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Xenograft studies indicate that some solid tumors and leukemias are organized as cellular hierarchies sustained by cancer stem cells (CSCs). Despite the promise of the CSC model, its relevance in humans remains uncertain. Here we show that acute myeloid leukemia (AML) follows a CSC model on the basis of sorting multiple populations from each of 16 primary human AML samples and identifying which co
BACKGROUND: Myelodysplastic syndromes are clinically heterogeneous disorders characterized by clonal hematopoiesis, impaired differentiation, peripheral-blood cytopenias, and a risk of progression to acute myeloid leukemia. Somatic mutations may influence the clinical phenotype but are not included in current prognostic scoring systems.METHODS: We used a combination of genomic approaches, includin
Though many individual transcription factors are known to regulate hematopoietic differentiation, major aspects of the global architecture of hematopoiesis remain unknown. Here, we profiled gene expression in 38 distinct purified populations of human hematopoietic cells and used probabilistic models of gene expression and analysis of cis-elements in gene promoters to decipher the general organizat
The frequencies of antigen-specific CD4+ T cells in samples of human tissue have been difficult to determine accurately ex vivo, particularly for autoimmune diseases such as multiple sclerosis or type 1 diabetes. Conventional approaches involve the expansion of primary T cells in vitro to increase the numbers of cells, and a subsequent assessment of the frequencies of antigen-specific T cells in t
Ocean acidification (OA) describes a change in the ocean's carbonate chemistry. Whereas its chemical processes are largely understood, the biological and socioeconomic consequences particularly in relation to fisheries are less known. Norway is a major fishing nation worldwide and is potentially affected by OA. To improve the understanding of the socioeconomic consequences of OA, we conducted a ri
CD8(+) T cells in chronic viral infections such as HIV develop functional defects including loss of interleukin-2 (IL-2) secretion and decreased proliferative potential that are collectively termed 'exhaustion'. Exhausted T cells express increased amounts of multiple inhibitory receptors, such as programmed death-1 (PD-1), that contribute to impaired virus-specific T cell function. Although revers
Haemophilia A. Thirty-one pregnant women, obligate or probable carriers of haemophilia A, requested prenatal diagnosis if sex determination showed the foetus to be a male. In 11 of the 31 cases the foetuses were females; in two, the genetic variant of the disease rendered prenatal diagnosis impossible; and in two, the mother aborted spontaneously. From the remaining 16 male foetuses, blood samples
We present a systematic comparison of the results from our non-equilibrium Green's function formalism with a large number of AlGaAs-GaAs terahertz quantum cascade lasers previously published in the literature. Employing identical material and simulation parameters for all samples, we observe that the discrepancies between measured and calculated peak currents are similar for samples from a given g
Heart transplantation (HT) is a life saving procedure, but a limited donor supply forces the surgeons to prioritize the recipients. The understanding of factors that predict mortality could help the doctors with this task. The objective of this study is to find locally optimal feature sets to predict survival of HT patients for different time periods. To this end, we applied logistic regression to
Planeter är mycket vanliga i vår galax. De senaste 20 åren har man upptäckt att de flesta solliknande stjärnor har planeter kretsande omkring sig. Man vet också att det finns en stor variation av exoplaneter. Runt 50\% av alla solliknande stjärnor har superjordar (planeter med en massa eller radie mellan jordens och Neptunus) kretsande tätt intill sig vilket gör solsystemet otypiskt. Man har hittaOver the past 20 years we have discovered that exoplanets are common in the Galaxy, and are far more diverse than anyone expected. Half of all Sun-like stars are accompanied by at least one super-Earth (a planet with a size between Earth and Neptune), many planets have very high eccentricities indicative of a dynamical origin, and a small fraction of stars are accompanied by hot Jupiters, whose or
Targeted genome editing technology can correct the sickle cell disease mutation of the β-globin gene in hematopoietic stem cells. This correction supports production of red blood cells that synthesize normal hemoglobin proteins. Here, we demonstrate that Transcription Activator-Like Effector Nucleases (TALENs) and the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/Cas9 nuclease
We examined the efficiency, specificity, and mutational signatures of zinc finger nucleases (ZFNs), transcriptional activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 systems designed to target the gene encoding the transcriptional repressor BCL11A, in human K562 cells and human CD34+progenitor cells. ZFNs and TALENs were delivere
Nitric oxide (NO) acts as a modulator of neuronal transmission in mature neuronal systems, including the retina. Recently, NO has also been suggested to have a trophic function during development. We examined immunocytochemically the distribution of NO-producing cells in developing and transplanted rabbit retinas. An antibody detecting the neuronal isoform of its biosynthetic enzyme, nitric oxide
The evoked release of purines from rabbit retinae preloaded with [(3)H]adenosine was studied in vitro. Potassium (8.6-43.6 mM) and ouabain (1 or 10 microM) increased the release of radioactivity in a concentration-dependent manner. The K(+)-evoked release was significantly reduced when the superfusion was carried out at 2-4 degrees C. The effect of K(+) (8.6, 13.6 and 23.6 mM) and of ouabain (1 mi
The distribution of neurons expressing preproenkephalin (PPE) mRNA in the brain of the salmon was investigated by means of non-radioactive in situ hybridization, and directly compared with the distribution of enkephalin-immunoreactive (ENKir) neurons. This approach, utilized here for the first time in a non-mammalian vertebrate for the identification of neurons containing opioid peptides, permitte
The distribution of neurones expressing neuropeptide Y (NPY) mRNA in the brain of the goldfish was investigated using a non-radioactive in situ hybridization technique. Neurones expressing NPY mRNA were located in cell groups previously shown to exhibit NPY immunoreactivity in the ventral telencephalon, thalamus, optic tectum and a region adjacent to the locus coeruleus. In addition, neurones expr
The expression of mRNA coding for brain-derived neurotrophic factor (BDNF) and for its functional receptor, the full-length tyrosine kinase receptor trkB (trkB mRNA), was examined in early postnatal and adult rat retina by in situ hybridization using digoxygenin and radioactively-labeled oligonucleotide probes. BDNF and trkB mRNAs are expressed in the ganglion cell layer at postnatal-days (PN) 1,
The distribution of neuronal nitric oxide synthase (NOS) immunoreactivity was examined in rat and rabbit retinas and was compared with the distribution of nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactivity and vasoactive intestinal peptide (VIP) immunoreactivity. An antibody raised against a C-terminal fragment of a cloned rat cerebellar NOS was used to localise NOS immunore
