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  • 1
    ISSN: 1573-0417
    Keywords: acid deposition ; Adirondacks ; diatoms ; lake acidification ; paleoecology ; sediment chemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract Paleoecological analysis of the sediment record of 12 Adirondack lakes reveals that the 8 clearwater lakes with current pH 〈 5.5 and alkalinity 〈 10 μeq l-1 have acidified recently. The onset of this acidification occurred between 1920 and 1970. Loss of alkalinity, based on quanitative analysis of diatom assemblages, ranged from 2 to 35 μeq l-1. The acidification trends are substantiated by several lines of evidence including stratigraphies of diatom, chrysophyte, chironomid, and cladoceran remains, Ca:Ti and Mn:Ti ratios, sequentially extracted forms of Al, and historical fish data. Acidification trends appear to be continuing in some lakes, despite reductions in atmospheric sulfur loading that began in the early 1970s. The primary cause of the acidification trend is clearly increased atmospheric deposition of strong acids derived from the combustion of fossil fuels. Natural processes and watershed disturbances cannot account for the changes in water chemistry that have occurred, but they may play a role. Sediment core profiles of Pb, Cu, V, Zn, S, polycyclic aromatic hydrocarbons, magnetic particles, and coal and oil soot provide a clear record of increased atmospheric input of materials associated with the combustion of fossil fuels beginning in the late 1800s and early 1900s. The primary evidence for acidification occurs after that period, and the pattern of water chemistry response to increased acid inputs is consistent with current understanding of lake-watershed acidification processes.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-0417
    Keywords: Chaoborus ; Chaoboridae ; Diptera ; fish ; acidification ; paleolimnology ; Adirondacks ; Bosmina
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Geosciences
    Notes: Abstract Paleolimnological analyses of Chaoborus mandibles were used to assess the status of fish populations over the previous 150 to 300 years in five lakes from the Adirondack region of New York State. Windfall Pond (pH 6.5) has not acidified and currently has viable fish populations. Big Moose Lake (pH 5.0) has acidified in recent years, and the number of fish populations declined from 14 in the 1930's to seven in the early 1980's. The occurrence of only migratory Chaoborus (subgenus Sayomyia) in the cores indicated the long term presence of fish populations in Windfall Pond and Big Moose Lake. Brooktrout Lake (pH 5.0), Deep Lake (pH 4.7) and Upper Wallface Pond (pH 4.8) have all acidified in recent years, and all three are currently fishless. Chaoborus (Sayomyia) was present throughout the Brooktrout Lake core, but the entirely limnetic species, C. americanus, appeared in the topmost interval in the core. The appearance of C. americanus in the top of the core indicated a recent elimination of fish from Brooktrout Lake, probably during the 1970's. Elimination of fish by the 1940's was inferred for Deep Lake because C. americanus appeared above the 1930 level and replaced C. trivittatus as the dominant. Dominance of C. americanus throughout the Upper Wallface Pond core indicated that planktivorous fish were never present. These results strongly suggest that stratigraphic analyses of Chaoborus mandibles provide a useful assessment of the general status of historical fish populations in Adirondack lakes. The technique should be useful in other regions, as well as for applications other than those concerning lake acidification.
    Type of Medium: Electronic Resource
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  • 3
    Publication Date: 2012-09-21
    Description: Recent data reveal an important role for B cells in the pathogenesis of chronic GVHD (cGVHD). Patients with cGVHD have delayed B-cell reconstitution and elevated BAFF to B-cell ratios compared to patients without cGVHD. The mechanisms promoting and sustaining B-cell activation in this disease, however, remain unknown. As BAFF increases murine B-cell metabolism and survival and maintains autoreactive B-cell clones, we performed ex vivo analyses of peripheral B cells from 51 patients who either had or did not have active cGVHD and were greater than 1 year from the time of allogeneic hematopoietic stem cell transplantation. We found that B cells from patients with active cGVHD were in a heightened metabolic state and were resistant to apoptosis. Exogenous BAFF treatment amplified cell size and survival in B cells from these patients. We found significantly increased signaling through ERK and AKT that associated with decreased levels of proapoptotic Bim, suggesting a mechanistic link between elevated BAFF levels and aberrant B-cell survival. Thus, we identify a role for BAFF in the pathogenesis of cGVHD and define B-cell activation and survival pathways suitable for novel therapeutic development in cGVHD.
    Keywords: Transplantation
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 4
    Publication Date: 2014-03-28
    Description: Although B cells have emerged as important contributors to chronic graft-versus-host-disease (cGVHD) pathogenesis, the mechanisms responsible for their sustained activation remain unknown. We previously showed that patients with cGVHD have significantly increased B cell–activating factor (BAFF) levels and that their B cells are activated and resistant to apoptosis. Exogenous BAFF confers a state of immediate responsiveness to antigen stimulation in normal murine B cells. To address this in cGVHD, we studied B-cell receptor (BCR) responsiveness in 48 patients who were 〉1 year out from allogeneic hematopoietic stem cell transplantation (HSCT). We found that B cells from cGVHD patients had significantly increased proliferative responses to BCR stimulation along with elevated basal levels of the proximal BCR signaling components B cell linker protein (BLNK) and Syk. After initiation of BCR signaling, cGVHD B cells exhibited increased BLNK and Syk phosphorylation compared with B cells from patients without cGVHD. Blocking Syk kinase activity prevented relative post-HSCT BCR hyper-responsiveness of cGVHD B cells. These data suggest that a lowered BCR signaling threshold in cGVHD associates with increased B-cell proliferation and activation in response to antigen. We reveal a mechanism underpinning aberrant B-cell activation in cGVHD and suggest that therapeutic inhibition of the involved kinases may benefit these patients.
    Keywords: Transplantation
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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  • 5
    Publication Date: 2015-06-26
    Description: Novel therapies for chronic graft-versus-host disease (cGVHD) are needed. Aberrant B-cell activation has been demonstrated in mice and humans with cGVHD. Having previously found that human cGVHD B cells are activated and primed for survival, we sought to further evaluate the role of the spleen tyrosine kinase (Syk) in cGVHD in multiple murine models and human peripheral blood cells. In a murine model of multiorgan system, nonsclerodermatous disease with bronchiolitis obliterans where cGVHD is dependent on antibody and germinal center (GC) B cells, we found that activation of Syk was necessary in donor B cells, but not T cells, for disease progression. Bone marrow–specific Syk deletion in vivo was effective in treating established cGVHD, as was a small-molecule inhibitor of Syk, fostamatinib, which normalized GC formation and decreased activated CD80/86 + dendritic cells. In multiple distinct models of sclerodermatous cGVHD, clinical and pathological disease manifestations were not eliminated when mice were therapeutically treated with fostamatinib, though both clinical and immunologic effects could be observed in one of these scleroderma models. We further demonstrated that Syk inhibition was effective at inducing apoptosis of human cGVHD B cells. Together, these data demonstrate a therapeutic potential of targeting B-cell Syk signaling in cGVHD.
    Keywords: Transplantation
    Print ISSN: 0006-4971
    Electronic ISSN: 1528-0020
    Topics: Biology , Medicine
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