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VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics

Insulin resistance and lower muscle quality (strength divided by mass) are hallmarks of type 2 diabetes (T2D). Here, we explore whether alterations in muscle stem cells (myoblasts) from individuals with T2D contribute to these phenotypes. We identify VPS39 as an important regulator of myoblast differentiation and muscle glucose uptake, and VPS39 is downregulated in myoblasts and myotubes from indi

Lung Metastases - Diagnostic, Prognostic and Molecular Aspects with Focus on Colorectal Cancer

In Sweden 4200 patients are diagnosed with lung cancer and 6500 patients with colorectal cancer (CRC) annually. The lungs are a common site for metastases. Immunohistochemistry (IHC) is a helpful aid in diagnostics of a pulmonary tumour. Selected patients with metastatic CRC undergo pulmonary metastasectomy and knowledge about which patients benefit from it is important. In this thesis IHC markers

Algorithms and Methods for Robust Processing and Analysis of Mass Spectrometry Data

Liquid chromatography-mass spectrometry (LC-MS) and mass spectrometry imaging (MSI) are two techniques that are routinely used to study proteins, peptides, and metabolites at a large scale. Thousands of biological compounds can be identified and quantified in a single experiment with LC-MS, but many studies fail to convert this data to a better understanding of disease biology. One of the primary

Harnessing the ECM Microenvironment to Ameliorate Mesenchymal Stromal Cell-Based Therapy in Chronic Lung Diseases

It is known that the cell environment such as biomechanical properties and extracellular matrix (ECM) composition dictate cell behaviour including migration, proliferation, and differentiation. Important constituents of the microenvironment, including ECM molecules such as proteoglycans and glycosaminoglycans (GAGs), determine events in both embryogenesis and repair of the adult lung. Mesenchymal

SARs for the antiparasitic plant metabolite pulchrol. : 3. Combinations of new substituents in A/B-rings and A/C-rings

The natural products pulchrol and pulchral, isolated from the roots of the Mexican plant Bourreria pulchra, have previously been shown to possess an antiparasitic activity toward Trypanosoma cruzi, Leishmania braziliensis and L. amazonensis, protozoa responsible for the Chagas disease and leishmaniasis. These infections have been classified as neglected diseases, and still require the development

Yield of additional metabolic studies in neurodevelopmental disorders

The timing and yield of metabolic studies for patients with neurodevelopmental disorders is a matter of continuing debate. We determined the yield of additional or repeated metabolic studies in patients with neurodevelopmental disorders. Patients referred to a tertiary diagnostic center for patients with unexplained neurodevelopmental disorders were included. Initial metabolic studies had been per

Two mass-spectrometric techniques for quantifying serine enantiomers and glycine in cerebrospinal fluid : Potential confounders and age-dependent ranges

BACKGROUND: The recent discovery and specific functions of D-amino acids in humans are bound to lead to the revelation of D-amino acid abnormalities in human disorders. Therefore, high-throughput analysis techniques are warranted to determine D-amino acids in biological fluids in a routine laboratory setting. METHODS: We developed 2 chromatographic techniques, a nonchiral derivatization with chira

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- In certain inborn errors of metabolism, an allogeneic stem cell transplantation is able to prevent disease progression. - This is only possible when the stem cell transplantation (SCT) is performed early in life, before cerebral involvement has occurred. - In addition to bone marrow and peripheral blood, unrelated umbilical cord blood appears to be an effective stem cell source as well. - There

Cerebrospinal fluid d-serine and glycine concentrations are unaltered and unaffected by olanzapine therapy in male schizophrenic patients

N-Methyl d-aspartate (NMDA)-receptor hypofunction has been implicated in the pathophysiology of schizophrenia and d-serine and glycine add-on therapy to antipsychotics has shown beneficial effects in schizophrenic patients. Nevertheless, previous studies have not shown consistently altered d-serine concentrations in cerebrospinal fluid (CSF) of schizophrenic patients. To confirm and extend these r

Setting the foundations: Individual rights, public interest, scientific research and biobanking

The EU lacks competence to regulate research in a comprehensive manner, yet furthering research is one of its aspirations. Data protection, however, is an area within which the EU has legislated extensively. During the development of the General Data Protection Regulation (GDPR), an important issue to tackle was how to balance the EU aspirations, on the one hand, with limited competences in resear

Faint Rapid Red Transients from Neutron Star - CO White Dwarf Mergers

Mergers of neutron stars (NS) and white dwarfs (WD) may give rise to observable explosive transientevents. We use 3D hydrodynamical (SPH) simulations, as well as 2D hydrodynamical-thermonuclearsimulations (using the FLASH AMR code) to model the disruption of CO-WDs by NSs, whichproduce faint transient events. We post-process the simulations using a large nuclear network andmake use of the SuperNu