Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus

Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 × 10(-8), odds ratio = 1.70) and Korean (P = 8.33 × 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-κB subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.     

The value of data

Data citation and the derivation of semantic constructs directly from datasets have now both found their place in scientific communication. The social challenge facing us is to maintain the value of traditional narrative publications and their relationship to the datasets they report upon while at the same time developing appropriate metrics for citation of data and data constructs.     

Accumulation of 2-micron latex particles in mouse Peyer's patches during chronic latex feeding

2-micron latex particles accumulated in macrophages in intestinal Peyer's patches of mice given latex suspensions as drinking fluid for 2 months. The number of particles accumulating was a direct (but nonlinear) function of the number ingested. Some of the latex particles were still present in Peyer's patches 6 weeks after the cessation of latex feeding.     

Monoclonal antibodies identify a cell-surface antigen associated with an activated cellular oncogene

A variety of antigens have been identified on the surface of the malignant cell. However, identical antigens are often found on non-malignant cells of the same or different histological origin, or of a different stage of embryonic development. Many of these tumour-associated antigens appear to be only incidentally expressed on neoplastic cells. Clearly, it would be of great interest to identify cell-surface antigens whose expression is associated specifically with the transformed state and linked directly with the mechanisms responsible for transformation. The detection of activated cellular oncogenes in human and animal cancer cells by the technique of DNA transfection has allowed the isolation of genetic elements which are thought to have a critical role in malignancy. Here, in an effort to identify cell-surface antigens associated with the neoplastic process, we have generated hybridomas which secrete monoclonal antibodies that react specifically with cell-surface determinants found on NIH 3T3 cells transformed by transfection with a group of rat neuroblastoma oncogenes. These antibodies bind to and immunoprecipitate a phosphoprotein of relative molecular mass 185,000 (185 K) from a DNA donor rat neuroblastoma and 13 independent rat neuroblastoma DNA transfectants. There was no antibody reactivity with normal NIH 3T3 cells or with NIH 3T3 cells transformed by various other agents.     

Demonstration of particulate accumulations in solid tissue

Summary We describe a histological clearing procedure involving partial tissue hydrolysis by pancreatin and demonstrate its application. Changes in distribution of 5.7-m latex particles in mouse liver and heart muscle 6 months after i.v. latex injection were quantitated. The method is useful for studies of long-term redistribution of particles in vivo and for locating large, infrequent particles which are difficult to find by ordinary tissue-sectioning techniques.Acknowledgments. Research supported by U.S. Department of Energy under contract EY-76-C-02-0016 and U.S. Environmental Protection Agency under contract 79-D-X-05333. The assistance of Mr Willie White is gratefully acknowledged. We are indebted to Mr William Marin for photomicrography.The research described in this report involved animals maintained in animal care facilities fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

Vertical extension of the subglacial drainage system into basal crevasses

Water plays a first-order role in basal sliding of glaciers and ice sheets and is often a key constituent of accelerated glacier motion. Subglacial water is known to occupy systems of cavities and conduits at the interface between ice and the underlying bed surface, depending upon the history of water input and the characteristics of the substrate. Full understanding of the extent and configuration of basal water is lacking, however, because direct observation is difficult. This limits our ability to simulate ice dynamics and the subsequent impacts on sea-level rise realistically. Here we show that the subglacial hydrological system can have a large volume of water occupying basal crevasses that extend upward from the bed into the overlying ice. Radar and seismic imaging combined with in situ borehole measurements collected on Bench Glacier, Alaska, reveal numerous water-filled basal crevasses with highly transmissive connections to the bed. Some crevasses extend many tens of metres above the bed and together they hold a volume of water equivalent to at least a decimetre layer covering the bed. Our results demonstrate that the basal hydrologic system can extend high into the overlying ice mass, where basal crevasses increase water-storage capacity and could potentially modulate basal water pressure. Because basal crevasses can form under commonly observed glaciological conditions, our findings have implications for interpreting and modelling subglacial hydrologic processes and related sliding accelerations of glaciers and ice sheets.