-phosphate, which we previously documented as being vital to preconditioning-induced stroke protection, mediates peripheral vascular integrity via junctional protein regulation. We used a hypoxic preconditioning (HPC) model in adult wild-type and SphK2-null mice to examine the isoform-specific role of SphK2 signaling for ischemic tolerance to transient middle cerebral artery occlusion and attendant BBB protection. Reductions in infarct volume and BBB permeability in HPC-treated mice were completely lost in SphK2-null mice. Hypoxic preconditioning-induced attenuation of postischemic BBB disruption in wild types, evidenced by reduced extravascular immunoglobulin G intensity, suggests direct protection of BBB integrity. Measurement of BBB junctional protein status in response to HPC revealed SphK2-dependent increases in triton-insoluble claudin-5 and VE-cadherin, which may serve to strengthen the BBB before stroke. Postischemic loss of VE-cadherin, occludin, and zona occludens-1 in SphK2-null mice with prior HPC suggests that SphK2-dependent protection of these adherens and tight junction proteins is compulsory for HPC to establish a vasculoprotective phenotype. Further elucidation of the mediators of this endogenous, HPC-activated lipid signaling pathway, and their role in protecting the ischemic BBB, may provide new therapeutic targets for cerebrovascular protection in stroke patients.
36
Ronaldson, Patrick T., Kristin M. DeMarco, Lucy Sanchez-Covarrubias, Christine M. Solinsky та Thomas P. Davis. "Transforming Growth Factor-β Signaling Alters Substrate Permeability and Tight Junction Protein Expression at the Blood-Brain Barrier during Inflammatory Pain". Journal of Cerebral Blood Flow & Metabolism 29, № 6 (2009): 1084–98. http://dx.doi.org/10.1038/jcbfm.2009.32.
Full textAbstract:
Our laboratory has shown that peripheral inflammatory pain induced by λ-carrageenan (CIP) can increase blood-brain barrier (BBB) permeability and alter tight junction (TJ) protein expression leading to changes in BBB functional integrity. However, the intracellular signaling mechanisms involved in this pathophysiologic response have not been elucidated. Transforming growth factor (TGF)-β signaling pathways are known to regulate vascular integrity and permeability. Therefore, we examined the function of TGF-β signaling at the BBB in rats subjected to CIP. During CIP, serum TGF-β1 and protein expression of the TGF-β receptor activin receptor-like kinase-5 (ALK5) were reduced. Brain permeability to 14C-sucrose was increased and expression of TJ proteins (i.e., claudin-5, occludin, zonula occluden (ZO-1)) were also altered after 3 h CIP. Pharmacological inhibition of ALK5 with the selective inhibitor SB431542 further enhanced brain uptake of 14C-sucrose, increased TJ protein expression (i.e., claudin-3, claudin-5, occludin, ZO-1), and decreased nuclear expression of TGF-β/ALK5 signaling molecules (i.e., Smad2, Smad3), which suggests a role for TGF-β/ALK5 signaling in the regulation of BBB integrity. Interestingly, administration of exogenous TGF-β before CIP activated the TGF-β/ALK5 pathway and reduced BBB permeability to 14C-sucrose. Taken together, our data show that TGF-β/ALK5 signaling is, in part, involved in the regulation of BBB functional integrity.
37
Persidsky, Yuri, David Heilman, James Haorah, et al. "Rho-mediated regulation of tight junctions during monocyte migration across the blood-brain barrier in HIV-1 encephalitis (HIVE)." Blood 107, no. 12 (2006): 4770–80. http://dx.doi.org/10.1182/blood-2005-11-4721.
Full textAbstract:
AbstractThe blood-brain barrier (BBB) is compromised during progressive HIV-1 infection, but how this occurs is incompletely understood. We studied the integrity of tight junctions (TJs) of brain microvascular endothelial cells (BMVECs) in an in vitro BBB system and in human brain tissues with HIV-1 encephalitis (HIVE). A downregulation of TJ proteins, claudin-5 and occludin, paralleled monocyte migration into the brain during HIVE. Because small G proteins (such as Rho) can play a role in BMVEC TJ assembly, an artificial BBB system explored the relationship among TJs, Rho/Rho kinase (RhoK) activation, and transendothelial monocyte migration. Coculture of monocytes with endothelial cells led to Rho activation and phosphorylation of TJ proteins. Rho and RhoK inhibitors blocked migration of infected and uninfected monocytes. The RhoK inhibitor protected BBB integrity and reversed occludin/claudin-5 phosphorylation associated with monocyte migration. BMVEC transfection with a constitutively active mutant of RhoK led to dislocation of occludin from the membrane and loss of BMVEC cell contacts. When dominant-negative RhoK-transfected BMVECs were used in BBB constructs, monocyte migration was reduced by 84%. Thus, loss of TJ integrity was associated with Rho activation caused by monocyte brain migration, suggesting that Rho/RhoK activation in BMVECs could be an underlying cause of BBB impairment during HIVE.
38
Arima, Yasunobu, Daisuke Kamimura, Lavannya Sabharwal, et al. "Regulation of Immune Cell Infiltration into the CNS by Regional Neural Inputs Explained by the Gate Theory." Mediators of Inflammation 2013 (2013): 1–8. http://dx.doi.org/10.1155/2013/898165.
Full textAbstract:
The central nervous system (CNS) is an immune-privileged environment protected by the blood-brain barrier (BBB), which consists of specific endothelial cells that are brought together by tight junctions and tight liner sheets formed by pericytes and astrocytic end-feet. Despite the BBB, various immune and tumor cells can infiltrate the CNS parenchyma, as seen in several autoimmune diseases like multiple sclerosis (MS), cancer metastasis, and virus infections. Aside from a mechanical disruption of the BBB like trauma, how and where these cells enter and accumulate in the CNS from the blood is a matter of debate. Recently, using experimental autoimmune encephalomyelitis (EAE), an animal model of MS, we found a “gateway” at the fifth lumber cord where pathogenic autoreactive CD4+ T cells can cross the BBB. Interestingly, this gateway is regulated by regional neural stimulations that can be mechanistically explained by the gate theory. In this review, we also discuss this theory and its potential for treating human diseases.
39
Tran, Nam D., Steven S. Schreiber, and Mark Fisher. "Astrocyte Regulation of Endothelial Tissue Plasminogen Activator in a Blood-Brain Barrier Model." Journal of Cerebral Blood Flow & Metabolism 18, no. 12 (1998): 1316–24. http://dx.doi.org/10.1097/00004647-199812000-00006.
Full textAbstract:
Expression of tissue plasminogen activator (tPA) substantially determines endothelial-dependent fibrinolysis. We used a blood-brain barrier (BBB) model to analyze regulation of brain capillary endothelial tPA and its inhibitor, plasminogen activator inhibitor-1 (PAI-1). This model consists of coculture of murine astrocytes with bovine brain capillary endothelial cells grown as capillary-like structures (CS); after 1 week, astrocytes become extensively associated with CS, and the BBB-associated enzyme γ-glutamyl transpeptidase is present. We measured tPA and PAI-1 mRNA and tPA activity in this model. Reverse transcription-polymerase chain reaction (RT-PCR) studies showed similar tPA and PAI-1 mRNA levels after 1 day mono-culture (endothelial cells only) versus astrocyte-endothelial coculture preparations. After 7 days (i.e., when elements of the BBB are present), astrocyte-endothelial cocultures (compared with endothelial mono-cultures) showed a 50.7% ± 27.1% (mean ± SD) reduction in tPA mRNA ( P < 0.03) and a 183.3% ± 86.9% increase in PAI-1 mRNA expression ( P < 0.02). Moreover, 7-day cocultures demonstrated reduced tPA activity compared with mono-cultures (14.6 ± 2.9 IU/mL versus 30.2 ± 7.7 IU/mL, P < 0.01); 1-day cocultures and mono-cultures had similar tPA activity. These findings demonstrate that astrocytes regulate brain capillary endothelial expression of tPA when elements of the BBB phenotype are present in this model. These data suggest an important role for astrocytes in the regulation of brain capillary endothelial fibrinolysis.
40
Osipova, Elena D., Oxana V. Semyachkina-Glushkovskaya, Andrey V. Morgun, et al. "Gliotransmitters and cytokines in the control of blood-brain barrier permeability." Reviews in the Neurosciences 29, no. 5 (2018): 567–91. http://dx.doi.org/10.1515/revneuro-2017-0092.
Full textAbstract:
AbstractThe contribution of astrocytes and microglia to the regulation of neuroplasticity or neurovascular unit (NVU) is based on the coordinated secretion of gliotransmitters and cytokines and the release and uptake of metabolites. Blood-brain barrier (BBB) integrity and angiogenesis are influenced by perivascular cells contacting with the abluminal side of brain microvessel endothelial cells (pericytes, astrocytes) or by immune cells existing (microglia) or invading the NVU (macrophages) under pathologic conditions. The release of gliotransmitters or cytokines by activated astroglial and microglial cells is provided by distinct mechanisms, affects intercellular communication, and results in the establishment of microenvironment controlling BBB permeability and neuroinflammation. Glial glutamate transporters and connexin and pannexin hemichannels working in the tight functional coupling with the purinergic system serve as promising molecular targets for manipulating the intercellular communications that control BBB permeability in brain pathologies associated with excessive angiogenesis, cerebrovascular remodeling, and BBB-mediated neuroinflammation. Substantial progress in deciphering the molecular mechanisms underlying the (patho)physiology of perivascular glia provides promising approaches to novel clinically relevant therapies for brain disorders. The present review summarizes the current understandings on the secretory machinery expressed in glial cells (glutamate transporters, connexin and pannexin hemichannels, exocytosis mechanisms, membrane-derived microvesicles, and inflammasomes) and the role of secreted gliotransmitters and cytokines in the regulation of NVU and BBB permeability in (patho)physiologic conditions.
41
Simpson, Ian A., Padmavathi Ponnuru, Marianne E. Klinger, et al. "A Novel Model for Brain Iron Uptake: Introducing the Concept of Regulation." Journal of Cerebral Blood Flow & Metabolism 35, no. 1 (2014): 48–57. http://dx.doi.org/10.1038/jcbfm.2014.168.
Full textAbstract:
Neurologic disorders such as Alzheimer's, Parkinson's disease, and Restless Legs Syndrome involve a loss of brain iron homeostasis. Moreover, iron deficiency is the most prevalent nutritional concern worldwide with many associated cognitive and neural ramifications. Therefore, understanding the mechanisms by which iron enters the brain and how those processes are regulated addresses significant global health issues. The existing paradigm assumes that the endothelial cells (ECs) forming the blood—brain barrier (BBB) serve as a simple conduit for transport of transferrin-bound iron. This concept is a significant oversimplification, at minimum failing to account for the iron needs of the ECs. Using an in vivo model of brain iron deficiency, the Belgrade rat, we show the distribution of transferrin receptors in brain microvasculature is altered in luminal, intracellular, and abluminal membranes dependent on brain iron status. We used a cell culture model of the BBB to show the presence of factors that influence iron release in non-human primate cerebrospinal fluid and conditioned media from astrocytes; specifically apo-transferrin and hepcidin were found to increase and decrease iron release, respectively. These data have been integrated into an interactive model where BBB ECs are central in the regulation of cerebral iron metabolism.
42
Lam, Tina I., Phyllis M. Wise, and Martha E. O'Donnell. "Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressin." American Journal of Physiology-Cell Physiology 297, no. 2 (2009): C278—C289. http://dx.doi.org/10.1152/ajpcell.00093.2009.
Full textAbstract:
Blood-brain barrier (BBB) Na transporters are essential for brain water and electrolyte homeostasis. However, they also contribute to edema formation during the early hours of ischemic stroke by increased transport of Na from blood into brain across an intact BBB. We previously showed that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia, aglycemia, and AVP and that inhibition of the cotransporter by intravenous bumetanide significantly reduces edema and infarct in the rat middle cerebral artery occlusion (MCAO) model of stroke. More recently, we found evidence that intravenous cariporide (HOE-642), a highly potent Na/H exchange inhibitor, also reduces brain edema after MCAO. The present study was conducted to investigate which Na/H exchange protein isoforms are present in BBB endothelial cells and to evaluate the effects of ischemic factors on BBB Na/H exchange activity. Western blot analysis of bovine cerebral microvascular endothelial cells (CMEC) and immunoelectron microscopy of perfusion-fixed rat brain revealed that Na/H exchanger isoforms 1 and 2 (NHE1 and NHE2) are present in BBB endothelial cells. Using microspectrofluorometry and the pH-sensitive dye BCECF, we found that hypoxia (2% O2, 30 min), aglycemia (30 min), and AVP (1–200 nM, 5 min) significantly increased CMEC Na/H exchange activity, assessed as Na-dependent, HOE-642-sensitive H+ flux. We found that AVP stimulation of CMEC Na/H exchange activity is dependent on intracellular Ca concentration and is blocked by V1, but not V2, vasopressin receptor antagonists. Our findings support the hypothesis that a BBB Na/H exchanger, possibly NHE1 and/or NHE2, is stimulated during ischemia to participate in cerebral edema formation.
43
Ramsey, Phil. "Commercial Public Service Broadcasting in the United Kingdom: Public Service Television, Regulation, and the Market." Television & New Media 18, no. 7 (2016): 639–54. http://dx.doi.org/10.1177/1527476416677113.
Full textAbstract:
The commercial public service broadcasters (PSBs) in the United Kingdom (UK) make a significant contribution to the country’s public service television system, alongside the BBC. Operating under the UK communications regulator Ofcom, the commercial PSB channels ITV, Channel 4, and Channel 5 are required to broadcast varying levels of public service content. This places these channels in a different category to all other market broadcasters in the UK. By taking a critical political economy of communication approach, this article examines how the regulatory system functions to secure public service provision in television. A particular focus is placed on the first-run originations quotas, which govern the levels of programming that are originally produced or commissioned by a commercial PSB, and broadcast for the first time in the UK. It is argued that while fulfilling the public service remit, the commercial PSBs gain significant benefits that contribute to the underpinning of their business models.
44
Nakamura, Kuniyuki, Tomoko Ikeuchi, Kazuki Nara, et al. "Perlecan regulates pericyte dynamics in the maintenance and repair of the blood–brain barrier." Journal of Cell Biology 218, no. 10 (2019): 3506–25. http://dx.doi.org/10.1083/jcb.201807178.
Full textAbstract:
Ischemic stroke causes blood–brain barrier (BBB) breakdown due to significant damage to the integrity of BBB components. Recent studies have highlighted the importance of pericytes in the repair process of BBB functions triggered by PDGFRβ up-regulation. Here, we show that perlecan, a major heparan sulfate proteoglycan of basement membranes, aids in BBB maintenance and repair through pericyte interactions. Using a transient middle cerebral artery occlusion model, we found larger infarct volumes and more BBB leakage in conditional perlecan (Hspg2)-deficient (Hspg2−/−-TG) mice than in control mice. Control mice showed increased numbers of pericytes in the ischemic lesion, whereas Hspg2−/−-TG mice did not. At the mechanistic level, pericytes attached to recombinant perlecan C-terminal domain V (perlecan DV, endorepellin). Perlecan DV enhanced the PDGF-BB–induced phosphorylation of PDGFRβ, SHP-2, and FAK partially through integrin α5β1 and promoted pericyte migration. Perlecan therefore appears to regulate pericyte recruitment through the cooperative functioning of PDGFRβ and integrin α5β1 to support BBB maintenance and repair following ischemic stroke.
45
Yang, Changjun, Kimberly E. Hawkins, Sylvain Doré, and Eduardo Candelario-Jalil. "Neuroinflammatory mechanisms of blood-brain barrier damage in ischemic stroke." American Journal of Physiology-Cell Physiology 316, no. 2 (2019): C135—C153. http://dx.doi.org/10.1152/ajpcell.00136.2018.
Full textAbstract:
As part of the neurovascular unit, the blood-brain barrier (BBB) is a unique, dynamic regulatory boundary that limits and regulates the exchange of molecules, ions, and cells between the blood and the central nervous system. Disruption of the BBB plays an important role in the development of neurological dysfunction in ischemic stroke. Blood-borne substances and cells have restricted access to the brain due to the presence of tight junctions between the endothelial cells of the BBB. Following stroke, there is loss of BBB tight junction integrity, leading to increased paracellular permeability, which results in vasogenic edema, hemorrhagic transformation, and increased mortality. Thus, understanding principal mediators and molecular mechanisms involved in BBB disruption is critical for the development of novel therapeutics to treat ischemic stroke. This review discusses the current knowledge of how neuroinflammation contributes to BBB damage in ischemic stroke. Specifically, we provide an updated overview of the role of cytokines, chemokines, oxidative and nitrosative stress, adhesion molecules, matrix metalloproteinases, and vascular endothelial growth factor as well as the role of different cell types in the regulation of BBB permeability in ischemic stroke.
46
Xu, W., Y. Mansour, C. Siggers, and M. B. Hughes. "Developing utility harmonic regulations based on IEEE STD 519-B.C, Hydro's approach." IEEE Transactions on Power Delivery 10, no. 3 (1995): 1423–31. http://dx.doi.org/10.1109/61.400925.
Full text
47
Corre, I., and S. Hermouet. "Regulation of colony-stimulating factor 1-induced proliferation by heterotrimeric Gi2 proteins." Blood 86, no. 5 (1995): 1776–83. http://dx.doi.org/10.1182/blood.v86.5.1776.bloodjournal8651776.
Full textAbstract:
Receptors for hematopoietic cytokines possess intrinsic tyrosine- kinases or are associated with tyrosine-kinases; interactions between metabolic pathways activated by tyrosine-kinases and heterotrimeric G proteins are suspected, but not yet proven. To investigate whether alteration of G protein function affects signal transduction of hematopoietic cytokines, we expressed mutant Gi2 proteins in BAC 1.2F5 cells, a murine macrophage cell line that is dependent from monocyte- macrophage colony-stimulating factor (CSF 1) for its proliferation. Mutations made in alpha subunits constitutively activate (alpha i2- Q205L) or inactivate (alpha i2-G204A) Gi2 heterotrimers. We show that expression of alpha i2-Q205L in BAC 1.2F5 cells does not induce independence from CSF 1, but reduces the cells' requirement in CSF 1, shortens the length of the G1 phase and the cell doubling time in response to CSF 1, and protects cells from death by apoptosis induced by CSF 1 withdrawal, exposure to H2O2 or heat shock, but not mitoxantrone. More importantly, expression of alpha i2-G204A, a dominant negative mutant, inhibits BAC 1.2F5 cell proliferation in response to CSF 1, increases the length of the G1 phase and the cell doubling time, and accelerates apoptotic cell death after withdrawal of CSF 1, exposure to H2O2 or heat shock. We conclude that the metabolic pathways regulated by Gi2 proteins and CSF 1 tyrosine-kinase receptors converge on a common effector necessary for the regulation of macrophage survival and proliferation.
48
Hsuchou, Hung, Abba J. Kastin, Xiaojun Wu, Hong Tu, and Weihong Pan. "Corticotropin-Releasing Hormone Receptor-1 in Cerebral Microvessels Changes during Development and Influences Urocortin Transport across the Blood-Brain Barrier." Endocrinology 151, no. 3 (2009): 1221–27. http://dx.doi.org/10.1210/en.2009-1039.
Full textAbstract:
In this study we tested the hypothesis that receptor-mediated transport of urocortin across the blood-brain barrier (BBB) undergoes developmental changes. Urocortin is a peptide produced by both selective brain regions and peripheral organs, and it is involved in feeding, memory, mood, cardiovascular functions, and immune regulation. In BBB studies with multiple-time regression analysis, we found that neonatal mice had a significant influx of 125I-urocortin. By contrast, adult mice did not transport urocortin across the BBB. Quantitative RT-PCR showed that corticotropin-releasing hormone receptor (CRHR)-1 was developmentally regulated in enriched cerebral microvessels as well as hypothalamus, being significantly higher in neonatal than adult mice. This change was less dramatic in agouti viable yellow mice, a strain that develops adult-onset obesity. The level of expression of CRHR1 mRNA was 33-fold higher in the microvessels than in hypothalamic homogenates. The mRNA for CRHR2 was less abundant in both regions and less prone to changes with development or the agouti viable yellow mutation. Supported by previous findings of receptor-mediated endocytosis of urocortin, these results suggest that permeation of urocortin across the BBB is dependent on the level of CRHR1 expression in cerebral microvessels. These novel findings of differential regulation of CRH receptor subtypes help elucidate developmental processes in the brain, particularly for the urocortin system.
49
Al-Fatlawi, Suhail Hussein. "Islam's Attitude towards Democracy Comparative Study in International Human Rights Law." Journal of Politics and Law 9, no. 1 (2016): 73. http://dx.doi.org/10.5539/jpl.v9n1p73.
Full textAbstract:
<p>Democracy was established in the Greek cities in the fifth century B.C. It is a liberal western system. In this regard, various Islamic countries applied democracy as a political and legal system where the people elect their representatives in the legislative authority in order to put the legal regulations that organize the human behavior.</p>The research included a brief idea about liberal democracy, its history and objectives, the political and legal system in the Islamic state, the dispute among Muslim scholars on the application of democracy in the Islamic states; some Muslim scholars refuse to apply democracy since the legal system in Islam relies on the Holly Qor'an and the Prophet's speeches, which are a biding regulation for Muslims, while other authors believe that Islam accepts democracy and others think that Islam should have its special democracy that differs from the liberal democracy. This paper discussed the political and legal systems that were applied the Islamic state during the history of Islam. Finally the paper presented the most conclusions and recommendations reached by the researcher.
50
Nishibori, Masahiro, Dengli Wang, Daiki Ousaka, and Hidenori Wake. "High Mobility Group Box-1 and Blood–Brain Barrier Disruption." Cells 9, no. 12 (2020): 2650. http://dx.doi.org/10.3390/cells9122650.
Full textAbstract:
Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood–brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer’s amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption.