scholarly journals On-site education of VEGF-recruited monocytes improves their performance as angiogenic and arteriogenic accessory cells

2013 ◽  
Vol 210 (12) ◽  
pp. 2611-2625 ◽  
Author(s):  
Inbal Avraham-Davidi ◽  
Simon Yona ◽  
Myriam Grunewald ◽  
Limor Landsman ◽  
Clement Cochain ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
Target Organ ◽  
Functional Changes ◽  
Small Vessels ◽  
Accessory Cells ◽  
Improved Performance

Adult neovascularization relies on the recruitment of monocytes to the target organ or tumor and functioning therein as a paracrine accessory. The exact origins of the recruited monocytes and the mechanisms underlying their plasticity remain unclear. Using a VEGF-based transgenic system in which genetically tagged monocytes are conditionally summoned to the liver as part of a VEGF-initiated angiogenic program, we show that these recruited cells are derived from the abundant pool of circulating Ly6Chi monocytes. Remarkably, however, upon arrival at the VEGF-induced organ, but not the naive organ, monocytes undergo multiple phenotypic and functional changes, endowing them with enhanced proangiogenic capabilities and, importantly, with a markedly increased capacity to remodel existing small vessels into larger conduits. Notably, monocytes do not differentiate into long-lived macrophages, but rather appear as transient accessory cells. Results from transfers of presorted subpopulations and a novel tandem transfer strategy ruled out selective recruitment of a dedicated preexisting subpopulation or onsite selection, thereby reinforcing active reprogramming as the underlying mechanism for improved performance. Collectively, this study uncovered a novel function of VEGF, namely, on-site education of recruited “standard” monocytes to become angiogenic and arteriogenic professional cells, a finding that may also lend itself for a better design of angiogenic therapies.

scholarly journals Association between antenatal blood pressure and 5-year postpartum retinal arteriolar structural and functional changes

2019 ◽  
Vol 4 (1) ◽  
pp. e000355 ◽  
Author(s):  
Ralene Sim ◽  
Izzuddin Aris ◽  
Yap-Seng Chong ◽  
Tien Yin Wong ◽  
Ling-jun Li
Keyword(s):  
Blood Pressure ◽  
Mediation Analysis ◽  
Degrees Of Freedom ◽  
Underlying Mechanism ◽  
Structure And Function ◽  
Functional Changes ◽  
Microvascular Changes ◽  
And Function ◽  
Retinal Arteriolar

ObjectiveStudies have shown that hypertensive disorders of pregnancy (HDP) are associated with both postpartum retinal microvascular changes and cardiovascular (CV) risks. However, the underlying mechanism of HDP transitioning to microvascular and macrovascular changes remains unknown, due to the interaction between microvasculature and CV risks. In this study, we examined whether associations between antenatal systolic blood pressure (SBP) and postpartum retinal arteriolar changes are independent of postpartum CV risks.MethodsWe included 276 Singaporean mothers attending both baseline index pregnancy (2009–2010) and 5-year postpartum follow-up visits (2014–2015). We measured SBP at baseline. At follow-up, we assessed retinal microvascular structure and function with retinal photography and dynamic vessel analyser, together with CV risks using a validated 2008 Framingham Risk Score (FRS). We performed a traditional four-step mediation analysis using linear regression by adjusting for a series of baseline characteristics: age, ethnicity, college degree, prepregnancy body mass index and gestational diabetes mellitus diagnosis at baseline.ResultsWe found that each 10 mm Hg increase in baseline SBP was associated with reduced arteriolar calibre (−1.3 µm; 95% CI −3.0 to 0.2) and fractal dimension (−0.4 degrees of freedom (df); −1.0 to 0.2), and significantly with increased arteriolar constriction (0.5%; 0.001 to 1.0) at 5-year postpartum. Even though baseline SBP was associated with postpartum FRS, the latter was not associated with any retinal arteriolar measures. Therefore, no further mediation analysis was required.ConclusionOur study suggested that elevated SBP during pregnancy was associated with suboptimal retinal arteriolar structure and function independent of postpartum CV risks.

scholarly journals Ascorbic acid improves thrombotic function of platelets during living donor liver transplantation by modulating the function of the E3 ubiquitin ligases c-Cbl and Cbl-b

2019 ◽  
Vol 47 (5) ◽  
pp. 1856-1867
Author(s):  
Ji Hye Kwon ◽  
Doyeon Kim ◽  
Hyojin Cho ◽  
Byung Seop Shin
Keyword(s):  
Liver Transplantation ◽  
Ascorbic Acid ◽  
Normal Saline ◽  
Living Donor ◽  
Living Donor Liver Transplantation ◽  
Underlying Mechanism ◽  
Donor Liver ◽  
Functional Changes ◽  
Donor Liver Transplantation ◽  
C And N

Objective To investigate the effect of ascorbic acid (AA) on hemostatic function during living donor liver transplantation (LDLT). Methods Blood samples from 21 LDLT recipients were taken within 30 minutes after induction and at 120 minutes after reperfusion. Rotational thromboelastography (TEG) and western blot analysis were used to analyze for fibrinolysis and functional changes in c-Cbl and Cbl-b, respectively. TEG test samples were prepared as one of three groups: C group (0.36 mL of blood), N group (0.324 mL of blood + 0.036 mL of 0.9% normal saline), and A group (0.324 mL of blood + 0.036 mL of 200 µmol/L-AA dissolved in 0.9% normal saline). Results AA decreased fibrinolysis and increased clot rigidity at baseline and 120 minutes after reperfusion. Cbl-b expression was significantly increased at baseline and 120 minutes after reperfusion in the A group compared with the C and N groups. However, c-Cbl phosphorylation was most significantly decreased in the A group at baseline and 120 minutes after reperfusion. Conclusion AA can significantly decrease fibrinolysis and improve clot rigidity in LT recipients during LDLT, and functional changes in Cbl-b and c-Cbl might represent the underlying mechanism. AA may be considered for use during LDLT to decrease hyperfibrinolysis.

Tailoring the photocatalytic activity of layered perovskites by opening the interlayer vacancy via ion-exchange reactions

CrystEngComm ◽  
2015 ◽  
Vol 17 (45) ◽  
pp. 8703-8709 ◽  
Author(s):  
Yingqi Wang ◽  
Xiaofang Lai ◽  
Xujie Lü ◽  
Yanting Li ◽  
Qinglong Liu ◽  
...  
Keyword(s):  
Photocatalytic Activity ◽  
Ion Exchange ◽  
Exchange Reaction ◽  
Underlying Mechanism ◽  
Effective Model ◽  
Layered Perovskite ◽  
Exchange Reactions ◽  
Ion Exchange Reaction ◽  
Improved Performance ◽  
Layered Perovskites

The photocatalytic activity of the layered perovskite K2La2Ti3O10 was regulated by an ion-exchange reaction with a series of cations – Ca2+, Sr2+, and Ba2+. The underlying mechanism of the improved performance and an effective model for designing the photocatalyst were discussed.

scholarly journals Diphtheria toxin induced but not CSF1R inhibitor mediated microglia ablation model leads to the loss of CSF/ventricular spaces in vivo that is independent of cytokine upregulation

2022 ◽  
Vol 19 (1) ◽  
Author(s):  
Alicia Bedolla ◽  
Aleksandr Taranov ◽  
Fucheng Luo ◽  
Jiapeng Wang ◽  
Flavia Turcato ◽  
...  
Keyword(s):  
Diphtheria Toxin ◽  
Pathological Condition ◽  
Underlying Mechanism ◽  
Cytokine Profile ◽  
Edema Formation ◽  
Functional Changes ◽  
Genetic Ablation ◽  
The Brain ◽  
Ablation Model

Abstract Background Two recently developed novel rodent models have been reported to ablate microglia, either by genetically targeting microglia (via Cx3cr1-creER: iDTR + Dtx) or through pharmacologically targeting the CSF1R receptor with its inhibitor (PLX5622). Both models have been widely used in recent years to define essential functions of microglia and have led to high impact studies that have moved the field forward. Methods Using either Cx3cr1-iDTR mice in combination with Dtx or via the PLX5622 diet to pharmacologically ablate microglia, we compared the two models via MRI and histology to study the general anatomy of the brain and the CSF/ventricular systems. Additionally, we analyzed the cytokine profile in both microglia ablation models. Results We discovered that the genetic ablation (Cx3cr1-iDTR + Dtx), but not the pharmacological microglia ablation (PLX5622), displays a surprisingly rapid pathological condition in the brain represented by loss of CSF/ventricles without brain parenchymal swelling. This phenotype was observed both in MRI and histological analysis. To our surprise, we discovered that the iDTR allele alone leads to the loss of CSF/ventricles phenotype following diphtheria toxin (Dtx) treatment independent of cre expression. To examine the underlying mechanism for the loss of CSF in the Cx3cr1-iDTR ablation and iDTR models, we additionally investigated the cytokine profile in the Cx3cr1-iDTR + Dtx, iDTR + Dtx and the PLX models. We found increases of multiple cytokines in the Cx3cr1-iDTR + Dtx but not in the pharmacological ablation model nor the iDTR + Dtx mouse brains at the time of CSF loss (3 days after the first Dtx injection). This result suggests that the upregulation of cytokines is not the cause of the loss of CSF, which is supported by our data indicating that brain parenchyma swelling, or edema are not observed in the Cx3cr1-iDTR + Dtx microglia ablation model. Additionally, pharmacological inhibition of the KC/CXCR2 pathway (the most upregulated cytokine in the Cx3cr1-iDTR + Dtx model) did not resolve the CSF/ventricular loss phenotype in the genetic microglia ablation model. Instead, both the Cx3cr1-iDTR + Dtx ablation and iDTR + Dtx models showed increased activated IBA1 + cells in the choroid plexus (CP), suggesting that CP-related pathology might be the contributing factor for the observed CSF/ventricular shrinkage phenotype. Conclusions Our data, for the first time, reveal a robust and global CSF/ventricular space shrinkage pathology in the Cx3cr1-iDTR genetic ablation model caused by iDTR allele, but not in the PLX5622 ablation model, and suggest that this pathology is not due to brain edema formation but to CP related pathology. Given the wide utilization of the iDTR allele and the Cx3cr1-iDTR model, it is crucial to fully characterize this pathology to understand the underlying causal mechanisms. Specifically, caution is needed when utilizing this model to interpret subtle neurologic functional changes that are thought to be mediated by microglia but could, instead, be due to CSF/ventricular loss in the genetic ablation model.

Mindfulness and Fear Extinction: A Brief Review of Its Current Neuropsychological Literature and Possible Implications for Posttraumatic Stress Disorder

2017 ◽  
Vol 121 (5) ◽  
pp. 792-814 ◽  
Author(s):  
Auretta S. Kummar
Keyword(s):  
Posttraumatic Stress Disorder ◽  
Posttraumatic Stress ◽  
Stress Disorder ◽  
Underlying Mechanism ◽  
Brain Regions ◽  
Fear Extinction ◽  
Future Research ◽  
Functional Changes ◽  
Positive Effects ◽  
Current State

Research in the neuroscience of mindfulness has grown rapidly in recent years. This includes empirical investigations into structural and functional changes in several brain regions—particularly, the hippocampus, the prefrontal cortex, and the amygdala—in association with the practice of mindfulness. Of interest to the current paper is that such brain regions are also implicated in empirical research focusing on fear extinction. While fear extinction has, therefore, been suggested as one of the possible mechanisms to underlie the positive effects of mindfulness, the conceptual links and research implications have lacked specific focus and detailed discussion in the literature. The purpose of this paper is, therefore, two-fold. First, this paper briefly reviews the extant literature on the neuropsychological mechanisms underlying mindfulness—particularly that, which has been found to be similarly implied in fear extinction—and hence, suggests future research directions based on its current state in the literature. Second, this paper explores the implications of this for fear-based psychopathologies, specifically for posttraumatic stress disorder (PTSD). Discussion from this paper suggests the idea of fear extinction as an underlying mechanism of mindfulness to be one that is still preliminary, yet promising; in turn, elucidating the need for further methodologically rigorous study to specifically determine fear extinction as a result of mindfulness, as well as to incorporate neuroimaging techniques in supporting the existing literature that have found preliminary support of mindfulness for PTSD.

scholarly journals From lethal to beneficial - contrasting dietary effects of freshwater mixotrophs on zooplankton

2021 ◽  
Author(s):  
Csaba F Vad ◽  
Claudia Schneider ◽  
Robert Fischer ◽  
Martin J Kainz ◽  
Robert Ptacnik
Keyword(s):  
Food Webs ◽  
Nutritional Quality ◽  
Underlying Mechanism ◽  
Dietary Quality ◽  
High Quality ◽  
Dietary Effects ◽  
Functional Changes ◽  
Climate Change Effects ◽  
Aquatic Food ◽  
Mixotrophic Algae

1. The importance of mixotrophic algae as key bacterivores in microbial food webs is increasingly acknowledged, but their effects on consumers is less understood, with previous studies having revealed contrasting results. In freshwater, this may be related to fundamental differences in the nutritional quality of two major mixotrophic groups. While cryptophytes are generally considered as high-quality food for zooplankton, chrysophytes (golden algae) are often referred to be toxic. 2. Using four chrysophyte species, we performed a comparative study as an attempt to generalize their dietary quality by (1) revealing their stoichiometric and biochemical profiles, and (2) quantifying their dietary effects in feeding bioassays with Daphnia longispina. We compared the observed effects to a known high-quality reference food (Cryptomonas sp.) and a starvation control as a reference for potential toxicity. 3. We found dramatic differences in survival and growth of D. longispina depending on the chrysophyte species provided as food. Even within the same genus, dietary quality ranged from deleterious to high. As this was not reflected in differences in cellular stoichiometry and fatty acid profiles, we suggest that toxicity may be the underlying mechanism. 4. Our results suggest that the dietary effects of chrysophytes cannot be generalised. Besides, the fact that a species previously reported to be deleterious turned out to be a beneficial food source suggests that toxic effects may dynamically vary depending on environmental cues, mode of nutrition or the investigated strain. 5. To fully understand the nutritional value of mixotrophic algae in aquatic food webs, representatives of multiple taxa need to be tested under a range of environmental conditions. This is also needed for a better predictive capability of climate change effects, as it may not only promote the dominance of mixotrophic algae, but also induce functional changes related to their nutritional quality.

scholarly journals THE GRADIENT OF PERMEABILITY OF THE SKIN VESSELS AS INFLUENCED BY HEAT, COLD, AND LIGHT

1932 ◽  
Vol 55 (3) ◽  
pp. 431-439 ◽  
Author(s):  
Stephen Hudack ◽  
Philip D. McMaster
Keyword(s):  
Vascular Permeability ◽  
Vessel Wall ◽  
Functional Changes ◽  
Small Vessels ◽  
Vascular Walls ◽  
Gradient Of Permeability

The mounting gradient of permeability along the small vessels of the corium is essentially unaltered by active hyperemia produced by heat, cold, or light. Only when the vascular walls are so damaged that rapid leakage ensues, as shown by the development of edema, does the permeability of the capillary web as a whole approximate that of the venules. It is plain that the normal gradient of vascular permeability depends upon the integrity of the vessel wall. The method of experiment described can be utilized for a study of the functional changes which result in the lesions due to burning and freezing.

scholarly journals Ultrastructural Characterization of Corpus Cavernosum of Ageing, Orchidectomy and Diabetes Rat Experimental Models

2008 ◽  
Vol 14 (S3) ◽  
pp. 97-98 ◽  
Author(s):  
A.L. Cordeiro ◽  
A. Figueiredo ◽  
F. Godinho ◽  
I. Martins ◽  
P. Vendeira ◽  
...  
Keyword(s):  
Risk Factors ◽  
Smooth Muscle ◽  
Corpus Cavernosum ◽  
Experimental Models ◽  
Ultrastructural Organization ◽  
Structural Elements ◽  
Functional Changes ◽  
Small Vessels ◽  
Ultrastructural Characterization

Small vessels of the penis are very sensitive to structural and functional changes, and small disturbances can conduce to any degree of erectile dysfunction (ED). For this motive, ED is now considered as an early manifestation of atherosclerosis and consequently a precursor of systemic vascular disease. Ageing, diabetes and hipogonadic states are recognized risk factors for ED, contributing together to vascular damage of penile tissue. Penile trabeculae of corpus cavernosum in the rat, constituted by connective tissue with abundant collagen fibrils, scarce fibroblasts and fibroelastic components, support smooth muscle fibers in subendothelium location. Corpus cavernosum structural elements act in concert, allowing increase of intra-cavernous arterial flow and smooth muscle relaxing, processes which are fundamental to penis erection. The purpose of this study is to clarify ultrastructural organization of corpus cavernosum of experimental rat models of known ED-risk factors.

Neurologic Manifestations of Organic Chemicals

2017 ◽  
Author(s):  
John L. O’Donoghue
Keyword(s):  
Nervous System ◽  
Underlying Mechanism ◽  
Clinical Situation ◽  
Organic Chemical ◽  
Organic Chemicals ◽  
Neurologic Manifestations ◽  
Specific Chemical ◽  
Functional Changes ◽  
Naturally Occurring ◽  
Pathological Appearance

Organic chemicals can produce many different effects on the nervous system. The nervous system functions are affected by a variety of different organic chemicals. Organic chemicals that induce neurotoxicity may be naturally occurring or synthetic. Those that are naturally occurring products of plants or animals are referred to as “toxins,” whereas those that are synthetic are referred to as “toxicants”; however, publications and regulations sometimes use these terms interchangeably. Underlying these functional changes are cellular and subcellular changes that mediate the clinical and pathological appearance of the neurotoxicity. The ability to make a diagnosis of organic-chemical-induced neurotoxicity is dependent on being able to link a clinical situation with an exposure in a dose-related manner. Treatment and management of organic-chemical-induced neurotoxicity in affected individuals is dependent upon the specific chemical involved and the underlying mechanism by which toxicity occurs.

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