Methane transport from the active layer to lakes in the Arctic using Toolik Lake,Alaska, as a case study

Methane emissions in the Arctic are important, and may be contributing to global warming. While methane emission rates from Arctic lakes are well documented, methods are needed to quantify the relative contribution of active layer groundwater to the overall lake methane budget. Here we report measurements of natural tracers of soil/groundwater, radon, and radium, along with methane concentration in Toolik Lake, Alaska, to evaluate the role active layer water plays as an exogenous source for lake methane. Average concentrations of methane, radium, and radon were all elevated in the active layer compared with lake water (1.6 × 10⁴ nM, 61.6 dpm⋅m⁻³, and 4.5 × 10⁵ dpm⋅m⁻³ compared with 1.3 × 10² nM, 5.7 dpm⋅m⁻³, and 4.4 × 10³ dpm⋅m⁻³, respectively). Methane transport from the active layer to Toolik Lake based on the geochemical tracer radon (up to 2.9 g⋅m⁻²⋅y⁻¹) can account for a large fraction of methane emissions from this lake. Strong but spatially and temporally variable correlations between radon activity and methane concentrations (r² > 0.69) in lake water suggest that the parameters that control methane discharge from the active layer also vary. Warming in the Arctic may expand the active layer and increase the discharge, thereby increasing the methane flux to lakes and from lakes to the atmosphere, exacerbating global warming. More work is needed to quantify and elucidate the processes that control methane fluxes from the active layer to predict how this flux might change in the future and to evaluate the regional and global contribution of active layer water associated methane inputs.Methane is a powerful greenhouse gas estimated to be responsible for approximately one-fifth of man-made global warming, and its concentration has been increasing (1). The largest natural source of methane is wetlands (2), including a major component from northern high-latitude regions containing permafrost (3). Observations in the Siberian Arctic show high rates of methane release from both the coastal seabed and land-based permafrost soils (4, 5). Previous research has also documented extensive methane release from Arctic lakes, primarily via ebullition, with significant spatial variability within and between lakes (6, 7). Methane in Arctic lakes forms by microbial production (methanogenesis) in the water column and/or within anaerobic lake sediments (8). However, it is possible that some fraction of the observed methane is not produced within the lakes but is rather transported to the lakes from external, land-based sources through subterranean groundwater discharge (SGD) (9) (Fig. 1). Specifically, water in the active layer (the surficial layer of the soil system above the permafrost that thaws every summer) could be transported into lakes and rivers during the thaw season (May−August) (10). Groundwater in some temperate climate regions can be highly enriched in methane (11), and groundwater discharge contributions to the methane budget of the coastal ocean and lakes in temperate climate have been reported (12, 13). This conduit of methane transport may be particularly important in regions where organic-rich soils and anaerobic conditions promote methane production in the soil, such as in the Arctic (14). SGD occurs everywhere at the land−water interface in lakes, rivers, and the ocean, and evidence of water flow through the active layer in permafrost-dominated regions is found in springs, in open water reaches and base flow of rivers, in talik, and in the distribution of halophytic vegetation (15, 16). Methane fluxes sourced from land into lakes and coastal waters in the Arctic have not been directly measured. The organic-rich soils and anaerobic conditions in the active layer in the Arctic are prime conditions for methane production, and this methane could be transported to lakes and coastal waters.Fig. 1.(A) Schematic diagram of active layer water-associated methane flux to Arctic lakes and related climate feedbacks. Warming for more than a century has resulted in various degrees of permafrost thawing. As climate warms, permafrost stability is likely ...     

Tolerability and efficacy of GM-CSF [Leucomax] in patients with small cell lung cancer treated with intensive chemotherapy

The aim of this study was to evaluate tolerability and efficacy of Leucomax (Sandoz/Schering Plough) used for neutropenia in patients with small cell lung cancer (SCLC) treated with etoposide and cisplatin. The potential influence of granulocyte-macrophage colony stimulating factor (GM-CSF) on chemotherapy relative dose intensity (RDI) was also evaluated. The chemotherapy used was the following, cisplatin 50 mg m^-2 i.v. 1 and 7 day, etoposide 170 mg m^-2 i.v. 3-5 days, q 3-4 weeks. Patients received a median of six cycles (range 2-8) over 4-36 weeks (median: 20). Thirty-two consecutive patients were treated, six were excluded. Eleven patients received GM-CSF 5 /zg kg"1 s.c. due to absolute neutrophil count (ANC), 1000/mm3 until recovery (ANC > 2000 mm3) or during 7 days, and thereafter prophylactically 24 hours post subsequent chemotherapy cycles for 7 days. Four patients received single GM-CSF course during the terminal disease phase. In 11 patients, there was no neutropenia requiring GM-CSF during the whole treatment course. Toxicity of chemotherapy was high, including thrombocytopenia, neutropenia, anaemia, mucositis, fever and hypotension. GM-CSF toxicity was the following, first dose reaction - one patient, local erythema - two patients, arthralgia - one patient, hypotension, chills, fever requiring GM-CSF discontinuation one patient RDI of cisplatin/etoposide was 0.77/0.62 in GM-CSF group, and 0.90/ 0.80 in patients who didn’t receive Leucomax. Overall objective response rate to chemotherapy and complete response rate were 80% (21/26), 26% (7/26) and median survival of all patients was 10 months. Median disease free survival was 8 months. Four patients are alive, two patients lost during progression, 20 died. Administration of GM-CSF did not appear to improve RDI of chemotherapy, overall response rate (RR) nor survival in this phase I/II clinical study. RDI of chemotherapy was reduced in patients receiving GM-CSF due to thrombocytopenia and/or extrahaematologic toxicity of chemotherapy.     

Effects of 8-Chloroadenosine-3',5'-Monophosphate in Combination with Irradiation in L5178Y Mouse Lymphoblasts

The effect of a new anticancer drug, 8-chloroadenosine 3',5'-monophosphate (8-Cl-cAMP-), a site selective cAMP analog, that inhibits growth of cancer cells in vitro, was examined in L5178Y (LY) murine lymphoma cells. Two LY sublines were used, grown in full Fisher's medium: LY-R, radiation resistant and LY-S, radiation sensitive. The latter was also adapted to grow in simplified medium. In the full medium conversion of 8-Cl-cAMP to 8-chloroadenosine presumably was the case of cytotoxicity. In the simplified medium this conversion was limited and the cytotoxic effect much less pronounced. Cytotoxicity was equal in LY-R and LY-S cells and it was not related to changes in the cell cycle distribution; the latter were observed in LY-S, but not in LY-R cells. There was no interaction of the drug with x-rays in LY cells grown either in full or simplified medium.     

Local parastomal hernia repair with biological mesh is safe and effective

Purpose

The goal of this study was to evaluate the efficacy, morbidity and safety of local parastomal hernia repair using biological mesh.

The concentration of adenine nucleotides in platelets of patients with primary chronic glomerulonephritis

Nephrotic syndrome (n.s.) is associated with numerous blood coagulation abnormalities and a marked predisposition to thromboembolism. Increased aggregation and activation of platelets in patients with glomerulonephritis (g.l.n. p.t.s.) may partly explain this status. The aim of this study was to measure the platelets adenine nucleotides concentration. The study was performed in 57 patients with a renal biopsy confirmed primary glomerulonephritis and 24 sex and age matched healthy volunteers which served as a control group. The patients were divided into two subgroups: subgroup I/A--36 patients with the symptoms of the nephrotic syndrome and subgroup I/B--21 patients with chronic glomerulonephritis and proteinuria but without the symptoms of nephrotic syndrome. Concentration of adenine nucleotides in platelets was measured using HPLC. In the subgroup I/A significantly lower levels of ATP, ADP and AMP concentrations in platelets were observed comparing to control subjects. Simultaneously significant correlation between both ATP and ADP concentration and plasma levels of albumin, total cholesterol, LDL-cholesterol, triglycerides and fibrinogen were found in g.l.n. p.t.s. SUMMARY AND CONCLUSIONS: 1. Significantly lower concentrations of adenine nucleotides in platelets of gln pts with the nephrotic syndrome may result from their activation. 2. Protein and lipid metabolism as well as fibrinogen seem to influence ATP and ADP concentrations in platelets of g.l.n. p.t.s.     

AbetaPP-overexpression and proteasome inhibition increase alphaB-crystallin in cultured human muscle: relevance to inclusion-body myositis

Amyloid-beta precursor protein (AbetaPP) and its fragment amyloid-beta (Abeta) are increased in s-IBM muscle fibers and appear to play an important role in the pathogenic cascade. alphaB-Crystallin (alphaBC) was shown immunohistochemically to be accumulated in s-IBM muscle fibers, but the stressor(s) influencing alphaBC accumulation was not identified. We now demonstrate, using our experimental IBM model based on genetic overexpression of AbetaPP into cultured normal human muscle fibers, that: (1) AbetaPP overexpression increased alphaBC 3.7-fold (p=0.025); (2) additional inhibition of proteasome with epoxomicin increased alphaBC 7-fold (p=0.002); and (3) alphaBC physically associated with AbetaPP and Abeta oligomers. We also show that in biopsied s-IBM muscle fibers, alphaBC was similarly increased 3-fold (p=0.025) and physically associated with AbetaPP and Abeta oligomers. We propose that increased AbetaPP is a stressor increasing alphaBC expression in s-IBM muscle fibers. Determining the consequences of alphaBC association with Abeta oligomers could have clinical therapeutic relevance.     

Mutational Hotspot in the SARS-CoV-2 Spike Protein N-Terminal Domain Conferring Immune Escape Potential

Global efforts are being made to monitor the evolution of SARS-CoV-2, aiming for early identification of genotypes providing increased infectivity or virulence. However, viral lineage-focused tracking might fail in early detection of advantageous mutations emerging independently across phylogenies. Here, the emergence patterns of Spike mutations were investigated in sequences deposited in local and global databases to identify mutational hotspots across phylogenies and we evaluated their impact on SARS-CoV-2 evolution. We found a striking increase in the frequency of recruitment of diverse substitutions at a critical residue (W152), positioned in the N-terminal domain (NTD) of the Spike protein, observed repeatedly across independent phylogenetic and geographical contexts. These mutations might have an impact on the evasion of neutralizing antibodies. Finally, we found that NTD is a region exhibiting particularly high frequency of mutation recruitments, suggesting an evolutionary path in which the virus maintains optimal efficiency of ACE2 binding combined with the flexibility facilitating the immune escape. We conclude that adaptive mutations, frequently present outside of the receptor-binding domain, can emerge in virtually any SARS-CoV-2 lineage and at any geographical location. Therefore, surveillance should not be restricted to monitoring defined lineages alone.     

In vivo imaging of the human eye using a 2-photon-excited fluorescence scanning laser ophthalmoscope

BackgroundNoninvasive assessment of metabolic processes that sustain regeneration of human retinal visual pigments (visual cycle) is essential to improve ophthalmic diagnostics and to accelerate development of new treatments to counter retinal diseases. Fluorescent vitamin A derivatives, which are the chemical intermediates of these processes, are highly sensitive to UV light; thus, safe analyses of these processes in humans are currently beyond the reach of even the most modern ocular imaging modalities.MethodsWe present a compact, 2-photon-excited fluorescence scanning laser ophthalmoscope and spectrally resolved images of the human retina based on 2-photon excitation (TPE) with near-infrared light. A custom Er:fiber laser with integrated pulse selection, along with intelligent postprocessing of data, enables excitation with low laser power and precise measurement of weak signals.ResultsWe demonstrate spectrally resolved TPE fundus images of human subjects. Comparison of TPE data between human and mouse models of retinal diseases revealed similarity with mouse models that rapidly accumulate bisretinoid condensation products. Thus, visual cycle intermediates and toxic byproducts of this metabolic pathway can be measured and quantified by TPE imaging.ConclusionOur work establishes a TPE instrument and measurement method for noninvasive metabolic assessment of the human retina. This approach opens the possibility for monitoring eye diseases in the earliest stages before structural damage to the retina occurs.FundingNIH, Research to Prevent Blindness, Foundation for Polish Science, European Regional Development Fund, Polish National Agency for Academic Exchange, and Polish Ministry of Science and Higher Education.     

Adhesion of peripheral blood mononuclear cells to vascular endothelium in patients with systemic sclerosis (scleroderma)

Objective. Perivascular infiltrates in skin, subcutaneous tissue, and internal organs are a characteristic feature of early systemic sclerosis (SSc). We studied the first step of migration of peripheral blood mononuclear cells (PBMC) through the vessel wall to the extravascular space, i.e., adhesion of PBMC to endothelial cells (EC), in patients with various forms of SSc (limited scleroderma, diffuse scleroderma, and the transitional form). Methods. Radioisotope-labeled patient PBMC were coincubated with umbilical cord EC in vitro, and the percentage adhesion was measured. Results. Adhesion of PBMC to EC was markedly decreased, while adhesion of isolated active rosetteforming cells (ARFC) was significantly increased, in SSc patients compared with healthy controls. Decreased adhesion of PBMC to EC was found to correlate with a diminished percentage of ARFC in the peripheral blood. Preincubation of PBMC from healthy donors with interleukin-2 (IL-2) enhanced their adhesion to EC, while preincubation of PBMC from SSc patients with this cytokine resulted in a decrease in adhesion in 10 of 14 individuals. IL-1, interferon-γ, and transforming growth factor β had no significant effect on adhesion of SSc patient PBMC to EC. Differences in adhesion of PBMC to EC among the SSc subgroups were not significant. Conclusion. Our findings suggest that in SSc, activation of subpopulations of PBMC leads to their enhanced adhesion to vascular endothelium in vivo and to migration of these cells to the extravascular space, resulting in the elimination from the peripheral blood of those PBMC with high ability to adhere to EC.