Dissolved organic carbon (DOC) has received considerable attention in freshwater research, particularly since the early 2000s when increasing trends became apparent. However, remaining questions need ...to be resolved to address future effects of DOC on surface waters. This study was undertaken to determine (1) the relative importance of acidity and ionic strength in driving DOC increases in waters recovering from acidification and (2) the role played by long-term acid rain effects on soil. Data obtained from temporal and spatial monitoring of 142 headwater streams throughout the Adirondack region of New York (USA) were used to evaluate chemical relationships involving DOC. Year-round monitoring of three streams of differing acidification status were combined with intermittent stream surveys during spring snowmelt throughout this 24,243 km2 region that is recovering from acidification of soils and surface waters.
Despite acidic deposition decreases reaching levels estimated for the early 1900s, DOC concentrations exhibited linear increases from the early 2000s through 2019. Ionic strength or conductivity showed consistent inverse relationships with DOC in all data comparisons from 2004‐05 to 2018‐19. In contrast, relationships between pH and DOC did not support increasing pH as an important factor in DOC increases. Inconsistent relationships between pH and DOC were due to strongly acidic organic acids that remain unprotonated throughout the pH range of these waters and limited weak-acid deprotonation below pH 6.2. Decreasing ionic strength increases DOC solubility by expanding the diffuse double layer, which fosters disaggregation of organic matter and dispersion of colloids. This affect controlled DOC solubilization below a pH of approximately 6.2. Distinguishing between ionic strength and pH effects is important because further large reductions in acidic deposition are not expected but continued soil-water dilution is likely from soil-Ca2+ depletion and the decreasing rate of Ca2+ leaching by SO42− and NO3−, which are still being released from soil organic matter.
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•DOC in surface waters continues to increase despite low acid rain levels.•Decreases in ionic strength, not acidity are increasing soil carbon solubility.•Soil‑calcium depletion is a key factor in ongoing decreases in ionic strength.•Ionic strength decreases will continue driving further increases in DOC.•pH is not controlling DOC in drainage waters, DOC is instead controlling pH.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Gut dysbiosis is commonly observed in patients with cirrhosis and chronic gastrointestinal disorders; however, its effect on antitumor immunity in the liver is largely unknown. Here we studied how ...the gut microbiome affects antitumor immunity in cholangiocarcinoma. Primary sclerosing cholangitis (PSC) or colitis, two known risk factors for cholangiocarcinoma which promote tumor development in mice, caused an accumulation of CXCR2
polymorphonuclear myeloid-derived suppressor cells (PMN-MDSC). A decrease in gut barrier function observed in mice with PSC and colitis allowed gut-derived bacteria and lipopolysaccharide to appear in the liver and induced CXCL1 expression in hepatocytes through a TLR4-dependent mechanism and an accumulation of CXCR2
PMN-MDSCs. In contrast, neomycin treatment blocked CXCL1 expression and PMN-MDSC accumulation and inhibited tumor growth even in the absence of liver disease or colitis. Our study demonstrates that the gut microbiome controls hepatocytes to form an immunosuppressive environment by increasing PMN-MDSCs to promote liver cancer. SIGNIFICANCE: MDSCs have been shown to be induced by tumors and suppress antitumor immunity. Here we show that the gut microbiome can control accumulation of MDSCs in the liver in the context of a benign liver disease or colitis.
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Limitations in current diagnostic procedures warrant identification of new methodologies to improve diagnoses of cancer patients. In this context, long non-coding RNAs (lncRNAs) have emerged as ...stable biomarkers which are expressed abundantly in tumors. Importantly, these can be detected at all stages of tumor development, and thus may provide potential biomarkers and/or therapeutic targets. Recently, we suggested that aberrant levels of lncRNAs can be used to determine the invasive and metastatic potential of tumor cells. Further, direct correlations of lncRNAs with cancer-derived inflammation, metastasis, epithelial-to-mesenchymal transition, and other hallmarks of cancer indicate their potential as biomarkers and targets for cancer. Thus, in this review we have discussed the importance of small nucleolar RNA host gene 12 (SNHG12), a lncRNA, as a potential biomarker for a variety of cancers. A meta-analysis of a large cohort of cancer patients revealed that SNHG12 may also serve as a potential target for cancer-directed interventions due to its involvement in unfolded protein responses, which many tumor cells exploit to both evade immune-mediated attack and enhance the polarization of effector immune cells (e.g., macrophages and T cells). Thus, we propose that SNHG12 may serve as both a biomarker and a druggable therapeutic target with promising clinical potential.
It has been shown in many solid tumors that the overexpression of the pro-survival Bcl-2 family members Bcl-xL and Mcl-1 confers resistance to a variety of chemotherapeutic agents. Mcl-1 is a ...critical survival protein in a variety of cell lineages and is critically regulated via ubiquitination.
The Mcl-1, Bcl-xL and USP9X expression patterns in human lung and colon adenocarcinomas were evaluated via immunohistochemistry. Interaction between USP9X and Mcl-1 was demonstrated by immunoprecipitation-western blotting. The protein expression profiles of Mcl-1, Bcl-xL and USP9X in multiple cancer cell lines were determined by western blotting. Annexin-V staining and cleaved PARP western blotting were used to assay for apoptosis. The cellular toxicities after various treatments were measured via the XTT assay.
In our current analysis of colon and lung cancer samples, we demonstrate that Mcl-1 and Bcl-xL are overexpressed and also co-exist in many tumors and that the expression levels of both genes correlate with the clinical staging. The downregulation of Mcl-1 or Bcl-xL via RNAi was found to increase the sensitivity of the tumor cells to chemotherapy. Furthermore, our analyses revealed that USP9X expression correlates with that of Mcl-1 in human cancer tissue samples. We additionally found that the USP9X inhibitor WP1130 promotes Mcl-1 degradation and increases tumor cell sensitivity to chemotherapies. Moreover, the combination of WP1130 and ABT-737, a well-documented Bcl-xL inhibitor, demonstrated a chemotherapeutic synergy and promoted apoptosis in different tumor cells.
Mcl-1, Bcl-xL and USP9X overexpression are tumor survival mechanisms protective against chemotherapy. USP9X inhibition increases tumor cell sensitivity to various chemotherapeutic agents including Bcl-2/Bcl-xL inhibitors.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Surgical Treatment of Early Glottic Cancer Silver, Jennifer A; Turkdogan, Sena; Roy, Catherine F ...
Otolaryngologic clinics of North America
56, Issue:
2
Journal Article
Peer reviewed
The incidence of all head and neck malignancies is rising worldwide, with carcinoma of the larynx constituting approximately 1% of all cancers. Early glottic cancer responds quite favorably to ...surgical intervention due to its early presentation, coupled with the low rate of regional and distant metastases. This article focuses on various approaches to the surgical treatment of early glottic cancer. Details include the clinical and radiological evaluation of laryngeal cancer, the goals of treatment, current surgical options for early disease, approach to surgical resection margins and management of nodal disease, and complications associated with each treatment modality.
There is a limited understanding of host defense mechanisms targeting intracellular pathogens that proliferate in a lysosome. Coxiella burnetii is a model bacterial pathogen capable of replicating in ...the hydrolytic and acidic environment of the lysosome. It has been shown that gamma interferon (IFNγ)-stimulated host cells restrict C. burnetii replication by a mechanism that involves host IDO1 depletion of tryptophan. Host cells deficient in IDO1 activity, however, retain the ability to restrict C. burnetii replication when stimulated with IFNγ, which suggests additional mechanisms of host defense. This study identified syntaxin 11 (STX11) as a host protein that contributes to IFNγ-mediated suppression of C. burnetii replication. STX11 is a SNARE protein; SNARE proteins are proteins that mediate fusion of host vesicles with specific subcellular organelles. Depletion of STX11 using either small interfering RNA (siRNA)- or CRISPR-based approaches enhanced C. burnetii replication intracellularly. Stable expression of STX11 reduced C. burnetii replication in epithelial cells and macrophages, which indicates that this STX11-dependent cell-autonomous response is operational in multiple cell types and can function independently of other IFNγ-induced factors. Fluorescently tagged STX11 localized to the
-containing vacuole (CCV), and STX11 restriction was found to involve an interaction with STX8. Thus, STX11 regulates a vesicle fusion pathway that limits replication of this intracellular pathogen in a lysosome-derived organelle.
Cell intrinsic defense mechanisms are used by eukaryotic cells to restrict the replication and dissemination of pathogens. This study identified a human protein called syntaxin 11 (STX11) as a host restriction factor that inhibits the intracellular replication of Coxiella burnetii. Syntaxins regulate the delivery of cargo inside vesicles by promoting specific membrane fusion events between donor and acceptor vesicles. Data presented here demonstrate that STX11 regulates an immunological defense pathway that controls replication of pathogens in lysosome-derived organelles, which provides new insight into the function of this SNARE protein.
Long-term changes in the chemistry of wet deposition and lake water were investigated in the Adirondack Region of New York. Marked decreases in concentrations of SO4 2- and H+ in wet deposition have ...occurred at two sites since the late 1970s. These decreases are consistent with long-term declines in emissions of sulfur dioxide (SO2) in the eastern United States. Changes in wet NO3 - deposition and nitrogen oxides (NO x ) emissions have been minor over the same interval. Virtually all Adirondack Lakes have shown marked decreases in concentrations of SO4 2-, which coincide with decreases in atmospheric S deposition. Concentrations of NO3 - have also decreased in several Adirondack lakes. As atmospheric N deposition has not changed over this period, the mechanism contributing to this apparent increase in lake/watershed N retention is not evident. Decreases in concentrations of SO4 2- + NO3 - have resulted in increases in acid-neutralizing capacity (ANC) and pH and resulted in a shift in the speciation of monomeric Al from toxic inorganic species toward less toxic organic forms in some lakes. Nevertheless, many lakes continue to exhibit pH values and concentrations of inorganic monomeric Al that are critical to aquatic biota. Extrapolation of rates of ANC increase suggests that the time frame of chemical recovery of Adirondack Lakes will be several decades if current decreases in acidic deposition are maintained.
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IJS, KILJ, NUK, PNG, UL, UM
A 4
year study surveyed 131 lakes across New York State beginning in 2003 to improve our understanding of mercury and gather information from previously untested waters. Our study focused on ...largemouth and smallmouth bass, walleye and yellow perch, common piscivorous fish shown to accumulate high mercury concentrations and species important to local fisheries. Fish from Adirondack and Catskill Forest Preserve lakes generally had higher mercury concentrations than those from lakes in other areas of the state. Variability between nearby individual lakes was observed, and could be due to differences in water chemistry, lake productivity or the abundance of wetlands in the watershed. We found the following factors impact mercury bioaccumulation: fish length, lake pH, specific conductivity, chlorophyll
a, mercury concentration in the water, presence of an outlet dam and amount of contiguous wetlands.
Lake water chemistry variables, dams, and wetlands play major roles in determining fish mercury concentrations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
With decreases in acid deposition, nitrogen:phosphorus (N:P) ratios in lakes are anticipated to decline, decreasing P limitation of phytoplankton and potentially changing current food web dynamics. ...This effect could be particularly pronounced in the Adirondack Mountains of New York State, a historic hotspot for effects of acid deposition. In this study, we evaluate spatial patterns of nutrient dynamics in Adirondack lakes and use these to infer potential future temporal trends. We calculated Mann–Kendall tau correlations among total phosphorus (TP), chlorophyll a, dissolved organic carbon (DOC), acid neutralizing capacity (ANC), and nitrate (NO3-) concentrations in 52 Adirondack Long Term Monitoring (ALTM) program lakes using samples collected monthly during 2008–2012. We evaluated the hypothesis that decreased atmospheric N and S deposition will decrease P limitation in freshwater ecosystems historically impacted by acidification. We also compared these patterns among lake watershed characteristics (i.e., seepage or lacking a surface outlet, chain drainage, headwater drainage, thin glacial till, medium glacial till). We found that correlations (P < 0.05) were highly dependent upon the different hydrologie flowpaths of seepage vs. drainage lakes. Differentiations among watershed till depth were also important in determining correlations due to water interaction with surficial geology. Additionally, we found low NO3-:TP (N:P mass) values in seepage lakes (2.0 in winter, 1.9 in summer) compared to chain drainage lakes (169.4 in winter, 49.5 in summer) and headwater drainage lakes (97.0 in winter, 10.9 in summer), implying a high likelihood of future shifts in limitation patterns for seepage lakes. With increasing DOC and decreasing NO3- concentrations coinciding with decreases in acid deposition, there is reason to expect changes in nutrient dynamics in Adirondack lakes. Seepage lakes may become N-limited, while drainage lakes may become less P-limited, both resulting in increased productivity. Long-term measurements of TP and chlorophyll a from the Adirondacks are needed to inform how future decreases in atmospheric N and S deposition will influence the trophic status of lake ecosystems throughout the region.
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BFBNIB, FZAB, GIS, IJS, INZLJ, KILJ, NLZOH, NMLJ, NUK, OILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK, ZRSKP
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