Altered Function Research Articles

Insights from serial cardiovascular magnetic resonance imaging show early progress in diastolic dysfunction relates to impaired right ventricular deformation

Latent pulmonary vascular disease is a distinct feature already in the early pathophysiology of masked heart failure with preserved ejection fraction (HFpEF) and associated with reduced right ventricular (RV) functional reserve. We hypothesized that serial real-time cardiovascular magnetic resonance (CMR) imaging at rest and during exercise-stress may detect early progress in pathophysiological alterations in HFpEF. Patients presenting with exertional dyspnoea and signs of diastolic dysfunction (E/e’>8, left ventricular (LV) ejection fraction > 50%) were prospectively enrolled in the HFpEF Stress Trial (NCT03260621). Rest and exercise-stress echocardiography, CMR and right heart catheterisation were performed at baseline. Pulmonary capillary wedge pressure (PCWP) was used for classification of HFpEF (≥ 15/25mmHg at rest/during exercise-stress) and non-cardiac dyspnoea (NCD). Repeat rest and exercise-stress CMR was performed in median 2.94 years after recruitment during which timeframe some HFpEF patients had undergone interatrial shunt device (IASD) implantation. Cardiovascular events were assessed after 4 years.Serial CMR scans were available for NCD n = 10, HFpEF n = 10 and HFpEF with IASD implantation following baseline diagnosis n = 6. RV long axis strain at rest and during exercise-stress decreased in HFpEF (p = 0.007 for both) but neither in NCD nor HFpEF with IASD. In contrast, in NCD, an improvement in LA LAS during exercise-stress (p = 0.028) was noted. There were no functional alterations in HFpEF patients who had undergone IASD implantation. RV functional deterioration may be a pathophysiological feature during early-stage disease progress in HFpEF. In this observational study RV functional deterioration was detected in HFpEF patients only but not patients with NCD and patients with HFpEF that were treated with IASD placement. These findings should next be explored in adequately powered future research trials. Clinicaltrials.gov: NCT03260621 (First posted date 24/08/2017).

The Role of Epigenetic Mechanisms in the Development of PM2.5-Induced Cognitive Impairment

PM2.5 is fine particulate matter with a diameter of less than 2.5 μm. Recent evidence has shown that exposure to PM2.5 markedly elevates the risk of neurodegenerative diseases, neurodevelopmental disorders, and cardiovascular diseases, which may culminate in cognitive impairment. Nevertheless, the precise mechanisms through which PM2.5 affects cognitive function are unclear. Recent studies have demonstrated that PM2.5-induced epigenetic alterations are associated with the development of cognitive impairment. Epigenetic alterations include modifications to DNA methylation, histone modifications, and non-coding RNAs. The underlying mechanisms of epigenetic alterations are related to inflammation, synaptic dysfunction, cardiovascular factors, and alterations in neuronal structure and function. This review reports the latest findings on the relationship between PM2.5-induced epigenetic alterations and the development of cognitive disorders, offering novel insights into the cognitive effects of air pollution.

Association between retinal morphological characteristics and visual function in myopic traction maculopathy.

To quantify retinal morphological characteristics in patients with myopic traction maculopathy (MTM), including myopic foveoschisis (MF), using optical coherence tomography angiography (OCTA) and investigate the correlation of MTM with visual function. This cross-sectional study included 19 eyes with myopic foveoschisis (MF) and foveal detachment (FD), 37 eyes with MF without FD, and 24 myopic eyes as control. OCTA was used to assess macular vessel density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), foveal avascular zone (FAZ) area, FAZ perimeter, acircularity index, retinal thickness, and retinal volume. Microperimetry was performed to evaluate macular sensitivity (MS) covering the central 20°, 10°, 2° field centered at fovea. Correlations between macular microcirculation parameters, best-corrected visual acuity (BCVA), and MS were determined. Compared to myopic controls, decreased macular parafoveal SCP VD, DCP VD, and the area VD in a 300 µm wide annulus surrounding the FAZ (FD-300), were found in the group of MF patients with FD, with (p = 0.007, 0.002, 0.005) respectively, and in the group of MF patients without FD, with (p = 0.01, 0.049, 0.009), respectively. In the MF without FD group, parafoveal SCP VD significantly correlated with BCVA, 2°MS, 10°MS, and 20°MS (p = 0.018, 0.002, 0.001, 0.029), FD-300 area density, retinal thickness, and retinal volume was significantly correlated with BCVA (p = 0.024, 0.015, 0.045). In the MF with FD group, DCP VD was significantly associated with 10° and 20° MS (p = 0.048, 0.014), as were retinal thickness and volume (all p < 0.05); however, FD-300 area density correlated significantly with BCVA (p = 0.014). Macular perfusion is closely associated with functional alterations in MTM. Macular VD could serve as a valuable biomarker for monitoring MTM progression and optimizing medical and surgical decisions.

Cerebellum abnormalities in vascular mild cognitive impairment with depression symptom patients: A multimodal magnetic resonance imaging study.

Subcortical vascular mild cognitive impairment (svMCI) frequently occurs alongside depression symptoms, significantly affecting patients' quality of life. While cognitive decline and depression symptoms are linked to cerebellar changes, the specific relationship between these changes and cognitive status in svMCI patients with depression symptoms remains unclear. This study aimed to investigates the gray matter volume and functional alterations in the cerebellum of svMCI patients, with and without depression symptoms, and their correlation with cognitive and depressive symptoms. We enrolled 16 svMCI patients with depression symptoms (svMCI+D), 15 without (svMCI-D), and 12 normal controls (NC). Multimodal MRI scans were conducted, assessing gray matter volume and resting-state functional connectivity (RSFC) in the cerebellum. Correlations between RSFC and clinical scores from the Montreal Cognitive Assessment (MoCA) and Hamilton Depression Scale (HAMD) were analyzed. Structural analysis indicated gray matter atrophy in left cerebellar lobules I_IV and VI (Cere6.L) in svMCI patients. svMCI+D patients showed reduced RSFC between Cere6.L and left cerebellar region IX and the left superior frontal gyrus (SFGdor.L). Both svMCI+D and svMCI-D groups showed increased RSFC between Cere6.L and the right caudate nucleus. RSFC between Cere6.L and SFGdor.L correlated negatively with HAMD scores in svMCI+D and positively with MoCA scores in svMCI-D. RSFC between Cere6.L and the right caudate nucleus also correlated positively with MoCA in the svMCI-D. Cerebellar abnormalities, including the gray matter atrophy and RSFC changes, are associated with svMCI, particularly when depression symptoms are present. These results suggest potential diagnostic and therapeutic implications for svMCI and emphasize the need for further research on the cerebellum's role in cognitive and emotional disorders.

Anxiety-like behavior and altered hippocampal activity in a transgenic mouse model of Fabry disease.

Fabry disease (FD) patients are known to be at high risk of developing neuropsychiatric symptoms such as anxiety, depression and cognitive deficits. Despite this, they are underdiagnosed and inadequately treated. It is unknown whether these symptoms arise from pathological glycosphingolipid deposits or from cerebrovascular abnormalities affecting neuronal functions in the central nervous system. We therefore aimed to fill this knowledge gap by exploring a transgenic FD mouse model with a combination of behavior, transcriptomic, functional and morphological assessments, with a particular focus on the hippocampus. Male FD mice exhibited increased anxiety-like behavior in the open field test, accompanied by a reduced exploratory drive in the Barnes maze, which could be related to the increased deposition of globotriaosylceramide (Gb3) identified in the dentate gyrus (DG). Hippocampus single-cell sequencing further revealed that Gb3 accumulation was associated with differential gene expression in neuronal and non-neuronal cell populations with granule, excitatory and interneurons, as well as microglia and endothelial cells as the main clusters with the most dysregulated genes. Particularly FD hippocampal neurons showed decreased electrical baseline activity in the DG and increased activity in the CA3 region of acutely dissected hippocampal slices. Our study highlights transcriptional and functional alterations in non-neuronal and neuronal cell clusters in the hippocampus of FD mice, which are suggested to be causally related to anxiety-like behavior developing as a consequence of FD pathology in mouse models of the disease and in patients.

Macrophage Polarisation in the Tumour Microenvironment: Recent Research Advances and Therapeutic Potential of Different Macrophage Reprogramming.

Macrophages are a critical component of the innate immune system, derived from monocytes, with significant roles in anti-inflammatory and anti-tumour activities. In the tumour microenvironment, however, macrophages are often reprogrammed into tumour-associated macrophages (TAMs), which promote tumour growth, metastasis, and therapeutic resistance. To review recent advancements in the understanding of macrophage polarisation and reprogramming, highlighting their role in tumour progression and potential as therapeutic targets. This is a review article synthesising findings from recent studies on macrophage polarisation and reprogramming in tumour biology. Not applicable (review of existing literature). Key studies were identified and summarised to explore mechanisms of macrophage polarisation and reprogramming, focusing on M1/M2 polarisation, metabolic and epigenetic changes, and pathway regulation. Macrophage reprogramming in the tumour microenvironment involves complex mechanisms, including phenotypic and functional alterations. These processes are influenced by M1/M2 polarisation, metabolic and epigenetic reprogramming, and various signalling pathways. TAMs play a pivotal role in tumour progression, metastasis, and therapy resistance, making them prime targets for combination therapies. Understanding the mechanisms underlying macrophage polarisation and reprogramming offers promising avenues for developing therapies to counteract tumour progression. Future research should focus on translating these insights into clinical applications for effective cancer treatment.

Reproductive outcomes in female mice offspring due to maternal metformin treatment.

Metformin has shown beneficial effects on reproduction in women. However, its use during pregnancy remains controversial, as metformin can cross the placenta. Most studies have focused on the metabolic impact on the offspring of treated mothers, with limited information regarding its reproductive effects. The aim of this study was to evaluate potential alterations in ovarian function and fertility in female offspring of mothers treated with metformin during pregnancy and lactation. C57BL/6 female mice were treated with metformin four weeks before mating, and the treatment was maintained during gestation and lactation. Seven weeks after weaning, metabolic parameters as well as ovarian and reproductive function of the offspring were analyzed. The offspring of treated mothers were lighter at birth and, in adulthood, they had more gonadal adipose tissue with no alterations in body weight. No changes in glucose metabolism were observed. Their follicular development was modified, with more early antral and atretic follicles and less primary and late antral follicles. Anti-Müllerian hormone expression and ovarian angiogenesis were increased. The estrous cycle, hormonal production and fertility were not affected by metformin exposure, however, the F2 generation showed higher body weight at birth. Metformin can induce fetal programming in animals exposed to it during development, impacting metabolism and ovarian functionality in adulthood. Under physiological conditions, these alterations do not result in reduced fertility or endocrine disruptions. Our data warrant studies in women to make informed decisions regarding metformin administration during critical developmental periods in clinical settings.

Alterations in LDL and HDL after an ischemic stroke associated with carotid atherosclerosis are reversed after 1year.

Approximately, 20% of ischemic strokes are attributed to the presence of atherosclerosis. Lipoproteins play a crucial role in the development of atherosclerosis, with LDL promoting atherogenesis and HDL inhibiting it. Therefore, both their concentrations and their biological properties are decisive factors in atherosclerotic processes. In this study, we examined the qualitative properties of lipoproteins in ischemic stroke patients with carotid atherosclerosis. Lipoproteins were isolated from the blood of healthy controls (n=27) and patients with carotid atherosclerosis (n=64) at 7days and 1year postischemic stroke. Compared to controls, patients' LDL 7days poststroke showed increased levels of apoC-III, triacylglycerol, and ceramide, along with decreased cholesterol and phospholipid content. LDL from patients induced more inflammation in macrophages than did LDL from controls. HDL isolated from patients 7days after stroke showed alterations in the apolipoprotein cargo, with reduced levels of apoA-I and increased levels of apoA-II, and apoC-III compared to controls. Patients' HDL also showed a higher electronegative charge than that of controls and partially lost its ability to counteract the modification of LDL and the inflammatory effects of modified LDL. One year after stroke onset, the composition of patients' LDL and HDL resembled those of the controls. In parallel, LDL and HDL gained positive charge, LDL became less prone to oxidation and aggregation, and HDL regained protective properties. In conclusion, LDL and HDL in ischemic stroke patients with carotid atherosclerosis exhibited alterations in composition and function, which were partially reversed 1year after stroke.

Fluconazole induces cardiovascular toxicity in zebrafish by promoting oxidative stress, apoptosis, and disruption of key developmental genes.

This study systematically evaluated the toxic effects of fluconazole on the cardiovascular development of zebrafish. Zebrafish embryos were treated with different concentrations of fluconazole (200, 400, and 800μg/ml) to observe its impact on heart development, reactive oxygen species (ROS) generation, apoptosis, and hemoglobin production. The results showed that as the concentration of fluconazole increased, significant changes in zebrafish heart structure were observed, along with a notable reduction in heart rate. Pericardial edema and cardiac morphological abnormalities were particularly prominent in the high-dose group. In addition, fluconazole treatment significantly increased ROS levels and induced apoptosis in cardiac cells. Enzyme-linked immunosorbent assay (ELISA) results showed that fluconazole treatment significantly increased the malondialdehyde (MDA) content and reduced superoxide dismutase (SOD) and catalase (CAT) activity, suggesting that oxidative stress and cell death may play a key role in its cardiotoxicity. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis revealed that fluconazole treatment significantly affected the expression of several key genes related to heart development and function, particularly cardiac myosin light chain 2 (cmlc2), ventricular myosin heavy chain (vmhc), and myosin heavy chain 6 (myh6), whose expression changes were closely associated with alterations in heart morphology and function. Transcriptomic analysis showed that several signaling pathways related to cardiac development, apoptosis, and metabolism were affected. In summary, this study reveals the multifaceted cardiotoxic mechanisms of fluconazole in zebrafish and provides new insights into drug safety assessment.

Altered local spontaneous activity and functional connectivity density in major depressive disorder patients with anhedonia.

The purpose of this study was to investigate the alterations of intrinsic brain function in major depressive disorder (MDD) patients with and without anhedonia based on whole-brain level by using two novel measures, four-dimensional spatial-temporal consistency of local neural activity (FOCA) and local functional connectivity density (lFCD). A total of 26 MDD patients with anhedonia (MDD-WA), 29 MDD patients without anhedonia (MDD-WoA), and 30 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning and intrinsic brain function was explored by FOCA and lFCD. A two-sample t-test was conducted to explore FOCA and lFCD differences between MDD patients and HCs, then analysis of covariance (ANCOVA) and post hoc tests were performed to obtain brain regions with significant differences among three groups. Finally, the diagnostic performance of FOCA and lFCD values with significant inter-group difference was evaluated using receiver operating characteristic (ROC) curves. Compared to HCs, MDD patients showed decreased FOCA in the right cuneus (CUN) and left postcentral gyrus (PoCG), as well as diminished lFCD in the right CUN and left calcarine fissure and surrounding cortex (CAL). Interestingly, the MDD-WA group was more likely to exhibit decreased FOCA in the left PoCG and reduced lFCD in the left CAL after consideration for the effect of anhedonia in MDD patients. The MDD-WA group further showed increased FOCA in the bilateral caudate (CAU) and right ventral anterior nucleus (VA) when comparing to HCs. Additionally, as compared with MDD-WoA group, the MDD-WA group presented decreased FOCA in the right middle occipital gyrus (MOG), which was also negatively associated with the severity of anhedonia in MDD patients. Finally, FOCA values of the right MOG exhibited excellent discriminant validity in differentiating MDD-WA from MDD-WoA, and the other individual or combined indices of FOCA or lFCD values in the aforementioned distinct brain regions presented significant utility in distinguishing between MDD or MDD-WA and HCs. The present findings suggest that aberrant intrinsic brain function in the left CAL, left PoCG, bilateral CAU, right VA, and, especially the right MOG may be associated with anhedonia in patients with MDD. Altered FOCA in the right MOG may have the potential to be a diagnostic neuroimaging biomarker for MDD patients with anhedonia.

Ligand-receptor interactions: A key to understanding microglia and astrocyte roles in epilepsy.

Epilepsy continues to pose significant social and economic challenges on a global scale. Existing therapeutic approaches predominantly revolve around neurocentric mechanisms, and fail to control seizures in approximately one-third of patients. This underscores the pressing need for novel and complementary treatment approaches to address this gap. An increasing body of literature points to a role for glial cells, including microglia and astrocytes, in the pathogenesis of epilepsy. Notably, microglial cells, which serve as pivotal inflammatory mediators within the epileptic brain, have received increasing attention over recent years. These immune cells react to epileptogenic insults, regulate neuronal processes, and play diverse roles during the process of epilepsy development. Additionally, astrocytes, another integral non-neuronal brain cells, have garnered increasing recognition for their dynamic contributions to the pathophysiology of epilepsy. Their complex interactions with neurons and other glial cells involve modulating synaptic activity and neuronal excitability, thereby influencing the aberrant networks formed during epileptogenesis. This review explores the alterations in microglial and astrocytic function and their mechanisms of communication following an epileptogenic insult, examining their contribution to epilepsy development. By comprehensively studying these mechanisms, potential avenues could emerge for refining therapeutic strategies and ameliorating the impact of this complex neurological disease.

Abstract TP336: Neuropathological changes in the chronic phase of ischemic stroke are marked by persistent alteration of microglial function and neurodegenerative phenotypes

Improvements in acute stroke treatment, including EVT and critical care management, have increased survival rates post-stroke. However, many stroke survivors have significant post-stroke disability and cognitive impairment. Despite this, the chronic progression and long-term sequelae of ischemic stroke pathology remains understudied. Methods: We examined the chronicity of neurobehavioral recovery and progressive neuropathology in young male (3 month) and middle-aged male and female (14 month) C57Bl/6 mice at 3 and 6 months after a 60-minute transient middle cerebral artery occlusion (tMCAO) or sham surgery ( n = 10-20/group ). Behavioral testing included NORT, fear conditioning (FC), and tail suspension. Immunohistochemistry (IHC) was performed on mouse brains, as well as post-mortem human brain samples from patients with a chronic infarct ( n = 6/group ), to assess demyelination (MBP), neuronal apoptosis (TUNEL/NeuN), and amyloid burden (Aβ-42). Flow cytometry was performed on the ipsilateral mouse brain hemisphere. RNA isolated from the ipsilateral hemisphere was sent for gene profiling. Results: In both young and middle-aged mice, depressive-like behavior persisted for 6 months post-stroke (PS) (p= &lt;0.0001), while cognitive function progressively worsened from 3 to 6 months, as seen by a reduction in the NORT (p=.0063) and FC (p=.0084). MRI imaging and IHC revealed cerebral atrophy, significant demyelination (mouse, p=.0361; human, p =.0001), and increased microglial density (p=.0059) in the hippocampus of both human and mice. TUNEL/NeuN staining showed ongoing neuronal degeneration in the human hippocampus, distal to the chronic infarct. Human chronic stroke hippocampus had increased amyloid burden compared to age-matched controls (p=.0677). Cytometric anyalses revealed disease-associated microglial (DAM) phenotypes were marked by increased senescence, cytokine production, and an altered redox state. Transcriptomic data showed significant chronic upregulation of DAM genes. Conclusion: Our findings demonstrate that ischemic stroke accelerates inflamm-aging and premature senescence within the chronic infarct microenvironment. Cellular senescence and chronic disease signatures may contribute to progressive cognitive impairment post-stroke. Identification of secondary injury processes, and late pathological events post-stroke, allude to a neurodegenerative etiology and may offer viable targets for delayed treatment to prevent further neurological decline.

Time-Frequency functional connectivity alterations in Alzheimer's disease and frontotemporal dementia: An EEG analysis using machine learning.

Alzheimer's disease (AD) and frontotemporal dementia (FTD) are prevalent neurodegenerative diseases characterized by altered brain functional connectivity (FC), affecting over 100 million people worldwide. This study aims to identify distinct FC patterns as potential biomarkers for differential diagnosis. Resting-state EEG data from 36 AD patients, 23 FTD patients, and 29 healthy controls were analyzed using time-frequency and bandpass filtering FC metrics. These metrics were estimated through Pearson's correlations, mutual information, and phase lag index, and served as input features in a support vector machine (SVM) with Leave-One-Out Cross-Validation for group classification. Both AD and FTD exhibited significantly decreased FC in the theta band within the frontal lobe and increased FC in the beta band in the posterior regions. Additionally, a decreased FC in central regions at theta band was observed uniquely in AD, but not in FTD. SVM classification accuracies reached 95% for AD and 86% for FTD. High classification accuracies underscore the potential of these FC alterations as reliable biomarkers for AD and FTD. This is the first study to integrate time-frequency and bandpass filtering FC metrics to reveal brain network alterations in AD and FTD, providing new insights for diagnostics and neurodegenerative pathologies.

Mapping alterations in the local synchrony of the cerebral cortex in Prader Willi syndrome.

Individuals with Prader Willi syndrome (PWS) often exhibit behavioral difficulties characterized by deficient impulse regulation and obsessive-compulsive features resembling those observed in obsessive-compulsive disorder. The genetic configuration of PWS aligns with molecular and neurophysiological findings suggesting dysfunction in the inhibitory gamma-aminobutyric acid (GABA) interneuron system may contribute to its clinical manifestation. In the cerebral cortex, this dysfunction is expressed as desynchronization of local neural activity. We used functional connectivity MRI to examine potential alterations in the local synchrony of the cerebral cortex in PWS. Whole-brain functional connectivity maps were generated using iso-distance average correlation (IDAC) measures in 22 patients with PWS and 22 control participants. Patients with PWS showed reduced local connectivity (weaker synchrony) in frontal areas, including the orbitofrontal cortex, ventral medial and lateral frontal regions, the anterior cingulate cortex, and sensory areas. The presence of obsessive-compulsive symptoms was significantly associated with the degree of functional structure alteration in part of the orbitofrontal and sensory cortices. In addition, abnormally heightened functional connectivity (stronger synchrony) was identified in the posterior cingulate cortex and the bilateral angular gyri, core components of the default mode network, with distance-dependent effects. Our findings of cortical synchrony alterations indicate a degree of overlap with the anatomy of the alterations previously observed in primary obsessive-compulsive disorder, while also suggesting the implication of GABAergic dysfunction in the pathophysiology of the disorder. Our observations may support the rational development of more specific therapeutic strategies in the treatment of behavioral disinhibition characteristic of PWS.

Insight into natural attenuation of tributyl phosphate by indigenous anaerobic microbes in soils: Implication by stable carbon isotope fractionation and microbial community structures.

Organophosphate esters (OPEs) are widespread in the environment, with high persistence and toxicity. However, the underlying mechanisms of anaerobic microbial degradation of OPEs remain elusive in the field environment. In this study, the natural attenuation mechanisms of tributyl phosphate (TnBP) by indigenous anaerobic microorganisms in soils were investigated by using compound-specific stable isotope analysis (CSIA) and characterization of microbial communities. The results indicated that dibutyl phosphate (DnBP) was the major degradation product of TnBP. Significant carbon isotope fractionation was observed for TnBP during the anaerobic microbial degradation, and the carbon isotope enrichment factor (εC) was determined to be -2.71±0.13‰. Unlike aerobic degradation with P-O bond cleavage, C-O bond cleavage was verified as the mode to removal a butyl side chain for TnBP to generate DnBP during the anaerobic microbial degradation. Microbial community analysis indicated that Sphingomonans, Nocardioides and Streptomyces were the important contributors to microbial degradation of TnBP in anoxic soils. TnBP altered microbial metabolic functions in anoxic soils, mainly enhancing the biosynthesis of ansamycins, ketone bodies and amino acids, and flagellar assembly, which promoted microbial degradation of TnBP. This study provided a better method to characterize the chemical bond cleavage mode and effect of OPEs on microbial communities, which was a prerequisite for the bioremediation of OPE pollution in soils.

Uneven-aged and even-aged forest management shape the soil fungal community composition in a boreal Norway spruce (Picea abies Karst) forest.

Forest management alters stand density, microclimate, and litter accrual, which all affect soil fungi. Mycorrhizal fungi play a key role in soil organic carbon (C) accumulation in boreal forests. We aimed to compare how uneven-aged continuous cover forestry (CCF) and even-aged rotation forest management (RFM) affect the soil fungal community, to draw conclusions on possible effects for long-term soil C storage. We compared uncut boreal Norway spruce forests to mature uneven-aged (CCF), even-aged and clear-cut forests (the latter two representing late and early stage in RFM). We compared their fungal community composition, species richness and diversity based on metabarcoding of bulk soil samples using sequences of the fungal ITS2 regions, and analysed the response of saprotrophic, ecto- and ericoid mycorrhizal fungal guilds to management practice. We found that fungal communities differed between all treatments, but species richness and diversity were not impacted. Clear-cuts were most dissimilar to the other treatments and the organic layer was more affected than the mineral soil. Abundance, diversity and richness of ectomycorrhizal fungi was declined in clear-cuts, leading to dominance of saprotrophic fungi. The abundance of functional guilds in even-aged and uneven-aged stands were similar to those in uncut stands. Ericoid mycorrhizae were more abundant in both stages of RFM, but their community composition was not affected by the forest management type. Despite the altered potential functionality, we found similar C stocks and cellulose decomposition rates in all treatments. This highlights the functional redundancy in the fungal community. Therefore, we conclude that CCF is unlikely to change the long-term soil C storage compared to unmanaged forests. The long-term effects of multiple clear-cutting cycles in RFM on the ecological functionality and possible effects on soil C storage should be further studied for example with sites that have been clear-cut more than once.

The ecology of poverty and children's brain development: A systematic review and quantitative meta-analysis of brain imaging studies.

A growing number of studies have demonstrated associations between poverty and brain structure and function. However, the strength of this association and the effects of poverty level (e.g., family or neighborhood poverty), age and sex on the association are strikingly inconsistent across studies. We aimed to synthesize findings on gray matter volume and task-based brain activation associated with poverty in youth samples and disentangle the effects of poverty level, age, and sex. In general, poverty was associated with alterations in volume and activation in the frontal, temporal, and subcortical regions. Among 14,188 participants and 14,057 participants, poverty was associated with smaller gray matter volumes in the amygdala and hippocampus, respectively. Moderator testing revealed that family poverty had a stronger association than neighborhood poverty and that poverty was related to slower development of amygdala volume. Among 2696 participants, convergent functional alterations associated with poverty were observed in the left middle temporal gyrus (MTG) and left middle frontal gyrus across all task domains, with the percentage of girls positively associated with increased activation in the precuneus. Subgroup analyses revealed that greater poverty was associated with deactivation in the left MTG for top-down control and hyperactivity in the right superior temporal gyrus, left superior frontal gyrus, left insula, cerebellum/left fusiform gyrus, and left amygdala/hippocampus for bottom-up processing. These findings provide insights into the neuroscience of poverty, suggesting implications for targeted interventions to support the cognitive and mental health of children living in poverty.

Childhood family environment and μ-opioid receptor availability in vivo in adulthood.

Animal studies have reported associations of early maternal separation with altered μ-opioid receptor function but data on humans are scarce. We now investigated whether childhood family environment is related to μ-opioid receptor availability in the human brain in adulthood. Healthy participants (n = 37-39 in the analyses) were recruited from the prospective population-based Young Finns Study (YFS) that started in 1980. Childhood family environment was evaluated in 1980, including scores for stress-prone life events, disadvantageous emotional family atmosphere, and adverse socioeconomic environment. We used positron emission tomography (PET) with radioligand [11C]carfentanil to measure μ-opioid receptor availability in adulthood. Age- and sex-adjusted analyses showed that exposure to stress-prone life events in childhood was related to lower μ-opioid receptor binding in the orbitofrontal cortex, hippocampus, putamen, amygdala, insula, thalamus, anterior cingulate cortex, and dorsal caudate in adulthood (when compared to participants not exposed to stress-prone life events). Unfavorable socioeconomic family environment or disadvantageous emotional family atmosphere was not associated with μ-opioid receptor availability in adulthood. In conclusion, exposure to environmental instability (i.e., to stress-prone life events below traumatic threshold) during early development is associated with dysregulation of the u-opioid receptor transmission in adulthood. The findings increase understanding of the neurobiological mechanisms involved in the associations between childhood adversities and adulthood mental disorders.

Alzheimer's disease may develop from changes in the immune system, cell cycle, and protein processing following alterations in ribosome function.

The prevalence of Alzheimer's disease (AD) is increasing as society ages. The details of AD pathogenesis have not been fully elucidated, and a comprehensive gene expression analysis of the process leading up to the onset of AD would be helpful for understanding the mechanism. We performed an RNA sequencing analysis on a cohort of 1227 Japanese blood samples, representing 424 AD patients, 543 individuals with mild cognitive impairment (MCI), and 260 cognitively normal (CN) individuals. A total of 883 and 1169 statistically significant differentially expressed genes (DEGs) were identified between CN and MCI (CN-MCI) and between MCI and AD (MCI-AD), respectively. Pathway analyses using these DEGs, followed by protein-protein interaction network analysis, revealed key roles of ribosomal function in MCI progression, whereas immune responses, cell cycle, and protein processing in endoplasmic reticulum were involved in AD progression. Our findings indicate that the onset of AD might be associated with gene expression changes in the immune system, cell cycle, and protein processing following alterations in the expression of ribosomal protein genes during the MCI stage, although validation using brain tissue samples will be necessary in the future. Given the known effectiveness of delaying MCI progression in preventing AD, the genes related to ribosomal function might emerge as biomarkers for early diagnosis.

Physiological impact of secondary nanoplastics on aquatic inhabitants in special reference to immunotoxicity.

Nanoplastic (NP) pollution poses serious health hazards to aquatic ecosystems, impacting various physiological systems of aquatic organisms. This review examines the complex interplay between NPs and different physiological systems. In the digestive system, NPs downregulate the hsp70-like gene in Mytilus galloprovincialis, leading to decreased metabolic processes and impaired digestion. Neural system exposure to NPs induces abnormal expression of genes like neurogenin1, GFAP, FBJ murine osteosarcoma viral oncogene, GAP-43, synapsin IIa, apoptosis regulator a, Bcl2 and Caspase a, and apoptosis-related cysteine peptidase. These genes play a crucial role in neurodevelopment, synaptic function and apoptosis regulation, potentially impacting neurobiology and cancer biology. NPs also affect reproduction, including gametogenesis, spawning, fertilization, embryogenesis and larval survivability. In the respiratory system, treatment with these causes inflammation in the lungs and gills, resulting in respiratory dysfunction. Moreover, this review investigates the complex interaction between NPs and the immune systems of both invertebrates (e.g., molluscs, arthropods, echinoderms) and vertebrates (e.g., zebrafish). NPs-induced alterations in immune cell function heightened the susceptibility to pathogens and disrupted immune signalling pathways. Subcellular inflammatory responses have been characterized by the secretion of inflammation-promoting and chemotactic cytokines such as irg1l, interleukin 1, interferon, interleukin 6, C-C motif chemokine ligand 20a and tumour necrosis factor. The assessment of the combined effects of NPs and other xenobiotics highlighted their possible synergistic impacts on aquatic fauna and the environment. This comprehensive review emphasizes the urgent need for further research to understand the cumulative effects of NPs on organism health and fitness across multiple physiological systems.