Annual and Seasonal Patterns of Burned Area Products in Arctic-Boreal North America and Russia for 2001-2020

Boreal and Arctic regions have warmed up to four times quicker than the rest of the planet since the 1970s. As a result, boreal and tundra ecosystems are experiencing more frequent and higher intensity extreme weather events and disturbances, such as wildfires. Yet limitations in ground and satellite data across the Arctic and boreal regions have challenged efforts to track these disturbances at regional scales. In order to effectively monitor the progression and extent of wildfires in the Arctic-boreal zone, it is essential to determine whether burned area (BA) products are accurate representations of BA. Here, we use 12 different datasets together with MODIS active fire data to determine the total yearly BA and seasonal patterns of fires in Arctic-boreal North America and Russia for the years 2001–2020. We found relatively little variability between the datasets in North America, both in terms of total BA and seasonality, with an average BA of 2.55 ± 1.24 (standard deviation) Mha/year for our analysis period, the majority (ca. 41%) of which occurs in July. In contrast, in Russia, there are large disparities between the products—GFED5 produces over four times more BA than GFED4s in southern Siberia. These disparities occur due to the different methodologies used; dNBR (differenced Normalized Burn Ratio) of short-term composites from Landsat images used alongside hotspot data was the most consistently successful in representing BA. We stress caution using GABAM in these regions, especially for the years 2001–2013, as Landsat-7 ETM+ scan lines are mistaken as burnt patches, increasing errors of commission. On the other hand, we highlight using regional products where possible, such as ABoVE-FED or ABBA in North America, and the Talucci et al. fire perimeter product in Russia, due to their detection of smaller fires which are often missed by global products

Purification of Reversibly Oxidized Proteins (PROP) Reveals a Redox Switch Controlling p38 MAP Kinase Activity

Oxidation of cysteine residues of proteins is emerging as an important means of regulation of signal transduction, particularly of protein kinase function. Tools to detect and quantify cysteine oxidation of proteins have been a limiting factor in understanding the role of cysteine oxidation in signal transduction. As an example, the p38 MAP kinase is activated by several stress-related stimuli that are often accompanied by in vitro generation of hydrogen peroxide. We noted that hydrogen peroxide inhibited p38 activity despite paradoxically increasing the activating phosphorylation of p38. To address the possibility that cysteine oxidation may provide a negative regulatory effect on p38 activity, we developed a biochemical assay to detect reversible cysteine oxidation in intact cells. This procedure, PROP, demonstrated in vivo oxidation of p38 in response to hydrogen peroxide and also to the natural inflammatory lipid prostaglandin J2. Mutagenesis of the potential target cysteines showed that oxidation occurred preferentially on residues near the surface of the p38 molecule. Cysteine oxidation thus controls a functional redox switch regulating the intensity or duration of p38 activity that would not be revealed by immunodetection of phosphoprotein commonly interpreted as reflective of p38 activity

Proteomic Profile of Reversible Protein Oxidation Using PROP, Purification of Reversibly Oxidized Proteins

Signal transduction pathways that are modulated by thiol oxidation events are beginning to be uncovered, but these discoveries are limited by the availability of relatively few analytical methods to examine protein oxidation compared to other signaling events such as protein phosphorylation. We report here the coupling of PROP, a method to purify reversibly oxidized proteins, with the proteomic identification of the purified mixture using mass spectrometry. A gene ontology (GO), KEGG enrichment and Wikipathways analysis of the identified proteins indicated a significant enrichment in proteins associated with both translation and mRNA splicing. This methodology also enabled the identification of some of the specific cysteine residue targets within identified proteins that are reversibly oxidized by hydrogen peroxide treatment of intact cells. From these identifications, we determined a potential consensus sequence motif associated with oxidized cysteine residues. Furthermore, because we identified proteins and specific sites of oxidation from both abundant proteins and from far less abundant signaling proteins (e.g. hepatoma derived growth factor, prostaglandin E synthase 3), the results suggest that the PROP procedure was efficient. Thus, this PROP-proteomics methodology offers a sensitive means to identify biologically relevant redox signaling events that occur within intact cells

The isothiocyanate class of bioactive nutrients covalently inhibit the MEKK1 protein kinase

<p>Abstract</p> <p>Background</p> <p>Dietary isothiocyanates (ITCs) are electrophilic compounds that have diverse biological activities including induction of apoptosis and effects on cell cycle. They protect against experimental carcinogenesis in animals, an activity believed to result from the transcriptional induction of "Phase 2" enzymes. The molecular mechanism of action of ITCs is unknown. Since ITCs are electrophiles capable of reacting with sulfhydryl groups on amino acids, we hypothesized that ITCs induce their biological effects through covalent modification of proteins, leading to changes in cell regulatory events. We previously demonstrated that stress-signaling kinase pathways are inhibited by other electrophilic compounds such as menadione. We therefore tested the effects of nutritional ITCs on MEKK1, an upstream regulator of the SAPK/JNK signal transduction pathway.</p> <p>Methods</p> <p>The activity of MEKK1 expressed in cells was monitored using in vitro kinase assays to measure changes in catalytic activity. The activity of endogenous MEKK1, immunopurified from ITC treated and untreated LnCAP cells was also measured by in vitro kinase assay. A novel labeling and affinity reagent for detection of protein modification by ITCs was synthesized and used in competition assays to monitor direct modification of MEKK1 by ITC. Finally, immunoblots with phospho-specific antibodies were used to measure the activity of MAPK protein kinases.</p> <p>Results</p> <p>ITCs inhibited the MEKK1 protein kinase in a manner dependent on a specific cysteine residue in the ATP binding pocket. Inhibition of MEKK1 catalytic activity was due to direct, covalent and irreversible modification of the MEKK1 protein itself. In addition, ITCs inhibited the catalytic activity of endogenous MEKK1. This correlated with inhibition of the downstream target of MEKK1 activity, i.e. the SAPK/JNK kinase. This inhibition was specific to SAPK, as parallel MAPK pathways were unaffected.</p> <p>Conclusion</p> <p>These results demonstrate that MEKK1 is directly modified and inhibited by ITCs, and that this correlates with inhibition of downstream activation of SAPK. These results support the conclusion that ITCs may carry out many of their actions by directly targeting important cell regulatory proteins.</p

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Selected peptides that were observed with a cysteine residue that had been biologically oxidized from proteins that were preferentially identified <i>before</i> H₂O₂ oxidation treatment of cells.

†<p>The total number of scans that were observed for that peptide. All of the scans tabulated passed a 3% FDR filter cutoff. The replicate analysis of 6 independent biological samples for both the control and H₂O₂ treated cells are shown. Data referred to in the text combine the replicate analyses.</p>‡<p>The eValue represents the best (i.e. smallest) OMSSA eValue score matched to the particular peptide sequence. This provides a relative measure of the overall confidence that the peptide was in the sample (i.e. a true positive), with 0.00E+000 representing the highest confidence.</p>*<p>Lower case “c” indicates location of carboxyamidomethyl derivatization(s).</p

Selected proteins identified using the PROP analysis that were preferentially identified <i>before</i> H₂O₂ oxidation treatment of cells.

†<p>Leading number indicates the number of unique peptides for a particular protein that were observed while the number in parentheses indicates the total number of scans that were observed for that protein. All of the scans tabulated passed a 3% FDR filter cutoff. An “X” indicates that no scans were observed that passed the FDR filter. The replicate analysis of 6 independent biological samples for both the control and H₂O₂ treated cells are shown. Data referred to in the text combine the replicate analyses.</p>‡<p>The pValue represents the product of the best (i.e. smallest) eValue score observed for each <i>unique</i> peptide sequence for the given protein. This provides a relative measure of the overall confidence that the protein was in the sample (i.e. a true positive), with 0.00E+000 representing the highest confidence.</p

PROP-proteomics procedure.

<p>Schematic diagram showing steps involved in the PROP-proteomics procedure that are described in detail in both <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032527#s2" target="_blank">Methods</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0032527#s3" target="_blank">Results</a>.</p

Selected proteins identified using the PROP analysis on six replicate cell cultures treated or not with H₂O₂ that were preferentially identified <i>after</i> H₂O₂ oxidation treatment of cells.

†<p>Leading number indicates the number of unique peptides for a particular protein that were observed while the number in parentheses indicates the total number of scans that were observed for that protein; in other words, a protein indicated as 3(13) had three unique peptides identified a total of 13 times. All of the scans tabulated passed a 3% FDR filter cutoff. An “X” indicates that no scans were observed that passed the FDR filter. The replicate analysis of 6 independent biological samples for both the control and H₂O₂ treated cells are shown. Data referred to in the text combine the replicate analyses.</p>‡<p>The pValue represents the product of the best (i.e. smallest) eValue score observed for each <i>unique</i> peptide sequence for the given protein. This provides a relative measure of the overall confidence that the protein was in the sample (i.e. a true positive), with 0.00E+000 representing the highest confidence.</p

Potential Consensus Sequence for Oxidized Cysteine Residues.

<p>The sequence logo representation of the frequency of the amino acid residues surrounding the oxidized cysteine residues, located at position “0”, that were identified from the PROP proteomics procedure.</p