Tumour-promoting inflammation is a “hallmark” of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these ...relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear.
We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10−8) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value (“q-value”) <0.05 was used as a threshold to define “strong evidence” to support associations and 0.05 ≤ q-value < 0.20 to define “suggestive evidence”. A colocalisation posterior probability (PPH4) >70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis.
We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10–1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20–1.69, q-value = 0.055, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53–0.81, q-value = 0.067, PPH4 = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88–0.97, q-value = 0.15, PPH4 = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48–4.10, q-value = 0.072, PPH4 = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk.
Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated.
Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654).
An interlaboratory exercise on 5-μm-thick chromium nitride (CrN) coated AISI 304 austenitic stainless steel coupons was undertaken to evaluate and compare test methods for adhesion of thin coatings. ...Test coupons were deposited with and without thin (25 and 50 nm) gold–palladium interlayers. These interlayers were designed to vary the effective adhesion of the CrN in a controlled way without significantly altering the CrN coating fracture properties. The interlaboratory exercise was conducted by an international group of laboratories examining Rockwell indentation, scratch testing, uniaxial tensile and four-point bend. None of the tests were able to discriminate between coupons with or without the interlayer. The new EU Community Bureau of Reference scratch test reference material (BCR-692), distributed to participants to assist in the calibration of scratch test instruments used in this study, was shown to be able to diagnose instrument problems.
Resilience Smith Aldrich, Rebekkah
2018, 2018-06-07, 2018-06-13, Letnik:
2
eBook
This thought-provoking treatment of timely topic offers important points of consideration for library administrators and managers, as well as scholars of urban planning, public policy, disaster ...recovery, and related disciplines.
O-linked N-acetylglucosamine (O-GlcNAc) is a reversible posttranslational modification of Ser and Thr residues on cytosolic and nuclear proteins of higher eukaryotes catalyzed by O-GlcNAc transferase ...(OGT). O-GlcNAc has recently been found on Notch1 extracellular domain catalyzed by EGF domain-specific OGT. Aberrant O-GlcNAc modification of brain proteins has been linked to Alzheimer's disease (AD). However, understanding specific functions of O-GlcNAcylation in AD has been impeded by the difficulty in characterization of O-GlcNAc sites on proteins. In this study, we modified a chemical/enzymatic photochemical cleavage approach for enriching O-GlcNAcylated peptides in samples containing ∼100 μg of tryptic peptides from mouse cerebrocortical brain tissue. A total of 274 O-GlcNAcylated proteins were identified. Of these, 168 were not previously known to be modified by O-GlcNAc. Overall, 458 O-GlcNAc sites in 195 proteins were identified. Many of the modified residues are either known phosphorylation sites or located proximal to known phosphorylation sites. These findings support the proposed regulatory cross-talk between O-GlcNAcylation and phosphorylation. This study produced the most comprehensive O-GlcNAc proteome of mammalian brain tissue with both protein identification and O-GlcNAc site assignment. Interestingly, we observed O-β-GlcNAc on EGF-like repeats in the extracellular domains of five membrane proteins, expanding the evidence for extracellular O-GlcNAcylation by the EGF domain-specific OGT. We also report a GlcNAc-β-1,3-Fuc-α-1-O-Thr modification on the EGF-like repeat of the versican core protein, a proposed substrate of Fringe β-1,3-N-acetylglucosaminyltransferases.
Abstract
While pet foods have been shifting towards grain-free foods, the majority still utilize cereals and their protein rich co-products. Corn gluten meal (CGM), soybean meal (SBM) and distillers ...dried grains (DDG) have been used in pet foods for decades. A new higher protein DDG (next generation-distillers dried grains; NG-DDG) has become available and merits evaluation. Therefore, the objective of this study was to determine the effect of NG-DDG in pet diets on digestibility and stool consistency in dogs, and palatability in dogs and cats. Twelve beagle dogs were fed diets with a similar ingredient base in which NG-DDG replaced SBM or CGM. Diets were formulated to be isonutritional, contain equal amounts of protein, and were supplemented with chromic oxide to estimate apparent total tract digestibility (ATTD). The DM digestibility for the dogs fed the CGM diet was higher (P < 0.05) than those fed the SBM diet (81.13 vs. 78.78%), with dogs fed NG-DDG intermediate to both (79.90%). The dogs fed CGM had great OM ATTD (P < 0.05) than dogs fed NG-DDG and SBM (85.26 vs. average 82.64%). The dogs fed SBM had lower CP ATTD (P < 0.05) than those fed CGM and NG-DDG (80.90 vs. average 83.72%). There were no differences (P>0.05) between dietary treatment for ATTD of crude fat, crude fiber, or energy (average 90.73, 10.03, or 73.17%, respectively). Dogs fed the diet containing NG-DDG had larger (P < 0.05) fecal mass than those fed SBM and CGM and had a similar fecal score to those fed SBM, but higher (P < 0.05) than those fed diets with CGM. In palatability assessment dogs had a preference (P < 0.05) for diets containing CGM over SBM and NG-DDG, but cats showed a preference for diets containing NG-DDG (P < 0.05) over those produced with CGM. These results indicate that NG-DDG is comparable to CGM and SBM in dog and cat diets.
While pet foods have been shifting towards grain-free foods, the majority still utilize cereals and their protein rich co-products. Corn gluten meal (CGM), soybean meal (SBM) and distillers dried ...grains (DDG) have been used in pet foods for decades. A new higher protein DDG (next generation-distillers dried grains; NG-DDG) has become available and merits evaluation. Therefore, the objective of this study was to determine the effect of NG-DDG in pet diets on digestibility and stool consistency in dogs, and palatability in dogs and cats. Twelve beagle dogs were fed diets with a similar ingredient base in which NG-DDG replaced SBM or CGM. Diets were formulated to be isonutritional, contain equal amounts of protein, and were supplemented with chromic oxide to estimate apparent total tract digestibility (ATTD). The DM digestibility for the dogs fed the CGM diet was higher (P < 0.05) than those fed the SBM diet (81.13 vs. 78.78%), with dogs fed NG-DDG intermediate to both (79.90%). The dogs fed CGM had great OM ATTD (P < 0.05) than dogs fed NG-DDG and SBM (85.26 vs. average 82.64%). The dogs fed SBM had lower CP ATTD (P < 0.05) than those fed CGM and NG-DDG (80.90 vs. average 83.72%). There were no differences (P>0.05) between dietary treatment for ATTD of crude fat, crude fiber, or energy (average 90.73, 10.03, or 73.17%, respectively). Dogs fed the diet containing NG-DDG had larger (P < 0.05) fecal mass than those fed SBM and CGM and had a similar fecal score to those fed SBM, but higher (P < 0.05) than those fed diets with CGM. In palatability assessment dogs had a preference (P < 0.05) for diets containing CGM over SBM and NG-DDG, but cats showed a preference for diets containing NG-DDG (P < 0.05) over those produced with CGM. These results indicate that NG-DDG is comparable to CGM and SBM in dog and cat diets.
The response of 316L austenitic stainless steel when untreated or sputter coated with CrN and S-phase (nitrogen supersaturated austenitic stainless steel) has been evaluated under sliding contact ...corrosion-wear situations. The lowest friction coefficient was recorded for the CrN coated material which also gave the best resistance to corrosion-wear. The S-phase coating reduced corrosion-wear compared to untreated 316L, but despite exhibiting the most electrochemically passive behaviour, was inferior to CrN. The corrosion-wear of the uncoated and S-phase coated 316L was dominated by mechanical wear, which in the latter case involved brittle fracture of the S- phase coating and/or fracture along the S-phase-substrate interface.
Abstract
Most pet foods utilize traditional ingredients like corn, wheat, and soy. These ingredients and other grains, such as distillers dried grains (DDG), have been used by the pet food industry. ...Corn-fermented protein (CFP) is a nutrient-dense enhancement on DDG but has not been evaluated in pet food. Therefore, it was the objective of this study to determine the effect of CFP in the production of extruded pet diets, and to determine the effect on nutrient utilization (digestibility) and stool consistency in dogs, and palatability in dogs and cats. Experimental diets with treatment protein sources (corn gluten meal CGM, soybean meal SBM, and CFP) were produced in triplicate using a single-screw extruder. Processing parameters and kibble samples were collected at timed intervals during diet production. Kibbles were evaluated for physical dimension and texture. No differences (P > 0.05) were observed in any physical dimension or texture parameters evaluated, with exception of radial expansion, which was lower (P < 0.05) for CFP kibble compared to others. The CFP kibble required a smaller (P < 0.05) mass restriction valve opening, to keep similar bulk density among dietary treatments. However, there was no difference (P > 0.05) in specific mechanical energy among treatments during diet production. Twelve beagles were fed the experimental diets in a 3 × 3 replicated Latin Square design in which four dogs were randomly assigned to each of three treatments for each period. Diets were formulated to be isonitrogenous and were supplemented with titanium dioxide to serve as an external marker in order to estimate apparent total tract digestibility. Dogs were housed individually and fed twice daily, and water was available ad libitum. Feces were collected after feedings. The diet produced with CGM was more digestible (P < 0.05) than CFP and SBM for dry matter, organic matter, crude protein, crude fat, and gross energy. Further, the CFP diet was also less (P < 0.05) digestible than the SBM diet for dry matter and organic matter. Dogs fed the diet containing CFP had higher (P < 0.05) fecal mass than those fed SBM and CGM. The CFP diet also resulted in a higher fecal score (P < 0.05) than those fed diets with the CGM diet, but similar (P > 0.05) to the SBM diet. For palatability assessment, dogs had a preference (P < 0.05) for CGM over SBM or CFP, but cats showed a preference (P < 0.05) for SBM and CFP over CGM. Results indicate that CFP is acceptable for use in dog and cat diets. Further research should be conducted to evaluate the use of these ingredients at lower inclusion levels.
Asthma has been reported to be more prevalent among Hispanics of Puerto Rican heritage than among other Hispanics and among Hispanics born in the United States or who immigrated as children than ...among those who came as adults; however, direct comparisons across Hispanic groups are lacking.
To test whether asthma is more prevalent among Hispanics of Puerto Rican heritage than among other Hispanic groups, whether asthma is associated with age of immigration, and whether chronic obstructive pulmonary disease varies by heritage in a large, population-based cohort of Hispanics in the United States.
The Hispanic Community Health Study/Study of Latinos researchers recruited a population-based probability sample of 16,415 Hispanics/Latinos, 18-74 years of age, in New York City, Chicago, Miami, and San Diego. Participants self-reported Puerto Rican, Cuban, Dominican, Mexican, Central American, or South American heritage; birthplace; and, if relevant, age at immigration. A respiratory questionnaire and standardized spirometry were performed with post-bronchodilator measures for those with airflow limitation.
The prevalence of physician-diagnosed asthma among Puerto Ricans (36.5%; 95% confidence interval, 33.6-39.5%) was higher than among other Hispanics (odds ratio, 3.9; 95% confidence interval, 3.3-4.6). Hispanics who were born in the mainland United States or had immigrated as children had a higher asthma prevalence than those who had immigrated as adults (19.6, 19.4, and 14.1%, respectively; P < 0.001). Current asthma, bronchodilator responsiveness, and wheeze followed similar patterns. Chronic obstructive pulmonary disease prevalence was higher among Puerto Ricans (14.1%) and Cubans (9.8%) than among other Hispanics (<6.0%), but it did not vary across Hispanic heritages after adjustment for smoking and prior asthma (P = 0.22), by country of birth, or by age at immigration.
Asthma was more prevalent among Puerto Ricans, other Hispanics born in the United States, and those who had immigrated as children than among other Hispanics. In contrast, the higher prevalence of chronic obstructive pulmonary disease among Puerto Ricans and Cubans was largely reflective of differential smoking patterns and asthma.
S-Glutathionylation (SSG) is an important regulatory posttranslational modification on protein cysteine (Cys) thiols, yet the role of specific cysteine residues as targets of modification is poorly ...understood. We report a novel quantitative mass spectrometry (MS)-based proteomic method for site-specific identification and quantification of S-glutathionylation across different conditions. Briefly, this approach consists of initial blocking of free thiols by alkylation, selective reduction of glutathionylated thiols, and covalent capture of reduced thiols using thiol affinity resins, followed by on-resin tryptic digestion and isobaric labeling with iTRAQ (isobaric tags for relative and absolute quantitation) for MS-based identification and quantification. The overall approach was initially validated by application to RAW 264.7 mouse macrophages treated with different doses of diamide to induce glutathionylation. A total of 1071 Cys sites from 690 proteins were identified in response to diamide treatment, with ~90% of the sites displaying >2-fold increases in SSG modification compared to controls. This approach was extended to identify potential SSG-modified Cys sites in response to H2O2, an endogenous oxidant produced by activated macrophages and many pathophysiological stimuli. The results revealed 364 Cys sites from 265 proteins that were sensitive to S-glutathionylation in response to H2O2 treatment, thus providing a database of proteins and Cys sites susceptible to this modification under oxidative stress. Functional analysis revealed that the most significantly enriched molecular function categories for proteins sensitive to SSG modifications were free radical scavenging and cell death/survival. Overall the results demonstrate that our approach is effective for site-specific identification and quantification of SSG-modified proteins. The analytical strategy also provides a unique approach to determining the major pathways and cellular processes most susceptible to S-glutathionylation under stress conditions.
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•Novel proteomics approach for site-specific quantification of S-glutathionylation.•>1000 Cys sites identified in RAW macrophages treated with diamide or H2O2.•364 Cys sites from 265 proteins identified as sensitive to H2O2 treatments.•Potential significance of SSG in oxidative stress signaling pathways revealed.
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