Situs inversus totalis(SIT)is a rare homozygous recessive disease caused by the mutation in PKD1L1,which is required for normal interaction with PKD2 and leads to different complications such as respiratory disorders,...Situs inversus totalis(SIT)is a rare homozygous recessive disease caused by the mutation in PKD1L1,which is required for normal interaction with PKD2 and leads to different complications such as respiratory disorders,brain disorders and even obesity.The present study was designed to find out the mutational effect on the binding of PKD2 with mutated PKD1L1,which leads to SIT.The three-dimensional(3D)structure of wild type and mutated PKD1L1 was predicted with>90%confidence using different online tools.The different online tools that were employed were SWISS-MODEL,Phyre2(normal&intensive)and i-TASSER.To compute the physiochemical properties of PKD1L1(wild&mutated)and PKD2 in silico approaches were employed using the ExPASy ProtParam tool.Physicochemical properties such as molecular weight,isoelectric point,the total number of negatively and positively charged residues,extinction coefficient,half-life,instability and aliphatic index,grand average of hydropathicity,and amino acid percentage were calculated.A lot of variability was observed in these parameters among PKD1L1 and PKD2,which accounted for diversification in their functional properties.The theoretical pI points showed that PKD1L1(whole)is more basic with 6.64 pI compared to its first chain TOPO_DOM(amino acids from 1–1748)has a pI of 5.62 which means it is basic while PKD2 have the lowest pI point of 5.34.Docking was performed using the PatchDock and ClusPro online tools.展开更多
Early life exposure to adverse conditions such as social life issues, economic problems, health issues, death and separation of loved ones produces stress. Stressful life events (SLEs) disturb the healthy quality of l...Early life exposure to adverse conditions such as social life issues, economic problems, health issues, death and separation of loved ones produces stress. Stressful life events (SLEs) disturb the healthy quality of life in multiple ways. The biological response to SLE includes the production and activation of stress hormones. It has been reported that adrenaline, noradrenalin, pituitary, cortisol, prolactin, growth and adrenocorticotropic hormones are responsive to SLE. It is observed that under psychological stress, the circulating level of cortisol and norepinephrine (NE) is higher than in normal subjects. Under stress glucocorticoids (GC), neuroendocrine, norepinephrine and catecholamine produce reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS cause oxidative damage and lower antioxidant capacity and protection. Persistent damaged DNA may lead to the initiation of cancer. It is said that the risk factor of immune dysfunction and cancer may be increased under stress conditions by regulation of iNOS. iNOS is most widely studied as it produces large amounts of nitric oxide which affects many vital processes including apoptosis and angiogenesis in leukemia cells. The regulation of the expression of iNOS is important to control the level of reactive oxygen and nitrogen species that can be lethal to the cell and its environment. It is reported that the microenvironment of a cell affects the expression of iNOS. Therefore, it is concluded that different cells breast, colon, esophagus, bladder, lung, oral cavity and prostate might show different expressions of iNOS. Expression of iNOS is higher in tumor cells than in normal controls. Different studies have been conducted to explore the relationship between iNOS and cancer. The aim of this study is to investigate the expression of iNOS in acute lymphocytic leukemia under stress conditions. The study was performed on ALL blood samples under stress and non-stressed conditions. Polymerase chain reaction (PCR) was performed and gene- specific primers were used to see the iNOS expression. The study showed that expression of iNOS is higher in the patient than in control under stress while non-stressed patients showed significant reduction in iNOS expression. Further research is required to validate the importance of psychological factors and iNOS in cancer.展开更多
文摘Situs inversus totalis(SIT)is a rare homozygous recessive disease caused by the mutation in PKD1L1,which is required for normal interaction with PKD2 and leads to different complications such as respiratory disorders,brain disorders and even obesity.The present study was designed to find out the mutational effect on the binding of PKD2 with mutated PKD1L1,which leads to SIT.The three-dimensional(3D)structure of wild type and mutated PKD1L1 was predicted with>90%confidence using different online tools.The different online tools that were employed were SWISS-MODEL,Phyre2(normal&intensive)and i-TASSER.To compute the physiochemical properties of PKD1L1(wild&mutated)and PKD2 in silico approaches were employed using the ExPASy ProtParam tool.Physicochemical properties such as molecular weight,isoelectric point,the total number of negatively and positively charged residues,extinction coefficient,half-life,instability and aliphatic index,grand average of hydropathicity,and amino acid percentage were calculated.A lot of variability was observed in these parameters among PKD1L1 and PKD2,which accounted for diversification in their functional properties.The theoretical pI points showed that PKD1L1(whole)is more basic with 6.64 pI compared to its first chain TOPO_DOM(amino acids from 1–1748)has a pI of 5.62 which means it is basic while PKD2 have the lowest pI point of 5.34.Docking was performed using the PatchDock and ClusPro online tools.
文摘Early life exposure to adverse conditions such as social life issues, economic problems, health issues, death and separation of loved ones produces stress. Stressful life events (SLEs) disturb the healthy quality of life in multiple ways. The biological response to SLE includes the production and activation of stress hormones. It has been reported that adrenaline, noradrenalin, pituitary, cortisol, prolactin, growth and adrenocorticotropic hormones are responsive to SLE. It is observed that under psychological stress, the circulating level of cortisol and norepinephrine (NE) is higher than in normal subjects. Under stress glucocorticoids (GC), neuroendocrine, norepinephrine and catecholamine produce reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS cause oxidative damage and lower antioxidant capacity and protection. Persistent damaged DNA may lead to the initiation of cancer. It is said that the risk factor of immune dysfunction and cancer may be increased under stress conditions by regulation of iNOS. iNOS is most widely studied as it produces large amounts of nitric oxide which affects many vital processes including apoptosis and angiogenesis in leukemia cells. The regulation of the expression of iNOS is important to control the level of reactive oxygen and nitrogen species that can be lethal to the cell and its environment. It is reported that the microenvironment of a cell affects the expression of iNOS. Therefore, it is concluded that different cells breast, colon, esophagus, bladder, lung, oral cavity and prostate might show different expressions of iNOS. Expression of iNOS is higher in tumor cells than in normal controls. Different studies have been conducted to explore the relationship between iNOS and cancer. The aim of this study is to investigate the expression of iNOS in acute lymphocytic leukemia under stress conditions. The study was performed on ALL blood samples under stress and non-stressed conditions. Polymerase chain reaction (PCR) was performed and gene- specific primers were used to see the iNOS expression. The study showed that expression of iNOS is higher in the patient than in control under stress while non-stressed patients showed significant reduction in iNOS expression. Further research is required to validate the importance of psychological factors and iNOS in cancer.
