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.

Spirometry is a lung function test, used to diagnose for example asthma and chronic obstructive pulmonary disease. The reference values for spirometry are determined by gender, height, age, and ethnicity. Swedish references are used for all patients in Sweden regardless of ethnic background. The aim of this study was to evaluate whether the Arab population living in Sweden can perform a spirometry examination with Swedish reference values. The study included seven Arab patients and 13 Swedish patients. Each patient was examined in dynamic (slow and forced), static spirometry, diffusion capacity and finally a reversibility test. The patient performed at least three maneuvers for each part of the test, where the patient breathed in and out maximally using several different techniques. Measurements examined were forced expiratory volume in 1 second, the ratio of forced expiratory volume in 1 second by forced vital capacity, vital capacity, and total lung capacity. A comparison between the spirometry value total lung capacity, was compared between the two methods static spirometry and diffusion capacity. All these values had a p-value above the significance level 0.05. Thus, there was no statistical evidence that there is a difference between the Arabic and Swedish population. According to the result of this study, the Arab population can undergo spirometry examinations with the existing Swedish reference values that exist. However, this is a strong conclusion for few individuals. Hence more research and studies are in need in the future.

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This master thesis studies how a morphological reduction aects theperformance of a biophysically detailed model of a medium spiny neuron. Themorphological reduction is done using a MATLAB toolbox developed forautomatic 3-dimensional morphological reduction. Two versions of the toolboxare developed in which dierent criteria are used during the merge. Theevaluation of the two toolboxes shows that keeping the absolute distance to thesoma of the branching points and the surface area of the dendrites gives a moreaccurate result than if these criteria are not used. These criteria are implementedin Toolbox 2. In total 8 models with dierent maximal compartment length arethen constructed using Toolbox 2. The number of compartments in the resultingmodels range from 1/2 to 1/10 of the compartments in the original model. Furtherthe performance of the reduced models are evaluated against the original model.The results of this evaluation shows that an increasing compartment length givesa decrease in consistency with the response of the original model. However theresponse of all models are largely similar to the original model. / I detta examensarbete studeras hur en biofysikt detaljerad modell av en mediumspiny neuron (direkt oversatt "medellang taggig neuron") paverkas av en reduceringav dess strukturella komplexitet. Denna strukturella reduktion gar till saatt fragmenten som formar modellen slas samman och bildar nya fragment. Denya fragmenten far da en langd motsvarande summan av de sammanslagna fragmentenslangd. For att underlatta den strukturella reduktionen utvecklas ocksa enverktygslada till MATLAB. Verktygsladan ar byggd for att automatiskt reduceraden 3-dimensionella strukturen av en modell baserat pa vissa kriterier. Tva versionerav vertygsladan utvecklas i vilka kriterierna som anvands vid reduktionenskiljer sig fran varandra. Utvarderingen av de bada versionerna visar att omavstandet mellan cellkarnan och de dendritiska forgreningspunkterna samt dentotala dendritiska arean ar konstant sa uppnas ett battre resultat an om dessakriterier inte uppfylls. Dessa kriterier implementeras i den andra versionen avvertygsladan, Toolbox 2. Med hjalp av Toolbox 2 tillverkas sedan 8 reducerademodeller som alla har reducerad struktur men olika maximal langd pa fragmenten.De reducerade Modellerna ar uppbyggda av mellan 1/2 och 1/10 av antalet fragmenti den ursprungliga modellen. De reducerade modellerna jamfors sedan medden ursprungliga modellen. Resultatet av jamforelsen visar att med okad fragmentlangd kommer ocksa en gradvis storre avvikelse fran den ursprungliga modellen.Detta till trots gav alla reducerade modeller en overraskande bra respons ialla test de utsattes for.

Genome-wide association studies (GWAS) has been in the heartof medical research for the last 5 years. These studies seek forcommon variants in the genome that are linked to risk for commoncomplex diseases (CCDs). Although GWAS has defined a numberof interesting genetic loci for a range of CCDs, the current GWASanalysis has limitation such as investigating the DNA variantsone-by-one focusing on the most significant DNA variants. As aconsequence, most risk variants for CCDs are, in my belief, stillhidden in the GWAS data. Herein, I use a method of GWASanalysis that considers risk-enrichment for groups of functionallyassociated genes defined by for example gene networks, believedto play a role in CCDs.In this method, a set of expression SNP (single nucleotidepolymorphism) was selected from genes which are known to berelated to coronary artery disease (CAD) in a way that a singleeSNP was chosen for each gene. Then using the data availablefrom the International HapMap Project and a GWAS data available,it is possible to find SNPs which are in strong linkage withthe initial set, which we call it expanded set. Depending on theassociation of the initial set to the CAD, expanded set can showan enrichment score greater or smaller compared to the null distributionset of SNPs with same properties of the expanded set.In conclusions, CCDs are not a consequence of isolated geneticvariants/genes in isolated pathways but instead sets of geneticvariants/genes acting in conjunction, cause CAD. Genetic riskenrichment analysis is a fairly simple and straightforward methodto determine to what extent a group of functionally associatedgenetic variants/genes are enriched for a given CCD. In addition,this analysis can perhaps help to decipher some of the 90-85% ofrisk variation in populations that remains unaccounted.

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