Quantitative identification of functional connectivity disturbances in neuropsychiatric lupus based on resting-state fMRI: a robust machine learning approach

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an autoimmune entity comprised of heterogenous syndromes affecting both the peripheral and central nervous system. Research on the pathophysiological substrate of NPSLE manifestations, including functional neuroimaging studies, is extremely limited. The present study examined person-specific patterns of whole-brain functional connectivity in NPSLE patients (n = 44) and age-matched healthy control participants (n = 39). Static functional connectivity graphs were calculated comprised of connection strengths between 90 brain regions. These connections were subsequently filtered through rigorous surrogate analysis, a technique borrowed from physics, novel to neuroimaging. Next, global as well as nodal network metrics were estimated for each individual functional brain network and were input to a robust machine learning algorithm consisting of a random forest feature selection and nested cross-validation strategy. The proposed pipeline is data-driven in its entirety, and several tests were performed in order to ensure model robustness. The best-fitting model utilizing nodal graph metrics for 11 brain regions was associated with 73.5% accuracy (74.5% sensitivity and 73% specificity) in discriminating NPSLE from healthy individuals with adequate statistical power. Closer inspection of graph metric values suggested an increased role within the functional brain network in NSPLE (indicated by higher nodal degree, local efficiency, betweenness centrality, or eigenvalue efficiency) as compared to healthy controls for seven brain regions and a reduced role for four areas. These findings corroborate earlier work regarding hemodynamic disturbances in these brain regions in NPSLE. The validity of the results is further supported by significant associations of certain selected graph metrics with accumulated organ damage incurred by lupus, with visuomotor performance and mental flexibility scores obtained independently from NPSLE patients. View Full-Text Keywords: neuropsychiatric systemic lupus erythematosus; rs-fMRI; graph theory; functional connectivity; surrogate data; machine learning; visuomotor ability; mental flexibilit

Management options influence seasonal CO2 soil emissions in Mediterranean olive ecosystems

Field trials were conducted at traditional Mediterranean olive agro-ecosystems grown at two locations (Italy –IT, Greece –GR). Groves were managed for many years using sustainable (S, cover crops, compost application, mulching of pruning biomass) or conventional (C) practices (e.g., soil tillage, burning of pruning residuals). The IT grove was rainfed (RAIN) while the GR was irrigated (IRR). This study examined the seasonal variation of soil CO2 emission (Rs) to explore the effect of the management options (C, S) on Rs at both sites. The second aim was to test the hypothesis that the seasonal Rs is differentially modulated by soil temperature and moisture, namely that (i) soil moisture limits Rs when it is below the lower limit of the readily available water (RAWLLim) and (ii) soil temperature above a threshold (max_T) reduces Rs even if soil moisture is non limiting. On the whole-season basis, the mean Rs rate at the rainfed site was 2.17 ± 0.06 (SE) at CRAIN and 2.32 ± 0.06 μmol CO2 m−2 s–1 at SRAIN plot, while at the irrigated site Rs was about 3.64 ± 0.11 (CIRR) and 4.05 ± 0.15 μmol CO2 m−2 s–1 (SIRR). The seasonal oscillation of Rs was consistent across locations and partitionable in three periods according to DOY (Day of Year) interval: Phase I (DOY 20–103 –GR; 20–118 -IT), Phase II (DOY 141÷257, GR; 142–257, IT) and Phase III (DOY 291–357, GR; 286–350, -IT). Pooling all the Rs data across sites and managements, max_T was ∼ 20 °C discriminating a differential response of Rs when soil moisture was < or > RAWLLim. These differential modulations exerted by temperature and moisture were integrated into a conditional model developed with a repeated random subsampling cross-validation procedure to effectively (R2 = 0.84) predict Rs. This paper mechanistically describes the interaction of the environment (soil moisture and temperature) and the management options (S, C) under various moisture conditions on Rs and would support carbon flux accounting procedures (e.g., regulating ecosystem services) tailored to the estimation of sink/source capability of traditional olive agro-ecosystem within environmental-friendly agricultural domains

Multitrophic Interaction in the Rhizosphere of Maize: Root Feeding of Western Corn Rootworm Larvae Alters the Microbial Community Composition

BACKGROUND: Larvae of the Western Corn Rootworm (WCR) feeding on maize roots cause heavy economical losses in the US and in Europe. New or adapted pest management strategies urgently require a better understanding of the multitrophic interaction in the rhizosphere. This study aimed to investigate the effect of WCR root feeding on the microbial communities colonizing the maize rhizosphere. METHODOLOGY/PRINCIPAL FINDINGS: In a greenhouse experiment, maize lines KWS13, KWS14, KWS15 and MON88017 were grown in three different soil types in presence and in absence of WCR larvae. Bacterial and fungal community structures were analyzed by denaturing gradient gel electrophoresis (DGGE) of the 16S rRNA gene and ITS fragments, PCR amplified from the total rhizosphere community DNA. DGGE bands with increased intensity were excised from the gel, cloned and sequenced in order to identify specific bacteria responding to WCR larval feeding. DGGE fingerprints showed that the soil type and the maize line influenced the fungal and bacterial communities inhabiting the maize rhizosphere. WCR larval feeding affected the rhiyosphere microbial populations in a soil type and maize line dependent manner. DGGE band sequencing revealed an increased abundance of Acinetobacter calcoaceticus in the rhizosphere of several maize lines in all soil types upon WCR larval feeding. CONCLUSION/SIGNIFICANCE: The effects of both rhizosphere and WCR larval feeding seemed to be stronger on bacterial communities than on fungi. Bacterial and fungal community shifts in response to larval feeding were most likely due to changes of root exudation patterns. The increased abundance of A. calcoaceticus suggested that phenolic compounds were released upon WCR wounding

Enhanced Botrytis cinerea resistance of Arabidopsis plants grown in compost may be explained by increased expression of defense-related genes, as revealed by microarray analysis

Composts are the products obtained after the aerobic degradation of different types of organic matter waste and can be used as substrates or substrate/soil amendments for plant cultivation. There is a small but increasing number of reports that suggest that foliar diseases may be reduced when using compost, rather than standard substrates, as growing medium. The purpose of this study was to examine the gene expression alteration produced by the compost to gain knowledge of the mechanisms involved in compost-induced systemic resistance. A compost from olive marc and olive tree leaves was able to induce resistance against Botrytis cinerea in Arabidopsis, unlike the standard substrate, perlite. Microarray analyses revealed that 178 genes were differently expressed, with a fold change cut-off of 1, of which 155 were up-regulated and 23 were down-regulated in compost-grown, as against perlite-grown plants. A functional enrichment study of up-regulated genes revealed that 38 Gene Ontology terms were significantly enriched. Response to stress, biotic stimulus, other organism, bacterium, fungus, chemical and abiotic stimulus, SA and ABA stimulus, oxidative stress, water, temperature and cold were significantly enriched, as were immune and defense responses, systemic acquired resistance, secondary metabolic process and oxireductase activity. Interestingly, PR1 expression, which was equally enhanced by growing the plants in compost and by B. cinerea inoculation, was further boosted in compost-grown pathogen-inoculated plants. Compost triggered a plant response that shares similarities with both systemic acquired resistance and ABA-dependent/independent abiotic stress responses

Regional cerebral perfusion correlates with anxiety in neuropsychiatric SLE: evidence for a mechanism distinct from depression

The study examined the hypothesis that hypoperfusion in brain areas known to be involved in emotional disturbances in primary psychiatric disorders is also linked to emotional difficulties in systemic lupus erythematosus (SLE) and that these are not secondary to the physical and social burden incurred by the disease. Nineteen SLE patients without overt neuropsychiatric manifestations (non-NPSLE), 31 NPSLE patients, and 23 healthy controls were examined. Dynamic susceptibility contrast MRI was used and cerebral blood flow and cerebral blood volume values were estimated in six manually selected regions of interest of brain regions suspected to play a role in anxiety and depression (dorsolateral prefrontal cortex, ventromedial prefrontal cortex, anterior cingulate cortex, hippocampi, caudate nuclei and putamen). NPSLE patients reported high rates of anxiety and depression symptomatology. Significantly reduced cerebral blood flow and cerebral blood volume values were detected in the NPSLE group compared to healthy controls in the dorsolateral prefrontal cortex and ventromedial prefrontal cortex, bilaterally. Within the NPSLE group, anxiety symptomatology was significantly associated with lower perfusion in frontostriatal regions and in the right anterior cingulate gyrus. Importantly, the latter associations appeared to be specific to anxiety symptoms, as they persisted after controlling for depression symptomatology and independent of the presence of visible lesions on conventional MRI. In conclusion, hypoperfusion in specific limbic and frontostriatal regions is associated with more severe anxiety symptoms in the context of widespread haemodynamic disturbances in NPSLE. © The Author(s) 2019

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: A resting-state f(unctional) MRI study

To examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE). Resting-state fMRI (rs-fMRI) was performed and anxiety and/or depression symptoms were assessed in 32 patients with NPSLE and 18 healthy controls (HC). Whole-brain time-shift analysis (TSA) maps, voxel-wise global connectivity (assessed through intrinsic connectivity contrast (ICC)) and within-network connectivity were estimated and submitted to one-sample t-tests. Subgroup differences (high vs low anxiety and high vs low depression symptoms) were assessed using independent-samples t-tests. In the total group, associations between anxiety (controlling for depression) or depression symptoms (controlling for anxiety) and regional TSA or ICC metrics were also assessed. Elevated anxiety symptoms in patients with NPSLE were distinctly associated with relatively faster haemodynamic response (haemodynamic lead) in the right amygdala, relatively lower intrinsic connectivity of orbital dlPFC, and relatively lower bidirectional connectivity between dlPFC and vmPFC combined with relatively higher bidirectional connectivity between ACC and amygdala. Elevated depression symptoms in patients with NPSLE were distinctly associated with haemodynamic lead in vmPFC regions in both hemispheres (lateral and medial orbitofrontal cortex) combined with relatively lower intrinsic connectivity in the right medial orbitofrontal cortex. These measures failed to account for self-rated, milder depression symptoms in the HC group. By using rs-fMRI, altered perfusion dynamics and functional connectivity was found in limbic and prefrontal brain regions in patients with NPSLE with severe anxiety and depression symptoms. Although these changes could not be directly attributed to NPSLE pathology, results offer new insights on the pathophysiological substrate of psychoemotional symptomatology in patients with lupus, which may assist its clinical diagnosis and treatment. © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ

Neuropsychiatric lupus or not? Cerebral hypoperfusion by perfusion-weighted MRI in normal-appearing white matter in primary neuropsychiatric lupus erythematosus

Objectives Cerebral perfusion abnormalities have been reported in systemic lupus erythematosus (SLE) but their value in distinguishing lupus from non-lupus-related neuropsychiatric events remains elusive. We examined whether dynamic susceptibility contrast-enhanced perfusion MrI (dSC-MrI), a minimally invasive and widely available method of cerebral perfusion assessment, may assist neuropsychiatric SLE (npSLE) diagnosis. Methods In total, 76patients with SLE (37 primary npSLE, 16 secondary npSLE, 23 non-npSLE) and 31 healthy controls underwent conventional MrI (cMrI) and dSC-MrI. Attribution of npSLE to lupus or not was based on multidisciplinary assessment including cMrI results and response to treatment. Cerebral blood volume and flow were estimated in 18 normal-appearing white and deep grey matter areas. results the most common manifestations were mood disorder, cognitive disorder and headache. patients with primary npSLE had lower cerebral blood flow and volume in several normal-appearing white matter areas compared with controls (p<0.0001) and lower cerebral blood flow in the semioval centre bilaterally, compared with non-npSLE and patients with secondary npSLE (p<0.001). A cut-off for cerebral blood flow of 0.77 in the left semioval centre discriminated primary npSLE from non-npSLE/secondary npSLE with 80% sensitivity and 67%–69% specificity. Blood flow values in the left semioval centre showed substantially higher sensitivity than cMrI (81% vs 19%–24%) for diagnosing primary npSLE with the combination of the two modalities yielding 94%–100% specificity in discriminating primary from secondary npSLE. conclusion primary npSLE is characterised by significant hypoperfusion in cerebral white matter that appears normal on cMrI. the combination of dSC-MrI-measured blood flow in the brain semioval centre with conventional MrI may improve npSLE diagnosis. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. no commercial use is permitted unless otherwise expressly granted

The Effect of Low Temperature on Physiological, Biochemical and Flowering Functions of Olive Tree in Relation to Genotype

Olive tree growth and reproduction are severely affected by temperature extremes, compromising fruit yield. In that aspect, the olive varieties “Koroneiki” and “Mastoidis” were employed in a mild cold stress experiment, imitating night frost incidents to assess their biochemical, physiological and reproductive functions in relation to genotype. The physiological performance of the stressed plants was not significantly altered, suggesting that both cultivars were well adapted to mild cold night stress. The biochemical response of the plants, regarding antioxidant enzymes, H2O2 and TBARS accumulation, confirmed that both cultivars could cope with the stress applied. The mRNA levels of the PPO gene, which participates in hydroxytyrosol biosynthesis and plant defense, were elevated after 24-h stress at 0 °C, in both cultivars with “Mastoidis” plants exhibiting higher levels for a longer period. Three more genes involved in hydroxytyrosol biosynthesis upregulated their expression levels as a response to cold stress. The numerous plant phenology aspects measured reinforced the conclusion that both cultivars responded to the stress applied. The results of the present study may contribute to better understanding olive tree adaptive responses to low temperature events, an abiotic stress condition that is often present in an open plantation, thus assisting farmers on breeding and cultivar selection