iScience最新文献_第3页

Effect of glycosylation on protein folding: From biological roles to chemical protein synthesis 糖基化对蛋白质折叠的影响：从生物学作用到化学蛋白质合成

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112605

Chunchun Hao , Qijie Zou , Xuerong Bai , Weiwei Shi

引用次数: 0

Computational design of diverse nuclear factor erythroid 2 activators with cellular antioxidative activity 具有细胞抗氧化活性的多种核因子红细胞2激活剂的计算设计

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112621

Mingyue Yuwen , Xiaoning Gao , Junli Ba , Jiayang Wu , Jun Kang , Sheng Ye , Cheng Zhu

{"title":"Computational design of diverse nuclear factor erythroid 2 activators with cellular antioxidative activity","authors":"Mingyue Yuwen , Xiaoning Gao , Junli Ba , Jiayang Wu , Jun Kang , Sheng Ye , Cheng Zhu","doi":"10.1016/j.isci.2025.112621","DOIUrl":"10.1016/j.isci.2025.112621","url":null,"abstract":"<div><div>Oxidative stress disrupts signaling pathways contributing to chronic diseases, while the KEAP1-NRF2 pathway is central to cellular antioxidant defenses. Current synthetic antioxidants struggle to activate this pathway efficiently or selectively. In this study, we employed deep learning algorithms to design miniproteins capable of activating NRF2. Five designed binders potently interfered with the KEAP1-NRF2 complex, exhibiting affinities ranging from 4.4 nM to 53.3 nM toward KEAP1. Two of these binders, designed through the motif scaffolding method, activated NRF2 in eukaryotic cells increasing antioxidant gene expression 3.8-fold and boosting cell survival across oxidative stress levels. Our approach illustrates the potential of integrated deep learning models to develop stable miniproteins that exhibit a variety of structural frameworks and thermodynamic characteristics. These designs hold promise for countering the cumulative effects of oxidative damage and for supporting the establishment of adaptive homeostasis within key antioxidative systems.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112621"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144134177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mapping protein-metabolite interactions in E. coli by integrating chromatographic techniques and co-fractionation mass spectrometry 结合色谱技术和共分离质谱法绘制大肠杆菌中蛋白质-代谢物相互作用图

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112611

Mateusz Wagner , Jieun Kang , Catherine Mercado , Venkatesh P. Thirumlaikumar , Michal Gorka , Hanne Zillmer , Jingzhe Guo , Romina I. Minen , Caroline F. Plecki , Katayoon Dehesh , Frank C. Schroeder , Dirk Walther , Aleksandra Skirycz

{"title":"Mapping protein-metabolite interactions in E. coli by integrating chromatographic techniques and co-fractionation mass spectrometry","authors":"Mateusz Wagner , Jieun Kang , Catherine Mercado , Venkatesh P. Thirumlaikumar , Michal Gorka , Hanne Zillmer , Jingzhe Guo , Romina I. Minen , Caroline F. Plecki , Katayoon Dehesh , Frank C. Schroeder , Dirk Walther , Aleksandra Skirycz","doi":"10.1016/j.isci.2025.112611","DOIUrl":"10.1016/j.isci.2025.112611","url":null,"abstract":"<div><div>Toward characterization of protein-metabolite interactomes, we recently introduced PROMIS, a co-fractionation-based mass spectrometry approach. However, the challenge lies in distinguishing true interactors from coincidental co-elution when a metabolite co-fractionates with numerous proteins. To address this, we integrated two chromatographic techniques—size exclusion and ion exchange—to enhance the mapping of protein-metabolite interactions (PMIs) in <em>Escherichia coli</em>. This integration aims to refine the PMI network by considering size and charge characteristics, resulting in 994 interactions involving 51 metabolites and 465 proteins. The PMI network is enriched for known and predicted interactions, providing validation. Furthermore, analyzing protein targets for different metabolites revealed functional insights, such as a connection between proteinogenic dipeptides and fatty acid biosynthesis. Notably, we uncovered an inhibitory interaction between the riboflavin degradation product lumichrome and orotate phosphoribosyltransferase, a key enzyme in <em>de novo</em> pyrimidine synthesis affecting biofilm formation. In summary, our integrated chromatographic approach significantly advances PMI mapping.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112611"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144084700","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Different populations of mouse egg cortical vesicles are responsible for post-fertilization zinc sparks and proteolysis of the zona pellucida 不同种群的小鼠卵皮质囊泡负责受精后的锌火花和透明带的蛋白质水解

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112606

Omar José , Boris Baibakov , Jurrien Dean

引用次数: 0

Cyanobacteria dynamically regulate phycobilisome-to-photosystem excitation energy transfer 蓝藻动态调节藻胆体到光系统的激发能转移

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112610

Ivo H.M. van Stokkum , Dariusz M. Niedzwiedzki , Parveen Akhtar , Avratanu Biswas , Petar H. Lambrev , Haijun Liu

引用次数: 0

Multi-analyte approach combining cfDNA sequencing and protein testing for early ovarian cancer detection 结合cfDNA测序和蛋白检测的多分析物方法用于早期卵巢癌的检测

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112617

Fenfen Wang (王芬芬) , Lingfang Wang (王玲芳) , Ziyu Xing (幸子玉) , Lingjia Lu (陆伶佳) , Zhuoqun Lin (林卓群) , Senmi Qian (钱森密) , Tao Zhu (朱滔) , Zhuyan Shao (邵株燕) , Lingjun Zhao (赵玲军) , Jie Dong (董婕) , Fangfang Qian (钱芳芳) , Yang Li (李阳) , Xiaojing Chen (陈晓静) , Siqi Yang (杨思琦) , Xiaodong Cheng (程晓东)

{"title":"Multi-analyte approach combining cfDNA sequencing and protein testing for early ovarian cancer detection","authors":"Fenfen Wang (王芬芬) , Lingfang Wang (王玲芳) , Ziyu Xing (幸子玉) , Lingjia Lu (陆伶佳) , Zhuoqun Lin (林卓群) , Senmi Qian (钱森密) , Tao Zhu (朱滔) , Zhuyan Shao (邵株燕) , Lingjun Zhao (赵玲军) , Jie Dong (董婕) , Fangfang Qian (钱芳芳) , Yang Li (李阳) , Xiaojing Chen (陈晓静) , Siqi Yang (杨思琦) , Xiaodong Cheng (程晓东)","doi":"10.1016/j.isci.2025.112617","DOIUrl":"10.1016/j.isci.2025.112617","url":null,"abstract":"<div><div>Non-invasive liquid biopsy is a promising strategy for ovarian cancer (OC) detection. We evaluated the feasibility and efficacy of a multi-analyte approach combining circulating tumor DNA (ctDNA) detection with protein biomarkers for early OC detection. At 95% specificity, CA125 and ctDNA alone exhibited an overall sensitivity of 79.0% and 58.7%, respectively; however, when CA125 was combined with ctDNA, sensitivity reached 85.5%. Integrating CA125 and human epididymis protein-4 (HE4) in the risk of ovarian malignancy algorithm (ROMA) index, yielded a sensitivity of 86.2%. When four additional proteins (HE4, cancer antigen 19-9, prolactin, and interleukin-6) were added to CA125 and ctDNA in the EarlySEEK model, sensitivity increased to 94.2%. Meanwhile, the EarlySEEK model was not affected by menopausal status, and outperformed CA125 in distinguishing benign and malignant ovarian tumors. These findings demonstrate that EarlySEEK could effectively identify OC at early stage when they are more likely to be curable.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112617"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144123681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Epigenetics: A link between toxicants and diseases 表观遗传学：毒素和疾病之间的联系

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112613

Anna Romanò , Christina Pagiatakis , Rosalba Gornati , Giovanni Bernardini , Roberto Papait

引用次数: 0

Altered brain activity during active forgetting in highly superior autobiographical memory: Evidence from an item-method directed forgetting 在高度卓越的自传式记忆中，主动遗忘时大脑活动的改变：来自项目法定向遗忘的证据

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112607

Valerio Santangelo , Tiziana Pedale , Sarah Daviddi , Ilenia Salsano , Simone Macrì , Patrizia Campolongo

{"title":"Altered brain activity during active forgetting in highly superior autobiographical memory: Evidence from an item-method directed forgetting","authors":"Valerio Santangelo , Tiziana Pedale , Sarah Daviddi , Ilenia Salsano , Simone Macrì , Patrizia Campolongo","doi":"10.1016/j.isci.2025.112607","DOIUrl":"10.1016/j.isci.2025.112607","url":null,"abstract":"<div><div>Individuals with highly superior autobiographical memory (HSAM) challenge current memory knowledge, yet it remains unclear if their superior memory stems from impaired forgetting. Using a directed forgetting paradigm, we examined this in 12 individuals with HSAM and 30 controls. During fMRI, participants viewed single words followed by “remember” or “forget” instructions. Five minutes later, participants performed a memory recognition task with old (previously studied) and new words. Behaviorally, both groups showed similar forgetting effects, recognizing fewer to-be-forgotten than to-be-remembered words. However, at the neural level, HSAM individuals showed increased activity in the dorsal and ventral frontoparietal regions during initial word presentation, prior to memory instructions. During active forgetting, they also showed increased activity in the anterior and posterior midline regions. These findings suggest that HSAM individuals require additional neural resources for active forgetting to compensate for their enhanced initial processing of stimuli, enabling them to match the forgetting performance of controls.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112607"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144107555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

KDM3A and KDM3B regulate alternative splicing in mouse pluripotent stem cells KDM3A和KDM3B调节小鼠多能干细胞的选择性剪接

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112612

Caleb M. Dillingham , Harshini Cormaty , Ellen C. Morgan , Andrew I. Tak , Dakarai E. Esgdaille , Paul L. Boutz , Rupa Sridharan

{"title":"KDM3A and KDM3B regulate alternative splicing in mouse pluripotent stem cells","authors":"Caleb M. Dillingham , Harshini Cormaty , Ellen C. Morgan , Andrew I. Tak , Dakarai E. Esgdaille , Paul L. Boutz , Rupa Sridharan","doi":"10.1016/j.isci.2025.112612","DOIUrl":"10.1016/j.isci.2025.112612","url":null,"abstract":"<div><div>Histone modifying enzymes are crucial in preserving cell identity by establishing a conducive chromatin environment for lineage specific transcription factor activity. Mouse pluripotent embryonic stem cells (mESCs) show lower levels of gene repression associated with histone modifications, facilitating rapid response to differentiation cues. The KDM3 family of histone demethylases removes repressive histone H3 lysine 9 dimethylation (H3K9me2). We uncover a surprising role for the KDM3 proteins in the post-transcriptional regulation of mESCs. Proteomic analysis shows KDM3A and KDM3B interacting with RNA processing factors such as EFTUD2 and PRMT5. Acute degradation of the endogenous KDM3A and KDM3B proteins resulted in altered splicing independent of H3K9me2 status or catalytic activity. These splicing changes partially resemble the splicing pattern of the more blastocyst-like ground state of pluripotency and occur in important chromatin and transcription factors such as <em>Dnmt3b</em> and <em>Tcf12</em>. Our findings reveal non-canonical roles of histone demethylating enzymes in splicing to regulate cell identity.</div></div>","PeriodicalId":342,"journal":{"name":"iScience","volume":"28 6","pages":"Article 112612"},"PeriodicalIF":4.6,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144167582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Leaves for high power density hydrovoltaic generators 叶片用于高功率密度水伏发电机

IF 4.6 2区综合性期刊

iScience Pub Date : 2025-05-08 DOI: 10.1016/j.isci.2025.112601

Neha M. Viradia , Ramesh Y. Adhikari

引用次数: 0