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During myocardial infarction (MI), macrophages (MØ) infiltrate the ischemic left ventricle (LV) and mediate cardiac remodeling and healing. Metabolic shifts in the LV and infiltrating MØs is a hallmark of the response to injury. Glutamine is a major metabolic fuel for cardiac muscle and MØs. However, the role of GLN metabolism in the remodeling heart after MI is not well understood. We used a model of permanent coronary artery ligation in adult male C57BL/6J mice to assess GLN metabolism in extracted cardiac MØs at post-MI days (D) 1, 3, and 7. Using untargeted metabolomics, we found time-dependent changes in metabolites related to GLN and glutamate (GLU) metabolism in cardiac MØs (p=6E-4). GLN levels were significantly increased at day 3, while GLU was decreased at day 7, and the GLN/GLU ratio was higher at both D3 and 7 compared to D1 post-MI. Using Seahorse extracellular flux analysis, GLN consumption in MØs was increased on D1 and 3. In the remote area of the heart (RA), genes for GLN-metabolizing enzymes (Glud1, Got1, Gpt1) were decreased at D3 and 7, indicating a loss of GLN metabolism. We then administered GLN (1 g/kg body weight, i.p.) daily post-MI for up to D3 or 7. Compared to vehicle, GLN administration increased ejection fraction at D3 (1.2-fold increase) and 7 post-MI (1.6-fold increase), and attenuated anterior and posterior wall thinning at D7 by 1.6-fold and 1.3-fold, respectively. GLN also restored expression of genes associated with GLN metabolism (Gls1, Glul, Got1, Gpt1, Glud1) in the RA, as well as glucose oxidation (Pdha1). GLN also restored Myh6 expression and attenuated Myh7 expression, indicating favorable expression of myosin heavy chains. However, GLN did not affect cardiac MØ phenotype, as assessed by flow cytometry and cytokine mRNA levels (Il1b, Tnf, Il6, Ccl2, Il18, and Il10). We then blocked GLN metabolism by administering BPTES (12.5 mg/kg daily i.p. in corn oil) to mice for 3 days post-MI. BPTES exacerbated anterior wall thinning (1.4-fold decrease) and further decreased EF (1.4-fold) after MI, and also increased expression of Myh7 in the RA. However, BPTES did not affect MØ phenotypes. In conclusion, dysregulation of GLN metabolism is a hallmark of post-MI cardiac remodeling, and enhancing GLN metabolism may improve cardiac function, but may not be effective for reducing MØ-mediated inflammation post-MI. Funding: NIDDK 1R01121411, P20GM104357, U54GM115428, AHA856365 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Brain response to visual stimulation can be probed quantitatively using functional magnetic resonance spectroscopy (fMRS), which relies on the blood oxygenation level dependent (BOLD) contrast mechanism. BOLD effect in fMRS is associated with changes in the areas, widths, and heights of the MR spectra. This study investigated the effect of spectral averaging scheme (NEX value) on BOLD changes in the spectra. Using a visual stimulus at 8 Hz in single and interleaved stimulation paradigms, the BOLD effects in spectra acquired from the occipital brain region of three healthy volunteers (mean age ± SD = 32.7 ± 3.5 years) were compared for two fMRS data sets acquired with two NEX values (“2” and “8”) available on a 3 T MR scanner. BOLD signal changes were estimated as percentage changes in spectral areas, heights, and widths of six cerebral metabolites and water using the SAGE software package (version 7). There was a general trend of lower BOLD effects with NEX = 8 in both stimulation paradigms. In the single stimulation paradigm, NEX = 8 was associated with significantly lower N-acetyl aspartate (NAA) spectral height (p = 0.03), creatine (p = 0.04) and choline (p = 0.02) spectral widths, and NAA (p = 0.03), water (p p = 0.02) spectral areas. In the interleaved stimulation paradigm, NEX = 8 was associated with significantly lower glutamate spectral height (p = 0.02), water (p = 0.03), and glutamine (p = 0.03) spectral widths, but there was no significant difference in all spectral areas between the two NEX values. Even though the two NEX values offered some differences in observable BOLD effects, their spectral areas were not significantly different in the interleaved visual stimulation experiments.

INTRODUCTION: Ion mobility-mass spectrometry is an emerging technology in the clinical setting for high throughput and high confidence molecular characterization from complex biological samples. Ion mobility spectrometry can provide isomer separations on the basis of molecular structure, the ability of which is increasing through technological developments that afford enhanced resolving power. Integrating multiple separation dimensions, such as liquid chromatography-ion mobility-mass spectrometry (LC-IM-MS) provide dramatic enhancements in the mitigation of molecular interferences for high accuracy clinical measurements. AREAS COVERED: Multidimensional separations with LC-IM-MS provide better selectivity and sensitivity in molecular analysis. Mass spectrometry imaging of tissues to inform spatial molecular distribution is improved by complementary ion mobility analyses. Biomarker identification in surgical environments is enhanced by intraoperative biochemical analysis with mass spectrometry and holds promise for integration with ion mobility spectrometry. New prospects in high resolving power ion mobility are enhancing analysis capabilities, such as distinguishing isomeric compounds. EXPERT OPINION: Ion mobility-mass spectrometry holds many prospects for the field of isomer identification, molecular imaging, and intraoperative tumor margin delineation in clinical settings. These advantages are afforded while maintaining fast analysis times and subsequently high throughput. High resolving power ion mobility will enhance these advantages further, in particular for analyses requiring high confidence isobaric selectivity and detection.

Deep ripping, in conjunction with gypsum and/or organic amendment, is known to be useful for removing physical constraints and improving crop yields in dispersive subsoils. However, the benefits are short-lived due to lateral movement of Na into soil between the rip lines, and slumping following the wetting of loosened soil, leaving low pore volume for air and water movement. This study evaluated the effect of high concentration polyacrylamide (PAM) solutions on stabilising soil structure, with a focus on PAM application on dispersive aggregates theoretically dislodged by ripping, as part of the subsoil decompaction. Three distinct soils (Vertosol, Kandosol, and Dermosol) from southern Queensland were treated to be sodic. These aggregates were further applied with PAM solutions under three scenarios, including: immersion, coating, and no application. In general, PAM stabilised soil aggregates with a concentration above 1.5 g L–1 when immersed into PAM solution or coated with PAM product, as compared to non-PAM-treated samples. The efficacy depended on PAM concentration, viscosity, soil type, and mechanical force. The concept of spraying PAM for stabilising the subsoil during tillage was proposed, as there is feasible potential for PAM to prolong the benefits of subsoil decompaction long enough through stabilising aggregate structure.

Native ion mobility-mass spectrometry (IM-MS) has emerged as an information-rich technique for gas phase protein structure characterization; however, IM resolution is currently insufficient for the detection of subtle structural differences in large biomolecules. This challenge has spurred the development of collision-induced unfolding (CIU) which utilizes incremental gas phase activation to unfold a protein in order to expand the number of measurable descriptors available for native protein ions. Although CIU is now routinely used in native mass spectrometry studies, the interlaboratory reproducibility of CIU has not been established. Here we evaluate the reproducibility of the CIU data produced across three laboratories (University of Michigan, Texas A&M University, and Vanderbilt University). CIU data were collected for a variety of protein ions ranging from 8.6-66 kDa. Within the same laboratory, the CIU fingerprints were found to be repeatable with root mean square deviation (RMSD) values of less than 5%. Collision cross section (CCS) values of the CIU intermediates were consistent across the laboratories, with most features exhibiting an interlaboratory reproducibility of better than 1%. In contrast, the activation potentials required to induce protein CIU transitions varied between the three laboratories. To address these differences, three source assemblies were constructed with an updated ion activation hardware design utilizing higher mechanical tolerance specifications. The production-grade assemblies were found to produce highly consistent CIU data for intact antibodies, exhibiting high precision ion CCS and CIU transition values, thus opening the door to establishing databases of CIU fingerprints to support future biomolecular classification efforts.

Structures for lossless ion manipulation-based high-resolution ion mobility (HRIM) interfaced with mass spectrometry has emerged as a powerful tool for the separation and analysis of many isomeric systems. IM-derived collision cross section (CCS) is increasingly used as a molecular descriptor for structural analysis and feature annotation, but there are few studies on the calibration of CCS from HRIM measurements. Here, we examine the accuracy, reproducibility, and practical applicability of CCS calibration strategies for a broad range of lipid subclasses and develop a straightforward and generalizable framework for obtaining high-resolution CCS values. We explore the utility of using structurally similar custom calibrant sets as well as lipid subclass-specific empirically derived correction factors. While the lipid calibrant sets lowered overall bias of reference CCS values from ∼2-3% to ∼0.5%, application of the subclass-specific correction to values calibrated with a broadly available general calibrant set resulted in biases0.4%. Using this method, we generated a high-resolution CCS database containing over 90 lipid values with HRIM. To test the applicability of this method to a broader class range typical of lipidomics experiments, a standard lipid mix was analyzed. The results highlight the importance of both class and arrival time range when correcting or scaling CCS values and provide guidance for implementation of the method for more general applications.

Previous work has demonstrated that copper complexation strategies can be used with tandem MS (MS/MS) and, more recently, ion mobility-mass spectrometry (IM-MS) to differentiate chiral isomers based upon enantiomeric-specific binding. In this study, we investigate the separation of chiral amino acids (AAs) forming trinuclear complexes that can be directly resolved by IM-MS analyses. Twenty standard AAs of both d- and l-chirality were investigated. Specific AAs including d/l-histidine, d/l-proline, d/l-glutamine, d/l-tyrosine, and d/l-tryptophan were evaluated as "chiral selectors" that, when combined with copper, were found to promote selective complexation with specific AA enantiomers. Significant enantiomer differentiation was observed in the IM spectra for hydrophobic AAs acids with peak-to-peak resolutions ranging from 0.63 to 1.15. Among the chiral selectors investigated, histidine provided the best enantioselectivity, followed by tryptophan, suggesting the aromatic structure plays an important role in forming chiral-specific ion complexes. Unlike MS/MS methods where chiral selectors with l-stereochemistry enhance the differentiation, the chirality of the selector was found to have no significant effect on observed IM separation with both d- and l-selectors providing similar resolutions but with inverted IM arrival time ordering. To investigate the structural differences between resolvable chiral complexes, a combination of MS/MS, collision cross-section (CCS) measurements, and molecular mechanics techniques was used. Candidate trinuclear structures of the stoichiometry [(Cu

Abnormalities of sleep are common in myotonic dystrophy type 1 (DM1), but few previous studies have combined polysomnography with detailed clinical measures and brain imaging. In the present study, domiciliary polysomnography, symptom questionnaires and cognitive evaluation were undertaken in 39 DM1-affected individuals. Structural brain MRI was completed in those without contra-indication (n = 32). Polysomnograms were adequate for analysis in 36 participants. Sleep efficiency was reduced, and sleep architecture altered in keeping with previous studies. Twenty participants (56%) had moderate or severe sleep-disordered breathing (apnoea-hypopnoea index [AHI] ≥ 15). In linear modelling, apnoeas were positively associated with increasing age and male sex. AHI ≥ 15 was further associated with greater daytime pCO2 and self-reported physical impairment, somnolence and fatigue. Percentage REM sleep was inversely associated with cerebral grey matter volume, stage 1 sleep was positively associated with occipital lobe volume and stage 2 sleep with amygdala volume. Hippocampus volume was positively correlated with self-reported fatigue and somnolence. Linear relationships were also observed between measures of sleep architecture and cognitive performance. Findings broadly support the hypothesis that changes in sleep architecture and excessive somnolence in DM1 reflect the primary disease process in the central nervous system.

The dispersive behavior dynamics of clay determine soil characteristics such as permeability and aggregate stability, and, consequently, crop productivity. Soil dispersion is heavily influenced by the ionicity of clay–cation bonds and has been shown to be related to the net negative charge and pH of the system. Little work has been done, however, which considers these factors together, especially for K and Mg clays. The objective of the present study was to investigate the effect of changing pH on the dispersive behavior of Mg and K homoionic clays, in comparison to Ca and Na clays under equivalent pH conditions. The clay fractions used here were extracted from three soils and have distinctly different mineralogies. These clays were treated to become homoionic with regard to Na, K, Ca, and Mg. Excess salts were removed by dialysis and pH was adjusted to 3, 4, 5, 6, 7, 8, 9, 10, and 11 for all clays, except Mg (pH range 3–7). Clay dispersion-flocculation dynamics were investigated, and the net negative charge, pH, electrical conductivity (EC), and turbidity were measured. Mg has a similar but less flocculative effect than Ca, while K has a similar but less dispersive effect than Na, under similar pH conditions. The dispersive behavior of Na, K, Mg, and Ca homoionic clays was correlated well with the ionicity of clay–cation bonds at equivalent pH, with the degree of clay dispersion being explained by the pH, EC, ionicity, ζ-potential, and mean particle size of the clay–cation system. A predictive model for dispersion was developed with its applicability and limitations discussed.

Motivation Mass spectrometry-based untargeted lipidomics aims to globally characterize the lipids and lipid-like molecules in biological systems. Ion mobility increases coverage and confidence by offering an additional dimension of separation and a highly reproducible metric for feature annotation, the collision cross-section (CCS). Results We present a data processing workflow to increase confidence in molecular class annotations based on CCS values. This approach uses class-specific regression models built from a standardized CCS repository (the Unified CCS Compendium) in a parallel scheme that combines a new annotation filtering approach with a machine learning class prediction strategy. In a proof-of-concept study using murine brain lipid extracts, 883 lipids were assigned higher confidence identifications using the filtering approach, which reduced the tentative candidate lists by over 50% on average. An additional 192 unannotated compounds were assigned a predicted chemical class. Availability and implementation All relevant source code is available at https://github.com/McLeanResearchGroup/CCS-filter. Supplementary information Supplementary data are available at Bioinformatics online.

The advent of clinical trials in myotonic dystrophy type 1 (DM1) necessitates the identification of reliable outcome measures to quantify different disease manifestations using minimal number of assessments. In this study, clinical correlations of mean masseter volume (mMV) were explored to evaluate its potential as a marker of muscle involvement in adult-onset DM1 patients. We utilised data from a preceding study, pertaining to 39 DM1 patients and 20 age-matched control participants. In this study participants had undergone MRI of the brain, completed various clinical outcome measures and had CTG repeats measured by small-pool PCR. Manual segmentation of masseter muscles was performed by a single rater to estimate mMV. The masseter muscle was atrophied in DM1 patients when compared to controls (p0.001). Significant correlations were found between mMV and estimated progenitor allele length (p = 0.001), modal allele length (p = 0.003), disease duration (p = 0.009) and and the Muscle Impairment Rating Scale (p = 0.008). After correction for lean body mass, mMV was also inversely correlated with self-reported myotonia (p = 0.014). This study demonstrates that changes in mMV are sensitive in reflecting the underlying disease process. Quantitative MRI methods demonstrate that data concerning both central and peripheral disease could be acquired from MR brain imaging studies in DM1 patients.

Cation ratio of soil structural stability (CROSS) and exchangeable dispersive percentage (EDP) have been recently proposed to replace the traditional sodium absorption ratio (SAR) and exchangeable sodium percentage (ESP) for predicting soil structural stability, in conjunction with the electrolyte concentration. Both CROSS and EDP incorporate the dispersive effects as coefficients transforming K and Mg effects to equivalent Na, and flocculative coefficient transforming Mg effect to equivalent Ca. However, these coefficients are derived from the flocculating power of Na, K, Mg and Ca based on a limited number of soil clays. This study re-examines the flocculating power for a broad range of soil clays by analysing their critical flocculation concentrations (CFCs). Soil clays from 17 contrasting soils were separated and chemically treated into Na, K, Mg and Ca homoionic clays. Within the same cation treatment, there were significant differences among the measured CFC values, which can be related to their different clay mineralogy and co-existing materials in soil clays. The dispersive coefficients of K and Mg, as well as the flocculative coefficient of Mg, were seen to vary substantially in respect to the generalised values used in CROSS and EDP. The absolute errors between the specified CROSS and generalised CROSS as well as the specified EDP and generalised EDP have been calculated for the 95th percentile of possible cation concentrations. In terms of CROSS, the dispersive coefficient a[K] and flocculative coefficient b[Mg] both contribute to the absolute error, with a[K] having a greater influence than b[Mg]. In terms of EDP, the dispersive coefficient a[K] played the dominant role in causing absolute error between the specified EDP and generalised EDP, while the role of dispersive coefficient c[Mg] was not significant. The outcome of this work indicates that the soil-specific coefficients should be used to minimise the possibility of undue soil structural degradation, while the generalised coefficients are only applicable to a small range of outcomes.

Irrigation water containing appreciable amount of magnesium (Mg) is increasingly used in farming. However, studies on the effect of Mg on soil permeability and structural stability are limited and the results are contradicting. In this study, four soils of different dominant clay mineralogy, specifically kaolinite, illite and montmorillonite, were used to investigate the effect of Mg on saturated hydraulic conductivity (Ksat), interaction with organic carbon and soil clay dispersion and to compare to the effect of Ca. The soils were packed in columns and leached with four groups of either Ca-Ca, Ca-Mg, Mg-Mg or Mg-Ca solutions at the successive concentrations of 0.5, 0.25, 0.1, 0.05, 0.025, 0.01, 0.005, 0.001 and 0.0001 M, and finally with deionised water. Ksat was measured and leachates were assessed for dissolved organic carbon (DOC) and dispersion as turbidity. The leached soils were tested for aggregate stability, mechanical dispersion and zeta potential. This study showed that Mg had a disaggregation effect on soil structural stability. As compared to Ca, Ksat on Mg treated cores were lower over a wide range of concentrations, desorption of DOC and turbidity from Mg clay surface was higher, although the dispersion in leachates was insignificant under both Mg and Ca treatments. The effect of Mg treatment was more pronounced on smectic and illitic soils. The decrease in Ksat was related to Mg induced disaggregation, due to intra-crystalline swelling and/or the inter-crystalline swelling in Mg treated soil clays.

Inflammation is associated with depressive symptoms and innate immune mechanisms are likely causal in some cases of major depression. Systemic inflammation also perturbs brain function and microstructure, though how these are related remains unclear. We recruited N = 46 healthy controls, and N = 83 depressed cases stratified by CRP (> 3 mg/L: N = 33; < 3 mg/L: N = 50). All completed clinical assessment, venous blood sampling for C-reactive protein (CRP) assay, and brain magnetic resonance imaging (MRI). Micro-structural MRI parameters including proton density (PD), a measure of tissue water content, were measured at 360 cortical and 16 subcortical regions. Resting-state fMRI time series were correlated to estimate functional connectivity between individual regions, as well as the sum of connectivity (weighted degree) of each region. Multiple tests for regional analysis were controlled by the false discovery rate (FDR = 5%). We found that CRP was significantly associated with PD in precuneus, posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC); and with functional connectivity between pC/pCC, mPFC and hippocampus. Depression was associated with reduced weighted degree of pC/pCC, mPFC, and other nodes of the default mode network (DMN). Thus CRP-related increases in proton density—a plausible marker of extracellular oedema—and changes in functional connectivity were anatomically co-localised with DMN nodes that also demonstrated significantly reduced hubness in depression. We suggest that effects of peripheral inflammation on DMN node micro-structure and connectivity may mediate inflammatory effects on depression.

Peripheral inflammation can cause depressive symptoms – but how? Here, we measured brain MRI functional connectivity and micro-structural parameters, including proton density (PD, a measure of tissue water), at 360 cortical and 16 subcortical brain regions in 46 healthy controls and 83 depressed cases. Blood C-reactive protein (CRP) was positively correlated with PD in key precuneus/posterior cingulate cortex (pC/pCC) and medial prefrontal cortex (mPFC) components of the default mode network (DMN). CRP concentration was associated with increased connectivity within the DMN (nodes pC/pCC, mPFC and hippocampus), but decreased connectivity between DMN and non-DMN nodes. Depressed cases had reduced weighted degree, a metric of hubness, in anatomically co-located DMN regions. Our interpretation is that low-grade peripheral inflammation is associated with increased water (oedema) within a few highly connected but metabolically vulnerable medial cortical nodes, and this “rock in the pond” serves to perturb the functional connectivity of large-scale cortico-subcortical systems associated with depression.

Background: \ud Systemic inflammation is associated with sickness behaviors such as low mood and fatigue. Activity patterns within the insula are suggested to coordinate these behaviors but have not been modeled. We hypothesized that mild systemic inflammation would result in changes in effective connectivity between the viscerosensory and the visceromotor regions of the insula.\ud \ud Methods: \ud We used a double-blind, crossover design to randomize 20 male subjects to receive either a Salmonella typhi vaccine or a placebo saline injection at two separate sessions. All participants underwent a resting-state functional magnetic resonance scan 3 hours after injection. We determined behavioral and inflammatory changes, using the Profile of Mood States questionnaire and interleukin-6 levels. We extracted effective connectivity matrices between bilateral mid/posterior (viscerosensory) and anterior (visceromotor) insular cortices using spectral dynamic causal modeling. We applied parametric empirical Bayes and mediation analysis to determine a vaccination effect on effective connectivity and whether this mediated behavioral changes.\ud \ud Results: \ud The vaccine condition was associated with greater interleukin-6 levels and greater fatigue 3 hours after the injection. Activity within the right mid/posterior insula increased the activity within the bilateral anterior insular regions. This connectivity was augmented by vaccination over a 99% posterior confidence threshold. The right mid/posterior insula-to-left anterior insula connectivity was significantly associated with fatigue and mediated the association between inflammation and increased fatigue scores.\ud \ud Conclusions: \ud These results demonstrate that increased effective connectivity between specific nodes of the insula can model and mediate the association between inflammation and fatigue in males.

Systemic inflammation has been associated with negative mood states and human sickness behaviour. Previous studies have shown an association between systemic inflammation and changes in task-related blood-oxygen-level-dependent activity and functional connectivity within large-scale networks. However, no study has examined the effect of inflammation on the magnitude of blood-oxygen-level-dependent low-frequency fluctuations at rest. We used a double-blind placebo-controlled crossover design to randomise 20 male subjects (aged 20–50 years) to receive either a Salmonella typhi vaccine or a placebo saline injection at two separate sessions. All participants underwent a resting-state functional magnetic resonance scan and a measure of inflammation (interleukin 6) and mood (Profile of Mood States) 3 h after injection. We compared the whole brain amplitude of low-frequency fluctuations between the vaccine and placebo conditions using a repeated measures design. Vaccine condition was associated with greater interleukin 6 levels (p

Land amendment irrigation (LAI) has become an increasingly useful practice in addressing sodic and alkaline coal seam methane gas (CSG) water for irrigation purposes. However, there is a paucity of information pertaining to rapid dilution of soil solution under LAI management. This study investigated the ability of land amendment to buffer soils against structure degradation under sequential irrigation with CSG water (electrical conductivity [EC], 3 dS/cm; sodium adsorption ratio [SAR], 100 mmolc/L; pH 8.4) and rainwater in a highly smectitic black Vertisol (BV) and kaolinitic Oxisol (OX) soil. Stoichiometric quantities of gypsum and sulfur amendments were applied for the LAI process to reduce sodicity and alkalinity to a target of SAR

Using saline and sodic waters for irrigating agricultural lands has increased worldwide, which may cause adverse effects on soil porosity, structural stability and permeability. However, few studies have investigated the effect of clay swelling, dispersion and migration on the reduction of saturated hydraulic conductivity (Ksat) by analysing the total porosity and pore size change through the profile. In this study, two soils with contrasting mineralogy was used and packed at two different bulk densities (1.0 and 1.2 g cm−3). Soil columns were leached with three types of sodium adsorption ratio (SAR) solutions, i.e. good quality water (GQW), SAR 10 and SAR 50 solutions, before distilled water (low ionic strength) was leached through. The results indicated that the application of distilled water decreased Ksat for all soils, particularly in the initially sodic water treated columns. The Ksat of leaching with distilled water in low density columns were generally higher, but showed more degree of reduction than more compacted columns, mainly related to the high initial porosity and macropores that enabled dispersed clay to move through the soil column and out in the leachate. The application of distilled water significantly reduced the proportion of macro and mesopores, whereas increased the proportion of micropores in both soils, particularly for soil columns initially treated high SAR solutions. When the dispersed clay was trapped within the column, the depth of clay accumulation was affected by a combined effect of packing density, soil type and water quality.