University of Hamburg

About: University of Hamburg is a education organization based out in Hamburg, Germany. It is known for research contribution in the topics: Population & Laser. The organization has 45564 authors who have published 89286 publications receiving 2850161 citations. The organization is also known as: Hamburg University.

Oncogenic IL7R gain-of-function mutations in childhood T-cell acute lymphoblastic leukemia.

Abstract: Interleukin 7 (IL-7) and its receptor, formed by IL-7Rα (encoded by IL7R) and γc, are essential for normal T-cell development and homeostasis Here we show that IL7R is an oncogene mutated in T-cell acute lymphoblastic leukemia (T-ALL) We find that 9% of individuals with T-ALL have somatic gain-of-function IL7R exon 6 mutations In most cases, these IL7R mutations introduce an unpaired cysteine in the extracellular juxtamembrane-transmembrane region and promote de novo formation of intermolecular disulfide bonds between mutant IL-7Rα subunits, thereby driving constitutive signaling via JAK1 and independently of IL-7, γc or JAK3 IL7R mutations induce a gene expression profile partially resembling that provoked by IL-7 and are enriched in the T-ALL subgroup comprising TLX3 rearranged and HOXA deregulated cases Notably, IL7R mutations promote cell transformation and tumor formation Overall, our findings indicate that IL7R mutational activation is involved in human T-cell leukemogenesis, paving the way for therapeutic targeting of IL-7R-mediated signaling in T-ALL

Chronic stretch of engineered heart tissue induces hypertrophy and functional improvement

Abstract: To examine the influence of chronic mechanical stretch on functional behavior of cardiac myocytes, we reconstituted embryonic chick or neonatal rat cardiac myocytes to a 3-dimensional engineered heart tissue (EHT) by mixing freshly isolated cells with neutralized collagen I and culturing them between two Velcro-coated silicone tubes, held at a fixed distance with a metal spacer. After 4 days, EHTs were subjected to a phasic unidirectional stretch for 6 days in serum-containing medium. Compared to unstretched controls, RNA/DNA and protein/cell ratios increased by 100% and 50%, respectively. ANF mRNA and alpha-sarcomeric actin increased by 98% and 40%, respectively. Morphologically, stretched EHTs exhibited improved organization of cardiac myocytes into parallel arrays of rod-shaped cells, increased cell length and width, longer myofilaments, and increased mitochondrial density. Thus, stretch induced phenotypic changes, generally referred to as hypertrophy. Concomitantly, force of contraction was two- to fourfold higher both under basal conditions and after stimulation with calcium or the beta-adrenergic agonist isoprenaline. Contraction kinetics were accelerated with a 14-44% decrease in twitch duration under all those conditions. In summary, we have developed a new in vitro model that allows morphological, molecular, and functional consequences of stretch to be studied under defined conditions. The main finding was that stretch of EHTs induced cardiac myocyte hypertrophy, which was accompanied by marked improvement of contractile function.

Sharper images by focusing soft X-rays with photon sieves

Abstract: Fresnel zone plates consisting of alternating transmissive and opaque circular rings can be used to focus X-rays1. The spatial resolution that can be achieved with these devices is of the order of the width of the outermost zone and is therefore limited by the smallest structure (20–40 nm) that can be fabricated by lithography today2. Here we show that a large number of pinholes distributed appropriately over the Fresnel zones make it possible to focus soft X-rays to spot sizes smaller than the diameter of the smallest pinhole. In addition, higher orders of diffraction and secondary maxima can be suppressed by several orders of magnitude. In combination with the next generation of synchrotron light sources (free-electron lasers) these ‘photon sieves’ offer new opportunities for high-resolution X-ray microscopy and spectroscopy in physical and life sciences.

Data Normalization Strategies for MicroRNA Quantification

Abstract: BACKGROUND: Different technologies, such as quantitative real-time PCR or microarrays, have been developed to measure microRNA (miRNA) expression levels. Quantification of miRNA transcripts implicates data normalization using endogenous and exogenous reference genes for data correction. However, there is no consensus about an optimal normalization strategy. The choice of a reference gene remains problematic and can have a serious impact on the actual available transcript levels and, consequently, on the biological interpretation of data. CONTENT: In this review article we discuss the reliability of the use of small RNAs, commonly reported in the literature as miRNA expression normalizers, and compare different strategies used for data normalization. SUMMARY: A workflow strategy is proposed for normalization of miRNA expression data in an attempt to provide a basis for the establishment of a global standard procedure that will allow comparison across studies.