Expression of Protease-Activated Receptor 1 and 2 and Anti-Tubulogenic Activity of Protease-Activated Receptor 1 in Human Endothelial Colony-Forming Cells

Endothelial colony-forming cells (ECFCs) are obtained from the culture of human peripheral blood mononuclear cell (hPBMNC) fractions and are characterised by high proliferative and pro-vasculogenic potential, which makes them of great interest for cell therapy. Here, we describe the detection of protease-activated receptor (PAR) 1 and 2 amongst the surface proteins expressed in ECFCs. Both receptors are functionally coupled to extracellular signal-regulated kinase (ERK) 1 and 2, which become activated and phosphorylated in response to selective PAR1- or PAR2-activating peptides. Specific stimulation of PAR1, but not PAR2, significantly inhibits capillary-like tube formation by ECFCs in vitro, suggesting that tubulogenesis is negatively regulated by proteases able to stimulate PAR1 (e.g. thrombin). The activation of ERKs is not involved in the regulation of tubulogenesis in vitro, as suggested by use of the MEK inhibitor PD98059 and by the fact that PAR2 stimulation activates ERKs without affecting capillary tube formation. Both qPCR and immunoblotting showed a significant downregulation of vascular endothelial growth factor 2 (VEGFR2) in response to PAR1 stimulation. Moreover, the addition of VEGF (50–100 ng/ml) but not basic Fibroblast Growth Factor (FGF) (25–100 ng/ml) rescued tube formation by ECFCs treated with PAR1-activating peptide. Therefore, we propose that reduction of VEGF responsiveness resulting from down-regulation of VEGFR2 is underlying the anti-tubulogenic effect of PAR1 activation. Although the role of PAR2 remains elusive, this study sheds new light on the regulation of the vasculogenic activity of ECFCs and suggests a potential link between adult vasculogenesis and the coagulation cascade

Falls and Physical Activity in Persons with Multiple Sclerosis

Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P \u3c .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P \u3e.05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis

A Convergent-Parallel Analysis on the Technical Assistance Provided by Information Technology Faculty Extensionists: Basis for Training and Extension Activities Plan

The study determined the satisfaction of the technical assistance conducted by faculty extensionists from a higher learning institution in Nueva Ecija, Philippines, during the academic year 2021-2022. It employed a mixed-method convergent-parallel method of study. It sought to describe the timeliness, quality of work, professionalism, courtesy, and achievement of the objectives of the technical assistance. Furthermore, it expressed the overall satisfaction of the beneficiaries with the conduct of the technical assistance using a quantitative approach. Qualitatively, using open-ended questions, the researchers analyzed the participants' responses using theme-generation techniques and identified the usefulness and impact of the technical assistance rendered to the employees and organization. The results generally revealed that the participants were satisfied with the service they received. A significant difference was seen in the level of difficulty experienced. The technical assistance provided has been practical. These participants' responses served as the basis for designing the college's training and extension development plan

Crafting a Network Plan for a Microfinancing Establishment and Its Branch Network through Virtual Private Network (VPN) Implementation

This study successfully designed a network plan incorporating a Virtual Private Network (VPN) for Kasipag Microfinancing Incorporated (KMI). Employing a developmental research design approach and following the network development life cycle stages of planning, analysis, design, and simulation, the researchers evaluated the feasibility of the network design for implementation in KMI. The findings strongly recommend KMI to proceed with the implementation of the designed network plan that includes a VPN, as it offers significant benefits and advantages. Implementing a VPN in KMI's network infrastructure will greatly enhance network security and enable secure remote access to valuable resources, which is particularly crucial in today's digital landscape emphasizing remote work and data privacy. The thorough simulation of the network plan confirms its feasibility and ensures KMI will have a reliable and efficient network infrastructure. Additionally, the implementation of the network plan will provide KMI with a competitive edge by enabling seamless communication and streamlined data transfer between branches. This will enhance collaboration, improve operational efficiency, and increase overall organizational effectiveness. The cost analysis conducted by the researchers guarantees that the project remains within budget, offering KMI a clear breakdown of expenses for informed decision-making. In conclusion, the recommended implementation of the network plan incorporating a VPN will empower KMI with improved network security, secure remote access, and a competitive advantage in the microfinancing industry. By embracing these advancements, KMI can foster growth, productivity, and success in the ever-evolving digital landscape

Amyloid β-peptide-dependent activation of human platelets:Essential role for Ca²⁼⁺ and ADP in aggregation and thrombus formation

Alzheimer's disease is associated with the accumulation of Aβ (amyloid β)-peptides in the brain. Besides their cytotoxic effect on neurons, Aβ-peptides are thought to be responsible for the atherothrombotic complications associated with Alzheimer's disease, which are collectively known as cerebrovascular disease. In the present study, we investigated the effect of Aβ-peptides on human platelet signal transduction and function. We discovered that the 25–35 domain of Aβ-peptides induce an increase in platelet intracellular Ca2+ that stimulates α-granule and dense granule secretion and leads to the release of the secondary agonist ADP. Released ADP acts in an autocrine manner as a stimulant for critical signalling pathways leading to the activation of platelets. This includes the activation of the protein kinases Syk, protein kinase C, Akt and mitogen-activated protein kinases. Ca2+-dependent release of ADP is also the main component of the activation of the small GTPase Rap1b and the fibrinogen receptor integrin αIIbβ3, which leads to increased platelet aggregation and increased thrombus formation in human whole blood. Our discoveries complement existing understanding of cerebrovascular dementia and suggest that Aβ-peptides can induce vascular complications of Alzheimer's disease by stimulating platelets in an intracellular Ca2+-dependent manner. Despite a marginal ADP-independent component suggested by low levels of signalling activity in the presence of apyrase or P2Y receptor inhibitors, Ca2+-dependent release of ADP by Aβ-peptides clearly plays a critical role in platelet activation. Targeting ADP signalling may therefore represent an important strategy to manage the cerebrovascular component of Alzheimer's disease.</jats:p

Falls and physical activity in persons with multiple sclerosis

Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry) in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS) score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample) reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P &lt; .05). However, when controlling for disability status there was no statistically significant difference between fallers and nonfallers (4092 versus 4373 steps/day; P &gt; .05). Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis

E-Cigarette: Exploring Awareness and Understanding of Students in a State University in the Philippines

Introduction: E-cigarettes (eCigs), battery-powered devices that heat e-liquid to produce an aerosol, are becoming more popular among young people. The popularity of pod-based devices, especially among teenagers and young people, may increase the risk of nicotine addiction and pose respiratory, cardiovascular, and mental health risks despite perceptions of safety.Objectives: This study explores university students\u27 awareness and understanding of e-cigarette smoking, focusing on socio-demographic factors.Methods: A descriptive-correlational approach was used with 389 University students who completed the questionnaire to gather the data needed for this study. Statistical tools, including frequency and percentages, mean, simple correlation, and ANOVA were used to analyze the data. Results: The study reveals that while students generally exhibit a high level of awareness and understanding of e-cigarettes, significant differences emerge in specific areas, such as the physical effects of e-cigarettes, based on smoking status and potential sources of influence. In addition, female students tend to have a higher awareness and understanding of eCigs. Conclusion: There is a need for gender-sensitive and targeted educational interventions that consider individual characteristics and external factors to enhance e-cigarette awareness among students in the university. Universities should also consider leveraging peer education, media campaigns, and family engagement as part of a holistic approach to increase awareness, particularly on the physical effects of e-cigarette use

Evidence for conventional superconductivity in Bi2_2PdPt and prediction of topological superconductivity in disorder-free γ\gamma-BiPd

We present comprehensive investigations into the structural, superconducting, and topological properties of Bi$_2$PdPt. Magnetization and heat capacity measurements performed on polycrystalline Bi$_2$PdPt demonstrate a superconducting transition at $\approx$ 0.8 K. Moreover, muon spin relaxation/rotation ($\mu$SR) measurements present evidence for a time reversal symmetry preserving, isotropically gapped superconducting state in Bi$_2$PdPt. We have also performed density-functional theory (DFT) calculations on Bi$_2$PdPt alongside the more general isostructural systems, BiPd$_{x}$Pt$_{1-x}$, of which Bi$_2$PdPt and $\gamma$-BiPd are special cases for $x=0.5$ and $x=1$ respectively. We have calculated the $Z_2$ topological index from our DFT calculations for a range of substitution fractions, $x$, between $x=0$ and $x=1$ characterizing the topology of the band structure. We find a non-trivial topological state when $x>0.75$ and a trivial topological state when $x<0.75$. Therefore our results indicate that BiPd$_{x}$Pt$_{1-x}$ could be a topological superconductor for $x>0.75$.Comment: 10 pages, 7 figure