scholarly journals Proteomics-Based Detection of Immune Dysfunction in an Elite Adventure Athlete Trekking Across the Antarctica

Proteomes ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 4 ◽  
Author(s):  
David C. Nieman ◽  
Arnoud J. Groen ◽  
Artyom Pugachev ◽  
Andrew J. Simonson ◽  
Kristine Polley ◽  
...  

Proteomics monitoring of an elite adventure athlete (age 33 years) was conducted over a 28-week period that culminated in the successful, solo, unassisted, and unsupported two month trek across the Antarctica (1500 km). Training distress was monitored weekly using a 19-item, validated training distress scale (TDS). Weekly dried blood spot (DBS) specimens were collected via fingerprick blood drops onto standard blood spot cards. DBS proteins were measured with nano-electrospray ionization liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) in data-independent acquisition (DIA) mode, and 712 proteins were identified and quantified. The 28-week period was divided into time segments based on TDS scores, and a contrast analysis between weeks five and eight (low TDS) and between weeks 20 and 23 (high TDS, last month of Antarctica trek) showed that 31 proteins (n = 20 immune related) were upregulated and 35 (n = 17 immune related) were downregulated. Protein–protein interaction (PPI) networks supported a dichotomous immune response. Gene ontology (GO) biological process terms for the upregulated immune proteins showed an increase in regulation of the immune system process, especially inflammation, complement activation, and leukocyte mediated immunity. At the same time, GO terms for the downregulated immune-related proteins indicated a decrease in several aspects of the overall immune system process including neutrophil degranulation and the antimicrobial humoral response. These proteomics data support a dysfunctional immune response in an elite adventure athlete during a sustained period of mental and physical distress while trekking solo across the Antarctica.

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1760-1760
Author(s):  
David Nieman ◽  
Arnoud Groen ◽  
Artyom Pugachev ◽  
Andrew Simonson ◽  
Kristine Polley ◽  
...  

Abstract Objectives Proteomics when combined with psychological, nutrition, and performance measures may serve as a useful monitoring system for immune dysfunction, training distress, and exercise-induced muscle damage and exhaustion in athletes. Global proteomics monitoring of an elite adventure athlete (age 33 years) was conducted over a 28-week period that culminated in the successful, unassisted 2-month trek across Antarctica (1500 km). Methods Training distress was monitored weekly using the 19-item, validated Training Distress Scale (TDS). Weekly dried blood spot (DBS) specimens were collected via fingerprick blood drops onto standard blood spot cards. DBS proteins were measured with nano-electrospray ionization liquid chromatography tandem mass spectrometry (nanoLC-MS/MS) in data-independent acquisition (DIA) mode, and 712 proteins were identified and quantified. Results The participant experienced a decrease of 11.4 kg in body mass during the Antarctica trek. The 28-week period was divided into time segments based on TDS scores, and a contrast analysis between weeks 5–8 (low TDS) and weeks 20–23 (high TDS, last month of Antarctica trek) showed that 31 proteins (n = 20 immune related, n = 14 nutrition related with n = 8 in dual roles) were upregulated and 35 (n = 17 immune related) were downregulated. Protein-protein interaction (PPI) networks and gene ontology (GO) biological process analysis supported an increase in plasma lipoprotein particle remodeling, regulation of lipid transport, retinoid metabolic process, and vitamin transport due to high energy intake (7048 kcal/d). PPI networks also supported a dichotomous immune response. GO terms for the upregulated immune proteins showed an increase in regulation of the immune system process, especially inflammation, complement activation, and leukocyte mediated immunity. GO terms for the downregulated immune-related proteins indicated a decrease in several aspects of the overall immune system process including neutrophil degranulation and the antimicrobial humoral response. Conclusions These proteomics data support a dysfunctional immune response in an elite adventure athlete during a sustained period of mental and physical distress, high energy intake, and significant loss of body mass while trekking solo across Antarctica. Funding Sources Standard Process, Inc., Palmyra, WI.


Toxins ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 339
Author(s):  
Pablo Ventoso ◽  
Antonio J. Pazos ◽  
Juan Blanco ◽  
M. Luz Pérez-Parallé ◽  
Juan C. Triviño ◽  
...  

Some diatom species of the genus Pseudo-nitzschia produce the toxin domoic acid. The depuration rate of domoic acid in Pecten maximus is very low; for this reason, king scallops generally contain high levels of domoic acid in their tissues. A transcriptomic approach was used to identify the genes differentially expressed in the P. maximus digestive gland after the injection of domoic acid. The differential expression analysis found 535 differentially expressed genes (226 up-regulated and 309 down-regulated). Protein–protein interaction networks obtained with the up-regulated genes were enriched in gene ontology terms, such as vesicle-mediated transport, response to stress, signal transduction, immune system process, RNA metabolic process, and autophagy, while networks obtained with the down-regulated genes were enriched in gene ontology terms, such as response to stress, immune system process, ribosome biogenesis, signal transduction, and mRNA processing. Genes that code for cytochrome P450 enzymes, glutathione S-transferase theta-1, glutamine synthase, pyrroline-5-carboxylate reductase 2, and sodium- and chloride-dependent glycine transporter 1 were among the up-regulated genes. Therefore, a stress response at the level of gene expression, that could be caused by the domoic acid injection, was evidenced by the alteration of several biological, cellular, and molecular processes.


2005 ◽  
Vol 65 (2) ◽  
pp. 203-209 ◽  
Author(s):  
J. M. Barreto-Medeiros ◽  
E. G. Feitoza ◽  
K. Magalhães ◽  
R. R. da Silva ◽  
F. M. Manhães-de-Castro ◽  
...  

The repercussion on the immune response of the expression of intraspecific aggressiveness in the face of a stressor agent was investigated in rats. Ninety-day-old animals were divided into three groups: the control group (only immunological measurements were performed), the foot-shock (FS) (animals individually receiving FS), and the intraspecific aggressive response (IAR) group (animals receiving FS and presenting IAR). For immunological measurements, blood samples were collected promptly at 7 and 15 days after FS or IAR. The FS reduced the total leukocyte amount presented. However, aggressiveness triggered not only reduction of the leukocytes, but also lymphocyte decrease and neutrophil increase. Moreover, an elevation in total leukocytes associated with an increase in the humoral immune response was also observed one week after IAR. In this study, the expression of intraspecific aggressiveness in the face of a stressor seemed to activate the immune system and to potentiate the antigen specific humoral response.


2021 ◽  
Author(s):  
Yi Wang ◽  
Xiaoxia Wang ◽  
Laurence Don Wai Luu ◽  
Shaojin Chen ◽  
Jin Fu ◽  
...  

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results suggest that protective immunity against SARS-CoV-2 can be achieved via multiple mechanisms and highlights the utility of a systems biology approach in defining molecular correlates of protection to vaccination.


Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 424
Author(s):  
Naren Gaowa ◽  
Wenli Li ◽  
Brianna Murphy ◽  
Madison Cox

This study aimed to investigate the changes in abomasum transcriptome and the associated microbial community structure in young calves with artificially dosed, adult rumen contents. Eight young bull calves were randomly dosed with freshly extracted rumen contents from an adult cow (high efficiency (HE), n = 4), or sterilized rumen content (Con, n = 4). The dosing was administered within 3 days of birth, then at 2, 4, and 6 weeks following the initial dosing. Abomasum tissues were collected immediately after sacrifice at 8 weeks of age. Five genera (Tannerella, Desulfovibrio, Deinococcus, Leptotrichia, and Eubacterium; P < 0.05) showed significant difference in abundance between the treatments. A total of 975 differentially expressed genes were identified (P < 0.05, fold-change > 1.5, mean read-counts > 5). Pathway analysis indicated that up-regulated genes were involved in immune system process and defense response to virus, while the down-regulated genes involved in ion transport, ATP biosynthetic process, and mitochondrial electron transport. Positive correlation (r > 0.7, P < 0.05) was observed between TRPM4 gene and Desulfovibrio, which was significantly higher in the HE group. TRPM4 had a reported role in the immune system process. In conclusion, the dosing of adult rumen contents to calves can alter not only the composition of active microorganisms in the abomasum but also the molecular mechanisms in the abomasum tissue, including reduced protease secretion and decreased hydrochloric acid secretion.


2021 ◽  
Vol 12 ◽  
Author(s):  
Karthikeyan Subbarayan ◽  
Kamatchi Ulagappan ◽  
Claudia Wickenhauser ◽  
Michael Bachmann ◽  
Barbara Seliger

There exists increasing evidence that people with preceding medical conditions, such as diabetes and cancer, have a higher risk of infection with SARS-CoV-2 and are more vulnerable to severe disease. To get insights into the possible role of the immune system upon COVID-19 infection, 2811 genes of the gene ontology term “immune system process GO: 0002376” were selected for coexpression analysis of the human targets of SARS-CoV-2 (HT-SARS-CoV-2) ACE2, TMPRSS2, and FURIN in tissue samples from patients with cancer and diabetes mellitus. The network between HT-SARS-CoV-2 and immune system process genes was analyzed based on functional protein associations using STRING. In addition, STITCH was employed to determine druggable targets. DPP4 was the only immune system process gene, which was coexpressed with the three HT-SARS-CoV-2 genes, while eight other immune genes were at least coexpressed with two HT-SARS-CoV-2 genes. STRING analysis between immune and HT-SARS-CoV-2 genes plotted 19 associations of which there were eight common networking genes in mixed healthy (323) and pan-cancer (11003) tissues in addition to normal (87), cancer (90), and diabetic (128) pancreatic tissues. Using this approach, three commonly applicable druggable connections between HT-SARS-CoV-2 and immune system process genes were identified. These include positive associations of ACE2—DPP4 and TMPRSS2—SRC as well as a negative association of FURIN with ADAM17. Furthermore, 16 drugs were extracted from STITCH (score &lt;0.8) with 32 target genes. Thus, an immunological network associated with HT-SARS-CoV-2 using bioinformatics tools was identified leading to novel therapeutic opportunities for COVID-19.


1977 ◽  
Vol 145 (3) ◽  
pp. 569-577 ◽  
Author(s):  
C G Fathman ◽  
D S Pisetsky ◽  
D H Sachs

Rat antisera raised against anti-nuclease antibodies from mouse strains A/J and SJL detect strain-specific idiotypic determinants related to the antigen-combining site. These antisera have been used to investigate the genetic linkage and strain distribution of the anti-nuclease idiotypes. Despite the existence of an H-2-linked immune response gene controlling the humoral response to nuclease, expression of the A/J anti-nuclease idiotype has been shown to be independent of genes in the H-2 region: the A/J idiotype was present in immune sera from strains A/J (H-2a) and A.BY (H-2b) but absent in sera from strains B10 (H-2b) and B10.A (H-2a). An analysis of the segregation of the A/J idiotype in offspring of the backcross (A/J x B10.A) x B10.A demonstrated linkage to the Ig-1e heavy chain allotype markers. In a small sample of backcross animals a very high apparent recombination frequency was observed, but further backcross analyses and progeny testing of putative recombinant animals will be required to substantiate this observation. Analysis of the A/J and SJL anti-nuclease idiotype markers in the BALB/c, CB.20, and BAB.14 strains indicate that these idiotypic markers may permit mapping of distinct variable region genes.


Mathematics ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1356
Author(s):  
Juan Carlos Chimal-Eguia

This work presents a mathematical model to investigate the current outbreak of the coronavirus disease 2019 (COVID-19) worldwide. The model presents the infection dynamics and emphasizes the role of the immune system: both the humoral response as well as the adaptive immune response. We built a mathematical model of delay differential equations describing a simplified view of the mechanism between the COVID-19 virus infection and the immune system. We conduct an analysis of the model exploring different scenarios, and our numerical results indicate that some theoretical immunotherapies are successful in eradicating the COVID-19 virus.


2020 ◽  
Author(s):  
Karthikeyan Subbarayan ◽  
Kamatchi Ulagappan ◽  
Claudia Wickenhauser ◽  
Barbara Seliger

Abstract Background There exists increasing evidence that people with preceding medical conditions, such as asthma, diabetes, cancers and heart disease, have a higher risk of infection with SARS-CoV-2 and are more vulnerable to severe disease.Methods To get insights into the role of the immune system upon COVID-19 infection, 2811 genes of the gene ontology term “immune system process GO: 0002376” were selected for analyses. The immune system genes potentially co-expressed with the human targets of SARS-CoV-2 (HT-SARS-CoV-2) ACE2, TMPRSS2 and FURIN were determined in tissue samples from patients with cancer and diabetes mellitus. The network between HT-SARS-CoV-2 and immune system process genes was analyzed based on functional protein associations using STRING. In addition, STITCH was employed to determine druggable targets.Results DPP4 was the only immune system process gene, which was coexpressed with the three HT-SARS-CoV-2 genes, while eight other immune genes were at least co-expressed with two HT-SARS-CoV-2 genes. STRING analysis between immune and HT-SARS-CoV-2 genes plotted 19 associations of 8 commonly networking genes in mixed healthy (323) and cancer (11003) tissues in addition to normal (87), cancer (90) and diabetic (128) pancreatic tissues. Using this approach, three druggable connections between HT-SARS-CoV-2 and immune system process genes were identified. They include positive associations of ACE2 - DPP4 and TMPRSS2 – SRC as well as a negative association of FURIN with ADAM17. Furthermore, the 16 drugs were extracted from STITCH (score <0.8) with 32 target genes.Conclusions This bioinformatics pipeline identified for the first time an immunological network associated with COVID-19 infection thereby postulating novel therapeutic opportunities.


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