Search results for: gene regulation

Authors: Daniela Monteiro

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Considering the entry into force of the new EU audit reform regarding statutory auditors, in effect in all member states since 2016, this research aims to identify which audit regulation rules are associated with a high-level audit quality on both its dimensions, i.e., the actual quality and the perceived quality, in relation to public interest entities, within the European Union, and whether those rules have the same impact on both dimensions. Its measurement was based on the following proxies: the quality of financial information through earnings management and the impact of qualified opinions on financial costs. We considered in the research regulation subjects such as auditors’ rotation and provision of services (NAS) and also the level of market concentration. The criteria to include these issues in the research was its contemplation of the new rules. We studied the period before the audit reform (2009-2015) when the regulation measures were less uniform. Besides the consideration of both dimensions of audit quality and several regulation measures, we believe our conclusions configure an important contribution to this research field, considering the involvement of the first 15 member states of the European Union. The results consolidate the assumption that the balance between competence and independence is not the only challenge related to the regulation of the audit profession. The evidence demonstrates that the balance between actual and perceived quality is also a relevant matter. The major conclusion is that the challenge is to keep balanced both actual and perceived audit quality whilst ensuring the independence and competence of auditors.

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Authors: Carlos Marden Cabral Coutinho, Jose Luis Bolzan de Morais

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The article proposed intends to analyze the possibility (and conditions) of a media regulation law in a democratic rule of law in the twenty-first century. To do so, will be presented initially the idea of the public sphere (by Jürgen Habermas), showing how it is presented as an interface between the citizen and the state (or the private and public) and how important is it in a deliberative democracy. Based on this paradigm, the traditional perception of the role of public information (such as system functional element) and on the possibility of media regulation will be exposed, due to the public nature of their activity. A critical argument will then be displayed from two different perspectives: a) the formal function of the current media information, considering that the digital age has fragmented the information access; b) the concept of a constructive democracy, which reduces the need for representation, changing the strategic importance of the public sphere. The question to be addressed (based on the comparative law) is if the regulation is justified in a polycentric democracy, especially when it operates under the digital age (with immediate and virtual communication). The proposal is to be presented in the sense that even in a twenty-first century the media in a democratic rule of law still has an extremely important role and may be subject to regulation, but this should be on terms very different (and narrower) from those usually defended.

Keywords: constructive democracy, media, digital age, public sphere

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Authors: Feng Zhang

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Kashin-Beck disease (KBD) is a chronic osteochondropathy. The mechanism of hand growth and development failure of KBD remains elusive now. In this study, we conducted a two-stage genome-wide association study (GWAS) of palmar length-width ratio (LWR) of KBD, totally involving 493 Chinese Han KBD patients. Affymetrix Genome Wide Human SNP Array 6.0 was applied for SNP genotyping. Association analysis was conducted by PLINK software. Imputation analysis was performed by IMPUTE against the reference panel of the 1000 genome project. In the GWAS, the most significant association was observed between palmar LWR and rs2071358 of COL2A1 gene (P value = 4.68×10-8). Imputation analysis identified 3 SNPs surrounding rs2071358 with significant or suggestive association signals. Replication study observed additional significant association signals at both rs2071358 (P value = 0.017) and rs4760608 (P value = 0.002) of COL2A1 gene after Bonferroni correction. Our results suggest that COL2A1 gene was a novel susceptibility gene involved in the growth and development failure of hand of KBD.

Keywords: Kashin-Beck disease, genome-wide association study, COL2A1, hand

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Authors: Han-Qin Zheng, Yi-Fan Chiang-Hsieh, Chia-Hung Chien, Wen-Chi Chang

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As the most important non-vascular plants, algae have many research applications, including high species diversity, biofuel sources, adsorption of heavy metals and, following processing, health supplements. With the increasing availability of next-generation sequencing (NGS) data for algae genomes and transcriptomes, an integrated resource for retrieving gene expression data and metabolic pathway is essential for functional analysis and systems biology in algae. However, gene expression profiles and biological pathways are displayed separately in current resources, and making it impossible to search current databases directly to identify the cellular response mechanisms. Therefore, this work develops a novel AlgaePath database to retrieve gene expression profiles efficiently under various conditions in numerous metabolic pathways. AlgaePath, a web-based database, integrates gene information, biological pathways, and next-generation sequencing (NGS) datasets in Chlamydomonasreinhardtii and Neodesmus sp. UTEX 2219-4. Users can identify gene expression profiles and pathway information by using five query pages (i.e. Gene Search, Pathway Search, Differentially Expressed Genes (DEGs) Search, Gene Group Analysis, and Co-Expression Analysis). The gene expression data of 45 and 4 samples can be obtained directly on pathway maps in C. reinhardtii and Neodesmus sp. UTEX 2219-4, respectively. Genes that are differentially expressed between two conditions can be identified in Folds Search. Furthermore, the Gene Group Analysis of AlgaePath includes pathway enrichment analysis, and can easily compare the gene expression profiles of functionally related genes in a map. Finally, Co-Expression Analysis provides co-expressed transcripts of a target gene. The analysis results provide a valuable reference for designing further experiments and elucidating critical mechanisms from high-throughput data. More than an effective interface to clarify the transcript response mechanisms in different metabolic pathways under various conditions, AlgaePath is also a data mining system to identify critical mechanisms based on high-throughput sequencing.

Keywords: next-generation sequencing (NGS), algae, transcriptome, metabolic pathway, co-expression

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Authors: Anida Causevic-Ramosevac, Sabina Semiz

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The aim of this study was to investigate the association of four single nucleotide polymorphisms (SNPs) - rs673548, rs693 in ApoB gene, rs1800775 in CETP gene and rs4846914 in GALNT2 gene with parameters of type 2 diabetes (T2D) and diabetic dyslipidemia in the population of Bosnia and Herzegovina (BH). Materials and methods: Our study involved 352 patients with T2D and 156 healthy subjects. Biochemical and anthropometric parameters were measured in all participants. DNA was extracted from the peripheral blood for the purpose of genetic testing. Polymorphisms in ApoB (rs673548, rs693), CETP (rs1800775) and GALNT2 (rs4846914) genes were analyzed by using Sequenom IPLEX platform. Results: Our results demonstrated significant associations for rs180075 polymorphism in CETP gene with levels of fasting insulin (p = 0.020; p = 0.027; p = 0.044), triglycerides (p = 0.046) and ALT (p = 0.031) activity in control group. In group of diabetic patients, results showed a significant association of rs673548 in ApoB gene with levels of fasting insulin (p = 0.008), HOMA-IR (p = 0.013), VLDL-C (p = 0.037) and CRP (p = 0.029) and rs693 in ApoB gene with BMI (p = 0.025), systolic blood pressure (p = 0.027), fasting insulin (p = 0.037) and HOMA-IR (p = 0.023) levels. Significant associations were also observed for rs1800775 in CETP gene with triglyceride (p = 0.023) levels and rs4846914 in GALNT2 gene with HbA1C (p = 0.013) and triglyceride (p = 0.043) levels. Conclusion: In conclusion, this is the first study that examined the impact of variations of candidate genes on a wide range of metabolic parameters in BH population. Our results suggest an association of variations of ApoB, CETP and GALNT2 genes with specific markers of T2D and dyslipidemia. Further studies would be needed in order to confirm these genetic effects in other ethnic groups as well.

Keywords: ApoB, CETP, dyslipidemia, GALNT2, type 2 diabetes

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Authors: Emanuela Chiarella, Annamaria Aloisio, Nisticò Clelia, Maria Mesuraca

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ZNF521 is a stem cell-associated transcription co-factor, that plays a crucial role in the homeostatic regulation of the stem cell compartment in the hematopoietic, osteo-adipogenic, and neural system. In normal hematopoiesis, primary human CD34+ hematopoietic stem cells display typically a high expression of ZNF521, while its mRNA levels rapidly decrease when these progenitors progress towards erythroid, granulocytic, or B-lymphoid differentiation. However, most acute myeloid leukemias (AMLs) and leukemia-initiating cells keep high ZNF521 expression. In particular, AMLs are often characterized by chromosomal translocations involving the Mixed Lineage Leukemia (MLL) gene, which MLL gene includes a variety of fusion oncogenes arisen from genes normally required during hematopoietic development; once they are fused, they promote epigenetic and transcription factor dysregulation. The chromosomal translocation t(9;11)(p21-22;q23), fusing the MLL gene with AF9 gene, results in a monocytic immune phenotype with an aggressive course, frequent relapses, and a short survival time. To better understand the dysfunctional transcriptional networks related to genetic aberrations, AML gene expression profile datasets were queried for ZNF521 expression and its correlations with specific gene rearrangements and mutations. The results showed that ZNF521 mRNA levels are associated with specific genetic aberrations: the highest expression levels were observed in AMLs involving t(11q23) MLL rearrangements in two distinct datasets (MILE and den Boer); elevated ZNF521 mRNA expression levels were also revealed in AMLs with t(7;12) or with internal rearrangements of chromosome 16. On the contrary, relatively low ZNF521 expression levels seemed to be associated with the t(8;21) translocation, that in turn is correlated with the AML1-ETO fusion gene or the t(15;17) translocation and in AMLs with FLT3-ITD, NPM1, or CEBPα double mutations. Invitro, we found that the enforced co-expression of ZNF521 in cord blood-derived CD34+ cells induced a significant proliferative advantage, improving MLL-AF9 effects on the induction of proliferation and the expansion of leukemic progenitor cells. Transcriptome profiling of CD34+ cells transduced with either MLL-AF9, ZNF521, or a combination of the two transgenes highlighted specific sets of up- or down-regulated genes that are involved in the leukemic phenotype, including those encoding transcription factors, epigenetic modulators, and cell cycle regulators as well as those engaged in the transport or uptake of nutrients. These data enhance the functional cooperation between ZNF521 and MA9, resulting in the development, maintenance, and clonal expansion of leukemic cells. Finally, silencing of ZNF521 in MLL-AF9-transformed primary CD34+ cells inhibited their proliferation and led to their extinction, as well as ZNF521 silencing in the MLL-AF9+ THP-1 cell line resulted in an impairment of their growth and clonogenicity. Taken together, our data highlight ZNF521 role in the control of self-renewal and in the immature compartment of malignant hematopoiesis, which, by altering the gene expression landscape, contributes to the development and/or maintenance of AML acting in concert with the MLL-AF9 fusion oncogene.

Keywords: AML, human zinc finger protein 521 (hZNF521), mixed lineage leukemia gene (MLL) AF9 (MLLT3 or LTG9), cord blood-derived hematopoietic stem cells (CB-CD34+)

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Authors: Amir Salamatzade, Marhamet HematPour

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Due to the increasing importance of psychological factors in the incidence and exacerbation of chronic diseases such as multiple sclerosis, the aim of this study was to determine the difference between emotional regulation strategies and psychological symptoms in patients with multiple sclerosis and normal people. The research method was causal-comparative (post-event). The statistical population of this research included all patients with multiple sclerosis referred to the MS Association of Rasht in the first quarter of 2021, approximately 350 people. The study sample also included 120 people (60 patients with multiple sclerosis and 60 normal people) who were selected by the available sampling method and completed the emotional regulation and anxiety, depression, and stress Lavibund and Lavibund (1995) questionnaires. Data were analyzed using an independent t-test and multivariate variance analysis. The results showed that there was a significant difference between the mean of emotional regulation strategies and the components of emotional reassessment and emotional inhibition between the two groups of patients with multiple sclerosis and normal individuals (p < 0.01). There is a significant difference between the mean of psychological symptoms and the components of depression, anxiety, and stress in the two groups of patients with multiple sclerosis and normal individuals. (p < 0.01). Based on this, it can be concluded that patients with multiple sclerosis have lower levels of emotional regulation strategies and higher levels of psychological symptoms than normal individuals.

Keywords: emotional regulation strategies, psychological symptoms, multiple sclerosis, normal Individuals

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Authors: Sabrina Servot, Annick St-Amand, Michel Rousseau, Valerie Simard, Evelyne Touchette

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Child maltreatment has a profound impact on children’s development. In its victims, internalizing and externalizing problems are highly prevalent, and sleep problems are common. Furthermore, the environment they live in is often disorganized, lacking routine and consistency. In non-maltreated children, several studies documented the important role of sleep regulation and sleep ecology. A poor sleep ecology (e.g., lack of sleep hygiene and bedtime routine, inappropriate sleeping location) may lead to sleep regulation problems (e.g., short sleep duration, nocturnal awakenings), and sleep regulation problems may increase the risk of behavior problems. Therefore, this scoping review aims to map evidence about sleep ecology and sleep regulation and the associations between sleep ecology, sleep regulation, and behavior problems in maltreated preschoolers. Literature from 1993 was searched in PsycInfo, Pubmed, Medline, Eric, and Proquest Dissertations and Theses. Articles and thesis were comprehensively reviewed based upon inclusion/exclusion criteria: 1) it concerns maltreated children aged 1-5 years, and 2) it addresses at least one of the following: sleep ecology, sleep regulation, and/or their associations with behavior problems in maltreated preschoolers. From the 650 studies screened, nine of them were included. Data were charted according to study characteristics, nature of variable documented, measures, analyses performed, and results of each study, then synthesized in a narrative summary. The main results show all included articles were quantitative. Foster children samples were used in four studies, children experienced different types of maltreatment in six studies, while one was specifically about sexually abused children. Regarding sleep ecology, only one study describing maltreated preschoolers’ sleep ecology was found, while seven studies documented sleep regulation. Among these seven studies, 17 different sleep variables (e.g., parasomnia, dyssomnia, total 24-h sleep duration) were used, each study documenting from one to nine of them. Actigraphic measures were employed in three studies, the others used parent-reported questionnaires or sleep diaries. Maltreated children’s sleep was described and/or compared to non-maltreated children’s sleep, or an intervention group, showing mild differences. As for associations between sleep regulation and behavior problems, five studies investigated it and performed correlational or linear regression analyses between sleep and behavior problems, revealing some significant associations. No study was found about associations between sleep ecology and sleep regulation, between sleep ecology and behavior problems, or between these three variables. In conclusion, literature about sleep ecology, sleep regulation, and their associations with behavior problems are far more scarce in maltreated preschoolers than in non-maltreated ones. At present, there is especially a paucity of research about sleep ecology and the association between sleep ecology and sleep regulation in maltreated preschoolers, while studies on non-maltreated children showed sleep ecology plays a major role in sleep regulation. In addition, as sleep regulation is measured in many different ways among the studies, it is difficult to compare their findings. Finally, it seems necessary that research fill these gaps, as recommendations could be made to clinicians working with maltreated preschoolers regarding the use of sleep ecology and sleep regulation as intervention tools.

Keywords: maltreated preschoolers, sleep ecology, sleep regulation, behavior problems

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Authors: Marija Ratkova Manovska, Mirko Prodanov, Dean Jankuloski, Katerina Blagoevska

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Staphylococci, which are widely found in the environment, animals, humans, and food products, include Staphylococcus aureus (S. aureus), the most significant pathogenic species in this genus. The virulence and toxicity of S. aureus are primarily attributed to the presence of specific genes responsible for producing toxins, biofilms, invasive components, and antibiotic resistance. Staphylococcal food poisoning, caused by the production of staphylococcal enterotoxins (SEs) by these strains in food, is a common occurrence. Globally, S. aureus food intoxications are typically ranked as the third or fourth most prevalent foodborne intoxications. For this study, a total of 333 milk samples and 1160 dairy product samples were analyzed between 2016 and 2020. The strains were isolated and confirmed using the ISO 6888-1:1999 "Horizontal method for enumeration of coagulase-positive staphylococci." Molecular analysis of the isolates, conducted using conventional PCR, involved detecting the 23s gene of S. aureus, the nuc gene, the mecA gene, and 11 genes responsible for producing enterotoxins (sea, seb, sec, sed, see, seg, seh, sei, ser, sej, and sep). The 23s gene was found in 93 (75.6%) out of 123 isolates of Staphylococcus spp. obtained from milk. Among the 76 isolates from dairy products, either S. aureus or the 23s gene was detected in 49 (64.5%) of them. The mecA gene was identified in three isolates from raw milk and five isolates from cheese samples. The nuc gene was present in 98.9% of S. aureus strains from milk and 97.9% from dairy products. Other Staphylococcus strains carried the nuc gene in 26.7% of milk strains and 14.8% of dairy product strains. Genes associated with SEs production were detected in 85 (69.1%) strains from milk and 38 (50%) strains from dairy products. In this study, 10 out of the 11 SEs genes were found, with no isolates carrying the see gene. The most prevalent genes detected were seg and sei, with some isolates containing up to five different SEs genes. These findings indicate the presence of enterotoxigenic staphylococci strains in the tested samples, emphasizing the importance of implementing proper sanitation and hygienic practices, utilizing safe raw materials, and ensuring adequate handling of finished products. Continued monitoring for the presence of SEs is necessary to ensure food safety and prevent intoxication.

Keywords: dairy products, milk, Staphylococci, enterotoxins, SE genes

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Authors: Mondal Indranil, Bhakat Debjyoti, Mukhopadayay Asish K., Chatterjee Nabendu S.

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CS6 is the prevalent CF in our region and deciphering its molecular regulators would play a pivotal role in reducing the burden of ETEC pathogenesis. In prokaryotes, most of the genes are under the control of one operon and the promoter present upstream of the gene regulates the transcription of that gene. Here the promoter of CS6 was characterized by computational method and further analyzed by β-galactosidase assay and sequencing. Promoter constructs and deletions were prepared as required to analyze promoter activity. The effect of different additives on the CS6 promoter was analysed by the β-galactosidase assay. Bioinformatics analysis done by Softberry/BPROM predicted fur, lrp, and crp boxes, -10 and -35 region upstream of the CS6 gene. The promoter construction in no promoter plasmid pTL61T showed that region -573 to +1 is actually the promoter region as predicted. Sequential deletion of the region upstream of CS6 revealed that promoter activity remains the same when -573bp to -350bp is deleted. But after the deletion of the upstream region -350 bp to -255bp, promoter expression decreases drastically to 26%. Further deletion also decreases promoter activity up to a little range. So the region -355bp to -255bp holds the promoter sequence for the CS6 gene. Additives like iron, NaCl, etc., modulate promoter activity in a dose-dependent manner. From the promoter analysis, it can be said that the minimum region lies between -254 and +1. Important region(s) lies between -350 bp to -255 bp upstream in the promoter, which might have important elements needed to control CS6 gene expression.

Keywords: microbiology, promoter, colonization factor, ETEC

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Authors: Selin Kara-Bahçekapılı, Bengisu Nehir Aydın

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Objective: In this study, it is aimed to examine the relationship between childhood traumas (overprotection-control, emotional/physical/sexual abuse, emotional/physical neglect), age, emotional regulation difficulties, and the tendency of violence in adults. In the study, the direct and indirect effects of 6 sub-factors of childhood traumas, emotion regulation difficulties, and age on tendency to violence are evaluated on a model that theoretically reveals. Method: The population of this cross-sectional study consists of individuals between the ages of 18-65 living in Turkey. The data from 527 participants were obtained by online surveys and convenience sampling method within the scope of the study. As a result of exclusion criteria and then outlier data analysis, the data of 443 participants were included in the analysis. Data were collected by demographic information form, childhood trauma scale, emotion regulation difficulty scale, and violence tendency scale. Research data were analyzed by SPSS and AMOS using correlation, path analysis, direct and indirect effects. Results: According to the research findings, the variables in the model explained 28.2% of the variance of the mean scores of the individuals' tendency to violence. Emotion regulation difficulties have the most direct effect on the tendency to violence (d=.387; p<.01). The effects of excessive protection and control, emotional neglect, and physical neglect variables on the tendency to violence are not significant. When the significant and indirect effects of the variables on tendency to violence over emotion regulation difficulties are examined, age has a negative effect, emotional neglect has a positive effect, emotional abuse has a positive effect, and overprotection-control has a positive effect. The indirect effects of sexual abuse, physical neglect, and physical abuse on tendency to violence are not significant. Childhood traumas and age variables in the model explained 24.1% of the variance of the mean scores of the individuals’ emotion regulation difficulties. The variable that most affects emotion regulation difficulties is age (d=-.268; p<.001). The direct effects of sexual abuse, physical neglect, and physical abuse on emotion regulation difficulties are not significant. Conclusion: The results of the research emphasize the critical role of difficulty in emotion regulation on the tendency to violence. Difficulty in emotion regulation affects the tendency to violence both directly and by mediating different variables. In addition, it is seen that some sub-factors of childhood traumas have direct and/or indirect effects on the tendency to violence. Emotional abuse and age have both direct and indirect effects on the tendency to violence over emotion regulation difficulties.

Keywords: childhood trauma, emotion regulation difficulties, tendency to violence, path analysis

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Authors: João Boaventura Branco De Matos

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Currently, in Brazil, there is a considerable collection of publications on the supplementary health sector, but the vast majority is limited to retrospective examination of the sector. The present contribution starts from the diagnosis of an overwhelming change in the role of the State and its institutions, as well as an accelerated and no less forceful change in the way of producing goods and services, resulting in a clash between these different waves (state and market). This shock produces unique energy, capable of imposing major changes in the most varied sectors. Based on this diagnosis, there was an opportunity to offer the perspective and propositional study of regulatory measures relevant to the best conduct and performance of this sector in the future.

Keywords: private health regulation, state and market, forecasts in Brazilian regulation, political economy

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Authors: F. M. El-Domyati, A. Atef, S. Edris, N. O. Gadalla, M. A. Al-Kordy, A. M. Ramadan, Y. M. Saad, H. S. Al-Zahrani, A. Bahieldin

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Transcriptome retrieved from SRA database of different tissues and treatments of C. roseus was assembled in order to detect tissue-specific transcription factors (TFs) and TFs possibly related to terpenoid indole alkaloids (TIA) pathway. A number of 290 TF-like transcripts along with 12 transcripts related to TIA biosynthetic pathway were divided in terms of co-expression in the different tissues, treatments and genotypes. Three transcripts encoding peroxidases 1 and 12 were downregulated in hairy root, while upregulated in mature leaf. Eight different transcripts of the TIA pathway co-expressed with TFs either functioning downstream tryptophan biosynthesis, e.g., tdc, str1 and sgd, or upstream vindoline biosynthesis, e.g., t16h, omt, nmt, d4h and dat. The results showed no differential expression of TF transcripts in hairy roots knocked down for tdc gene (TDCi) as compared to their wild type controls. There were several evidences of tissue-specific expression of TF transcripts in flower, mature leaf, root/hairy root, stem, seedling, hairy root and immature/mature leaves. Regulation included transcription factor families, e.g., bHLH, MYB and WRKY mostly induced by ABA and/or JA (or MeJA) and regulated during abiotic or biotic stress. The information of tissue-specific regulation and co-expression of TFs and genes in the TIA pathway can be utilized in manipulating alkaloid biosynthesis in C. roseus.

Keywords: SRA database, bHLH, MYB, WRKY, co-expression

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Authors: Hanania Nasan Shokry Abdelmasih

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The discipline of regulation is pretty complex and has its own terminology. other than written legal guidelines, there's also dwelling regulation, which refers to prison exercise. primary legal rules purpose at the happiness of individuals in social existence and feature different characteristics in unique branches including public or non-public regulation. on the other hand, law is a countrywide phenomenon. The law of 1 state and the legal device implemented at the territory of another state can be completely exceptional. individuals who are professionals in a specific discipline of regulation in a single united states may have inadequate know-how within the regulation of every other united states. today, similarly to the neighborhood nature of regulation, worldwide and even supranational regulation rules are implemented as a way to defend basic human values and make sure the protection of human rights around the sector. systems that offer algorithmic answers to prison problems using synthetic intelligence (AI) gear will perhaps serve to produce very meaningful consequences in phrases of human rights. but, algorithms to be used need to no longer be evolved with the aid of only pc professionals, however additionally want the contribution of folks who are familiar with law, values, judicial choices, and even the social and political culture of the society to which it'll provide answers. otherwise, even supposing the set of rules works perfectly, it may not be well suited with the values of the society in which it is applied. The present day traits involving using AI techniques in legal systems suggest that artificial law will come to be a brand new subject within the area of law.

Keywords: sustainable development, human rights, the right to development, the human rights-based approach to development, environmental rights, economic development, social sustainability human rights protection, human rights violations, workers’ rights, justice, security

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Authors: Ismail Ay

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In this study, it is aimed to analyze the relations of the factors such as the learned resourcefulness, self-efficacy, self-regulation and subjective well-being which are thought to affect the needs of the university students for psychological help and to determine if the subjective well-being mediates other factors in the prediction of the needs of the university students for psychological help. The population of the study is formed of undergraduates who get education in 16 faculties in the central campus of the University of Atatürk in the spring term of 2012-2013 academic years. The sample of the study is formed of 1205 undergraduates (female=666, 55,3 %; male=539, 44,7 %; average of age =21,49; Sd=2,18) selected from the mentioned universe by convenience sampling method. “Need for Psychological Help Scale” has been developed as a part of the study to determine the needs for psychological help. “Short Self-Regulation Questionnaire” has been adapted into Turkish to determine the self-regulation skills. Apart from these, Rosenbaum’s Learned Resourcefulness Scale, General Self-Efficacy Scale and to determine subjective well-being; Satisfaction with Life Scale and Positive and Negative Affect Scale have been used within the study. SPSS 22.0 and LISREL 9.1 have been used in the analysis of the data. Pearson product-moment correlation, descriptive analysis, factor analysis and path analysis to test the research hypothesis has been used in the study. According to obtained data, the learned resourcefulness factor does not predict the subjective well-being; however, it highly predicts the self-regulation and self-efficacy factors. It has been determined that the self-regulation and self-efficacy factors predict the subjective well-being in a positive way and medium level, and subjective well-being mediates self-regulation and self-efficacy factors to predict the needs for psychological help. It was also determined that subjective well-being predicts the needs for psychological help in a negative way and fair level. All these results have been discussed in terms of the related theories and literature, and several suggestions have been made.

Keywords: need for psychological help, self-regulation, self-efficacy, learned resourcefulness, subjective well-being, Maslow, psychological needs

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Authors: Ireneusz Majsterek, Karolina Przybylowska, Lukasz Dziki, Adam Dziki, Jacek Kabzinski

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Colorectal cancer (CRC) is one of the deadliest cancers. Every year we see an increase in the number of cases, and in spite of intensive research etiology of the disease remains unknown. For many years, researchers are seeking to associate genetic factors with an increased risk of CRC, so far it has proved to be a compelling link between the MMR system of DNA repair and hereditary nonpolyposis colorectal cancers (HNPCC). Currently, research is focused on finding the relationship between the remaining DNA repair systems and an increased risk of developing colorectal cancer. The aim of the study was to determine the relationship between gene polymorphisms Ser835Ser of XPF gene and Gly23Ala of XPA gene–elements of NER DNA repair system, and modulation of the risk of colorectal cancer in the Polish population. Determination of the molecular basis of carcinogenesis process and predicting increased risk will allow qualifying patients to increased risk group and including them in preventive program. We used blood collected from 110 patients diagnosed with colorectal cancer. The control group consisted of equal number of healthy people. Genotyping was performed by TaqMan method. The obtained results indicate that the genotype 23Gly/Ala of XPA gene is associated with an increased risk of colorectal cancer, while 23Ala/Ala as well as TCT allele of Ser835Ser of XPF gene may reduce the risk of CRC.

Keywords: NER, colorectal cancer, XPA, XPF, polymorphisms

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Authors: Sdiqeh Jalali, M. R. Khazdair

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Liver X receptors (LXR) have an essential role in the regulation of cholesterol metabolism, and their activation increase ABCG5 and ABCG8 genes expression for the improvement of cholesterol excretion from the body during reverse cholesterol transport (RCT). The aim of this study was to investigate the effects of high-intensity interval (HIT) and low intensity continuous (LIT) trainings on gene expression of these substances after a high-fat diet in Wistar rats. Materials and Methods: Fifteen male Wistar rats were divided into 3 groups: control group (n = 5), HIT exercise group (n = 5) and LIT exercise group (n = 5). All groups used a high-fat diet for 13 weeks, and the HIT and LIT groups performed the specific training program. The expression of LXRβ, ABCG5, and ABCG8 genes was measured after the training period. Findings: Data analysis showed significantly higher levels of LXRβ, ABCG5, and ABCG8 gene expression in HIT and LIT groups compared to the control group (P ≤ 0.05). Conclusion: HIT and LIT trainings after a high-fat diet have beneficial effects on RCT that prevent heart attack. Also, HIT training may have a greater effect on cholesterol excretion during the reverse cholesterol transport mechanism than LIT.

Keywords: liver X receptor, atherosclerosis, interval training, endurance training

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Authors: Gabriel Cucato, Marilia Correia, Wagner Domingues, Aline Palmeira, Paulo Longano, Nelson Wolosker, Raphael Ritti-Dias

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Women with peripheral arterial disease (PAD) present lower walking capacity in comparison with men. However, whether cardiovascular regulation is also different between genders is unknown. Thus, the aim of this study was to compare walking capacity and cardiovascular regulation between men and women with PAD. A total of 23 women (66±7 yrs) and 31 men (64±9 yrs) were recruited. Patients performed a 6-minute test and the onset claudication distance and total walking distance were measured. Additionally, cardiovascular regulation was assessed by arterial stiffness (pulse wave velocity and augmentation index) and heart rate variability (frequency domain). Independent T test or Mann-Whitney U test were performed. In comparison with men, women present lower onset claudication distance (108±66m vs. 143±50m; P=0.032) and total walking distance (286±83m vs. 361±91 m, P=0.007). Regarding cardiovascular regulation, there were no differences in heart rate variability SDNN (72±160ms vs. 32±22ms, P=0.587); RMSSD (75±209 vs. 25±22ms, P=0.726); pNN50 (11±17ms vs. 8±14ms, P=0.836) in women and men, respectively. Moreover, there were no difference in augmentation index (39±10% vs. 34±11%, P=0.103); pulse pressure (59±17mmHg vs. 56±19mmHg, P=0.593) and pulse wave velocity (8.6±2.6m\s vs. 9.0±2.7m/s, P=0.580). In conclusion, women have impaired walking capacity compared to men. However, sex differences were not observed on cardiovascular regulation in patients with PAD.

Keywords: exercise, intermittent claudication, cardiovascular load, arterial stiffness

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Authors: Irshad Ali Khan, Jian-Ping Lu, Xiao-Hong Liu, Fu-Cheng Lin

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This study reports the functional analysis of a gene MoNUC1 in M. oryzae, which is homologous to the Saccharomyces cerevisiae NUC1 encoding a mitochondrial nuclease protein. The MoNUC1 having a gene locus MGG_05324 is 1002-bp in length and encodes an identical protein of 333 amino acids. We disrupted the gene through gene disruption strategy and isolated two mutants confirmed by southern blotting. The deleted mutants were then used for phenotypic studies and their phenotypes were compared to those of the Guy-11 strain. The mutants were first grown on CM medium to find the effect of MoNUC1 gene disruption on colony growth and the mutants were found to show normal culture colony growth similar to that of the Guy-11 strain. Conidial germination and appressorial formation were also similar in both the mutants and Guy-11 strains showing that this gene plays no significant role in these phenotypes. For pathogenicity, the mutants and Guy-11 mycelium blocks were inoculated on blast susceptible barley seedlings and it was found that both the strains exhibited full pathogenicity showing coalesced and necrotic blast lesions suggesting that this gene is not involved in pathogenicity. Mating of the mutants with 2539 strain formed numerous perithecia showing that MoNUC1 is not essential for sexual reproduction in M. oryzae. However, the mutants were found to form reduced conidia (1.06±8.03B and 1.08±9.80B) than those of the Guy-11 strain (1.46±10.61A) and we conclude that this protein is not required for the blast fungus to cause pathogenicity but plays significant role in conidiation. Proteins of signal transduction pathways that could be disrupted/ intervened genetically or chemically could lead to antifungal products of important fungal cereal diseases and reduce rice yield losses. Tipping the balance toward understanding the whole of pathogenesis, rather than simply conidiation will take some time, but clearly presents the most exciting challenge of all.

Keywords: appressorium formation, conidiation, NUC1, Magnaporthe oryzae, pathogenicity

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Authors: R. Govender, T. C. Katsande, E. Madoroba, N. M. Thiebaut, D. Naidoo

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South African control over meat safety is managed by the Department of Agriculture, Forestry and Fisheries (DAFF). Veterinary services department in each of the nine provinces in the country is tasked with overseeing the farm and abattoir segments of the meat supply chain. Abattoirs are privately owned. The number of abattoirs over the years has increased. This increase has placed constraints on government resources required to monitor these abattoirs. This paper presents empirical research results on the hygienic processing of meat in high and low throughout abattoirs. This paper presents a case for the adoption of risk-based regulation as a method of government control over hygiene and safe meat processing at abattoirs in South Africa. Recommendations are made to the DAFF regarding policy considerations on risk-based regulation as a model of control in South Africa.

Keywords: risk-based regulation, abattoir, food control, meat safety

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Authors: Biswabandhu Bankura, Srikanta Guria, Madhusudan Das

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Purpose: Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones. We aimed to identify the spectrum of mutations in the TPO gene leading to hypothyroidism in the population of West Bengal to establish the genetic etiology of the disease. Methods: 200 hypothyroid patients (case) and their corresponding sex and age matched 200 normal individuals (control) were screened depending on their clinical manifestations. Genomic DNA was isolated from peripheral blood samples and TPO gene (Exon 7 to Exon 14) was amplified by PCR. The PCR products were subjected to sequencing to identify mutations. Results: Single nucleotide changes such as Glu 641 Lys, Asp 668 Asn, Thr 725 Pro, Asp 620 Asn, Ser 398 Thr, and Ala 373 Ser were found. Changes in the TPO were assayed in vitro to compare mutant and wild-type activities. Five mutants were enzymatically inactive in the guaiacol and iodide assays. This is a strong indication that the mutations are present at crucial positions of the TPO gene, resulting in inactivated TPO. Key Findings: The results of this study may help to develop a genetic screening protocol for goiter and hypothyroidism in the population of West Bengal.

Keywords: thyroid peroxidase, hypothyroidism, mutation, in vitro assay, transfection

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Authors: Biswabandhu Bankura, Srikanta Guria, Madhusudan Das

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Purpose: Thyroid peroxidase (TPO) is the key enzyme in the biosynthesis of thyroid hormones. We aimed to identify the spectrum of mutations in the TPO gene leading to hypothyroidism in the population of West Bengal to establish the genetic etiology of the disease. Methods: 200 hypothyroid patients (case) and their corresponding sex and age matched 200 normal individuals (control) were screened depending on their clinical manifestations. Genomic DNA was isolated from peripheral blood samples and TPO gene (Exon 7 to Exon 14) was amplified by PCR. The PCR products were subjected to sequencing to identify mutations. Results: Single nucleotide changes such as Glu 641 Lys, Asp 668 Asn, Thr 725 Pro, Asp 620 Asn, Ser 398 Thr, and Ala 373 Ser were found. Changes in the TPO were assayed in vitro to compare mutant and wild-type activities. Five mutants were enzymatically inactive in the guaiacol and iodide assays. This is a strong indication that the mutations are present at crucial positions of the TPO gene, resulting in inactivated TPO. Key Findings: The results of this study may help to develop a genetic screening protocol for goiter and hypothyroidism in the population of West Bengal.

Keywords: thyroid peroxidase, hypothyroidism, mutation, in vitro assay, transfection

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Authors: Negin Parsamanesh, Saman Ameri-Mahabadi, Ali Nikfar, Mojdeh Mansouri, Hossein Chiti, Gita Fatemi Abhari

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Duchenne muscular dystrophy (DMD) is a severe progressive X-linked neuromuscular illness that affects movement through mutations in dystrophin gene. The mutation leads to insufficient, lack of or dysfunction of dystrophin. The cause of DMD was determined in an Iranian family. Exome sequencing was carried out along with a complete physical examination of the family. In silico methods were applied to find the alteration in the protein structure. The homozygous variant in DMD gene (NM-004006.2) was defined as c.2732-2733delTT (p.Phe911CysfsX8) in exon 21. In addition, phylogenetic conservation study of the human dystrophin protein sequence revealed that phenylalanine 911 is one of the evolutionarily conserved amino acids. In conclusion, our study indicated a new deletion in the DMD gene in the affected family. This deletion with an X-linked inheritance pattern is new in Iran. These findings could facilitate genetic counseling for this family and other patients in the future.

Keywords: duchenne muscular dystrophy, whole exome sequencing, iran, metabolic syndrome

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Authors: Marina Passero, Tianhua Zhai, Zuyi (Jacky) Huang

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Alzheimer’s disease has become a major public health issue, as indicated by the increasing populations of Americans living with Alzheimer’s disease. After decades of extensive research in Alzheimer’s disease, only seven drugs have been approved by Food and Drug Administration (FDA) to treat Alzheimer’s disease. Five of these drugs were designed to treat the dementia symptoms, and only two drugs (i.e., Aducanumab and Lecanemab) target the progression of Alzheimer’s disease, especially the accumulation of amyloid-b plaques. However, controversial comments were raised for the accelerated approvals of either Aducanumab or Lecanemab, especially with concerns on safety and side effects of these two drugs. There is still an urgent need for further drug discovery to target the biological processes involved in the progression of Alzheimer’s disease. Excessive cholesterol has been found to accumulate in the brain of those with Alzheimer’s disease. Cholesterol can be synthesized in both the blood and the brain, but the majority of biosynthesis in the adult brain takes place in astrocytes and is then transported to the neurons via ApoE. The blood brain barrier separates cholesterol metabolism in the brain from the rest of the body. Various proteins contribute to the metabolism of cholesterol in the brain, which offer potential targets for Alzheimer’s treatment. In the astrocytes, SREBP cleavage-activating protein (SCAP) binds to Sterol Regulatory Element-binding Protein 2 (SREBP2) in order to transport the complex from the endoplasmic reticulum to the Golgi apparatus. Cholesterol is secreted out of the astrocytes by ATP-Binding Cassette A1 (ABCA1) transporter. Lipoprotein receptors such as triggering receptor expressed on myeloid cells 2 (TREM2) internalize cholesterol into the microglia, while lipoprotein receptors such as Low-density lipoprotein receptor-related protein 1 (LRP1) internalize cholesterol into the neuron. Cytochrome P450 Family 46 Subfamily A Member 1 (CYP46A1) converts excess cholesterol to 24S-hydroxycholesterol (24S-OHC). Cholesterol has been approved for its direct effect on the production of amyloid-beta and tau proteins. The addition of cholesterol to the brain promotes the activity of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), secretase, and amyloid precursor protein (APP), which all aid in amyloid-beta production. The reduction of cholesterol esters in the brain have been found to reduce phosphorylated tau levels in mice. In this work, a computational pipeline was developed to identify the protein targets involved in cholesterol regulation in brain and further to identify chemical compounds as the inhibitors of a selected protein target. Since extensive evidence shows the strong correlation between brain cholesterol regulation and Alzheimer’s disease, a detailed literature review on genes or pathways related to the brain cholesterol synthesis and regulation was first conducted in this work. An interaction network was then built for those genes so that the top gene targets were identified. The involvement of these genes in Alzheimer’s disease progression was discussed, which was followed by the investigation of existing clinical trials for those targets. A ligand-protein docking program was finally developed to screen 1.5 million chemical compounds for the selected protein target. A machine learning program was developed to evaluate and predict the binding interaction between chemical compounds and the protein target. The results from this work pave the way for further drug discovery to regulate brain cholesterol to combat Alzheimer’s disease.

Keywords: Alzheimer’s disease, drug discovery, ligand-protein docking, gene-network analysis, cholesterol regulation

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Authors: Alyaa Abdlwahab

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Cutaneous leishmaniasis represents a serious health problem in Syria; this problem has become noticeably aggravated after the civil war in the country. Leishmania tropica parasite is the main cause of cutaneous leishmaniasis in Syria. In order to control the disease, we need an effective vaccine against leishmania parasite. DNA vaccination remains one of the favorable approaches that have been used to face cutaneous leishmaniasis. Ribosomal protein S4 is responsible for important roles in Leishmania parasite life. DNA vaccine based on S4 gene has been used against infections by many species of Leishmania parasite but leishmania tropica parasite, so this gene represents a good candidate for DNA vaccine construction. After proving the existence of ribosomal protein S4 gene in a Syrian strain of Leishmania tropica (LCED Syrian 01), sequencing it and cloning it into pCI plasmid, BALB/C mice were inoculated with pCI-S4 DNA vaccine. The immune response was determined by monitoring the lesion progression in inoculated BALB/C mice for six weeks after challenging mice with Leishmania tropica (LCED Syrian 01) parasites. IL-12, IFN-γ, and IL-4 were quantified in draining lymph nodes (DLNa) of the immunized BALB/C mice by using the RT-qPCR technique. The parasite burden was calculated in the final week for the footpad lesion and the DLNs of the mice. This study proved the existence and the expression of the ribosomal protein S4 gene in Leishmania tropica (LCED Syrian 01) promastigotes. The sequence of ribosomal protein cDNA S4 gene was determined and published in Genbank; the gene size was 822 bp. Expression was also demonstrated at the level of cDNA. Also, this study revealed that pCI-S4 DNA vaccine induces TH1\TH2 response in immunized mice; this response prevents partially developing a dermal lesion of Leishmania.

Keywords: ribosomal protein S4, DNA vaccine, Leishmania tropica, BALB\c

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Authors: Gabrielle Veloso, Welison Ty

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Trait anxiety is a pervasive tendency to attend to and experience fears and worries to a disproportionate degree, across various situations. This study sought to determine if participants who undergo emotional working memory training will have significantly lower scores on the trait anxiety scales post-intervention. The study also sought to determine if emotional regulation mediated the relationship between working memory training and trait anxiety. Forty-nine participants underwent 20 days of computerized emotional working memory training called Emotional Dual n-back, which involves viewing a continuous stream of emotional content on a grid, and then remembering the location and color of items presented on the grid. Participants of the treatment group had significantly lower trait anxiety compared to controls post-intervention. Mediation analysis determined that working memory training had no significant relationship to anxiety as measured by the Beck’s Anxiety Inventory-Trait (BAIT), but was significantly related to anxiety as measured by form Y2 of the Spielberger State-Trait Anxiety Inventory (STAI-Y2). Emotion regulation, as measured by the Emotional Regulation Questionnaire (ERQ), was found not to mediate between working memory training and trait anxiety reduction. Results suggest that working memory training may be useful in reducing psychoemotional symptoms rather than somatic symptoms of trait anxiety. Moreover, it proposes for future research to further look into the mediating role of emotion regulation via neuroimaging and the development of more comprehensive measures of emotion regulation.

Keywords: anxiety, emotion regulation, working-memory, working-memory training

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Authors: Helan Satish, M. Ramasubba Reddy

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The simulation of an endocardial cell for gene mutation in the cardiac sodium ion channel NaV1.5, encoded by SCN5A gene, is discussed. The characterization of Brugada Syndrome by loss of function effect on SCN5A mutation due to L812Q mutant present in the DII-S4 transmembrane region of the NaV1.5 channel protein and its effect in an endocardial cell is studied. Ten Tusscher model of human ventricular action potential is modified to incorporate the changes contributed by L812Q mutant in the endocardial cells. Results show that BrS-associated SCN5A mutation causes reduction in the inward sodium current by modifications in the channel gating dynamics such as delayed activation, enhanced inactivation, and slowed recovery from inactivation in the endocardial cell. A decrease in the inward sodium current was also observed, which affects depolarization phase (Phase 0) that leads to reduction in the spike amplitude of the cardiac action potential.

Keywords: SCN5A gene mutation, sodium channel, Brugada syndrome, cardiac arrhythmia, action potential

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Authors: Musarat Ishaq, Tara Karnezis, Ramin Shayan

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Lipedema, a poorly understood chronic disease of adipose hyper-deposition, is often mistaken for obesity and causes significant impairment to mobility and quality-of-life. To identify molecular mechanisms underpinning lipedema, we employed comprehensive omics-based comparative analyses of whole tissue, adipocyte precursors (adipose-derived stem cells (ADSCs)), and adipocytes from patients with or without lipedema. Transcriptional profiling revealed significant differences in lipedema tissue, adipocytes, and ADSCs, with altered levels of mRNAs involved inproliferation and cell adhesion. One highly up-regulated gene in lipedema adipose tissue, adipocytes and ADSCs, ZIC4, encodes Zinc Finger Protein ZIC 4, a class of transcription factor which may be involved in regulating metabolism and adipogenesis. ZIC4 inhibition impaired the adipogenesis of ADSCs into mature adipocytes. Epigenetic regulation study revealed overexpression of ZIC4 is involved in decreased promoter DNA methylation and subsequent decrease in adipogenesis. These epigenetic modifications can alter adipocytes microenvironment and adipocytes differentiation. Our study show that epigenetic events regulate the ability of ADSCs to commit and differentiate into mature adipocytes by modulating ZIC4.

Keywords: lipedema, adipose-derived stem cells, adipose tisue, adipocytes, zinc finger protein, epigenetic

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Authors: Hayal Akyildirim Beğen, Özgür Emi̇nağaoğlu

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DNA barcoding is the method of description of species based on gene diversity. In current studies, registration, genetic identification and protection of especially endemic plants pecies are carried out by DNA barcoding techniques. Molecular studies are based on the amplification and sequencing of the barcode gene region by the PCR method. Endemic Campanula choruhensis Kit Tan & Sorger, Campanula troegera Damboldt and Campanula betulifolia K.Koch is widespread in Artvin, Erzurum and around Çoruh valley passing through it. Intense road and dam constructions are carried out in and around the distribution area of this species. This situation harms the habitat of the species and puts its extinction. In this study, the plastid matK barcode gene regions (650 bp) of three Campanula species were created. To make the identification of this species quickly and accurately, gene sequence compared with sequences of other Campanula L. species. As a result of phylogenetic analysis, C. choruhensis is close relative to C. betulifolia. Morphologically, these species were determined to be more similar to each other with flower and leaf characters. C. troegera formed a separate branch.

Keywords: campanula, DNA barcoding, endemic, türkiye, artvin

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Authors: Peng Hou

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Natural products produced from marine bacteria serve as an immense reservoir for anti-infective drugs and therapeutic agents. Nowadays, heterologous expression of gene clusters of interests has been widely adopted as an effective strategy for natural product discovery. Briefly, the heterologous expression flowchart would be: biosynthetic gene cluster identification, pathway construction and expression, and product detection. However, gene cluster capture using traditional Transformation-associated recombination (TAR) protocol is low-efficient (0.5% positive colony rate). To make things worse, most of these putative new natural products are only predicted by bioinformatics analysis such as antiSMASH, and their corresponding natural products biosynthetic pathways are either not expressed or expressed at very low levels under laboratory conditions. Those setbacks have inspired us to focus on seeking new technologies to efficiently edit and refractor of biosynthetic gene clusters. Recently, two cutting-edge techniques have attracted our attention - the CRISPR-Cas9 and Gibson Assembly. By now, we have tried to pretreat Brevibacillus laterosporus strain genomic DNA with CRISPR-Cas9 nucleases that specifically generated breaks near the gene cluster of interest. This trial resulted in an increase in the efficiency of gene cluster capture (9%). Moreover, using Gibson Assembly by adding/deleting certain operon and tailoring enzymes regardless of end compatibility, the silent construct (~80kb) has been successfully refactored into an active one, yielded a series of analogs expected. With the appearances of the novel molecular tools, we are confident to believe that development of a high throughput mature pipeline for DNA assembly, transformation, product isolation and identification would no longer be a daydream for marine natural product discovery.

Keywords: biosynthesis, CRISPR-Cas9, DNA assembly, refactor, TAR cloning

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