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Fluid transport in the perivascular space by the glia-lymphatic (glymphatic) system is important for the removal of solutes from the brain parenchyma, including peptides such as amyloid-beta which are implicated in the pathogenesis of Alzheimer’s disease. The glymphatic system is highly active in the sleep state and under the influence of certain of anaesthetics, while it is suppressed in the awak
Neurogenesis, the production of new neurons from neural stem cells, dramatically decreases during aging concomitantly with increased inflammation both systemically and in the brain. However, the precise role of inflammation and whether local or systemic factors drive the neurogenic decline during aging is poorly understood. Here, we identify CXCR5/5/CXCL13 signaling as a novel regulator of neuroge
The fate options of hematopoietic stem cells (HSCs) include self-renewal, differentiation, migration, and apoptosis. HSCs self-renewal divisions in stem cells are required for rapid regeneration during tissue damage and stress, but how precisely intracellular calcium signals are regulated to maintain fate options in normal hematopoiesis is unclear. S100A6 knockout (KO) HSCs have reduced total cell
Acute myeloid leukemia (AML) is defined by an accumulation of immature myeloid blasts in the bone marrow. To identify key dependencies of AML stem cells in vivo, here we use a CRISPR-Cas9 screen targeting cell surface genes in a syngeneic MLL-AF9 AML mouse model and show that CXCR4 is a top cell surface regulator of AML cell growth and survival. Deletion of Cxcr4 in AML cells eradicates leukemia c
Aberrantly expressed cytokines in the bone marrow (BM) niche are increasingly recognized as critical mediators of survival and expansion of leukemic stem cells. To identify regulators of primitive chronic myeloid leukemia (CML) cells, we performed a high-content cytokine screen using primary CD34+ CD38low chronic phase CML cells. Out of the 313 unique human cytokines evaluated, 11 were found to ex
Malignant melanoma is among the most aggressive skin cancers and it has among the highest metastatic potentials. Although surgery to remove the primary tumor is the gold standard treatment, once melanoma progresses and metastasizes to the lymph nodes and distal organs, i.e., metastatic melanoma (MM), the usual outcome is decreased survival. To improve survival rates and life span, advanced treatme
As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better ex
OBJECTIVE: While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide 1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortalit
Erythroid cell commitment and differentiation proceed through activation of a lineage-restricted transcriptional network orchestrated by a group of well characterized genes. However, the minimal set of factors necessary for instructing red blood cell (RBC) development remains undefined. We employed a screen for transcription factors allowing direct lineage reprograming from fibroblasts to induced
Neurotensin regulates both satiety and breast cancer growth in the experimental setting, but little is known about its role in the development of breast cancer or cardiometabolic disease in humans.
The pathogenesis of prostate cancer is unclear, although experimental evidence implicates androgens as playing an important role. Infertile men frequently suffer from some degree of hypogonadism and may hence be hypothesized to be at lower risk of developing prostate cancer than fertile men. To test this hypothesis, we conducted a case-control study nested within "the Malmö Diet and Cancer Study"
Sleep has a major impact on our wellbeing and how we perform.
Improvements in colorectal cancer (CRC) detection and treatment have led to greater numbers of CRC survivors, for whom there is limited evidence on which to provide dietary guidelines to improve survival outcomes. Higher intake of red and processed meat and lower intake of fibre are associated with greater risk of developing CRC, but there is limited evidence regarding associations with survival a
Catalytic active phases are often separated from inactive ones by their appearance/removal in heating/cooling experiments. Such experiments can reveal ignition, extinction, and often an associated hysteresis. The corresponding behavior and hysteresis under rapid gas composition changes in the milliseconds regime remain largely unexplored. However, such experiments can potentially be highly rewardi
A cell’s ability to sense and respond to the mechanical properties of the extracellular matrix (ECM) is essential for maintaining tissue homeostasis, and its disruption contributes to diseases such as fibrosis, cardiovascular disorders, and cancer. Effective mechanical coupling between the plasma membrane, the underlying filamentous actin (F-actin) cytoskeleton, and integrin-based adhesion complex
Background: Virtual imaging trials (VITs) are in silico studies that simulate medical imaging and disease processes, offering a cost-effective and reproducible addition to traditional imaging trials. While VITs are well established in breast imaging, most existing implementations simulate imaging based on static anatomical models, capturing only a single time point. This limits their ability to st
The International Agency for Research on Cancer has recently classified occupational exposure as a firefighter as carcinogenic (group 1A). Even though the occupation of firefighter is associated with high exposure to pollutants, it is challenging to carry out exposure studies to assess health risks due to the extreme conditions associated with firefighting. Routine monitoring of occupational expos
BACKGROUND AND AIMS: Atherosclerotic plaques are the leading cause of cardiovascular events. Single-cell approaches have identified diverse human plaque cell phenotypes but their spatial distribution and interactions remain unclear. Here, intercellular communication patterns in human plaque microenvironments were mapped to reveal novel targets to prevent atherosclerotic events.METHODS: Spatial tra
