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  • 1.
    Al-Dabagh, Huda
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Polycystic ovary syndrome: Gene expression array data from skeletal muscle in women with PCOS and controls2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women in their reproductive age. It is characterized by hyperandrogenism, menstrual cycle irregularities and polycystic ovarian morphology. PCOS can cause infertility and is usually associated with a number of metabolic dysfunctions such as insulin resistance and aberrant fat metabolism in major metabolic organs such as skeletal muscles. These dysfunctions increase the risk for developing diabetes and cardiovascular diseases. The exact etiology of PCOS is still unknow, but a number of genetic, epigenetic and environmental factors have been identified. In order to understand the links between PCOS and its related metabolic dysfunction, and to unravel its complex pathophysiology, extensive research is constantly done. In this study, 84 differentially expressed genes have been identified in skeletal muscles of women with PCOS (n=13) compared to controls (n=12) by array-based RNA profiling. Using gene set enrichment analysis, it is demonstrated that these genes are components of metabolic pathways that are related to fat metabolism and transport. In vitro verification of differential gene expression of 5 genes of interest in skeletal muscles from prenatally androgenized mice was done using RT-PCR, and shows statistically significant differential expression of 2 out of 5 genes. This study confirms the role of fat metabolism in PCOS pathogenesis and uses knowledge learned from obesity and diabetes to suggest directions for further research, which is warranted to develop new treatments that will; hopefully, reduce the devastating effects of PCOS on the lives of women and the economies of communities worldwide.

  • 2.
    Ameku, Faith-Grace
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Identification of disease-causing genes in fetus with fetal akinseia deformation sequence using next generation sequencing and in silico algorithms2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Fetal akinesia deformation sequence (FADS) is a rare disease clinically characterized by intrauterine growth restriction, arthrogryposis, and pulmonary hypoplasia. Rare diseases are not frequently investigated as they are defined as uncommon. However, more than 3% of the world’s population suffer from a type of rare disease. This equates to approximately 300 million people globally, indicating that rare diseases are not as sporadic as it appears. It is difficult to diagnose and treat rare diseases as limited research is conducted within these fields. Application of the recently developed next generation sequencing technique has become of aid in diagnosing and identifying genetic causes. In the current study, analysis of whole exome sequencing data on a fetus from a consanguineous family diagnosed with FADS was performed. The variants obtained were filtered using an artificial intelligence-based software. Candidate genes were studied, annotated, and mapped homozygously for identification and validation of the pathogenic variant. Results revealed four potential disease causing genes involved in various pathways and functions. Literature review and in silico analysis suggested that the fetus was experiencing a likely polygenic effect with phenotypes attributed to all four genes. In conclusion, further research is required for certification and determination of pathophysiology.

  • 3.
    Anders, Gianluca
    Högskolan i Skövde, Institutionen för hälsa och lärande.
    Analysis of the effects of LIN7A and LIN7C upregulation and knockdown in neuroblastoma cells2018Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Background: LIN7 are a group of proteins that play a pivotal role in membrane protein localization and are thus important for cell adhesion and polarity. LIN7 proteins are shown to be important in neuroblastoma outcome, possibly through interactions with Disc-Large proteins (DLG). DLG2 has been shown to directly affect the regulation of LIN7A. Previous studies into the role of LIN7 have given conflicting results as to its nature.

    Methods: In this study we transfected LIN7A and LIN7C in SK-N-AS cells through the use of plasmids for upregulation and siRNA for knockdown of these genes. We also evaluated the expression levels of specific genes related to pathways such as PI3K, autophagy/lysosomal activity, AKT, etc., both independently and related to LIN7 expression through the R2 platform. Genes of interest were selected and then analyzed through qPCR.

    Results: Many of the genes that were significantly correlated when compared to LIN7A/C through R2 showed no significant expression correlation after experimentation. Some more functionally close genes to LIN7 were affected in a more predictable way such as CASK being upregulated after LIN7 knockdown, PTEN being downregulated upon LIN7 plasmid transfection while others such as FOXO3 also showed significant alterations.

    Conclusion: Many of the pathways discussed in this study are better studied through protein analysis due to the nature of the function of LIN7 proteins, however some downstream transcript changes were analyzed. Unexpectedly, the knockdown of both LIN7A and LIN7C displayed similar behavior to upregulation of LIN7A or LIN7C, possibly meaning that extreme expression differences have similar regulatory outcomes for some affected genes.

  • 4.
    Azar, Meriana
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Can Norepinephrine be affected by human touch?2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Introduction: Physical contact is important in all human culture. Individuals can express different emotions in order to seek or offer physical support. Norepinephrine is one of the stress hormones, and is a part of the sympathetic nervous system, which can mediate anxiety and acute stress response. The level of norepinephrine during stress while holding someone´s hand is still underestimated. Aim: is to investigate the release of norepinephrine while getting touched once by a romantic partner and once by an unfamiliar stranger with the hypothesis that norepinephrine level would be greater while getting stroked by a stranger comparing to the partner.Method: 3 cat ELISA for the quantitative determination of norepinephrine from ImmuSmol. The data were analyzed with SPSS, non-parametrical Man Whitney-U test was carried out to do group wise comparison and time points comparison was done by Kruskal Wallis. Additionally, Spearman´s Correlation was conducted to compare norepinephrine correlation with other hormones like cortisol, oxytocin, and epinephrine. Result: no significant result have shown by comparing groups and by doing timepoints comparison. Spearman´s correlation have not shown a significant association between norepinephrine and other hormones. Conclusion: gentle touches whether it was from stranger or partner was not enough to elicit adifference in response. However, the original design aimed to focus on stimulating oxytocin and cortisol release. Thus, the design of the study should be changed for further investigation of the effect of social touches on norepinephrine.

  • 5.
    Bergman, Mattias
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Investigating how SNPs may affect relationship quality in romantic couples2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Meaningful relationships play a crucial role in human well-being by reducing stress, improving mental health, and decreasing morbidity. Internal factors such as genetic makeup is one factor that can affect relationship quality. The aim of this study was to explore if five different single nucleotide polymorphisms were associated with relationship quality in romantic couples and to find additional polymorphisms of interest through an extensive literature study. This association was examined by comparing genotypes for the rs53576 in the OXTR gene, 5-HTTLPR in the SLC6A4 gene, rs6295 in the HTR1A gene, rs41423247 in the NR3C1 gene and rs1360780 in the FKBP5 gene with couple satisfaction index scores. This data originated from a research project that had the overall aim to investigate the neural, endocrine, and genetic correlates of affective touch. Kruskal-Wallis tests were used to compare the couple satisfaction index scores to the different genotypes for the five polymorphism which showed no significant association with relationship quality. This resulted in a broad search for additional polymorphisms of interest where the rs3796863 in the CD38 gene appeared to be a promising candidate for association with relationship quality. Previous research indicated its association with anxiety, depression, and lower relationship satisfaction. In conclusion, no association could be observed between the five polymorphisms and relationship quality but the rs3796863 in the CD38 gene seem to have this association with relationship quality after conducting an extensive literature study. Additional laboratory experiments and statistical analyses would be needed to confirm this correlation.

  • 6.
    Bergsten, Niklas
    Högskolan i Skövde, Institutionen för vård och natur.
    PDIA3 and Prostate Cancer: Do changes in nucleotidesequence correspond tomalignancy?2012Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    PDIA3 interacts with the lectin chaperons; calnexin and calreticulin to surveythe folding of newly synthesized glycoproteins by the addition of N-linkedglycans. PDIA3 is also involved in transcaltachia signaling cascades andimmunogenicity. The purpose was to determine if there were any changespresent in the nucleotide sequence of the Pdia3 gene. To study this, fourprostate cell lines were examined by Sanger sequencing, two malignant(LNCaP, PC3) and two normal (PNT1A, PNT2). These were to be compared tothe nucleotide sequence from nine formalin fixed paraffin-embedded (FFPE)samples of different Gleason score and the sequence from three FFPE samplesof normal prostate tissue chosen from the Örebro Radical Cohort. The obtainedsequences were then analysed with several bioinformatics tools to determine ifthere were any changes present. The nucleotide sequence obtained from thesequencing indicated that none of the cell lines expressed the most redundantisofrom; CRA_c, but instead CRA_a and CRA_b. Surprisingly, the two normalcell lines (PNT1A and PNT2) produced similar scores in BLAST search forboth the CRA_a and the CRA_b isoforms. Software analysis of the translatedsequences predicted that LNCaP expressed a membrane bound form PDIA3while PC3 expressed a cytoplasmic variant of the protein. To confirm this,another sequencing reaction was performed. The second results indicated thatall cell lines expressed the same isoform, but that the isoforms were localizedto different intracellular compartments.

  • 7.
    Berrojo Romeyro Mascarenhas, Maria Ines
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    The circadian rhythm of the cells is dependent of the pH of the cell2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Circadian rhythms are endogenic autonomous oscillators of physiological activities resulting from 24-hour day/night cycles. Circadian rhythms regulate a wide variety of metabolic and physiological functions. This allows the organism to control its molecular, biochemical, physiological, and behavioural processes. Some studies have recently been performed on the relationship between cancer and circadian rhythm. In this paper we analyse the relationship between pH, the Pentose Phosphate Pathway, and the circadian through two databases of RNA sequence, GSE101988 and GSE74439. It was found that the Period and Cryptochrome family genes, which are linked to DNA damage response pathways, are more expressed than the control groups. At the same time, CLOCK and BMAL genes were inhibited. This, therefore, forms our supposition that the pH, through several mechanisms, does affect the circadian and thus the tumour progression. This is a very important study focus, because acidosis and alkalosis could be a biomarker for early tumour apparition in local tissues. In this databased research, BMAL1 (BMAL2) was observed to be more active than the key circadian regulator at lower pH. Together, the CRY family of genes was downregulated in both datasets. However, in the analysis involving Pentose Phosphate Pathway inhibition, p53 was up-regulated and G6PD was without any statistically significant improvement.

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  • 8.
    Brantingson Skogfält, Katarina
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Impact of insulin, glucagon and the I-G complex on cell viability and metabolism in Panc-12021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Cancer has been found not only to be a disease of genetic mutations, but also a metabolic state by which insulin and glucagon has an impact on cancer cells. Pancreatic adenocarcinoma (PDAC) is a highly lethal cancer with high risk of recurrence of cancer cells after cancer therapy treatment with a worse outcome. Healthy individuals are reported to have imbalance of blood glucose homeostasis, and an imbalance between secreted insulin and glucagon, which contribute to diabetes onset and might create a new complex between human insulin and glucagon. An increased risk of developing cancer has been seen in patients with type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D). Investigations were done on human insulin and glucagon and its formation into a new complex. Pancreatic cancer cell lines, Panc-1, were treated with these different peptides, in different concentrations, to find out the impact on cell viability. Lactate-Glo Assay were performed, investigating if there was a change of metabolism within the cells. A complex formation of insulin and glucagon from bovine and porcine, receptively, has previously been shown. Here it is reported of the existence of a new insulin-glucagon (I-G) complex made from human peptides. The I-G complex increase cancer cell viability, change the metabolism within the cells and act differently than from insulin and glucagon alone. The I-G complex interaction in cancer and diabetes, are to be further investigated.

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  • 9.
    Budnjo, Almir
    Högskolan i Skövde, Institutionen för biovetenskap.
    Gene expression of MAP2K1 and Cyclin D1 in BDII rat model of Endometrial cancer2016Independent thesis Basic level (degree of Bachelor), 10 poäng / 15 hpOppgave
    Abstract [en]

    Endometrial adenocarcinoma (EAC) is the most frequently diagnosed gynecological cancer of the female genital tract in the Western world. Research studies in EC is difficult to conduct on human tumor samples due to the complex nature of tumor arousal and genetic heterogeneousness in the human population. Therefore, inbred animal models can be promising tools to use in EC research due to similar histopathology and pathogenesis as humans. Studies performed on MAP2K1 and CCND1 has shown that their altered expression play a crucial role in carcinogenesis. CCND1 has been demonstrated to have oncogenic properties when overexpressed in human neoplasias.

    The aim of this study is to investigate gene expression levels of MAP2K1 and CCND1 in BDII rat model of endometrial adenocarcinoma cells. Quantitative real-time PCR was used to analyze expression levels of MAP2K1 and CCND1 genes in BDII/Han rat model of endometrial cancer cells using TaqMan approach. The differences in gene expression levels of MAP2K1 and CCND1 between pathologically EAC malignant and nonmalignant cells showed an upregulation of MAP2K1 and CCND1 in EAC malignant cells. The analyzed data presented observable mean differences between MAP2K1 and CCND1 in several endometrial cell lines that were examined.

    Although no statistical significance was reached, an alteration in gene expression levels in malignant and nonmalignant endometrial cells could be observed. Furthermore, this present study shows observable upregulation of MAP2K1 and CCND1 in endometrial carcinoma cells vs. nonmalignant endometrium cells and encourages further investigation of the role of CCND1 and MAP2K genes in endometrial carcinogenesis.

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  • 10.
    Cecchini, Valeria
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Human affective touch and its relation to endogenous release of dopamine2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    This current study aimed at investigating human affective touch and its relation to endogenous release of dopamine. The main experiment, which provided the material that was later analyzed in this project, was carried out at the University of Linköping, on 42 couples. The female participants engaged in fMRI scanning and provided blood samples, while gentle touch was administered, to the right dorsal armand palm, by the partner, or by a stranger. The plasma samples, that have been investigated in this study, were collected during seven different time points. The two functional runs of the experiment, featured the partner and stranger touch in a pseudorandomized manner. Blood samples were analyzed by ELISA, in particular by using the 3-CAT ELISA kit (ImmuSmol, BA E-6600). The collected data was analyzed performing Mann Whitney U tests and Spearman’s correlations. The maximum dopamine values, recorded during partner and stranger touch, in both functional runs, were significantly more elevated during partner touch (p=0.018). Spearman’s correlation was performed on the maximum dopamine and oxytocin values recorded, in both runs, during partner and stranger touch. These analyses detected non-significant relationships between the variables. The same kind of investigation was conducted on maximum noradrenaline and dopamine levels recorded during partner and stranger touch. These correlation studies, since they exhibited p values > 0.05, and small r coefficients,suggested that the relationships, between the variables mentioned above, were non-significant. To conclude, affective touch, from a loved one, is thought to affect dopamine endogenous release. Nevertheless, additional research is needed in order to establish more robust conclusions.

  • 11.
    Chehab Eddine, Salwa
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    A study of the effect of digitoxin on the immune response of panc-1 cell line compared to BxPC-3 cell line in vitro2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    This project had a focus on the effect of digitoxin on inflammation in cancer Panc-1 cell line compared to BxPC-3 cell line. Pancreatic cancer, especially the form pancreatic adenocarcinoma is the fourth cause for cancer deaths, seen in the Western world. The progression and the initiation of the disease is a consequence of an interplay between genetic and inflammation events that are linked. Digitoxin is a cardiac glycoside with effect on various cancer types. Panc-1 cells and BxPC-3 cells were treated with different concentrations of digitoxin for 48 hours. Cell viability was measured, ELISA to measure expression of pro-IL-1β and IL-1β, since they are involved in the pathway and qPCR to measure gene expression. Gene expression was done to see if digitoxin affected the genes in the inflammasome pathway. The cell viability decreased with increasing concentration of digitoxin for both cell lines. TNFα was mostly downregulated in both Panc-1 and BxPC-3. NF-κB was upregulated in both cell lines. IL-1β was upregulated in BxPC-3 while gene expression was not seen in Panc-1. Lastly, IL-18 was downregulated in Panc-1, but upregulated in BxPC-3. A downregulation of IL-1β protein expression was seen in Panc-1 and in BxPC-3, a downregulation of pro IL-1β in Panc-1 and a downregulation of pro IL-1β in BxPC-3 was seen in ELISA. This study might provide an insight that is valuable for the researchers in the future to treat cancer from the perspective of an immune disorder.

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  • 12.
    Cho, Youjung
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Effect of food intake regulation on the GIT expression of oxytocin and oxytocin receptors in rats: Version 22021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Obesity is a worldwide epidemic that can cause various health issues of different magnitudes. Recent findings have shown oxytocin’s involvement in regulating feeding behavior. Oxytocin communicates with the brain through circulation or nerves to signal satiety, consequently suppressing food intake. This suggests a potential treatment for obesity using oxytocin. Gastrointestinal tract was hypothesized to be a peripheral source of oxytocin system, thus expression of Oxt and Oxtr was investigated using 6GIT tissues of 12 male and 12 female rats, among which 6 were fasted for 16 hours and 6 were re-fed for 45 minutes. Then qPCR was performed to detect expressions. Oxt was not detected in any tissues while Oxtr was detected in the cecum and distal stomach in the original experiment and all tissues in the validation. In the original experiment, no significant differences in Oxtr expression between feeding conditions in male (p=1.000) and female (p=0.589) and between sexes in fasted (p=0.818) and re-fed (p=0.937) conditions were found in cecum. The validation showed no significant difference in Oxtr expression between sexes (p=0.293). Lastly, no significant differences in Oxtr expression between sexes in cecum (p=0.385; 95% CI= -5.589/2.685) and distal stomach (p=0.368; 95% CI= -3.451/1.605) were found. In conclusion, Oxt was not detected in the 6 GIT tissues while Oxtr was detected, however no significant differences were found to support food intake modulates Oxt and Oxtr expressions. Further research is needed to understand the mechanisms of anorexigenic effect of oxytocin to be utilized as a potential treatment for obesity.

  • 13.
    Claesson, Cim
    Högskolan i Skövde, Institutionen för vård och natur.
    Is Multiplex Ligation-dependent Probe Amplification a good method for screening formalin fixed paraffin embedded neuroblastoma tumors?2011Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Neuroblastoma is one of the most enigmatic solid tumors for scientists and pediatric oncologists. Neuroblastoma is primary a childhood form of cancer, consisting of neuroectodermal cells that originate from the neural crest and is destined for the  adrenal medulla and sympathetic nervous system. The Neuroblastoma group at The University of Gothenburg received formalin-fixed paraffin-embedded  tumor samples from Vietnam and this project was to examine if the quality of the DNA from, is good enough to run comparative genome hybridization array experiment  on by using a cheaper technique Multiplex  Ligation-dependent Probe Amplification   technique. Multiplex Ligation-dependent Probe Amplification (MRC Holland) is a multiplex PCR method that can detect abnormalities such as deletions and amplifications. By using probes consisting of one short synthetic arm with a PCR primer sequence Y at the 3´end, and one long probe with a stuffer sequence, and a PCR primer sequence X at the 5´end that can hybridize and ligate. If these probes ligate it is possible to amplify them by PCR just using specific primers for the X and Y sequences. The resulting amplification products can then be analyzed bycapillary electrophoresis. These patient that the DNA was derived from had all stage 4  neuroblastoma, and that is why they all present many aberrations. Among the fascinating data from this experiment, there are many patients with both 11q  deletions and has an extreme amplification of MYCN. In Sweden only a few cases has been discovered. In this material even though all patients are stage 4 patients, 16 have this combination.   

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  • 14.
    Damiani, Jana
    Högskolan i Skövde, Institutionen för biovetenskap.
    Activation of NLRP3 inflammasome leads to the differential secretion of interleukins 1*/18 possibly linked to pyroptosis in THP-1 cells2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Organisms are constantly exposed to microorganisms, some of which can cause disease, and yet, sickness only rarely occurs. Upon infection, the immune system is mobilized to eliminate the threat and re-establish homeostasis. The innate immune system, or “first line of defense”, is responsible for detecting infection and subsequently initiating inflammation. An important mediator of this process is the NLRP3 inflammasome, a molecular hub that coordinates the propagation of the immune response. Specifically, through the secretion of interleukins 1 and 18. These structurally related proteins are known to be secreted via unconventional pathways, however, the specificity of this matter remains inconclusive. One form of secretion suggested was “pyroptosis”, a form of cell death intended to enhance inflammation. The aim of this project was to quantify the secretion of structurally related interleukins-1/18 and evaluate the possible correlation with cell death over time. Samples were collected, interleukin release was quantified using sandwich ELISA and cell viability of stimulated cells was measured using the PrestoBlue assay. During prolonged inflammasome activation, IL-1 and IL-18 showed differences in their patterns of secretion and regulation. IL-1 was eventually downregulated whilst IL-18 maintained a constant increase over time. Strikingly, cell viability remained unchanged over the course of the experiment, demonstrating that pyroptosis is dispensable to the secretion of interleukins 1 and 18. Ultimately, the study of the relationship shared between these processes not only explains how immunity is founded, but also, uncovers the truths behind pathogenesis, how to prevent it and potentially find a cure for certain diseases.

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  • 15.
    Deshpande, Ananya
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    FGFlncRNA1 mediated chemokine activity in cancer2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Long noncoding RNAs are a highly heterogenous class of compounds and versatile regulators of the human genome. While several are identified and annotated, only a few have been functionally characterised. The Kanduri lab has established that FGFlncRNA1 is upregulated in several cancers and is involved in tumour cell proliferation and invasion. The aim of this study was to analyse the FGFlncRNA1/chemokine functional nexus in cancer. CCL20 and CXCL1 were identified as downstream targets of the lncRNA. Knockdown of the chemokines resulted in a significant reduction of proliferation, migration, and invasion. Furthermore, western blot analysis revealed the involvement of two pathways, MAPK/ERK and PI3K/AKT. These were detected through phosphorylated ERK and phosphorylated AKT protein levels. Overall, the present study demonstrated that FGFlncRNA1 may function as an oncogene in cancer progression by modulating CXCL1 and CCL20 activity, which assert their downstream activity through ERK and AKT signalling. This study bridges a small gap in the scientific community’s quest to decode the role of lncRNAs in cancer.

  • 16.
    Eduardo Venson, José
    et al.
    Institute of Informatics – INF, Universidade Federal do Rio Grande do Sul – UFRGS, Av. Bento Gonçalves, Porto Alegre, RS, Brazil / Animati - Computação aplicada à Saúde, Santa Maria, RS, Brazil.
    Bevilacqua, Fernando
    Högskolan i Skövde, Institutionen för informationsteknologi. Högskolan i Skövde, Forskningscentrum för Informationsteknologi. Universidade Federal da Fronteira Sul – UFFS, Chapecó, SC, Brazil.
    Onuki, Fabio
    Medvia Diagnósticos, Porto Alegre, RS, Brazil.
    Cordeiro d’Ornellas, Marcos
    Laboratory for Applied Computing – LaCA, Universidade Federal de Santa Maria – UFSM, Santa Maria, RS, Brazil.
    Anderson, Maciel
    Institute of Informatics – INF, Universidade Federal do Rio Grande do Sul – UFRGS, Av. Bento Gonçalves, Porto Alegre, RS, Brazil.
    Efficient medical image access in diagnostic environments with limited resources2016Inngår i: Research on Biomedical Engineering, ISSN 2446-4732, Vol. 32, nr 4, s. 347-357Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction

    A medical application running outside the workstation environment has to deal with several constraints, such as reduced available memory and low network bandwidth. The aim of this paper is to present an approach to optimize the data flow for fast image transfer and visualization on mobile devices and remote stationary devices.

    Methods

    We use a combination of client- and server-side procedures to reduce the amount of information transferred by the application. Our approach was implemented on top of a commercial PACS and evaluated through user experiments with specialists in typical diagnosis tasks. The quality of the system outcome was measured in relation to the accumulated amount of network data transference and the amount of memory used in the host device. Besides, the system's quality of use (usability) was measured through participants’ feedback.

    Results

    Contrarily to previous approaches, ours keeps the application within the memory constraints, minimizing data transferring whenever possible, allowing the application to run on a variety of devices. Moreover, it does that without sacrificing the user experience. Experimental data point that over 90% of the users did not notice any delays or degraded image quality, and when they did, they did not impact on the clinical decisions.

    Conclusion

    The combined activities and orchestration of our methods allow the image viewer to run on resource-constrained environments, such as those with low network bandwidth or little available memory. These results demonstrate the ability to explore the use of mobile devices as a support tool in the medical workflow.

  • 17.
    Enroth, Helena
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Retz, Karolina
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Sofie
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Andersson, Carl
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi. Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Svensson, Kristina
    Department of Clinical Microbiology, Unilabs AB, Skövde, Sweden.
    Ljungström, Lars
    Department of Infectious Diseases, Skaraborg Hospital, Skövde, Sweden.
    Tilevik, Diana
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Pernestig, Anna-Karin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningscentrum för Systembiologi.
    Evaluation of QuickFISH and maldi Sepsityper for identification of bacteria in bloodstream infection2019Inngår i: Infectious Diseases, ISSN 2374-4235, E-ISSN 2374-4243, Vol. 51, nr 4, s. 249-258Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Background: Early detection of bacteria and their antibiotic susceptibility patterns are critical to guide therapeutic decision-making for optimal care of septic patients. The current gold standard, blood culturing followed by subculture on agar plates for subsequent identification, is too slow leading to excessive use of broad-spectrum antibiotic with harmful consequences for the patient and, in the long run, the public health. The aim of the present study was to assess the performance of two commercial assays, QuickFISH® (OpGen) and Maldi Sepsityper™ (Bruker Daltonics) for early and accurate identification of microorganisms directly from positive blood cultures.

    Materials and methods: During two substudies of positive blood cultures, the two commercial assays were assessed against the routine method used at the clinical microbiology laboratory, Unilabs AB, at Skaraborg Hospital, Sweden.

    Results: The Maldi Sepsityper™ assay enabled earlier microorganism identification. Using the cut-off for definite species identification according to the reference method (>2.0), sufficiently accurate species identification was achieved, but only among Gram-negative bacteria. The QuickFISH®assay was time-saving and showed high concordance with the reference method, 94.8% (95% CI 88.4–98.3), when the causative agent was covered by the QuickFISH® assay.

    Conclusions: The use of the commercial assays may shorten the time to identification of causative agents in bloodstream infections and can be a good complement to the current clinical routine diagnostics. Nevertheless, the performance of the commercial assays is considerably affected by the characteristics of the causative agents.

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  • 18.
    Etezadi Amoli, Mahmood Reza
    Högskolan i Skövde, Institutionen för vård och natur.
    Evaluation of different modifications of TRIzol Reagent method for total RNA isolation from bull spermatozoa2013Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Transcriptional profile of spermatozoa can be used to assess male fertility; differences in spermatozoa attributes require adjustment of protocols for RNA isolation. Ten RNA precipitation modifications of heated TRIzol protocol were applied to total RNA extraction form bull spermatozoa. Motile spermatozoa were isolated from cryopreserved semen straws prepared from an ejaculate of a fertile bull. To evaluate total RNA purity and quantity, Ribogreen RNA detection system and Nanodrop 2000 were used. In RiboGreen assay, a consistent standard curve was not obtained, thus the measurements were ignored. Total RNA purity and concentrations also were assessed using Nanodrop. The A260/280 ratio obtained from Nanodrop showed a good range in the isolated total RNA samples (1.9±0.4). However, all RNA samples presented very low A260/230 ratios (≥1.26). It might be the effect of low concentration of the isolated total RNA. Statistical analysis of total RNA concentrations showed using manufacturer standard protocol had the highest concentration yield. Using either ethanol or Isopropanol as RNA precipitant and changing the incubation temperature had not significant effect on RNA concentration yields. However incubating samples in freezer overnight lowered the total RNA concentration. Using glycogen as a RNA carrier increased the total RNA precipitation yield. In other similar studies the highest total RNA concentration was obtained by using RNA carrier. Validating these findings by qRT-PCR and Bioanalyser might be helpful to enhance the total RNA extraction yield from bull sperm as well as for subsequent genomic studies of bull fertility.

  • 19.
    Fontes, Andre
    Högskolan i Skövde, Institutionen för hälsa och lärande. iMM, Portugal.
    Dynamics and differentiation patterns of careg-expressing ependymal cells in the spinal cord of transgenic zebrafish; the role of senescence in caudal fin regeneration2018Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Spinal cord injury (SCI) is a severe CNS injury with irreversible recovery of functions in mammalian species and consequent detrimental of social and psychological condition. It accounts for major economic resources in healthcare and current therapies of engrafting transplantation of in vitro neural cultures do not lead to functional recovery. Senescence has been shown as a dormant state where cells secrete several factors into the environment before they become phagocytized and cleared. These senescence-associated secretory phenotype (SASP) factors have been shown as crucial in the development and regeneration processes, and therefore new studies are taking place to understand if inducing the cellular senescence program is therapeutically beneficial at lesion sites. Here, we analysed the regeneration of the caudal fin of the zebrafish, which is a vertebrate model capable of regenerating tissue leading to full recovery. By quantifying proportion of senescent cells through several time points of caudal fin regeneration, through SA-β-gal staining, we assessed if there are differences between normal non-injured tissue and the regenerating and full regenerated tissue. It was revealed that the number of senescent cells increase during the regeneration process, but they become effectively cleared upon the fin is almost full regenerated. Although this confirms that there is in fact a development-programmed senescence (DPS) during regeneration, the proportion of cells after regeneration was lower than the non-injured tissue, which may be interest for the study of age-related senescence.

  • 20.
    Fredin, Sofia
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Class switching mechanism in antibodies: A conformational and structural investigation of the B-cell repertoire diversity of the CDR32021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    A process called class switching recombination (CSR) regulates the production of isotypes by enabling the switch of producing unspecific IgM or IgD to producing IgG, IgE, or IgA by causing an irreversible genomic rearrangement. Recent studies indicate a gap in the identification of the molecular mechanisms underlying CSR. This interdisciplinary project between bioinformatics and immunology aims to shed light onto these mechanisms and highlight differences in physicochemical properties in the B-cell repertoire to identify factors contributing to the decline in immune response with age and its relationships to CSR. The project is developed in line with the hypothesis that effective immune responses, and their resolution, require coordinated action from multiple different subclasses of antibodies. This is enabled by improvements in the high throughput sequencing techniques, which allows the B-cell repertoire to be revealed. The most variable portion of antibody molecules is the third complementarity determining region (CDR3) of the heavy chain. Hence, differences in hydrophobicity, pK value of the C-terminus peptide fragment, and the length of CDR3 were identified and accounted as factors that contribute to the decline in the immune response with age. Our understanding of how the immune response alters with age, is important for research applications in designing tailored vaccine strategies to ensure safety and efficacy. Development of in silico tools for the analysis of the B-cell repertoire is useful in extracting principles and functioning mechanisms that can be tested experimentally, helping in further characterizing CSR.

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  • 21.
    Gellerstedt, Martin
    Högskolan Väst, Sverige.
    Vad betyder referensintervallet för den enskilde individen?: Individens risk för falskt positiv2006Inngår i: Laboratoriet : Svenska laboratrisföreningens tidskrift, ISSN 0345-696X, nr 5, s. 16-18Artikkel i tidsskrift (Annet (populærvitenskap, debatt, mm))
  • 22.
    George, Maryan
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Adrenaline releases level on skin-to skin touches2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Human pleasant touches promote feelings of security, supportiveness, and wellbeing. Conversely, human unpleasant touches promote the body for either “fight or flight” or “short term acute stress” during emergencies, feeling of stress or danger. The promoted stress response is released from the hypothalamus by the sympathetic nerve system further to the spinal cord to reach the signals to the adrenal medulla, where stress hormones adrenaline is released. Adrenaline, which is characterized by a mimic sympathetic nerve system, interacts with α and β receptors on different organs. The aim for this study was to investigate whether the stroker (partner/stranger) touch effects on adrenaline hormone releases. The null hypothesis for this study entails a significant adrenaline reduction in partners’ touches compared with strangers’ touches. Indirect competitive ELISA method was used, and concentration data of a total of sixteen participants was obtained. Whitney-U test was carried out to compare group differences within stroker (stranger/partner) touches and adrenaline releasing level. In addition, correlation in adrenaline with noradrenaline and oxytocin hormones was obtained using Spearman’s correlation test. The significant p-value 0.05 was conducted. The result of this study showed no differences between stroker (partner/stranger) associated with adrenaline hormone release. Correlation between partner maximum (max) concentration data for both oxytocin and adrenaline had significant differences. However, max variables for adrenaline and noradrenaline within stroker did not show significant differences. The conclusion of this study is that the gentle touch stimulus used in this study was not enough to detect stress hormone in adrenaline.

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  • 23.
    Gerontaki, Kyriaki
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Studying the effects of Muscone on PANC-1 in vitro2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    In this project cancer was viewed as a metabolic disorder. The study focused on the effect of synthetic muscone on PANC-1 cells. Synthetic muscone is a ketone. Some cancers lack the potential to metabolise ketone bodies, mainly due to mitochondrial dysfunction. The Warburg effect is a biochemical phenomenon in which cancer cells favour metabolism through glycolysis instead of oxidative phosphorylation to produce ATP. The cells were treated with various concentrations of muscone for 24 and 48 hours. Three different assays were chosen to assess the effects of the treatment. These included an MTS-Assay to estimate the cell-viability, a Lactate-Glo kit to assess the lactate production after the treatment and Caspase 3/7 assay for the apoptotic effects of the treatment. Lactate is the end product of glycolysis, thus its decrease could be an indication of an effective treatment. Instead, the lactate produced exhibited an increasing tendency. Caspase activity was increased for concentration 500μΜ, whilst no effect was noted for the remaining concentrations tested. Expression of genes involved in glycolysis (HK2, GAPDH & PKM2), apoptotic pathways (CYCS), mitochondrial function (TFAM) and ketolytic activities (BDH1 & OXCT1) were chosen to be tested for a better understanding of the results derived from the assays. The expression of CYCS was in accordance with the findings of the MTS and Caspase assays for concentration 500μΜ, making its investigation promising for future research. Due to time restrictions most experiments were conducted once, thus no safe conclusions could be reached. However, we expect this pilot study to provide valuable insight for future researchers who aim to approach cancer treatment from a metabolic perspective.

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  • 24.
    Hassan, Ahmed
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Identifying the molecular cause of muscular dystrophy in consanguinous Iranian families using next generation sequencing2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Limb girdle muscular dystrophies (LGMD) are a group of muscular dystrophies characterised by wastage of distal skeletal muscles, with patients’ walking ability often progressively weakening over time. The majority of LGMDs follow an autosomal recessive inheritance pattern. This thesis project analysed the exome data of three unrelated individuals from the Middle East who were born of consanguineous unions. The individuals presented with recessively inherited muscular dystrophies. The aim of this project was to identify the underlying cause of the muscular dystrophy using next generation sequencing. Exome analysis, filtering for rare variants predicted as damaging using in silico predictive tools SIFT, Polyphen-2, MutationTaster, CADD, and homozygosity mapping followed by literature research identified potential homozygous causal variants in dysferlin, DYSF (NM_003494.3) c.4820T>C [p.Ile1607Thr], Activating Transcription Factor 6 Beta, ATF6B (NM_001136153.1) c.1793A>C [p.His598Leu], and Fibulin 2, FBLN2 (NM_001004019.1) c.3539G>A [p.Arg1180His]. In order to substantiate the supporting evidence of pathogenicity for the novel variants identified in this project, co-segregation analysis must be performed. Further exome studies investigating the presence of damaging variants of these genes in LGMD families is required in order to establish a stronger association between the novel genes identified in this thesis and LGMD. Finally, future studies involving knockdown experiments of the novel genes in Danio rerio (Zebrafish) so as to observe its effect on muscle tissue is recommended.

  • 25.
    Haug, Marianne
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Adiponectin's effects on brown adipose tissue structure and function2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Brown adipose tissue (BAT) functions as an energy expenditure organ through facilitating adaptive thermogenesis in the body. The process occurs in mitochondria where UCP-1 uncouples oxidative phosphorylation in aerobic respiration which causes loss of protons and leads to the generation of heat instead of ATP. Activation of BAT allows increasing energy expenditure and improving weight control. Therefore, since the rediscovery of metabolically active BAT in adults, it’s targeting/activation has been suggested to combat metabolic diseases like diabetes and cardiovascular diseases. One approach has been adiponectin replacement therapy which has given contradictory findings regarding adiponectin’s effects in BAT. Therefore, the current project studied BAT structure and function in APNtg mice with elevated levels of adiponectin. Results showed larger tissue in APNtg mice compared to control mice which should indicate improvement in energy homeostasis. This was studied through morphology findings via different stainings and RT-PCR, and mitochondrial activity via UCP-1 protein expression. All results in the current study indicated disruption of enlarged BAT structure in APNtg mice, which could hinder healthy tissue growth and lead to metabolic challenges inside the tissue. Problems with BAT functionality was shown to be compensated through browning and increased mitochondrial activity in white adipose tissue in response to cold-exposure. In conclusion, the current study proposes that enlarged BAT in APNtg mice is not fully functional and the need for thermoregulation might enhance browning and beige cell activation in white adipose tissue in these mice.

  • 26.
    Hernández Muñoz, Rosana
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Influence of oxytocin receptor and HPA-axis-related polymorphisms on the release of plasma oxytocin during affective touch2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Affective touch represents a key type of social interaction within human relationships and is thus involved in emotional well-being and social attachment. It provokes the synthesis and release of oxytocin (OXT), a neuropeptide associated with the creation and maintenance of social bonds. This study aims to investigate the possible relationships between several genetic polymorphisms -two OXTR SNPs (rs53576 and rs2254298) and four HPA-axis related SNPs (NR3C1 rs41423247, SLC6A4 5-HTTLPR, HTR1A rs6295, and FKBP5 rs1360780)- and the release of plasma oxytocin in response to affective touch. Blood samples were collected from 42 healthy female volunteers while two social interactions were taking place; they received affective touches from both their romantic partner and a stranger, in a randomized order to also check on the impact of social context (data already collected in a previous related research). PCR-RFLPanalysis was performed to genotype the SNP specifically selected in this study (rs2254298), and statistical analyses were conducted to explore these associations taking into consideration if the person touching is the romantic partner or a stranger. Our results show that these SNPs do not appear to be related to the plasma oxytocin response to affective touch, regardless of the toucher and the social context. These findings suggest that the SNPs studied do not have any influence in the oxytocin response in the context analysed and, therefore, could be discarded from further studies or, in contrast, investigated in other oxytocin-related scenarios. Nevertheless, duplication of results in a similar study with bigger data size is recommended.

  • 27.
    Inamahoro, Anny
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    The expression of ABC transporter in colorectal cancer: A study about ABCC5 and ABCC11 gene expression in colorectal cancer2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Introduction. Stage III colorectal cancer is treated with adjuvant chemotherapy based on 5-fluorouracil and leucovorin. Drug resistance to anticancer treatment might be due to adenosine triphosphate binding cassette transporter family members.Aim. The aim of study was to analyze the expression of two ABC transporters, known as ABCC5 and ABCC11, in tumor tissue obtained from stage III colorectal cancer patients and to correlate the results to clinical data including disease-free survival. Patients and Methods. The expression of ABCC5 and ABCC11 was analyzed in 488 patients out of which 225 were treated with 5-fluorouracil in combination with leucovorin whereas 263 did not receive any chemotherapy. Gene expression was determined using real time qPCR and related to clinical variables. Results. ABCC5 expression was associated with age (r =0.34, P =0.0001) and tumor location (P = 0.0001). ABCC5 expression was not associated with disease-free survival in both groups of treated (P=0.22) and untreated patients (P=0.83). ABCC11 was not associated with disease-free survival in the group of treated patients(P=0.35). Low expression of ABCC11 was significantly associated with a longer disease-free survival of untreated patients (P=0.01). Since the P-value was significant, a further analysis called cox regression multivariate analysis was performed in search of an interaction between the expression of ABCC11 and other covariates. Cox regression multivariate analysis showed that the expression of ABCC11 was an independent marker for disease-free survival in untreated patients [HR 0.67 (range 0.49-0.93), P=0.015]. Conclusions. None of the two analyzed genes predicted disease-free survival of patients treated with 5-fluorouracil.

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  • 28.
    Jahic, Sani
    Högskolan i Skövde, Institutionen för biovetenskap.
    Functional investigation of the potential therapeutic target gene DLG2 in an11q-deleted neuroblastoma cell line and effects of 1,25 vitamin D3 and retinoic acid combination treatments2016Independent thesis Advanced level (degree of Master (One Year)), 20 poäng / 30 hpOppgave
    Abstract [en]

    Neuroblastoma as a pediatric tumor develops in the sympathetic nervous system. DLG2 is a gene that encodes a member of the membrane-associated guanylate kinase (MAGUK) family and it resides in the chromosome region 11q. SK-N-AS is a neuroblastoma cell line with 11q deletion and consequently only one copy of the potential tumor suppressor gene DLG2. This study investigated synergistic effect by a combination treatment with 1,25(OH)2D3 and the vitamin A metabolite, retinoic acid.  Separately, SK-N-AS cells was transfected with expression vector pcDNA3.1+‐DYK that contained the DLG2-gene, followed by monitoring cell proliferation and qPCR, investigating the expression of the genes DLG2, DLG3, DLG4, VDR and PDIA3. Simultaneously, effects of knocked-down of DLG2, by siRNA transfection was monitored.  Transfection of expression plasmid with the DLG2 gene increased significantly gene expression in SK-N-AS cells with significant inhibition of the proliferation rate. Furthermore, silencing of DLG2 gene had no effect on the cell growth as well. Slower cell growth showed in combination treatment with 1,25(OH)2D3 (1nM) and 9-cis RA after 48 hours of treatment. Down-regulated VDR and possible missing RARRES3 could be the reason why SK-N-AS cell line showed resistance to the combination treatment with vitamin metabolites. All these results raised the question if another vitamin D synthetic analog could be a better choice for the future study of SK-N-AS cells. Moreover, overexpression of NAIP, large amounts of IGF-II, or not responsive RXR-VDR heterodimer to 1,25(OH)2D3 could be a potential explanation for the SK-N-AS cell unresponsiveness to the treatment.

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  • 29.
    Javeed, Ashir
    et al.
    Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
    Anderberg, Peter
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
    Ghazi, Ahmad Nauman
    Department of Software Engineering, Blekinge Institute of Technology, Karlskrona, Sweden.
    Noor, Adeeb
    Department of Information Technology, Faculty of Computing and Information Technology, King Abdulaziz University, Jeddah, Saudi Arabia.
    Elmståhl, Sölve
    EpiHealth: Epidemiology for Health, Lund University, SUS Malmö, Sweden.
    Sanmartin Berglund, Johan
    Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
    Breaking barriers: a statistical and machine learning-based hybrid system for predicting dementia2023Inngår i: Frontiers in Bioengineering and Biotechnology, E-ISSN 2296-4185, Vol. 11, artikkel-id 1336255Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Introduction: Dementia is a condition (a collection of related signs and symptoms) that causes a continuing deterioration in cognitive function, and millions of people are impacted by dementia every year as the world population continues to rise. Conventional approaches for determining dementia rely primarily on clinical examinations, analyzing medical records, and administering cognitive and neuropsychological testing. However, these methods are time-consuming and costly in terms of treatment. Therefore, this study aims to present a noninvasive method for the early prediction of dementia so that preventive steps should be taken to avoid dementia. Methods: We developed a hybrid diagnostic system based on statistical and machine learning (ML) methods that used patient electronic health records to predict dementia. The dataset used for this study was obtained from the Swedish National Study on Aging and Care (SNAC), with a sample size of 43040 and 75 features. The newly constructed diagnostic extracts a subset of useful features from the dataset through a statistical method (F-score). For the classification, we developed an ensemble voting classifier based on five different ML models: decision tree (DT), naive Bayes (NB), logistic regression (LR), support vector machines (SVM), and random forest (RF). To address the problem of ML model overfitting, we used a cross-validation approach to evaluate the performance of the proposed diagnostic system. Various assessment measures, such as accuracy, sensitivity, specificity, receiver operating characteristic (ROC) curve, and Matthew’s correlation coefficient (MCC), were used to thoroughly validate the devised diagnostic system’s efficiency. Results: According to the experimental results, the proposed diagnostic method achieved the best accuracy of 98.25%, as well as sensitivity of 97.44%, specificity of 95.744%, and MCC of 0.7535. Discussion: The effectiveness of the proposed diagnostic approach is compared to various cutting-edge feature selection techniques and baseline ML models. From experimental results, it is evident that the proposed diagnostic system outperformed the prior feature selection strategies and baseline ML models regarding accuracy. 

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  • 30.
    Javeed, Ashir
    et al.
    Aging Research Center, Karolinska Institutet, Solna, Stockholm, Sweden ; Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
    Sanmartin Berglund, Johan
    Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
    Dallora, Ana Luiza
    Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
    Saleem, Muhammad Asim
    Center of Excellence in Artificial Intelligence, Machine Learning and Smart Grid Technology, Chulalongkorn University, Bangkok, Thailand.
    Anderberg, Peter
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Department of Health, Blekinge Institute of Technology, Karlskrona, Sweden.
    Predictive Power of XGBoost_BiLSTM Model: A Machine-Learning Approach for Accurate Sleep Apnea Detection Using Electronic Health Data2023Inngår i: International Journal of Computational Intelligence Systems, ISSN 1875-6891, E-ISSN 1875-6883, Vol. 16, nr 1, artikkel-id 188Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Sleep apnea is a common disorder that can cause pauses in breathing and can last from a few seconds to several minutes, as well as shallow breathing or complete cessation of breathing. Obstructive sleep apnea is strongly associated with the risk of developing several heart diseases, including coronary heart disease, heart attack, heart failure, and stroke. In addition, obstructive sleep apnea increases the risk of developing irregular heartbeats (arrhythmias), which can lead to low blood pressure. To prevent these conditions, this study presents a novel machine-learning (ML) model for predicting sleep apnea based on electronic health data that provides accurate predictions and helps in identifying the risk factors that contribute to the development of sleep apnea. The dataset used in the study includes 75 features and 10,765 samples from the Swedish National Study on Aging and Care (SNAC). The proposed model is based on two modules: the XGBoost module assesses the most important features from feature space, while the Bidirectional Long Short-Term Memory Networks (BiLSTM) module classifies the probability of sleep apnea. Using a cross-validation scheme, the proposed XGBoost_BiLSTM algorithm achieves an accuracy of 97% while using only the six most significant features from the dataset. The model’s performance is also compared with conventional long-short-term memory networks (LSTM) and other state-of-the-art ML models. The results of the study suggest that the proposed model improved the diagnosis and treatment of sleep apnea by identifying the risk factors. 

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  • 31.
    Jokinen, Veera
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Investigation of immune regulatory mechanisms in myeloid cells: The role of IRAK3 in cancer immune responses2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    The Interleukin-1 receptor-associated kinase 3 (IRAK3) is a negative regulator of the pro-inflammatory NF-κB signalling pathway. The expression of IRAK3 is localised to monocytes and macrophages, where its expression is associated with an anti-inflammatory M2-macrophage phenotype. While IRAK3 expression is necessary to attenuate acute inflammatory responses, IRAK3 contributes to cancer development by aiding immune evasion and progression. 

    The aim of this study was to investigate the effect of IRAK3 in macrophages on their ability to co-stimulate T lymphocytes. CD14+ monocytes and CD3+ T lymphocytes were isolated from fresh buffy coats. CRISPR-Cas9 gene editing technique was employed to knockout IRAK3 in isolated monocytes. Transfected null and IRAK3 knockout macrophages were treated with conditioned media obtained from breast cancer cell lines MCF-7, MDA-MB-231, BT549 and HCC-1937. Conditioned media-treated macrophages were co-cultured with autologous and allogeneic CD3+ T lymphocytes. IFNg and granzyme B concentrations in co-culture supernatants were assessed with ELISA. T lymphocytes were analysed with FACS to immunophenotype and investigate proliferation of CD3+ T lymphocyte sub-populations. 

    The study concluded that breast cancer conditioned media induces IRAK3 expression in null macrophages, thus confirming that the anti-inflammatory function of IRAK3 can be exploited by cancer cells via secretion of soluble mediators. Most importantly, IRAK3 knockout macrophages treated with triple negative breast cancer cell line conditioned media exhibited M1 macrophage-like activity by promoting proliferation of effector T cells and their secretion of pro-inflammatory cytokines IFNγ and granzyme B. This observed pro-inflammatory function supports the role of IRAK3 as a possible novel cancer immunotherapy target.

  • 32.
    Jurcevic, Sanja
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Keane, Simon
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering.
    Borgmästars, Emmy
    Department of Surgical and Perioperative Sciences/Surgery, Umeå University, Sweden.
    Lubovac-Pilav, Zelmina
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Ejeskär, Katarina
    Högskolan i Skövde, Institutionen för hälsovetenskaper. Högskolan i Skövde, Forskningsmiljön hälsa, hållbarhet och digitalisering. Högskolan i Skövde, Institutionen för biovetenskap.
    Bioinformatics analysis of miRNAs in the neuroblastoma 11q-deleted region reveals a role of miR-548l in both 11q-deleted and MYCN amplified tumour cells2022Inngår i: Scientific Reports, E-ISSN 2045-2322, Vol. 12, nr 1, artikkel-id 19729Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Neuroblastoma is a childhood tumour that is responsible for approximately 15% of all childhood cancer deaths. Neuroblastoma tumours with amplification of the oncogene MYCN are aggressive, however, another aggressive subgroup without MYCN amplification also exists; rather, they have a deleted region at chromosome arm 11q. Twenty-six miRNAs are located within the breakpoint region of chromosome 11q and have been checked for a possible involvement in development of neuroblastoma due to the genomic alteration. Target genes of these miRNAs are involved in pathways associated with cancer, including proliferation, apoptosis and DNA repair. We could show that miR-548l found within the 11q region is downregulated in neuroblastoma cell lines with 11q deletion or MYCN amplification. In addition, we showed that the restoration of miR-548l level in a neuroblastoma cell line led to a decreased proliferation of these cells as well as a decrease in the percentage of cells in the S phase. We also found that miR-548l overexpression suppressed cell viability and promoted apoptosis, while miR-548l knockdown promoted cell viability and inhibited apoptosis in neuroblastoma cells. Our results indicate that 11q-deleted neuroblastoma and MYCN amplified neuroblastoma coalesce by downregulating miR-548l.

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  • 33.
    Kallio, Ellen
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Clinical assay for detection of SARS-COV-2 specific T cells2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    COVID-19 is a life-threatening infectious disease affecting mainly the upper-airways. This disease caused by the SARS-CoV-2 RNA virus has been causing millions of deaths worldwide since December 2019, and it was announced as a pandemic already in March 2020 by World Health Organization. In this study, the SARS-CoV-2 specific T cell activation was studied by using a novel whole blood method. The heparinized whole blood samples from 190 individuals, who had experienced mild /moderate symptoms or been exposed to COVID-19 in the work environment, were stimulated with S1 peptides and peptide-mix containing M, S, and N peptides of the SARS-CoV-2 genome. The samples were stained with OX40, CD25, CD69, and CD137 fluorescent marked antibodies to detect potential antibody markers specific to SARS-CoV-2 T cells. The stimulated samples were further analyzed using flow cytometric assay. Results showed that S1 peptide stimulated SARS-CoV-2 specific CD4+ T cells were significantly expressed among the infected individual whereas CD8+ T cell activation was not significantly detected. Also, OX40/CD25 antibody marker combination was found to be more potent than the combination of CD69/CD137 in the detection of activated CD4+ T cells. Previously reported pre-existing T cells for SARS-CoV-2 were studied in the samples activated by the peptide-mix. As expected, pre-existing T cells were detected among the individuals, who had not had SARS-CoV-2 infection. Overall, the study showed the potentiality of the new whole blood method in the detection of antibody-specific T cells. In order to introduce this method into clinical settings, it needs to be studied further.

  • 34.
    Kamara, Judy Njeri
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    The impact of p13α expression in the adult fruit fly exposed to high sugar diet elucidating the molecular link between diabetes and cancer2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Diabetes is one of the most common metabolic disorders in the world. Studies have shown that people with diabetes have a higher risk of developing cancer. P13α is a splice variant of PIK3CA gene which is often mutated in cancer linked to diabetes. Glucose metabolism and lipogenesis is dysregulated in type 2 diabetes. Gluconeogenesis, non-oxidative glycolysis and lipogenesis are increased, while the pentose phosphate pathway (PPP) is reduced. In this study the effect of p13α expression on Drosophila Melanogaster fed on high sugar diet (HSD) compared to normal diet was analyzed. Developmental speed, length and weight measurements were taken. Rate of survival and relative gene expression of six genes involved in glucose metabolism and lipogenesis were analyzed and compared within and between diets. Results obtained showed that p13α flies developed faster compared to controls on both diets. P13α male flies had lower survival rate on both diets. P13α flies on normal diet had higher average weight than control and lower average weight on HSD compared to control. P13α relative expression was reduced in the HSD compared to normal diet. Results obtained from gene expression analysis indicated differences in expression of all six genes analyzed in p13α flies compared to control flies; however the differences were not significant. In conclusion p13α expression in Drosophila seems to have an effect on development, weight and survival of the flies. However further research is needed in order to make a concrete conclusion on its effect on gene expression of the genes that were analysed.

  • 35.
    Katto, Juliaana
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Association of glut4 single nucleotide polymorphism with obstructive sleep apnea in the swedish riccadsa cohort2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Obstructive sleep apnea (OSA) is a sleep disorder affecting the respiratory airflow, characterized byoccasional interruptions in breathing (apnea) or decreased volume of respiration (hypopnea) during sleep. The disorder is estimated to affect 3-10% of the general population, with a negative impact onthe quality of life of the affected individuals. It is also strongly correlated with other health conditions, such as coronary artery disease (CAD) and type 2 diabetes. Given its prevalence and negative impact,it is paramount to find new treatment options, including prophylactic measures, to reduce personal suffering and healthcare costs. In an earlier study, a significant correlation was found between a GLUT4 polymorphism and OSA diagnosis in a Chinese population. The purpose of the present study was to investigate potential association between the rs5418 GLUT4 polymorphism and OSA in a Swedish population. This study also examined the relationship between GLUT4 and insulin resistance in this Swedish CAD cohort. A total of 149 genomic DNA samples from the Swedish Randomized Intervention with CPAP in Coronary Artery Disease and Sleep Apnea (RICCADSA) trial was genotyped for the GLUT4 rs5418 G/A polymorphism, using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results from this study did not identify a correlation between thers 5418 GLUT4 genotype and OSA, related diseases or clinical parameters. However, the frequency of A allele was found to be associated with the apnea-hypopnea index in OSA patients. The associations of GLUT4, OSA, and insulin resistance should be further investigated in a larger study group with a healthy control population included for a more conclusive result.

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  • 36.
    Khair Alla, Ahmed
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Identification of disease gene variants in two siblings with birth anomalies using whole exome sequencing (WES) and in-silico analysis2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Rare recessive disorders affect 3.5 % - 5.9% of the population worldwide. Most rare disorders are unclassified and are of unknown aetiology. Consanguinity is believed to increase the risk of rare recessive disorders in the offspring. In the current project, two siblings from consanguineous parents were born with severe skeletal and heart defects leading to death. This study aimed to uncover the potential genetic cause involved in the condition using Next Generation Sequencing and In-Silico analyses. First, the Whole Exome Sequencing data of the two affected siblings and their parents was analysed via the Variant-Calling Pipeline. The called gene-variants from the pipeline were filtered based on various In-silico analyses. Variant-dependent methods which included (Allele frequency, conservation, and pathogenicity prediction) and Disease-dependent methods that included (literature review, gene ontology, and pathway analysis) were used to confirm the deleteriousness of the identified rare variants. Three variants in three various genes were identified as candidates in the final list. The variants were then proven for autosomal recessive segregation in the family using homozygosity mapping. All identified variants are assumed to be involved in the observed phenotypes based on previously reported cases and In-Silico analysis.

  • 37.
    Kralj, Andrea
    Högskolan i Skövde, Institutionen för biovetenskap.
    The neurobiology underlying personality traits and conflict behavior: Examining the similarities in brain regions between agreeableness, aggression and dominating conflict style2018Independent thesis Basic level (degree of Bachelor), 15 poäng / 22,5 hpOppgave
    Abstract [en]

    Conflicts are part of our everyday life and the field of psychology describes how specific personality traits relate to specific conflict styles. However, the question remaining is why these relations exist? Recently, personality neuroscience has begun pinning down the neurobiology of personality traits, providing a deeper understanding of the human behavior. The present thesis utilizes the Five Factor Model (FFM; Costa & McCrae, 1990) of personality to investigate the neurobiology underlying the inverse relation between the specific personality trait of Agreeableness and dominating conflict style (a conflict management style characterized by aggressiveness, authoritarianism and/or need for dominance). Agreeableness overlaps both empathy and aggression which can work as each other’s opposites in explaining conflict behaviors. The goal of the thesis was to investigate whether the inverse relation between Agreeableness and dominating conflict style can be explained by brain regions. Brain regions such as the medial prefrontal cortex and regions involving anterior cingulate appear to be the most prominent neurobiology describing the relation. Serotonin is the neural substance involved in most cortical and subcortical brain structures and it also regulates the suppression of aggression, making it an important substance both within Agreeableness and the preference for dominating conflict style. The thesis will sum up with a discussion including some limitations within the research and further aspects such the consequences of the findings will be discussed.

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  • 38.
    Kristofersdottir, Isidora Anna
    Högskolan i Skövde, Institutionen för biovetenskap.
    Effect of FGF21 on short-term white adipocyte adiponectin secretion2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Reduced levels of white adipocyte hormone adiponectin have been observed in obese individuals with type 2 diabetes (T2D). Higher adiponectin levels are monotonically associated with a lower risk of T2D and hence increasing circulating adiponectin levels is of great interest in diabetic research. A novel compound, called fibroblast growth factor 21 (FGF21), is showing great potential in treatment of obesity and T2D. In animal models with obesity and T2D FGF21 increases glucose uptake, improves lipid homeostasis, decreases fat mass and increases circulating adiponectin levels. In this study, theaim is to explore the acute effect of FGF21 on white adipocyte adiponectin secretion. Adiponectinsecretion experiments were performed on primary murine adipocytes incubated with FGF21 for 30minutes and adiponectin levels were measured with ELISA and normalised to total protein content.To study the signalling pathway of FGF21, a separate batch of murine adipocytes were pretreated with an Epac and PI3K inhibitor prior to addition of FGF21. Results from this thesis show that FGF21potently stimulates short-term adiponectin release via PI3K-dependent pathways with no effect on adiponectin synthesis.

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  • 39.
    Kureia, Nadin
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Studying the impact of Ketone Ester HVMN on PANC-1 in vitro2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Cancer is considered to be one of the top deadly diseases, characterized by uncontrolled dividing of cells and reprogrammed metabolism. Cancer cells usually use high amounts of glucose, so they can produce the required energy for survival and proliferation, this process is called aerobic glycolysis. Studies have shown the inability of cancer using ketone bodies as fuel to generate ATP, therefore using ketone supplements could be an advantage in the fight of cancer. The aim of this thesis is to investigate the effect of ketone ester HVMN treatment, and investigate possible mechanism of its efficacy. Several methods were implemented, cell viability assay, glycolysis assay, apoptosis assay, and gene expression of several genes. This study showed a decrease in cell viability - when treating PANC-1 with different concentrations of the HVMN ketone ester, a significant decrease was recorded in the treatment concentrations of 5 and 50 mM after 24- and 48-hours. The lactate production was generally high for all concentrations of HVMN ketone ester as well as an increased apoptosis for all concentrations but only significant for treatment concentration of 1mM. The results also showed a significant increase in the expression levels of TFAM and cytochrome c (mt-CO1) indicating a functional mitochondrion. Increase mitochondrial activity suggest that ketogenic treatment HVMN induces a metabolic shift in cancer cells leading to the inhibition of glycolysis pathway, decreasing cell viability and inducing apoptosis.

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  • 40.
    Larsson, Susanna
    et al.
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Holmgren, Sandra
    VERIGRAFT, Gothenburg, Sweden.
    Jenndahl, Lachmi
    VERIGRAFT, Gothenburg, Sweden.
    Ulfenborg, Benjamin
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Strehl, Raimund
    VERIGRAFT, Gothenburg, Sweden.
    Synnergren, Jane
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy at University of Gothenburg, Sweden.
    Ghosheh, Nidal
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Proteome of Personalized Tissue-Engineered Veins2023Inngår i: ACS Omega, E-ISSN 2470-1343, Vol. 9, nr 13, s. 14805-14817Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Vascular diseases are the largest cause of death globally and impose a major global burden on healthcare. The gold standard for treating vascular diseases is the transplantation of autologous veins, if applicable. Alternative treatments still suffer from shortcomings, including low patency, lack of growth potential, the need for repeated intervention, and a substantial risk of developing infections. The use of a vascular ECM scaffold reconditioned with the patient's own cells has shown successful results in preclinical and clinical studies. In this study, we have compared the proteomes of personalized tissue-engineered veins of humans and pigs. By applying tandem mass tag (TMT) labeling LC/MS-MS, we have investigated the proteome of decellularized (DC) veins from humans and pigs and reconditioned (RC) DC veins produced through perfusion with the patient's whole blood in STEEN solution, applying the same technology as used in the preclinical studies. The results revealed high similarity between the proteomes of human and pig DC and RC veins, including the ECM texture after decellularization and reconditioning. In addition, functional enrichment analysis showed similarities in signaling pathways and biological processes involved in the immune system response. Furthermore, the classification of proteins involved in immune response activity that were detected in human and pig RC veins revealed proteins that evoke immunogenic responses, which may lead to graft rejection, thrombosis, and inflammation. However, the results from this study imply the initiation of wound healing rather than an immunogenic response, as both systems share the same processes, and no immunogenic response was reported in the preclinical and clinical studies. Finally, our study assessed the application of STEEN solution in tissue engineering and identified proteins that may be useful for the prediction of successful transplantations. 

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  • 41.
    Lövfors, William
    et al.
    Department of Biomedical Engineering, Linköping University, Sweden ; Department of Mathematics, Linköping University, Sweden ; School of Medical Sciences and Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Sweden.
    Magnusson, Rasmus
    Högskolan i Skövde, Institutionen för biovetenskap. Högskolan i Skövde, Forskningsmiljön Systembiologi.
    Jönsson, Cecilia
    Department of Biomedical Engineering, Linköping University, Sweden ; Department of Health, Medicine and Caring Sciences, Linköping University, Sweden.
    Gustafsson, Mika
    Department of Physics, Chemistry and Biology, Linköping University, Sweden.
    Olofsson, Charlotta S.
    Department of Physiology/Metabolic Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Sweden.
    Cedersund, Gunnar
    Department of Biomedical Engineering, Linköping University, Sweden ; School of Medical Sciences and Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, Sweden ; Center for Medical Image Science and Visualization (CMIV), Linköping University, Sweden.
    Nyman, Elin
    Department of Biomedical Engineering, Linköping University, Sweden.
    A comprehensive mechanistic model of adipocyte signaling with layers of confidence2023Inngår i: npj Systems Biology and Applications, E-ISSN 2056-7189, Vol. 9, nr 1, artikkel-id 24Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Adipocyte signaling, normally and in type 2 diabetes, is far from fully understood. We have earlier developed detailed dynamic mathematical models for several well-studied, partially overlapping, signaling pathways in adipocytes. Still, these models only cover a fraction of the total cellular response. For a broader coverage of the response, large-scale phosphoproteomic data and systems level knowledge on protein interactions are key. However, methods to combine detailed dynamic models with large-scale data, using information about the confidence of included interactions, are lacking. We have developed a method to first establish a core model by connecting existing models of adipocyte cellular signaling for: (1) lipolysis and fatty acid release, (2) glucose uptake, and (3) the release of adiponectin. Next, we use publicly available phosphoproteome data for the insulin response in adipocytes together with prior knowledge on protein interactions, to identify phosphosites downstream of the core model. In a parallel pairwise approach with low computation time, we test whether identified phosphosites can be added to the model. We iteratively collect accepted additions into layers and continue the search for phosphosites downstream of these added layers. For the first 30 layers with the highest confidence (311 added phosphosites), the model predicts independent data well (70–90% correct), and the predictive capability gradually decreases when we add layers of decreasing confidence. In total, 57 layers (3059 phosphosites) can be added to the model with predictive ability kept. Finally, our large-scale, layered model enables dynamic simulations of systems-wide alterations in adipocytes in type 2 diabetes. 

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  • 42.
    Magnusson, Sara
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Transcriptome analysis of the sumo cycle enzymes in rhabdomyosarcoma cells: Rhabdomyosacroma and SUMO network2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    The Small Ubiquitin-like Modifier (SUMO) moiety is a member of the superfamily of ubiquitin-like proteins (UbLs) including Ubiquitin, Nedd8, FAT10, ISG15 and ATGs. Several proteins are attached by the UbLs through a fine and tuned enzymatic cascade called post-translational modifications (PTM). SUMOylation is the drug-targetable PTM regulated by SUMO and its specific conjugating E1, E2, E3 and deconjugating SENPs enzymes. This PTM regulates several cellular functions, such as cell growth, gene regulation and apoptosis, while deregulation of SUMOylation reaction has been related to promote tumorigenic features. The correlation between different cancer subtypes and SUMO network has previously been described, but this has not been investigated in Rhabdomyosarcoma (RMS) tumor. Rhabdomyosarcoma is a heterogeneous group of malignancies and is derived from primitive myogenic precursors. The most common RMS subtypes are embryonal (ERMS) and alveolar (ARMS). The aim of this project was to investigate whether the SUMO PTM is altered in RMS disease and identify if the deregulation can also contribute to the progression, invasion and radioresistance of RMS tumors. We produced the complete SUMO transcriptome of six different Rhabdomyosarcoma cell lines and validated some targets with specific antibodies. Interestingly, rearrangement of the expression of the SUMO enzymes was discovered among the RMS cells. This evidence suggests that SUMO has the potential to be the next cellular network to study in RMS cells. In the future, the aim is to identify potential SUMO RMS network biomarkers that describe the pathology of the disease and adopt commercial and new drugs to interfere with the deregulated SUMO network by reducing or blocking the metastasis features of RMS.

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  • 43.
    Melnyk, Vladyslav
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Association between NT-proBNP rs198389-polymorphism and obstructive sleep apnea2020Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    The Obstructive Sleep Apnea (OSA) disorder may lead to serious complications. The development of OSA is influenced in general by combination of both genetic and environmental factors. In particular, Single Nucleotide Polymorphisms (SNPs) were suggested to contribute to the development of OSA and its severity. The current project focused on the SNP on rs198389 site of the Brain natriuretic peptide (BNP) gene, hypothesizing its association with OSA. BNP produces both BNP hormone and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). It has been previously found that SNP on the rs198389 site of the BNP gene affects the cardiovascular health and blood circulating levels of BNP and NT-proBNP.This project is the novel study to investigate the associations of rs198389 SNP of the BNP gene in the Swedish Randomized Intervention with Constant positive airway pressure treatment in Coronary Artery Disorder and Sleep Apnea (RICCADSA) cohort. The cohort represents patients with both Sleep Apnea (SA) and Coronary Artery Disorder (CAD). Genotypes for rs198389 SNP were identified for 157 DNA samples from RICCADSA cohort by using the PCR and Restriction Fragment Length Polymorphism (RFLP) analysis. Statistical analysis was performed to find the associations between rs198389 genotypes and OSA severity, its comorbidities, as well as circulating levels of NT-proBNP.An association between BNP rs198389 polymorphism and the proportion of Acute Myocardial Infarction (AMI) baseline cases was detected for OSA patients. No other statistically significant associations were found. Further studies are suggested with larger cohort, including healthy control population, to validate the produced results.

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  • 44.
    Mickeviciute, Ruta
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Association of ACE and PAI-1 gene polymorphisms with clinical outcomes of obstructive sleep apnea2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Obstructive sleep apnoea (OSA) is a sleeping disorder leading to complications such as daytime-sleepiness, migraines and snoring and is often associated with coronary artery disease (CAD). Studies have suggested the contribution of genetic factors in aetiology of OSA. Angiotensin converting enzyme (ACE) is involved in the regulation of blood pressure and PAI-1 (plasminogen activator-inhibitor-1 encoded by SERPINE1) in fibrinolysis and breakdown of blood clots; both of these two proteins are implicated in OSA. In the present work potential correlation between OSA, and two single nucleotide polymorphisms in ACE (rs4646994, deletion/insertion of ALU sequence) and SERPINE1 (rs1799764, 4G/5G) genes were examined in a Swedish CAD cohort. Chi-square test, Kruskal-Wallis test, Mann–Whitney U test and multinomial logistics regression were used to analyse the genotyping data. A significant correlation between the heterozygote genotype at ACE rs4646994 and incidence of OSA was identified. The distribution of SERPINE1 rs1799764 genotypes was not in equilibrium in the cohort with the most prevalent homozygous 4G/4G genotype, suggesting a correlation between this genotype and development of CAD. No significant association between rs1799764 genotypes and occurrence of OSA or PAI-1 serum levels was found. However, a significant association between the rs1799764 4G/4G genotype and uncontrolled blood pressure was identified. High PAI-1 serum levels were additionally found to be associated with obesity and angiotensin II receptor-blockers. In summary, our analysis suggested ACE rs4646994 heterozygote genotype is strongly correlated with OSA and its severity, and there is a strong correlation between SERPINE1 rs1799764 homozygote 4G/4G genotype and uncontrollable blood pressure.

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  • 45.
    Mirzaei, Maryam
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Gene expression analysis of the adipose tissue in women with polycystic ovary syndrome (PCOS) and a PCOS-like mouse model2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Polycystic Ovary Syndrome (PCOS) is the most common endocrinopathy among reproductive age women which is a major cause of reproductive and metabolic irregularities. The features of PCOS are oligo/anovulation, hyperandrogenism, polycystic ovaries. These features are associated with hirsutism, acne, infertility, insulin resistance, obesity and inflammation. Commonly, adipose tissue of women with PCOS display abnormalities which are linked to inflammation and insulin resistance that are central factors in PCOS. This study focused on the aberrant mechanisms in adipocytes that are related to PCOS etiology. For this purpose, gene expression in adipose tissue of women with PCOS was analysed and compared to healthy controls. The statistical analysis of an Illumina microarray data set yielded a list of significantly differentially expressed genes, and gene set enrichment analysis revealed that the upregulated genes (PTPN6, HLA-DRB1 and MYD88) are involved in pathways that are related to immunity, and the downregulated genes (such as PER2) contribute to circadian rhythm. Expression of these genes were verified in adipose tissue of PCOS-like mouse models, using quantitative Real-Time Polymerase Chain Reaction (qPCR). However, the results of gene expression verification do not lie in accordance with what is expected, since no differences in expression of the selected genes in adipose tissue of PCOS-like mouse models were observed. In conclusion, only adipose tissue of women with PCOS showed differences in the expression of key genes which have pathologic role in PCOS. These genes play critical role in systemic inflammation, insulin resistance and hyperandrogenism.

  • 46.
    Moreno Mejías, María del Mar
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    Investigate response to gluten in a diabetes mouse model2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Diabetes Mellitus Type I (DMT1) is a disease characterised by the autoimmune destruction of β-cells in the pancreas. As a result, glucose homeostasis is altered, and severe hyperglycaemia and hypoglycaemia episodes can occur, risking the patient's health and life. DMT1 prevalence has increased in the past years, being linked to a rise in obesity and Body Mass Index. Although treated patients have a relatively good quality of life, new treatment approaches and preventive strategies are being investigated. Previous studies have reported the protective impact a gluten-free diet has for DMT1 pathogenesis, but how it effectuates its effect is yet unknown. In this experiment, gene expression was studied in different parts of the gastrointestinal tract of nonobese diabetic mice (NOD mice) who received either a gluten-free or a gluten-containing diet. Genes studied codified for gluconeogenesis enzymes, glucose and amino acids transporters, gene expression regulatory enzymes and inflammation mediators. The methods used were RT-qPCR for gene expression quantification and the 2-ΔΔCT Method to analyse the data obtained. A One-Sample T-test and a Bonferroni correction were done, and Pck1, Fbp1, Gstm3 and Ifit1 were found to be differentially expressed between the gluten-free and control groups. A correlation between gluten intake and inflammation seems to exist, although further gene expression analysis should be performed in the liver to determine precisely how gluconeogenesis varies in both organs. If results were to be favourable, a gluten-free diet could be advised for individuals genetically predisposed to DMT1 to prevent the disease.

  • 47.
    Najmabadi, Sepideh
    Högskolan i Skövde, Institutionen för hälsa och lärande.
    Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein family member2019Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    Laing distal myopathy is inherited in an autosomal dominant manner usually before the age of five that initially involves the dorsiflexion in the ankles’ and in big toes to the finger extensors. Weakness of the flexor muscles in the neck is seen in most affected individuals and mild facial weakness is also often present. Hypertrophic or dilated cardiomyopathy, starting at birth to respectively second or third decade of life, is the symptom in the affected humans.This study performed on Drosophila melanogaster, has evaluated whether feeding MuRF1 enzyme (which has a similar role as ABBA enzyme) to Drosophila larvae, in different concentrations, will have a positive effect on the larvae’s muscular abilities through an analysis of their manifestation, the distance they manage to crawl and the time it takes for them to turn from a ventral up to dorsal up position.The result show no significant impact on larvae ability to turn or crawl between different groups fed with MuRF1 enzyme, nor between the two control groups, wild larvae and mutated larvae. Other studies have proven that there is a significant difference in muscular ability between wild and mutated larvae, so explanations to why this study did not manage to replicate these results were evaluated. The study found that how many days has passed since hatching has a significant impact on performance of turning and crawling for wild larvae that are not treated with enzyme.There are a number of improvement suggestions to the experimental design and the methodology to enable a proper evaluation of the research aim of this thesis. Future research on the topic should implement these and redo the experiments and measurements of this study. In addition, the quantity of larvae that reaches pupa stage should be captured to evaluate whether the MuRF1 enzyme has a positive impact on mutated larvae reaching pupation stage. The most important parts of the improvement proposals to measure the ability of larvae when they are about the same age, as this was proven with statistical significance to have an impact on crawling and turning.

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  • 48.
    Nordin, Anna
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    CTCF rearrangement in the context of Wnt signaling2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    CTCF is a DNA binding protein proposed to act both as a classical transcription factor and as a regulator of chromatin conformation. CTCF is essential in mammals, but the full extent of its involvement in gene regulation is unknown. The canonical Wnt signaling pathway, a vital determinant during development, drives specific gene expression programs. Connections have been made between CTCF and other developmental processes, but its actions in Wnt signaling remain elusive. The aim of this study was to explore whether CTCF binds DNA differentially as a result of Wnt signaling, and how this would affect gene expression. Cleavage Under Targets and Release Using Nuclease technology was used to map the genome-wide binding of CTCF to DNA in HEK293T cells in Wnt ON and OFF conditions. β-catenin and TCF/LEF knockout cell lines were also used to test CTCF’s reliance on these factors. Differentially bound loci were interrogated bioinformatically and correlated with gene expression data. Results revealed novel β-catenin and TCF/LEF dependent CTCF binding sites upon Wnt stimulation. Some loci had no apparent connections to gene regulation, while others correlated with differentially expressed Wnt target genes. Individual instances of Wnt-induced CTCF binding to enhancer regions of target genes suggested that CTCF mediated enhancer-promoter interactions, contributing to differential gene expression. Overall, the results indicate a new role for CTCF in Wnt signaling that warrants further investigation The generation of a CTCF knockout cell line would allow more detailed analysis of the requirement of CTCF for the Wnt signaling response. 

  • 49.
    Olson, Nasrine
    et al.
    Swedish School of Library and Information Science (SSLIS), University of Borås, Borås, Sweden.
    Bae, Juhee
    Högskolan i Skövde, Institutionen för informationsteknologi. Högskolan i Skövde, Forskningscentrum för Informationsteknologi.
    Biosensors-Publication Trends and Knowledge Domain Visualization2019Inngår i: Sensors, E-ISSN 1424-8220, Vol. 19, nr 11, artikkel-id 2615Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    The number of scholarly publications on the topic of biosensors has increased rapidly; as a result, it is no longer easy to build an informed overview of the developments solely by manual means. Furthermore, with many new research results being continually published, it is useful to form an up-to-date understanding of the recent trends or emergent directions in the field. This paper utilizes bibliometric methods to provide an overview of the developments in the topic based on scholarly publications. The results indicate an increasing interest in the topic of biosensor(s) with newly emerging sub-topics. The US is identified as the country with highest total contribution to this area, but as a collective, EU countries top the list of total contributions. An examination of trends over the years indicates that in recent years, China-based authors have been more productive in this area. If research contribution per capita is considered, Singapore takes the top position, followed by Sweden, Switzerland and Denmark. While the number of publications on biosensors seems to have declined in recent years in the PubMed database, this is not the case in the Web of Science database. However, there remains an indication that the rate of growth in the more recent years is slowing. This paper also presents a comparison of the developments in publications on biosensors with the full set of publications in two of the main journals in the field. In more recent publications, synthetic biology, smartphone, fluorescent biosensor, and point-of-care testing are among the terms that have received more attention. The study also identifies the top authors and journals in the field, and concludes with a summary and suggestions for follow up research.

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  • 50.
    Riazantseva, Lola
    Högskolan i Skövde, Institutionen för hälsovetenskaper.
    The genes controlling NHEJ in neuroblastoma2021Independent thesis Basic level (degree of Bachelor), 20 poäng / 30 hpOppgave
    Abstract [en]

    This study has been made in order to investigate the non-homologous end joining (NHEJ) pathway and the genes involved in this system, particularly their roles in neuroblastoma. The study aims to identify the expression levels of genes included in the pathway in neuroblastoma samples of varying clinical characteristics, classifications and behaviors to see how these differs. This opens the discussion and possibility to further research if the NHEJ pathway candidates for targeting therapeutically in order to enhance the outcomes of patients treated for the disease. The results of this study shows associations between XRCC6, XRCC5, PRKDC, XLF and XRCC4, which is involved in the NHEJ pathway, and poor outcomes, unfavorable clinical characteristics and behaviors of tumors in which these are highly expressed. XRCC5, XRCC6, and XRCC4 are suggested to be suitable biomarkers used to predict the treatment outcomes of neuroblastoma patients in order to investigate which ones that would benefit the most from which therapy. XLF and XRCC4 are also suggested to be targeted as an additional therapy method to the conventional ones in order to enhance the therapeutic effect of these, these would be targeted for knockdown to inhibit the NHEJ pathway causing an increased radio sensitivity. DCLRE1C has been associated to positive clinical characteristics and outcomes, it is suggested that these could be enhanced by upregulation of this gene using miR-888-5p inhibition. However, additional studies must be done in order to investigate the roles of these genes in neuroblastoma and the possibilities to target these for therapy further. 

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