Annexin 7 mobilizes calcium from endoplasmic reticulum stores in brain

AbstractMobilization of intracellular calcium from inositol-1,4,5-triphosphate (IP3)-sensitive endoplasmic reticulum (ER) stores plays a prominent role in brain function. Mice heterozygous for the annexin A7 (Anx7) gene have a profound reduction in IP3 receptor function in pancreatic islets along with defective insulin secretion. We examined IP3-sensitive calcium pools in the brains of Anx7 (+/−) mice by utilizing ATP/Mg2+-dependent 45Ca2+ uptake into brain membrane preparations and tissue sections. Although the Anx7 (+/−) mouse brain displayed similar levels of IP3 binding sites and thapsigargin-sensitive 45Ca2+ uptake as that seen in wild-type mouse brain, the Anx7 (+/−) mouse brain Ca2+ pools showed markedly reduced sensitivity to IP3. A potent and saturable Ca2+-releasing effect of recombinant ANX7 protein was demonstrated in mouse and rat brain membrane preparations, which was additive with that of IP3. We propose that ANX7 mobilizes Ca2+ from an endoplasmic reticulum-like pool, which can be recruited to enhance IP3-mediated Ca2+ release

Sizes of Masing Parts of Massive Star Forming Regions

It is shown that the images, line profiles, and time evolution of different interstellar masing transitions can be explained by the hypothesis that the population inversions giving birth to masers take place in turbulent regions with extents that are orders of magnitude greater than the sizes of the maser spots. It is shown that the images of methanol masers in the turbulent model persist within considerable time and do not prevent measurement of the annual parallaxes using data on the 12 GHz methanol maser positions.Показано, что изображения, профили линий и временная эволюция различных переходов межзвездных мазеров могут быть объяснены в рамках гипотезы о том, что инверсия населенностей, приводящая к появлению мазеров, возникает в турбулентных районах с размерами, превышающими размеры мазерных пятен на порядки величины. Показано также, что изображения метанольных мазеров в турбулентной модели остаются неизменными в течение продолжительного времени, что позволяет проводить измерения годичных параллаксов по данным о положениях метанольных мазеров на 12 ГГц.Показано, що зображення, профілі ліній та часову еволюцію різних переходів міжзоряних мазерів можна пояснити в межах гіпотези про те, що інверсія населеностей, котра призводить до появи мазерів, виникає в турбулентних районах з розмірами, вищими за такі мазерних плям на порядки величини. Показано також, що зображення метанольних мазерів у турбулентній моделі залишаються незмінними протягом довгого часу, що дозволяє вимірювати річні паралакси за даними про розташування метанольних мазерів на 12 ГГц

Systematics of Leading Particle Production

Using a QCD inspired model developed by our group for particle production, the Interacting Gluon Model (IGM), we have made a systematic analysis of all available data on leading particle spectra. These data include diffractive collisions and photoproduction at HERA. With a small number of parameters (essentially only the non-perturbative gluon-gluon cross section and the fraction of diffractive events) good agreement with data is found. We show that the difference between pion and proton leading spectra is due to their different gluon distributions. We predict a universality in the diffractive leading particle spectra in the large momentum region, which turns out to be independent of the incident energy and of the projectile type.Comment: 13 pages, Latex, 4 ps figures. To appear in Phys. Rev.

Asymmetric Bethe-Salpeter equation for pairing and condensation

The Martin-Schwinger hierarchy of correlations are reexamined and the three-particle correlations are investigated under various partial summations. Besides the known approximations of screened, ladder and maximally crossed diagrams the pair-pair correlations are considered. It is shown that the recently proposed asymmetric Bethe-Salpeter equation to avoid unphysical repeated collisions is derived as a result of the hierarchical dependencies of correlations. Exceeding the parquet approximation we show that an asymmetry appears in the selfconsistent propagators. This form is superior over the symmetric selfconsistent one since it provides the Nambu-Gorkov equations and gap equation for fermions and the Beliaev equations for bosons while from the symmetric form no gap equation results. The selfenergy diagrams which account for the subtraction of unphysical repeated collisions are derived from the pair-pair correlation in the three-particle Greenfunction. It is suggested to distinguish between two types of selfconsistency, the channel-dressed propagators and the completely dressed propagators, with the help of which the asymmetric expansion completes the Ward identity and is $\Phi$-derivable.Comment: 12 pages. 26 figure

Cosmic Ray Energy Spectra and Mass Composition at the Knee - Recent Results from KASCADE -

Recent results from the KASCADE experiment on measurements of cosmic rays in the energy range of the knee are presented. Emphasis is placed on energy spectra of individual mass groups as obtained from an two-dimensional unfolding applied to the reconstructed electron and truncated muon numbers of each individual EAS. The data show a knee-like structure in the energy spectra of light primaries (p, He, C) and an increasing dominance of heavy ones (A > 20) towards higher energies. This basic result is robust against uncertainties of the applied interaction models QGSJET and SIBYLL which are used in the shower simulations to analyse the data. Slight differences observed between experimental data and EAS simulations provide important clues for further improvements of the interaction models. The data are complemented by new limits on global anisotropies in the arrival directions of CRs and by upper limits on point sources. Astrophysical implications for discriminating models of maximum acceleration energy vs galactic diffusion/drift models of the knee are discussed based on this data.Comment: 8 pages, 7 figures, to appear in Nuclear Physics B, Proceedings Supplements, as part of the volume for the CRIS 2004, Cosmic Ray International Seminar: GZK and Surrounding

CP-rays in simplicial cones

An interior point of a triangle is called CP-point if its orthogonal projection on the line containing each side lies in the relative interior of that side. In classical mathematics, interest in the concept of regularity of a triangle is mainly centered on the property of every interior point of the triangle being a CP-point. We generalize the concept of regularity using this property, and extend this work to simplicial cones in ℝ n , and derive necessary and sufficient conditions for this property to hold in them. These conditions highlight the geometric properties of Z-matrices. We show that these concepts have important ramifications in algorithmic studies of the linear complementarity problem. We relate our results to other well known properties of square matrices.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47921/1/10107_2005_Article_BF01582265.pd

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

A surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes.

OnlinePublAims/Introduction: Autoantibodies to pancreatic islet antigens identify young children at high risk of type 1 diabetes. On a background of genetic susceptibility, islet autoimmunity is thought to be driven by environmental factors, of which enteric viruses are prime candidates. We sought evidence for enteric pathology in children genetically atrisk for type 1 diabetes followed from birth who had developed islet autoantibodies (“seroconverted”), by measuring mucosa-associated cytokines in their sera. Materials and Methods: Sera were collected 3 monthly from birth from children with a first-degree type 1 diabetes relative, in the Environmental Determinants of Islet Autoimmunity (ENDIA) study. Children who seroconverted were matched for sex, age, and sample availability with seronegative children. Luminex xMap technology was used to measure serum cytokines. Results: Of eight children who seroconverted, for whom serum samples were available at least 6 months before and after seroconversion, the serum concentrations of mucosaassociated cytokines IL-21, IL-22, IL-25, and IL-10, the Th17-related cytokines IL-17F and IL23, as well as IL-33, IFN-c, and IL-4, peaked from a low baseline in seven around the time of seroconversion and in one preceding seroconversion. These changes were not detected in eight sex- and age-matched seronegative controls, or in a separate cohort of 11 unmatched seronegative children. Conclusions: In a cohort of children at risk for type 1 diabetes followed from birth, a transient, systemic increase in mucosa-associated cytokines around the time of seroconversion lends support to the view that mucosal infection, e.g., by an enteric virus, may drive the development of islet autoimmunity.Leonard C Harrison, Esther Bandala-Sanchez, Helena Oakey, Peter G Colman, Kelly Watson, Ki Wook Kim, Roy Wu, Emma E Hamilton-Williams, Natalie L Stone, Aveni Haynes, Rebecca L Thomson, Peter J Vuillermin, Georgia Soldatos, William D Rawlinson, Kelly J McGorm, Grant Morahan, Simon C Barry, Richard O Sinnott, John M Wentworth, Jennifer J Couper, Megan AS Penno, on behalf of the ENDIA Study Grou

LRG1 destabilizes tumor vessels and restricts immunotherapeutic potency

Background: A poorly functioning tumor vasculature is pro-oncogenic and may impede the delivery of therapeutics. Normalizing the vasculature, therefore, may be beneficial. We previously reported that the secreted glycoprotein leucine-rich α-2-glycoprotein 1 (LRG1) contributes to pathogenic neovascularization. Here, we investigate whether LRG1 in tumors is vasculopathic and whether its inhibition has therapeutic utility. Methods: Tumor growth and vascular structure were analyzed in subcutaneous and genetically engineered mouse models in wild-type and Lrg1 knockout mice. The effects of LRG1 antibody blockade as monotherapy, or in combination with co-therapies, on vascular function, tumor growth, and infiltrated lymphocytes were investigated. Findings: In mouse models of cancer, Lrg1 expression was induced in tumor endothelial cells, consistent with an increase in protein expression in human cancers. The expression of LRG1 affected tumor progression as Lrg1 gene deletion, or treatment with a LRG1 function-blocking antibody, inhibited tumor growth and improved survival. Inhibition of LRG1 increased endothelial cell pericyte coverage and improved vascular function, resulting in enhanced efficacy of cisplatin chemotherapy, adoptive T cell therapy, and immune checkpoint inhibition (anti-PD1) therapy. With immunotherapy, LRG1 inhibition led to a significant shift in the tumor microenvironment from being predominantly immune silent to immune active. Conclusions: LRG1 drives vascular abnormalization, and its inhibition represents a novel and effective means of improving the efficacy of cancer therapeutics. Funding: Wellcome Trust (206413/B/17/Z), UKRI/MRC (G1000466, MR/N006410/1, MC/PC/14118, and MR/L008742/1), BHF (PG/16/50/32182), Health and Care Research Wales (CA05), CRUK (C42412/A24416 and A17196), ERC (ColonCan 311301 and AngioMature 787181), and DFG (CRC1366)