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Heterokaryon-based reprogramming of human B lymphocytes for pluripotency requires Oct4 but not Sox2

Differentiated cells can be reprogrammed through the formation of heterokaryons and hybrid cells when fused with embryonic stem (ES) cells. Here, we provide evidence that conversion of human B-lymphocytes towards a multipotent state is initiated much more rapidly than previously thought, occurring in transient heterokaryons before nuclear fusion and cell division. Interestingly, reprogramming of h

Acquisition and extinction of gene expression programs are separable events in heterokaryon reprogramming

Although differentiated cells normally retain cell-type-specific gene expression patterns throughout their lifetime, cell identity can sometimes be modified or reversed in vivo by transdifferentiation, or experimentally through cell fusion or by nuclear transfer. To examine the epigenetic changes that are required for the dominant conversion of lymphocytes to muscle, we generated heterokaryons bet

Altered expression of CD1d molecules and lipid accumulation in the human hepatoma cell line HepG2 after iron loading

Iron overload in the liver may occur in clinical conditions such as hemochromatosis and nonalcoholic steatohepatitis, and may lead to the deterioration of the normal liver architecture by mechanisms not well understood. Although a relationship between the expression of ICAM-1, and classical major histocompatibility complex (MHC) class I molecules, and iron over-load has been reported, no relations

Red blood cells as modulators to T cell growth and survival

T cell homeostasis is largely controlled by a balance between cell death and survival and anomalies in either process account for a number of diseases linked to excessive or faulty T cell growth. Yet, the influence that cells outside the immunological system have on these processes has only recently received attention. Accumulated evidence indicate that homeostasis of the CD4+ and CD8+ T cell pool

Red blood cells upregulate cytoprotective proteins and the labile iron pool in dividing human T cells despite a reduction in oxidative stress

We have recently reported that red blood cells (RBC) promote T cell growth and survival by inhibiting activation-induced T cell death. In the present study, we have examined parameters of oxidative stress and intracellular iron in activated T cells and correlated these data with the expression of ferritin, heme oxygenase-1 (HO-1), and the transferrin receptor CD71. T cells growing in the presence

Red blood cells promote survival and cell cycle progression of human peripheral blood T cells independently of CD58/LFA-3 and heme compounds

Red blood cells (RBC) are known to modulate T cell proliferation and function possibly through downregulation of oxidative stress. By examining parameters of activation, division, and cell death in vitro, we show evidence that the increase in survival afforded by RBC is due to the maintenance of the proliferative capacity of the activated T cells. We also show that the CD3+CD8+ T cell subset was p

High-throughput identification of small molecules that affect human embryonic vascular development

Birth defects, which are in part caused by exposure to environmental chemicals and pharmaceutical drugs, affect 1 in every 33 babies born in the United States each year. The current standard to screen drugs that affect embryonic development is based on prenatal animal testing; however, this approach yields low-throughput and limited mechanistic information regarding the biological pathways and pot

Sailing through marketing : A critical assessment of spatiality in marketing literature

Marketing has historically been entangled with the study of geography, which has become a very popular focus in the marketing literature nowadays. However, spatially-oriented perspectives in marketing tend to rest on a conceptual divide between place-oriented and space-oriented thinking, thus inhibiting the production of more eclectic and creative spatial knowledge. This conceptual paper endeavors

Differences in the epigenetic and reprogramming properties of pluripotent and extra-embryonic stem cells implicate chromatin remodelling as an important early event in the developing mouse embryo

Background. During early mouse development, two extra-embryonic lineages form alongside the future embryo: the trophectoderm (TE) and the primitive endoderm (PrE). Epigenetic changes known to take place during these early stages include changes in DNA methylation and modified histones, as well as dynamic changes in gene expression. Results. In order to understand the role and extent of chromatin-b

Hepatocytes and IL-15 : A favorable microenvironment for T cell survival and CD8+ T cell differentiation

Human intrahepatic lymphocytes are enriched in CD1d-unrestricted T cells coexpressing NKR. Although the origin of this population remains controversial, it is possible to speculate that the hepatic microenvironment, namely epithelial cells or the cytokine milieu, may play a role in its shaping. IL-15 is constitutively expressed in the liver and has a key role in activation and survival of innate a

A comparative study of anion-exchange membranes tethered with different hetero-cycloaliphatic quaternary ammonium hydroxides

Quaternary ammonium (QA) cations with high alkaline stability are crucial for the long term performance of anion-exchange membrane (AEM) fuel cells. Here, we have tethered poly(phenylene oxide) (PPO) with 8 different hetero-cycloaliphatic QA cations via pentyl spacer chains. The thermal and alkaline stability, as well as hydroxide ion conductivity, were systematically evaluated with the primary ai

Children with respiratory tract infections in Swedish primary care; prevalence of antibiotic resistance in common respiratory tract pathogens and relation to antibiotic consumption

Background: The majority of antibiotics consumed in developed countries are prescribed in primary care. However, little is known about resistance levels in the primary care population. Method: Nasopharyngeal cultures were obtained from children, 0-10 years of age, seeking care at their Primary Health Care Centre with symptoms of respiratory tract infection. Parental questionnaires were used to ret

Forming Planets via Pebble Accretion

The detection and characterization of large populations of pebbles in protoplanetary disks have motivated the study of pebble accretion as a driver of planetary growth. This review covers all aspects of planet formation by pebble accretion, from dust growth over planetesimal formation to the accretion of protoplanets and fully grown planets with gaseous envelopes. Pebbles are accreted at a very hi

Stacked multi-level long pulse modulator topology for ESS

The European Spallation Source (Lund, Sweden) is an under construction multi-disciplinary research facility to be based around a Linear Particle Accelerator which is to provide 2.86 ms long proton pulses at 2 GeV at a pulse repetition rate of 14 Hz, representing an average beam power of 5 MW. To accommodate the requirements of the proton linac, a large number of klystrons driven by power electroni

Impact of prior therapy on the efficacy and safety of oral ixazomib-lenalidomide-dexamethasone vs. placebo-lenalidomide-dexamethasone in patients with relapsed/refractory multiple myeloma in TOURMALINE-MM1

Prior treatment exposure in patients with relapsed/refractory multiple myeloma may affect outcomes with subsequent therapies. We analyzed efficacy and safety according to prior treatment in the phase 3 TOURMALINE-MM1 study of ixazomib-lenalidomide-dexamethasone (ixazomib-Rd) versus placebo-Rd. Patients with relapsed/refractory multiple myeloma received ixazomib-Rd or placebo-Rd. Efficacy and safet

Monitoring progression of clinical reasoning skills during health sciences education using the case method - A qualitative observational study

Background: Outcome- or competency-based education is well established in medical and health sciences education. Curricula are based on courses where students develop their competences and assessment is also usually course-based. Clinical reasoning is an important competence, and the aim of this study was to monitor and describe students' progression in professional clinical reasoning skills durin

Playing Multi-Action Adversarial Games : Online Evolutionary Planning versus Tree Search

We address the problem of playing turn-based multi-action adversarial games, which include many strategy games with extremely high branching factors as players take multiple actions each turn. This leads to the breakdown of standard tree search methods, including Monte Carlo Tree Search (MCTS), as they become unable to reach a sufficient depth in the game tree. In this paper we introduce Online Ev

NOX2-dependent immunosuppression in chronic myelomonocytic leukemia

Chronic myelomonocytic leukemia (CMML) is a myeloproliferative and myelodysplastic neoplasm with few treatment options and dismal prognosis. The role of natural killer (NK) cells and other antileukemic lymphocytes in CMML is largely unknown. We aimed to provide insight into the mechanisms of immune evasion in CMML with a focus on immunosuppressive reactive oxygen species (ROS) formed by the myeloi

Manipulation of laser-accelerated proton beam profiles by nanostructured and microstructured targets

Nanostructured and microstructured thin foils have been fabricated and used experimentally as targets to manipulate the spatial profile of proton bunches accelerated through the interaction with high intensity laser pulses (6×1019 W/cm2). Monolayers of polystyrene nanospheres were placed on the rear surfaces of thin plastic targets to improve the spatial homogeneity of the accelerated proton beams