Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells

Human bone marrow stromal cells (BMSC) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key stromal cell functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key stromal cell regulator and found that EGR1 was highly expressed in prospectivelyisolated primary BMSC, down-regulated upon culture, and low in noncolony-forming CD45neg stromal cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSC. Overexpression of EGR1 in stromal cells induced potent hematopoietic stroma support as indicated by an increased production of transplantable CD34+ CD90+ hematopoietic stem cells in expansion co-cultures. The improvement in bone marrow stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28. Furthermore, EGR1 overexpression markedly decreased stromal cell proliferation whereas EGR1 knoc

AEgIS Experiment: Measuring the Acceleration g of the Earth's Gravitational Field on Antihydrogen Beam

The AEgIS experiment [1] aims at directly measuring the gravitational acceleration g on a beam of cold antihydrogen (H) to a precision of 1%, performing the first test with antimatter of the (WEP) Weak Equivalence Principle. The experimental apparatus is sited at the Antiproton Decelerator (AD) at CERN, Geneva, Switzerland. After production by mixing of antiprotons with Rydberg state positronium atoms (Ps), the atoms will be driven to fly horizontally with a velocity of a few 100 ms−1 for a path length of about 1 meter. The small deflection, few tens of μm, will be measured using two material gratings (of period ∼ 80 μm) coupled to a position-sensitive detector working as a moiré deflectometer similarly to what has been done with matter atoms [2]. The shadow pattern produced by the beam will then be detected by reconstructing the annihilation points with a spatial resolution (∼ 2 μm) of each antiatom at the end of the flight path by the sensitive-position detector. During 2012 the experimental apparatus has been commissioned with antiprotons and positrons. Since the AD will not be running during 2013,during the refurbishment of the CERN accelerators, the experiment is currently working with positrons, electrons and protons, in order to prepare the way for the antihydrogen production in late 2014

Stimulatory effect of Echinacea purpurea extract on the trafficking activity of mouse dendritic cells: revealed by genomic and proteomic analyses

<p>Abstract</p> <p>Background</p> <p>Several <it>Echinacea </it>species have been used as nutraceuticals or botanical drugs for "immunostimulation", but scientific evidence supporting their therapeutic use is still controversial. In this study, a phytocompound mixture extracted from the butanol fraction (BF) of a stem and leaf (S+L) extract of <it>E. purpurea </it>([BF/S+L/Ep]) containing stringently defined bioactive phytocompounds was obtained using standardized and published procedures. The transcriptomic and proteomic effects of this phytoextract on mouse bone marrow-derived dendritic cells (BMDCs) were analyzed using primary cultures.</p> <p>Results</p> <p>Treatment of BMDCs with [BF/S+L/Ep] did not significantly influence the phenotypic maturation activity of dendritic cells (DCs). Affymetrix DNA microarray and bioinformatics analyses of genes differentially expressed in DCs treated with [BF/S+L/Ep] for 4 or 12 h revealed that the majority of responsive genes were related to cell adhesion or motility (<it>Cdh10</it>, <it>Itga6</it>, <it>Cdh1</it>, <it>Gja1 </it>and <it>Mmp8</it>), or were chemokines (<it>Cxcl2, Cxcl7) </it>or signaling molecules (<it>Nrxn1, Pkce </it>and <it>Acss1</it>). TRANSPATH database analyses of gene expression and related signaling pathways in treated-DCs predicted the JNK, PP2C-α, AKT, ERK1/2 or MAPKAPK pathways as the putative targets of [BF/S+L/Ep]. In parallel, proteomic analysis showed that the expressions of metabolic-, cytoskeleton- or NF-κB signaling-related proteins were regulated by treatment with [BF/S+L/Ep]. <it>In vitro </it>flow cytometry analysis of chemotaxis-related receptors and <it>in vivo </it>cell trafficking assay further showed that DCs treated with [BF/S+L/Ep] were able to migrate more effectively to peripheral lymph node and spleen tissues than DCs treated as control groups.</p> <p>Conclusion</p> <p>Results from this study suggest that [BF/S+L/Ep] modulates DC mobility and related cellular physiology in the mouse immune system. Moreover, the signaling networks and molecules highlighted here are potential targets for nutritional or clinical application of <it>Echinacea </it>or other candidate medicinal plants.</p

A Moiré Deflectometer for Antimatter

The precise measurement of forces is one way to obtain deep insight into the fundamental interactions present in nature. In the context of neutral antimatter, the gravitational interaction is of high interest, potentially revealing new forces that violate the weak equivalence principle. Here we report on a successful extension of a tool from atom optics - the moirè deflectometer - for a measurement of the acceleration of slow antiprotons. The setup consists of two identical transmission gratings and a spatially resolving emulsion detector for antiproton annihilations. Absolute referencing of the observed antimatter pattern with a photon pattern experiencing no deflection allows the direct inference of forces present. The concept is also straightforwardly applicable to antihydrogen measurements as pursued by the AEgIS collaboration. The combination of these very different techniques from high energy and atomic physics opens a very promising route to the direct detection of the gravitational acceleration of neutral antimatter

Gender differences in first episode psychotic mania

Background : The aim of this paper was to delineate the impact of gender on premorbid history, onset, and 18 month outcomes of first episode psychotic mania (FEPM) patients. Methods : Medical file audit assessment of 118 (male = 71; female = 47) patients with FEPM aged 15 to 29 years was undertaken on clinical and functional measures. Results : Males with FEPM had increased likelihood of substance use (OR = 13.41, p &lt; .001) and forensic issues (OR = 4.71, p = .008), whereas females were more likely to have history of sexual abuse trauma (OR = 7.12, p = .001). At service entry, males were more likely to be using substances, especially cannabis (OR = 2.15, p = .047), had more severe illness (OR = 1.72, p = .037), and poorer functioning (OR = 0.96, p = .045). During treatment males were more likely to decrease substance use (OR = 5.34, p = .008) and were more likely to be living with family (OR = 4.30, p = .009). There were no gender differences in age of onset, psychopathology or functioning at discharge. Conclusions : Clinically meaningful gender differences in FEPM were driven by risk factors possibly associated with poor outcome. For males, substance use might be associated with poorer clinical presentation and functioning. In females with FEPM, the impact of sexual trauma on illness course warrants further consideration

Distribution of the Octopamine Receptor AmOA1 in the Honey Bee Brain

Octopamine plays an important role in many behaviors in invertebrates. It acts via binding to G protein coupled receptors located on the plasma membrane of responsive cells. Several distinct subtypes of octopamine receptors have been found in invertebrates, yet little is known about the expression pattern of these different receptor subtypes and how each subtype may contribute to different behaviors. One honey bee (Apis mellifera) octopamine receptor, AmOA1, was recently cloned and characterized. Here we continue to characterize the AmOA1 receptor by investigating its distribution in the honey bee brain. We used two independent antibodies produced against two distinct peptides in the carboxyl-terminus to study the distribution of the AmOA1 receptor in the honey bee brain. We found that both anti-AmOA1 antibodies revealed labeling of cell body clusters throughout the brain and within the following brain neuropils: the antennal lobes; the calyces, pedunculus, vertical (alpha, gamma) and medial (beta) lobes of the mushroom body; the optic lobes; the subesophageal ganglion; and the central complex. Double immunofluorescence staining using anti-GABA and anti-AmOA1 receptor antibodies revealed that a population of inhibitory GABAergic local interneurons in the antennal lobes express the AmOA1 receptor in the cell bodies, axons and their endings in the glomeruli. In the mushroom bodies, AmOA1 receptors are expressed in a subpopulation of inhibitory GABAergic feedback neurons that ends in the visual (outer half of basal ring and collar regions) and olfactory (lip and inner basal ring region) calyx neuropils, as well as in the collar and lip zones of the vertical and medial lobes. The data suggest that one effect of octopamine via AmOA1 in the antennal lobe and mushroom body is to modulate inhibitory neurons

Particle tracking at cryogenic temperatures: the Fast Annihilation Cryogenic Tracking (FACT) detector for the AEgIS antimatter gravity experiment

The AEgIS experiment is an interdisciplinary collaboration between atomic, plasma and particle physicists, with the scientific goal of performing the first precision measurement of the Earth’s gravitational acceleration on antimatter. The principle of the experiment is as follows: cold antihydrogen atoms are synthesized in a Penning-Malmberg trap and are Stark accelerated towards a moire deflectometer, the classical counterpart of an atom interferometer, and annihilate on a position sensitive detector. Crucial to the success of the experiment is an antihydrogen detector that will be used to demonstrate the production of antihydrogen and also to measure the temperature of the anti-atoms and the creation of a beam. The operating requirements for the detector are very challenging: it must operate at close to 4 K inside a 1 T solenoid magnetic field and identify the annihilation of the antihydrogen atoms that are produced during the 1 µs period of antihydrogen production. Our solution — called the FACT detector — is based on a novel multi-layer scintillating fiber tracker with SiPM readout and off the shelf FPGA based readout system. This talk will present the design of the FACT detector and detail the operation of the detector in the context of the AEgIS experiment

Horizontal Career Changes as an Alternative to Premature Exit From Work

Certain workplaces are called jobs with limited tenure. Due to physical or psychosocial risk factors, often coupled with qualification mismatches, workers cannot grow old in them. That may lead to premature exit into retirement, to a period of drawing a work incapacity pension or to a long spell of unemployment. A horizontal career change, which enables the worker to move on to a less burdening workplace while preserving social status, is a possible solution. The objective of the “Horizontal career change—a new job opportunity for older employees” project is to develop a model of career changes for workers employed in jobs with limited tenure and to implement it in the form of an information- and communication technology-based tool. Possible applications range from individual career planning, through institutionalized vocational reintegration, to personnel development in small and medium-sized enterprises

Data-driven weathering layer statics for hardrock imaging: Solutions based on first-breaks and surface waves

Seismic methods are routinely used for hardrock imaging and mineral-exploration purposes. However, hardrock seismic data requires careful processing, where weathering layer - refraction static corrections have shown to be of great importance for successful imaging. In our study, six differently obtained data-driven weathering layer static solutions are analyzed and compared using a seismic dataset from a mining site in Sweden. Three of the six approaches utilize first-breaks and are based on (1) the standard refraction-inversion method (RI), (2) the application of the RI after adding additional first-breaks via supervirtual seismic interferometry (SVSI), and (3) a tomography-based static solution (Tomostatics). The other three approaches employ surface-waves and are based on (4) the direct transformation of SW dispersion curves, (5) joint inversion of dispersion curves as well as first-breaks and (6) surface-wave tomography. All tested methods were successful in enhancing coherency of the main ore body reflection. A crosscutting reflection can also be seen following the first-break based refraction statics, with highest coherency seen after the application of the SVSIenhanced RI refraction statics. The examples presented suggest that these methods can be complementary and in the absence of notable first-breaks, surface waves can be utilized to estimate weathering layer static corrections

Non-functional trace amine-associated receptor 1 variants in patients with mental disorders

Background: The G protein-coupled receptor (GPCR) trace amine-associated receptor 1 (TAAR1) is expressed across brain areas involved in emotions, reward and cognition, and modulates monoaminergic and glutamatergic neurotransmissions. TAAR1 is stimulated with nanomolar affinity by 3-iodothyronamine (T1AM), an endogenous messenger considered a novel branch of thyroid hormone signaling. The human gene for TAAR1 maps to locus 6q23, within a region associated with major mental disorders. Materials and Methods: We screened a cohort of patients with major mental disorders (n = 104) and a group of healthy controls (n = 130) for TAAR1 variants. HEK293 cells were transiently transfected with: i) wild-type TAAR1 and ii) mutated TAAR1, either in homozygous or heterozygous state. Cell surface expression and Gs/adenylyl cyclase activation upon administration of β-phenylethylamine (PEA), T1AM, and RO5166017, were assessed. Results: We detected 13 missense variants in TAAR1 coding region, with a significant enrichment in patients as compared to healthy controls (11 vs. 1, 1 variant in both groups, p &lt; 0.01). In silico analysis identified four dysfunctional variants, all in patients. Three of these-R23C, Y131C, and C263R-were functionally characterized. In cells co-transfected with wild-type and mutated TAAR1, we observed a significant reduction of cell surface expression. In heterozygosity, the three TAAR1 variants substantially dampened Gs signaling in response to PEA, and, more robustly, to T1AM. Co-stimulation with PEA and RO5166017 did not yield any improvement in Gs signaling. R23C, Y131C, and C263R are rare in the general population and map in functionally important highly conserved positions across TAAR1 orthologous and paralogous genes. Conclusions: Our findings suggest that disruptions of TAAR1 activity may be relevant to the pathophysiology of mental disorders, thereby providing a promising target for novel psychopharmacological interventions