A5050009863- Cancer-related molecular mechanisms research
- RNA modifications and cancer
- Metabolism, Diabetes, and Cancer
- MicroRNA in disease regulation
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Epigenetics and DNA Methylation
- Adipokines, Inflammation, and Metabolic Diseases
- Caveolin-1 and cellular processes
- Lipid metabolism and biosynthesis
- Genomics and Phylogenetic Studies
- Lipid metabolism and disorders
- Antioxidant Activity and Oxidative Stress
- Conducting polymers and applications
- Analytical Chemistry and Sensors
- Phosphodiesterase function and regulation
- Birth, Development, and Health
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Glutathione Transferases and Polymorphisms
- Protein Kinase Regulation and GTPase Signaling
- Genetics, Aging, and Longevity in Model Organisms
- Retinoids in leukemia and cellular processes
- Electrochemical Analysis and Applications
- Invertebrate Immune Response Mechanisms
Linköping University
2009-2024
Max Planck Institute of Immunobiology and Epigenetics
2013-2014
Linnaeus University
2008
Type 2 diabetes (T2D) is strongly linked to obesity and an adipose tissue unresponsive insulin. The insulin resistance due defective signaling, but details remain largely unknown. We examined signaling in adipocytes from T2D patients, contrary findings animal studies, we observed attenuation of activation mammalian target rapamycin (mTOR) complex with raptor (mTORC1). As a consequence, mTORC1 downstream effects were also affected T2D: feedback by signal-mediator receptor substrate-1 (IRS1)...
The global rise in obesity and steady decline sperm quality are two alarming trends that have emerged during recent decades. In parallel, evidence from model organisms shows paternal diet can affect offspring metabolic health a process involving tRNA-derived small RNA (tsRNA). Here, we report human acutely sensitive to nutrient flux, both terms of motility changes tsRNA. Over the course 2-week intervention, which first introduced healthy followed by rich sugar, increased stabilized at high...
A principal metabolic function of adipocytes is to synthesize triacylglycerol (TG) from exogenous fatty acids. The level acids has be tightly controlled in the adipocyte, as they can act detergents that rapidly dissolve plasma membrane, causing cell lysis if allowed accumulate. Fatty therefore have efficiently converted TG and stored central lipid droplet. We report intact primary oleic acid was taken up directly a novel subclass caveolae specifically contains protein perilipin. Isolated...
Reduced sensitivity to insulin in adipose, muscle, and liver tissues is a hallmark of type 2 diabetes. Animal models patients with diabetes exhibit elevated levels circulating retinol-binding protein (RBP4), RBP4 can induce resistance mice. However, little known about how affects signaling. We examined the mechanisms action primary human adipocytes. RBP4-treated adipocytes exhibited same molecular defects signaling, via IRS1 MAP kinase, as from Without affecting autophosphorylation receptor,...
ZnO nanorods with 80nm diameter and 700nm length grown on the tip of a borosilicate glass capillary (0.7μm in diameter) were used to create highly sensitive pH sensor for monitoring vivo biological process within single cells. The nanorods, functionalized by proton H3O+ hydroxyl OH− groups, exhibit pH-dependent electrochemical potential difference versus Ag∕AgCl microelectrode. was linear over large dynamic range (4–11), which could be understood terms change surface charge during...
Caveolae are plasma membrane invaginations with several functions, one of which appears to be organize receptor mediated signalling. Here we report that in primary human subcutaneous adipocytes the insulin was localized caveolae by electron microscopy/immunogold detection and isolating from membranes. Part substrate 1 (IRS1), immediate downstream signal mediator, colocalized caveolae, as demonstrated immunofluorescence microscopy, immunogold microscopy transfected recombinant HA‐IRS1. In...
Insulin resistance is a primary characteristic of type 2 diabetes and likely causally related to the pathogenesis disease. It result defects in signal transduction from cell surface receptor insulin target effects. We found that insulin-stimulated phosphorylation serine 307 (corresponding 302 murine sequence) immediate downstream mediator protein receptor, substrate-1 (IRS1), required for efficient signaling this attenuated adipocytes patients with diabetes. Inhibition by rapamycin mimicked...
Insulin resistance is a cardinal feature of type 2 diabetes and also consequence trauma such as surgery. Directly after surgery cell isolation, adipocytes were insulin resistant, but this was reversed overnight incubation in 10% CO at 37 °C. Tyrosine phosphorylation the receptor substrate (IRS)1 sensitive, protein kinase B (PKB) downstream metabolic effects exhibited that by incubation. MAP‐kinases ERK1/2 p38 strongly phosphorylated surgery, dephosphorylated during reversal resistance....
We have examined the concentration of β-carotene in fat isolated abdominal subcutaneous adipocytes obtained from lean (BMI<23 kg/m2), non-obese with higher BMI (23≤BMI<28 obese (BMI≥28 and a group subjects type 2 diabetes. The was 50% lower obese/diabetic groups compared groups. Interestingly, total amount adipocyte stores each subject constant among all Triacylglycerol constituted 92±1% (by weight) lipids this increased to 99±2% diabetes (p<0.05). cholesteryl esters cases <0.1 g per 100...
In adipocytes, PDE3B (phosphodiesterase 3B) is an important regulatory effector in signalling pathways controlled by insulin and cAMP-increasing hormones. Stimulation of 3T3-L1 adipocytes with or the β3-adrenergic receptor agonist CL316243 (termed CL) indicated that preferentially phosphorylated/activated associated internal membranes (endoplasmic reticulum/Golgi), whereas CL caveolae. siRNA (small interfering RNA)-mediated KD (knockdown) CAV-1 (caveolin-1) resulted down-regulation...
Caveolae are nearly ubiquitous plasma membrane domains that in adipocytes vary size between 25 and 150 nm. They constitute sites of entry into the cell as well platforms for signalling. We have previously reported membrane‐associated caveolae lack surface access can be identified by electron microscopy. now report identification, after density gradient ultracentrifugation, a subclass very high‐density apparently closed were not labelled protein labelling intact cells. These contained...
Insulin resistance and type 2 diabetes (T2D) are closely linked to obesity. Numerous prospective studies have reported on weight gain, insulin resistance, signaling in experimental animals, but not humans. We examined adipocytes from lean volunteers, before at the end of a 4-wk period consuming fast-food, high-calorie diet that led gain. also patients with T2D. During diet, subjects gained 10% body 19% total fat, stayed (body mass index = 24.3 kg/m2) developed moderate systemic resistance....
In both insects and vertebrates, each olfactory sensory neuron (OSN) expresses one odorant receptor (OR) from a large genomic repertoire. How is specified tantalizing question addressing fundamental aspects of cell differentiation. Here, we demonstrate that the corepressor Atrophin (Atro) segregates OR gene expression between OSN classes in Drosophila. We show knockdown Atro result either loss or gain broad set ORs. Each phenotypic group correlated with two opposing Notch fates, responding,...
Small RNA (sRNA) sequencing has been critical for our understanding of many cellular processes, including gene regulation. Nonetheless, the varying biochemical properties sRNA, such as 5´ nucleotide modifications, make sRNA subspecies incompatible with common protocols sequencing. Here we describe 5XP-seq that outlines a novel strategy captures more complete picture sRNA. By tagging 5´P during library preparation, combines an open approach includes all types 5'-terminal modifications (5´X),...
Aims, Patients & Methods Dietary factors may regulate the epigenome. We aimed to explore whether a diet intervention, including excess sugar, affects methylome in human sperm, and describe sperm methylome. used Whole Genome Bisulfite Sequencing (WGBS) analyze DNA methylation taken at three time points from 15 males during intervention; i) baseline, ii) after one week on standardized diet, iii) an additional high-sugar providing 150% of their estimated total energy expenditure.
Aims: Increasing concentrations of dietary sugar results in a linear accumulation triglycerides male Drosophila, while inducing U-shaped obesity response their offspring. Here, using combination proteomics and small RNA (sRNA) sequencing, we aimed at understanding the molecular underpinning sperm for such plasticity. Results: Proteomic analysis seminal vesicles revealed that increasing resulted bell-shaped induction proteins involved metabolic/redox regulation. Using stains vivo redox...
Abstract Early‐life stress can result in life‐long effects that impact adult health and disease risk, but little is known about how such programming established maintained. Here, we show epigenetic memories be initiated the Drosophila embryo before major wave of zygotic transcription, higher‐order chromatin structures are established. An early short heat shock results elevated levels maternal miRNA reduced a subgroup genes stage 5 embryos. Using Dicer‐1 mutant, stress‐induced decrease one...
Abstract Motivation Feature-based counting is commonly used in RNA-sequencing (RNA-seq) analyses. Here, sequences must align to target features (like genes or non-coding RNAs) and related with different compositions are counted into the same feature. Consequently, sequence integrity lost, making results less traceable against raw data. Small RNA (sRNA) often maps multiple shows an incredible diversity form function. Therefore, applying feature-based strategies may increase risk of...
Summary Preconception parental environment can reproducibly program offspring phenotype without altering the DNA sequence, yet mechanisms underpinning this ‘epigenetic inheritance’ remains elusive. Here, we demonstrate existence of an intact piRNA-pathway in mature Drosophila sperm and show that pathway modulation alters gene transcription a sequence-specific manner. We map dynamic small RNA content developing find carry highly distinct cargo. By biochemical pulldown, identify subset bound...