TRPV3 in keratinocytes transmits temperature information to sensory neurons via ATP

Transient receptor potential V3 (TRPV3) and TRPV4 are heat-activated cation channels expressed in keratinocytes. It has been proposed that heat-activation of TRPV3 and/or TRPV4 in the skin may release diffusible molecules which would then activate termini of neighboring dorsal root ganglion (DRG) neurons. Here we show that adenosine triphosphate (ATP) is such a candidate molecule released from keratinocytes upon heating in the co-culture systems. Using TRPV1-deficient DRG neurons, we found that increase in cytosolic Ca(2+)-concentration in DRG neurons upon heating was observed only when neurons were co-cultured with keratinocytes, and this increase was blocked by P2 purinoreceptor antagonists, PPADS and suramin. In a co-culture of keratinocytes with HEK293 cells (transfected with P2X(2) cDNA to serve as a bio-sensor), we observed that heat-activated keratinocytes secretes ATP, and that ATP release is compromised in keratinocytes from TRPV3-deficient mice. This study provides evidence that ATP is a messenger molecule for mainly TRPV3-mediated thermotransduction in skin. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00424-009-0703-x) contains supplementary material, which is available to authorized users

Change in Life Expectancy Across Countries

This paper used machine learning (ML) techniques to examine which factors contribute the greatest to life expectancy levels. Firstly, through background research, life expectancy was found to be an effective representation of a country’s overall health. Next, initial data analysis was done to analyze which features of the data were relevant to this study by looking at the factors affecting life expectancy. After the features were selected, three ML models were fitted to the data: multiple linear regression, random forest regression, and decision tree regression. The ML models were instrumental in identifying how these features interact with each other and life expectancy. The random forest regression model returned the highest R-squared value so that is the model used for this study. The R-squared value communicates how accurately the model makes predictions compared to the actual test data. To decide which of the features affected life expectancy greatest, feature importance was used. Feature importance is a metric that shows how greatly features are affecting the output value in an ML model. After running feature importance on the random forest regression model, the graph showed that the gross domestic product (GDP) of the country most greatly affected life expectancy. GDP encompasses the value of total final output of goods and services produced by the economy of a nation in a year. This conveys the importance of economic involvement to a country’s overall health. When a resource-constrained country does better economically and improves its GDP, it increases output of goods and services resulting in job creation and more money in the nation. The additional financial resources will provide an opportunity for resource constrained nations to spend more money on institutions like health care and education which in turn impact life expectancy positively

Identification of a Calcium Signalling Pathway of S-[6]-Gingerol in HuH-7 Cells

Calcium signals in hepatocytes control cell growth, proliferation, and death. Members of the transient receptor potential (TRP) cation channel superfamily are candidate calcium influx channels. NF?B activation strictly depends on calcium influx and often induces antiapoptotic genes favouring cell survival. Previously, we reported that S-[6]-gingerol is an efficacious agonist of the transient receptor potential cation channel subfamily V member 1 (TRPV1) in neurones. In this study, we tested the effect of S-[6]-gingerol on HuH-7 cells using the Fluo-4 calcium assay, RT-qPCR, transient cell transfection, and luciferase measurements. We found that S-[6]-gingerol induced a transient rise in in HuH-7 cells. The increase in induced by S-[6]-gingerol was abolished by preincubation with EGTA and was also inhibited by the TRPV1 channel antagonist capsazepine. Expression of TRPV1 in HuH-7 cells was confirmed by mRNA analysis as well as a test for increase of by TRPV1 agonist capsaicin and its inhibition by capsazepine. We found that S-[6]-gingerol induced rapid NF?B activation through TRPV1 in HuH-7 cells. Furthermore, S-[6]-gingerol-induced NF?B activation was dependent on the calcium gradient and TRPV1. The rapid NF?B activation by S-[6]-gingerol was associated with an increase in mRNA levels of NF-B-target genes: cIAP-2, XIAP, and Bcl-2 that encode antiapoptotic proteins

ThermoTRP Channels in Nociceptors: Taking a Lead from Capsaicin Receptor TRPV1

Nociceptors with peripheral and central projections express temperature sensitive transient receptor potential (TRP) ion channels, also called thermoTRP’s. Chemosensitivity of thermoTRP’s to certain natural compounds eliciting pain or exhibiting thermal properties has proven to be a good tool in characterizing these receptors. Capsaicin, a pungent chemical in hot peppers, has assisted in the cloning of the first thermoTRP, TRPV1. This discovery initiated the search for other receptors encoding the response to a wide range of temperatures encountered by the body. Of these, TRPV1 and TRPV2 encode unique modalities of thermal pain when exposed to noxious heat. The ability of TRPA1 to encode noxious cold is presently being debated. The role of TRPV1 in peripheral inflammatory pain and central sensitization during chronic pain is well known. In addition to endogenous agonists, a wide variety of chemical agonists and antagonists have been discovered to activate and inhibit TRPV1. Efforts are underway to determine conditions under which agonist-mediated desensitization of TRPV1 or inhibition by antagonists can produce analgesia. Also, identification of specific second messenger molecules that regulate phosphorylation of TRPV1 has been the focus of intense research, to exploit a broader approach to pain treatment. The search for a role of TRPV2 in pain remains dormant due to the lack of suitable experimental models. However, progress into TRPA1’s role in pain has received much attention recently. Another thermoTRP, TRPM8, encoding for the cool sensation and also expressed in nociceptors, has recently been shown to reduce pain via a central mechanism, thus opening a novel strategy for achieving analgesia. The role of other thermoTRP’s (TRPV3 and TRPV4) encoding for detection of warm temperatures and expressed in nociceptors cannot be excluded. This review will discuss current knowledge on the role of nociceptor thermoTRPs in pain and therapy and describes the activator and inhibitor molecules known to interact with them and modulate their activity

Removal of Heavy Metals Using Modified Limestone Media: Zinc and Cadmium

Heavy metal contamination is a serious concern throughout the world. Increased concentrations in drinking water have many negative impacts on human health. Limestone is an inexpensive and simple media for removing high concentrations of heavy metals from drinking water supplies. Ferric based media is commonly used to remove zinc, cadmium, lead, arsenic and other heavy metals. The drinking water standards set by the US EPA for cadmium, zinc and arsenic are 0.005 mg/L, 5 mg/L and 0.010 mg/L respectively. Bangladesh, parts of India, China and the United States have high concentrations of arsenic in drinking water. Although many technologies exist for heavy metal removal, most of these are complicated and are associated with high costs making them ineffective and unfavorable to be used in impoverished areas. We propose a novel method that combines the benefits of limestone with the capacity of ferric media in an iron-coated limestone based material. Samples of water with various concentrations of zinc and cadmium were prepared and batch tests were performed using both uncoated and iron coated limestone and are compared in removal efficiency. Kinetics studies showed that zinc is removed to a maximum level after 24 hours, while cadmium takes only 15 minutes. The effect of pH on removal of heavy metals was also studied. Metals are analyzed using Inductively Coupled Plasma Emission Spectroscopy (ICP-ES). Limestone is readily available and is also easy to coat with iron, making this material a cost effective and affordable method to be used by developing countries

A Characterization of Caffeine Imprinted Polypyrrole Electrode

Nanotechnology holds great potential for improving our lives by creating many new materials and devices in medical sciences, electronics and also in energy production. Molecularly imprinted polymers (MIPs) are highly stable synthetic polymers that possess molecular recognition properties due to cavities created in the polymer matrix that are complementary to an analyte both in shape and in positioning of functional groups. These MIPs have been widely employed for diverse applications (e.g., in chromatographic separation, drug screening, chemosensors, catalysis, immunoassays etc) due to their specificity towards the target molecules and high stability against physicochemical perturbations. Conductive polymers, (CPs) such as polypyrrole, can be likened to semiconductors because of small band gaps and low electronic mobility. CPs are exploited as an excellent tool for the preparation of nanocomposites with nano scaled biomolecules. Polypyrrole (Ppy) was the first of this key family of compounds to show high conductivity. So, electrically conducting polypyrrole (Ppy) has numerous applications. In this study, caffeine imprinted electrodes (CIE) were prepared and characterized. This research project mainly focused on three important aspects: &#;To determine the thickness of the polymeric film. &#;To determine the Limit of detection (LOD) of the polymeric film at different conditions. &#;To determine the Analytical Sensitivity (γ) of the polymeric film at varied conditions. In summary these are conclusions stated: •The thickness of the electrode increased with an increase in the number of pulses. The film thickness increased linearly up to an application of 30 pulses and after 30 pulses, an increase in slope occurred with again a linear correlation up to the maximum applied number of pulses, 42. This change in slope may indicate a different mechanism taking place. •LOD is improved as the caffeine load is reduced from 10.0 to 3.0 mM and as the number of pulses is reduced from 36 to 24. •γ increases the number of pulses increase from 24 to 36 and also increases as the caffeine load increases

New era in plant alternative splicing analysis enabled by advances in high-throughput sequencing (HTS) technologies

Alternative splicing (AS) is a crucial posttranscriptional mechanism of gene expression which promotes transcriptome and proteome diversity. At the molecular level, splicing and AS involves recognition and elimination of intronic regions of a precursor messenger RNA (pre-mRNA) and joining of exonic regions to generate the mature mRNA. AS generates more than one mRNA transcript (transcripts) differing in coding and/or untranslated regions (UTRs). AS can be classified into four major types including the exon skipping (ES), intron retention (IR), alternative donor (AD), and alternative acceptor (AA), of which IR is the most prevalent event in plants (Mandadi and Scholthof, 2015). In addition to these AS types, a subfamily of IR called exitrons, which has dual features of introns and protein-coding exons were first reported in Arabidopsis thaliana (Arabidopsis) and later also found in humans (Marquez et al., 2015). These spliced transcripts influence multiple biological processes such as growth, development and response to biotic and abiotic stresses in plants (Filichkin et al., 2015; Mandadi and Scholthof, 2015; Wang et al., 2018a).Fil: Bedre, Renesh. Texas A&m University Commerce; Estados UnidosFil: Irigoyen, Sonia. Texas A&m University Commerce; Estados UnidosFil: Petrillo, Ezequiel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Fisiología, Biología Molecular y Neurociencias. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Fisiología, Biología Molecular y Neurociencias; ArgentinaFil: Mandadi, Kranthi. Texas A&m University Commerce; Estados Unido

Numerical analysis of hybrid server immersed in synthetic dielectric fluid

In recent years there has been a phenomenal development in cloud computing, networking, virtualization, and storage, which has increased the demand for data centers. With this increase, there is a demand for higher CPU (Central Processing Unit) performance and an increase in the Thermal Design Power (TDP). Maintaining the CPU temperature within the specified parameters for air-cooled servers is a challenge in thermal engineering (due to performance). One of the components of the Data Centers with the largest energy consumption is the cooling system, which uses over 40% of the energy. Advancements in DRAMs and the increased support of CPUs (Central Processing Unit) led to higher power consumption up to 15 W per DRAM and supporting up to 12 DRAMs per CPU. This demands efficient cooling for the overall chassis. In single-phase immersion cooling, electronic components are typically submerged in a thermally conductive dielectric fluid allowing it to conduct heat away from all electrical parts. Therefore, the use of direct contact liquid cooling in data centers with high power dense components has recently been encouraged. In this paper we propose a numerical investigation of effects and improvements when attaching a cold plate to high heat flux components in an immersion cooled environment. Given their extremely low thermal resistance, cold plates have been demonstrated to have higher heat dissipation rates, and it has been noted that they increase CPU/GPU clock rates (frequency/performance). In this study, the coolant used in the cold plate is PG25 (Dynalene Propylene Glycol) and the fluid used in the tank is a commercially available synthetic dielectric fluid EC-100. The model is built in such a way that only the CPU is cooled using cold plates and the remaining components are cooled by immersion cooling. A baseline CFD (Computational Fluid Dynamics) model using an air-cooled server with heat sinks is compared to the immersion cold server with cold plates attached to the CPU. Results discuss the impact on the temperatures of the components and predict the cooling capabilities of all the components in different test cases which can be used as a trend

Employee HR Connect Portal

Employee HR Connect Portal is essential in order to track employee time, project time. This portal can be hosted on any java based web server or application server and will be accessible via web-browsers. This portal is very user- friendly. Employee HR Connect Portal will be a useful tool to identify supply and demand of human resources. We have three main modules to maintain records of employee, department and project. Employee HR Connect Portal is very helpful for auditing. Through this portal we can judge the potentiality of the employee