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The casein kinase 1A1 gene (CSNK1A1) is a putative tumor suppressor gene located in the common deleted region for del(5q) myelodysplastic syndrome (MDS). We generated a murine model with conditional inactivation of Csnk1a1 and found that Csnk1a1 haploinsufficiency induces hematopoietic stem cell expansion and a competitive repopulation advantage, whereas homozygous deletion induces hematopoietic s
Efforts to develop more effective therapies for acute leukemia may benefit from high-throughput screening systems that reflect the complex physiology of the disease, including leukemia stem cells (LSCs) and supportive interactions with the bone marrow microenvironment. The therapeutic targeting of LSCs is challenging because LSCs are highly similar to normal hematopoietic stem and progenitor cells
Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by an impaired epidermal barrier, dysregulation of innate and adaptive immunity, and a high susceptibility to bacterial colonization and infection. In the present study, bacterial biofilm was visualized by electron microscopy at the surface of AD skin. Correspondingly, Staphylococcus aureus (S. aureus) isolates from lesion
We used an invivo small hairpin RNA (shRNA) screening approach to identify genes that are essential for MLL-AF9 acute myeloid leukemia (AML). We found that Integrin Beta 3 (Itgb3) is essential for murine leukemia cells invivo and for human leukemia cells in xenotransplantation studies. In leukemia cells, Itgb3 knockdown impaired homing, downregulated LSC transcriptional programs, and induced diffe
In this issue of Cancer Cell, Skrtic et al. demonstrate that inhibition of mitochondrial ribosomes with tigecycline, a known antimicrobial, selectively kills leukemia cells. This finding highlights the metabolic susceptibility of leukemia cells to mitochondrial translational inhibition and identifies a compound with significant efficacy in an in vivo preclinical model.
We analysed cancer risks in patients with urinary tract stones but some features of the generated results alarmed us about possible surveillance bias, which we describe in this report. We used nationwide Swedish hospital records to identify patients with urinary tract stones (N = 211,718) and cancer registration data for cancer patients for years 1987 to 2012. Standardized incidence ratios (SIRs)
Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apopt
Increasing global production fragmentation allows for emission displacement, which may counteract advanced nation’s domestic reductions of production-related carbon emissions. Consequently, input-output analysis has become a common tool to measure countries’ carbon footprint and emission trade balances based on national consumption instead of domestically produced CO2 emissions. Nevertheless, trad
Många sjukdomar som inte beror på virus eller bakterier kopplas ofta till genetik. Vår förståelse kring hur gener påverkar vår hälsa har ökat dramatiskt med molekylärbiologins framfart. Sedan 1930-talet har det utvecklats nya tekniker för att tyda gener och dess DNA. Länge var gener ett ganska abstrakt koncept, man visste att det fanns något som fördes vidare genom generationerna men inte exakt vaTo find true genetic associations in complex diseases, such as allergic rhinitis and chronic rhinosinusitis, is a difficult task. Both are polygenetic diseases where it is believed that genetic variation in several genes make up their phenotypes. In addition, the environment of the affected individuals also play an important role, further obscuring eventual associations. Today most genetic associa
The studies presented were designed to highlight the impact of pancreatic enzymes on glycemic control and insulin response. Blood glucose and plasma insulin levels were monitored after intravenous, oral or direct gut glucose tolerance tests (GTT) in 6 pigs with an intact gastrointestinal tract and in 12 pigs following duodenal-jejunal bypass (DJB) surgery. In the intact pigs, pancreatic enzymes (C
Occupational exposure to soot, rich in polycyclic aromatic hydrocarbons (PAH), has been associated with increased risk of cardiovascular disease (CVD). However, our knowledge about PAH exposure and early markers of CVD remains limited. In this cross-sectional study of 151 chimney sweeps and 152 controls, we investigated occupational exposure to PAH and early markers of CVD. Blood pressure (BP) (ch
The physical properties of polycrystalline materials depend on their microstructure, which is the nano- to centimeter scale arrangement of phases and defects in their interior. Such microstructure depends on the shape, crystallographic phase and orientation, and interfacing of the grains constituting the material. This article presents a new non-destructive 3D technique to study centimeter-sized b
A major hallmark of Parkinson's disease (PD) is the presence of Lewy bodies (LBs) in certain neuronal tissues. LBs are protein-rich inclusions, in which α-synuclein (α-syn) is the most abundant protein. Since these inclusions are not present in healthy individuals, despite the high concentration of α-syn in neurons, it is important to investigate whether natural control mechanisms are present to e
Endohedral metallofullerenes, formed by encaging Gd inside fullerenes like C80, can exhibit enhanced proton relaxitivities compared with other Gd-chelates, making them the promising contrast agents for magnetic resonance imaging (MRI). However, the underlying key energy scales of Gd x Sc3-x N@C80 (x = 1-3) remain unclear. Here, we carry out resonant inelastic X-ray scattering (RIXS) experiments on
High chromium white cast irons (HCCI) with high hardness and abrasiveness owing to a particular combination of hard primary and eutectic carbides were used as workpiece materials for longitudinal turning with binderless cBN (bcBN) and high cBN (hcBN) tools. The materials with low and high Si content were used in as-cast and quenched states. Binderless cBN is prone to cratering and flank wear, whil
The AGATA (Advanced GAmma Tracking Array) tracking detector is being designed to far surpass the performance of the previous generation, Compton-suppressed arrays. In this paper, a characterization of AGATA is provided based on data from the second GSI campaign. Emphasis is placed on the proper corrections required to extract the absolute photopeak efficiency and peak-to-total ratio. The performan
The unified knowledge on power converter design and manufacturing technology establishes a powerful tool, where the cost and topology realization can be analyzed simultaneously. This paper collects the design practice and cost estimation of various components in a power electronics converter and unites that to a choice of the assembling and manufacturing processes and resulting cost of the complet
