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Sensory plasticity caused by up-down regulation encodes the information of short-term learning and memory

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-13 DOI: 10.1016/j.isci.2025.112215

Ping-Zhou Wang , Ming-Hai Ge , Pan Su , Piao-Ping Wu , Lei Wang , Wei Zhu , Rong Li , Hui Liu , Jing-Jing Wu , Yu Xu , Jia-Lu Zhao , Si-Jia Li , Yan Wang , Li-Ming Chen , Tai-Hong Wu , Zheng-Xing Wu

{"title":"Sensory plasticity caused by up-down regulation encodes the information of short-term learning and memory","authors":"Ping-Zhou Wang , Ming-Hai Ge , Pan Su , Piao-Ping Wu , Lei Wang , Wei Zhu , Rong Li , Hui Liu , Jing-Jing Wu , Yu Xu , Jia-Lu Zhao , Si-Jia Li , Yan Wang , Li-Ming Chen , Tai-Hong Wu , Zheng-Xing Wu","doi":"10.1016/j.isci.2025.112215","DOIUrl":"10.1016/j.isci.2025.112215","url":null,"abstract":"<div><div>Learning and memory are essential for animals’ well-being and survival. The underlying mechanisms are a major task of neuroscience studies. In this study, we identified a circuit consisting of ASER, RIC, RIS, and AIY, is required for short-term salt chemotaxis learning (SCL) in <em>C. elegans</em>. ASER NaCl-sensation possesses are remodeled by salt/food-deprivation pared conditioning. RIC integrates the sensory information of NaCl and food availability. It excites ASER and inhibits AIY by tyramine/TYRA-2 and octopamine/OCTR-1 signaling pathways, respectively. By the salt conditioning, RIC NaCl calcium response to NaCl is depressed, thus, the RIC excitation of ASER and inhibition of AIY are suppressed. ASER excites RIS by FLP-14/FRPR-10 signaling. RIS inhibits ASER via PDF-2/PDFR-1 signaling in negative feedback. ASER sensory plasticity caused by RIC plasticity and RIS negative feedback are required for both learning and memory recall. Thus, the sensation plasticity encodes the information of the short-term SCL that facilitates animal adaptation to dynamic environments.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112215"},"PeriodicalIF":4.6,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anterior hypothalamic nucleus drives distinct defensive responses through cell-type-specific activity

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-12 DOI: 10.1016/j.isci.2025.112097

Cindy Yookyung Hong , Jessica Sofia Din , Hannah Chang , Jee Yoon Bang , Jun Chul Kim

{"title":"Anterior hypothalamic nucleus drives distinct defensive responses through cell-type-specific activity","authors":"Cindy Yookyung Hong , Jessica Sofia Din , Hannah Chang , Jee Yoon Bang , Jun Chul Kim","doi":"10.1016/j.isci.2025.112097","DOIUrl":"10.1016/j.isci.2025.112097","url":null,"abstract":"<div><div>Innate defensive behaviors are essential for survival, allowing animals to appropriately respond to predatory threats. The anterior hypothalamic nucleus (AHN), a key region in the medial hypothalamic defense system, contains both GABAergic and glutamatergic neurons, reflecting a sophisticated balance between inhibitory and excitatory signaling. However, the specific behavioral functions of these neuronal populations have not been systemically examined. Here, we utilized fiber photometry and optogenetic stimulation to investigate the roles of AHN GABAergic, glutamatergic, and CaMKIIa+ neuronal activities in mediating innate defensive behaviors. Our results indicate that AHN GABAergic neurons mediate anxiety-associated investigatory behaviors, while AHN glutamatergic neurons drive escape and freezing responses. The AHN CaMKIIa+ neurons, which exhibit significant heterogeneity, suggest a more nuanced role, potentially balancing escape and freezing responses. Our study provides a foundation for future investigations into the neural circuits underlying innate defensive behaviors and its dysregulation in neuropsychiatric conditions including PTSD and panic disorder.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112097"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

FMNL2/SRC-mediated androgen receptor translocation into the nucleus promotes enzalutamide resistance of prostate cancer

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-12 DOI: 10.1016/j.isci.2025.112205

Jianpeng Yu , Yukui Gao , Mingpeng Zhang , Yue Gao , Chun Wang , Yuanjie Niu , Zhiqun Shang

{"title":"FMNL2/SRC-mediated androgen receptor translocation into the nucleus promotes enzalutamide resistance of prostate cancer","authors":"Jianpeng Yu , Yukui Gao , Mingpeng Zhang , Yue Gao , Chun Wang , Yuanjie Niu , Zhiqun Shang","doi":"10.1016/j.isci.2025.112205","DOIUrl":"10.1016/j.isci.2025.112205","url":null,"abstract":"<div><div>Enzalutamide, a second-generation androgen receptor (AR) antagonist, has represented the association with improved overall survival in men with prostate cancer (PCa). However, PCa patients receiving enzalutamide will eventually develop resistance through various mechanisms without effective regimens. Here, we observed a higher level of formin-like 2 (FMNL2) in enzalutamide-resistant PCa cells. Functionally, FMNL2 knockdown partially re-sensitized enzalutamide-resistant PCa cells. Mechanistically, FMNL2 directly interacted with SRC kinase through FMNL2-FH1 and SRC-SH3 domain, which induced AR translocation from the cytoplasm to the nucleus, resulting in increased expression of the AR-targeted genes and leading to resistance to enzalutamide. Consistently, SRC inhibitor dasatinib rescued enzalutamide sensitivity and inhibited the proliferation of enzalutamide-resistant cancer cells. Taken together, our findings demonstrate a substantial role for FMNL2/SRC interaction in the regulation of AR translocation, suggesting that targeting FMNL2-mediated SRC activation might be a potential therapeutic strategy for enzalutamide-resistant PCa and dasatinib could be an option.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112205"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143695938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular basis of circadian rhythm divergence between diurnal and nocturnal lepidoperans

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-12 DOI: 10.1016/j.isci.2025.112206

Guiyun Li , Qian Cui , Shirui Zheng , Kaixiang Zhang , Yaohui Wang , Shuai Zhan , Gangqi Fang

{"title":"Molecular basis of circadian rhythm divergence between diurnal and nocturnal lepidoperans","authors":"Guiyun Li , Qian Cui , Shirui Zheng , Kaixiang Zhang , Yaohui Wang , Shuai Zhan , Gangqi Fang","doi":"10.1016/j.isci.2025.112206","DOIUrl":"10.1016/j.isci.2025.112206","url":null,"abstract":"<div><div>Understanding the molecular basis of nocturnal and diurnal behaviors is crucial to uncovering adaptive specialization. Here, we employed the black cutworm (<em>Agrotis ipsilon</em>, BCW) to examine the rhythmic gene repertoire in nocturnal species. Daily eclosion patterns confirmed BCW’s nocturnal behavior. We generated daily transcriptomes for BCW and compared them with those of the diurnal monarch butterfly (<em>Danaus plexippus</em>). Both species share a core set of genes with rhythmic expression, indicating a fundamental timekeeping mechanism in Lepidoptera. Notably, metabolism-related genes exhibited significant phase shifts between BCW and the monarch butterfly, suggesting that metabolic differences underpin their contrasting behaviors. Additionally, while phototransduction genes in monarch butterflies show marginal rhythmicity, in BCW these genes are governed by light sensitivity rather than circadian regulation. This study provides molecular insights into the diversification of behavioral traits between diurnal and nocturnal insects.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112206"},"PeriodicalIF":4.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Spinal implant wear particles: Generation, characterization, biological impacts, and future considerations

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112193

Renata Ganko , Aswini Madhavan , Waeel Hamouda , Sathish Muthu , Amit Jain , S. Tim Yoon , Hiba El-Rozz , Divya Cyril , Moreica Pabbruwe , Joanne L. Tipper , Javad Tavakoli

{"title":"Spinal implant wear particles: Generation, characterization, biological impacts, and future considerations","authors":"Renata Ganko , Aswini Madhavan , Waeel Hamouda , Sathish Muthu , Amit Jain , S. Tim Yoon , Hiba El-Rozz , Divya Cyril , Moreica Pabbruwe , Joanne L. Tipper , Javad Tavakoli","doi":"10.1016/j.isci.2025.112193","DOIUrl":"10.1016/j.isci.2025.112193","url":null,"abstract":"<div><div>The generation of wear debris from orthopedic implants is a known cause of implant failure, particularly in joint replacements. While much research has focused on wear particles from knee and hip implants, spinal implants, such as total disc replacements (TDRs), have received less attention despite their increasing clinical use. Spinal implants face unique biomechanical challenges, including a wider range of motion and higher loads, leading to complex tissue interactions. Studies reveal that TDR wear particles, though similar in size to those from knee implants, cause a stronger immune response, with more macrophages and giant cells found in the surrounding tissue. This may explain the high revision rates seen in spinal surgeries, with some interventions failing in over 30% of cases within 10 years. The younger population undergoing spinal surgery, combined with the productivity losses associated with implant failure, underscores the need for greater understanding. This review discusses recent research on the generation, characterization, and biological impacts of spinal implant wear debris. It draws on retrieval analysis, wear simulation, <em>in vivo</em> models, and a survey conducted with the AO Spine Knowledge Forum Degenerative to assess current clinical practices and highlight gaps in knowledge. Additionally, this critical review explores future strategies to reduce the biological impact of wear particles and improve the safety and longevity of spinal implants through better therapeutics and design innovations. By combining literature and clinical insights, this paper aims to guide future research in addressing the complexities of spinal implant wear and its biological consequences.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112193"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Short-loop engineering strategy for enhancing enzyme thermal stability

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112202

Wenlong Zhu , Yiheng Liu , Hui Cao , Luo Liu , Tianwei Tan

引用次数: 0

Versatile roles of annexin A4 in clear cell renal cell carcinoma: Impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112198

Maximilian Wess , Manuel Rogg , Constance Gueib-Picard , Annika Merz , Anna L. Kössinger , Tobias Feilen , Grigor Andreev , Martin Werner , Ian J. Frew , Markus Grabbert , Oliver Schilling , Christoph Schell

{"title":"Versatile roles of annexin A4 in clear cell renal cell carcinoma: Impact on membrane repair, transcriptional signatures, and composition of the tumor microenvironment","authors":"Maximilian Wess , Manuel Rogg , Constance Gueib-Picard , Annika Merz , Anna L. Kössinger , Tobias Feilen , Grigor Andreev , Martin Werner , Ian J. Frew , Markus Grabbert , Oliver Schilling , Christoph Schell","doi":"10.1016/j.isci.2025.112198","DOIUrl":"10.1016/j.isci.2025.112198","url":null,"abstract":"<div><div>Clear cell renal cell carcinoma (ccRCC) is the most prevalent renal malignancy with a poor prognosis when metastasized. The invasive growth of cancer cells relates to membrane-damaging forces, but the relevance of plasma membrane repair machinery in ccRCC remains incompletely understood. Employing proteomics, analysis of scRNA-sequencing data, and multiplex imaging, we identified ANXA4 as selectively expressed in ccRCC, with distinct localization patterns at the plasma and nuclear membranes. Genetic titration studies demonstrated that reduced ANXA4 expression impairs membrane repair and invasive capabilities. Further segmentation analysis of ANXA4-low tumors showed a distinct composition of the tumor microenvironment, with increased tumor-infiltrating lymphocytes and acellular extracellular matrix deposition. Transcriptomic analysis demonstrated alterations in epithelial-mesenchymal transition and immune signaling signatures in ANXA4-low tumors. Transcription factor enrichment analysis identified ELF3 as a regulator of invasive properties. Our integrative approach uncovered multiple roles for ANXA4 in modulating membrane repair, transcriptional regulation, and shaping the ccRCC tumor microenvironment composition.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112198"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143684880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112201

Alfred Yu , Camille Fang , Li Xuan Tan , Aparna Lakkaraju , Luca Della Santina , Yvonne Ou

{"title":"Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration","authors":"Alfred Yu , Camille Fang , Li Xuan Tan , Aparna Lakkaraju , Luca Della Santina , Yvonne Ou","doi":"10.1016/j.isci.2025.112201","DOIUrl":"10.1016/j.isci.2025.112201","url":null,"abstract":"<div><div>During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, understanding the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here, we analyzed microglia-mediated synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to hyper-ramified morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially protects ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting that microgliosis is the primary mechanism for increased synapse colocalization early after neuronal injury.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112201"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Cdk5 inhibitor restores cognitive function and alleviates type 2 diabetes in mice

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112200

Sangita Paul , Remya Chandran , Dileep K. Vijayan , Juhi Bhardwaj , Praveen Singh , Poornima Shetty , Srinivas Cheruku , Sajith Meleveetil , Binukumar Balachandran Krishnamma

{"title":"A Cdk5 inhibitor restores cognitive function and alleviates type 2 diabetes in mice","authors":"Sangita Paul , Remya Chandran , Dileep K. Vijayan , Juhi Bhardwaj , Praveen Singh , Poornima Shetty , Srinivas Cheruku , Sajith Meleveetil , Binukumar Balachandran Krishnamma","doi":"10.1016/j.isci.2025.112200","DOIUrl":"10.1016/j.isci.2025.112200","url":null,"abstract":"<div><div>Type 2 diabetes (T2D) is a metabolic disorder commonly linked with cognitive decline, increasing patients’ susceptibility to dementia. Alzheimer’s disease (AD) has a strong connection with hyperglycemia and insulin dysregulation. Interestingly, certain anti-diabetic drugs have shown potential in reducing T2D-induced cognitive impairment. Previous studies, including ours, have highlighted the dysregulation of cyclin-dependent kinase 5 (Cdk5) activity in both T2D and AD, which may contribute to pathological changes in these conditions. Thus, targeting the Cdk5 kinase could offer a therapeutic approach for T2D and cognitive deterioration. Our research identifies Cdk5 as a key link between T2D and cognitive decline. By screening the KINACore library, we discovered two new brain-penetrant Cdk5 inhibitors, BLINK11 and BLINK15. In a high-fat diet-induced T2D model, these inhibitors improved blood glucose levels, obesity, and cognitive function. BLINK11, in particular, shows promise as a therapeutic candidate for treating cognitive impairment associated with T2D.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112200"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143706138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Human activity’s impact on urban vegetation in China during the COVID-19 lockdown: An atypical anthropogenic disturbance

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-03-11 DOI: 10.1016/j.isci.2025.112195

Yujie Li , Shaodong Huang , Panfei Fang , Yuying Liang , Jia Wang

{"title":"Human activity’s impact on urban vegetation in China during the COVID-19 lockdown: An atypical anthropogenic disturbance","authors":"Yujie Li , Shaodong Huang , Panfei Fang , Yuying Liang , Jia Wang","doi":"10.1016/j.isci.2025.112195","DOIUrl":"10.1016/j.isci.2025.112195","url":null,"abstract":"<div><div>The COVID-19 lockdown led to reduced industrial and transportation emissions in Chinese cities, improving air quality and affecting large-scale vegetation. This study examines changes in net primary productivity (NPP) across 283 prefecture-level cities in China (PCC) during the lockdown, focusing on aerosol optical depth (AOD), nighttime light (NTL), temperature, and precipitation. Results from spring 2020 show that 53.5% of cities experienced increased NPP, with greater gains in cities with high industrial and traffic activity due to reduced AOD. Structural equation modeling revealed that urban characteristics, particularly industrial levels, influenced NPP primarily through changes in AOD, with human activity shifts playing a larger role than climate factors. In cities with substantial NPP changes, human activity effects were especially pronounced. These findings highlight the complex interactions among urban characteristics, environmental changes, and vegetation responses, offering insights for ecological management and urban planning in the face of future disruptions.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 4","pages":"Article 112195"},"PeriodicalIF":4.6,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0