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The sensitivity of the climate system to changes in radiative forcing is crucial for our understanding of past and future climates. Especially important are feedbacks related to melting of ice sheets like the Greenland ice sheet (GIS) and its potential impact on the Atlantic meridional overturning circulation (AMOC). These effects are likely to delay and dampen predicted long-term warming trends. Estimates of climate sensitivity may be deduced from palaeoclimate-reconstructions, but this raises the question whether past climate sensitivity is applicable to the future. Therefore we have analysed the impact of GIS melt water on the AMOC strength in two past warm climates (last interglacial and early present interglacial) and three future scenarios with three different model parameter sets. These model parameter sets represent three different model sensitivities to freshwater perturbation: low, moderate and high. In both the moderate and high sensitivity versions, we find for lower GIS melt rates (below 54 mSv, Sv = 10 m/s) a clear difference between past and future warm climates in the sensitivity of the AMOC to GIS melt. This difference is connected to the convective activity in the Labrador Sea and the amount of additional surface freshening due to sea ice melting. In contrast, for higher GIS melt rates (over 54 mSv) we find similar reductions of the AMOC strength in all cases. Considering the low sensitivity version of our model, we find that for all GIS melt rates the influence of freshwater forcing on the AMOC is independent of the background climate. Our results and implications are thus strongly determined by the parameter set considered in our model. Nonetheless, our results from two out of three model versions suggest that proxy-based reconstructions of past AMOC sensitivity to GIS melt are likely to be misleading if interpreted for future applications. [ABSTRACT FROM AUTHOR]

The relatively warm early Holocene climate in the Nordic Seas, known as the Holocene Thermal Maximum (HTM), is often associated with an orbitally forced summer insolation maximum at 10 ka BP. The spatial and temporal response recorded in proxy data in the North Atlantic and the Nordic Seas reveal a complex interaction of mechanisms active in the HTM. Previous studies have investigated the impact of the Laurentide Ice Sheet (LIS), as a remnant from a previous glacial period, altering climate conditions with a continuous supply of melt water to the Labrador Sea and adjacent seas and with a downwind cooling effect from the remnant LIS. In our present work we extend this approach by investigating the impact of the Greenland Ice Sheet (GIS) on the early Holocene climate and the HTM. Reconstructions suggest melt rates of 13 mSv for 9 ka BP, which result in our model in a ocean surface cooling of up to 2K near Greenland. Reconstructed summer SST gradients agree best with our simulation including GIS melt, confirming that the impact of early Holocene GIS is crucial for understanding the HTM characteristics in the Nordic Seas area. This implies that the modern and near-future GIS melt can be expected to play an active role in the climate system in the centuries to come. [ABSTRACT FROM AUTHOR]

Tests for antivimentin antibodies (AVA) were performed on 50 systemic lupus erythematosus (SLE) and 63 control sera by indirect immunofluorescence and enzyme linked immunosorbent assay (ELISA). The prevalence was significantly raised in SLE (38% and 50% of sera positive for IgM-AVA and IgG-AVA, respectively, by immunofluorescence; 36% and 64% of sera positive for IgM-AVA and IgG-AVA, respectively, by ELISA) in comparison with the control sera. A significant correlation existed between IgM-AVA, on the one hand, and anticardiolipin antibodies (ACA) and anti-single-stranded DNA (ssDNA), on the other. A stepwise principal component analysis demonstrated that IgM-AVA and IgG-AVA accounted for 71% of the total variance in SLE (50 patients x 5 parameters = total variance). Twenty ACA positive serum samples from patients with syphilis were therefore tested for the presence of AVA, but hardly any were found to be positive. IgM-AVA from patients with SLE were inhibited by cardiolipin and absorbed with ssDNA. An association between AVA positivity and arthralgia was also shown in SLE. [ABSTRACT FROM PUBLISHER]

CD47 protects healthy cells from macrophage attack by binding to signal regulatory protein α (SIRPα), while its upregulation in cancer prevents immune clearance. Systemic treatment with CD47 antibodies requires a weakened Fc-mediated effector function or lower CD47-binding affinity to prevent side effects. Our approach combines "the best of both worlds," i.e., maximized CD47 binding and full Fc-mediated immune activity, by exploiting gene therapy for paracrine release. We developed a plasmid vector encoding for the secreted fusion protein sCV1-hIgG1, comprising highly efficient CD47-blocking moiety CV1 and Fc domain of human immunoglobulin G1 (IgG1) with maximized immune activation. sCV1-hIgG1 exhibited a potent bystander effect, blocking CD47 on all cells via fusion protein secreted from only a fraction of cells or when transferring transfection supernatant to untransfected cells. The CpG-free plasmid ensured sustained secretion of sCV1-hIgG1. In orthotopic human triple-negative breast cancer in CB17-severe combined immunodeficiency (SCID) mice, ex vivo transfection significantly delayed tumor growth and eradicated one-third of tumors. In intratumoral transfection experiments, CD47 blockage and increased migration of macrophages into the tumor were observed within 17 h of a single injection. Natural killer (NK) cell-mediated lysis of sCV1-hIgG1-expressing cells was demonstrated in vitro . Taken together, this approach also opens the opportunity to block, in principle, any immune checkpoints., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Sustainable land management requires reliable information about soil hydraulic properties. Among these properties, available water-holding capacity (AWC) is a key attribute, as it quantifies the amount of water available for plants that the soil can hold. Since direct measurements of AWC are costly, pedotransfer functions (PTF) are often used to estimate AWC, leveraging statistical relationships with properties that are easier to measure, such as texture, bulk density, and organic carbon content. This study evaluates visible near-infrared spectroscopy (vis-NIR) as an alternative approach to predict volumetric water content at field capacity (FC) and permanent wilting point (PWP) - AWC being the difference between PWP and FC. A suite of 970 vis-NIR soil spectra, recorded from air-dried, 2-mm, sieved soil samples, were associated with FC and PWP analytical data obtained from New Zealand's National Soils Database. Partial least squares (PLS) regression and support vector machines on PLS latent variables (PLS-SVM) were used for spectroscopic modelling. With root mean squared errors below 7% and 5% for FC and PWP, respectively, our results indicate that vis-NIR spectroscopy can be used to quantitatively predict volumetric water content at FC and PWP.

According to current climate projections, Mediterranean countries are at high risk for an even pronounced susceptibility to changes in the hydrological budget and extremes. These changes are expected to have severe direct impacts on the management of water resources, agricultural productivity and drinking water supply. Current projections of future hydrological change, based on regional climate model results and subsequent hydrological modeling schemes, are very uncertain and poorly validated. The Rio Mannu di San Sperate Basin, located in Sardinia, Italy, is one test site of the CLIMB project. The Water Simulation Model (WaSiM) was set up to model current and future hydrological conditions. The availability of measured meteorological and hydrological data is poor as it is common for many Mediterranean catchments. In this study we conducted a soil sampling campaign in the Rio Mannu catchment. We tested different deterministic and hybrid geostatistical interpolation methods on soil textures and tested the performance of the applied models. We calculated a new soil texture map based on the best prediction method. The soil model in WaSiM was set up with the improved new soil information. The simulation results were compared to standard soil parametrization. WaSiMs was validated with spatial evapotranspiration rates using the triangle method (Jiang and Islam, 1999). WaSiM was driven with the meteorological forcing taken from 4 different ENSEMBLES climate projections for a reference (1971-2000) and a future (2041-2070) times series. The climate change impact was assessed based on differences between reference and future time series. The simulated results show a reduction of all hydrological quantities in the future in the spring season. Furthermore simulation results reveal an earlier onset of dry conditions in the catchment. We show that a solid soil model setup based on short-term field measurements can improve long-term modeling results, which is especially important in ungauged catchments., (Copyright © 2015 Elsevier B.V. All rights reserved.)

We used observed climate data, an ensemble of four GCM-RCM combinations (global and regional climate models) and the water balance model mGROWA to estimate present and future groundwater recharge for the intensively-used Thau lagoon catchment in southern France. In addition to a highly resolved soil map, soil moisture distributions obtained from SAR-images (Synthetic Aperture Radar) were used to derive the spatial distribution of soil parameters covering the full simulation domain. Doing so helped us to assess the impact of different soil parameter sources on the modelled groundwater recharge levels. Groundwater recharge was simulated in monthly time steps using the ensemble approach and analysed in its spatial and temporal variability. The soil parameters originating from both sources led to very similar groundwater recharge rates, proving that soil parameters derived from SAR images may replace traditionally used soil maps in regions where soil maps are sparse or missing. Additionally, we showed that the variance in different GCM-RCMs influences the projected magnitude of future groundwater recharge change significantly more than the variance in the soil parameter distributions derived from the two different sources. For the period between 1950 and 2100, climate change impacts based on the climate model ensemble indicated that overall groundwater recharge will possibly show a low to moderate decrease in the Thau catchment. However, as no clear trend resulted from the ensemble simulations, reliable recommendations for adapting the regional groundwater management to changed available groundwater volumes could not be derived., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: Repeated induction of ventricular fibrillation with ensuing alterations in electroencephalogram and jugular venous oxygen saturation is common practice during insertion of transvenous implantable cardioverters/defibrillators. We investigated whether these functional changes are also associated with cerebral injury., Design: Prospective study., Setting: University hospital., Patients: We studied 45 patients undergoing implantable cardioverter/defibrillator insertion. Eleven patients with cardiac pacemaker implantation, which was performed in the same manner yet without the necessity to induce ventricular fibrillation, served as controls., Measurements and Main Results: Serum neuron-specific enolase and S100 were determined before, immediately postoperatively, and 2 hrs postoperatively. In a randomly composed subgroup, neuron-specific enolase was also determined 6 and 24 hrs after surgery. Implantable cardioverter/defibrillator patients only showed an increase of both markers postoperatively. Median neuron-specific enolase values climbed from a preoperative 9.9 to 12.3 and 14.4 microg/L at 2 and 24 hrs after surgery, respectively. This increase was associated with the number of shocks and the cumulative time in circulatory arrest. The highest median S100 level (0.075 microg/L) was reached 2 hrs after the procedure. Neuron-specific enolase and S100 were extremely elevated (13.7 and 0.970 microg/L, respectively) in one patient after an extended episode of ventricular fibrillation. Plasma hemoglobin levels were in the normal range in implantable cardioverter/defibrillator patients throughout the observation period., Conclusions: Apparently, even brief successive periods of global cerebral ischemia cause neuronal damage without obvious severe neurologic deficits. However, they may be related to subtle postoperative neurologic or cognitive dysfunctions that a number of implantable cardioverter/defibrillator patients exhibit after implantation.

This study aims to describe a novel antinuclear antibody directed to proteins only accessible during the mitosis: anti-"dividing cell antigen" (DCA) antibody. A total of 709 disease-associated and control sera was tested by indirect immunofluorescence using a variety of cell lines as substrate. Cells were treated with enzymes and antibodies absorbed with nuclear antigens. Antibodies to DNA, histone subfractions, and synthetic peptides were evaluated using enzyme-linked immunosorbent assays. Cell extracts were electrophoresed before and after synchronization and sera tested on the blots. The anti-DCA antibody was demonstrated in 10 of 183 SLE patients but virtually never in other connective tissue diseases. The DCA was sensitive to HCl and proteolytic enzymes and the anti-DCA binding inhibited by histones H2A and H2B. Differences of anti-H2A and anti-H2B were observed between anti-DCA antibody-positive and anti-DCA antibody-negative sera, and antibodies specific for the 1-15 region of H2A, the 1-25 region of H2B and the 1-29 region of H4 were more frequent in the former sera than in the latter. The anti-DCA antibody was shown to react with a 60-kDa protein. Our findings suggest that the anti-DCA antibody is directed to a protein complex containing H2A and H2B.

Fifty-six human immunodeficiency virus-1-positive asymptomatic carriers were tested for the presence of a variety of nonorgan-specific autoantibodies. Antinuclear antibodies were detected in 34 sera, of which 27 were directed to the mitotic spindle apparatus and all were of the IgG isotype. Anti-Golgi complex, anti-centriole, and anti-vimentin antibodies were also present in 20.4, and 4 sera, respectively. Ten patients had less than 500 CD4-carrying T lymphocytes per cubic millimeter. Nine of them had more than one autoantibody. No correlation could be demonstrated between the number of autoantibodies and the level of serum immunoglobulins.

A number of non-organ-specific autoantibodies, such as antibodies to vimentin, centriole, the midbody of chromatin and the Golgi apparatus, were detected in the sera of patients with infectious mononucleosis or nasopharyngeal carcinoma, by using an indirect immunofluorescence technique. There was no significant correlation between the titers of anti-Epstein-Barr virus antibodies and those of autoantibodies. Our findings suggest that the autoantibody production is antigen-driven.

Twenty-five patients with idiopathic Raynaud's phenomenon were followed prospectively for a mean period of 48 months. Clinical and laboratory assessments were performed on admission and on followup. The sera were analyzed for the presence of autoantibodies (antinuclear, antiskeleton and antiorganelle antibodies). Sixteen patients were antinuclear antibody positive and 2 anticentromere antibody positive. Eight patients produced antivimentin, 5 antimitochondrial, 4 anti-Golgi complex, and 3 anticentriol antibodies. Eleven patients produced antidesmosome antibodies. Only one patient (anti-RNP and antidesmosome antibody positive) developed a systemic disease (mixed connective tissue disease) during followup. The initial screening of sera may help to classify Raynaud's phenomenon as idiopathic more accurately.

The determination of non-organ-specific autoantibodies is a major tool in the serological diagnosis of rheumatic disorders. Antinuclear antibodies (ANA) are routinely determined by indirect immunofluorescence (IFL) testing on cryostat sections, but the use of cultured cell lines now allows to detect new antibody specificities that are obscured on tissue sections. Titres and IFL patterns of antibodies add further information to the interpretation of results. Homogeneous or perimembranous patterns point to systemic lupus erythematosus (SLE) which is better characterized by the presence of antibodies to double-stranded DNA or to the Smith-antigen (Sm-antigen) detected by other methods. Antibodies to extractable nuclear antigens (ENA) are strongly correlated with connective tissue disease, the main representatives of which may now be identified serologically by the presence of marker anti-ENA antibodies.

A subset of B cells expressing the CD5 marker, a 67 KD molecule, has been implicated in the pathogenesis of autoimmune disease. To study the immunoglobulin repertoire of CD5+ B cells we investigated chronic lymphocytic leukemic (CLL) cells, since the majority of the malignant clones express CD5. CLL were induced to secrete their IgM in vitro by phorbol 12-myristate 13-acetate (PMA) and the supernatants screened for binding to a panel of autoantigens. Twelve out of 14 CLL clones were autoreactive, binding to Fc of IgG, ssDNA, dsDNA, histones, cardiolipin, or cytoskeletal components. Many also bound to more than one antigen tested for, showing multispecificity. Our data suggest that a high proportion of CD5+ B cells are programmed to secrete multispecific autoantibodies.

The detection of circulating serum antibodies that react with various nuclear or cytoplasmic antigens of cell substrates has become an established investigation in the diagnosis of autoimmune diseases. Antinuclear antibodies as well as some non-organ-specific anticytoplasmic autoantibodies might be of diagnostic significance. Some examples are anti-mitochondrial antibodies in autoimmune liver diseases, anti-cytoskeletal antibodies in chronic active hepatitis, polymyositis and infectious diseases and microsomal antibodies in juvenile cryptogenic liver cirrhosis. New techniques and methods such as indirect immunofluorescence on tissue culture substrates, enzymelinked immunoassays and immunoblotting tests now form the basis of further studies. These tests allow a more sensitive and specific assay for lysosomal and Golgi apparatus antigens. It may be possible to more precisely associate particular anti-cytoplasmic antibodies that react with autoimmune diseases.