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Soaking small molecules into the solvent channels of protein crystals is the most common method of obtaining crystalline complexes with ligands such as substrates or inhibitors. The solvent channels of some protein crystals are large enough to allow the incorporation of macromolecules, but soaking of protein guests into protein crystals has not been reported. Such protein host crystals (here given
Splicing and translation are two of the key steps of post-transcriptional regulation of gene expression. Their tight regulation is essential for development, whereas their deregulation is involved in cancer pathogenesis. Nevertheless, many of the molecular mechanisms controlling these processes are still unknown. Hence, the main aim of this thesis is to elucidate novel regulatory mechanisms that a
Acute myeloid leukemia (AML) is a highly heterogeneous blood disease which is characterized by different mutations and chromosomal rearrangements. Nearly 60% of genetic alterations have been found in AML patients involve in signaling pathways including signaling of tyrosine kinase receptor FLT3. FLT3 mutations emerged as one of the most common mutations in AML which represent around 35% of all AML
Objectives: Ventilator-associated pneumonia (VAP) is difficult to diagnose using clinical criteria and no biomarkers have yet been proved to be sufficiently accurate. The use of the neutrophil-derived Heparin-binding protein (HBP) as a biomarker for pneumonia was investigated in this exploratory case–control study in two intensive care units at a tertiary referral hospital. Methods: Patients with
The hematopoietic microenvironment, also referred to as hematopoietic niche, is a functional three-dimensional (3D) unit of the bone marrow (BM) that planar culture systems cannot recapitulate. Existing limitations of 2D protocols are driving the development of advanced 3D methodologies, capable of superior modeling of the native organization and interactions between hematopoietic cells and their
ApoE is a well-known lipid-binding protein that plays a main role in the metabolism and transport of lipids. More recently, apoE-derived peptides have been shown to exert antimicrobial effects. Here, we investigated the antibacterial activity of apoE using in vitro assays, advanced imaging techniques, and in vivo mouse models. The formation of macromolecular complexes of apoE and endotoxins from G
As no one symptom can predict disease severity or the need for dedicated medical support in coronavirus disease 2019 (COVID-19), we asked whether documenting symptom time series over the first few days informs outcome. Unsupervised time series clustering over symptom presentation was performed on data collected from a training dataset of completed cases enlisted early from the COVID Symptom Study
Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case-control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 year
Purpose: Improved early diagnosis and determination of aggressiveness of prostate cancer (PC) is important to select suitable treatment options and to decrease over-treatment. The conventional marker is total prostate specific antigen (PSA) levels in blood, but lacks specificity and ability to accurately discriminate indolent from aggressive disease. Experimental design: In this study, we sought t
Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highli
Based on a nationwide register data we recently reported a link between male infertility and increased risk of early onset prostate cancer. However, mortality due to prostate cancer, which can be regarded as the ultimate proxy for its clinical significance, especially in the context of over-diagnosis and over-treatment, could not be explored in the previous study, since the follow-up period in mos
α-Synuclein is a membrane-interacting protein involved in Parkinson’s disease. Here we have investigated the co-association of α-synuclein and lipids from ganglioside-containing model membranes. Our study relies on the reported importance of ganglioside lipids, which are found in high amounts in neurons and exosomes, on cell-to-cell prion-like transmission of misfolded α-synuclein. Samples taken a
The COVID-19 pandemic has led to enhanced hygiene procedures and use of personal protective equipment, but also to increased attention to occupational skin disease in healthcare workers. The occurrence of hand and facial skin disease in > 5,000 Swedish healthcare workers was investigated in a questionnaire survey. Levels of skin exposure related to hygiene procedures and personal protective equipm
Leveraging the biocatalytic machinery of living organisms for fabricating functional bioelectronic interfaces, in vivo, defines a new class of micro-biohybrids enabling the seamless integration of technology with living biological systems. Previously, we have demonstrated the in vivo polymerization of conjugated oligomers forming conductors within the structures of plants.Here, we expand this conc
Background & Aims: There is an unclear association between intake of fish and long-chain n-3 polyunsaturated fatty acids (n-3 LC-PUFAs) and colorectal cancer (CRC). We examined the association between fish consumption, dietary and circulating levels of n-3 LC-PUFAs, and ratio of n-6:n-3 LC-PUFA with CRC using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) coh
Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic lo
