Spatial Regulation Research Articles

The stability of the Opi1p repressor for phospholipid biosynthetic gene expression in Saccharomyces cerevisiae is dependent on its interactions with Scs2p and Ino2p

The yeast Saccharomyces cerevisiae Opi1p negatively regulates phospholipid biosynthetic genes. Under derepressing conditions, Opi1p binds to the endoplasmic reticulum/nuclear membrane with the aid of the membrane protein Scs2p and phosphatidic acids under derepressing conditions. Under repressing conditions, it enters the nucleus to inhibit the positive transcription factors Ino2p and Ino4p. While the spatial regulation of Opi1p is understood, the regulation of its abundance remains unclear. We investigated the role of Scs2p and Ino2p in Opi1p stability by overexpressing these proteins in yeast cells. Opi1p was stable in the presence of Scs2p, but mutations in residues required for interaction with Scs2p caused Opi1p unstable. Even in the absence of Scs2p, Opi1p remained stable in the strain having a mutation to increase phosphatidic acid levels. Conversely, overproduction of Ino2p reduced Opi1p stability, whereas a mutant Ino2p that cannot interact with Opi1p did not. Additionally, Opi1p was stable in strains lacking Ino2p or with a mutated Ino2p-binding domain. These findings suggest that regulation, adding another layer to the regulation of phospholipid biosynthetic gene expression by Opi1p.

Multi-Objective Optimization of Urban Gas Station Site Selection Under Territorial Spatial Planning Constraints

The traditional process for selecting urban gas station sites often emphasizes economic benefits and return on investment, frequently overlooking mandatory and guiding constraints established by territorial spatial planning regulations. This neglect can compromise the effective layout and future growth of cities, potentially affecting their long-term development. To address this issue, this study develops a systematic framework for urban gas station site selection that integrates both mandatory and guiding constraints. By conducting detailed analyses of feasible construction areas and fuel demand, the framework quantifies relevant indicators and establishes a comprehensive index system for site selection. A multi-objective optimization model employing genetic algorithms was utilized to maximize fuel demand coverage, minimize inter-station redundancy, and achieve optimal site coverage. This framework was applied to the central urban area of Lishui City, China, as a case study. The site selection schemes achieved a coverage rate exceeding 90%, an inter-station redundancy rate around 30%, and a demand coverage rate surpassing 90%, optimizing the key objectives. Compared to traditional methods that often ignore territorial spatial planning constraints, this framework effectively avoids conflicts with urban planning and regulatory requirements. It enhances infrastructure coordination, supports environmental sustainability, and exhibits strong adaptability to diverse urban contexts, thus offering valuable support for practical decision-making.

Responsibility of Land Deed Officials: Implications of Legal Convergence on the Harmonization and Integration of Collateral Law and Telematics Law

The dynamics of the convergence of telematics law within the national legal system, notably in the area of land, are represented by the Minister of Agrarian Affairs and Spatial Planning's Regulation Number 5 of 2020, which also serves as the head of the National Land Agency. One of the effects of land digitization is the Ministerial Regulation, which has changed the mortgage rights registration process from a traditional system to an electronic or digital one. Despite being virtual, the digitalization of Mortgage Rights registration involves actual legal actions with clear legal ramifications. The Land Deed Official is directly involved in the electronic execution of Mortgage Rights, which is governed by the Regulation of the Minister of Agrarian Affairs and Spatial Planning / Head of the National Land Agency number 5 of 2020. The objective of this study is to investigate the consequences of the convergence of the Law on Mortgage Rights and the Telecommunication Law. This convergence results in the creation of digital-based Mortgage Rights via an integrated Electronic Mortgage Registration system, which is also known as the Electronic Mortgage System. The role and obligations of the Land Deed Official are also affected by this. This study employs a prescriptive, normative-juridical methodology. Based on the research findings, it is known that the conversion of the collateral registration system from a traditional system to a digital system is affected by the convergence of telematics legislation and the law of collateral guarantees. Because of the discord and breakdown of the Mortgage Law, the Electronic Information and Transactions Law, and the Regulations of the Land Deed Official, this also affects the status and legal obligations of the Land Deed Official, who fails to maintain the principle of justice..

Optimal planning of SOP in distribution network considering 5G BS collaboration

AbstractThe flexibility of soft open point (SOP) in spatial power regulation enhances the distribution network's (DN) integration of large‐scale renewable energy sources. However, the high cost of SOP and its limited capability for temporal power regulation impede its widespread adoption. Given the rapid expansion of 5G base stations (BSs), utilizing their energy storage to participate in DN planning and operation optimization provides a promising solution. Therefore, this paper proposes an optimal planning method of SOP in DN, considering collaborations with 5G BSs. The objective is to enhance DN’s power regulation in both temporal and spatial dimensions, while minimizing the investment cost of SOP and fully utilizing the unused capacity in base station energy storage (BSES). Firstly, the flexible regulation models of SOP and 5G BS are established, with the real‐time dispatchability of BSES formulated. Then, a bi‐level optimization model is proposed, where the planning layer aims to minimize the total cost, while the operational layer aims to decrease the average voltage deviation. Additionally, an improved Shapley value method based on interactive power is developed for benefit allocation, which enhances the engagement of 5G BSs to participate in DN regulation. The effectiveness of proposed method is validated by simulation results.

Brassinosteroid signaling represses ZINC FINGER PROTEIN11 to regulate ovule development in Arabidopsis.

Brassinosteroid (BR) signaling and the C-class MADS-box gene AGAMOUS (AG) play important roles in ovule development in Arabidopsis (Arabidopsis thaliana). However, how BR signaling integrates with AG functions to control the female reproductive process remains elusive. Here, we showed that the regulatory role of BR signaling in proper ovule development is mediated by the transcriptional repressor gene ZINC FINGER PROTEIN 11 (ZFP11), which is a direct target of AG. ZFP11 expression initiates from the placenta upon AG induction and becomes prominent in the funiculus of ovule primordia. Plants harboring zfp11 mutations showed reduced placental length with decreased ovule numbers and some aborted ovules. During ovule development, the transcription factor BRASSINAZOLE-RESISTANT 1 (BZR1), which functions downstream of BR signaling, inhibits ZFP11 expression in the chalaza and nucellus. Weakened BR signaling leads to stunted integuments in ovules, resulting from the direct repression of INNER NO OUTER (INO) and WUSCHEL (WUS) by extended ZFP11 expression in the chalaza and nucellus, respectively. In addition, the zfp11 mutant shows reduced sensitivity to BR biosynthesis inhibitors and can rescue outer integument defects in brassinosteroid insensitive 1 (bri1) mutants. Thus, the precise spatial regulation of ZFP11, which is activated by AG in the placenta and suppressed by BR signaling in the central and distal regions of ovules, is essential for ensuring sufficient ovule numbers and proper ovule formation.

A Genetically Encoded Sensor for Real-Time Monitoring of Poly-ADP-Ribosylation Dynamics In Vitro and in Cells.

ADP-ribosylation, the transfer of ADP-ribose (ADPr) from nicotinamide adenine dinucleotide (NAD+) groups to proteins, is a conserved post-translational modification (PTM) that occurs most prominently in response to DNA damage. ADP-ribosylation is a dynamic PTM regulated by writers (PARPs), erasers (ADPr hydrolases), and readers (ADPR binders). PARP1 is the primary DNA damage-response writer responsible for adding a polymer of ADPR to proteins (PARylation). Real-time monitoring of PARP1-mediated PARylation, especially in live cells, is critical for understanding the spatial and temporal regulation of this unique PTM. Here, we describe a genetically encoded FRET probe (pARS) for semiquantitative monitoring of PARylation dynamics. pARS feature a PAR-binding WWE domain flanked with turquoise and Venus. With a ratiometric readout and excellent signal-to-noise characteristics, we show that pARS can monitor PARP1-dependent PARylation temporally and spatially in real-time. pARS provided unique insights into PARP1-mediated PARylation kinetics in vitro and high-sensitivity detection of PARylation in live cells, even under mild DNA damage. We also show that pARS can be used to determine the potency of PARP inhibitors in vitro and, for the first time, in live cells in response to DNA damage. The robustness and ease of use of pARS make it an important tool for the PARP field.

Spatial Simulation and Optimization of Cropping Structure Under Climate and Land Use Change Conditions Considering Synergistic Economic Benefits and Carbon Reduction in Crop Growth Processes

AbstractThe climate and land use changes caused by the natural environment and socioeconomic development have potential impacts on the green and sustainable development of agriculture. To accommodate agricultural production under multiple scenarios of future climate and land‐use change, this study proposes a “simulation–optimization” modeling approach based on a crop growth model with a synergistic “carbon emission–economic benefit” approach. This approach is based on climate change conditions and it accurately simulates future land use changes and crop growth processes, establishes a carbon emission intensity optimization model, and generates a spatial planting structure optimization and regulation scheme based on intelligent optimization algorithms under changing scenarios. The results of the model application show that the planting structure option in the future scenario can increase economic benefit by up to 14.8% compared to the current scenario while simultaneously reducing total greenhouse gas emissions by 6.77%. Correlation analysis of planting area, irrigation water volume, carbon intensity value and unilateral water use efficiency can be used to obtain the coordination level of each county under different regulation scenarios. This “simulation–optimization” modeling approach provides an effective approach to achieve synergistic and coordinated development of regional agricultural benefits and carbon reduction by fine‐tuning the planting structure, which promotes low‐carbon and high‐quality development of regional agriculture.

A Photo-Switchable Peptide Fibril Esterase.

Recent attempts to mimic enzyme catalysis using simple, short peptides have been successful in enhancing various reactions, but the on-demand, temporal or spatial regulation of such processes by external triggers remains a great challenge. Light irradiation is an ideal trigger for regulating molecular functionality, since it can be precisely manipulated in time and space, and because most reaction mediums do not react to light. We herein report the selection of a photo-switchable amphiphilic peptide catalyst from a small library of isomeric peptides, each containing an azobenzene-based light responsive group and a catalytic histidine residue. In its native fibrillar form, the selected peptide is efficiently and enantio-selectively active for ester hydrolysis, but after irradiation by UV light inducing trans-to-cis azobenzene isomerization, the fibrils disassemble to amorphous aggregates that are much less catalytically active. Significantly, this esterase-like activity can be manipulated multiple times, as the fibrillar peptide assembly is reversibly reduced and restored upon alternate irradiation by UV and visible light, respectively. We propose that this research may shine light on the origin of complex functions in early chemical evolution. Furthermore, it paves the way to regulate additional functions for peptide nanotechnology, such as replication, charge transfer, and delivery.

MetaDegron: multimodal feature-integrated protein language model for predicting E3 ligase targeted degrons.

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized. To tackle on this challenge, here we develop a novel deep-learning framework, namely MetaDegron, for predicting E3 ligase targeted degron by integrating the protein language model and comprehensive featurization strategies. Through extensive evaluations using benchmark datasets and comparison with existing method, such as Degpred, we demonstrate the superior performance of MetaDegron. Among functional features, MetaDegron allows batch prediction of targeted degrons of 21 E3 ligases, and provides functional annotations and visualization of multiple degron-related structural and physicochemical features. MetaDegron is freely available at http://modinfor.com/MetaDegron/. We anticipate that MetaDegron will serve as a useful tool for the clinical and translational community to elucidate the mechanisms of regulation of protein homeostasis, cancer research, and drug development.

Abstract C003: Multimodal and multiplexed spatial regulation of the breast collagen proteome: Comparative analysis in Black and White women from normal breast tissue and triple-negative breast cancer

Abstract Non-Hispanic Black women (BW) are diagnosed with more aggressive breast cancer subtypes at younger ages and have higher mortality rates compared to non-Hispanic White women (WW). Within the breast microenvironment emergent data shows that stromal collagen plays a significant role in aggressiveness of breast cancer linked to ancestral traits. However, the molecular composition of collagen stroma has yet to be linked to ancestry and aggressiveness of breast cancer. The purpose of this study was to evaluate the microenvironment within ancestry-defined normal breast and triple-negative breast cancer (TNBC) to understand spatial regulation of collagen stroma that may link to ancestral differences in cancer. Multimodal, multiplexed spatial analyses were performed. Techniques included Second Harmonic Generation (SHG) to measure collagen fibers, mass spectrometry imaging to measure the collagen proteome, and mass-tagged antibody panels to investigate immune signatures in TNBC. Normal breast tissues were obtained from the Susan G. Komen Tissue Bank, African American (AA; n=20) and European American (EA; n=20) samples were annotated with risk scores, age, Body Mass Index (BMI), Breast Imaging-Reporting and Data System (BI-RADS), continental ancestry, and family history. Triple-negative breast cancer (TNBC, n=80) tissues from BW with extensive clinical annotations including age, BMI, stage, metastasis, and survival were evaluated in comparison to 20+ TNBC tissues from WW. In the normal breast cohort, evaluation of BMI (overweight and obese) within ancestry groups showed significant but opposing differences in fiber width measurements. As BMI increases, AA showed statistically thicker fibers while EA showed statistically thinner fibers. At the protein level, two types of collagens were significantly higher in EA and one type is higher in AA. Within the TNBC cohort, collagen fiber length and width measurements by SHG were significantly shorter and thinner in stage II compared to stage I but no other stage comparisons were significant. This may indicate that ECM remodeling occurs at earlier stages in TNBC. Initial analyses showed that collagen peptide intensities significantly vary by TNBC stage (75 peptides, ANOVA test FDR p-value < 0.05). In the cohort of women who survived, 90 ECM peptides significantly correlated with collagen fiber widths, indicating a relationship between collagen physical and molecular properties within a defined region. Seven immune markers defined differences in survival when grouped by high vs low expression within tumor regions. These markers include CD20 (Hazard Ratio HR = 7.99, p-value = 0.002) and PD-1 (HR = 3.68, p-value = 0.048), which have both been studied in breast cancer. Current work focuses on collagen peptide post-translational modifications that may differ in TNBC patients by vital status and are detected in normal breast at risk of cancer. These findings support that molecular composition in breast stroma contributes to aggressive ancestral traits of breast cancer risk and triple-negative breast cancer. Citation Format: Jaclyn B. Dunne, Heather Jensen-Smith, Laura Spruill, Taylor S. Hulahan, Jade K. Macdonald, George E. Sandusky, M. A. Hollingsworth, Anand S. Mehta, Richard R. Drake, Jeffrey R. Marks, Harikrishna Nakshatri, Marvella E. Ford, Peggi M. Angel. Multimodal and multiplexed spatial regulation of the breast collagen proteome: Comparative analysis in Black and White women from normal breast tissue and triple-negative breast cancer [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C003.

Plasma membrane curvature regulates the formation of contacts with the endoplasmic reticulum.

Contact sites between the endoplasmic reticulum (ER) and plasma membrane (PM) play a crucial role in governing calcium regulation and lipid homeostasis. Despite their significance, the factors regulating their spatial distribution on the PM remain elusive. Inspired by observations in cardiomyocytes, where ER-PM contact sites concentrate on tubular PM invaginations known as transverse tubules, we hypothesize that PM curvature plays a role in ER-PM contact formation. Through precise control of PM invaginations, we show that PM curvatures locally induce the formation of ER-PM contacts in cardiomyocytes. Intriguingly, the junctophilin family of ER-PM tethering proteins, specifically expressed in excitable cells, is the key player in this process, whereas the ubiquitously expressed extended synaptotagmin-2 does not show a preference for PM curvature. At the mechanistic level, we find that the low-complexity region (LCR) and membrane occupation and recognition nexus (MORN) motifs of junctophilins can bind independently to the PM, but both the LCR and MORN motifs are required for targeting PM curvatures. By examining the junctophilin interactome, we identify a family of curvature-sensing proteins-Eps15 homology domain-containing proteins-that interact with the MORN_LCR motifs and facilitate the preferential tethering of junctophilins to curved PM. These findings highlight the pivotal role of PM curvature in the formation of ER-PM contacts in cardiomyocytes and unveil a mechanism for the spatial regulation of ER-PM contacts through PM curvature modulation.

Study on temperature regulation function of green spaces at community scale in high-density urban areas and planning design strategies

In recent years, the frequency of extreme high-temperature events has gradually increased. To better understand the impact of urban green space coverage's spatial pattern on land surface temperature (LST), this study selected three sample areas along the urban-rural gradient in Shanghai. Using LST inversion and resampling methods, LST data for different grid sizes were obtained for spring, summer, and winter in the 2010s, 2015s, and 2020 s. A boosting regression tree model was employed to determine the key indicators affecting LST and effective cooling thresholds. The impact of green quality, structure, and pattern at the community scale on LST was discussed, providing feasible suggestions for green space planning and design in different urban spaces. The study found significant differences in the spatial patterns of green areas and LST among the three sample regions. The quantity and integrity of green spaces in the Huangpu, Minhang, and Songjiang sample areas have progressively improved, with overall green coverages of 19 %, 38 %, and 43 %, respectively. As grid size increases, the relative influence of fractional vegetation coverage (FVC) on LST generally decreases, whereas the relative influence of green structure and patterns gradually increases. Taking the summer of the 2020 s as an example, the influence of FVC on the three study sample areas was 80.79, 83.36, and 87.18 at a 30 m grid size, which decreased to 48.87, 40.59, and 47.64 at a 120 m grid size. The green structure's impact rose from 13.09, 15.22, and 10.6–30.01, 51.82, and 38.5; the influence of green patterns increased from 6.12, 1.42, and 2.21–21.13, 7.6, and 13.86. Key indicators affecting LST include FVC (Fractional Vegetation Coverage), AREA (Green Patch Area), PD (Patch Density), COHESION (Patch Cohesion Index), and ED (Edge Density). High temperatures in summer are one of the ecological issues that need special attention in Shanghai's green space design. Setting the green space proportion to 35 % while avoiding fragmentation and low vegetation coverage can achieve effective cooling. This study's main advancement lies in utilizing machine learning algorithms to identify the principal green spatial pattern impact factors and key thresholds influencing LST at the community scale in Shanghai. The related results and proposed strategies provide a research framework and strong basis for special regulations in urban green space system planning concerning urban thermal environments. They offer references for urban renewal and new town planning to address climate change and urban high-temperature issues, such as clear requirements for optimal green space area at the community scale, community park spatial layout and quantity regulations, and urban park planning design suggestions. This study also highlights obstacles in the practical application of planning and design strategies, which can help avoid difficulties in implementing planning policies. It attempts to set goals for community-scale vegetation planning in China from a policy perspective and provides relevant recommendations.

The mRNA dynamics underpinning translational control mechanisms of Drosophila melanogaster oogenesis.

Advances in the study of mRNAs have yielded major new insights into post-transcriptional control of gene expression. Focus on the spatial regulation of mRNAs in highly polarized cells has demonstrated that mRNAs translocate through cells as mRNA:protein granules (mRNPs). These complex self-assemblies containing nuclear and cytoplasmic proteins are fundamental to the coordinated translation throughout cellular development. Initial studies on translational control necessitated fixed tissue, but the last 30 years have sparked innovative live-cell studies in several cell types to deliver a far more nuanced picture of how mRNA-protein dynamics exert translational control. In this review, we weave together the events that underpin mRNA processes and showcase the pivotal studies that revealed how a multitude of protein factors engage with a transcript. We highlight a mRNA's ability to act as a 'super scaffold' to facilitate molecular condensate formation and further moderate translational control. We focus on the Drosophila melanogaster germline due to the extensive post-transcriptional regulation occurring during early oogenesis. The complexity of the spatio-temporal expression of maternal transcripts in egg chambers allows for the exploration of a wide range of mechanisms that are crucial to the life cycle of mRNAs.

Fluctuating hydrodynamics of active particles interacting via taxis and quorum sensing: static and dynamics

Abstract In this article we derive and test the fluctuating hydrodynamic description of active particles interacting via taxis and quorum sensing, both for mono-disperse systems and for mixtures of co-existing species of active particles. We compute the average steady-state density profile in the presence of spatial motility regulation, as well as the structure factor and intermediate scattering function for interacting systems. By comparing our predictions to microscopic numerical simulations, we show that our fluctuating hydrodynamics correctly predicts the large-scale static and dynamical properties of the system. We also discuss how the theory breaks down when structures emerge at scales smaller or comparable to the persistence length of the particles. When the density field is the unique hydrodynamic mode of the system, we show that active Brownian particles, run-and-tumble particles and active Ornstein–Uhlenbeck particles, interacting via quorum-sensing or chemotactic interactions, display undistinguishable large-scale properties. This form of universality implies an interesting robustness of the predicted physics but also that large-scale observations of patterns are insufficient to assess their microscopic origins. In particular, our results predict that chemotaxis-induced and motility-induced phase separation should share strong qualitative similarities at the macroscopic scale.

Dynamic Organization of Neuronal Extracellular Matrix Revealed by HaloTag-HAPLN1.

The brain's extracellular matrix (ECM) regulates neuronal plasticity and animal behavior. ECM staining shows a net-like structure around a subset of neurons, a ring-like structure at the nodes of Ranvier, and diffuse staining in the interstitial matrix. However, understanding the structural features of ECM deposition across various neuronal types and subcellular compartments remains limited. To visualize the organization pattern and assembly process of the hyaluronan-scaffolded ECM in the brain, we fused a HaloTag to hyaluronan proteoglycan link protein 1, which links hyaluronan and proteoglycans. Expression or application of the probe in primary rat neuronal cultures enables us to identify spatial and temporal regulation of ECM deposition and heterogeneity in ECM aggregation among neuronal populations. Dual-color birthdating shows the ECM assembly process in culture and in vivo. Sparse expression in mouse brains of either sex reveals detailed ECM architectures around excitatory neurons and developmentally regulated dendritic ECM. Our study uncovers extensive structural features of the brain's ECM, suggesting diverse roles in regulating neuronal plasticity.

The Structure of Cilium Inner Junctions Revealed by Electron Cryo-tomography.

The cilium is a microtubule-based organelle critical for many cellular functions. Its assembly initiates at a basal body and continues as an axoneme that projects out of the cell to form a functional cilium. This assembly process is tightly regulated. However, our knowledge of the molecular architecture and the mechanism of assembly is limited. By applying electron cryotomography and subtomogram averaging, we obtained subnanometer resolution structures of the inner junction in three distinct regions of the cilium: the proximal region of the basal body, the central core of the basal body, and the flagellar axoneme. The structures allowed us to identify several basal body and axoneme components. While a few proteins are distributed throughout the entire length of the organelle, many are restricted to particular regions of the cilium, forming intricate local interaction networks and bolstering local structural stability. Finally, by knocking out a critical basal body inner junction component Poc1, we found the triplet MT was destabilized, resulting in a defective structure. Surprisingly, several axoneme-specific components were found to "infiltrate" into the mutant basal body. Our findings provide molecular insight into cilium assembly at its inner Junctions, underscoring its precise spatial regulation.

Spatial regulation of NMN supplementation on brain lipid metabolism upon subacute and sub-chronic PM exposure in C57BL/6 mice

BackgroundAtmospheric particulate matter (PM) exposure-induced neuroinflammation is critical in mediating nervous system impairment. However, effective intervention is yet to be developed.ResultsIn this study, we examine the effect of β-nicotinamide mononucleotide (NMN) supplementation on nervous system damage upon PM exposure and the mechanism of spatial regulation of lipid metabolism. 120 C57BL/6 male mice were exposed to real ambient PM for 11 days (subacute) or 16 weeks (sub-chronic). NMN supplementation boosted the level of nicotinamide adenine dinucleotide (NAD+) in the mouse brain by 2.04 times. This augmentation effectively reduced neuroinflammation, as evidenced by a marked decrease in activated microglia levels across various brain regions, ranging from 29.29 to 85.96%. Whole brain lipidomics analysis revealed that NMN intervention resulted in an less increased levels of ceramide (Cer) and lysophospholipid in the brain following subacute PM exposure, and reversed triglyceride (TG) and glycerophospholipids (GP) following sub-chronic PM exposure, which conferred mice with anti-neuroinflammation response, improved immune function, and enhanced membrane stability. In addition, we demonstrated that the hippocampus and hypothalamus might be the most sensitive brain regions in response to PM exposure and NMN supplementation. Particularly, the alteration of TG (60:10, 56:2, 60:7), diacylglycerol (DG, 42:6), and lysophosphatidylcholine (LPC, 18:3) are the most profound, which correlated with the changes in functional annotation and perturbation of pathways including oxidative stress, inflammation, and membrane instability unveiled by spatial transcriptomic analysis.ConclusionsThis study demonstrates that NMN intervention effectively reduces neuroinflammation in the hippocampus and hypothalamus after PM exposure by modulating spatial lipid metabolism. Strategies targeting the improvement of lipid homeostasis may provide significant protection against brain injury associated with air pollutant exposure.

Crosstalk between ubiquitination and translation in neurodevelopmental disorders.

Ubiquitination is one of the most conserved post-translational modifications and together with mRNA translation contributes to cellular protein homeostasis (proteostasis). Temporal and spatial regulation of proteostasis is particularly important during synaptic plasticity, when translation of specific mRNAs requires tight regulation. Mutations in genes encoding regulators of mRNA translation and in ubiquitin ligases have been associated with several neurodevelopmental disorders. RNA metabolism and translation are regulated by RNA-binding proteins, critical for the spatial and temporal control of translation in neurons. Several ubiquitin ligases also regulate RNA-dependent mechanisms in neurons, with numerous ubiquitination events described in splicing factors and ribosomal proteins. Here we will explore how ubiquitination regulates translation in neurons, from RNA biogenesis to alternative splicing and how dysregulation of ubiquitin signaling can be the underlying cause of pathology in neurodevelopmental disorders, such as Fragile X syndrome. Finally we propose that targeting ubiquitin signaling is an attractive novel therapeutic strategy for neurodevelopmental disorders where mRNA translation and ubiquitin signaling are disrupted.

The influence of spatial distribution and transcriptional regulation of secondary metabolites on the bioactivities of Adenophora triphylla (Japanese lady bell)

The distribution of secondary metabolites in plant tissues plays a crucial role in determining their pharmacological properties. In this study, we investigated the dynamics of the bioactive compounds in Adenophora triphylla, a medicinal herb with diverse therapeutic applications.The anti-inflammatory properties of the EtOAc fraction from the aerial part extract (A_ EtF) exhibited an IC50 value of 27.2 ± 2.3 μg/mL, significantly surpassing that of the EtOAc fraction from the root extract (R_EtF) with an IC50 of 38.9 ± 2.9 μg/mL. Similarly, the anti-melanogenic activity of A_EtF (IC50 = 68.9 ± 2.3 μg/mL) outperformed that of R_EtF (IC50 = 90.0 ± 5.5 μg/mL). Analysis of the distinct chemical profiles of these tissues using UPLC-ESI-Q-TOF-MS revealed that the distribution of secondary metabolites contributes to the observed variations in pharmacological properties between the aerial parts and roots. Transcriptome analysis further elucidated spatially regulated genes associated with secondary metabolism, highlighting the role of AbtYABBYs as potential regulators of phenylpropanoid biosynthesis. To validate their function, these genes were transiently expressed in tobacco leaves via agro-infiltration, confirming their role in modulating polyphenolic compound biosynthesis. Our findings underscore the importance of understanding spatial gene expression patterns for harnessing the complete pharmacological potential of medicinal plants. This study provides valuable insights into the spatial regulation of secondary metabolism and lays the groundwork for targeted manipulation of plant bioactivity for therapeutic and industrial applications.

Resolving 3-Dimensional Genomic Landscape of CD4+ T Cells in the Peripheral Blood of Patients with Psoriasis

A precise regulation of gene expression depends on the accuracy of the 3-dimensional (3D) structure of chromatin; however, the effects of the 3D genome on gene expression in psoriasis remain unknown. In this study, we conducted Hi-C and RNA sequencing on CD4+ T cells collected from 5 patients with psoriasis and 3 healthy controls and constructed a comprehensive 3D chromatin interaction map to delineate the genomic hierarchies, including A/B compartments, topologically associated domains, and chromatin loops. Then, the specific superenhancers related to psoriasis were identified by Hi-C and H3K27ac chromatin immunoprecipitation sequencing data. Subsequently, comprehensive analyses were carried out on the differentially expressed genes that are associated with altered topologically associated domains, loops, and superenhancers in psoriasis. Finally, we screened the candidate target genes and examined the potential functional SNP in psoriasis affected by disruptions of the spatial organization. This study provides a comprehensive reference for examining the 3D genome interactions in psoriasis and elucidating the interplay between spatial organization disruption and gene regulation. We hope that our findings can help clarify the mechanisms underlying the pathogenesis of psoriasis and shed light on the role of 3D genomic structure, therefore informing potential therapeutic approaches.