scholarly journals The Role of Dll4/Notch Signaling in Normal and Pathological Ocular Angiogenesis: Dll4 Controls Blood Vessel Sprouting and Vessel Remodeling in Normal and Pathological Conditions

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Ivan Lobov ◽  
Natalia Mikhailova
Keyword(s):  
Blood Vessel ◽  
Transmembrane Protein ◽  
Mammalian Species ◽  
Vascular Development ◽  
Critical Role ◽  
Notch Pathway ◽  
The Body ◽  
Therapeutic Effects ◽  
Pathological Conditions

Background. Retina is the highest oxygen-demanding and vascularized tissue in the body. Retinal development and function require proper vascularization and blood vessel function and integrity. Dll4 is most prominently expressed in the endothelium of angiogenic blood vessels and in quiescent arteries and capillaries in all tissues and organs of the mammalian species, and it is the key regulator of blood vessel sprouting.Results. Dll4 is a transmembrane protein that acts as a ligand for Notch receptors 1 and 4. Genetic deletion of Dll4 causes severe abnormalities in embryonic and postnatal vascular development. Deletion of even a single Dll4 allele results in almost complete embryonic lethality due to severe vascular abnormalities, the phenomenon called haploinsufficiency indicating the critical role of Dll4/Notch in vascular development. Dll4/Notch pathway interplays at multiple levels with other signaling pathways including VEGF, Wnt/Fzd, and genes controlling vascular toning. Multiple studies of the effects of Dll4 inhibition were performed in the developing retina to elucidate the key functions of Dll4 in normal and pathological angiogenesis. Several genetic approaches and therapeutic molecules were tested to evaluate the biological and therapeutic effects of acute and prolonged Dll4 inhibition in the eye and oncology.Conclusions. All current studies demonstrated that Dll4 controls blood vessel sprouting, growth, and remodeling in normal and pathological conditions as well as arterial-venous differentiation. Genetic and therapeutic Dll4 modulation studies show that Dll4 inhibition can promote blood vessel sprouting and might be useful to stimulate vessel growth in the ischemic retina and Dll4 is the key modulator of the postangiogenic vascular remodeling that ultimately defines vascular patterning.

Mast cells in neuropathic pain: an increasing spectrum of their involvement in pathophysiology

2017 ◽  
Vol 28 (7) ◽  
pp. 759-766 ◽  
Author(s):  
Gunjanpreet Kaur ◽  
Nirmal Singh ◽  
Amteshwar Singh Jaggi
Keyword(s):  
Neuropathic Pain ◽  
Mast Cells ◽  
Critical Role ◽  
Experimental Models ◽  
The Body ◽  
Pathological Conditions ◽  
Dual Action ◽  
Time Of Administration ◽  
Different Parts

AbstractMast cells are immunological cells that are diversely distributed in different parts of the body. Their role in various pathological conditions such as hypersensitivity, atherosclerosis, pulmonary hypertension, and male infertility has been reported by different scientists. Apart from these, a number of studies have shown their important role in pathogenesis of neuropathic pain of diverse aetiology. They have been found to release active mediators, primarily histamine and serotonin on degranulation in response to different stimuli including chemical, nerve damage, toxin or disease-related conditions. The mast cells stabilizer has shown pain attenuating effects by preventing degranulation of mast cells. Similarly, compound 48/80 (first dose 200 μg/100 g and after 6-h interval, second dose of 500 μg/100 g) caused the degranulation of the accumulated endoneurial histamine and 5-HT antagonists have shown pain relieving effects by attenuating the effects of histamine and serotonin, respectively. On the other hand, the mast cell degranulator compound 48/80 has shown dual action depending on its time of administration. The present review discusses the critical role of mast cells in the generation and maintenance of neuropathic pain in experimental models.

scholarly journals Emerging Role of AP-1 Transcription Factor JunB in Angiogenesis and Vascular Development

2021 ◽  
Vol 22 (6) ◽  
pp. 2804
Author(s):  
Yasuo Yoshitomi ◽  
Takayuki Ikeda ◽  
Hidehito Saito-Takatsuji ◽  
Hideto Yonekura
Keyword(s):  
Endothelial Cells ◽  
Transcription Factor ◽  
Blood Vessel ◽  
Vascular Endothelial Cells ◽  
Vascular Development ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial ◽  
Blood Vessel Formation ◽  
Vessel Formation

Blood vessels are essential for the formation and maintenance of almost all functional tissues. They play fundamental roles in the supply of oxygen and nutrition, as well as development and morphogenesis. Vascular endothelial cells are the main factor in blood vessel formation. Recently, research findings showed heterogeneity in vascular endothelial cells in different tissue/organs. Endothelial cells alter their gene expressions depending on their cell fate or angiogenic states of vascular development in normal and pathological processes. Studies on gene regulation in endothelial cells demonstrated that the activator protein 1 (AP-1) transcription factors are implicated in angiogenesis and vascular development. In particular, it has been revealed that JunB (a member of the AP-1 transcription factor family) is transiently induced in endothelial cells at the angiogenic frontier and controls them on tip cells specification during vascular development. Moreover, JunB plays a role in tissue-specific vascular maturation processes during neurovascular interaction in mouse embryonic skin and retina vasculatures. Thus, JunB appears to be a new angiogenic factor that induces endothelial cell migration and sprouting particularly in neurovascular interaction during vascular development. In this review, we discuss the recently identified role of JunB in endothelial cells and blood vessel formation.

Extase scopique, sédimentation langagičre et inscription corporelle. Les images dans la civilisation contemporaine

PARADIGMI ◽  
2009 ◽  
pp. 71-83
Author(s):  
Jean-Jacques Wunenburger
Keyword(s):  
Key Words ◽  
The Body ◽  
Pathological Conditions ◽  
Image Informatics

- Linguistic Sedimentation, and Bodily Inscription At present, we are exposed to an excessive offer of images, which raises a problem of assimilation. Subjects are increasingly passive, in ways that can border on pathological conditions. Yet, it is not so much a question of condemning this situation as of finding a way of re-symbolizing images, saving them from mere contemplation and inserting them in a process of contextualisation. Such a process requires an understanding of the role of the body and of the incorporation of images along the lines of Bachelard's intuition of the "resisting" nature of images. This raises the possibility of an education to images suited to the present age.Key words: Alienation, Education, Embodiment, Image, Informatics, Symbolisation.Parole chiave: Alienazione, Educazione, Immagine, Incorporazione, Informatica, Simbolizzazione.

Adoption of students' loan schemes: the contingent role of financial knowledge

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Gloria Ocran ◽  
Livingstone Divine Caesar
Keyword(s):  
Critical Role ◽  
Financial Education ◽  
The Body ◽  
Financial Knowledge ◽  
Relative Advantage ◽  
Research Approach ◽  
Content Type ◽  
Four Dimensions ◽  
Behavioural Factors

PurposeDespite the introduction of structural reforms to the students' loan scheme (SLS) in Ghana's higher education sector, patronage is still low. This paper aims to examine the complexity of technological and behavioural factors underpinning the low rate of students' loan adoption in Ghana. It further contributes to the body of knowledge by exploring the moderating role of financial knowledge in the hypothesized relationships.Design/methodology/approachUsing a positivistic research approach, a sample of 700 tertiary students with experience in accessing SLSs were surveyed. An 88% response rate was realized and the data analysed using descriptive statistics, exploratory and confirmatory factor analysis.FindingsFour dimensions of technological factors (relative advantage, trialability, observability and compatibility) and two of behavioural factors (attitude and control behaviour) were positively related to adoption of the SLS. Financial knowledge only moderated the relationship between compatibility, attitude, behavioural control and students' loan adoption.Practical implicationsFinancial knowledge plays a critical role in influencing the investment decisions of people. Management of SLSs needs to offer financial education to targeted parents/students to clear misconceptions. It is also imperative that all other technical challenges are addressed to enhance adoption rates for the SLS. Review of guarantor requirements is needed also.Originality/valueThis paper introduces financial knowledge as a moderating variable to investigate the hypothesized relationships. It offers a developing country insight into how technological/behavioural factors and financial knowledge might be impacting adoption of SLSs.

Cell Delivery and Recirculation

2004 ◽  
Author(s):  
W. Mark Saltzman
Keyword(s):  
Tissue Engineering ◽  
Cell Adhesion ◽  
Cell Fate ◽  
Critical Role ◽  
Cell Movement ◽  
The Body ◽  
Associated Proteins ◽  
Adult Organism ◽  
Adenine Deaminase

Perhaps the simplest realization of tissue engineering involves the direct administration of a suspension of engineered cells—cells that have been isolated, characterized, manipulated, and amplified outside of the body. One can imagine engineering diverse and useful properties into the injected cells: functional enzymes, secretion of drugs, resistance to immune recognition, and growth control. We are most familiar with methods for manipulating the cell internal chemistry by introduction or removal of genes; for example, the first gene therapy experiments involved cells that were engineered to produce a deficient enzyme, adenine deaminase (see Chapter 2). But genes also encode systems that enable cell movement, cell mechanics, and cell adhesion. Conceivably, these systems can be modified to direct the interactions of an administered cell with its new host. For example, cell adhesion signals could be introduced to provide tissue targeting, cytoskeleton-associated proteins could be added to alter viscosity and deformability (in order to prolong circulation time), and motor proteins could be added to facilitate cell migration. Ideally, cell fate would also be engineered, so that the cell would move to the appropriate location in the body, no matter how it was administered; for example, transfused liver cells would circulate in the blood and, eventually, crawl into the liver parenchyma. Cells find their place in developing organisms by a variety of chemotactic and adhesive signals, but can these same signaling mechanisms be engaged to target cells administered to an adult organism? We have already considered the critical role of cell movement in development in Chapter 3. In this chapter, the utility of cell trafficking in tissue engineering is approached by first considering the normal role of cell recirculation and trafficking within the adult organism. Most cells can be easily introduced into the body by intravenous injection or infusion. This procedure is particularly appropriate for cells that function within the circulation; for example, red blood cells (RBCs) and lymphocytes. The first blood transfusions into humans were performed by Jean-Baptiste Denis, a French physician, in 1667. This early appearance of transfusion is startling, since the circulatory system was described by William Harvey only a few decades earlier, in 1628.

scholarly journals Transcranial Magnetic Stimulation Over the Human Medial Posterior Parietal Cortex Disrupts Depth Encoding During Reach Planning

2020 ◽  
Vol 31 (1) ◽  
pp. 267-280
Author(s):  
Rossella Breveglieri ◽  
Annalisa Bosco ◽  
Sara Borgomaneri ◽  
Alessia Tessari ◽  
Claudio Galletti ◽  
...  
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Parietal Cortex ◽  
Magnetic Stimulation ◽  
Posterior Parietal Cortex ◽  
Critical Role ◽  
The Body ◽  
Visually Guided ◽  
Visually Guided Reaching ◽  
Posterior Parietal

Abstract Accumulating evidence supports the view that the medial part of the posterior parietal cortex (mPPC) is involved in the planning of reaching, but while plenty of studies investigated reaching performed toward different directions, only a few studied different depths. Here, we investigated the causal role of mPPC (putatively, human area V6A–hV6A) in encoding depth and direction of reaching. Specifically, we applied single-pulse transcranial magnetic stimulation (TMS) over the left hV6A at different time points while 15 participants were planning immediate, visually guided reaching by using different eye-hand configurations. We found that TMS delivered over hV6A 200 ms after the Go signal affected the encoding of the depth of reaching by decreasing the accuracy of movements toward targets located farther with respect to the gazed position, but only when they were also far from the body. The effectiveness of both retinotopic (farther with respect to the gaze) and spatial position (far from the body) is in agreement with the presence in the monkey V6A of neurons employing either retinotopic, spatial, or mixed reference frames during reach plan. This work provides the first causal evidence of the critical role of hV6A in the planning of visually guided reaching movements in depth.

scholarly journals Bmal1 regulates circadian expression of cytochrome P450 3a11 and drug metabolism in mice

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Yanke Lin ◽  
Shuai Wang ◽  
Ziyue Zhou ◽  
Lianxia Guo ◽  
Fangjun Yu ◽  
...  
Keyword(s):  
Circadian Clock ◽  
Drug Exposure ◽  
Defense Mechanism ◽  
Critical Role ◽  
The Body ◽  
Cellular Regulation ◽  
Circadian Expression ◽  
Distal Promoter ◽  
Daily Time

Abstract Metabolism is a major defense mechanism of the body against xenobiotic threats. Here we unravel a critical role of Bmal1 for circadian clock-controlled Cyp3a11 expression and xenobiotic metabolism. Bmal1 deficiency decreases the mRNA, protein and microsomal activity of Cyp3a11, and blunts their circadian rhythms in mice. A screen for Cyp3a11 regulators identifies two circadian genes Dbp and Hnf4α as potential regulatory mediators. Cell-based experiments confirm that Dbp and Hnf4α activate Cyp3a11 transcription by their binding to a D-box and a DR1 element in the Cyp3a11 promoter, respectively. Bmal1 binds to the P1 distal promoter to regulate Hnf4α transcriptionally. Cellular regulation of Cyp3a11 by Bmal1 is Dbp- and Hnf4α-dependent. Bmal1 deficiency sensitizes mice to toxicities of drugs such as aconitine and triptolide (and blunts circadian toxicity rhythmicities) due to elevated drug exposure. In summary, Bmal1 connects circadian clock and Cyp3a11 metabolism, thereby impacting drug detoxification as a function of daily time.

scholarly journals The Essential Role of anxA2 in Langerhans Cell Birbeck Granules Formation

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 974 ◽  
Author(s):  
Shantae M. Thornton ◽  
Varsha D. Samararatne ◽  
Joseph G. Skeate ◽  
Christopher Buser ◽  
Kim P. Lühen ◽  
...  
Keyword(s):  
Immune Responses ◽  
Antigen Processing ◽  
Viral Antigen ◽  
Essential Role ◽  
Critical Role ◽  
The Body ◽  
Birbeck Granules ◽  
Transmission Electron ◽  
Antigen Presenting

Langerhans cells (LC) are the resident antigen presenting cells of the mucosal epithelium and play an essential role in initiating immune responses. LC are the only cells in the body to contain Birbeck granules (BG), which are unique cytoplasmic organelles comprised of c-type lectin langerin. Studies of BG have historically focused on morphological characterizations, but BG have also been implicated in viral antigen processing which suggests that they can serve a function in antiviral immunity. This study focused on investigating proteins that could be involved in BG formation to further characterize their structure using transmission electron microscopy (TEM). Here, we report a critical role for the protein annexin A2 (anxA2) in the proper formation of BG structures. When anxA2 expression is downregulated, langerin expression decreases, cytoplasmic BG are nearly ablated, and the presence of malformed BG-like structures increases. Furthermore, in the absence of anxA2, we found langerin was no longer localized to BG or BG-like structures. Taken together, these results indicate an essential role for anxA2 in facilitating the proper formation of BG.

scholarly journals The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2182 ◽  
Author(s):  
Oliver K Fuller ◽  
Martin Whitham ◽  
Suresh Mathivanan ◽  
Mark A Febbraio
Keyword(s):  
Physical Activity ◽  
Extracellular Vesicles ◽  
Potential Role ◽  
The Body ◽  
Therapeutic Effects ◽  
Health And Wellbeing ◽  
Systemic Factors ◽  
Diabetes And Obesity

Physical activity has systemic effects on the body, affecting almost every organ. It is important not only for general health and wellbeing, but also in the prevention of diseases. The mechanisms behind the therapeutic effects of physical activity are not completely understood; however, studies indicate these benefits are not confined to simply managing energy balance and body weight. They also include systemic factors which are released into the circulation during exercise and which appear to underlie the myriad of benefits exercise can elicit. It was shown that along with a number of classical cytokines, active tissues also engage in inter-tissue communication via extracellular vesicles (EVs), specifically exosomes and other small EVs, which are able to deliver biomolecules to cells and alter their metabolism. Thus, EVs may play a role in the acute and systemic adaptations that take place during and after physical activity, and may be therapeutically useful in the treatment of a range of diseases, including metabolic disorders such as type 2 diabetes and obesity; and the focus of this review, neurological disorders such as Alzheimer’s disease.

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