Structure-function Associations Research Articles

Extensive Chromatin Structure-Function Associations Revealed by Accurate 3D Compartmentalization Characterization.

A/B compartments are observed in Hi-C data and coincide with eu/hetero-chromatin. However, many genomic regions are ambiguous under A/B compartment scheme. We develop MOSAIC (MOdularity and Singular vAlue decomposition-based Identification of Compartments), an accurate compartmental state detection scheme. MOSAIC reveals that those ambiguous regions segregate into two additional compartmental states, which typically correspond to short genomic regions flanked by long canonical A/B compartments with opposite activities. They are denoted as micro-compartments accordingly. In contrast to the canonical A/B compartments, micro-compartments cover ∼30% of the genome and are highly dynamic across cell types. More importantly, distinguishing the micro-compartments underpins accurate characterization of chromatin structure-function relationship. By applying MOSAIC to GM12878 and K562 cells, we identify CD86, ILDR1 and GATA2 which show concordance between gene expression and compartmental states beyond the scheme of A/B compartments. Taken together, MOSAIC uncovers fine-scale and dynamic compartmental states underlying transcriptional regulation and disease.

Deviation From Model of Normal Aging in Alzheimer’s Disease: Application of Deep Learning to Structural MRI Data and Cognitive Tests

Background. Psychophysiological and cognitive tests as well as other functional studies can detect pre-symptomatic stages of dementia. When assembled with structural data, cognitive tests diagnose NDs more reliably thus becoming a multimodal diagnostic tool. Objective. Our main goal is to improve screening for dementia by studying an association between the brain structure and its function. Hypothetically, the brain structure-function association has features specific for either diseaserelated cognitive deterioration or normal neurocognitive slowing while aging. Materials and methods. We studied a total number of 287 cognitively normal cases, 646 of mild cognitive impairment, and 369 of Alzheimer’s disease. To work out a new marker of neurodegeneration, we created a convolutional neural network-based regression model and predicted the cognitive status of the cognitively preserved examinee from the brain MRI data. This was a model of normal aging. A big deviation from the model suggests a high risk of accelerated cognitive decline. Results. The deviation from the model of normal aging can accurately distinguish cognitively normal subjects from MCI patients (AUC = 0.9957). We also achieved creditable performance in the MCI-versus-AD classification (AUC = 0.9793). We identified a considerable difference in the MMSE test between A-positive and A-negative demented individuals according to ATN-criteria (6.27±1.82 vs 5.32±1.9; p < 0.05). Conclusion. The deviation from the model of normal aging can be potentially used as a marker of dementia and as a tool for differentiating Alzheimer’s disease from non-Alzheimer’s dementia. To find and justify a reliable threshold levels, further research is required.

Neural Presbyacusis in Humans Inferred from Age-Related Differences in Auditory Nerve Function and Structure.

A common complaint of older adults is difficulty understanding speech, particularly in challenging listening conditions. Accumulating evidence suggests that these difficulties may reflect a loss and/or dysfunction of auditory nerve (AN) fibers. We used a novel approach to study age-related changes in AN structure and several measures of AN function, including neural synchrony, in 58 older adults and 42 younger adults. AN activity was measured in response to an auditory click (compound action potential; CAP), presented at stimulus levels ranging from 70 to 110 dB pSPL. Poorer AN function was observed for older than younger adults across CAP measures at higher but not lower stimulus levels. Associations across metrics and stimulus levels were consistent with age-related AN disengagement and AN dyssynchrony. High-resolution T2-weighted structural imaging revealed age-related differences in the density of cranial nerve VIII, with lower density in older adults with poorer neural synchrony. Individual differences in neural synchrony were the strongest predictor of speech recognition, such that poorer synchrony predicted poorer recognition of time-compressed speech and poorer speech recognition in noise for both younger and older adults. These results have broad clinical implications and are consistent with an interpretation that age-related atrophy at the level of the AN contributes to poorer neural synchrony and may explain some of the perceptual difficulties of older adults.SIGNIFICANCE STATEMENT Differences in auditory nerve (AN) pathophysiology may contribute to the large variations in hearing and communication abilities of older adults. However, current diagnostics focus largely on the increase in detection thresholds, which is likely because of the absence of indirect measures of AN function in standard clinical test batteries. Using novel metrics of AN function, combined with estimates of AN structure and auditory function, we identified age-related differences across measures that we interpret to represent age-related reductions in AN engagement and poorer neural synchrony. Structure-function associations are consistent with an explanation of AN deficits that arise from age-related atrophy of the AN. Associations between neural synchrony and speech recognition suggest that individual and age-related deficits in neural synchrony contribute to speech recognition deficits.

Comparison of the 24-2 and 24-2C Visual Field Grids in Determining the Macular Structure-Function Relationship in Glaucoma.

The 24-2C grid showed significantly greater structure-function (S-F) associations in the global and regional sectors than the 24-2 visual field (VF) grid in open-angle glaucoma eyes. The aim was to compare a Humphrey Field Analyzer (HFA) Swedish Interactive Threshold Algorithm-Faster (SITA-faster) 24-2C grid to a conventional HFA 24-2 grid regarding macular S-F relationships. The macular ganglion cell-inner plexiform layer thickness (mGCIPLT) was measured at different parafoveal sectors using spectral-domain optical coherence tomography in 150 eyes from 150 healthy, preperimetric, and perimetric glaucoma subjects. The central visual field mean sensitivity (VFMS) on the decibel and 1/L scales and the parafoveal mGCIPLT were matched topographically in 4 sectors and the strengths of the S-F relationships were assessed using "weighted" correlation coefficients and compared between 24-2C and 24-2 VF test grids. There were significant global and sectoral correlations between the mGCIPLT and VFMS using both VF grids. The S-F correlations between the average/hemimacular mGCIPLT and the corresponding VFMS using a 24-2C grid were however significantly greater in both the entire and perimetric glaucoma groups (P<0.05), except for the average mGCIPLT of the perimetric glaucoma group in the 1/L scale (P=0.065). The 24-2C grid showed significantly greater S-F associations in the superotemporal and inferotemporal parafoveal sectors than the 24-2 VF grid (both P<0.05). A 24-2C grid may offer an advantage over the conventional 24-2 VF grid in assessing macular S-F relationships.

Strengthened structure–function relationships of the corticospinal tract by free water correction after stroke

The corticospinal tract is the most intensively investigated tract of the human motor system in stroke rehabilitative research. Diffusion-tensor-imaging gives insights into its microstructure, and transcranial magnetic stimulation assesses its excitability. Previous data on the interrelationship between both measures are contradictory. Correlative or predictive models which associate them with motor outcome are incomplete. Free water correction has been developed to enhance diffusion-tensor-imaging by eliminating partial volume with extracellular water, which could improve capturing stroke-related microstructural alterations, thereby also improving structure-function relationships in clinical cohorts. In the present cross-sectional study, data of 18 chronic stroke patients and 17 healthy controls, taken from a previous study on cortico-cerebellar motor tracts, were re-analysed: The data included diffusion-tensor-imaging data quantifying corticospinal tract microstructure with and without free water correction, transcranial magnetic stimulation data assessing recruitment curve properties of motor evoked potentials and detailed clinical data. Linear regression modelling was used to interrelate corticospinal tract microstructure, recruitment curves properties and clinical scores. The main finding of the present study was that free water correction substantially strengthens structure-function associations in stroke patients: Specifically, our data evidenced a significant association between fractional anisotropy of the ipsilesional corticospinal tract and its excitability (P = 0.001, adj. R2 = 0.54), with free water correction explaining additional 20% in recruitment curve variability. For clinical scores, only free water correction leads to the reliable detection of significant correlations between ipsilesional corticospinal tract fractional anisotropy and residual grip (P = 0.001, adj. R2 = 0.70) and pinch force (P < 0.001, adj. R2 = 0.72). Finally, multimodal models can be improved by free water correction as well. This study evidences that corticospinal tract microstructure directly relates to its excitability in stroke patients. It also shows that unexplained variance in motor outcome is considerably reduced by free water correction arguing that it might serve as a powerful tool to improve existing models of structure-function associations and potentially also outcome prediction after stroke.

Biosynthesis and characterization of deuterated chitosan in filamentous fungus and yeast

Deuterated chitosan was produced from the filamentous fungus Rhizopus oryzae, cultivated with deuterated glucose in H2O medium, without the need for conventional chemical deacetylation. After extraction and purification, the chemical composition and structure were determined by Fourier-transform infrared spectroscopy (FTIR), nuclear magnetic resonance (NMR), and small-angle neutron scattering (SANS). 13C NMR experiments provided additional information about the position of the deuterons in the glucoseamine backbone. The NMR spectra indicated that the deuterium incorporation at the non-exchangeable hydrogen positions of the aminoglucopyranosyl ring in the C3 – C5 positions was at least 60–80 %. However, the C2 position was deuterated at a much lower level (6%). Also, SANS showed that the structure of deuterated chitosan was very similar compared to the non-deuterated counterpart. The most abundant radii of the protiated and deuterated chitosan fibers were 54 Å and 60 Å, respectively, but there is a broader distribution of fiber radii in the protiated chitosan sample. The highly deuterated, soluble fungal chitosan described here can be used as a model material for studying chitosan-enzyme complexes for future neutron scattering studies. Because the physical behavior of non-deuterated fungal chitosan mimicked that of shrimp shell chitosan, the methods presented here represent a new approach to producing a high quality deuterated non-animal-derived aminopolysaccharide for studying the structure-function association of biocomposite materials in drug delivery, tissue engineering and other bioactive chitosan-based composites.

Optical coherence tomography indices in the diagnosis and discrimination of stages of primary open-angle glaucoma in an African population.

The objective of this study was to determine the structure-function association of the optical coherence tomography (OCT) indices (retinal nerve fibre layer (RNFL), ganglion cell complex (GCC) and optic nerve head (ONH) parameters) with the visual field sensitivity and their diagnostic ability at different stages of primary open-angle glaucoma (POAG) among a population West-African descent. The study was a clinic-based prospective study which employed purposive sampling in the recruitment of clinically diagnosed POAG and non-glaucoma patients. OCT and visual field test (VFT) results were collated. Classification of the POAG cases was done using the Hodapp-Parrish-Anderson criteria. ROC was used for assessing the diagnostic ability of OCT indices. Pearson's correlation was used to assess the structure-function association. P value < 0.05 was considered statistically significant. Of the 497 subjects (497 eyes), 301 (60.6%) were males and 196 (39.4%) were females. The average, superior and inferior RNFL and GCC showed a strong positive correlation with the visual field sensitivity, but the average RNFL had the highest correlation (r = 0.673, p < 0.001). The parameters of the ONH showed a moderate-to-weak correlation with the visual field sensitivity. However, there was no significant correlation between structure and function in early POAG (p > 0.05). Superior GCC showed the highest diagnostic ability for POAG (AUC = 0.655; p < 0.001) comparable to the RNFL. Macula (GCC) and (RNFL) have a comparable ability to diagnose POAG at all the stages of POAG and can be used complimentarily for glaucoma assessment and diagnosis.

Hallucination-Specific structure-function associations in schizophrenia

Combining structural (sMRI) and functional magnetic resonance imaging (fMRI) data in schizophrenia patients with and without auditory hallucinations (9 SZ_AVH, 12 SZ_nAVH), 18 patients with bipolar disorder, and 22 healthy controls, we examined whether cortical thinning was associated with abnormal activity in functional brain networks associated with auditory hallucinations. Language-task fMRI data were combined with mean cortical thickness values from 148 brain regions in a constrained principal component analysis (CPCA) to identify brain structure-function associations predictable from group differences. Two components emerged from the multimodal analysis. The “AVH component” highlighted an association of frontotemporal and cingulate thinning with altered brain activity characteristic of hallucinations among patients with AVH. In contrast, the “Bipolar component” distinguished bipolar patients from healthy controls and linked increased activity in the language network with cortical thinning in the left occipital-temporal lobe. Our findings add to a body of evidence of the biological underpinnings of hallucinations and illustrate a method for multimodal data analysis of structure-function associations in psychiatric illness.

Pitch and Duration Mismatch Negativity and Heschl's Gyrus Volume in First-Episode Schizophrenia-Spectrum Individuals.

Background. The mismatch negativity (MMN) brainwave indexes novelty detection. MMN to infrequent pitch (pMMN) and duration (dMMN) deviants is reduced in long-term schizophrenia. Although not reduced at first psychosis, pMMN is inversely associated with left hemisphere Heschl's gyrus (HG) gray matter volume within 1 year of first hospitalization for schizophrenia-spectrum psychosis, consistent with pathology of left primary auditory cortex early in disease course. We examined whether the relationship was present earlier, at first psychiatric contact for psychosis, and whether the same structural-functional association was apparent for dMMN. Method. Twenty-seven first-episode schizophrenia-spectrum (FESz) and 27 matched healthy comparison (HC) individuals were compared. EEG-derived pMMN and dMMN were measured by subtracting the standard tone waveform (80%) from the pitch- and duration-deviant waveforms (10% each). HG volumes were calculated from T1-weighted structural magnetic resonance imaging using Freesurfer. Results. In FESz, pMMN amplitudes at Fz were inversely associated with left HG (but not right) gray matter volumes, and dMMN amplitudes were associated significantly with left HG volumes and at trend-level with right HG. There were no structural-functional associations in HC. Conclusions. pMMN and dMMN index gray matter reduction in left hemisphere auditory cortex early in psychosis, with dMMN also marginally indexing right HG volumes. This suggest conjoint functional and structural pathology that affects the automatic detection of novelty with varying degrees of penetrance prior to psychosis. These brainwaves are sensitive biomarkers of pathology early in the psychotic disease course, and may serve as biomarkers of disease progression and as therapeutic outcome measures.

Влияние недостатка ночного сна на когнитивную установку по показателям взаимодействия ритмов ЭЭГ

The aim of the study is investigation of nighttime sleep effect on the performance of a cognitive setting in terms of the coupling of EEG rhythms. The coupling of 5 rhythm: beta-1, beta-2, gamma, alpha and theta rhythms of EEG during the formation and testing of cognitive set was studied for 120 students (17 with short-term night sleep and 15 with a full night sleep). Multi-channel EEG was recorded. EEG evaluation was carried out by continuous wavelet transform based on the “mother” complex Morlet wavelet in the range of 1–35 Hz. Maps of the distribution of the values of the modulus of the wavelet transformation coefficient, which reflect amplitude changes of the potentials were analyzed. The Pearson correlation coefficient was a measure evaluating the coupling of EEG rhythms. The subjects with a short night’s sleep showed almost all of the relations of EEG rhythms (8 couples) during the formation stage of presentation. Students with a full night’s sleep showed statistically significant coupling of the following pairs of rhythms: alpha–beta-1, alpha–gamma and beta-2–gamma. Students with short-term night sleep demonstrated the 3 significant couples: alpha–beta-1, beta-1–gamma and beta-2–gamma during the testing stage. Well-slept students showed an increase in the number of connections (6 couples) in relation to the stage of formation of the set due to the addition of connections with the theta rhythm. The obtained data could indicate that the thalamo-cortical and cortico-hippocampal structural-functional associations work differently in the groups of subjects.

Parallel Reaction Monitoring reveals structure-specific ceramide alterations in the zebrafish

Extensive characterisations of the zebrafish genome and proteome have established a foundation for the use of the zebrafish as a model organism; however, characterisation of the zebrafish lipidome has not been as comprehensive. In an effort to expand current knowledge of the zebrafish sphingolipidome, a Parallel Reaction Monitoring (PRM)-based liquid chromatography–mass spectrometry (LC–MS) method was developed to comprehensively quantify zebrafish ceramides. Comparison between zebrafish and a human cell line demonstrated remarkable overlap in ceramide composition, but also revealed a surprising lack of most sphingadiene-containing ceramides in the zebrafish. PRM analysis of zebrafish embryogenesis identified developmental stage-specific ceramide changes based on long chain base (LCB) length. A CRISPR-Cas9-generated zebrafish model of Farber disease exhibited reduced size, early mortality, and severe ceramide accumulation where the amplitude of ceramide change depended on both acyl chain and LCB lengths. Our method adds an additional level of detail to current understanding of the zebrafish lipidome, and could aid in the elucidation of structure-function associations in the context of lipid-related diseases.

Contributions of White Matter Connectivity and BOLD Modulation to Cognitive Aging: A Lifespan Structure-Function Association Study.

The ability to flexibly modulate brain activation to increasing cognitive challenge decreases with aging. This age-related decrease in dynamic range of function of regional gray matter may be, in part, due to age-related degradation of regional white matter tracts. Here, a lifespan sample of 171 healthy adults (aged 20-94) underwent magnetic resonance imaging (MRI) scanning including diffusion-weighted imaging (for tractography) and functional imaging (a digit n-back task). We utilized structural equation modeling to test the hypothesis that age-related decrements in white matter microstructure are associated with altered blood-oxygen-level-dependent (BOLD) modulation, and both in turn, are associated with scanner-task accuracy and executive function performance. Specified structural equation model evidenced good fit, demonstrating that increased age negatively affects n-back task accuracy and executive function performance in part due to both degraded white matter tract microstructure and reduced task-difficulty-related BOLD modulation. We further demonstrated that poorer white matter microstructure integrity was associated with weakened BOLD modulation, particularly in regions showing positive modulation effects, as opposed to negative modulation effects. This structure-function association study provides further evidence that structural connectivity influences functional activation, and the two mechanisms in tandem are predictive of cognitive performance, both during the task, and for cognition measured outside the scanner environment.

Structure-function associations of successful associative encoding

Functional magnetic resonance imaging (MRI) studies have demonstrated a critical role of hippocampus and inferior frontal gyrus (IFG) in associative memory. Similarly, evidence from structural MRI studies suggests a relationship between gray-matter volume in these regions and associative memory. However, how brain volume and activity relate to each other during associative-memory formation remains unclear. Here, we used joint independent component analysis (jICA) to examine how gray-matter volume and brain activity would be associated during associative encoding, especially in medial-temporal lobe (MTL) and IFG. T1-weighted images were collected from 27 young adults, and functional MRI was employed during intentional encoding of object pairs. A subsequent recognition task tested participants’ memory performance. Unimodal analyses using voxel-based morphometry revealed that participants with better associative memory showed larger gray-matter volume in left anterior hippocampus. Results from the jICA revealed one component that comprised a covariance pattern between gray-matter volume in anterior and posterior MTL and encoding-related activity in IFG. Our findings suggest that gray matter within the MTL modulates distally distinct parts of the associative encoding circuit, and extend previous studies that demonstrated MTL-IFG functional connectivity during associative memory tasks.

A comparative multivariate analysis of nitrilase enzymes: An ensemble based computational approach

Nitrilases, member of nitrilase superfamily catalyse the hydrolysis of different nitriles to corresponding amides and acids. In this article, we demonstrate two-fold computational comparative analysis on coding gene sequences, amino acid sequences, three-dimensional structure of the nitrilases from different species and discovered conserved motifs linked with related species. A large ensemble-based dataset was utilized from bacteria, fungi, plants and animals. Here, we used comparative genomics, motif analyses and Bayesian phylogenetic analyses in combination with structural analyses [molecular dynamics simulation, principal component analysis (PCA), dynamic cross correlation (DCCM), root mean squared inner product (RMSIP), free energy surface (FES)] to investigate the evolution, ecological relationship and structure-function association of nitrilase family. The inferred evolutionary tree displayed nitrilase gene clusters to be shared among bacteria, fungi and plants. Structural analysis revealed that the folding of catalytic sites is similar among species; however, the loop region varies. We provide evidence based on PCA that the nitrilases are clustered into different clades due to variation in side chains. Numerous of significant correlations were found between sequence clades and the structural discriminating properties of nitrilases originating from different species. The results are consistent with the hypothesis that bacterial nitrilases are in ecological and evolutionary relationships with fungi and plants during plant-pathogen interaction to large extent. This compact and detail results also open new dimensions for further studying and improvement of industrially important nitrilase enzymes.

APOE-ε4 risk variant for Alzheimer's disease modifies the association between cognitive performance and cerebral morphology in healthy middle-aged individuals.

The APOE-ε4 genotype is the highest genetic risk factor for Alzheimer's disease (AD). In cognitively unimpaired individuals, it has been related to altered brain morphology, function and earlier amyloid beta accumulation. However, its impact on cognitive performance is less evident. Here, we examine the impact of APOE-ε4 allele load in modulating the association between cognitive functioning and brain morphology in middle-aged healthy individuals. A high-resolution structural MRI scan was acquired and episodic memory (EM) as well as executive functions (EFs) were assessed in a sample of 527 middle-aged unimpaired individuals hosting a substantial representation of ε4-homozygous (N = 64). We adopted a voxel-wise unbiased method to assess whether the number of APOE-ε4 alleles significantly modified the associations between gray matter volumes (GMv) and performance in both cognitive domains.Even though the APOE-ε4 allele load did not exert a direct impact on any cognitive measures, it reversed the relationships between GMv and cognitive performance in a highly symmetrical topological pattern. For EM, interactions mapped onto the inferior temporal gyrus and the dorsal anterior cingulate cortex. Regarding EFs, significant interactions were observed for processing speed, working memory, and visuospatial attention in distinct brain regions. These results suggest that APOE-ε4 carriers display a structure-function association corresponding to an older age than their chronological one. Our findings additionally indicate that APOE-ε4 carriers may rely on the integrity of multiple compensatory brain systems in order to preserve their cognitive abilities, possibly due to an incipient neurodegeneration. Overall this study provides novel insights on the mechanisms through which APOE-ε4 posits an increased AD risk.

The extracellular topographical environment influences ovarian cancer cell behaviour

The importance of the biophysical cellular environment in cancer development has been increasingly recognised but so far has been only superficially studied. Here we investigated the effect of cell-like substrate topography on ovarian cancer cell behaviour and potential underlying signalling pathways. We observed changes in cell morphology in response to substrate topography, which implies modification of structure-function associations. Differences in focal adhesion signalling and Rho/ROCK activity suggested their involvement in the biomechanically-driven cellular responses. Cell-like topography was also shown to modulate the MAPK pathway and hence potentially regulate cell proliferation. The selective regulation of the cells by the mechanotransduction pathways that we noted has wide ranging implications for understanding cancer development. We established that the physical architecture of cell culture substrate is sufficient to influence cancer cell behaviour, independent of genetic composition or biochemical milieu.

Brain structure and neurological and behavioural functioning in infants born preterm.

To examine: (1) relationships between brain structure, and concurrently assessed neurological and behavioural functioning, in infants born preterm at term-equivalent age (TEA; approximately 38-44wks); and (2) whether brain structure-function relationships differ between infants born very (24-29wks) and moderate-late (32-36wks) preterm. A total of 257 infants (91 very preterm, 166 moderate-late preterm; 120 males, 137 females) had structural magnetic resonance imaging (MRI) and neurological and behavioural assessments (Prechtl's general movements assessment, Neonatal Intensive Care Unit Network Neurobehavioral Scale [NNNS] and Hammersmith Neonatal Neurological Examination [HNNE]). Two hundred and sixty-three infants (90 very preterm, 173 moderate-late preterm; 131 males, 132 females) had diffusion MRI and assessments. Associations were investigated between assessment scores and global brain volumes using linear regressions, regional brain volumes using Voxel-Based Morphometry, and white matter microstructure using Tract-Based Spatial Statistics. Suboptimal scores on some assessments were associated with lower fractional anisotropy and/or higher axial, radial, and mean diffusivities in some tracts: NNNS attention and reflexes, and HNNE total score and tone, were associated with the corpus callosum and optic radiation; NNNS quality of movement with the corona radiata; HNNE abnormal signs with several major tracts. Brain structure-function associations generally did not differ between the very and moderate-late preterm groups. White matter microstructural alterations may be associated with suboptimal neurological and behavioural performance in some domains at TEA in infants born preterm. Brain structure-function relationships are similar for infants born very preterm and moderate-late preterm. Brain volume is not related to neurological/behavioural function in infants born preterm at term. White matter microstructure is related to some neurological/behavioural domains at term. Brain-behaviour relationships are generally similar for infants born very preterm and moderate-late preterm.

Altered Functional Interactions of Inhibition Regions in Cognitively Normal Parkinson's Disease.

Deficient inhibitory control in Parkinson’s disease (PD) is often observed in situations requiring inhibition of impulsive or prepotent behaviors. Although activation of the right-hemisphere frontal-basal ganglia response inhibition network is partly altered in PD, disturbances in interactions of these regions are poorly understood, especially in patients without cognitive impairment. The present study investigated context-dependent connectivity of response inhibition regions in PD patients with normal cognition and control participants who underwent fMRI while performing a stop signal task. PD participants were tested off antiparkinsonian medication. To determine if functional disturbances depended on underlying brain structure, aberrant connectivity was correlated with brain volume and white-matter tissue diffusivity. We found no group differences in response inhibition proficiency. Yet the PD group showed functional reorganization in the long-range connectivity of inhibition regions, despite preserved within network connectivity. Successful inhibition in PD differed from the controls by strengthened connectivity of cortical regions, namely the right dorsolateral prefrontal cortex, pre-supplementary motor area and right caudal inferior frontal gyrus, largely with ventral and dorsal attention regions, but also the substantia nigra and default mode network regions. Successful inhibition in controls was distinguished by strengthened connectivity of the right rostral inferior frontal gyrus and subcortical inhibition nodes (right caudate, substantia nigra, and subthalamic nucleus). In both groups, the strength of context-dependent connectivity correlated with various indices of response inhibition performance. Mechanisms that may underlie aberrantly stronger context-specific connectivity include reduced coherence within reorganized systems, compensatory mechanisms, and/or the reorganization of intrinsic networks. In PD, but not controls, abnormally strengthened connectivity was linked to individual differences in underlying brain volumes and tissue diffusivity, despite no group differences in structural variables. The pattern of structural-functional associations suggested that subtle decreases in tissue diffusivity of underlying tracts and posterior cortical volumes may undermine the enhancement of normal cortical-striatal connectivity or cause strengthening in cortical-cortical connectivity. These novel findings demonstrate that functionally reorganized interactions of inhibition regions predates the development of inhibition deficits and clinically significant cognitive impairment in PD. We speculate that altered interactions of inhibition regions with attention-related networks and the dopaminergic system may presage future decline in inhibitory control.

RDNA- and rRNA-derived communities present divergent assemblage patterns and functional traits throughout full-scale landfill leachate treatment process trains

Understanding the influences of microbial interactions and niche heterogeneities on microbial communities and functional traits is critical for determining its engineering and ecological significance. However, little is known about microbial community assemblage and functional gene expression throughout full-scale landfill leachate treatment plants. Here, we applied a combination of 16S rRNA and rDNA amplicon sequencing, shotgun metagenomic, and qPCR approaches to unveil the ecological associations between distinct communities, functional gene expression and nitrogen cycling processes. By comparing the rDNA and rRNA-derived communities, the rRNA/rDNA ratios suggested that 57.2% of rare taxa were active, and their abundance decreased as increasing of potential activities. In particular, rDNA- and rRNA-based communities exhibited divergent assemblage patterns, and stronger intra-associations among core taxa in the rRNA-based communities than in rDNA-based communities. Furthermore, results regarding both bacterial assemblage and functional traits indicated that the habitat filtering and niche differentiation (treatment units) exerted selection on microbial communities based on functional traits, particular for key ecological functions related to nitrogen cycling. Collectively, our findings provide insights into structure-function associations at the local level and shed light on ecological rules guiding rDNA- and rRNA-based community assembly in landfill leachate treatment systems.

Differing Structural and Functional Patterns of Optic Nerve Damage in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

To assess differential patterns of axonal loss and demyelination in the optic nerve in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). Cross-sectional study. One hundred ninety-two participants, including 136 MS patients (272 eyes), 19 NMOSD patients (38 eyes), and 37 healthy control participants (74 eyes). All participants underwent spectral-domain OCT scans and multifocal visual evoked potential (mfVEP) recordings. High-resolution magnetic resonance imaging (MRI) with the diffusion protocol also was performed in all patients. Ganglion cell-inner plexiform layer (GCIPL) thickness and mfVEP amplitude and latency at 5 eccentricities; global and temporal retinal nerve fiber layer thickness. In optic neuritis (ON) eyes, the NMOSD patients had more severe GCIPL loss (P < 0.001) and mfVEP amplitude reduction (P < 0.001) compared with MS patients, whereas in contrast, mfVEP latency delay was more evident in MS patients (P < 0.001). The NMOSD patients showed more morphologic and functional loss at the foveal to parafoveal region, whereas the MS patients showed evenly distributed damage at the macula. Correlation analysis demonstrated a strong structure-function (OCT-mfVEP) association in the NMOSD patients, which was only moderate in the MS patients. In non-ON (NON) eyes, the MS patients showed significantly thinner GCIPL than controls (P < 0.001), whereas no GCIPL loss was observed in NON eyes in NMOSD. In addition, a significant correlation was found between all OCT and mfVEP measures in MS patients, but not in NMOSD patients. MRI demonstrated significant lesional load in the optic radiation in MS compared to NMOSD eyes (P= 0.002), which was related to the above OCT and mfVEP changes in NON eyes. Our study demonstrated different patterns of ON damage in NMOSD and MS. In MS, the ON damage was less severe, with demyelination as the main pathologic component, whereas in NMOSD, axonal loss was more severe compared with myelin loss. The disproportional mfVEP amplitude and latency changes suggested predominant axonal damage within the anterior visual pathway as the main clinical feature of NMOSD, in contrast to MS, where demyelination spreads along the entire visual pathway.