Observations of, and sources of the spatial and temporal variability of ozone in the middle atmosphere on climatological time scales (OZMAP) and equatorial dynamics: Seasonal variations of ozone trends

The long term trends (least square linear regression with time) of ozone content at seven European, seven North American, three Japanese and two tropical stations during 21 years (1964 to 1984) are analyzed. In all regions negative trends are observed during the 1970s, but are partly compensated by limited periods of positive trends during the late 1960s and late 1970s. Solely the North American ozone data show negative trends in all 10 year periods. When the long term ozone trends are evaluated for each month of the year separately, a seasonal variation is revealed, which in Europe and North America has largest negative trends in late winter and spring. While in Europe the negative trends in winter/spring are partly compensated by positive trends in summer, in North America the summer values reach only zero, retaining the significant negative trend in annual mean values. In contrast to the antarctic ozone hole, the spring reduction of ozone in Europe and in North America is associated with stratospheric temperatures increasing in the analyzed period and therefore is consistent with the major natural ozone production and loss processes

A next generation measurement of the electric dipole moment of the neutron at the FRM II

In this paper we discuss theoretical motivations and the status of experimental searches to find time-reversal symmetry-violating electric dipole moments (EDM). Emphasis is given to a next generation search for the EDM of the neutron, which is currently being set up at the FRM II neutron source in Garching, with an ultimate sensitivity goal of 5 × 10−28 cm (3σ). The layout of the apparatus allows for the detailed investigation of systematic effects by combining various means of magnetic field control and polarized UCN optics. All major components of the installations are portable and can be installed at the strongest available UCN beam

Primary B-Cell Deficiencies Reveal a Link between Human IL-17-Producing CD4 T-Cell Homeostasis and B-Cell Differentiation

IL-17 is a pro-inflammatory cytokine implicated in autoimmune and inflammatory conditions. The development/survival of IL-17-producing CD4 T cells (Th17) share critical cues with B-cell differentiation and the circulating follicular T helper subset was recently shown to be enriched in Th17 cells able to help B-cell differentiation. We investigated a putative link between Th17-cell homeostasis and B cells by studying the Th17-cell compartment in primary B-cell immunodeficiencies. Common Variable Immunodeficiency Disorders (CVID), defined by defects in B-cell differentiation into plasma and memory B cells, are frequently associated with autoimmune and inflammatory manifestations but we found no relationship between these and Th17-cell frequency. In fact, CVID patients showed a decrease in Th17-cell frequency in parallel with the expansion of activated non-differentiated B cells (CD21lowCD38low). Moreover, Congenital Agammaglobulinemia patients, lacking B cells due to impaired early B-cell development, had a severe reduction of circulating Th17 cells. Finally, we found a direct correlation in healthy individuals between circulating Th17-cell frequency and both switched-memory B cells and serum BAFF levels, a crucial cytokine for B-cell survival. Overall, our data support a relationship between Th17-cell homeostasis and B-cell maturation, with implications for the understanding of the pathogenesis of inflammatory/autoimmune diseases and the physiology of B-cell depleting therapies

Site-1 protease function is essential for the generation of antibody secreting cells and reprogramming for secretory activity

The unfolded protein response (UPR) and activation of XBP1 is necessary for high secretory efficiency and functional differentiation of antibody secreting cells (ASCs). The UPR additionally includes a branch in which membrane-bound transcription factors, exemplified by ATF6, undergo intramembrane-proteolysis by the sequential action of site-1 (MBTPS1/S1P) and site-2 proteases (MBTPS2/S2P) and release of the cytoplasmic domain as an active transcription factor. Such regulation is shared with a family of CREB3-related transcription factors and sterol regulatory element-binding proteins (SREBPs). Of these, we identify that the CREB3 family member CREB3L2 is strongly induced and activated during the transition from B-cell to plasma cell state. Inhibition of site-1 protease leads to a profound reduction in plasmablast number linked to induction of autophagy. Plasmablasts generated in the presence of site-1 protease inhibitor segregated into CD38high and CD38low populations, the latter characterized by a marked reduction in the capacity to secrete IgG. Site-1 protease inhibition is accompanied by a distinctive change in gene expression associated with amino acid, steroid and fatty acid synthesis pathways. These results demonstrate that transcriptional control of metabolic programs necessary for secretory activity can be targeted via site-1 protease inhibition during ASC differentiation