Regional Function Research Articles

Identification and Functional Study of Enhancers of EYA1: The Causative Gene of Branchio-Oto-Renal Syndrome

Introduction: Branchio-oto-renal syndrome (BOR syndrome) is a rare genetic disorder with an incidence of 1 in 40,000, affecting the development of multiple organs, including the branchio, ear, and kidney. It is responsible for 2% of childhood deafness. Currently, variants in the coding regions of the main causative genes, such as EYA1, SIX1, and SIX5, explain only half of the disease’s etiology. Therefore, there is a need to explore the non-coding regions, which constitute the majority of the genome, especially the regulatory regions, as potential new causative factors. Method: In this study, we focused on the EYA1 gene, which accounts for over 40% of BOR syndrome cases, and conducted a screening of candidate enhancers within a 250-kb region upstream and downstream of the gene using comparative genomics. We characterized the enhancer activities of these candidates in zebrafish using the Tol2 transposon system. Results: Our findings revealed that out of the 11 conserved non-coding elements (CNEs) examined, four exhibited enhancer activity. Notably, CNE16.39 and CNE16.45 displayed tissue-specific enhancer activity in the ear. CNE16.39 required the full-length 206 bp sequence for inner-ear-specific expression, while the core functional region of CNE16.45 was identified as 136 bp. Confocal microscopy results demonstrated that both CNE16.39 and CNE16.45 drove the expression of GFP in the sensory region of the crista of the inner ear in zebrafish, consistent with the expression pattern of eya1. Conclusion: This study contributes to the understanding of the regulatory network governing EYA1 expression and offers new insights to further clarify the pathogenic role of EYA1 in BOR syndrome.

Effect of sourdough addition on gluten‐free sorghum bread fortified with plant‐based protein and dietary fiber: Functional, textural, and structural properties

AbstractBackground and ObjectivesThe production of high‐quality gluten‐free bread still poses a major technological challenge. The objective of this study was to investigate the effects of sourdough fermentation and structural/nutritional enrichment on gluten‐free sorghum bread quality. Lactic acid bacteria (Lactobacillus casei and Lactobacillus acidophilus) and yeast (Saccharomyces cerevisiae) were used as starter cultures.FindingsThe bread crust color and titratable acidity were comparable; although, the crumb color of sourdough bread made with L. acidophilus was measured darker. In both starter cultures, sourdough bread had a softer texture than the control, with significant (p < .05) differences in hardness, adhesiveness, cohesiveness, and gumminess values. The sourdough bread showed similar Fourier Transformed Infraredtransformed infrared (FTIR) spectra with the control bread, with four major peaks in the functional group region (4000–1200 cm−1) and a unique peak in the fingerprint region (1200–600 cm−1).ConclusionBreads made with L. acidophilus (at 20% and 30% addition levels) showed better quality attributes such as softer texture, higher total phenolic content (97.75 mg GAE/100 g), and antioxidant capacity (341.49 µmol TEAC/100 g).Significance and NoveltyThe results suggested that selected lactic acid bacteria‐based sorghum sourdough might be a promising ingredient for the development of gluten‐free bread with improved quality and nutritional value.

Investigation of causal relationships between cortical structure and osteoporosis using two-sample Mendelian randomization.

The mutual interaction between bone characteristics and brain had been reported previously, yet whether the cortical structure has any relevance to osteoporosis is questionable. Therefore, we applied a two-sample bidirectional Mendelian randomization analysis to investigate this relationship. We utilized the bone mineral density measurements of femoral neck (n = 32,735) and lumbar spine (n = 28,498) and data on osteoporosis (7300 cases and 358,014 controls). The global surficial area and thickness and 34 specific functional regions of 51,665 patients were screened by magnetic resonance imaging. For the primary estimate, we utilized the inverse-variance weighted method. The Mendelian randomization-Egger intercept test, MR-PRESSO, Cochran's Q test, and "leave-one-out" sensitivity analysis were conducted to assess heterogeneity and pleiotropy. We observed suggestive associations between decreased thickness in the precentral region (OR = 0.034, P = 0.003) and increased chance of having osteoporosis. The results also revealed suggestive causality of decreased bone mineral density in femoral neck to declined total cortical surface area (β = 1400.230mm2, P = 0.003), as well as the vulnerability to osteoporosis and reduced thickness in the Parstriangularis region (β = -0.006mm, P = 0.002). Our study supports that the brain and skeleton exhibit bidirectional crosstalk, indicating the presence of a mutual brain-bone interaction.

Inter-individual, hemispheric and sex variability of brain activations during numerosity processing

Numerosity perception is a fundamental and innate cognitive function shared by both humans and many animal species. Previous research has primarily focused on exploring the spatial and functional consistency of neural activations that were associated with the processing of numerosity information. However, the inter-individual variability of brain activations of numerosity perception remains unclear. In the present study, with a large-sample functional magnetic resonance imaging (fMRI) dataset (n = 460), we aimed to localize the functional regions related to numerosity perceptions and explore the inter-individual, hemispheric, and sex differences within these brain regions. Fifteen subject-specific activated regions, including the anterior intraparietal sulcus (aIPS), posterior intraparietal sulcus (pIPS), insula, inferior frontal gyrus (IFG), inferior temporal gyrus (ITG), premotor area (PM), middle occipital gyrus (MOG) and anterior cingulate cortex (ACC), were delineated in each individual and then used to create a functional probabilistic atlas to quantify individual variability in brain activations of numerosity processing. Though the activation percentages of most regions were higher than 60%, the intersections of most regions across individuals were considerably lower, falling below 50%, indicating substantial variations in brain activations related to numerosity processing among individuals. Furthermore, significant hemispheric and sex differences in activation location, extent, and magnitude were also found in these regions. Most activated regions in the right hemisphere had larger activation volumes and activation magnitudes, and were located more lateral and anterior than their counterparts in the left hemisphere. In addition, in most of these regions, males displayed stronger activations than females. Our findings demonstrate large inter-individual, hemispheric, and sex differences in brain activations related to numerosity processing, and our probabilistic atlas can serve as a robust functional and spatial reference for mapping the numerosity-related neural networks.

Digital metamaterials with nanoscale silicon/Sb2Se3 pixels for reconfigurable integrated mode converters

Waveguide-integrated reconfigurable nanophotonic devices are of importance for on-chip all-optical connection and flexible photonic circuits. In this paper, we propose inversely designed reconfigurable TE0-to-TE1 and TE0-to-TE2 mode converters based on digital metamaterials consisting of nanoscale silicon and non-loss phase change material Sb2Se3 pixels. The design strategy combines finite element method, density method and method of moving asymptotes. Only 73 and 56 optimization iterations are taken to obtain the optimal digital metamaterials for targeted mode conversions. The footprints of ultra-compact functional regions are 0.92 and 1.04 square center wavelengths, respectively. TE0-to-TE1 and TE0-to-TE2 mode conversions with high transmission efficiency and output mode purity are realized with crystalline Sb2Se3, while TE0 mode directly pass through with amorphous Sb2Se3. Meanwhile, by cascading these two mode converters, TE1-to-TE2 mode conversion is achieved as well. Moreover, the robustness of these designs is demonstrated by introducing random wrong pixels.

Phytomedicine Fructus Aurantii-derived two absorbed compounds unlock antidepressant and prokinetic multi-functions via modulating 5-HT3/GHSR

Ethnopharmacological relevanceFructus Aurantii (FA), a well-known phytomedicine, has been employed to evoke antidepressant and prokinetic multi-functions. Therein, systematically identifying bioactive components and the referred mechanism is essential for FA. Aim of the studyThis study was planned to answer “2 W” (What and Why), such as which components and pathways contribute to FA's multi-functions. We aimed to identify bioactive compounds as the key for opening the lock of FA's multi-functions, and the molecule mechanisms are their naturally matched lock cylinder. Materials and methodsThe phytochemical content of FA extract was determined, and the compounds were identified in rats pretreated with FA using liquid chromatography with mass spectrometry (LC-MS). The contribution strategy was used to assess bioactive compounds’ efficacy (doses = their content in FA) in model rats with the mechanism. The changes in functional brain regions were determined via 7.0 T functional magnetic resonance imaging-blood oxygen level-dependent (fMRI-BOLD). ResultEight phytochemicals’ content was detected, and merely six components were identified in rats in vivo. Meranzin hydrate + hesperidin (MH), as the primary contributor of FA, exerted antidepressant and prokinetic effects (improvement of indexes for immobility time, gastric emptying, intestinal transit, CRH, ghrelin, ACTH, DA, NA, 5-HT, CORT, and 5-HT3) by regulating 5-HT3/Growth hormone secretagogue receptor (GHSR) pathway. These results were validated by 5-HT2A, 5-HT3, and GHSR receptor antagonists combined with molecule docking. MH restored the excessive BOLD activation of the left accumbens nucleus, left corpus callosum and hypothalamus preoptic region. ConclusionAbsorbed MH accounts for FA's anti-depressant and prokinetic efficacy in acutely-stressed rats, primarily via 5-HT3/GHSR shared regulation.

Multi-Granularity Graph Convolution Network for Major Depressive Disorder Recognition.

Major depressive disorder (MDD) is the most common psychological disease. To improve the recognition accuracy of MDD, more and more machine learning methods have been proposed to mining EEG features, i.e. typical brain functional patterns and recognition methods that are closely related to depression using resting EEG signals. Most existing methods typically utilize threshold methods to filter weak connections in the brain functional connectivity network (BFCN) and construct quantitative statistical features of brain function to measure the BFCN. However, these thresholds may excessively remove weak connections with functional relevance, which is not conducive to discovering potential hidden patterns in weak connections. In addition, statistical features cannot describe the topological structure features and information network propagation patterns of the brain's different functional regions. To solve these problems, we propose a novel MDD recognition method based on a multi-granularity graph convolution network (MGGCN). On the one hand, this method applies multiple sets of different thresholds to build a multi-granularity functional neural network, which can remove noise while fully retaining valuable weak connections. On the other hand, this method utilizes graph neural network to learn the topological structure features and brain saliency patterns of changes between brain functional regions on the multi-granularity functional neural network. Experimental results on the benchmark datasets validate the superior performance and time complexity of MGGCN. The analysis shows that as the granularity increases, the connectivity defects in the right frontal(RF) and right temporal (RT) regions, left temporal(LT) and left posterior(LP) regions increase. The brain functional connections in these regions can serve as potential biomarkers for MDD recognition.

Small secreted effector protein from Fusarium sacchari suppresses host immune response by inhibiting ScPi21-induced cell death.

Fusarium sacchari is one of the primary pathogens causing pokkah boeng disease, which impairs the yield and quality of sugarcane around the world. Understanding the molecular mechanisms of the F. sacchari effectors that regulate plant immunity is of great importance for the development of novel strategies for the persistent control of pokkah boeng disease. In a previous study, Fs00367 was identified to inhibit BAX-induced cell death. In this study, Fs00367nsp (without signal peptide) was found to suppress BAX-induced cell death, reactive oxygen species bursts and callose accumulation. The amino acid region 113-142 of Fs00367nsp is the functional region. Gene mutagenesis indicated that Fs00367 is important for the full virulence of F. sacchari. Ayeast two-hybrid assay revealed an interaction between Fs00367nsp and sugarcane ScPi21 in yeast that was further confirmed using bimolecular fluorescence complementation, pull-down assay and co-immunoprecipitation. ScPi21 can induce plant immunity, but this effect could be blunted by Fs00367nsp. These results suggest that Fs00367 is a core pathogenicity factor that suppresses plant immunity through inhibiting ScPi21-induced cell death. The findings of this study provide new insights into the molecular mechanisms of effectors in regulating plant immunity.

A multi-objective site selection of electric vehicle charging station based on NSGA-II

The planning of charging infrastructure is crucial to developing electric vehicles. Planning for charging stations requires considering several variables, including building costs, charging demand, and coverage levels. It might be advantageous to use a multi-objective optimization method based on the NSGA-II. We need to address the current problems in choosing the location of electric vehicle charging stations. Firstly, urban land use is divided into five functional areas, and the TF-IDF algorithm is applied to the division of functional areas. A combined clustering algorithm is proposed to cluster POIs in functional areas into several clusters and determine the cluster centers as charging demand points. We Analyze charging practices and travel patterns of electric car users, fit the charging likelihood of various functional regions, and calculate the charging demand of each charging demand point in the study area. Introduce the NSGA-II algorithm and consider the charging station's progressive coverage to fit the actual area covered by the charging station.Taking the maximization of system benefits and the maximization of the minimum coverage level as the optimization objectives to carry out multi-objective optimization. Finally, we take the charging station planning in the urban area of Hohhot as an example and provide different site selection planning schemes. The planning schemes for different numbers of charging stations are analyzed to obtain a charging station planning scheme that takes into account both objectives.

Causal associations between chronic heart failure and the cerebral cortex: results from Mendelian randomization study and integrated bioinformatics analysis.

Chronic heart failure (CHF) patients exhibit alterations in cerebral cortical structure and cognitive function. However, the mechanisms by which CHF affects cortical structure and functional regions remain unknown. This study aims to investigate potential causal relationship between CHF and cerebral cortical structure through Mendelian randomization (MR). The research utilized genome-wide association studies (GWAS) to explore the causal association between CHF and cerebral cortical structure. The results were primarily analyzed using the inverse-variance weighted (IVW). The reliability of the data was verified through horizontal pleiotropy and heterogeneity analysis by MR-Egger intercept test and Cochran's Q-test, respectively. Replication analysis was conducted in the Integrative Epidemiology Unit (IEU) OpenGWAS project for further validation. In addition, we collected mediator genes that mediate causality to reveal potential mechanisms. Integrated bioinformatics analysis was conducted using the Open Target Genetics platform, the STRING database, and Cytoscape software. The IVW results did not reveal any significant causal association between genetically predicted CHF and the overall structure of the cerebral cortex or the surface area (SA) of the 34 functional regions of the cerebral cortex (P > 0.05). However, the results revealed that CHF increased the thickness (TH) of pars opercularis (IVW: β = 0.015, 95% CI: 0.005-0.025, P = 3.16E-03). Replication analysis supported the causal association between CHF and pars opercularis TH (IVW: β = 0.02, 95% CI: 0.010-0.033, P = 1.84E-04). We examined the degree centrality values of the top 10 mediator genes, namely CDKN1A, CELSR2, NME5, SURF4, PSMA5, TSC1, RPL7A, SURF6, PRDX3, and FTO. Genetic evidence indicates a positive correlation between CHF and pars opercularis TH.

Systematic functional interrogation of genome-wide association studies locus 17p13.3 deciphered role and genetic control of FAM57A in colorectal cancer development.

Genome-wide association studies (GWAS) have identified over 150 risk loci linked to colorectal cancer (CRC), including the 17p13.3 locus with the tag single nucleotide polymorphism (SNP) rs12603526 in the Asian population. However, the specific causal gene and the functional regulatory mechanisms in this region remain unresolved, necessitating further investigation to elucidate the underlying mechanisms of CRC. We employed an RNA interference-based functional approach to identify genes critical for CRC cell proliferation at the GWAS locus 17p13.3. Bioinformatic fine-mapping analysis was conducted to prioritize causal variants. A large-scale study involving 7,013 cases and 7,329 controls from a Chinese population, along with another cohort of 5,158 cases and 20,632 controls from the UK Biobank, was performed to validate the association between the candidate variant and the gene. A series of biological experiments was conducted to explore the function of the candidate gene and its regulatory mechanisms. We identified FAM57A as a key oncogene that promotes CRC cell proliferation, and confirmed its carcinogenic role through in vitro proliferation assays. The variant rs526835 was prioritized as a causal candidate for CRC risk, located in a functional region with enhancer properties, and showed a significant quantitative association with FAM57A expression. The rs526835 [T] variant was associated with a 1.17-fold increase in CRC risk [95% confidence interval (95% CI): 1.11-1.23, P=1.23×10-9] in the large-scale Chinese cohort, which was further corroborated in the UK Biobank cohort. Mechanistically, we demonstrated that rs526835 enhances a promoter-enhancer interaction mediated by the transcription factor JUN, leading to increased expression of FAM57A. We reveal the underlying mechanisms of CRC predisposition at the GWAS locus 17p13.3. Additionally, our findings highlight the critical role of FAM57A in CRC pathogenesis and introduce a novel enhancer-promoter interaction between FAM57A and rs526835, which could inform future precision prevention and personalized cancer therapies.

Efficacy and safety of deep brain stimulation in mesencephalic locomotor region for motor function in patients with post-stroke hemiplegia: a study protocol for a multi-center double-blind crossover randomized controlled trial.

Deep brain stimulation (DBS) is a potential treatment for improving movement disorder. However, few large-sample studies can reveal its efficacy and safety. This study aims to initially explore the efficacy and safety of DBS in the mesencephalic locomotor region (MLR) on motor function in patients with post-stroke hemiplegia. This multicenter, prospective, double-blind, randomized crossover clinical trial aims to assess the safety and effectiveness of Deep Brain Stimulation (DBS) in the mesencephalic locomotor region (MLR) for patients with moderate to severe post-stroke hemiplegia. Sixty-two patients with stable disease after a year of conservative treatment will be enrolled and implanted with deep brain electrodes. Post-surgery, patients will be randomly assigned to either the DBS group or the control group, with 31 patients in each. The DBS group will receive electrical stimulation 1 month later, while the control group will undergo sham stimulation. Stimulation will be discontinued after 3 and 6 months, followed by a 2-week washout period. Subsequently, the control group will receive electrical stimulation, while the DBS group will undergo sham stimulation. Both groups will resume electrical stimulation at the 9th and 12th-month follow-ups. Post-12-month follow-up, motor-related scores will be collected for analysis, with the Fugl-Meyer Assessment Upper Extremity Scale (FMA-UE) as the primary metric. Secondary outcomes include balance function, neuropsychiatric behavior, fall risk, daily living activities, and quality of life. This study aims to provide insights into the therapeutic benefits of DBS for post-stroke hemiplegia patients. We proposed this study for the first time to comprehensively explore the effectiveness and safety of DBS in improving motor function for post-stroke hemiplegia, and provide evidence for DBS in the treatment of post-stroke hemiplegia. Study limitations are related to the small sample size and short study period. Clinicaltrials.gov, identifier NCT05968248.

Examining the influence of child nutritional disorders on early childhood development in Bangladesh: insights from the multiple indicator cluster survey.

The objective of this study was to explore the relationship between various forms of child nutritional disorders and early childhood development in Bangladesh. We analysed data from the nationally representative cross-sectional 2019 Multiple Indicator Cluster Survey. Early childhood development was evaluated using the Early Childhood Development Index (ECDI), which comprised 10 yes-or-no questions across four domains: literacy-numeracy, physical well-being, socio-emotional development, and learning abilities. Nutritional disorders (e.g. stunting, wasting, and underweight) were measured based on the World Health Organization's height and weight guidelines. To investigate the relationships between child development and nutritional disorders, we used multilevel logistic regression models. Bangladesh. Data of 9,455 children aged 3 and 4 years. Approximately 38 % of the children analysed experienced a nutritional disorder, with stunting being the most prevalent at 28·15 %. Overall, 25·27 % did not meet expected developmental progress measured by the ECDI. Stunted children were more likely to be off track developmentally, while those without any nutritional disorder were more likely to be on track. Socio-demographic factors, including age, sex, attendance in early childhood education programme, maternal education, maternal functional difficulties, region, and income, were identified as determinants of ECDI. Childhood nutrition and socio-demographic factors significantly affect multiple developmental domains and overall ECDI among children aged 3-4 years. Prioritising policies and programmes that improve nutrition and address these determinants are crucial for fostering optimal development in children.

Mapping the landscape of HPV integration and characterising virus and host genome interactions in HPV-positive oropharyngeal squamous cell carcinoma.

Human papillomavirus (HPV) integration into the host genome is an important factor in HPV(+)OPSCC carcinogenesis, in conjunction with HPV oncoproteins E6/E7. However, a well-studied investigation about virus-host interaction still needs to be completed. Our objective is to characterise HPV integration to investigate potential mechanisms of tumourigenesis independent of E6/E7 oncoproteins. High-throughput viral integration detection was performed on 109 HPV(+)OPSCC tumours with relevant clinicopathological information. Of these tumours, 38 tumours underwent targeted gene sequencing, 29 underwent whole exome sequencing and 26 underwent RNA sequencing. HPV integration was detected in 94% of tumours (with a mean integration count of 337). Tumours occurring at the tonsil/oropharyngeal wall that exhibit higher PD-L1 expression demonstrated increased integration sites (p=.024). HPV exhibited a propensity for integration at genomic sites located within specific fragile sites (FRA19A) or genes associated with functional roles such as cell proliferation and differentiation (PTEN, AR), immune evasion (CD274) and glycoprotein biosynthesis process (FUT8). The viral oncogenes E2, E4, E6 and E7 tended to remain intact. HPV fragments displayed enrichment within host copy number variation (CNV) regions. However, insertions into genes related to altered homologous recombination repair were infrequent. Genes with integration had distinct expression levels. Fifty-nine genes whose expression level was affected by viral integration were identified, for example, EPHB1, which was reported to be involved in cellular protein metabolic process. HPV can promote oncogenesis through recurrent integration into functional host genome regions, leading to subsequent genomic aberrations and gene expression disruption. This study characterises viral integrations and virus-host interactions, enhancing our understanding of HPV-related carcinogenesis mechanisms.

Mechanism of drug resistance in HIV-1 protease subtype C in the presence of Atazanavir

AIDS is one of the deadliest diseases in the history of humankind caused by HIV. Despite the technological development, curtailing the viral infection inside human host still remains a challenge. Therapies such as HAART uses a combination of drugs to inhibit the viral activity. One of the important targets includes HIV protease and inhibiting its activity will minimize the production of mature structural proteins. However, the genetic diversity and the occurrence of drug resistant mutations adds complexity to effective drug design. In this study, we aimed at understanding the drug binding mechanism of one such subtype, namely subtype C and its insertion variant L38HL. We performed multiple molecular dynamics simulations along with binding free energy analysis of wild-type and L38HL bound to Atazanavir (ATV). From the analysis, we revealed that the insertion alters the hydrogen bond and hydrophobic interaction networks. The alterations in the interaction networks increase flexibility at the hinge-fulcrum interface. Further, the effects of these changes affect flap tip curling. Moreover, the changes in the hinge-fulcrum-cantilever interface alters the concerted motion of the functional regions leading to change in the direction of flap movement thus causing a subtle change in the active site volume. Additionally, formation of intramolecular hydrogen bonds in the ATV docked to L38HL restricted the movement of R1 and R2 groups thereby altering the interactions. Overall, the changes in the flexibility of flap together with the changes in the active site volume and compactness of the ligand provide insights for increased binding affinity of ATV with L38HL.

Hierarchical Dynamic Graph Convolutional Network With Interpretability for EEG-Based Emotion Recognition.

Graph convolutional networks (GCNs) have shown great prowess in learning topological relationships among electroencephalogram (EEG) channels for EEG-based emotion recognition. However, most existing GCN-only methods are designed with a single spatial pattern, lacking connectivity enhancement within local functional regions and ignoring the data dependencies of EEG original data. In this article, hierarchical dynamic GCN (HD-GCN) is proposed to explore dynamic multilevel spatial information among EEG channels, with discriminative features of EEG signals as auxiliary information. Specifically, representation learning in topological space consists of two branches: one for extracting global dynamic information and one for exploring augmentation information in local functional regions. In each branch, a layerwise adjacency matrix is utilized to enrich the expressive power of GCN. Furthermore, a data-dependent auxiliary information module (AIM) is developed to capture multidimensional fusion features. Extensive experiments on two public datasets, SJTU emotion EEG dataset (SEED) and DREAMER, demonstrate that the proposed method consistently exceeds state-of-the-art methods. Interpretability analysis of the proposed model is performed, discovering the active brain regions and important electrode pairs related to emotion.

Unsupervised Joint Domain Adaptation for Decoding Brain Cognitive States From tfMRI Images.

Recent advances in large model and neuroscience have enabled exploration of the mechanism of brain activity by using neuroimaging data. Brain decoding is one of the most promising researches to further understand the human cognitive function. However, current methods excessively depends on high-quality labeled data, which brings enormous expense of collection and annotation of neural images by experts. Besides, the performance of cross-individual decoding suffers from inconsistency in data distribution caused by individual variation and different collection equipments. To address mentioned above issues, a Join Domain Adapative Decoding (JDAD) framework is proposed for unsupervised decoding specific brain cognitive state related to behavioral task. Based on the volumetric feature extraction from task-based functional Magnetic Resonance Imaging (tfMRI) data, a novel objective loss function is designed by the combination of joint distribution regularizer, which aims to restrict the distance of both the conditional and marginal probability distribution of labeled and unlabeled samples. Experimental results on the public Human Connectome Project (HCP) S1200 dataset show that JDAD achieves superior performance than other prevalent methods, especially for fine-grained task with 11.5%-21.6% improvements of decoding accuracy. The learned 3D features are visualized by Grad-CAM to build a combination with brain functional regions, which provides a novel path to learn the function of brain cortex regions related to specific cognitive task in group level.

Chromatin binding protein HMGN1 promotes HBV cccDNA transcription and replication by regulating the phosphorylation of histone 3

Background and aimsDirect elimination of cccDNA remains a formidable obstacle due to the persistent and stable presence of cccDNA in hepatocyte nuclei. The silencing of cccDNA transcription enduringly is one of alternative strategies in the treatment of hepatitis B. Protein binding to cccDNA plays an important role in its transcriptional regulation; thus, the identification of key factors involved in this process is of great importance. Approaches and resultsIn the present study, high mobility group nucleosome binding domain 1 (HMGN1) was screened out based on our biotin-avidin enrichment system. First, chromatin immunoprecipitation and fluorescent in situ hybridization assays confirmed the binding of HMGN1 with cccDNA in the nucleus. Second, functional experiments in HBV-infected cells showed that the promoting effect of HMGN1 on HBV transcription and replication depended on the functional region of the nucleosomal binding domain, while transfection of the HMGN1 mutant showed no influence on HBV compared with the vector. Third, further mechanistic exploration revealed that the silencing of HMGN1 increased the level of phosphorylase CLK2 and promoted H3 phosphorylation causing the reduced accessibility of cccDNA. Moreover, silenced HMGN1 was mimicked in HBV (r) cccDNA mouse model of HBV infection in vivo. The results showed that silencing HMGN1 inhibited HBV replication in vivo. ConclusionsIn summary, our study identified that a host protein can bind to cccDNA and promote its transcription, providing a candidate strategy for anti-HBV targeting to interfere with the transcriptional activity of cccDNA microchromosomes.

A practical guide for combining functional regions of interest and white matter bundles.

Diffusion-weighted imaging (DWI) is the primary method to investigate macro- and microstructure of neural white matter in vivo. DWI can be used to identify and characterize individual-specific white matter bundles, enabling precise analyses on hypothesis-driven connections in the brain and bridging the relationships between brain structure, function, and behavior. However, cortical endpoints of bundles may span larger areas than what a researcher is interested in, challenging presumptions that bundles are specifically tied to certain brain functions. Functional MRI (fMRI) can be integrated to further refine bundles such that they are restricted to functionally-defined cortical regions. Analyzing properties of these Functional Sub-Bundles (FSuB) increases precision and interpretability of results when studying neural connections supporting specific tasks. Several parameters of DWI and fMRI analyses, ranging from data acquisition to processing, can impact the efficacy of integrating functional and diffusion MRI. Here, we discuss the applications of the FSuB approach, suggest best practices for acquiring and processing neuroimaging data towards this end, and introduce the FSuB-Extractor, a flexible open-source software for creating FSuBs. We demonstrate our processing code and the FSuB-Extractor on an openly-available dataset, the Natural Scenes Dataset.

Genetic Mapping of prod E.3.3 , a New Lethal Allele of prod.

The E.3.3 mutation was generated in a Flp/FRT EMS screen for conditional mutations that cause growth and developmental defects in a genetic background that blocks apoptosis. The mutations were conditional, based on the Dark 82 allele being present on the starting chromosome, and blocking canonical apoptosis in a homozygous state. The E.3.3 mosaic eyes exhibit defects in eye development including patches of rough eye and irregular surface structure. Whole Genome Sequencing and complementation mapping revealed E.3.3 as an allele of prod . Prod is a DNA-binding protein that binds satellite repeats and is involved in chromocenter formation during mitosis. Here we present a novel allele of prod , prod E.3.3 , that disrupts the functional region of the Prod protein resulting in disruption of typical eye structure, likely due to disruption of chromatid separation during development.