Review of Pulse Monitoring System

Technology has evolved over the years and revolutionized our lives that have enabled the evolution of fields such as monitoring systems. This paper describes the development of a wireless heartbeat and monitoring system based on a Arduino at a reasonable cost with great effect. This paper describes a technique of measuring the heart rate through a fingertip and Arduino. Most monitoring system that are used today is a system must be designed so that patient can be monitored remotely in real time. The paper consists of sensors which measures heartbeat of a patient which is controlled by the Arduino. Both the readings are displayed in Application. The heartbeat sensor counts the heartbeat for specific interval of time and estimates Beats per Minute. Finally, the data are displayed in the Application at the receiving end

Acetylation of p53 stimulates miRNA processing and determines cell survival following genotoxic stress

It is widely accepted that different forms of stress activate a common target, p53, yet different outcomes are triggered in a stress-specific manner. For example, activation of p53 by genotoxic agents, such as camptothecin (CPT), triggers apoptosis, while non-genotoxic activation of p53 by Nutlin-3 (Nut3) leads to cell-cycle arrest without significant apoptosis. Such stimulus-specific responses are attributed to differential transcriptional activation of various promoters by p53. In this study, we demonstrate that CPT, but not Nut3, induces miR-203, which downregulates anti-apoptotic bcl-w and promotes cell death in a p53-dependent manner. We find that acetylation of K120 in the DNA-binding domain of p53 augments its association with the Drosha microprocessor and promotes nuclear primary miRNA processing. Knockdown of human orthologue of Males absent On the First (hMOF), the acetyltransferase that targets K120 in p53, abolishes induction of miR-203 and cell death mediated by CPT. Thus, this study reveals that p53 acetylation at K120 plays a critical role in the regulation of the Drosha microprocessor and that post-transcriptional regulation of gene expression by p53 via miRNAs plays a role in determining stress-specific cellular outcomes

The role of cGMP-dependent protein kinases in bone cell growth and survival

Skeletal integrity is preserved by continuous bone remodeling by osteoblasts and osteoclasts. While the careful regulation between bone formation and resorption is known to be a hallmark of bone maintenance, the signaling mechanisms which drive each of these processes are incompletely understood. Estrogens and fluid shear stress are known to exert positive effects on osteoblast proliferation and osteocyte survival. Both stimuli have been shown to rapidly increase nitric oxide (NO) production in a number of cell types, suggesting an activation of the NO/cGMP/PKG pathway. NO is involved in regulating cell survival and proliferation in different cell types. In the first part of the dissertation, we show that estrogen-mediated osteocytes survival is regulated through the NO/cGMP pathway. Trypan blue, TUNEL, and cleaved caspase 3 staining show the inability of estrogen to protect osteocytes from etoposide-induced apoptosis in the presence of pharmacological inhibitors of NOS, soluble guanylate cyclase, and PKG, or siRNA targeting PKG. The pro-survival effects of estrogen were mimicked by a membrane-permeable analog of cGMP. We show that PKGs function in a dual mechanism to prevent apoptosis; PKGII activates Akt and ERK, and PKGI[alpha] directly phosphorylates the Bcl-2 family member, BAD. cGMP is also involved in regulating mRNA expression of pro-apoptotic genes. The second part of this dissertation focuses on the role of PKGII in mechanotransduction. We first analyzed the effects of the NO/cGMP pathway on downstream fos family gene expression. We determined that fos genes were induced upon fluid shear stress through a NO/cGMP/PKGII mechanism activating MEK and ERK. We found that PKGII is recruited to a complex containing SHP-1, SHP-2, Src, and [alpha]v[Beta]₃ integrins in response to fluid shear stress. SHP-1 is directly phosphorylated by PKGII, and in turn, dephosphorylates and activates Src, allowing for downstream ERK signaling. In conclusion, we reveal a integral role for NO/cGMP/PKG signaling in the maintenance of bone integrit

The role of cGMP-dependent protein kinases in bone cell growth and survival

Skeletal integrity is preserved by continuous bone remodeling by osteoblasts and osteoclasts. While the careful regulation between bone formation and resorption is known to be a hallmark of bone maintenance, the signaling mechanisms which drive each of these processes are incompletely understood. Estrogens and fluid shear stress are known to exert positive effects on osteoblast proliferation and osteocyte survival. Both stimuli have been shown to rapidly increase nitric oxide (NO) production in a number of cell types, suggesting an activation of the NO/cGMP/PKG pathway. NO is involved in regulating cell survival and proliferation in different cell types. In the first part of the dissertation, we show that estrogen-mediated osteocytes survival is regulated through the NO/cGMP pathway. Trypan blue, TUNEL, and cleaved caspase 3 staining show the inability of estrogen to protect osteocytes from etoposide-induced apoptosis in the presence of pharmacological inhibitors of NOS, soluble guanylate cyclase, and PKG, or siRNA targeting PKG. The pro-survival effects of estrogen were mimicked by a membrane-permeable analog of cGMP. We show that PKGs function in a dual mechanism to prevent apoptosis; PKGII activates Akt and ERK, and PKGI[alpha] directly phosphorylates the Bcl-2 family member, BAD. cGMP is also involved in regulating mRNA expression of pro-apoptotic genes. The second part of this dissertation focuses on the role of PKGII in mechanotransduction. We first analyzed the effects of the NO/cGMP pathway on downstream fos family gene expression. We determined that fos genes were induced upon fluid shear stress through a NO/cGMP/PKGII mechanism activating MEK and ERK. We found that PKGII is recruited to a complex containing SHP-1, SHP-2, Src, and [alpha]v[Beta]₃ integrins in response to fluid shear stress. SHP-1 is directly phosphorylated by PKGII, and in turn, dephosphorylates and activates Src, allowing for downstream ERK signaling. In conclusion, we reveal a integral role for NO/cGMP/PKG signaling in the maintenance of bone integrit

Acetylation of p53 stimulates miRNA processing and determines cell survival following genotoxic stress.

It is widely accepted that different forms of stress activate a common target, p53, yet different outcomes are triggered in a stress-specific manner. For example, activation of p53 by genotoxic agents, such as camptothecin (CPT), triggers apoptosis, while non-genotoxic activation of p53 by Nutlin-3 (Nut3) leads to cell-cycle arrest without significant apoptosis. Such stimulus-specific responses are attributed to differential transcriptional activation of various promoters by p53. In this study, we demonstrate that CPT, but not Nut3, induces miR-203, which downregulates anti-apoptotic bcl-w and promotes cell death in a p53-dependent manner. We find that acetylation of K120 in the DNA-binding domain of p53 augments its association with the Drosha microprocessor and promotes nuclear primary miRNA processing. Knockdown of human orthologue of Males absent On the First (hMOF), the acetyltransferase that targets K120 in p53, abolishes induction of miR-203 and cell death mediated by CPT. Thus, this study reveals that p53 acetylation at K120 plays a critical role in the regulation of the Drosha microprocessor and that post-transcriptional regulation of gene expression by p53 via miRNAs plays a role in determining stress-specific cellular outcomes

Type II cGMP-dependent Protein Kinase Mediates Osteoblast Mechanotransduction*S⃞

Continuous bone remodeling in response to mechanical loading is critical for skeletal integrity, and interstitial fluid flow is an important stimulus for osteoblast/osteocyte growth and differentiation. However, the biochemical signals mediating osteoblast anabolic responses to mechanical stimulation are incompletely understood. In primary human osteoblasts and murine MC3T3-E1 cells, we found that fluid shear stress induced rapid expression of c-fos, fra-1, fra-2, and fosB/ΔfosB mRNAs; these genes encode transcriptional regulators that maintain skeletal integrity. Fluid shear stress increased osteoblast nitric oxide (NO) synthesis, leading to activation of cGMP-dependent protein kinase (PKG). Pharmacological inhibition of the NO/cGMP/PKG signaling pathway blocked shear-induced expression of all four fos family genes. Induction of these genes required signaling through MEK/Erk, and Erk activation was NO/cGMP/PKG-dependent. Treating cells with a membrane-permeable cGMP analog partly mimicked the effects of fluid shear stress on Erk activity and fos family gene expression. In cells transfected with small interfering RNAs (siRNA) specific for membrane-bound PKG II, shear- and cGMP-induced Erk activation and fos family gene expression was nearly abolished and could be restored by transducing cells with a virus encoding an siRNA-resistant form of PKG II; in contrast, siRNA-mediated repression of the more abundant cytosolic PKG I isoform was without effect. Thus, we report a novel function for PKG II in osteoblast mechanotransduction, and we propose a model whereby NO/cGMP/PKG II-mediated Erk activation and induction of c-fos, fra-1, fra-2, and fosB/ΔfosB play a key role in the osteoblast anabolic response to mechanical stimulation