347 research outputs found

    Development of a MALDI MS-based platform for early detection of acute kidney injury

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    Purpose: Septic acute kidney injury (AKI) is associated with poor outcome. This can partly be attributed to delayed diagnosis and incomplete understanding of the underlying pathophysiology. Our aim was to develop an early predictive test for AKI based on the analysis of urinary peptide biomarkers by MALDI-MS. Experimental design: Urine samples from 95 patients with sepsis were analyzed by MALDI-MS. Marker search and multimarker model establishment were performed using the peptide profiles from 17 patients with existing or within the next 5 days developing AKI and 17 with no change in renal function. Replicates of urine sample pools from the AKI and non-AKI patient groups and normal controls were also included to select the analytically most robust AKI markers. Results: Thirty-nine urinary peptides were selected by cross-validated variable selection to generate a support vector machine multidimensional AKI classifier. Prognostic performance of the AKI classifier on an independent validation set including the remaining 61 patients of the study population (17 controls and 44 cases) was good with an area under the receiver operating characteristics curve of 0.82 and a sensitivity and specificity of 86% and 76%, respectively. Conclusion and clinical relevance: A urinary peptide marker model detects onset of AKI with acceptable accuracy in septic patients. Such a platform can eventually be transferred to the clinic as fast MALDI-MS test format

    Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

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    Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3, or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification

    Differential spatial repositioning of activated genes in Biomphalaria glabrata snails infected with Schistosoma mansoni

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    Copyright @ 2014 Arican-Goktas et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article has been made available through the Brunel Open Access Publishing Fund.Schistosomiasis is an infectious disease infecting mammals as the definitive host and fresh water snails as the intermediate host. Understanding the molecular and biochemical relationship between the causative schistosome parasite and its hosts will be key to understanding and ultimately treating and/or eradicating the disease. There is increasing evidence that pathogens that have co-evolved with their hosts can manipulate their hosts' behaviour at various levels to augment an infection. Bacteria, for example, can induce beneficial chromatin remodelling of the host genome. We have previously shown in vitro that Biomphalaria glabrata embryonic cells co-cultured with schistosome miracidia display genes changing their nuclear location and becoming up-regulated. This also happens in vivo in live intact snails, where early exposure to miracidia also elicits non-random repositioning of genes. We reveal differences in the nuclear repositioning between the response of parasite susceptible snails as compared to resistant snails and with normal or live, attenuated parasites. Interestingly, the stress response gene heat shock protein (Hsp) 70 is only repositioned and then up-regulated in susceptible snails with the normal parasite. This movement and change in gene expression seems to be controlled by the parasite. Other differences in the behaviour of genes support the view that some genes are responding to tissue damage, for example the ferritin genes move and are up-regulated whether the snails are either susceptible or resistant and upon exposure to either normal or attenuated parasite. This is the first time host genome reorganisation has been seen in a parasitic host and only the second time for any pathogen. We believe that the parasite elicits a spatio-epigenetic reorganisation of the host genome to induce favourable gene expression for itself and this might represent a fundamental mechanism present in the human host infected with schistosome cercariae as well as in other host-pathogen relationships.NIH and Sandler Borroughs Wellcome Travel Fellowshi

    Pharmacological induction of ferritin prevents osteoblastic transformation of smooth muscle cells

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    Vascular calcification is a frequent complication of atherosclerosis, diabetes and chronic kidney disease. In the latter group of patients, calcification is commonly seen in tunica media where smooth muscle cells (SMC) undergo osteoblastic transformation. Risk factors such as elevated phosphorus levels and vitamin D3 analogues have been identified. In the light of earlier observations by our group and others, we sought to inhibit SMC calcification via induction of ferritin. Human aortic SMC were cultured using β-glycerophosphate with activated vitamin D3 , or inorganic phosphate with calcium, and induction of alkaline phosphatase (ALP) and osteocalcin as well as accumulation of calcium were used to monitor osteoblastic transformation. In addition, to examine the role of vitamin D3 analogues, plasma samples from patients on haemodialysis who had received calcitriol or paricalcitol were tested for their tendency to induce calcification of SMC. Addition of exogenous ferritin mitigates the transformation of SMC into osteoblast-like cells. Importantly, pharmacological induction of heavy chain ferritin by 3H-1,2-Dithiole-3-thione was able to inhibit the SMC transition into osteoblast-like cells and calcification of extracellular matrix. Plasma samples collected from patients after the administration of activated vitamin D3 caused significantly increased ALP activity in SMC compared to the samples drawn prior to activated vitamin D3 and here, again induction of ferritin diminished the osteoblastic transformation. Our data suggests that pharmacological induction of ferritin prevents osteoblastic transformation of SMC. Hence, utilization of such agents that will cause enhanced ferritin synthesis may have important clinical applications in prevention of vascular calcification

    Examining the Effect of Prototypical Leadership Style on Leader Effectiveness: Mediating role of Perceived Integrity and Moderating Role of Leader-leader Exchange

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    Objective The main premise of social identity theory is that some leaders represent their group's identity and thus prescribe what followers should think, feel and do as members of the group. In this regard, prototypical leadership refers to a leadership style in which the leader is regarded as a representative of group identity of the followers and reflects the standards, values, and norms shared by the group members, and distinguishing them from other groups. The concept of prototypical leadership, at least in indigenous research, is an under-research topic. Therefore, the purpose of this article is to investigate this concept in the statistical population of the research in relation to other variables in the field of leadership, namely leader effectiveness, perceived integrity of the leader, and leader-leader exchange. Methods In this research, the effect of prototypical leadership on leadership effectiveness was examined. In the meantime, the mediating role of perceived leader's integrity and the moderating role of leader-leader exchange in the relationship between these two variables were measured. The study is considered an applied research in terms of its purpose, and is a descriptive survey in terms of data collection method. The study's statistical population consisted of employees working in teams at a telecommunications and information technology services company. In other words, in this company, organizational processes were carried out in the form of teams consisting of several members, a team leader and a team manager. Standard questionnaires were used to measure research variables. A statistical sample of 293 individuals was selected based on the tests used and G-Power software. Data were analyzed by structural equation modeling and partial least squares approach with Smart-PLS3 software.   Results Research hypotheses were confirmed except for the first hypothesis. The results of the research data analysis showed that prototypical leadership does not have a significant direct effect on the leader's effectiveness, but this relationship is established through the mediating role of the leader's perceived integrity. In other words, the relationship between prototypical leadership and leader effectiveness required a mediating link, and the perceived integrity of the leader as a mediating variable played the role of this mediating link. Prototypical leadership had a significant effect on the leader's perceived integrity, and the positive effect of the leader's perceived integrity on the leader's effectiveness was also significant. In addition, the research results showed that leader-leader exchange has a significant moderating effect on the relationship between prototypical leadership and the leader's perceived integrity. Conclusion In this research, the prototypical leadership variable was investigated as a concept that was not addressed in internal research, in the field of leadership and especially the leadership of work teams. The results of the research showed that this leadership style increases the effectiveness of team leadership through the perception of the leader's integrity and leader-leader exchange, and facilitates the application of leadership and its scope of inclusion. From a theoretical point of view, the present research, by introducing new variables such as prototypical leadership and leader-leader exchange, can be a suitable starting point for clarifying these under-researched concepts in the fields of organizational leadership and have a special contribution for conducting future indigenous research in this field

    Examining the Role of Social Capital Components on Explaining Organizational Pessimism

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    Abstract Purpose: The purpose of this research is to investigate the role of social capital components on explaining organizational pessimism as a behavioral challenge in Payam Noor universities in Guilan province.Methodology: The present research in terms of method; It is quantitative, with comparative logic, and in terms of purpose, it is practical and developmental. The statistical population of the research, the centers of Payam Noor University in Guilan province were selected in the number of 23 centers, the total number of human resources (academic faculty and administrative staff) is 588 people, and 220 people were selected as a sample using the cluster sampling method based on Cochran's formula. became The data collection tool is a researcher-made questionnaire. The questionnaire used was obtained from an exploratory study. In order to analyze the data, the mean, standard deviation method was used in the descriptive statistics section by SPSS23 statistical software, and in the inferential statistics section, the structural equation modeling method was used using Smart PLS3 statistical software.Research findings: The research findings indicate that the structural, relational and functional factors of social capital have an effect on organizational pessimism and explain it, and among the identified factors, the greatest intensity is related to the relational component, with the impact coefficient -0.672 and the factor load is 0.840.Conclusion: The special achievement of the present research shows the importance that by improving relations and increasing interactions among employees and professors and supporting management of such communication, the field of pessimism will be reduced to a great extent. Based on this, in terms of application, it can be claimed that by relying on the three elements of social capital, the level of organizational pessimism can be reduced in Payam Noor University, Guilan Province. Also, in terms of domestic research innovation with such a theme, it has not been seen in the country from a topical and spatial point of view.Introduction Considering that Payam Noor University is one of the active higher education centers in the country and provides a diverse range of services to students from various social categories, investigating negative behaviors and their consequences such as organizational pessimism and the prevalence of such malpractices , among its professors and employees, it can have long-term useful consequences for university managers and supervisors.Also, considering the high amount of work that Payam Noor University employees do and the fact that the dominant organizational structure of Iran's government organizations is bureaucratic, there is no doubt that the issue of job burnout, one of the most important aspects of which is organizational pessimism among The employees of government organizations, especially the employees of universities and educational centers, are increasing, and if such issues and problems are not addressed, in the long term, it will lead to a decrease in the job performance of employees and a decrease in organizational productivity.Therefore, dealing with behavioral issues with regard to the social capital component and playing its role can be very helpful. According to the explanations provided, the researchers in the current research are in line with answering this question, whether social capital can be the role of explaining behavioral dysfunctions such as organizational pessimism?Case study Payam Noor University of  Guilan ProvinceMaterials and Methods The current research follows the paradigm of positivism in terms of philosophical foundations, and its orientation is of an applied and developmental type, because it seeks to apply the findings in the same context as the statistical community under investigation, and on the other hand, it adds to the boundaries of organizational and behavioral knowledge. Also, in terms of the research approach, it is of a comparative type and it aims to test the hypotheses by using a framework and a conceptual model. Also, the nature of the current research is quantitative research and the research environment is field and the collected data were collected in the real environment. In terms of the goal, the current research aims to explain and describe the investigated phenomena, the horizon of the research is also cross-sectional. The statistical population of the research, the centers of Payam Noor University in Guilan province were selected in the number of 23 centers, the total number of human resources (academic faculty and administrative staff) is 588 people and 220 people were selected as a sample based on the Cochran formula by cluster sampling method. . The data collection tool is a researcher-made questionnaire. The questionnaire used was obtained from an exploratory study. In order to analyze the data, the mean, standard deviation method was used in the descriptive statistics section by SPSS 23 statistical software, and in the inferential statistics section, the structural equation modeling method was used using SmartPLS statistical software.Discussion and Results The research findings indicate that the structural, relational and functional factors of social capital have an effect on organizational pessimism and explain it, and among the identified factors, the greatest intensity is related to the relational component, with the impact coefficient -0.672 and the factor load is 0.840.ConclusionThe special achievement of the present research shows the importance that by improving relations and increasing interactions among employees and professors and supporting management of such communication, the field of pessimism will be reduced to a great extent. Based on this, in terms of application, it can be claimed that by relying on the three elements of social capital, the level of organizational pessimism can be reduced in Payam Noor University, Guilan Province. Also, in terms of domestic research innovation with such a theme, it has not been seen in the country from a topical and spatial point of view
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