Decreased gray matter volume and dynamic functional alterations in medicine-free obsessive-compulsive disorder.

BACKGROUND: Previous studies discovered the presence of abnormal structures and functions in the brain regions of patients with obsessive-compulsive disorder (OCD). Nevertheless, whether structural changes in brain regions are coupled with alterations in dynamic functional connectivity (dFC) at rest in medicine-free patients with OCD remains vague. METHODS: Three-dimensional T1-weighed magnetic resonance imaging (MRI) and resting-state functional MRI were performed on 50 medicine-free OCD and 50 healthy controls (HCs). Firstly, the differences in gray matter volume (GMV) between OCD and HCs were compared. Then, brain regions with aberrant GMV were used as seeds for dFC analysis. The relationship of altered GMV and dFC with clinical parameters in OCD was explored using partial correlation analysis. Finally, support vector machine was applied to examine whether altered multimodal imaging data might be adopted to distinguish OCD from HCs. RESULTS: Our findings indicated that GMV in the left superior temporal gyrus (STG) and right supplementary motor area (SMA) was reduced in OCD, and the dFC between the left STG and the left cerebellum Crus I and left thalamus, and between the right SMA and right dorsolateral prefrontal cortex (DLPFC) and left precuneus was decreased at rest in OCD. The brain regions both with altered GMV and dFC values could discriminate OCD from HCs with the accuracy of 0.85, sensitivity of 0.90 and specificity of 0.80. CONCLUSION: The decreased gray matter structure coupling with dynamic function in the left STG and right SMA at rest may be crucial in the pathophysiology of OCD. TRIAL REGISTRATION: Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (registration date: 08/11/2017; registration number: ChiCTR-COC-17,013,301).

Anatomical distance affects functional connectivity at rest in medicine-free obsessive-compulsive disorder.

BACKGROUND: Brain functional abnormalities at rest have been observed in obsessive-compulsive disorder (OCD). However, whether and how anatomical distance influences functional connectivity (FC) at rest is ambiguous in OCD. METHODS: Using resting-state functional magnetic resonance imaging data, we calculated the FC of each voxel in the whole-brain and divided FC into short- and long-range FCs in 40 medicine-free patients with OCD and 40 healthy controls (HCs). A support vector machine (SVM) was used to determine whether the altered short- and long-range FCs could be utilized to distinguish OCD from HCs. RESULTS: Patients had lower short-range positive FC (spFC) and long-range positive FC (lpFC) in the left precentral/postcentral gyrus (t = -5.57 and -5.43; P < 0.05, GRF corrected) and higher lpFC in the right thalamus/caudate, left thalamus, left inferior parietal lobule (IPL) and left cerebellum CrusI/VI (t = 4.59, 4.61, 4.41, and 5.93; P < 0.05, GRF corrected). Furthermore, lower spFC in the left precentral/postcentral gyrus might be used to distinguish OCD from HCs with an accuracy of 80.77%, a specificity of 81.58%, and a sensitivity of 80.00%. CONCLUSION: These findings highlight that anatomical distance has an effect on the whole-brain FC patterns at rest in OCD. Meanwhile, lower spFC in the left precentral/postcentral gyrus might be applied in distinguishing OCD from HCs.

Decreased Nucleus Accumbens Connectivity at Rest in Medication-Free Patients with Obsessive-Compulsive Disorder.

Background: Patients with obsessive-compulsive disorder (OCD) experience deficiencies in reward processing. The investigation of the reward circuit and its essential connectivity may further clarify the pathogenesis of OCD. Methods: The current research was designed to analyze the nucleus accumbens (NAc) functional connectivity at rest in medicine-free patients with OCD. Forty medication-free patients and 38 gender-, education-, and age-matched healthy controls (HCs) were recruited for resting-state functional magnetic resonance imaging. Seed-based functional connectivity (FC) was used to analyze the data. LIBSVM (library for support vector machines) was designed to identify whether altered FC could be applied to differentiate OCD. Results: Patients with OCD showed remarkably decreased FC values between the left NAc and the bilateral orbitofrontal cortex (OFC) and bilateral medial prefrontal cortex (MPFC) and between the right NAc and the left OFC at rest in the reward circuit. Moreover, decreased left NAc-bilateral MPFC connectivity can be deemed as a potential biomarker to differentiate OCD from HCs with a sensitivity of 80.00% and a specificity of 76.32%. Conclusion: The current results emphasize the importance of the reward circuit in the pathogenesis of OCD.

Altered Functional Connectivity Strength at Rest in Medication-Free Obsessive-Compulsive Disorder.

Background: Previous studies explored the whole-brain functional connectome using the degree approach in patients with obsessive-compulsive disorder (OCD). However, whether the altered degree values can be used to discriminate OCD from healthy controls (HCs) remains unclear. Methods: A total of 40 medication-free patients with OCD and 38 HCs underwent a resting-state functional magnetic resonance imaging (rs-fMRI) scan. Data were analyzed with the degree approach and a support vector machine (SVM) classifier. Results: Patients with OCD showed increased degree values in the left thalamus and left cerebellum Crus I and decreased degree values in the left dorsolateral prefrontal cortex, right precuneus, and left postcentral gyrus. SVM classification analysis indicated that the increased degree value in the left thalamus is a marker of OCD, with an acceptable accuracy of 88.46%, sensitivity of 87.50%, and specificity of 89.47%. Conclusion: Altered degree values within and outside the cortical-striatal-thalamic-cortical (CSTC) circuit may cocontribute to the pathophysiology of OCD. Increased degree values of the left thalamus can be used as a future marker for OCD understanding-classification.

Genome-Wide Identification and Characterization of Wheat 14-3-3 Genes Unravels the Role of TaGRF6-A in Salt Stress Tolerance by Binding MYB Transcription Factor.

14-3-3 proteins are a large multigenic family of general regulatory factors (GRF) ubiquitously found in eukaryotes and play vital roles in the regulation of plant growth, development, and response to stress stimuli. However, so far, no comprehensive investigation has been performed in the hexaploid wheat. In the present study, A total of 17 potential 14-3-3 gene family members were identified from the Chinese Spring whole-genome sequencing database. The phylogenetic comparison with six 14-3-3 families revealed that the majority of wheat 14-3-3 genes might have evolved as an independent branch and grouped into ε and non-ε group using the phylogenetic comparison. Analysis of gene structure and motif indicated that 14-3-3 protein family members have relatively conserved exon/intron arrangement and motif composition. Physical mapping showed that wheat 14-3-3 genes are mainly distributed on chromosomes 2, 3, 4, and 7. Moreover, most 14-3-3 members in wheat exhibited significantly down-regulated expression in response to alkaline stress. VIGS assay and protein-protein interaction analysis further confirmed that TaGRF6-A positively regulated slat stress tolerance by interacting with a MYB transcription factor, TaMYB64. Taken together, our findings provide fundamental information on the involvement of the wheat 14-3-3 family in salt stress and further investigating their molecular mechanism.

Abnormal structure and function of white matter in obsessive-compulsive disorder.

BACKGROUND: Abnormal structure and function of gray matter (GM) have been discovered in the cortico-striatal-thalamic-cortical (CSTC) circuit in obsessive-compulsive disorder (OCD). The GM structure and function may be influenced by the structure and function of the white matter (WM). Therefore, it is crucial to explore the characteristics of WM in OCD. METHODS: Diffusion tensor imaging and resting-state functional magnetic resonance imaging data of 52 patients with OCD and 39 healthy controls (HCs) were collected. The tract-based spatial statistics, amplitude of low-frequency fluctuations (ALFF), and structural-functional coupling approaches were utilized to explore the WM structure and function. Furthermore, the relationship between the abnormal WM structure and function and clinical symptoms of OCD was investigated using Pearson's correlation. Support vector machine was performed to evaluate whether patients with OCD could be identified with the changed WM structure and function. RESULTS: Compared to HCs, the lower fractional anisotropy (FA) values of four clusters including the superior corona radiata, anterior corona radiata, right superior longitudinal fasciculus, corpus callosum, left posterior corona radiata, fornix, and the right anterior limb of internal capsule, reduced ALFF/FA ratio in the left anterior thalamic radiation (ATR), and the decreased functional connectivity between the left ATR and the left dorsal lateral prefrontal cortex within CSTC circuit at rest were observed in OCD. The decreased ALFF/FA ratio in the left ATR negatively correlated with Yale-Brown Obsessive-Compulsive Scale obsessive thinking scores and Hamilton Anxiety Rating Scale scores in OCD. Furthermore, the features that combined the abnormal WM structure and function performed best in distinguishing OCD from HCs with the appropriate accuracy (0.80), sensitivity (0.82), as well as specificity (0.80). CONCLUSION: Current research discovered changed WM structure and function in OCD. Furthermore, abnormal WM structural-functional coupling may lead to aberrant GM connectivity within the CSTC circuit at rest in OCD. TRIAL REGISTRATION: Study on the mechanism of brain network in obsessive-compulsive disorder with multi-model magnetic resonance imaging (ChiCTR-COC-17013301).

Two multimodal neuroimaging subtypes of obsessive-compulsive disorder disclosed by semi-supervised machine learning.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a highly heterogeneous mental condition with a diverse symptom. Existing studies classified OCD on the basis of conventional phenomenology-based taxonomy ignoring the fact that the same subtype identified in accordance with clinical symptom may have different mechanisms and treatment responses. METHODS: This research involved 50 medicine-free patients with OCD and 50 matched healthy controls (HCs). All the participants were subjected to structural and functional magnetic resonance imaging (MRI). Voxel-based morphometry (VBM) and amplitude of low frequency fluctuation (ALFF) were used to evaluate gray matter volume (GMV) and spontaneous neuronal activities at rest respectively. Similarity network fusion (SNF) was utilized to integrate GMVs and spontaneous neuronal activities, and heterogeneity by discriminant analysis was applied to characterise OCD subtypes. RESULTS: Two OCD subtypes were identified: Subtype 1 exhibited decreased GMVs (i.e., left inferior temporal gyrus, right supplementary motor area and right lingual gyrus) and increased ALFF value (i.e., right orbitofrontal cortex), whereas subtype 2 exhibited increased GMVs (i.e., left cuneus, right precentral gyrus, left postcentral gyrus and left hippocampus) and decreased ALFF value (i.e., right caudate nucleus). Furthermore, the altered GMVs was negatively correlated with abnormal ALFF values in both subtype 1 and 2. LIMITATIONS: This study requires further validation via a larger, independent dataset and should consider the potential influences of psychotropic medication on OCD patients' brain activities. CONCLUSIONS: Results revealed two reproducible subtypes of OCD based on underlying multimodal neuroimaging and provided new perspectives on the classification of OCD.

Phylogenomic analysis of phenylalanine ammonia-lyase (PAL) multigene family and their differential expression analysis in wheat (Triticum aestivum L.) suggested their roles during different stress responses.

Phenylalanine ammonia-lyase (PAL) is a key enzyme in the phenylalanine metabolism pathway and plays an important role in plant growth and stress response. It has been widely reported in plants, but less studied in wheat. In this study, 54 PAL genes were identified in the wheat genome. Based on phylogenetic analysis, the 54 TaPAL genes were divided into four groups (I, II, III, and IV). Then, the expression levels of TaPALs under biotic stresses were analyzed by transcriptome data analysis. The results showed that 31 genes were up-regulated and one gene was down-regulated after inoculation with Fusarium graminearum, 11 genes were up-regulated and 14 genes were down-regulated after inoculation with Puccinia striiformis, and 32 up-regulated and three down-regulated genes after inoculation with powdery mildew. The expression patterns of the five TaPALs were further analyzed by qRT-PCR. After inoculation with F. graminearum, the expression levels of five TaPALs were up-regulated. However, the TaPALs (expect TaPAL49) were down-regulated when inoculated with P. striiformis. Finally, the functions of TaPAL32 and TaPAL42 in resistance of wheat to the stripe rust were further analyzed by virus induced gene silencing (VIGS) assays. The results showed that the disease severity of TaPAL32 and TaPAL42 silenced plants was higher than that of control plants at 14 days after inoculation. It indicated that these two genes played a positive role in wheat stripe rust resistance. This study provided new evidence support for the functional study of PAL genes in wheat, and provided potential application value for the breeding of wheat resistant varieties.

Genome-wide identification of long intergenic non-coding RNAs for Ralstonia solanacearum resistance in tomato (Solanum lycopersicum).

There is growing evidences indicating that long intergenic ncRNAs (lincRNAs) play key roles in plant development and stress responses. To research tomato lincRNA functions during the interaction between tomato and Ralstonia solanacearum, RNA-seq data of tomato plants inoculated with R. solanacearum was analyzed. In this study, 315 possible lincRNAs were identified from RNA-seq data. Then 23 differentially expressed lincRNAs between tomato plants inoculated with R. solanacearum and control were identified and a total of 171 possible target genes for these differentially expressed lincRNAs were predicted. Through GO and KEGG analysis, we found that lincRNA might be involved in jasmonic acid and ethylene signaling pathways to respond to tomato bacterial wilt infection. Furthermore, lincRNA may also be involved in regulating the expression of AGO protein. Subsequently, analysis of expression patterns between differentially expressed lincRNAs and adjacent mRNAs by qRT-PCR revealed that part of lincRNAs and their possible target genes exhibited positive correlation. Taken together, these results suggest that lincRNAs play potential roles in tomato against R. solanacearum infection and will provide fundamental information about the lincRNA-based plant defense mechanisms.

Altered Regional Activity and Network Homogeneity within the Fronto-Limbic Network at Rest in Medicine-Free Obsessive-Compulsive Disorder.

Functional abnormalities in brain areas within the fronto-limbic network have been widely reported in obsessive-compulsive disorder (OCD). However, region- and network-level brain activities of the fronto-limbic network at rest have not been simultaneously investigated in OCD. In this study, 40 medicine-free and non-comorbidity patients with OCD and 38 age-, education-, and gender-matched healthy controls (HCs) underwent a resting-state functional magnetic-resonance-imaging scan. Fractional amplitude of low-frequency fluctuations (fALFF), network homogeneity (NH), and support vector machine were used to analyze the data. Patients with OCD showed increased fALFF in the right orbital frontal cortex (OFC), increased NH in the left OFC, and decreased NH in the right putamen. Decreased NH of the right putamen was negatively correlated with the Y-BOCS total and compulsive behavior scores. Furthermore, a combination of NH in the left OFC and right putamen could be applied to differentiate OCD from HCs with optimum specificity and sensitivity. The current findings emphasize the crucial role of the fronto-limbic network in the etiology of OCD.

Genome-wide identification of ZF-HD gene family in Triticum aestivum: Molecular evolution mechanism and function analysis.

ZF-HD family genes play important roles in plant growth and development. Studies about the whole genome analysis of ZF-HD gene family have been reported in some plant species. In this study, the whole genome identification and expression profile of the ZF-HD gene family were analyzed for the first time in wheat. A total of 37 TaZF-HD genes were identified and divided into TaMIF and TaZHD subfamilies according to the conserved domain. The phylogeny tree of the TaZF-HD proteins was further divided into six groups based on the phylogenetic relationship. The 37 TaZF-HDs were distributed on 18 of 21 chromosomes, and almost all the genes had no introns. Gene duplication and Ka/Ks analysis showed that the gene family may have experienced powerful purification selection pressure during wheat evolution. The qRT-PCR analysis showed that TaZF-HD genes had significant expression patterns in different biotic stress and abiotic stress. Through subcellular localization experiments, we found that TaZHD6-3B was located in the nucleus, while TaMIF4-5D was located in the cell membrane and nucleus. Our research contributes to a comprehensive understanding of the TaZF-HD family, provides a new perspective for further research on the biological functions of TaZF-HD genes in wheat.

Disrupted Asymmetry of Inter- and Intra-Hemispheric Functional Connectivity at Rest in Medication-Free Obsessive-Compulsive Disorder.

Disrupted functional asymmetry of cerebral hemispheres may be altered in patients with obsessive-compulsive disorder (OCD). However, little is known about whether anomalous brain asymmetries originate from inter- and/or intra-hemispheric functional connectivity (FC) at rest in OCD. In this study, resting-state functional magnetic resonance imaging was applied to 40 medication-free patients with OCD and 38 gender-, age-, and education-matched healthy controls (HCs). Data were analyzed using the parameter of asymmetry (PAS) and support vector machine methods. Patients with OCD showed significantly increased PAS in the left posterior cingulate cortex, left precentral gyrus/postcentral gyrus, and right inferior occipital gyrus and decreased PAS in the left dorsolateral prefrontal cortex (DLPFC), bilateral middle cingulate cortex (MCC), left inferior parietal lobule, and left cerebellum Crus I. A negative correlation was found between decreased PAS in the left DLPFC and Yale-Brown Obsessive-compulsive Scale compulsive behavior scores in the patients. Furthermore, decreased PAS in the bilateral MCC could be used to distinguish OCD from HCs with a sensitivity of 87.50%, an accuracy of 88.46%, and a specificity of 89.47%. These results highlighted the contribution of disrupted asymmetry of intra-hemispheric FC within and outside the cortico-striato-thalamocortical circuits at rest in the pathophysiology of OCD, and reduced intra-hemispheric FC in the bilateral MCC may serve as a potential biomarker to classify individuals with OCD from HCs.