Characterization of a Lamellocyte Transcriptional Enhancer Located within the misshapen Gene of Drosophila melanogaster

Drosophila has emerged as an excellent model system in which to study cellular and genetic aspects of hematopoiesis. Under normal developmental conditions and in wild-type genetic backgrounds, Drosophila possesses two types of blood cells, crystal cells and plasmatocytes. Upon infestation by a parasitic wasp or in certain altered genetic backgrounds, a third hemocyte class called the lamellocyte becomes apparent. Herein we describe the characterization of a novel transcriptional regulatory module, a lamellocyte-active enhancer of the misshapen gene. This transcriptional control sequence appears to be inactive in all cell types of the wild-type larva, including crystal cells and plasmatocytes. However, in lamellocytes induced by wasp infestation or by particular genetic conditions, the enhancer is activated and it directs reporter GFP or DsRed expression exclusively in lamellocytes. The lamellocyte control region was delimited to a 140-bp intronic sequence that contains an essential DNA recognition element for the AP-1 transcription factor. Additionally, mutation of the kayak gene encoding the dFos subunit of AP-1 led to a strong suppression of lamellocyte production in tumorous larvae. As misshapen encodes a protein kinase within the Jun N-terminal kinase signaling pathway that functions to form an active AP-1 complex, the lamellocyte-active enhancer likely serves as a transcriptional target within a genetic auto-regulatory circuit that promotes the production of lamellocytes in immune-challenged or genetically- compromised animals

A Rydberg Quantum Simulator

Following Feynman and as elaborated on by Lloyd, a universal quantum simulator (QS) is a controlled quantum device which reproduces the dynamics of any other many particle quantum system with short range interactions. This dynamics can refer to both coherent Hamiltonian and dissipative open system evolution. We investigate how laser excited Rydberg atoms in large spacing optical or magnetic lattices can provide an efficient implementation of a universal QS for spin models involving (high order) n-body interactions. This includes the simulation of Hamiltonians of exotic spin models involving n-particle constraints such as the Kitaev toric code, color code, and lattice gauge theories with spin liquid phases. In addition, it provides the ingredients for dissipative preparation of entangled states based on engineering n-particle reservoir couplings. The key basic building blocks of our architecture are efficient and high-fidelity n-qubit entangling gates via auxiliary Rydberg atoms, including a possible dissipative time step via optical pumping. This allows to mimic the time evolution of the system by a sequence of fast, parallel and high-fidelity n-particle coherent and dissipative Rydberg gates.Comment: 8 pages, 4 figure

Sagittal jaw position in relation to body posture in adult humans – a rasterstereographic study

BACKGROUND: The correlations between the sagittal jaw position and the cranio – cervical inclination are described in literature. Only few studies focus on the sagittal jaw position and the body posture using valid and objective orthopaedic examination methods. The aim of this study was to test the hypothesis that patients with malocclusions reveal significant differences in body posture compared to those without (upper thoracic inclination, kyphotic angle, lordotic angle and lower lumbar inclination). METHODS: Eighty-four healthy adult patients (with a mean age = 25.6 years and ranging from 16.1 to 55.8 years) were examined with informed consent. The orthodontic examination horizontal overjet (distance between upper and lower incisors) was determined by using an orthodontic digital sliding calliper. The subjects were subdivided in respect of the overjet with the following results: 18 revealed a normal overjet (Class I), 38 had an increased overjet (Class II) and 28 had an reversed overjet (Class III). Rasterstereography was used to carry out a three – dimensional back shape analysis. This method is based on photogrammetry. A three-dimensional shape was produced by analysing the distortion of parallel horizontal white light lines projected on the patient's back, followed by mathematical modelling. On the basis of the sagittal profile the upper thoracic inclination, the thoracic angle, the lordotic angle and the pelvic inclination were determined with a reported accuracy of 2.8° and the correlations to the sagittal jaw position were calculated by means of ANOVA, Scheffé and Kruskal-Wallis procedures. RESULTS: Between the different overjet groups, no statistically significant differences or correlations regarding the analysed back shape parameters could be obtained. However, comparing males and females there were statistically significant differences in view of the parameters 'lordotic angle' and 'pelvic inclination'. CONCLUSION: No correlations between overjet and variables of the thoracic, lordotic or the pelvic inclination could be observed

Controlled Collisions for Multiparticle Entanglement of Optically Trapped Atoms

Entanglement lies at the heart of quantum mechanics and in recent years has been identified as an essential resource for quantum information processing and computation. Creating highly entangled multi-particle states is therefore one of the most challenging goals of modern experimental quantum mechanics, touching fundamental questions as well as practical applications. Here we report on the experimental realization of controlled collisions between individual neighbouring neutral atoms trapped in the periodic potential of an optical lattice. These controlled interactions act as an array of quantum gates between neighbouring atoms in the lattice and their massively parallel operation allows the creation of highly entangled states in a single operational step, independent of the size of the system. In the experiment, we observe a coherent entangling-disentangling evolution in the many-body system depending on the phase shift acquired during the collision between neighbouring atoms. This dynamics is indicative of highly entangled many-body states that present novel opportunities for theory and experiment.Comment: 17 pages, including 5 figures, accepted for publication in Natur

Prognostic Value of [18F]-Fluoro-Deoxy-Glucose PET/CT, S100 or MIA for Assessment of Cancer-Associated Mortality in Patients with High Risk Melanoma

PURPOSE: To assess the prognostic value of FDG PET/CT compared to the tumor markers S100B and melanoma inhibitory activity (MIA) in patients with high risk melanoma. METHODS: Retrospective study in 125 consecutive patients with high risk melanoma that underwent FDG PET/CT for re-staging. Diagnostic accuracy and prognostic value was determined for FDG PET/CT as well as for S100B and MIA. As standard of reference, cytological, histological, PET/CT or MRI follow-up findings as well as clinical follow-up were used. RESULTS: Of 125 patients, FDG PET/CT was positive in 62 patients. 37 (29.6%) patients had elevated S100B (>100 pg/ml) and 24 (20.2%) had elevated MIA (>10 pg/ml) values. Overall specificities for FDG PET/CT, S100B and MIA were 96.8% (95% CI, 89.1% to 99.1%), 85.7% (75.0% to 92.3%), and 95.2% (86.9% to 98.4%), corresponding sensitivities were 96.8% (89.0% to 99.1%), 45.2% (33.4% to 55.5%), and 36.1% (25.2% to 48.6%), respectively. The negative predictive values (NPV) for PET/CT, S100B, and MIA were 96.8% (89.1% to 99.1%), 61.4% (50.9% to 70.9%), and 60.6% (50.8% to 69.7%). The positive predictive values (PPV) were 96.7% (89.0% to 99.1%), 75.7% (59.9% to 86.6%), and 88.0% (70.0% to 95.8%). Patients with elevated S100B- or MIA values or PET/CT positive findings showed a significantly (p<0.001 each, univariate Cox regression models) higher risk of melanoma associated death which was increased 4.2-, 6.5- or 17.2-fold, respectively. CONCLUSION: PET/CT has a higher prognostic power in the assessment of cancer-associated mortality in melanoma patients compared with S100 and MIA

Glia-Pinealocyte Network: The Paracrine Modulation of Melatonin Synthesis by Tumor Necrosis Factor (TNF)

The pineal gland, a circumventricular organ, plays an integrative role in defense responses. The injury-induced suppression of the pineal gland hormone, melatonin, which is triggered by darkness, allows the mounting of innate immune responses. We have previously shown that cultured pineal glands, which express toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1), produce TNF when challenged with lipopolysaccharide (LPS). Here our aim was to evaluate which cells present in the pineal gland, astrocytes, microglia or pinealocytes produced TNF, in order to understand the interaction between pineal activity, melatonin production and immune function. Cultured pineal glands or pinealocytes were stimulated with LPS. TNF content was measured using an enzyme-linked immunosorbent assay. TLR4 and TNFR1 expression were analyzed by confocal microscopy. Microglial morphology was analyzed by immunohistochemistry. In the present study, we show that although the main cell types of the pineal gland (pinealocytes, astrocytes and microglia) express TLR4, the production of TNF induced by LPS is mediated by microglia. This effect is due to activation of the nuclear factor kappa B (NF-kB) pathway. In addition, we observed that LPS activates microglia and modulates the expression of TNFR1 in pinealocytes. As TNF has been shown to amplify and prolong inflammatory responses, its production by pineal microglia suggests a glia-pinealocyte network that regulates melatonin output. The current study demonstrates the molecular and cellular basis for understanding how melatonin synthesis is regulated during an innate immune response, thus our results reinforce the role of the pineal gland as sensor of immune status