Interferons in Sjögren’s Syndrome: Genes, Mechanisms, and Effects

Sjögren’s syndrome (SS) is a common, progressive autoimmune exocrinopathy distinguished by dry eyes and mouth and affects ∼0.7% of the European population. Overexpression of transcripts induced by interferons (IFN), termed as an “IFN signature,” has been found in SS patients. Four microarray studies have been published in SS that identified dysregulated genes within type I IFN signaling in either salivary glands or peripheral blood of SS patients. The mechanism of this type I IFN activation is still obscure, but several possible explanations have been proposed, including virus infection-initiated and immune complex-initiated type I IFN production by plasmacytoid dendritic cells. Genetic predisposition to increased type I IFN signaling is supported by candidate gene studies showing evidence for association of variants within IFN-related genes. Once activated, IFN signaling may contribute to numerous aspects of SS pathophysiology, including lymphocyte infiltration into exocrine glands, autoantibody production, and glandular cell apoptosis. Thus, dysregulation of IFN pathways is an important feature that can be potentially used as a serum biomarker for diagnosis and targeting of new treatments in this complex autoimmune disease

Gene expression profiling of epithelium-associated FcRL4(+) B cells in primary Sjogren's syndrome reveals a pathogenic signature

In primary Sjögren's syndrome (pSS), FcRL4+ B cells are present in inflamed salivary gland tissue, within or in close proximity to ductal epithelium. FcRL4 is also expressed by nearly all pSS-related mucosa-associated lymphoid tissue (MALT) B cell lymphomas, linking FcRL4 expression to lymphomagenesis. Whether glandular FcRL4+ B cells are pathogenic, how these cells originate, and how they functionally differ from FcRL4- B cells in pSS is unclear. This study aimed to investigate the phenotype and function of FcRL4+ B cells in the periphery and parotid gland tissue of patients with pSS. First, circulating FcRL4+ B cells from 44 pSS and 54 non-SS-sicca patients were analyzed by flow cytometry. Additionally, RNA sequencing of FcRL4+ B cells sorted from parotid gland cell suspensions of 6 pSS patients was performed. B cells were sorted from cell suspensions as mini bulk (5 cells/well) based on the following definitions: CD19+CD27-FcRL4- ('naive'), CD19+CD27+FcRL4- ('memory'), and CD19+FcRL4+ B cells. We found that, although FcRL4+ B cells were not enriched in blood in pSS compared with non-SS sicca patients, these cells generally exhibited a pro-inflammatory phenotype. Genes coding for CD11c (ITGAX), T-bet (TBX21), TACI (TNFRSF13B), Src tyrosine kinases and NF-κB pathway-related genes were, among others, significantly upregulated in glandular FcRL4+ B cells versus FcRL4- B cells. Pathway analysis showed upregulation of B cell activation, cell cycle and metabolic pathways. Thus, FcRL4+ B cells in pSS exhibit many characteristics of chronically activated, pro-inflammatory B cells and their gene expression profile suggests increased risk of lymphomagenesis. We postulate that these cells contribute significantly to the epithelial damage seen in the glandular tissue and that FcRL4+ B cells are an important treatment target in pSS

1976 Research Progress Reports; Fruit and Vegetable Processing and Food Technology

Evaluation of tomato cultivars for processing / W. A. Gould, R. Stillabower and D. Grindell -- Using tomato seeds / J. R. Geisman -- Evaluation of snap bean cultivars for processing / W. A. Gould and R. Stillabower -- Flame sterilization of canned green beans / J. R. Mount and W. A. Gould -- Flame sterilization of canned peas / J. R. Ice, J. R. Mount and W. A. Gould -- Flame sterilization of other canned products / John Mount and W. A. Gould -- Determination of factors affecting heat penetration in flame sterilized canned whole kernel sweet corn / R. Joseph and W. A. Gould -- Geotrichum candidum: the new FDA indicator of plant sanitation for the food processing industry / J. G. Fox and W. A. Gould -- Recycling spent pickling brines ; Uses for the outer green leaves of cabbage / J. R. Geisman -- The development of a fish spread by the utilization of freshwater drum from Lake Erie / J. D. Morgan and W. A. Gould -- Development of a sausage product from Lake Erie freshwater drum / S. Hauck and W. A. Gould -- Utilization of Lake Erie freshwater drum for fish sticks / W. Stone and W. A. Gould -- Acidification and thermal processing of tripolyphosphate treated freshwater drum fillets / T. F. Chin and W. A. Gould -- Effect of lipid and fatty acid composition on keeping quality / Andrew C. Peng -- Grape lipids / P. A. Higgins and A. C. Peng -- The effect of maturation on the lipid content of 'Concord' grapes / John A. Bauman and James F. Gallander -- Stability of ascorbic acid in fortified apple juice / M. I. Mahmoud and W. A. Gould -- Wine deacidification with mixed cultures of Schizosaccharomyces pombe and Saccharomyces cerevisiae ; The effect of bacterial inoculum on malo-lactic fermentation in wines ; Concentrations of tartaric and malic acids of several wine varieties grown in Ohio / J. F. Gallander and J. F. Stetso

Plio-Pleistocene trends in ice rafted debris on the Lomonosov Ridge

Although more than 700 sediment cores exist from the Arctic Ocean, the Plio-Pleistocene evolution of the basin and its marginal seas remains virtually unknown. This is largely due the shallow penetration of most of these records, and difficulties associated with deriving chronologies for the recovered material. The Integrated Ocean Drilling Program’s (IODP) Expedition 302 (Arctic Coring Expedition, ACEX) recovered 197 m of Neogene/Quaternary sediment from the circumpolar regions of the Lomonosov Ridge. As detailed analyses of this material emerge, research is beginning to formulate a long-term picture of paleoceanographic changes in the central Arctic Ocean. This paper reviews the ACEX Plio-Pleistocene age model, identifies uncertainties, and addresses ways in which these may be eliminated. Within the established stratigraphic framework, a notable reduction in the abundance of ice rafted debris (IRD) occurs in the early part of the Pleistocene and persists until Marine Isotope Stage 6 (MIS 6). Therefore, while global oceanographic proxies indicate the gradual growth of terrestrial ice-sheets during this time, IRD delivery to the central Arctic Ocean remained comparatively low and stable. Within the resolution of existing data, the Pleistocene reduction in IRD is synchronous with predicted changes in both the inflow of North Atlantic and Pacific waters, which in modern times are known to exert a strong influence on sea ice stability

Tracking the provenance of Greenland-sourced, Holocene aged, individual sand-sized ice-rafted debris using the Pb-isotope compositions of feldspars and 40Ar/39Ar ages of hornblendes

The provenance of sand-sized ice-rafted debris (IRD) sourced from Greenland is currently difficult to determine. Such knowledge, if it could be ascertained with a high degree of certainty, could be applied to the Greenland-proximal marine records to improve both our understanding of modern-day spatial patterns of iceberg rafting and the past history of the Greenland Ice Sheet (GIS). Recent studies have highlighted the utility of the Pb-isotope composition of individual sand-sized feldspars and the 40Ar/39Ar ages of individual sand-sized hornblendes in this regard. However, before any such provenance toolkit can be applied to the palaeo-record, it is necessary first to determine whether this approach can be used to track the sources of known recent Greenland-proximal IRD deposition. To this end we present new records of the Pb-isotope composition and the 40Ar/39Ar ages of individual sand-sized grains of feldspars and hornblendes, respectively, from modern Greenland glacifluvial and fjord sands and Holocene to modern Greenland-proximal marine sediments. These new data demonstrate that sand-sized feldspars and hornblendes glacially eroded by the GIS exhibit distinct intra- and inter-tectonic terrane differences in their Pb-isotope compositions and ages and that these differences are clearly expressed in the geochemistry and geochronology of sand-sized IRD deposited in marine sediments around Greenland. Although overlap exists between some Greenland-proximal IRD ‘source fields’ defined by these data, our approach has the potential to both better understand spatial patterns of Greenland-derived IRD in the modern day as well as during past episodes of iceberg calving

Variants at multiple loci implicated in both innate and adaptive immune responses are associated with Sjögren’s syndrome

Sjögren’s syndrome is a common autoimmune disease (~0.7% of European Americans) typically presenting as keratoconjunctivitis sicca and xerostomia. In addition to strong association within the HLA region at 6p21 (Pmeta=7.65×10−114), we establish associations with IRF5-TNPO3 (Pmeta=2.73×10−19), STAT4 (Pmeta=6.80×10−15), IL12A (Pmeta =1.17×10−10), FAM167A-BLK (Pmeta=4.97×10−10), DDX6-CXCR5 (Pmeta=1.10×10−8), and TNIP1 (Pmeta=3.30×10−8). Suggestive associations with Pmeta<5×10−5 were observed with 29 regions including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2, and PHIP amongst others. These results highlight the importance of genes involved in both innate and adaptive immunity in Sjögren’s syndrome

Implementation of Novel Biomarkers in the Diagnosis, Prognosis, and Management of Acute Kidney Injury: Executive Summary from the Tenth Consensus Conference of the Acute Dialysis Quality Initiative (ADQI)

Detection of acute kidney injury is undergoing a dynamic revolution ofbiomarker technology allowing greater, earlier, and more accuratedetermination of diagnosis, prognosis, and with powerful implication formanagement. Biomarkers can be broadly considered as any measurablebiologic entity or process that allows differentiation between normalfunction and injury or disease. The ADQI (Acute Dialysis QualityInitiative) had its Ninth Consensus Conference dedicated to synthesisand formulation of the existing literature on biomarkers for thedetection of acute kidney injury in a variety of settings. In the papersthat accompany this summary, ADQI workgroups fully develop key conceptsfrom a summary of the literature in the domains of early diagnosis,differential diagnosis, prognosis and management, and concurrentphysiologic and imaging measures