Biology subjects

Vik, A.

Publications and source records attributed to Vik, A..

4 recordsLinked to original sources

bioRxiv2024

Alternative Macrophage Activation Requires Granulocyte-Derived Lipids

Lipid metabolism is important for alternative (M2) macrophage activation, but it remains unclear whether it is essential for this process, and the underlying mechanisms have yet to be determined. It is also unclear how the M2 phenotype is induced during the resolution of inflammation and tissue repair. We used large-scale RNA-sequencing and high-throughput lipidomics approaches to identify that during blood coagulation, granulocytes release certain lipids that are loaded onto high-density lipoproteins (HDLs), which then act via scavenger receptors SR-B1 and SR-B3 - to mediate the expression of 26 of 32 M2-associated genes and oxidative phosphorylation (OXPHOS) in macrophages. We found that in the absence of these lipids, interleukin-4 (IL-4) induced only 6 of 32 M2 markers, and this cytokine alone failed to induce OXPHOS. We also found that the HDL-associated C18:0, C18:2, and C20:3 fatty acids (FAs) were the lipids that most potently induced the M1-to-M2 transition. Furthermore, we determined that during IL-4-mediated inflammation, the inhibition of blood coagulation, or platelet and granulocyte depletion, results in a substantial decrease in M2 marker expression. Thus, this study identified that granulocyte-derived FAs mediate the reprogramming of macrophages towards the M2 phenotype, thereby bridging the processes of blood coagulation, inflammation, and repair. HighlightsO_LIActivation of macrophages with IL-4 or IL-13 requires indispensable cofactor C_LIO_LIThe cofactor consists of high-density lipoproteins (HDLs) complexed with lipids C_LIO_LIDuring blood coagulation, granulocytes produce lipids that are loaded on HDLs C_LIO_LIHDL-associated fatty acids were the most potent lipids to induce M2 phenotype C_LI Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=176 SRC="FIGDIR/small/580795v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1a208acorg.highwire.dtl.DTLVardef@e7822dorg.highwire.dtl.DTLVardef@113672eorg.highwire.dtl.DTLVardef@db0eff_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2023

Insect immune resolution with EpOME/DiHOME and its dysregulation by their analogs leading to pathogen hypersensitivity

Epoxyoctadecamonoenoic acids (EpOMEs) are epoxide derivatives of linoleic acid (9,12-octadecadienoic acid: LA). They are metabolized into dihydroxyoctadecamonoenoic acids (DiHOMEs) in mammals. Unlike in mammals where they act as adipokines or lipokines, EpOMEs act as immunosuppressants in insects. However, the functional link between EpOMEs and pro-immune mediators such as PGE2 is not known. In addition, the physiological significance of DiHOMEs is not clear in insects. This study analyzed the physiological role of these C18 oxylipins using a lepidopteran insect pest, Spodoptera exigua. Immune challenge of S. exigua rapidly upregulated the expression of the phospholipase A2 gene to trigger C20 oxylipin biosynthesis, followed by the upregulation of genes encoding EpOME synthase (SE51385) and a soluble epoxide hydrolase (Se-sEH). The sequential gene expression resulted in the upregulations of the corresponding gene products such as PGE2, EpOMEs, and DiHOMEs. Interestingly, only PGE2 injection without the immune challenge significantly upregulated the gene expression of SE51825 and Se-sEH. The elevated levels of EpOMEs acted as immunosuppressants by inhibiting cellular and humoral immune responses induced by the bacterial challenge, in which 12,13-EpOME was more potent than 9,10-EpOME. However, DiHOMEs did not inhibit the cellular immune responses but upregulated the expression of antimicrobial peptides selectively suppressed by EpOMEs. The negative regulation of insect immunity by EpOMEs and their inactive DiHOMEs were further validated by synthetic analogs of the linoleate epoxide and corresponding diol. Furthermore, inhibitors specific to Se-sEH used to prevent EpOME degradation significantly suppressed the immune responses. The data suggest a physiological role of C18 oxylipins in resolving insect immune response. Any immune dysregulation induced by EpOME analogs or sEH inhibitors significantly enhanced insect susceptibility to the entomopathogen, Bacillus thuringiensis. Author summaryUpon immune challenge, recognition signal triggers insect immunity to remove the pathogens by cellular and humoral responses. Various immune mediators propagate the immune signals to nearby tissues, in which polyunsaturated fatty acid (PUFA) derivatives play crucial roles. However, little was known on how the insects terminate the activated immune responses after pathogen neutralization. Interestingly, C20 PUFA was detected at the early infection stage and later C18 PUFAs were induced in a lepidopteran insect, Spodoptera exigua. This study showed the role of epoxyoctadecamonoenoic acids (EpOMEs) in the immune resolution at the late infection stage to quench the excessive and unnecessary immune responses. In contrast, dihydroxy-octadecamonoenoates (DiHOMEs) were the hydrolyzed and inactive forms of EpOMEs. The hydrolysis is catalyzed by soluble epoxide hydrolase (sEH). Inhibitors specific to sEH mimicked the immunosuppression induced by EpOMEs. Furthermore, the inhibitor treatments significantly enhanced the bacterial virulence of Bacillus thuringiensis against S. exigua. This study proposes a negative control of the immune responses using EpOME/DiHOME in insects.

immunology↗

bioRxiv2019

Longitudinal stability of the brain functional connectome is associated with episodic memory performance in aging

The brain functional connectome forms a relatively stable and idiosyncratic backbone that can be used for identification or \"fingerprinting\" of individuals with a high level of accuracy. While previous cross-sectional evidence has demonstrated increased stability and distinctiveness of the brain connectome during the course of childhood and adolescence, less is known regarding the longitudinal stability in middle and old age. Here we collected structural and resting state functional MRI data at two time-points separated by 2-3 years in 75 middle-aged and older adults (age 49-80, SD = {+/-} 6.91 years) which allowed us to assess the long-term stability of the functional connectome. We show that the connectome backbone generally remains stable over a 2-3 year time frame in middle- and old age. Independent of age, cortical volume was associated with the connectome stability of several canonical resting-state networks, suggesting that the connectome backbone relates to the structural integrity of the cortex. Moreover, individual longitudinal stability of subcortical and default mode networks were associated with differences in cross-sectional and longitudinal measures of episodic memory performance, supporting the functional relevance. The findings encourage the use of connectome stability analyses for understanding individual differences in cognitive aging. Furthermore, the observation that age-related changes in episodic memory performance relates to the stability of subcortical and default mode networks, provides new longitudinal evidence for the importance of these networks in maintaining mnemonic processing in old age.

neuroscience↗

bioRxiv2018

Lateral ventricle volume trajectories predict response inhibition in older age - a longitudinal brain imaging and machine learning approach

ObjectiveIn a three-wave ~6 yrs longitudinal study we investigated if expansion of lateral ventricle (LV) volumes (regarded as a proxy for brain parenchyma loss) predicts performance on a test of response inhibition.\n\nParticipants and MethodsAnatomical trajectories of left (LH) and right (RH) lateral ventricle volumes across the three study-waves were quantified using the Longitudinal Stream in Freesurfer 5.3 and modelled using a linear mixed-effects (LME) algorithm. All participants (N = 74, mean age 60.7 yrs at inclusion, 48 females) performed the Color-Word Interference Test (CWIT). Response time on the third condition was used as a measure of response inhibition (RI) and divided into three classes (fast, medium and slow). The Extreme Gradient Boosting (XGBoost) algorithm was used for calculating the relative importance of selected LV volume features from the LME model in predicting RI class. Finally, the two most important extracted features were fed into a 10-fold cross-validation framework, estimating the accuracy, precision and recall of the RI class prediction.\n\nResultsFour LME based features were selected to characterize LV volume trajectories: steepness of LV volume change and the LV volume at the time of inclusion, each from the right and left hemisphere. The XGBoost procedure selected the steepness measure from the right and the volume at inclusion from the left hemisphere as the two most important features to predict RI performance. The 10-fold cross validation procedure showed a recall, precision and accuracy score (.40 - .50) that were clearly above chance level.\n\nConclusionMeasures of the LV volume trajectories gave a fairly good prediction of response inhibition performance, confirming the role of LV volume as a biomarker of cognitive function in older adults. Future studies should investigate the value of the lateral ventricle volume trajectories as predictors of cognitive preservation or decline into older age.

neuroscience↗