Climate Impacts From a Removal of Anthropogenic Aerosol Emissions.

Limiting global warming to 1.5 or 2.0°C requires strong mitigation of anthropogenic greenhouse gas (GHG) emissions. Concurrently, emissions of anthropogenic aerosols will decline, due to coemission with GHG, and measures to improve air quality. However, the combined climate effect of GHG and aerosol emissions over the industrial era is poorly constrained. Here we show the climate impacts from removing present-day anthropogenic aerosol emissions and compare them to the impacts from moderate GHG-dominated global warming. Removing aerosols induces a global mean surface heating of 0.5-1.1°C, and precipitation increase of 2.0-4.6%. Extreme weather indices also increase. We find a higher sensitivity of extreme events to aerosol reductions, per degree of surface warming, in particular over the major aerosol emission regions. Under near-term warming, we find that regional climate change will depend strongly on the balance between aerosol and GHG forcing.

Analysis of intraepithelial lymphocytes from major histocompatibility complex (MHC)-deficient mice: no evidence for a role of MHC class II antigens in the positive selection of V delta 4+ gamma delta T cells.

Three-color flow cytometric analysis was carried out with intraepithelial lymphocytes from mice deficient in expression of major histocompatibility complex (MHC) antigens. These experiments were done to address the possible role of MHC class II molecules in the positive selection of V delta 4+ gamma delta T cells. By analyzing mice deficient MHC class II antigens alone or in combination with MHC class I antigens, no evidence was found for positive selection of V delta 4+ cells among CD8 alpha + or CD4-CD8- subpopulations of gamma delta T cell receptor-positive cells. Because V delta 4+, CD8 alpha + cells were reported to be positively selected on I-Ek and hybrid I-Ek/b molecules, class II-deficient animals were crossed with I-Ek transgenic mice and progeny examined for V delta 4 expression. Again, no evidence for positive selection was found. Interestingly, in MHC class I-deficient animals, the total number of gamma delta T cells was about twofold higher than in control and MHC class II-deficient mice and the proportion of V delta 4-expressing cells was correspondingly decreased. Taken together, these results cast doubt on a major role for conventional MHC antigens in shaping the gamma delta T cell repertoire of intraepithelial lymphocytes.

T cell receptor repertoire of gamma delta cells generated from the 14-day embryonic mouse thymus.

Whole, undisrupted 14 day mouse fetal thymus lobes cultured in the presence of 10 U/ml IL-2 generate a heterogeneous population of gamma delta-expressing T cells. Phenotypic analysis has shown that the majority of gamma delta T cells in such cultures stain with the anti-V gamma 3-specific mAb 536. To investigate the V gamma T-cell receptor diversity of cultured fetal thymocytes, cDNA was prepared and amplified using the polymerase chain reaction. The DNA fragments obtained were subsequently cloned and sequenced and compared with those obtained from fresh and organ-cultured 14 day fetal thymus lobes. Results obtained tend to support a positive selection model of gamma delta T cell differentiation.

Long-range chromosomal mapping of the carcinoembryonic antigen (CEA) gene family cluster.

A long-range physical map of the carcinoembryonic antigen (CEA) gene family cluster, which is located on the long arm of chromosome 19, has been constructed. This was achieved by hybridization analysis of large DNA fragments separated by pulse-field gel electrophoresis and of DNA from human/rodent somatic cell hybrids, as well as the assembly of ordered sets of cosmids for this gene region into contigs. The different approaches yielded very similar results and indicate that the entire gene family is contained within a region located at position 19q13.1-q13.2 between the CYP2A and the D19S15/D19S8 markers. The physical linkage of nine genes belonging to the CEA subgroup and their location with respect to the pregnancy-specific glycoprotein (PSG) subgroup genes have been determined, and the latter are located closer to the telomere. From large groups of ordered cosmid clones, the identity of all known CEA subgroup genes has been confirmed either by hybridization using gene-specific probes or by DNA sequencing. These studies have identified a new member of the CEA subgroup (CGM8), which probably represents a pseudogene due to the existence of two stop codons, one in the leader and one in the N-terminal domain exons. The gene order and orientation, which were determined by hybridization with probes from the 5' and 3' regions of the genes, are as follows: cen/3'-CGM7-5'/3'-CGM2-5'/5'-CEA-3'/5'-NCA-3'/5'-CGM1- 3'/3'-BGP-5'/3'- CGM9-5'/3'-CGM6-5'/5'-CGM8-3'/PSGcluster/qter.

Culture conditions dictate whether mouse fetal thymus lobes generate predominantly gamma/delta or alpha/beta T cells.

Thymus lobes from 14 day-old mouse embryos cultured submerged in r-IL-2 generated a mixture of CD8 alpha+/CD4- and CD8-/CD4- gamma delta TcR expressing cells (Ceredig et. al. 1989). Based upon Northern analysis with TcR constant region probes, no alpha beta T cells could be identified in these cultures. Submerged lobes also showed responsiveness to IL-7. In contrast, when cultured at an air liquid interface as organ cultures (OC), most cells appeared to express alpha beta TcR (Ceredig 1988). Thus depending on the mode of culture, fetal thymus lobes generate predominantly gamma delta or alpha beta T cells; it is unclear how this difference is regulated. Previous phenotypic and functional experiments suggested that gamma delta T cells may be present in OC. In order to study gamma delta T cells in both submerged lobe and OC, we have carried out three colour flow microfluorimetric analysis of gamma delta TcR, abTcR, CD3, J11d and CD8 beta expression by subpopulations of CD8 alpha and CD4 defined thymocytes. In addition, using V gamma-specific oligonucleotides and the polymerase chain reaction, we have begun identifying and sequencing the V gamma repertoire of gamma delta T cells in these mouse fetal thymus cultures.

The human pregnancy-specific glycoprotein genes are tightly linked on the long arm of chromosome 19 and are coordinately expressed.

The pregnancy-specific glycoprotein (PSG) genes encode a group of proteins which are found in large amounts in placenta and maternal serum. In situ hybridization analyses of metaphase chromosomes reveal that all the human pregnancy-specific glycoprotein (PSG) genes are located on the long arm of chromosome 19 (19q13.2-13.3), overlapping the region containing the closely-related carcinoembryonic antigen (CEA) gene subgroup. Higher resolution analyses indicate that the PSG genes are closely linked within an 800kb SacII restriction endonuclease fragment. This has been confirmed through restriction endonuclease mapping and DNA sequence analyses of isolated genomic clones, which show that at least some of these genes are located in very close proximity. Further, these studies have helped to identify a new member of the PSG gene subfamily (PSG7). DNA/RNA hybridization analyses, using gene-specific oligonucleotide probes based on published sequences, showed that five from six PSG genes tested are coordinately transcribed in the placenta. Due to the close proximity of these genes and their coordinated expression pattern, common transcriptional regulatory elements may exist.