Integrins are transmembrane adhesion receptors that bind extracellular matrix (ECM) proteins and signal bidirectionally to regulate cell adhesion and migration. In many cell types, integrins cluster ...at cell-ECM contacts to create the foundation for adhesion complexes that transfer force between the cell and the ECM. Even though the temporal and spatial regulation of these integrin clusters is essential for cell migration, how cells regulate their formation is currently unknown. It has been shown that integrin cluster formation is independent of actin stress fiber formation, but requires active (high-affinity) integrins, phosphoinositol-4,5-bisphosphate (PIP2), talin, and immobile ECM ligand. Based on these observations, we propose a minimal model for initial formation of integrin clusters, facilitated by localized activation and binding of integrins to ECM ligands as a result of biochemical feedback between integrin binding and integrin activation. By employing a diffusion-reaction framework for modeling these reactions, we show how spatial organization of bound integrins into clusters may be achieved by a local source of active integrins, namely protein complexes formed on the cytoplasmic tails of bound integrins. Further, we show how such a mechanism can turn small local increases in the concentration of active talin or active integrin into integrin clusters via positive feedback. Our results suggest that the formation of integrin clusters by the proposed mechanism depends on the relationships between production and diffusion of integrin-activating species, and that changes to the relative rates of these processes may affect the resulting properties of integrin clusters.
Rigid polyurethane foam (PUF) filled with mixture of alumina trihydrate (ATH) and triphenyl phosphate (TPP) as fire retardant additive was prepared with water as a blowing agent. In this study, the ...ATH content was varied from 10 to 100 parts per hundred polyol by weight (php), and TPP was used at a higher loading of ATH (75 and 100 php) in a ratio of 1 : 5 to enhance the processing during PUF preparation. The effects of ATH on properties such as density, compressive strength, morphological, thermal conductivity, thermal stability, flame-retardant (FR) behavior, and smoke characteristics were studied. The density and compressive strength of the ATH-filled PUF decreased initially and then increased with further increase in ATH content. There was no significant change in the thermal stability with increasing ATH loading. We determined the FR properties of these foam samples by measuring the limiting oxygen index (LOI), smoke density, rate of burning, and char yield. The addition of ATH with TPP to PUF significantly decreased the flame-spread rate and increased LOI. The addition of TPP resulted in easy processing and also improved FR characteristics of the foam.
Sixteen Indian commercial carrot cultivars were analysed for variations in β-carotene, total phenolics, total flavonoids, total monomeric anthocyanin and antioxidant activity. Antioxidant activity ...was measured using four in vitro assays viz. ferric reducing antioxidant power (FRAP), cupric reducing antioxidant power (CUPRAC), 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and Trolox equivalent antioxidant capacity assays (TEAC). Additionally six colour attributes were evaluated. Among carrot cultivars, significant differences (p<0.05) were obtained with respect to antioxidant composition and antioxidant activity. Total phenols and total flavonoids varied from 7.98 to 291.48mg/100g fresh weight (fw) and 3.00 to 111.70mg/100g fw respectively. Chemometric tools like principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) were applied to understand possible classification Indian carrot cultivars based on colour properties, bioactive antioxidant compounds and antioxidant potentiality. PCA revealed that the first two components represented 92.9% of the total variability in the total variation. AHC classified cultivars into four main groups on the basis of the measured parameters. Black coloured genotype was found to be rich source of phenols, flavonoids and anthocyanin with very high antioxidant activity. Orange cultivars were found to be rich sources for β-carotene compared to red & black cultivars.
•Chemometrics (PCA & HCA) was used to classify and reveal the pattern in data.•Antioxidant composition differed among carrot cultivars with respect to colour.•Black cultivars were found to be rich source for hydrophilic antioxidants.•Orange cultivars were found to be rich source for β-carotene.
Using CLEO-c data, we confirm the observation of D0→ωη by BESIII. In the Dalitz plot of D0→KS0ηπ0, we find a background in the KS0(→π+π−)π0 projection with a m(π+π−π0) equal to the ω(782) mass. In a ...direct search for D0→ωη we find a clear signal and measure BFD0→ωη=(1.78±0.19±0.15)×10−3, in good agreement with BESIII.
An efficient synthesis of thiopyrimidines with different substituents in position 2 is described. A rapid, mild and high yielding microwave-assisted one-pot cyclization of 5-substituted 2-amino ...thiophene-3-carboxamide derived from Gewald reaction1 with T3P and different acids gives the corresponding thiopyrimidines. The significant feature of this method includes less reaction time, high purity and reduced toxicity of the reaction.
The existence of mitogen activated protein kinases (MAPKs) in platelets has been known for more than 20 years. Since that time hundreds of reports have been published describing the conditions that ...cause MAPK activation in platelets and their role in regulating diverse platelet functions from the molecular to physiological level. However, this cacophony of reports, with inconsistent and sometimes contradictory findings, has muddied the waters leading to great confusion. Since the last review of platelet MAPKs was published more than a decade ago, there have been more than 50 reports, including the description of novel knockout mouse models, that have furthered our knowledge. Therefore, we undertook an extensive literature review to delineate what is known about platelet MAPKs. We specifically discuss what is currently known about how MAPKs are activated and what signaling cascades they regulate in platelets incorporating recent findings from knockout mouse models. In addition, we will discuss the role each MAPK plays in regulating distinct platelet functions. In doing so, we hope to clarify the role for MAPKs and identify knowledge gaps in this field that await future researchers. In addition, we discuss the limitations of current studies with a particular focus on the off-target effects of commonly used MAPK inhibitors. We conclude with a look at the clinical utility of MAPK inhibitors as potential antithrombotic therapies with an analysis of current clinical trial data.
Alpha globin is expressed in the endothelial cells of human resistance arteries where it binds to endothelial nitric oxide synthase and limits release of the vasodilator nitric oxide. Genomic ...deletion of the alpha globin gene (HBA) is common among Black Americans and could lead to increased endothelial nitric oxide signaling and reduced risk of hypertension.
Community-dwelling US adults aged 45 years or older were enrolled and examined from 2003 to 2007, followed by telephone every 6 months, and reexamined from 2013 to 2016. At both visits, trained personnel performed standardized, in-home blood pressure measurements and pill bottle review. Prevalent hypertension was defined as systolic blood pressure ≥ 140mmHg or diastolic blood pressure ≥ 90mmHg or anti-hypertensive medication use. Droplet digital PCR was used to determine HBA copy number. The associations of HBA copy number with prevalent hypertension, resistant hypertension, and incident hypertension were estimated using multivariable regression.
Among 9,684 Black participants, 7,439 (77%) had hypertension at baseline and 1,044 of those had treatment-resistant hypertension. 1,000 participants were not hypertensive at baseline and participated in a follow up visit; 517 (52%) developed hypertension over median 9.2 years follow-up. Increased HBA copy number was not associated with prevalent hypertension (PR = 1.00; 95%CI 0.98,1.02), resistant hypertension (PR = 0.95; 95%CI 0.86,1.05), or incident hypertension (RR = 0.96; 95%CI 0.86,1.07).
There were no associations between increased HBA copy number and risk of hypertension. These findings suggest that variation in alpha globin gene copy number does not modify the risk of hypertension among Black American adults.
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