Biology subjects

Yang, Y.

Publications and source records attributed to Yang, Y..

At least 505 records · Page 28Linked to original sources

bioRxiv2024

Functional diversification of the MADS-box gene family in fine-tuning the dimorphic transition of Talaromyces marneffei

The dynamic transition between yeast and hypha is a crucial adaptive mechanism for many human pathogenic fungi, including Talaromyces marneffei, a thermodimorphic fungus responsible for causing fatal talaromycosis. In the current study, we elucidated the roles of the MADS-box gene family in fine-tuning the dimorphic transition in T. marneffei through functional diversification. Utilizing adaptive laboratory evolution, we identified an enrichment of MADS-box genes in mutants deficient in yeast-to- mycelium transition. Further phylogenetic analyses revealed a significant expansion of MADS-box gene family within T. marneffei. Functional genetic manipulations revealed that overexpression of mads9, as opposed to its paralog mads10, effectively impeded the hyphal-to-yeast transition. Through integrating RNA sequencing (RNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq), we demonstrated that mads9 and the previously characterized madsA modulated the rate of hyphal-to-yeast conversion by orchestrating metabolic pathways and membrane dynamics, respectively, with mutual regulation via shared target genes. Our findings illuminated the distinct functional roles of the MADS-box family in regulating dimorphic transitions in T. marneffei, offering new insights into fungal adaptability.

microbiology↗

bioRxiv2024

Mapping Global Causal Responses to Noninvasive Modulation of Genetically and Spatially Targeted Neural Populations with Sonogenetic-fPET

Despite significant progress in brain circuit mapping over recent decades, a major challenge remains: no method currently allows for the noninvasive modulation of genetically and spatially defined neural populations while simultaneously monitoring their global effects throughout the brain and body. Here, we present sonogenetic-fPET, a technique that integrates sonogenetics with [18F]-2-fluoro-2-deoxy-D-glucose functional positron emission tomography (FDG-fPET) to overcome this challenge. Sonogenetics enables noninvasive, spatially targeted modulation of neurons genetically engineered to express the ultrasound-sensitive ion channel TRPV1, while FDG-fPET captures glucose metabolic changes triggered by this stimulation across the brain and body. We demonstrate the effectiveness of this technique by targeting neurons in the dorsal striatum, showcasing its capability to map global network responses to specific neuronal activation. Incorporating an acoustic hologram for sonogenetics further enables flexible modulation of different brain regions within a single mouse while concurrently mapping the resulting network activity. In summary, sonogenetic-fPET offers a tool for dissecting the global responses of the brain and body to the noninvasive modulation of genetically and spatially defined neuronal populations.

neuroscience↗

bioRxiv2024

Prefrontal cortex dopamine responds to the total valence of stimuli

The prefrontal cortex (PFC) dopamine system plays an essential role in cognitive flexibility, working memory and psychiatric disease, but determining the conditions under which dopamine in the PFC is released remains an open problem. Both rewarding and aversive stimuli have been found to trigger release, but studies have disagreed on whether the valence of a stimulus or other variables like novelty and salience are the most important. Here we report on recordings of dopamine-dependent fluorescence using a high-sensitivity dopamine indicator. We deliver an array of rewarding, aversive and mixed valence stimuli, as well as stimuli without any obvious valence. We observe that stimuli without valence, as well as the omission of expected stimuli, do not lead to large changes in fluorescence, even when these stimuli and omissions are both novel and engaging. In contrast, both rewarding and aversive stimuli lead to increases in fluorescence, with the most rewarding and most aversive stimuli leading to the largest increases. We test the effect of adding an aversive component to a rewarding stimulus and find that the increases in fluorescence are consistent with a summation of the rewarding and aversive components. We propose that dopamine release in the PFC responds to the total valence of a stimulus, in contrast with the traditional view of basal ganglia dopamine release that depends on the net valence.

neuroscience↗

bioRxiv2024

Integrative Omics reveals genetic basis and TaMYB7-A1's function in wheat WUE and drought resilience

Improving water use efficiency (WUE) and drought resistance in wheat is critical for ensuring global food security under changing climate conditions. Here, we integrated multi-omic data, including population-scale phenotyping, transcriptomics, and genomics, to dissect the genetic and molecular mechanisms underlying WUE and drought resilience in wheat. Genome-wide association studies (GWAS) revealed 8,135 SNPs associated with WUE-related traits, identifying 258 conditional and non-conditional QTLs, many of which co-localized with known drought-resistance genes. Pan-transcriptome analysis uncovered tissue-specific expression patterns, core and unique gene functions, and dynamic sub-genomic biases in response to drought. eQTL mapping pinpointed 146,966 regulatory loci, including condition-specific hotspots enriched for genes involved in water regulation, osmoregulation, and photosynthesis. Integration of Weighted gene co-expression network analysis (WGCNA), Summary-data-based Mendelian Randomization (SMR) and GWAS, eQTLs identified 207 candidate causal genes as key regulators for WUE-related traits in wheat, such as TaMYB7-A1. Functional analyses found that TaMYB7-A1 enhances drought tolerance by promoting root growth, reducing oxidative stress, and improving osmotic regulation, enabling better water access and survival under stress. It also increases photosynthesis efficiency and WUE, boosting yield under drought without compromising performance in well-watered conditions, making it ideal target for breeding. Our findings provide a comprehensive omic framework for understanding the genetic architecture of WUE and drought resistance, offering valuable targets for breeding resilient wheat varieties.

plant biology↗

bioRxiv2024

FTO (fat-mass and obesity-associated protein) deficiency aggravates age-dependent depression-like behaviors and cognitive impairment

AbstractO_ST_ABSBackgroundC_ST_ABSThe demethylase fat mass and obesity-related protein (FTO) is strongly associated with depression. Aging is a risk factor for synaptic plasticity damage in the brain and leads to neurocognitive dysfunctions. However, whether FTO is associated with susceptibility to depression in different age groups remains unknown. MethodsWe subjected 3-and 12-month-old C57BL/6J male mice to 6 weeks of chronic unpredictable mild stress (CUMS) and 3 weeks of hippocampal injection of FTO knockdown adeno-associated virus 9 shRNA (FTO-KD AAV9). Finally, 36 male mice in each 3-month-old and 12-month-old groups were divided into three groups (n=12): Sham, CUMS, and FTO-KD. After 6 weeks, we assessed behavioral deficits (depressive and anxiety-like behaviors and cognitive impairment) by behavioral tests and hippocampal neuronal damage (dendritic spine density, neuronal atrophy, and expression of proteins associated with synaptic plasticity) by molecular biochemical experiments. ResultsThe results showed that 12-month-old C57BL/6J mice were more likely to develop depression-like behavior and spatial learning and memory impairment induced by CUMS than 3-month-old mice. Chronic stress-induced depression-like behavior and cognitive impairment worsened after the FTO-KD intervention. In the hippocampus of 3-and 12-month-old mice, CUMS induced the downregulation of FTO, nerve growth factor (NGF), reelin, and synaptic plasticity-related proteins. It also caused abnormal BDNF-TrkB signaling, reduced density of dendritic spines, and an increased number of neuronal pyknotic nuclei, leading to neuronal disarray, which was more significant in 12-month-old animals. FTO deficiency accelerated neuronal damage in the hippocampus of 12-month-old CUMS mice. ConclusionsThis study provides rodent evidence that FTO deficiency may increase the susceptibility to depression in older adults by impairing hippocampal neuronal function and neuronal synaptic plasticity in an age-dependent manner. This suggests that the development of FTO activators may be an effective treatment for depression in older adults.

neuroscience↗

bioRxiv2024

A CRISPR/SpCas9M-reporting system for efficient and rapid genome editing in Caulobacter crescentus

As members of the -proteobacteria group, Caulobacter crescentus and its relatives are known for their asymmetric life cycle and comprehensive applications in gene delivery, agricultural biotechnology, and the production of high-value compounds. However, genetic manipulations of these bacteria are often time-consuming and labor-intensive due to the lack of efficient genome editing tools. Here, we report a practical CRISPR/SpCas9M-reporting system that overcomes the limitations of SpCas9 expression, enabling efficient, markerless, and rapid genome editing in C. crescentus. As a demonstration, we successfully knocked out two genes encoding the scaffold proteins, achieving apparent editing efficiencies up to 80%. Key components, including the Cas protein, Cas inducer, sgRNA, homologous arms, and reporter, were systematically analyzed and optimized to enhance the editing efficiency or decrease the cell lethality. A nearly zero off-target ratio was observed after the curing of the editor plasmid in editing strains. Furthermore, we applied the CRISPR/SpCas9M-reporting system to two C. crescentus relatives, Agrobacterium fabrum and Sinorhizobium meliloti, establishing it as an efficient and reliable editing strategy. We anticipate that this system could be applied to other hard-to-edit organisms, accelerating both basic and applied research in -proteobacteria.

bioengineering↗

bioRxiv2024

Simple One-step Vial-based Pretreatment for Deep Single-cell Proteomics and Its Application to Oocyte Aging

Single-cell proteomics is a pivotal technology for studying cellular phenotypes, offering unparalleled insights into cellular heterogeneity and dynamic functions. Technical improvement in mass spectrometry instrument and sample preparation has made single-cell proteomics feasible in recent years. Yet, developing a simple and robust sample preparation method to enable deep proteomics profiling of single cells remains a significant challenge. Herein, we developed a simple one-step vial-based pretreatment (SOViP) for deep label-free single-cell proteomics. SOViP integrates all sample preparation procedures into a single step in autosampler vials, yet it is highly efficient and high-throughput. SOViP can be finished within [~]2 h, with hands-on time limited to merely a few minutes. We show that on average over 6,500 can be quantified from a single mouse oocyte using SOViP. In total 6,983 protein groups were identified from single mouse oocytes across an entire reproductive lifespan, offering a valuable proteomics resource for oocyte aging. Unique molecular characteristics of oocytes at different ages were revealed, and a classifier consisting of ten proteins demonstrated accurate age-group classification and fertility-level prediction. Although demonstrated using mouse oocytes in this study, SOViP is adaptable to rare cell samples and other large cells, including follicles and preimplantation embryo cells, among others.

biochemistry↗

bioRxiv2024

Dynamic interplay between RNA N6-methyladenosine modification and porcine reproductive and respiratory syndrome virus infection

N6-methyladenosine (m6A) has attracted significant attention for its role in various biological processes, including RNA stability, translation, and the immune response. Understanding the role of m6A in viral infections is crucial to deep the complex interaction between virus and host cells. Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) is a significant pathogen affecting swine health worldwide. Here, we firstly identified the m6A peaks in the PRRSV genome by m6A RNA immunoprecipitation sequencing (m6A-seq). Seven m6A-enriched regions within the PRRSV genome were detected, with one located in the N protein-coding region and the others distributed across nonstructural protein-coding regions. Notably, the Nsp2-coding region contained the highest m6A peak, spanning approximately 178 nucleotides. Functional analyses demonstrated a positive correlation between m6A modification levels and PRRSV replication in porcine alveolar macrophages (PAMs), as modulating the expression of m6A methyltransferases and demethylases significantly influenced viral replication. Moreover, treatment with the universal methylation inhibitor 3-deazaadenosine (3-DAA) effectively suppressed PRRSV replication, suggesting its potential as a novel anti-PRRSV therapeutic. To further elucidate the role of m6A in PRRSV infection, we analyzed the m6A landscape in PAMs infected with pandemic and highly pathogenic PRRSV strains. Among the 4,677 transcripts exhibiting altered m6A modification levels, the MAPK14 gene as well as other genes in p38/MAPK signaling pathway potentially emerged as the preliminary targets of m6A-mediated epigenetic regulation during PRRSV infection. These findings provide new insights into the epigenetic mechanisms underlying PRRSV infection and may facilitate the development of targeted anti-PRRSV strategies and therapeutics. IMPORTANCEThe involvement of m6A in viral genome has broader implications for our understanding of virus evolution and pathogenicity. The ability of viruses to adapt to their hosts and exploit host cellular mechanisms is a critical factor in their success as pathogens. As m6A is a modification that can be manipulated by both host and virus, studying its role in viral infections may reveal new insights into viral evolution. Understanding how different viruses utilize m6A could inform strategies for developing antiviral therapies that target these interactions. Such therapies could disrupt the ability of viruses to exploit m6A modifications, potentially reducing their virulence and enhancing host defenses.

microbiology↗

bioRxiv2024

Motor protein-assisted glycan translocation and sequencing using nanopores

The glycan sequencing remains a significant bottleneck in glycoscience. While nanopore platforms have achieved substantial progress in single-molecule nucleic acid sequencing, their application to glycan sequencing has faced considerable challenges, with limited advancements to date. In this study, we propose a novel strategy for controlling glycan translocation through the MspA nanopore as an initial step toward glycan sequencing. By conjugating the target glycan with a helicase-controlled single-stranded DNA, we successfully achieved sequencing reads of up to eleven glycans. For the first time, we isolated glycan-associated electrical signals, enabling the translocation, stretching, and controlled speed of neutral glycans through the nanopore. This method provides a platform for obtaining glycan read lengths and identifying different glycan modifications, demonstrating the capability to resolve monosaccharide composition and glycosidic linkages. To further improve resolution, we propose engineered M2-MspA to reduce the pore constriction size and enhance precision by minimizing the random thermal motion of the translocating glycan. These modifications are expected to increase the sequencing accuracy and reliability. This work represents the first proof-of-concept demonstration of glycan chain nanopore sequencing and lays a promising foundation for the development of single-molecule glycan fingerprinting and sequencing technologies. We anticipate that this approach will significantly advance the development and commercialization of nanopore-based glycan sequencing techniques.

bioengineering↗

bioRxiv2024

Combining Glycosidases and Nanopore Technology for Glycan Sequencing

The efficient characterization of glycan structures remains a critical challenge. Direct glycan sequencing technologies with improved sensitivity and throughput are still needed. Here, we propose a glycan sequencing strategy based on glycosidase -assisted nanopore sensing. We used engineered nanopore -hemolysin (M113R/T115A), which provided high-resolution discrimination of monosaccharide volume differences and sensitivity to variations in glycan chain length. By utilizing the specificity of glycosidases, we sequentially hydrolyzed the terminal residues of the glycan chains and detected the characteristic shifts in electrical signals generated by the translocation of hydrolysis products. The accuracy of recognition of hydrolysis fragments achieved over 90 % using machine learning. This allowed us to efficiently and conveniently determine the sequence of consecutive monosaccharide units in the glycan chains. Based on this principle, we conducted a proof-of-concept demonstration on actual samples and verified the accuracy via HPLC-MS. We achieved the sequencing of consecutive units in glycan chains, confirming the theoretical feasibility of glycosidase -assisted nanopore glycan sequencing. With future optimization, the development of arrayed nanopore glycan sequencing technology based on hydrolysis strategy will provide an innovative approach for rapid decoding of glycans, which could promote the progress of glycomics research and glycobiology.

biochemistry↗

bioRxiv2024

Natural killer cell dysfunction drives keloid pathogenesis

Keloids, characterized by excessive scar tissue resulting from abnormal wound healing, are primarily driven by hyperproliferative fibroblasts and overproduction of extracellular matrix. Although human natural killer (NK) cells are known for their role in inhibiting uncontrolled cell growth through cytokines like IFN-{gamma} and TNF-, they also produce amphiregulin (AREG), which paradoxically promotes cell proliferation and survival. The involvement of NK cells in keloid pathogenesis, however, remains largely unexplored. This study uncovers remarkable functional changes in NK cells within both lesional skin and the blood of keloid patients. In the skin, NK cell-produced IFN-{gamma} plays a pivotal role in limiting keloid progression by inducing fibroblast apoptosis and curbing excessive extracellular matrix production, while NK cell-derived AREG actively opposes these protective effects. Notably, TGF-{beta}-driven fibroblasts in keloid lesions further dampen NK cell IFN-{gamma} production, revealing a complex and dynamic cellular interplay. In the bloodstream of keloid patients, a distinct NK cell subset emerges, marked by elevated interferon-stimulated genes (ISGs) and diminished IFN-{gamma} production, which correlates with increased plasma IFN-{beta} levels. This elevated IFN-{beta} serves as a key initiating factor, driving NK cell exhaustion through impaired mitochondrial function and metabolic disruption. These findings highlight a critical mechanism underlying the functional abnormalities of keloid-associated NK cells and emphasize the influence of both local and systemic factors in shaping NK cell responses in keloid pathogenesis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/624588v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@7501f4org.highwire.dtl.DTLVardef@1d34de5org.highwire.dtl.DTLVardef@19f1c47org.highwire.dtl.DTLVardef@f98882_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIIn the skin, NK cell-derived IFN-{gamma} is crucial for suppressing keloid fibroblast proliferation and extracellular matrix production. C_LIO_LIAREG from NK cells counteracts the inhibitory effects of IFN-{gamma} on keloid progression. C_LIO_LIIn the blood, elevated IFN-{beta} in keloid patients drives the emergence of ISG+NK cells with reduced IFN-{gamma} production. C_LIO_LIIFN-{beta} induces mitochondrial dysfunction and functional exhaustion in NK cells. C_LI

immunology↗

bioRxiv2024

Cardiolipin-mimic lipid nanoparticles without antibody modification delivered senolytic in-vivo CAR-T therapy for inflamm-aging

mRNA-based in vivo CAR T cell engineering offers advantages over ex vivo therapies, including streamlined manufacturing and transient expression. However, current delivery requires antibody-modified vehicles with manufacturing challenges. In this study, inspired by cardiolipin, we identified a cardiolipin-like di-phosphoramide lipid that improved T cell transfection without targeting ligands, both in vivo and in vitro. The T cell-favored tropism is likely due to the lipids packing, shape, and rigidity. Encapsulating circular RNA further prolonged mRNA expression in the spleen and T cells. Using PL40 lipid nanoparticles, we delivered mRNA encoding a CAR targeting the senolytic and inflammatory antigen urokinase-type plasminogen activator receptor (uPAR), alleviating uPAR-related liver fibrosis and rheumatoid arthritis (RA). Single cell sequencing in humans confirmed uPARs relevance to senescence and inflammation in RA. To further enhance clinical translation, we screened and humanized scFvs against uPAR, establishing PL40 mRNA encoding a circular human uPAR CAR, with potential for treating aging-inflamed disorders. One Sentence SummaryWeve developed a unique class of Cardiolipin-mimic lipids that facilitate mRNA delivery to T cells in vivo without the need for antibody modification, enhancing the treatment of liver fibrosis and rheumatoid arthritis through circular CAR uPAR RNA and propelling the clinical application of humanized CAR against human uPAR.

bioengineering↗

bioRxiv2024

Green Elegance T2T: An upgraded telomere-to-telomere genome assembly and annotation of looseleaf lettuce (Lactuca sativa var. crispa)

Lettuce (Lactuca sativa L.), a globally important vegetable crop, is cultivated in various horticultural varieties. Looseleaf lettuce is one of the main varieties that are consumed. Here, we report a telomere-to-telomere (T2T) genome assembly of looseleaf lettuce (L. sativa var. crispa cv. Green Elegance). By combining the sequencing data of previously reported Green Elegance v1.2, the 42.20 Gb clean ultra-long reads produced by Oxford Nanopore Technology were used to close the gaps and upgrade the genome assembly. After filling 11 gaps in Green Elegance v1.2, the final gapless telomere-to-telomere genome assembly is 2.58 Gb in length with a contig N50 of 282.47 Mb, containing nine centromeres and 18 telomeres. The genome contained 41,375 protein-coding genes, of which 99.10% were functionally annotated. This T2T genome of looseleaf lettuce will be valuable for the identification of genetic variation and the advancement of lettuce breeding.

genomics↗

bioRxiv2024

Astrocyte-specific secretome profiling reveals its correlation with neurological disorders

Secreted proteins mediate intercellular communication throughout the lives of multicellular organisms. However, due to the lack of new technology for secreted protein capturing, the progress of "secretomics lags behind. Here, we report a two-step secretome enrichment method (tsSEM) combining unnatural amino acid labeling and click chemistry-based biorthogonal reaction, which enables in vitro secretome profiling in the presence of serum. Using this novel method, we systematically investigated the secretome of human iPSCs-derived astrocytes (iAst) in different disease models and identified a panel of astrocyte-secreted proteins that are responsible for its non-cell autonomous toxicity under disease conditions. Furthermore, we validated two astrocytes-derived novel neurotrophic proteins, FAM3C and KITLG, which we identified from disease models, and found that they could boost neurite outgrowth, protect neurons, and promote neural progenitor proliferation. Our study highlights the utility of secretome profiling of iAst and demonstrates its applications in disease study and target identification and validation in drug development.

neuroscience↗

bioRxiv2024

Early-Life Immune Activation Shapes Microglial Responses and Reduces Abeta Pathology in 5xFAD mice

Early infection in life has been implicated in increasing the risk for neurological disorders. Here we performed single-cell sequencing of microglia and monocytes from 6-month-old WT and 5xFAD mice subjected to one dose of LPS (1mg/kg) at postnatal day 9. We successfully mapped disease-associated microglia (DAM) and perivascular macrophages in our data and demonstrated a subpopulation of microglia that adopted a monocyte-like profile, marked by Lyz2, Tmsb10, Lgals1and Lgals3. This unique subset appeared in response to early systemic LPS challenge and AD pathology but diminished in the presence of double stimulus. Different cytokines were altered in the brain and periphery as seen using mesoscale plates. GM-CSF and MIP-1 levels were altered in an amyloid-{beta}(A{beta})-dependent manner in hippocampus. MIP-1{beta} and IFN-{gamma} were altered upon early LPS stimulation. In the periphery, we found MMP-9 was significantly increased in serum samples from 5xFAD mice. Interestingly, early LPS stimulation significantly elevated TNF- in serum from WT and 5xFAD mice, but was reduced in the hippocampus due to A{beta} pathology. The LPS treatment in 5xFAD mice had a tendency to improve the short-term memory deficit. Taken together, we observed long-lasting effects from early life stress, including activation of inflammation in the periphery and brain through modulation of different signaling cascades.

neuroscience↗

bioRxiv2024

AACDB: Antigen-Antibody Complex Database -- a Comprehensive Database Unlocking Insights into Interaction Interface

Antibodies are critical components of the vertebrate immune system and possess a wide array of biomedical applications. Elucidating the complex interactions between antibodies and antigens is an important step in drug development. However, the complex and vast nature of the data presents significant challenges in accurately identifying and comprehending these interactions. To overcome these challenges and deepen our understanding of the antibody-antigen interface, we developed the Antigen-Antibody Complex Database (AACDB). The current version provides a comprehensive collection of 7,498 manually processed antigen-antibody complexes, ensuring accuracy and detail. This database provides extensive metadata and rectifies annotation errors found in the PDB database. Furthermore, it integrates data on antibody developability and antigen-drug target relationships, making it valuable for assisting new antibody therapies development. Notably, the database includes comprehensive paratope and epitope annotation information, thereby serving as a valuable benchmark for immunoinformatics research. The AACDB interface is designed to be user-friendly, providing researchers with powerful search and visualization tools that enable effortless querying, manipulation, and visualization of complex data. Researchers can access AACDB completely online at http://i.uestc.edu.cn/AACDB. Regular updates are promised to ensure the timely provision of scientific and valuable information.

bioinformatics↗

bioRxiv2024

Curcumin attenuates microglia-mediated chronic neuropathic pain through CDK5 /p35 signaling pathway

Curcumin is a phenolic compound derived from turmeric, one of the main ingredients of curry powder, which is widely used for its antioxidant, anti-inflammatory and immunomodulatory effects. Curcumin has been reported to help relieve pain, such as neuropathic pain caused by injury or disease, but the specific mechanism of its antinociceptive effect on pathological pain is unclear. Cyclin-dependent kinase 5 (Cdk5) is a key control point for the release of neurotransmitters from presynaptic vesicles. Cdk5 and its activator p35 couple to regulate key signaling cascades, thereby participating in the pain process. In this study, we established a NP model by chronic constriction injury (CCI) of the bilateral sciatic nerve in rats and evaluated behavioral hyperalgesia using mechanical and hot and cold tests. Protein expression and distribution were evaluated using western blotting and immunofluorescence. The results showed that Iba-1 and Cdk5/p35 were co-localized in the dorsal horn and dorsal root ganglia, respectively. After CCI, the expression of Cdk5 and p35 was upregulated in the dorsal horn and dorsal root ganglia, while intraperitoneal injection of curcumin significantly reversed the activation of Cdk5/p35 protein and alleviated the hyperalgesia in rats. In addition, the injection of curcumin reduced the co-localization expression of Iba-1 and Cdk5/p35, indicating that curcumin inhibited the activation of Cdk5/p35 protein in the dorsal horn and dorsal root ganglia, thereby affecting the activation of microglia, thereby having a destructive effect on the neuronal cell plasticity and synaptic structure remodeling in the development of NP. Our study provides new evidence that Cdk5/p35 in the dorsal horn and dorsal root ganglia is related to the occurrence of NP, introduces microglia as the basis for the long-term maintenance of NP, and provides insights into the molecular mechanisms involved in the analgesic effect of curcumin. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/623498v1_ufig1.gif" ALT="Figure 1"> View larger version (80K): org.highwire.dtl.DTLVardef@125fc20org.highwire.dtl.DTLVardef@cba7d3org.highwire.dtl.DTLVardef@772291org.highwire.dtl.DTLVardef@17e87e3_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Multi-dimensional social relationships shape social attention in monkeys

Social relationships guide individual behavior and ultimately shape the fabric of society. Primates exhibit particularly complex, differentiated, and multidimensional social relationships, which form interwoven social networks, reflecting both individual social tendencies and specific dyadic interactions. How the patterns of behavior that underlie these social relationships emerge from moment-to-moment patterns of social information processing remains unclear. Here, we assess social relationships among a group of four monkeys, focusing on aggression, grooming, and proximity. We show that individual differences in social attention vary with individual differences in patterns of general social tendencies and patterns of individual engagement with specific partners. Oxytocin administration altered social attention and its relationship to both social tendencies and dyadic relationships, particularly grooming and aggression. Our findings link the dynamics of visual information sampling to the dynamics of primate social networks.

neuroscience↗