Joe Bugyi wanted to expand the transportation company he founded during World War II into Toledo
but he didn’t know anyone in the area
who then worked for commercial vehicle systems supplier Dana
hoping for a referral from someone he trusted
The only person his son could offer up was himself
So Nagle Jr. left his job, opened the terminal with wife Joanne in 1977, and went to work forming relationships with the local foodservice community. And those connections helped them start their own trucking business, Nagle Toledo
in 1984 after Bugyi closed his company due to industry deregulation
the firm still is fortified by fast friendships and familial bonds
“We’re focused on making sure this company continues to thrive because we have 120 families who count on us,” said Nagle’s son
who helped his parents start the company and now serves as president and CEO
“We want to make sure they have a good home—one they could potentially retire from.”
doing so for decades is exceedingly difficult
The 2008 Great Recession forced the refrigerated carrier to downsize
the COVID-19 pandemic inflated operating expenses
and today’s soft freight market is stifling rates
But Nagle’s long-standing emphasis on building relationships is buoying the business
“Trucking isn’t a job to us,” Ed said
going to work at the truck stop where his parents originally rented an office
He helped his parents create Nagle Toledo in June 1984
and then welcomed his three brothers into the family business: Steve a few months later
The brothers ran the company together until Mike left in 2008
leaving Ed as sole owner—until the next generation takes up the torch
as part of its operations implementation team
and Jeff is “doing very well” in financial services
I’ll buy it and find someone to run it,’” he said
He loves the life and figures he has 10-15 years left in his career
But he’s already working to identify his replacement because he cares too much about Nagle’s employees to leave their fate undetermined
“We have to make sure this company survives,” he said
The operation today includes five companies: Nagle Toledo
which maintains the operating authority; Nagle Equipment
home to the trucks and trailers; Nagle Leasing
including two warehouses; and Nagle Logistics Group
Nagle today employs 66 drivers and 115 total people
hauling fresh and frozen products for food retailers across the Northeast
Nagle moved from a leased space to Walbridge
The 15-acre property boasts a 15,000-sq.-ft
The combined operation generated $25.7 million in 2023
with $13.6 million in truckload revenue and $10.2 million from third-party logistics services—and Ed is optimistic about further expansion
“We expect to see good growth over the next five to seven years in logistics and dedicated transportation
and somewhat in over-the-road,” he said
The post-2008 “commoditization” of long-haul trucking devalued relationships
especially when capacity was overly abundant
as it is now in the wake of the spot market high that followed the pandemic
That’s why Nagle is focused on cultivating dedicated business
which is the group’s fastest-growing segment
generating $9 million in service of local manufacturers last year
“The dedicated division is important because it’s two partners who depend on each other,” Ed explained
“They need us to produce their goods
We actually include our profit as a cost of doing business
So it’s not as subject to market fluctuations
you’re at the mercy of economic pressures.”
Dedicated services strengthen relationships
providing long-term stability for customers and employees
who are then more likely to provide personalized
“extra-mile” care to the people they interact with on a daily basis
“The big carriers run phenomenal programs
but they’re ‘cookie cutter.’ If you want their best pricing
you must do everything the same way as the rest of their customers,” Ed contended
along with Nagle’s third-party shop business—which last year generated an additional $1.9 million in revenue—also allows the carrier to withstand persistent freight recessions and keep expanding at a measured pace
“We’re not going to grow the fleet just to grow the fleet,” Ed said
“What’s important to us is to maintain an OR [operating ratio] that is acceptable
Trying to run at 98 or 99.5% just to have bragging rights about how big you are is of no interest to us.”
and 12 non-CDL holders who deliver parts in straight trucks—and caring for them is of great interest
hiring and retaining dependable drivers is increasingly difficult
According to the American Trucking Associations
trucking is short 60,000 drivers—and Nagle only hires drivers with at least two years of experience
“The biggest challenge we have right now is finding quality drivers,” Nagle COO James White said
“And what we’re seeing is drivers have a lot of options
so we might get one who is here three months
they’re going elsewhere because they were offered a different rate.”
The carrier primarily pulls “no-touch freight” from manufacturing facilities to distribution centers
so its drivers—who average 62 years of age—don’t do a lot of heavy lifting
Nagle drops trailers 75-80% of the time to prevent unproductive detentions
and pays OTR drivers a weekly salary while dedicated drivers are paid an hourly rate issued weekly
Nagle regularly invests in equipment that appeals to drivers and advanced technology that promotes safety
including forward- and driver-facing Samsara cameras that monitor for distracted driving and driver fatigue
“That technology is priceless,” said Darrell Tarry
The system also unlocks coaching opportunities
but Nagle maintains a strict policy on cell phone usage
which Ed insists is “the most under-reported cause of accidents in this country.”
The first incident results in three unpaid days off
the second leads to five—and a third triggers termination
the threat of a nuclear verdict is so great that we have an incredible responsibility to all of our employees to make sure a lawsuit doesn’t put us out of business,” Ed said
Nagle's fleet of 78 temperature-controlled trailers and 40 dry vans
as well as customer trucks and trailers in a mutually beneficial affiliation
are maintained by nine mechanics and two parts managers
but because we see the pros and cons other fleets experience
it helps us make decisions,” Ed said
“We’re learning about different types of fuel-water separators
the more confidence you have in the decisions you make.” Nagle
offers up informed equipment recommendations to customers—whose repeat business bolsters the group’s bottom line
Nagle also is extending tractor trade cycles by a year to boost profitability in the soft freight environment
so even if we have an unexpected $30,000 repair to make
that’s still better than spending $200,000 on a new tractor in this market,” he said
And he isn’t overly concerned about maintenance costs rising because the six-bay shop administers an “over-the-top” maintenance program supported by intelligent telematics that enable “predictive” maintenance
The carrier runs Thermo King S-700 transport refrigeration units with TracKing telematics
“It’s a game changer for me,” Tarry said
“It takes what four people used to do down to a simple one-person assignment
I check it three times a day to make sure everything is rolling smoothly.”
The refrigerated trailers are Utility Trailers equipped with P.S.I
tire inflation systems and Samsara tracking devices
enough to maintain “ice cream” temperatures due to the S-700’s cooling capacity
and flat floors that are well suited for palletized freight
They’re heavier than aluminum duct floors but more durable
so we’re now hoping to achieve a 10-year [trailer] life,” he said
Nagle’s tractors are Freightliner Cascadias equippedmwith Thermo King APUs
and Ex-Guard grille guards—an invaluable investment
“They have saved us over $100,000 in repairs
since we started equipping them,” he maintained
He’s equally appreciative of the Cascadia
“It’s been a great truck for us,” he said
“It offers driver comfort and accessibility and gives us good value.”
Nagle sticks with Thermo King for the “phenomenal” aftersales support—and because the manufacturer was the only brand in town when Nagle bought its first truck in 1984
“Toledo has a nice Carrier Transicold dealer now
but we’ve maintained such a solid connection with Thermo King and have great familiarity with their product,” Ed said
And the carrier now runs Utility trailers because of his appreciation for the Wannemacher family
which owns Double A Trailer Sales in Delphos
“We’ve followed the product line they carry because of our relationship,” Ed stated
“So we typically don’t make decisions based on pricing. Double A is trustworthy and ethical
The carrier also depends on its OEM network to inform its approach to zero-emission vehicle adoption
“I’m confident our company will never run electric trucks,” Ed predicted
“I don’t believe the technology is appropriate or sustainable
ATRI published a study saying there aren’t enough rare-earth minerals on this planet to provide all consumers and commercial industries with electric vehicles
And we’re just pushing pollution away from the United States to poorer countries that do the mining.”
EVs also are heavier and more expensive than diesel-powered tractors
so they won’t make any sense until customers demand them
“We can’t afford to be the guinea pig for these new technologies,” Ed said
Ed is focused on strengthening its most important relationships—the ones with employees and customers—by growing dedicated and third-party logistics services
if the company finds the right partner to anchor the facility
And association involvement aids their cause
uniting stakeholders large and small in the shared goal of improving trucking safety
Ed is a former Ohio Trucking Association chairman
and he’s the current Truckload Carriers Association vice chair to ATA
and he is wholly committed to uplifting Nagle
“This is who we are,” Ed said
“Trucking isn’t just in our blood
has nearly 20 years of experience as a journalist
He spent 15 writing and editing for daily newspapers
and began covering the commercial vehicle industry in 2018
He was named editor of Bulk Transporter and Refrigerated Transporter magazines in July 2020
The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article
activities on preceding journals at which the article was previously under consideration are not shown (for instance submission
All content on this site: Copyright © 2025 Elsevier B.V.
ReginaNews‘One of a kind’: Historic Regina home now occupied by well-known bakeryBy Wayne MantykaPublished: February 27, 2025 at 10:56AM EST
Twitter feed ©2025 BellMedia All Rights Reserved
Metrics details
Identifying molecular alterations occurring during cancer progression is essential for a deeper understanding of the underlying biological processes
Here we have analyzed cancerous and healthy prostate biopsies using nanoLC-MS(MS) to detect proteins with altered expression and N-glycosylation
We have identified 75 proteins with significantly changing expression during disease progression
The biological processes involved were assigned based on protein–protein interaction networks
These include cellular component organization
Multiple glycoproteins were identified with aberrant glycosylation in prostate cancer
where differences in glycosite-specific sialylation
and galactosylation were the most substantial
Many of the glycoproteins with altered N-glycosylation were extracellular matrix constituents
and are heavily involved in the establishment of the tumor microenvironment
Pathological Grades (G) range from 1–3 while Gleason Grades (GG) range from 1 to 5
intermediate (G2 and GG2-3) and high-risk groups (G3 and GG4-5)
our objective was to identify molecular changes in PCa
analyzing a large number (95) of TMA core biopsy samples
This allows us to detect relatively small differences in protein abundances with a high statistical power
We have compared protein expression levels and changes in N-glycosylation features among various pathological grades of PCa and healthy tissues
Workflow of the analysis of the TMA samples
The “Results” section is divided into three major parts: (i) the molecular differences between healthy and cancerous prostate tissue; (ii) the molecular changes with PCa grade progression
and differences between distinct grades and healthy tissue; (iii) and the biological processes altered in PCa
While the first two sections are based on data from both the proteomics (containing protein intensities) and glycoproteomics datasets (containing glycopeptide intensities and metrics calculated from them)
the third one is based on proteomics data only
Before describing the results of the three aforementioned sections
a general characterization of the two datasets (proteomics and glycoproteomics) is provided
MaxQuant quantified 653 proteins altogether in the 95 supernatant samples analyzed. From these, proteins that were found in less than 60% of any of the sample groups were excluded. Missing values were then imputed as described in the “Methods” section
Altogether 145 glycopeptides were quantified in 95 samples with high confidence
corresponding to 22 glycoproteins with 29 glycosites and 53 different glycans
Over 75% of the identified glycopeptides carried complex-type glycans
More than half of these structures were biantennary
while tri- and tetra-antennary types and unmatured structures were also present
The average antenna sialylation was 20.1% across all samples
while 28.7% of antenna containing structures held at least one sialic acid
The average fucosylation was 37.8% across all samples
All 29 glycosites identified carried several different glycans
and also showed considerable diversity regarding glycan type
To reveal changes specific to the distinct glycosites
metrics were calculated for them individually as well
Volcano plot displaying proteins differentially expressed (fold-change at least 2) between healthy and PCa tissues
while blue dots represent proteins underexpressed in PCa
In the glycoproteomics dataset, 7 glycopeptides were found with significantly different abundances between the normal and PCa groups (Supplementary Fig. S5)
fucosylated complex-type glycans with different levels of galactosylation and sialylation
glycopeptide expression was lower in PCa tissues: four glycoforms of Immunoglobulin gamma-1 heavy chain (IGG1) N299
and one glycoform of Prothrombin (THRB) N121
The other two showed higher expression levels in PCa: one glycoform of Microfibril-associated glycoprotein 4 (MFAP4) N137 and one glycoform of Biglycan (PGS1) N270
Significant differences were also detected between normal and PCa tissues when comparing the levels of sialylation, fucosylation, and galactosylation at distinct glycosites. The differences in glycosite-specific sialylation, fucosylation, and galactosylation are summarized in Fig. 3.
Glycosite-specific alterations in sialylation (A)
and galactosylation (C) between healthy and PCa tissues (with standard error displayed)
(D) summarizes the direction and volume of the differences in the case of all three metrics (Normal—PCa)
in the case of sialylation and galactosylation they did not
To uncover molecular alterations among pathological grades and normal tissue, Analysis of Variance (ANOVA) was performed (FDR controlled at 0.05) on both proteomics and glycoproteomics data separately. For exact parameters see the “Methods” section
Significantly changing proteins among different grades of PCa and healthy tissue divided into two sub-groups based on hierarchical clustering: upregulated (A) and downregulated (B)
Glycopeptides with significant changes between different Grades of PCa and healthy tissues
Glycopeptides are annotated as follows: glycoprotein—glycosite—attached glycan (H hexose
Changes in the fucosylation of CO6A2 (A) and in the protein expression of different CO6 subunits (B) between different Grades of PCa and healthy tissues
alterations between Gleason grades and healthy tissue were investigated as well
The number of samples analyzed in the different GG groups was as follows: 7 in GG2
The data analysis was carried out similarly to that of pathological grades
Comparison of the proteomics results based on Grade groups and Gleason grades
(A) Venn diagram of proteins identified as significant
(B) Classification of the 49 PCa samples analyzed
The size of the boxes is proportional to the sample sizes (green—Gleason grades
(C) Heatmap of the 57 common proteins in both proteomics datasets
G3) and groups created from Gleason grades (GG2; GG3 and GG4; GG5)
Most of the underexpressed proteins were associated with cellular component organization (34 out of 51)
while the overexpressed proteins were predominantly affiliated with metabolic processes (60 out of 72)
As the focus of this paper is on finding potential biomarkers through exploring alterations in the glycosylation between healthy and PCa tissues combined with proteomics data
only glycoproteins displaying significant changes are discussed individually
the differences in protein expression and glycosylation are both reported
and they are compared to relevant previous studies on PCa or cancer in general
the most significant biological processes are also discussed
These changes however reflect only overall tendencies
they are not necessarily true for all of the glycosylation sites
This is supported by our data: the average fucosylation level of PPAP N94 increased from 47 to 83% in PCa
but significant changes in glycosylation have not been reported yet
and we also detected significant changes in both fucosylation and sialylation on POSTN N599
an increase from 24 to 72% and a decrease from 83 to 44% respectively
We have found that the sialylation of THRB N121 was downregulated significantly in PCa
Our results revealed that both sites of MFAP4 showed modified glycosylation in PCa: decreased sialylation on N87 and increased expression of the glycan N4H5S1F1 on N137
The latter glycoform might be a useful indicator in detecting PCa at an early stage
as this increased expression was detected between normal and G1 samples
This suggests their potential usefulness as a clinical marker
Whether the alterations in the glycosylation of these proteins is PCa specific or not
especially in the context of their biomarker status
our results indicate that alterations between PCa and Normal tissue glycosylation occur primarily on the glycosite level
while overall glycosylation may be unaffected
altered glycosylation does not necessarily indicate differential expression on the protein level
The glycoproteins with significant differences in glycosylation were all secreted either to blood or the ECM
and most of them are characterized as an unfavorable prognostic cancer marker by the Pathology Atlas
As altered protein glycosylation in cancer has been proven to be nonrandom
this suggests that further investigation of the glycosylation
and cancer specificity of these potential prognostic markers and identification of their exact roles is reasonable and could lead to further advancement in understanding the function of glycosylation in cancer development and PCa prognosis
and Ammonium-bicarbonate were purchased from Merck (Darmstadt
and Iodoacetamide were obtained from Thermo Scientific (Waltham
Methanol was purchased from VWR International (Debrecen
RapiGest surfactant was obtained from Waters (Milford
Four different TMA slides were purchased from US Biomax (Derwood, MD, USA): BNS19011, PR481, PR483c, PR633. All of them contained formalin-fixed paraffin-embedded (FFPE) cores with a diameter of 1.5 mm and a thickness of 5 μm. The specification sheets are available at https://biomax.us with information about each core including age
Each TMA core contains on average approximately 1 µg protein
the TMA slides were baked at 60 °C for 2 h following the supplier’s instructions to prevent tissue detachment
de-paraffinization was carried out by incubating the slides in different solvents/solutions sequentially as follows: xylene for 2 × 3 min
10 mM NH4HCO3 (water) for 5 min and finally water for 1 min
the slides were placed in antigen retrieval buffer (20 mM Tris–HCl
the proteins in TMA cores were reduced using RapiGest and DTT in 1 µL of 20% glycerol for 20 min at 55 °C
then alkylated using IAA in 1 µL of 25 mM ammonium bicarbonate (ABC) puffer and 20% glycerol for 20 min at room temperature in the dark
each one lasting for 40 min at 37 °C in a humidified box
LysC-Trypsin mixture was added in a 1:25 ratio
the extraction of the protein digest was done by repeatedly pipetting 1 µL 10% acetic acid extraction solvent five times on the cores
and clean-up was performed using C18 spin columns (Thermo Scientific) using the manufacturer’s protocol
The resulting samples were dried down and stored at -20 °C for further usage
Samples were reconstituted in 15 µL 1% FA and 150 µL ice-cold acetone was added and the solution was stored at -20 °C overnight
Then the samples were centrifuged at 13,000 g for 10 min
then resuspended in 10 µL of injection solvent and subsequently stored in the autosampler unit until analysis
Samples were analyzed using a Maxis II QTOF instrument (Bruker Daltonik GmbH
Germany) equipped with CaptiveSpray nanoBooster ion source coupled to a Dionex UltiMate 3000 RSLCnano system (Sunnyvale
Peptides were separated on an Acquity M-Class BEH130 C18 analytical column (1.7 μm
MA) using gradient elution (isocratic hold at 4% for 11 min
then elevating B solvent content to 25% in 75 min
and to 40% in 15 min) following trapping on an Acclaim PepMap100 C18 (5 μm
Solvent A consisted of water + 0.1% formic acid
Solvent B was acetonitrile + 0.1% formic acid
and the sample loading buffer was 0.1% TFA and 0.01% heptafluorobutiric acid in water
with a dynamic MS/MS exclusion of the same precursor ion for 2 min
or if its intensity is at least 3 times larger than previously
Preferred charge states were set between + 2 and + 5
MS spectra were acquired at 3 Hz in the 150–2200 m/z range
while MS/MS spectra at 4 or 16 Hz depending on the intensity of the precursor
Mixed energy spectra were collected at 100% collision energy for 80% of the cycle time and 50% collision energy for 20% of the cycle time
spectra were recorded over the mass range of 300–3000 m/z at 1 Hz
raw data were recalibrated using the Compass DataAnalysis software 4.3 (Bruker Daltonics
The software identified the glycopeptides according to their exact mass
The minimum required interaction score was set to the highest confidence (0.900)
for active interaction sources “Textmining” was excluded
Experimental data has been submitted to the MassIVE data repository with the ID: MSV000087329
EAU-ESTRO-SIOG guidelines on prostate cancer
Artificial intelligence assistance significantly improves Gleason grading of prostate biopsies by pathologists
Underestimation of Gleason score at prostate biopsy reflects sampling error in lower volume tumours
Effects of replacing PSA with Stockholm3 for diagnosis of clinically significant prostate cancer in a healthcare system–the Stavanger experience
Advantages of replacing the total PSA assay with the assay for PSA-α1-antichymotrypsin complex for the screening and management of prostate cancer
Recent advances in image-guided targeted prostate biopsy
and combined biopsy for prostate cancer diagnosis
Artificial intelligence for diagnosis and grading of prostate cancer in biopsies: A population-based
Automated deep-learning system for Gleason grading of prostate cancer using biopsies: A diagnostic study
Current and future perspectives of liquid biopsies in genomics-driven oncology
New prostate cancer grade grouping system predicts survival after radical prostatectomy
Prostate cancer grading: A decade after the 2005 modified system
Controversial issues in Gleason and International Society of Urological Pathology (ISUP) prostate cancer grading: proposed recommendations for international implementation
The molecular taxonomy of primary prostate cancer
Special issue “Diagnostic biomarkers in prostate cancer”
Oxidative stress and antioxidant status in high-risk prostate cancer subjects
An update on the prognostic and predictive serum biomarkers in metastatic prostate cancer
Novel biomarkers for the detection of prostate cancer
Emerging biomarkers in the diagnosis of prostate cancer
Serum N-glycan profiling is a potential biomarker for castration-resistant prostate cancer
Prostate-specific antigen glycoprofiling as diagnostic and prognostic biomarker of prostate cancer
Identifying prostate carcinoma by MALDI-Imaging
Targeted proteomic strategy for clinical biomarker discovery
Proteomic analysis of conditioned media from the PC3
and 22Rv1 prostate cancer cell lines: discovery and validation of candidate prostate cancer biomarkers
Recent advances in software tools for more generic and precise intact glycopeptide analysis
High sensitivity proteomics of prostate cancer tissue microarrays to discriminate between healthy and cancerous tissue
Workflow for combined proteomics and glycomics profiling from histological tissues
Site-specific N-glycosylation of HeLa cell glycoproteins
High-performance liquid chromatography coupled to mass spectrometry methodology for analyzing site-specific N-glycosylation patterns
Cell surface protein glycosylation in cancer
Focal adhesion kinase controls prostate cancer progression via intrinsic kinase and scaffolding functions
Smooth muscle contraction and growth of stromal cells in the human prostate are both inhibited by the Src family kinase inhibitors
functions and clinical applications in cancer
Analysing differential gene expression in cancer
Role of tumor microenvironment in tumorigenesis
Glycosylation in cancer: mechanisms and clinical implications
The complexity and dynamics of the tissue glycoproteome associated with prostate cancer progression
MALDI mass spectrometry imaging of N-linked glycans in cancer tissues
Elevated serum sialic acid levels predict prostate cancer as well as bone metastases
Reactive stroma component COL6A1 is upregulated in castration-resistant prostate cancer and promotes tumor growth
Integrated proteomic and glycoproteomic analyses of prostate cancer cells reveal glycoprotein alteration in protein abundance and glycosylation
Human prostatic acid phosphatase: Structure
Quantitative glycoproteomic analysis of optimal cutting temperature-embedded frozen tissues identifying glycoproteins associated with aggressive prostate cancer
Thrombin expression in prostate: A novel finding
Thrombin and factor XII drive prostate tumor growth in vivo
and angiogenesis: Evidence for a thrombin-regulated dormant tumor phenotype
Immunoglobulin G glycosylation in aging and diseases
IgG silencing induces apoptosis and suppresses proliferation
migration and invasion in LNCaP prostate cancer cells
Glycosylation status of serum immunoglobulin G in patients with prostate diseases
Papakonstantinou, M. et al. N-Glycosylation of IgG Immunoglobulin and its clinical significance. J. Biomed. 4, 35–43. https://doi.org/10.7150/jbm.33922 (2019)
Integrated analysis of microfibrillar-associated proteins reveals MFAP4 as a novel biomarker in human cancers
Microfibril associated protein 4 (MFAP4) is a carrier of the tumor associated carbohydrate sialyl-Lewis x (sLex) in pancreatic adenocarcinoma
A pathology atlas of the human cancer transcriptome
Urinary glycoproteins associated with aggressive prostate cancer
High-throughput detection of low abundance sialylated glycoproteins in human serum by TiO 2 enrichment and targeted LC-MS/MS analysis: Application to a prostate cancer sample set
MaxQuant enables high peptide identification rates
individualized ppb-range mass accuracies and proteome-wide protein quantification
Accurate and sensitive peptide identification with Mascot Percolator
Ggplot2: Elegrant Graphics for Data Analysis (Springer
Byonic: Advanced peptide and protein identification software
R: A Language and Environment for Statistical Computing
RStudio: Integrated Development Environment for R
Systematic evaluation of normalization methods for glycomics data based on performance of network inference
STRING v11: Protein–protein association networks with increased coverage
supporting functional discovery in genome-wide experimental datasets
Download references
is grateful for funding by the National Research
Development and Innovation Office (OTKA PD 121187 and OTKA FK 131603) and acknowledges the support of the János Bolyai Research Scholarship of the Hungarian Academy of Sciences
2018-1.2.1-NKP-2018-00005 has been implemented with the support provided from the National Research
Development and Innovation Fund of Hungary
financed under the 2018-1.2.1-NKP funding scheme
Faculty of Chemical Technology and Biotechnology
Budapest University of Technology and Economics
1St Department of Pathology and Experimental Cancer Research
annotated the tissue biopsy digital images
All authors read and approved the final manuscript
The authors declare no competing interests
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations
Download citation
DOI: https://doi.org/10.1038/s41598-021-95417-5
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.
Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.
Volume 8 - 2021 | https://doi.org/10.3389/fnut.2021.702352
This article is part of the Research TopicRecent Breakthrough in Gluten ContaminationView all 9 articles
The use of pure oats (oats cultivated with special care to avoid gluten contamination from wheat
and barley) in the gluten-free diet (GFD) represents important nutritional benefits for the celiac consumer
emerging evidence suggests that some oat cultivars may contain wheat gliadin analog polypeptides
it is necessary to screen oats in terms of protein and epitope composition to be able to select safe varieties for gluten-free applications
The overall aim of our study is to investigate the variability of oat protein composition directly related to health-related and techno-functional properties
Elements of an oat sample population representing 162 cultivated varieties from 20 countries and the protein composition of resulting samples have been characterized
Size distribution of the total protein extracts has been analyzed by size exclusion-high performance liquid chromatography (SE-HPLC) while the 70% ethanol-extracted proteins were analyzed by RP-HPLC
Protein extracts separated into three main groups of fractions on the SE-HPLC column: polymeric proteins
avenins (both containing three subgroups based on their size)
representing respectively 68.79–86.60
and 2.89–11.85% of the total protein content
The ratio of polymeric to monomeric proteins varied between 1.37 and 3.73
Seventy-six reversed phase-HPLC-separated peaks have been differentiated from the ethanol extractable proteins of the entire population
Their distribution among the cultivars varied significantly
The number of appearances of peaks also showed large variation: one peak has been found in 107 samples
which appeared in less than five cultivars
An estimation method for ranking the avenin-epitope content of the samples has been developed by using MS spectrometric data of collected RP-HPLC peaks and bioinformatics methods
Using ELISA methodology with the R5 antibody
a high number of the investigated samples were found to be contaminated with wheat
The benefits of both applications of oats as human food sources are directly related to the protein composition of the oats used
producing these food products: the inclusion of oats in the diet of celiac patients has been a controversial issue
Oats are a less likely candidate to trigger CD due to their protein composition
all of the important techno-functional properties of oats are directly related to the ratio of polymeric and monomeric proteins in the sample
Oats are, in general, considered to have low CD-triggering potential due to their lower prolamin content, higher digestibility, and lower affinity to MHC (Major Histocompatibility Complex) molecules associated with CD compared with that of wheat prolamins (24)
The legal gluten-free threshold of 20 mg/kg gluten applies to these oat products as well
Although pure oats are considered to be safe for most patients with celiac, there are a number of studies suggesting that oats may be able to trigger CD on their own, but only affected the minority of the population with celiacs connected to individual sensitivity and the condition of the intestine (39). In a study by Lundin et al. (40)
a single patient developed complete villous atrophy
This patient produced T cells that showed affinity to avenins and were used to identify two avenin epitopes (PYPEQEEPF and PYPEQEQPF) that may have been responsible for triggering villous atrophy
These results were limited to this single patient
but they raised questions about the presence of celiac-related epitopes in oat avenins
there is a great variety of potential immune reactivity of oat cultivars
which can generate a higher or lower degree of immune response in patients with celiac disease
The overall aim of our study is to demonstrate the variability of oat protein composition directly related to health-related and techno-functional properties
we summarize our findings related to genetic factors in an international population of different oat cultivars that have been analyzed using a complex relatively fast and cost-effective protein separation methodology
suitable for characterizing large sample populations
and the resulting data have been evaluated
While the data collected in this study on the overall protein composition
including the ratio of polymeric to monomeric oat proteins
can be directly related to functional properties
the results of the detailed analysis of avenin proteins can help breeders to select oat lines with suitable storage protein composition
monitoring the effects of growing conditions on the protein composition of oat as well as the relationships between the protein composition and the techno-functional properties
is in progress and planned to be reported in subsequent publications
The oat samples were derived from small plot field growing
samples were stored in a dry and cold warehouse
The dehulling was made with Satake grain testing mill TM-05 (Satake Engineering Co
and grinding of hulled grains was carried out with a Retsch MM 400 ball mill (Retsch GmbH
Germany) in a gluten-free laboratory environment
which was monitored with the R-Biopharm RIDASCREENRIDA®QUICK Gliadin test stripes (Art
The protein content of oat flours was determined by the Dumas method (N × 5.95), an adaptation of the AOAC official method (51) using an automated protein analyzer (LECO FP-528
The final SE buffer solution was prepared by mixing 90 ml of solution A + 110 ml of solution B + 600 ml MQ H2O + 4-g SDS
Single grains from different samples were placed in 2 ml Eppendorf tubes with a 72-mm-diameter steel ball bearing placed on top of the grain
The tubes were lysed using a Qiagen®TissueLyser II (Qiagen GmbH
Germany) at 27 strokes/s frequency for 7 min
Flour from each tube (10 mg) was weighed in fresh 2 ml Eppendorf tubes
and 1 ml of an SE-HPLC extraction buffer was added to each tube
Vortex-Genie®2 at setting 6 for 30 min
They were subsequently centrifuged for 15 min at 13,000 rpm
The supernatant was then aspirated using a 1 ml syringe
The supernatant was then passed through a 0.45 μl filter into an HPLC vial
The vials were placed in an Agilent Technologies 1200 series HPLC instrument and were analyzed using the following parameters: a Mobile Phase of 50% acetonitrile (ACN)
with 0.1% trifluoroacetic acid (TFA) and 50% water HPLC grade
with 0.1% trifluoroacetic acid (TFA) was used
The SE column (Agilent AdvanceBio Sec 300A
4.6 × 300 mm) was washed for 60 min with 100% water to 100% acetonitrile and stabilized for 1 h before commencing the analysis
at 120-bar pressure; the injection volume was 10 μl at a flow rate of 0.350 μl/min
The SE-HPLC separation resulted in 10 peaks (P1-P10)
polymeric globulin proteins eluted first (P1-P5)
while the four latest eluted little peaks (P7-P10) (integrated together) contained the soluble non-avenin proteins
About 10 μl of extracts were injected into a C18 reversed-phase ZORBAX 300SB-C18 column (4.6 mm × 150 mm
maintained at 60°C column temperature and at 50-bar column pressure
The applied eluents were 67% ultrapure water (Buffer A1) and 33% acetonitrile (Buffer B1)
The separation was carried out using a linear gradient from 33 to 80% Buffer B1 over 65 min at a flow rate of 1 ml/min
RP-HPLC analyses have been carried out with three replicate injections from two replicate extracts
In order to detect gluten contamination from wheat
oat samples were analyzed with the R-Biopharm RIDASCREEN® Gliadin assay (catalog number: R7001
Extraction and the ELISA procedure were carried out in line with the kit instructions
1 g of oat flour samples was weighed in 50 ml Falcon tubes
catalog number: R7016) was pipetted to each sample under a chemical hood
the samples were incubated at 50°C for 40 min in a shaking water bath (OLS Aqua Pro
After cooling the samples to room temperature
30 ml 80 V/V% ethanol was added to the samples
followed by 1 h of shaking on a table-top shaker (1,500 rpm
The samples then were centrifuged for 10 min at 2,500 × g at room temperature (LISA
Supernatants were diluted 1:12.5 with the sample diluent solution provided to the kit (the concentrate was pre-diluted prior to use according to the kit manual)
About 150 μl of kit standards and samples were loaded to a transfer plate in duplicate
100 μl of each sample and standard was transferred to the ELISA plate with a multichannel pipette
The plate was incubated for 30 min at room temperature and then was washed with the pre-diluted wash buffer provided for the assay in line with the kit instructions (ELx50 automatic plate washer
100 μl of the pre-diluted conjugate was added to all wells followed by 30 min of incubation at room temperature
50 μl substrate and 50 μl chromogen were added to all wells
and the plate was incubated for 30 min at room temperature covered by aluminum foil
100 μl of stop solution was added to all the wells
and absorbance values were obtained at 450 nm using a plate spectrophotometer (iMark
Data were analyzed with the Microplate Manager 6 software (BioRad
USA) using the cubic spline fit to create a standard curve
The results were the subject of further calculations to obtain the reporting unit of mg/kg gluten as per the kit instructions
The immunodominant T cell epitopes of oat DQ2.5-ave-1a (PYPEQEEPF), DQ2.5-ave-1b (PYPEQEQPF) (56, 57), DQ2.5-ave-1c (PYPEQEQPI) (48), and DQ2.5-ave-2 (PYPEQQPF) were predicted, and the epitope containing avenin levels in different oat varieties was calculated based on the study by Tanner et al. (58). Sollid et al. (47) determined the celiac disease–relevant
internationally agreed T cell epitopes recognized by CD4+T cells
The study of Tanner even included the DQ2.5-ave-2 that contained only the minority of the investigated oat varieties
calculated from their amino acid composition and
converted to [mg/100 g sample] units by multiplying the mg/100 g avenin values by the SE-HPLC-based avenin content and by the protein content of the samples
Using proteomics data of Tanner in such a way is based on the assumption that their data
which are based on the detailed study on a single cultivar (cv
is representative for oat cultivars in general
The approach to the prediction of epitopes from RP-HPLC data is strictly reliable when these data would be supported and confirmed by amino acid sequence data
demonstrating (at least in a representative number of cultivars)
the actual presence and amounts of intact avenin epitope sequences in the distinguished HPLC peaks
the predicted epitope levels can be interpreted as the measure of the possible variation of epitope contents in the cultivars in the sample population rather than the exact epitope levels in the individual samples
The cumulative amounts of the presumably immune reactive avenin proteins per variety were determined and expressed as a percentage of the sample mass by combining the peak data of RP- and SE-HPLC separation and protein content of the samples
In the cases of both SE- and RP-HPLC analyses
and coefficient of variation have been calculated based on the six replicate data derived from the three replicate injections of two replicate extracts
The calculations have been carried out using MS Excel functions
Sample groups have been characterized by the variation of the above-mentioned mean values of different protein compositional data
different notations are used for describing the variation among the replicate measurements of a given sample (mean
and cv) and the variation among the means of different measurements in a group of samples (mean
In case of parameters derived more than one, standard deviations were calculated based on the Gaussian error propagation law (59) from the means and standard deviation values (σ) from the individual parameters: in case of the cumulative amount of epitopes
the geometrical mean of the four standard deviations were used while the following equation was used for the determination of the standard deviation of the avenin levels in mg/100 g samples unit:
where nA and nB are the number of peaks in samples A and B, nA, B is the number of peaks with identical elution times in samples A and B, ei is a weighting factor describing the relative intensity of peaks with identical elution time. Cluster analysis was carried out applying the similarity matrices with the Morpheus R package (https://software.broadinstitute.org/morpheus/)
ANOVA test and multiple comparisons of mean values based on the least significant difference (LSD) by Student t-test were carried out as implemented in the NCSS 2021 Statistical Software (2021), (NCSS, LLC. Kaysville, Utah, USA, ncss.com/software/ncss)
Protein composition of the oat flour samples has been characterized on two levels: distribution of the total protein content after size-based separation was determined with SE-HPLC
followed by the RP-HPLC-based determination of the qualitative and quantitative composition of the avenin fraction
More than 99% of the total amount of oat flour proteins has been extracted in the first step of the extraction procedure of Gupta et al. (52)
Comparison of samples has been carried out
clearly indicating that the ethanol-soluble proteins are eluted as one single peak (P6)
The typical SE-HPLC profile of the total oat protein extract (T) and 70% ethanol extract of oat flour (E)
The reproducibility of the peak intensity measurements has been monitored by calculating the mean, stdev, and cv values for each peak from their six replicate analysis data (Supplementary Table 2)
Based on the averages of cv values calculated from the data of the 6 replicates among the 162 samples
and non-avenin monomeric protein group measurements are 5.018
The distribution of the proteins among the three main groups and inside of the polymeric fraction shows a well-defined trend all around the 162 samples
The polymeric fraction represents about three-quarters of the total protein content (Mean: 73.14%
max: 86.60%); the amount of the avenin fraction is varied between 8.86 and 27.72% (mean: 19.38%)
while the amount of the monomeric globulin fraction is between 2.89 and 11.85% (mean: 7.29)
the relative amounts of the five subfractions of the polymeric proteins show a P1 < P2 > P3 >> P4 ⋙ P5 trend
Comparing the relative distribution of the proteins in the different geographic regions (R1-R8), it was found (Table 1) that the total amount of polymeric proteins and its distribution among the five subfractions (with the exception of P2)
and the ratio of the polymeric to monomeric globulin proteins
show significant differences among the eight geographic groups
Statistical analysis on the variation of the size-based distribution of the total proteins of oats samples among the different geographic regions
Compared to the data in the rest of the geographic groups
the highest amount of polymeric proteins (means: 75.10 and 74.65%) and polymeric to monomeric protein ratio (means: 11.89 and 13.47%) were found in the R1 and R7
The cause of these values derived from significantly higher amounts of P1 fraction found in the R1 and R7 groups (means: 25.65 and 17.35%
compensated only partly with the significantly lower values of P3 (6.29 and 8.94%
Beyond the apparently uniform avenin levels observed at the comparison of mean values in the different geographic groups
some extremely low (AUS05: 8.86%) and extremely high (AUS14: 27.72%) avenin contents were observed
These cultivars could have great potential to be applied to nutrition-related breeding programs
characterizing individual RP-HPLC peaks by using the mass spectrometric methodology
As it was observed in previous studies (for example
most of the avenin polypeptides are eluted in two elution time intervals: 20 peaks have been found in the 25.75-32-min interval and 37 in the 38–47.25-min interval
representing the 45.58 and 48.42% of the total avenin content
The number of appearances of a peak with a given retention time in different samples was found to be extremely variable
There are three peaks with the retention times of 25.75
and 35.00 min found only in three cultivars
while the peak with the retention of 42.39 min was found in 107 samples
Characteristic peaks in the six similarity clusters of avenin protein RP-HPLC profiles and the origin-based distribution of oat samples among the clusters
Some interesting observations can be made, investigating the distribution of samples in the different clusters based on their origin (Table 2)
and R8 groups are scattered in different clusters
most of the samples in R6 group are together in Cluster C
but not in A or B cluster; 18 from the 40 samples in R7 can be found in Cluster F
and 36 from the 39 samples in R1 are located in Cluster A
Differences among the avenin composition of the samples are significantly enlarged if the amounts of the different peaks are used in similarity calculation (S'%) instead of the presence/absence-based comparison (S%)
Expression levels of avenins with the same retention times in different samples have been found largely not uniform among the peaks
The reproducibility of the peak intensity measurements has been monitored through the 1,530 peaks found in the whole sample population by calculating the mean
and cv values for each peak from their six replicate analysis data
resulting in a 7.18% for the average value for the cv values
The r2 value between elution times and cv values of peak intensities of peaks eluted at a given elution time was found to be 0.0036
while a strong negative correlation was found between the peak intensities
and their reproducibility (r2 = 0.7934): in the 10–15% peak intensity interval
11% in the 5–10 and 10–15% intensity intervals
Applying the data provided by Tanner et al. (58) for the composition of avenin fraction of the oat variety cv.
the amounts of the celiac-related oat epitope-containing components of the 162 oat samples have been predicted based on their RP-HPLC analysis results
containing conserved avenin types: peak 3 (R.T
Peak 3 contained the gliadin-like avenin (L0L6J0)
peak 8 contained an Asat-Prolamin10 protein and a 23539 Da avenin (Q09072)
with an alternative name celiac immunoreactive protein 2 or gamma-avenin-3 (Q09097) and an Asat-Prolamin71 protein
the predominant avenin epitope is the DQ2.5-ave-1a (PYPEQEEPF)
the DQ2.5-ave-1b (PYPEQEQPF) and DQ2.5-ave-1c (PYPEQEQPI)
all the above mentioned three avenin epitopes occurred
Satisfactory reproducibility has been observed for the individual and cumulated epitope levels (average cv values calculated for the 162 samples for the DQ2.5-ave1a
and DQ2.5-ave1c epitopes and for their cumulated value: 0.096
The cv values for the avenin levels expressed in [mg/100 g sample] units varied between 0.003 and 0.129 with an average of 0.062
For the pure oat line development study, a small population consisting of 32 Australian and 35 Hungarian samples (Supplementary Table 5) was selected from the basic population for ELISA testing
Samples were selected to cover a wide range of crude protein content using samples with sufficient available amounts
The presence of potential gluten contamination from other cereals was tested with the R5 ELISA method of R-Biopharm
19 Australian and 24 Hungarian samples of the investigated oat varieties were uncontaminated
deemed appropriate for the requirements of pure oat cultivation in terms of purity
Our results confirm that gluten contamination of oats is a serious problem and must be carefully addressed when providing seeds for growing pure oats
The aim of our work was to carry out a high-throughput analytical screening completed with immune analytic measurements to develop a reliable prediction method for estimating the amount of avenin proteins and those that contain celiac-related epitopes
This special prediction method utilizes the combined application of SE- and RP-HPLC separation of the total protein content of the oat flour samples and differentiates the absolute levels of the four main avenin epitopes of the samples
and also provides the celiac-related epitope
containing avenin content in the oat flour (g/100 g)
Interestingly, no application of SE-HPLC on characterizing oat proteins is reported in the critical work of Sunilkumar and Tareke (62)
which reviewed the analytical methods for measurement of oat proteins by covering 2,000 works published between 1970 and 2015
However, the application of size-related analytical techniques like SE-HPLC has a large potential to be used in selecting oat lines for industrial ingredient use (61)
and oat flours using mixtures of four cultivars each to account for the genetic variability between different cultivars
including the most relevant cultivars in Germany 2012
It reveals that the examined commercial oat flour samples were
the high variability of avenin fraction composition and biodiversity of cultivated oat varieties are in agreement with the results of several research groups who are experts of this field
significantly reduce the immunoreactivity of avenins and thus of oat-based foods
These findings were confirmed by the study of Hardy and co-workers in a large-scale oat challenge proved that the ingestion of oat is safe for patients with celiac without intestinal damage and serological relapse
Because pure oat consumption carries a low risk for patients
the researchers declare that the strict control of production systems of pure oat is of utmost importance
and the regular follow-up of the patients with CD is recommended
Based on the R5 R-Biopharm RIDASCREEN® Gliadin assay of the selected subpopulation showed that 35% of the samples were contaminated
This highlights the necessity of improving the pure oat line and developing very sensitive and specific analytical methods for the sake of food safety
All observations described above were derived from a reasonably large study where the carefully executed experiments were carried out with 2 × 3 replicates
The resulting data have been thoroughly analyzed statistically
taking into consideration the non-trivial characteristics of cumulative and complex parameters
where the actual results were derived from several independent measurements with experimental errors
The reproducibility of the two chromatographic separations
seems to be satisfactory with the relative errors being under 12%
These positive experimental characteristics
do not avoid two principal limitations of the prediction method introduced here:
The reliability of the predicted information derived from this prediction process strongly depends on the validity of the assumption that the proteomic data (derived from the analysis of one single cultivar) are representative of oat cultivars in general
The predicted epitope levels should be validated by detailed proteomic analysis to avoid this limitation
Because of the limited resolution of the RP-HPLC separation of avenin proteins
the predicted epitope levels have to be interpreted as upper limits
large qualitative and quantitative differences have been observed in the avenin composition of the samples investigated: both the individual and cumulative amounts of the four oat avenin epitopes show large variation
while certain cultivars do not contain all the four different epitopes
there is no variety among the 106 samples not containing any DQ2.5-ave epitopes
with the maximum number of 46 cultivars (28.40%)
containing 26–50 mg/100 g epitopes
Two cultivars have been found with epitope levels of less than 5 mg/100 g (HUN31 and AUS04); these rarely found low levels could be utilized in breeding for healthy oat varieties
Variation of the amounts of celiac-related avenin epitopes among 106 oat samples
As the results of the large variation of epitope levels in the whole sample population, significant differences among the origin-based subgroups can be observed (Table 4) for the amounts of DQ2.5-ave-1a and DQ2.5-ave-1c
The highest F value (5.6672) was found for the cumulative epitope levels data expressed as [mg/100 g sample] what can be explained by the fact that these values do not only derive from the variation in avenin composition
but they are varied by the total amount of avenin proteins as well as the protein content of the samples
shows significantly lower levels in the Australian samples (47.52 mg/100 g sample) compared with the South African and South American samples (117.92 and 123.61 mg/100 g samples)
ANOVA comparison on the predicted celiac-related avenin epitope contents of samples in the eight regions of origin
The celiac-related epitope content of an oat sample is determined by its avenin composition, but the relative expression levels of both avenin- and non-avenin-type polypeptides can overwrite the ranking of the overall epitope levels in the samples, as it is illustrated in Figure 2: In the samples in the circled interval of the figure
the epitope levels expressed in mg/100 g avenin protein unit are misleading
underestimating the amount of epitopes taken by the consumed oat
Demonstrating the importance of expression levels of avenin and non-avenin proteins in the ranking of relative celiac epitope amounts of oat samples by the comparison of ranking samples based on the amount of celiac-related epitopes expressed in (mg/100 g avenin) and (mg/100 g sample) units
Relative celiac-related epitope levels in samples in the red circle are largely underestimated by the simple comparisons of the epitope levels in the samples
not taking into account the total protein content and its avenin content
Circled data with red and green indicate under- and overestimated epitope levels using [mg/100 g avenin] units
not considering the contribution of protein content and avenin content of the sample
As it is well established for all cereal crops
both the protein content and protein composition are highly affected by the growing conditions
including both environmental and agrotechnical factors
Based on an unpublished large project carried out in our laboratory
investigating the alteration of the protein composition of 180 oat cultivars under rainfed and irrigated conditions
protein content of the samples of the same cultivar can be altered by 15 relative percentages while the ratio of polymeric and avenin proteins can vary by 38 relative percent caused by the water availability
The observation illustrated in Figure 2 underlines the need for quantitative characterization of the overall protein composition rather than simply concentrating on the avenin composition
estimating the celiac-related epitope content of oat samples
Utilization of oats lines for human consumption requires the use of a reliable methodology of monitoring the presence and quantity of epitope containing components in the samples
and a better understanding of chemical composition and technological properties is needed
Both of these aspects require the active use of quantitative protein analytical techniques for the characterization of the whole spectra of oats proteins
The application of detailed protein composition data has huge potential both in evaluating oats breeding lines in the pre-breeding selection phase and in monitoring oats-containing products in the food industry
The combination of SE- and RP-HPLC methodology with active use of available proteomic data seems to be a satisfactory tool for these types of applications
Relating SE-HPLC-related quantitative protein analytical data to functional properties of oat samples like water and oil-binding capacity
emulsifying and foaming properties and even rheological properties of oats-containing doughs are in progress to utilize the data collected in this study
Despite these valid and serious above mentioned limitations of the prediction method developed in this work
with the lack of any other (better) relatively high throughput and cheap method
what is applicable to large sample populations the method is suitable to be used as a preselection screening tool in oat breeding in its present form already
Ongoing attempts to carry out further individual RP peak proteomic validation studies on different oat varieties
will make our prediction method much more accurate in the future
The original contributions generated for the study are included in the article/Supplementary Material
further inquiries can be directed to the corresponding author/s
and OV provided samples and sample preparation
and ST performed experiments and analyzed data
All authors contributed to the article and approved the submitted version
The authors declare that this study received funding from the “GalgaGabona” Project (2017-1.3.1-VKE-2017-00004
and from the BME-Biotechnology TKP grant of EMMI (BME TKP-BIO)
GG was supported by the János Bolyai Research Scholarship of the Hungarian Academy of Sciences by the ÚNKP-18-4-BME-393
and ÚNKP-20-5-BME-292 National Excellence Program of the Ministry for Innovation and Technology from the source of the National Research
The funders were not involved in the study design
the writing of this article or the decision to submit it for publication
and SP were employed by company Cereal Research Non-Profit Ltd
KS was employed by company First Pest Mill and Bakery Ltd
The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations
Any product that may be evaluated in this article
or claim that may be made by its manufacturer
is not guaranteed or endorsed by the publisher
The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2021.702352/full#supplementary-material
Gluten and wheat sensitivities- An overview
CrossRef Full Text | Google Scholar
Adverse reactions to wheat or wheat components
Nutrient intakes during diets including unkilned and large amounts of oats in celiac disease
Navigating the gluten-free boom: the dark side of gluten free diet
Oats: characteristics and quality requirements
Cambridge: Woodhead Publishing Limited (2010)
CrossRef Full Text | Google Scholar
Safety of adding oats to a gluten-free diet for patients with celiac disease: systematic review and meta-analysis of clinical and observational studies
Oat safety for celiac disease patients: theoretical analysis correlates adverse symptoms in clinical studies to contaminated study oats
Comprehensive analysis of oat avenanthramides using hybrid quadrupole-Orbitrap mass spectrometry: possible detection of new compounds
Cholesterol-lowering effects of oat β-glucan
Bioactive oat b-glucan reduces LDL cholesterol in Caucasians and non-Caucasians
Effect of 6 weeks' consumption of β-glucan-rich oat products on cholesterol levels in mildly hypercholesterolaemic overweight adults
(Second Edition) Chemistry and Technology American Associate of Cereal Chemists International (2011)
CrossRef Full Text | Google Scholar
Profiling of nutritional and health-related compounds in oat varieties
Final rule for food labelling: health claims; Oats and coronary heart disease
Oats can diversify a gluten-free diet in celiac disease and dermatitis herpetiformis
State-of-the-art incorporation of oats into a gluten-free diet
CrossRef Full Text | Google Scholar
Oats: understanding the science international journal of food science and nutrition
Celiac disease: current concepts in diagnosis and treatment
PubMed Abstract | CrossRef Full Text | Google Scholar
1–22.s doi: 10.1016/B978-012373739-7.50003-4
CrossRef Full Text | Google Scholar
The intestinal T cell response to alpha-gliadin in adult celiac disease is focused on a single deamidated glutamine targeted by tissue transglutaminase
Celiac lesion T cells recognize epitopes that cluster in regions of gliadins rich in proline residues
Structural basis for gluten intolerance in celiac sprue
The pros and cons of using oat in a gluten-free diet for celiac patients
Coeliac disease and oats: a systematic review
PubMed Abstract | CrossRef Full Text | Google Scholar
PubMed Abstract | CrossRef Full Text | Google Scholar
ACG clinical guidelines: diagnosis and management of celiac disease
Why oats are safe and healthy for celiac disease patients
Safety of oats in children with celiac disease: a double-blind
Gluten contamination of commercial oat products in the United States
PubMed Abstract | CrossRef Full Text | Google Scholar
Gluten contamination in the Canadian commercial oat supply
Pure oats as part of the Canadian gluten-free diet in celiac disease: the need to revisit the issue
Definition of the “Purity Protocol” for producing gluten-free oats
Oats in healthy gluten-free and regular diets: a perspective
Commission Implementing Regulation on the requirements for the provision of information to consumers on the absence or reduced presence of gluten in food
Food labeling: gluten-free labeling of foods
Celiac disease and gluten-free oats: a Canadian position based on a literature review
Persistent duodenal intraepithelial lymphocytosis despite a long-term strict gluten-free diet in celiac disease
Oats induced villous atrophy in coeliac disease
Diversity of oat varieties in eliciting the early inflammatory events in celiac disease
Molecular and immunological characterization of gluten proteins isolated from oat cultivars that differ in toxicity for celiac disease
Identification and molecular characterization of oat peptides implicated on celiac immune response
Sensitive detection of cereal fractions that are toxic to celiac disease patients by using monoclonal antibodies to a main immunogenic wheat peptide
a next generation immunoassay for gluten toxicity
Diversity in oat potential immunogenicity: basis for the selection of oat varieties with no toxicity in coeliac disease
Update 2020: nomenclature and listing of celiac disease-relevant gluten epitopes recognized by CD4+ T cells
Ingestion of oats and barley in patients with celiac disease mobilizes cross-reactive T cells activated by avenin peptides and immuno-dominant hordein peptides
Celiac disease and non-celiac gluten sensitivity
In: Determination of Gluten Peptides Associated with Celiac Disease by Mass Spectrometry
CrossRef Full Text | Google Scholar
Modern approaches in the identification and quantification of immunogenic peptides in cereals by LC-MS/MS
Association of Official Analytical Chemists
Biochemical basis of flour properties in bread wheats
I Effects of variation in the quantity and size distribution of polymeric protein
CrossRef Full Text | Google Scholar
Use of size-exclusion high-performance liquid chromatography in the study of wheat flour proteins: an improved chromatographic procedure
Rapid molecular size distribution analysis of wheat storage protein
CrossRef Full Text | Google Scholar
Analysis of gluten proteins in grain and flour blends by RP-HPLC
In: Wheat Gluten Proceedings 7th International Workshop
136–9 doi: 10.1039/9781847552372-00136
CrossRef Full Text | Google Scholar
Characterization of cereal toxicity for celiac disease patients based on protein homology in grains
The molecular basis for oat intolerance in patients with celiac disease
Preparation and characterization of avenin-enriched oat protein by chill precipitation for feeding trials in celiac disease
Rapid and automated characterisation of seed genotype using Micrograd electrophoresis and pattern-matching software
Nutritional and functional characterization of different oat (Avena sativa L.) cultivars
(2020) 23:1373–85 doi: 10.1080/10942912.2020.1806297
CrossRef Full Text | Google Scholar
Review of analytical methods for measurement of oat proteins: The need for standardized methods
Identification of oat cultivars by combining polyacrylamide gel electrophoresis and reversed-phase high-performance liquid chromatography
Reversed-phase high-performance liquid chromatography of oat proteins: application of cultivar comparison and analysis of the effect of wet processing
Characterization of celiac disease related oat proteins: bases for the development of high quality oat varieties suitable for celiac patients
Isolation and characterization of gluten protein types from wheat
barley and oats for use as reference materials
Inheritance and distribution of variation at four avenin loci in North American oat germ plasm
CrossRef Full Text | Google Scholar
Proteomic profiling of 16 cereal grains and the application of targeted proteomics to detect wheat contamination
quantitative mapping of T cell epitopes in gluten in celiac disease
Avenin diversity analysis of the genus Avena (oat)
PubMed Abstract | CrossRef Full Text | Google Scholar
in relation to their safety for celiac patients
Long-term consumption of oats in adult celiac disease patients
Identification and analysis of multivalent proteolytically resistant peptides from gluten: implications for celiac sprue
Tömösközi S and Békés F (2021) Investigation of Protein and Epitope Characteristics of Oats and Its Implications for Celiac Disease
Received: 29 April 2021; Accepted: 23 August 2021; Published: 29 September 2021
Copyright © 2021 Gell, Bugyi, Florides, Birinyi, Réder, Szegő, Mucsi, Schall, Ács, Langó, Purgel, Simon, Varga, Vida, Veisz, Tömösközi and Békés. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY)
distribution or reproduction in other forums is permitted
provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited
in accordance with accepted academic practice
distribution or reproduction is permitted which does not comply with these terms
*Correspondence: Gyöngyvér Gell, Z2VsbC5neW9uZ3l2ZXJAYXRrLmh1
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations
Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher
94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish
7-foot-tall model rocket for their rocketry badges
assembling of the motor and launching the rocket
The large rocket was built for the last stage in the rocketry program
in which cadets build a rocket capable of carrying a small payload to 300 feet
Bugyi and Thrasher carried a large payload to 3,000 feet
The launch was a success and the rocket was returned on a 45-inch parachute to a field nearby
One of the missions of the Civil Air Patrol is aerospace education
The cadet model rocketry program is one small part of that mission
The local squadron meets 6:30 to 8:30 p.m. Monday evenings at the East Bangor Fire Station. For information, contact Capt. Rod Thrasher at 570-242-5722 or cathrasher@yahoo.com or visit capsquad807.webs.com. Information on the national Civil Air Patrol program can be found at gocivilairpatrol.com
Use of and/or registration on any portion of this site constitutes acceptance of our User Agreement, (updated 8/1/2024) and acknowledgement of our Privacy Policy, and Your Privacy Choices and Rights (updated 1/1/2025)
© 2025 Advance Local Media LLC. All rights reserved (About Us)
The material on this site may not be reproduced
except with the prior written permission of Advance Local
Community Rules apply to all content you upload or otherwise submit to this site
YouTube's privacy policy is available here and YouTube's terms of service is available here
Ad Choices
Air Force Auxiliary Civil Air Patrol Local Squadron 807 launched a large model rocket
seven-foot tall model rocket for their rocketry badges
assembly of the motor and launch of the rocket
They have to build a rocket capable of carrying a small payload to 300 feet
they carried a large payload to 3,000 feet
"It was an awesome experience that has grown to become a hobby."
One of the missions of the Civil Air Patrol is aerospace education
The cadet model rocketry program is just a small part of that mission
The cadets must build and fly five rockets from simple and small to larger and more complex
They must also pass three written tests: history of rocketry
laws of rocketry and modern model rocketry
After they complete all of the requirements
they are awarded the CAP Model Rocketry Badge
The objective of the aerospace education mission of CAP is to promote an understanding and appreciation of the impact of aviation and aerospace in participants' everyday lives
The local squadron meets Mondays from 6:30 to 8:30 p.m
Rod Thrasher at 570-242-5722 or cathrasher@yahoo.com or www.capsquad807.webs.com
Information on the national Civil Air Patrol program can be found at www.gocivilairpatrol.com
Community and the strong foundations provided by faith are among the touchstones for the new Executive Director of the Diocese of Saskatoon Catholic Foundation
Raissa Bugyi will begin her new role July 5
Her appointment was announced May 27 by Ray Kolla
Chair of the Diocese of Saskatoon Catholic Foundation
the fund-raising arm that supports the work of the Roman Catholic Diocese of Saskatoon
“On behalf of the Catholic Foundation and Bishop Mark Hagemoen
I am delighted to announce the appointment of a new Executive Director for the Diocese of Saskatoon Catholic Foundation,” said Kolla in a letter to parishes
“Raissa comes to us with a deep understanding and appreciation for the importance of community and faith
Most recently she has served as Executive Director of Preston Park II Retirement Residence in Saskatoon
and has extensive experience in marketing and management,” Kolla said
Announcement from Diocese of Saskatoon Catholic Foundation – PDF
Raissa Bugyi will succeed Executive Director Don Gorsalitz, who has served as the Executive Director of the Catholic Foundation since it was established. Gorsalitz is leaving that role in order to focus more time on his consulting firm, DCG Philanthropic Services Inc.
On behalf of the Catholic Foundation board and the diocese of Saskatoon
Kolla thanked Don Gorsalitz for his “dedication
commitment and outstanding service.”
“Don’s generosity in providing his expertise
professionalism and passion in a volunteer capacity
leading the Catholic Foundation through its establishment and growth
and his many stewardship and fund-raising accomplishments in our diocese over the years has had an immeasurable impact on our diocesan Church and the wider community,” said Kolla
Bishop Mark Hagemoen said: ““We will miss Don Gorsalitz very very much
He has contributed so much to building our diocese
I am very grateful that God has provided us Raissa
to build on the good work and strong foundation established by Don.”
Raissa (pronounced “Ray-sha”) Bugyi was born in Lestock
as a member of Our Lady of Perpetual Help Parish
She points to the faith and the example of her parents as the foundation for her own sense of community
“It is those roots that matter so much,” she said
describing the great example her parents provided as she was growing up
If one more person came for a Christmas meal or a family meal
That strong spirit of generosity and service is behind Bugyi’s interest in philanthropy and working with the community to make the world a better place
to provide an opportunity for them to give
and to help them to realize that when you give
The blessings of serving at Preston Park II have reinforced that firm belief
“The people I have met here do not realize how much they have given back to me,” says Bugyi
Children and youth are another priority for Bugyi
we can do so much more to give our kids solid roots.”
everybody has challenges and hardships – it is what we do with that experience that matters
And when you have a sense of community and of acceptance and belonging it comes easier.”
Bugyi and her husband moved to New Zealand for a time
before returning to Canada to live and work in Meadow Lake and then Humboldt
she and her husband set up their own business
selling it after nine years to move with their four children to Saskatoon in 2013
In her time at Preston Park II Bugyi says she has worked to “establish a community within a community.”
Listening and compassion have been integral to her leadership at the retirement residence
“We worked to create an experience that sets up everyone for success
that lets each person know ‘there is a place for you here.’”
In his message to the diocese about the appointment
board Chair Ray Kolla looked ahead to the ongoing mission of the Diocese of Saskatoon Catholic Foundation
as we continue the Catholic Foundation’s mission to provide the financial resources for current and future needs of our diocese through good stewardship practices
fund-raising and helping parishioners to be actively engaged and supported through their faith journey,” Kolla said
© 2022-2023 Roman Catholic Diocese of Saskatoon
The Roman Catholic Diocese of Saskatoon does not necessarily endorse
the content of any external sites linked from or listed on this website
ReginaNewsThis Regina bakery is taking its cakes to a Food Network competitionBy Mackenzie ReadPublished: September 04, 2021 at 5:21PM EDT
New York graduated 168 troopers today from the State Police Academy in Albany.
“These new members of the New York State Police will serve one of the most prestigious and challenging roles in society as law enforcement personnel,” Gov. Andrew Cuomo said in a statement.
The officers completed 26 weeks of training. They received a salary of $50,374 while in the academy and will get a base salary of $66,905 when they start in the job.
For the first 10 weeks, they’ll participate in a field-training program.
Here’s a list of the graduating troopers Thursday, their hometowns and where they will be stationed.
A new option to help prevent food waste while saving money has arrived in Saskatchewan
The phone app Too Good To Go allows businesses to sell food nearing its best before date — that would otherwise be wasted — at discounted prices
the service launched in Canada in July 2021
More than 6,000 Canadian businesses are currently registered
Subscribe now to read the latest news in your city and across Canada
Create an account or sign in to continue with your reading experience
baskets of surplus food are posted at around one third of the original price
and customers can choose one in their location to pick up
There are 40 businesses signed up so far in Saskatoon and 39 in Regina
While the app officially launched in the province Thursday
has already been using the service for the past week
“I have one package right now three days a week
not many of his customers would buy sale items at reduced prices
was that he doesn’t have to market the service
“They approached me and I thought that would be an awesome idea
who owns Prairie Doughnut and Poutine in Saskatoon
began using the app last week and also said it has been successful so far
“I’ve had about 40 to 45 orders in the past five days,” he said
By signing up you consent to receive the above newsletter from Postmedia Network Inc
The next issue of Headline News will soon be in your inbox
Interested in more newsletters? Browse here.
“We always give fresh doughnuts to everyone
if I made around 40 or 50 doughnuts but if somebody asked for just 12 doughnuts
then what should I do with the remaining doughnuts?”
Shah said he has given doughnuts away and donated them in the past
“But sometimes it is hard to get some people to walk in here who want to try doughnuts,” he said
People can order and come here and they can get whatever we have left.”
Too Good To Go’s senior public relations manager
said when it comes to the guidelines of the food that can be sold on the app
“nothing that can’t be sold for full retail value can be sold on the app.”
She said the app is not a way for companies to extend the life of the food
“A really good example is pizza cannot be under those heat lamps for more than three hours
so then it also cannot be in a Too Good To Go bag for that period either.”
She added the bag might contain items that are on their best before date
or one day past it if it was packed the night before
Soteroff said new stores are frequently joining
and the app could expand to smaller Saskatchewan markets in the future
Their strategy is to start in more populated cities and move out from there
“We don’t want to be in a super remote area where there is just one store because it makes for a bad consumer experience and a bad business experience,” Soteroff said
App users can filter their search based on categories like produce
baked goods or prepared meals and stores assign a time window for pickup
participating businesses across the country have earned a combined $10 million on food that would otherwise go to waste
There is a $2 operational fee the app takes from every transaction
Food scraps, yard waste, pizza boxes, napkins and tissues can go into the carts, diverting around 50 per cent of the average household’s waste from the landfill. The carts will begin being delivered on Saturday.
transmission or republication strictly prohibited
This website uses cookies to personalize your content (including ads), and allows us to analyze our traffic. Read more about cookies here. By continuing to use our site, you agree to our Terms of Use and Privacy Policy
You can manage saved articles in your account
Enjoy some moments from the big day in form of some of the many pictures taken by Aleksi Sutinen
Actin depolymerizing factors (ADFs) are among the key proteins involved in regulation of actin
This study used various biochemical and structural biology methods to uncover several key aspects of ADFs from the malaria parasite and its vector
The results show that ADFs from the malaria parasite can bind different phosphoinositides
and the binding may be regulated by phosphorylation
The parasite ADFs also bind to actin in a pH dependent manner
This study also presents the three-dimensional structure of the ADF from the Anopheles mosquito
The structure is different from that of the parasite ADFs
The mosquito ADF interacts tightly with actin
(https://www.oulu.fi/en/theses/structure-and-function-actin-depolymerizing-factors-malaria-parasite-and-its-vector)
“Jesus calls each of us to be a beacon of light for the world, urging us not to turn away from others in an attitude of indifference, and allow our light to illumine and support others.” – Bishop Mark Hagemoen, 2024 BAA message
The 2024 Bishop’s Annual Appeal is underway across the Roman Catholic Diocese of Saskatoon, with Bishop Mark Hagemoen recently announcing the 2024 theme, “On the Pilgrimage of Hope,” echoing the theme of the upcoming Jubilee 2025 celebrations announced by Pope Francis
The goal for the 2024 Appeal is $1.4 million
Initiated some 40 years ago by the late Bishop James Mahoney, today the Bishop’s Annual Appeal is an undertaking led by the Diocese of Saskatoon Catholic Foundation, the fund-raising arm for the diocese of Saskatoon
“The Bishop’s Annual Appeal has a long history — even a legacy — in the diocese,” said Bishop Mark Hagemoen at a breakfast for parish leaders and BAA volunteers held Sept
immediately before a day-long diocesan gathering to launch another ministry year
there is this practical question of how do we resource the good work and the service we need to do,” the bishop said
“The Bishop’s Annual Appeal is about the mission of the church – full stop,” Hagemoen added later at the Administration Day gathering
as he reflected upon the diocesan Pastoral Plan priority to “Move from Maintenance to Mission.”
“We all need to be engaged in the support of the mission.”
and donors for their support for the Bishop’s Annual Appeal
which funds outreach and faith formation across the diocese
Diocese of Saskatoon Foundation Executive Director Raissa Bugyi provided an overview of this year’s Appeal
including the release of a BAA video offering a glimpse into the impact of programs funded through the diocesan Appeal
Executive Director of the Diocese of Saskatoon Catholic Foundation
provided an overview of the 2024 Appeal at a morning meeting Sept
During the Administration Day gathering of parish leaders later in the day Sept
the bishop’s delegate for the Annual Appeal
also spoke about its legacy and its importance
he witnessed his parents place a priority on charitable giving and on supporting their parish
even when money was tight — and he also recalled the first time they were asked to donate to something more — to the diocesan Appeal
It was a call to join together with other Catholics across the diocese
to offer ministry and outreach that a single parish probably could not do all on its own
“It is a call to share in something bigger,” Cooper said
also encouraging pastors and leaders to make their own gift to the Appeal first
“We can’t ask for what we don’t give ourselves.”
pastor and rector of the Cathedral of the Holy Family in Saskatoon
spoke about the impact of the BAA in the diocese
In his annual written and video message about the 2024 Appeal
Bishop Hagemoen provided an overview of its impact in the diocese
“Through the various ministries supported by the Bishop’s Annual Appeal
the faithful of the Roman Catholic Diocese of Saskatoon bring hope to others,” he said
teach catechism to our children and young people
and provide pastoral care to the hospitalized and sick
We also provide reconciliation and healing to those in prison
We are supporting and training new priests and deacons to lead us
fostering faith growth through youth and adult ministries
We continue to invite lay adults into the Catholic faith
as well as support and train adult leaders for ministry and service.”
Hagemoen and Bugyi both expressed their gratitude to parishes
and volunteers for their support of the Bishop’s Annual Appeal over the years
Bishop’s BAA 2024 Message: (PDF in English) / (PDF in French)
More information and online giving: dscf.ca/baa
Kiply Lukan Yaworski is the communications coordinator for the Roman Catholic Diocese of Saskatoon – rcdos.ca
Saskatoon Bishop Mark Hagemoen joined residents and guests at St
27 to celebrate the memorial of the saint who founded the Ursuline order of consecrated religious women
and to dedicate a new mural highlighting the history and ministry of the Ursulines of Prelate
The feast day celebration at St. Angela Merici Residence began with Mass concelebrated by Bishop Hagemoen and Fr
Lector for the celebration of the Eucharist was Sr
OSU; cantor was Director of Spiritual Care and Mission Judy Gatin; with music ministry led by Sr
a mural describing the history and the ministry of the Ursulines of Prelate was dedicated
The St. Angela Merici faith-based residence — established by the Ursulines in Saskatoon and now operated by Emmanuel Care — was named in honour of the saint who started the Company of St
The Ursulines of Prelate were established in St
Joseph’s Colony (now the western portion of the diocese of Saskatoon) more than 100 years ago
beginning with three sisters from Germany – Mother Clementia Graffelder
who came to establish schools at the invitation of Fr
During the dedication celebration on the Feast of St
Angela Merici Residence and the mural project
of the Ursulines of Prelate at a dedication for a new “Educating For Life” mural about the history and ministry of the Ursulines of Prelate
“This personal care home was originally built in 1986 as a retirement home for the Ursuline Sisters
there have been many changes and some significant transformations.”
the Sisters in residence were still quite active
with some still engaged in volunteer ministry in the community
“As years passed the needs of the resident Sisters were changing…until in 2000 we hired the first care aides
more lay staff were added in all departments – care of the Sisters
a Personal Care Home license was granted for the facility to operate according to Saskatchewan Health Authority Policies
and receive residents other than Ursuline Sisters
we acted on a decision our community had made in 2015 to transfer ownership and management of St
Angela Merici Residence to Emmanuel Care – the Catholic Health Corporation of Saskatchewan
2020 – just before the pandemic was declared.”
the Ursulines of Prelate began the process of finding homes for museum artifacts located in a Heritage Room in the building
“It was decided to dismantle the Heritage Room and donate its contents to schools
parishes and organizations that would use them to continue our mission of ‘Educating for Life.’ This was a major task
and was completed just a few months ago,” said Lewans
“In order to preserve our story and some of the more valuable artifacts of the Ursuline Sisters
we asked and received permission from Anne Miller
to create the display you see before you,” she explained
effort and love” that the leadership team put into planning the display
“The mural is a brief history of our Ursuline Congregation
and the cabinet of artifacts contains tangible items that illustrate part of that history” she said
“It certainly is appropriate for us to dedicate it today on the feast of St
Angel Merici who is both the foundress of the Ursuline Order and also the patron saint of this residence
Lewans also acknowledged the work of professional designer Deanna Miller who helped the OSU leadership team design the mural
“Thank you very much Deanna; we could not have done this without you
I also acknowledge the practical work of 77 Signs
the company that printed and installed the mural and did the necessary carpentry work.”
RELATED: Ursulines of Prelate celebrate their centennial in 2019 – ARTICLE
RELATED: Ursulines of Bruno celebrate their centennial in 2013 – ARTICLE
the content of any external sites linked from or listed on this website.