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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
Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimer's disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel
Ischemic stroke, caused by middle cerebral artery occlusion, leads to long-lasting formation of new striatal neurons from neural stem/progenitor cells (NSPCs) in the subventricular zone (SVZ) of adult rodents. Concomitantly with this neurogenic response, SVZ exhibits activation of resident microglia and infiltrating monocytes. Here we show that depletion of circulating monocytes, using the anti-CC
A method for synthesizing representative weather data for future climate out of regional climate models (RCMs) was introduced previously for the energy simulation of buildings (Nik, 2016). The method suggests creating one typical and two extreme data sets based on the distribution of the outdoor dry bulb temperature (Tdrybulb). This article extends the application of such weather data in the hygro
Growth orientation is important for understanding why some young firms grow but not others, but research remains silent on the intermediary mechanisms mediating the growth orientation–firm growth relationship. We study 282 Swedish firms and show that various innovative activities mediate the growth orientation–firm growth relationship. These mediating innovative activities include informal activit
