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Article ; Online: Obsessive-compulsive disorder and gut microbiota dysregulation.

Rees, Jon C

2014 Volume 82, Issue 2, Page(s) 163–166

Abstract: Obsessive-compulsive disorder (OCD) is a debilitating disorder for which the cause is not known and treatment options are modestly beneficial. A hypothesis is presented wherein the root cause of OCD is proposed to be a dysfunction of the gut microbiome ... ...

Abstract	Obsessive-compulsive disorder (OCD) is a debilitating disorder for which the cause is not known and treatment options are modestly beneficial. A hypothesis is presented wherein the root cause of OCD is proposed to be a dysfunction of the gut microbiome constituency resulting in a susceptibility to obsessional thinking. Both stress and antibiotics are proposed as mechanisms by which gut microbiota are altered preceding the onset of OCD symptomology. In this light, pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) leading to episodic OCD is explained not by group A beta-hemolytic streptococcal infections, but rather by prophylactic antibiotics that are administered as treatment. Further, stressful life events known to trigger OCD, such as pregnancy, are recast to show the possibility of altering gut microbiota prior to onset of OCD symptoms. Suggested treatment for OCD would be the directed, specie-specific (re)introduction of beneficial bacteria modifying the gut microbiome, thereby ameliorating OCD symptoms. Special considerations should be contemplated when considering efficacy of treatment, particularly the unhealthy coping strategies often observed in patients with chronic OCD that may need addressing in conjunction with microbiome remediation.
MeSH term(s)	Anti-Bacterial Agents/chemistry ; Anxiety ; Central Nervous System/physiology ; Feces ; Female ; Humans ; Intestines/microbiology ; Microbiota ; Models, Theoretical ; Obsessive-Compulsive Disorder/complications ; Obsessive-Compulsive Disorder/etiology ; Obsessive-Compulsive Disorder/microbiology ; Pregnancy
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2014-02
Publishing country	United States
Document type	Journal Article
ZDB-ID	193145-3
ISSN	1532-2777 ; 0306-9877
ISSN (online)	1532-2777
ISSN	0306-9877
DOI	10.1016/j.mehy.2013.11.026
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Article ; Online: Detection of methicillin-resistant Staphylococcus aureus using phage amplification combined with matrix-assisted laser desorption/ionization mass spectrometry.

Rees, Jon C / Barr, John R

Analytical and bioanalytical chemistry

2017 Volume 409, Issue 5, Page(s) 1379–1386

Abstract: Antibiotic resistance continues to contribute significantly to morbidity and mortality across the world. Developing new tests for antibiotic-resistant bacteria is a core action to combat resistant infections. We describe a method that uses phage ... ...

Abstract	Antibiotic resistance continues to contribute significantly to morbidity and mortality across the world. Developing new tests for antibiotic-resistant bacteria is a core action to combat resistant infections. We describe a method that uses phage amplification detection (PAD) combined with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to rapidly identify Staphylococcus aureus and determine phenotypic susceptibility to cefoxitin. Samples tested for S. aureus are incubated together with bacteriophage in the presence and absence of cefoxitin and subjected to rapid trypsin digestion followed by MALDI-MS analysis. Tryptic peptides derived from amplified phage proteins can be detected by MALDI-MS, as validated by time-of-flight (TOF)/TOF analysis of each peptide combined with database searching. Methicillin-resistant S. aureus show significant phage amplification in the presence of cefoxitin, while methicillin-sensitive S. aureus show no phage amplification relative to a no-antibiotic control. We also show that PAD methodology can be implemented on an FDA-approved commercial MALDI-MS bacterial identification system to identify S. aureus and determine antibiotic susceptibility. The novelty of this assay includes the use of phage-derived tryptic peptides as detected by MALDI-MS to monitor the results of PAD on an instrument common to many modern microbiology laboratories.
Language	English
Publishing date	2017-02
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-016-0070-3
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Article: Detection of methicillin-resistant Staphylococcus aureus using phage amplification combined with matrix-assisted laser desorption/ionization mass spectrometry

Rees, Jon C / John R. Barr

Analytical and bioanalytical chemistry. 2017 Feb., v. 409, no. 5

2017

Abstract	Antibiotic resistance continues to contribute significantly to morbidity and mortality across the world. Developing new tests for antibiotic-resistant bacteria is a core action to combat resistant infections. We describe a method that uses phage amplification detection (PAD) combined with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to rapidly identify Staphylococcus aureus and determine phenotypic susceptibility to cefoxitin. Samples tested for S. aureus are incubated together with bacteriophage in the presence and absence of cefoxitin and subjected to rapid trypsin digestion followed by MALDI-MS analysis. Tryptic peptides derived from amplified phage proteins can be detected by MALDI-MS, as validated by time-of-flight (TOF)/TOF analysis of each peptide combined with database searching. Methicillin-resistant S. aureus show significant phage amplification in the presence of cefoxitin, while methicillin-sensitive S. aureus show no phage amplification relative to a no-antibiotic control. We also show that PAD methodology can be implemented on an FDA-approved commercial MALDI-MS bacterial identification system to identify S. aureus and determine antibiotic susceptibility. The novelty of this assay includes the use of phage-derived tryptic peptides as detected by MALDI-MS to monitor the results of PAD on an instrument common to many modern microbiology laboratories.
Keywords	antibiotic resistance ; bacteria ; bacteriophages ; cefoxitin ; databases ; desorption ; mass spectrometry ; methicillin ; methicillin-resistant Staphylococcus aureus ; morbidity ; mortality ; peptides ; phenotype ; proteins ; trypsin
Language	English
Dates of publication	2017-02
Size	p. 1379-1386.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ISSN	1618-2642
DOI	10.1007/s00216-016-0070-3
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Article ; Online: Stability of lipids in plasma and serum: Effects of temperature-related storage conditions on the human lipidome.

Reis, Gregory B / Rees, Jon C / Ivanova, Anna A / Kuklenyik, Zsuzsanna / Drew, Nathan M / Pirkle, James L / Barr, John R

Journal of mass spectrometry and advances in the clinical lab

2021 Volume 22, Page(s) 34–42

Abstract: Large epidemiological studies often require sample transportation and storage, presenting unique considerations when applying advanced lipidomics techniques. The goal of this study was to acquire lipidomics data on plasma and serum samples stored at ... ...

Abstract	Large epidemiological studies often require sample transportation and storage, presenting unique considerations when applying advanced lipidomics techniques. The goal of this study was to acquire lipidomics data on plasma and serum samples stored at potential preanalytical conditions (e.g., thawing, extracting, evaporating), systematically monitoring lipid species for a period of one month. Split aliquots of 10 plasma samples and 10 serum samples from healthy individuals were kept in three temperature-related environments: refrigerator, laboratory benchtop, or heated incubator. Samples were analyzed at six different time points over 28 days using a Bligh & Dyer lipid extraction protocol followed by direct infusion into a lipidomics platform using differential mobility with tandem mass spectrometry. The observed concentration changes over time were evaluated relative to method and inter-individual biological variability. In addition, to evaluate the effect of lipase enzyme levels on concentration changes during storage, we compared corresponding fasting and post-prandial plasma samples collected from 5 individuals. Based on our data, a series of low abundance free fatty acid (FFA), diacylglycerol (DAG), and cholesteryl ester (CE) species were identified as potential analytical markers for degradation. These FFA and DAG species are typically produced by endogenous lipases from numerous triacylglycerols (TAGs), and certain high abundance phosphatidylcholines (PCs). The low concentration CEs, which appeared to increase several fold, were likely mass-isobars from oxidation of other high concentration CEs. Although the concentration changes of the high abundant TAG, PC, and CE precursors remained within method variability, the concentration trends of FFA, DAG, and oxidized CE products should be systematically monitored over time to inform analysts about possible pre-analytical biases due to degradation in the study sample sets.
Language	English
Publishing date	2021-10-19
Publishing country	Netherlands
Document type	Journal Article
ISSN	2667-145X
ISSN (online)	2667-145X
DOI	10.1016/j.jmsacl.2021.10.002
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Article ; Online: Integrated Quantitative Targeted Lipidomics and Proteomics Reveal Unique Fingerprints of Multiple Metabolic Conditions.

Ivanova, Anna A / Rees, Jon C / Parks, Bryan A / Andrews, Michael / Gardner, Michael / Grigorutsa, Eunice / Kuklenyik, Zsuzsanna / Pirkle, James L / Barr, John R

Biomolecules

2022 Volume 12, Issue 10

Abstract: Aberrations in lipid and lipoprotein metabolic pathways can lead to numerous diseases, including cardiovascular disease, diabetes, neurological disorders, and cancer. The integration of quantitative lipid and lipoprotein profiling of human plasma may ... ...

Abstract	Aberrations in lipid and lipoprotein metabolic pathways can lead to numerous diseases, including cardiovascular disease, diabetes, neurological disorders, and cancer. The integration of quantitative lipid and lipoprotein profiling of human plasma may provide a powerful approach to inform early disease diagnosis and prevention. In this study, we leveraged data-driven quantitative targeted lipidomics and proteomics to identify specific molecular changes associated with different metabolic risk categories, including hyperlipidemic, hypercholesterolemic, hypertriglyceridemic, hyperglycemic, and normolipidemic conditions. Based on the quantitative characterization of serum samples from 146 individuals, we have determined individual lipid species and proteins that were significantly up- or down-regulated relative to the normolipidemic group. Then, we established protein-lipid topological networks for each metabolic category and linked dysregulated proteins and lipids with defined metabolic pathways. To evaluate the differentiating power of integrated lipidomics and proteomics data, we have built an artificial neural network model that simultaneously and accurately categorized the samples from each metabolic risk category based on the determined lipidomics and proteomics profiles. Together, our findings provide new insights into molecular changes associated with metabolic risk conditions, suggest new condition-specific associations between apolipoproteins and lipids, and may inform new biomarker discovery in lipid metabolism-associated disorders.
MeSH term(s)	Humans ; Lipidomics ; Proteomics ; Lipid Metabolism ; Lipids ; Lipid Metabolism Disorders ; Biomarkers/metabolism
Chemical Substances	Lipids ; Biomarkers
Language	English
Publishing date	2022-10-08
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12101439
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Article ; Online: Simultaneous Identification and Susceptibility Determination to Multiple Antibiotics of Staphylococcus aureus by Bacteriophage Amplification Detection Combined with Mass Spectrometry.

Rees, Jon C / Pierce, Carrie L / Schieltz, David M / Barr, John R

Analytical chemistry

2015 Volume 87, Issue 13, Page(s) 6769–6777

Abstract: The continued advance of antibiotic resistance in clinically relevant bacterial strains necessitates the development and refinement of assays that can rapidly and cost-effectively identify bacteria and determine their susceptibility to a panel of ... ...

Abstract	The continued advance of antibiotic resistance in clinically relevant bacterial strains necessitates the development and refinement of assays that can rapidly and cost-effectively identify bacteria and determine their susceptibility to a panel of antibiotics. A methodology is described herein that exploits the specificity and physiology of the Staphylococci bacteriophage K to identify Staphylococcus aureus (S. aureus) and determine its susceptibility to clindamycin and cefoxitin. The method uses liquid chromatography-mass spectrometry to monitor the replication of bacteriophage after it is used to infect samples thought to contain S. aureus. Amplification of bacteriophage K indicates the sample contains S. aureus, for it is only in the presence of a suitable host that bacteriophage K can amplify. If bacteriophage amplification is detected in samples containing the antibiotics clindamycin or cefoxitin, the sample is deemed to be resistant to these antibiotics, respectively, for bacteriophage can only amplify in a viable host. Thus, with a single work flow, S. aureus can be detected in an unknown sample and susceptibility to clindamycin and cefoxitin can be ascertained. This Article discusses implications for the use of bacteriophage amplification in the clinical laboratory.
MeSH term(s)	Anti-Bacterial Agents/pharmacology ; Bacteriophages/genetics ; Mass Spectrometry/methods ; Microbial Sensitivity Tests ; Staphylococcus aureus/drug effects ; Staphylococcus aureus/isolation & purification
Chemical Substances	Anti-Bacterial Agents
Language	English
Publishing date	2015-06-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021/acs.analchem.5b00959
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Article ; Online: Modeling bacteriophage amplification as a predictive tool for optimized MALDI-TOF MS-based bacterial detection.

Cox, Christopher R / Rees, Jon C / Voorhees, Kent J

Journal of mass spectrometry : JMS

2012 Volume 47, Issue 11, Page(s) 1435–1441

Abstract: Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a valuable tool for rapid bacterial detection and identification but is limited by the need for relatively high cell count samples, which have been grown under ...

Abstract	Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a valuable tool for rapid bacterial detection and identification but is limited by the need for relatively high cell count samples, which have been grown under strictly controlled conditions. These requirements can be eliminated by the natural infection of a viable bacterial species of interest with a host-specific phage. This produces a rapid increase in phage protein concentrations in comparison to bacterial concentrations, which can in turn be exploited as a method for signal amplification during MALDI-TOF MS. One drawback to this approach is the requirement for repetitive, time-consuming sample preparation and analysis applied over the course of a phage infection to monitor phage concentrations as a function of time to determine the MALDI-TOF MS detection limit. To reduce the requirement for repeated preparation and analysis, a modified phage therapy model was investigated as a means for predicting the time during a given phage infection when a detectable signal would occur. The modified model used a series of three differential equations composed of predetermined experimental parameters including phage burst size and burst time to predict progeny phage concentrations as a function of time. Using Yersinia pestis with plague diagnostic phage φA1122 and Escherichia coli with phage MS2 as two separate, well-characterized model phage-host pairs, we conducted in silico modeling of the infection process and compared it with experimental infections monitored in real time by MALDI-TOF MS. Significant agreement between mathematically calculated phage growth curves and those experimentally obtained by MALDI-TOF MS was observed, thus verifying this method's utility for significant time and labor reduction.
MeSH term(s)	Bacteria/isolation & purification ; Bacteria/metabolism ; Bacteria/virology ; Bacteriological Techniques/methods ; Bacteriophages/genetics ; Bacteriophages/metabolism ; Computer Simulation ; Escherichia coli/isolation & purification ; Escherichia coli/metabolism ; Escherichia coli/virology ; Models, Biological ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Yersinia pestis/isolation & purification ; Yersinia pestis/metabolism ; Yersinia pestis/virology
Language	English
Publishing date	2012-11
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1221763-3
ISSN	1096-9888 ; 1076-5174
ISSN (online)	1096-9888
ISSN	1076-5174
DOI	10.1002/jms.3087
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Article: Simultaneous Identification and Susceptibility Determination to Multiple Antibiotics of Staphylococcus aureus by Bacteriophage Amplification Detection Combined with Mass Spectrometry

Rees, Jon C / Barr John R / Pierce Carrie L / Schieltz David M

Analytical chemistry. 2015 July 07, v. 87, no. 13

2015

Abstract	The continued advance of antibiotic resistance in clinically relevant bacterial strains necessitates the development and refinement of assays that can rapidly and cost-effectively identify bacteria and determine their susceptibility to a panel of antibiotics. A methodology is described herein that exploits the specificity and physiology of the Staphylococci bacteriophage K to identify Staphylococcus aureus (S. aureus) and determine its susceptibility to clindamycin and cefoxitin. The method uses liquid chromatographyâmass spectrometry to monitor the replication of bacteriophage after it is used to infect samples thought to contain S. aureus. Amplification of bacteriophage K indicates the sample contains S. aureus, for it is only in the presence of a suitable host that bacteriophage K can amplify. If bacteriophage amplification is detected in samples containing the antibiotics clindamycin or cefoxitin, the sample is deemed to be resistant to these antibiotics, respectively, for bacteriophage can only amplify in a viable host. Thus, with a single work flow, S. aureus can be detected in an unknown sample and susceptibility to clindamycin and cefoxitin can be ascertained. This Article discusses implications for the use of bacteriophage amplification in the clinical laboratory.
Keywords	antibiotic resistance ; bacteria ; bacteriophages ; cefoxitin ; clindamycin ; liquid chromatography ; mass spectrometry ; multiple drug resistance ; physiology ; Staphylococcus aureus
Language	English
Dates of publication	2015-0707
Size	p. 6769-6777.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	1508-8
ISSN	1520-6882 ; 0003-2700
ISSN (online)	1520-6882
ISSN	0003-2700
DOI	10.1021%2Facs.analchem.5b00959
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Article ; Online: The small HDL particle hypothesis of Alzheimer's disease.

Alzheimer's & dementia : the journal of the Alzheimer's Association

2022 Volume 19, Issue 2, Page(s) 391–404

Abstract: We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. ... ...

Abstract	We propose the hypothesis that small high-density lipoprotein (HDL) particles reduce the risk of Alzheimer's disease (AD) by virtue of their capacity to exchange lipids, affecting neuronal membrane composition and vascular and synaptic functions. Concentrations of small HDLs in cerebrospinal fluid (CSF) and plasma were measured in 180 individuals ≥60 years of age using ion mobility methodology. Small HDL concentrations in CSF were positively associated with performance in three domains of cognitive function independent of apolipoprotein E (APOE) ε4 status, age, sex, and years of education. Moreover, there was a significant correlation between levels of small HDLs in CSF and plasma. Further studies will be aimed at determining whether specific components of small HDL exchange across the blood, brain, and CSF barriers, and developing approaches to exploit small HDLs for therapeutic purposes.
MeSH term(s)	Humans ; Alzheimer Disease/cerebrospinal fluid ; Apolipoproteins E ; Apolipoprotein E4 ; Brain ; Cognition ; Amyloid beta-Peptides/cerebrospinal fluid
Chemical Substances	Apolipoproteins E ; Apolipoprotein E4 ; Amyloid beta-Peptides
Language	English
Publishing date	2022-04-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2211627-8
ISSN	1552-5279 ; 1552-5260
ISSN (online)	1552-5279
ISSN	1552-5260
DOI	10.1002/alz.12649
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Article: Simultaneous detection of two bacterial pathogens using bacteriophage amplification coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.

Rees, Jon C / Voorhees, Kent J

Rapid communications in mass spectrometry : RCM

2005 Volume 19, Issue 19, Page(s) 2757–2761

Abstract: The simultaneous analysis of multiple target microorganisms using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) with bacteriophage amplification is discussed. Following infection of target bacteria with ... ...

Abstract	The simultaneous analysis of multiple target microorganisms using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) with bacteriophage amplification is discussed. Following infection of target bacteria with specific bacteriophages, proteins contained in the progeny phage are utilized as a secondary biomarker for the target bacterium. Escherichia coli when mixed with MS2 and MPSS-1 phages specific for E. coli and Salmonella spp., respectively, at levels below their corresponding detection limits, produced only the protein (13.7 kDa) characteristic of the MS2. Likewise, Salmonella spp. when mixed with the two phages only produced a protein (13.5 kDa) characteristic of MPSS-1. When the two bacteria and the two phages were mixed together, proteins characteristic of MS2 and MPSS-1 were observed indicating that both bacteriophages had been amplified. Identification of each bacterium was made based on the presence of the secondary bacteriophage biomarkers. No deleterious effects on bacteriophage amplification were observed because of the presence of multiple bacteria or bacteriophages.
MeSH term(s)	Bacteriophages/metabolism ; Colony Count, Microbial/methods ; Escherichia coli/isolation & purification ; Escherichia coli/virology ; Salmonella/isolation & purification ; Salmonella/virology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Viral Proteins/analysis
Chemical Substances	Viral Proteins
Language	English
Publishing date	2005
Publishing country	England
Document type	Comparative Study ; Evaluation Studies ; Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	58731-x
ISSN	1097-0231 ; 0951-4198
ISSN (online)	1097-0231
ISSN	0951-4198
DOI	10.1002/rcm.2107
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