Cell Chemical Biology最新文献_第5页

Reducing CRISPR-Cas9 off-target effects by optically controlled chemical modifications of guide RNA 通过光控化学修饰引导 RNA 减少 CRISPR-Cas9 的脱靶效应

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-10-17 DOI: 10.1016/j.chembiol.2024.09.006

Qianqian Qi , Xingyu Liu , Wei Xiong , Kaisong Zhang , Wei Shen , Yuanyuan Zhang , Xinyan Xu , Cheng Zhong , Yan Zhang , Tian Tian , Xiang Zhou

引用次数: 0

Uncovering lipid dynamics in Staphylococcus aureus osteomyelitis using multimodal imaging mass spectrometry 利用多模态成像质谱法揭示金黄色葡萄球菌骨髓炎的脂质动态变化

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-10-17 DOI: 10.1016/j.chembiol.2024.09.005

Christopher J. Good , Casey E. Butrico , Madeline E. Colley , Lauren N. Emmerson , Katherine N. Gibson-Corley , James E. Cassat , Jeffrey M. Spraggins , Richard M. Caprioli

{"title":"Uncovering lipid dynamics in Staphylococcus aureus osteomyelitis using multimodal imaging mass spectrometry","authors":"Christopher J. Good , Casey E. Butrico , Madeline E. Colley , Lauren N. Emmerson , Katherine N. Gibson-Corley , James E. Cassat , Jeffrey M. Spraggins , Richard M. Caprioli","doi":"10.1016/j.chembiol.2024.09.005","DOIUrl":"10.1016/j.chembiol.2024.09.005","url":null,"abstract":"<div><div>Osteomyelitis occurs when Staphylococcus aureus invades the bone microenvironment, resulting in a bone marrow abscess with a spatially defined architecture of cells and biomolecules. Imaging mass spectrometry and microscopy are tools that can be employed to interrogate the lipidome of S. aureus-infected murine femurs and reveal metabolic and signaling consequences of infection. Here, nearly 250 lipids were spatially mapped to healthy and infection-associated morphological features throughout the femur, establishing composition profiles for tissue types. Ether lipids and arachidonoyl lipids were altered between cells and tissue structures in abscesses, suggesting their roles in abscess formation and inflammatory signaling. Sterols, triglycerides, bis(monoacylglycero)phosphates, and gangliosides possessed ring-like distributions throughout the abscess, suggesting a hypothesized dysregulation of lipid metabolism in a population of cells that cannot be discerned with traditional microscopy. These data provide insight into the signaling function and metabolism of cells in the fibrotic border of abscesses, likely characteristic of lipid-laden macrophages.</div></div>","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"31 10","pages":"Pages 1852-1868.e5"},"PeriodicalIF":6.6,"publicationDate":"2024-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inviting new connections with science with public art in Philadelphia 费城公共艺术吸引人们与科学建立新联系

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-10-17 DOI: 10.1016/j.chembiol.2024.07.014

Sarah J. McAnulty

引用次数: 0

Enhancer reprogramming underlies therapeutic utility of a SMARCA2 degrader in SMARCA4 mutant cancer 增强子重编程是SMARCA2降解剂在SMARCA4突变癌症中发挥治疗作用的基础

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-10-07 DOI: 10.1016/j.chembiol.2024.09.004

Sasikumar Kotagiri, Nicholas Blazanin, Yuanxin Xi, Yanyan Han, Md Qudratullah, Xiaobing Liang, Yawen Wang, Poonam Pandey, Hira Mazhar, Truong Nguyen Lam, Anand Kamal Singh, Jing Wang, Yonathan Lissanu

{"title":"Enhancer reprogramming underlies therapeutic utility of a SMARCA2 degrader in SMARCA4 mutant cancer","authors":"Sasikumar Kotagiri, Nicholas Blazanin, Yuanxin Xi, Yanyan Han, Md Qudratullah, Xiaobing Liang, Yawen Wang, Poonam Pandey, Hira Mazhar, Truong Nguyen Lam, Anand Kamal Singh, Jing Wang, Yonathan Lissanu","doi":"10.1016/j.chembiol.2024.09.004","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.09.004","url":null,"abstract":"Genomic studies have identified frequent mutations in subunits of the SWI/SNF (switch/sucrose non-fermenting) chromatin remodeling complex including SMARCA4 and ARID1A in non-small cell lung cancer (NSCLC). Genetic evidence indicates that the paralog SMARCA2 is synthetic lethal to SMARCA4 suggesting SMARCA2 is a valuable therapeutic target. However, the discovery of selective inhibitors of SMARCA2 has been challenging. Here, we utilized structure-activity relationship (SAR) studies to develop YD23, a potent and selective proteolysis targeting chimera (PROTAC) targeting SMARCA2. Mechanistically, we show that SMARCA2 degradation induces reprogramming of the enhancer landscape in SMARCA4-mutant cells with loss of chromatin accessibility at enhancers of genes involved in cell proliferation. Furthermore, we identified YAP/TEADas key partners to SMARCA2 in driving growth of SMARCA4-mutant cells. Finally, we show that YD23 has potent tumor growth inhibitory activity in SMARCA4-mutant xenografts. These findings provide the mechanistic basis for development of SMARCA2 degraders as synthetic lethal therapeutics against SMARCA4-mutant lung cancers.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"9 27 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas 从假单胞菌中发现非典型 C16-三萜类化合物并进行生物合成

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-09-26 DOI: 10.1016/j.chembiol.2024.09.002

Xu-Hua Mo, Qing-Yin Pu, Tilo Lübken, Gui-Hong Yu, Mert Malay, Paul M. D’Agostino, Tobias A.M. Gulder

{"title":"Discovery and biosynthesis of non-canonical C16-terpenoids from Pseudomonas","authors":"Xu-Hua Mo, Qing-Yin Pu, Tilo Lübken, Gui-Hong Yu, Mert Malay, Paul M. D’Agostino, Tobias A.M. Gulder","doi":"10.1016/j.chembiol.2024.09.002","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.09.002","url":null,"abstract":"Biosynthesis of sodorifen with a unique C16-bicyclo[3.2.1]octene framework requires an S-adenosyl methionine-dependent methyltransferase SodC and terpene cyclase SodD. While bioinformatic analyses reveal a wide distribution of the sodCD genes organization in bacteria, their functional diversity remains largely unknown. Herein, two sodorifen-type gene clusters, pcch and pcau, from Pseudomonas sp. are heterologously expressed in Escherichia coli, leading to the discovery of two C16 terpenoids. Enzymatic synthesis of these compounds is achieved using the two (SodCD-like) pathway-specific enzymes. Enzyme assays using different combinations of methyltransferases and terpene synthases across the pcch, pcau, and sod pathways reveal a unifying biosynthetic mechanism: all three SodC-like enzymes methylate farnesyl pyrophosphate (FPP) with subsequent cyclization to a common intermediate, pre-sodorifen pyrophosphate. Structural diversification of this joint precursor solely occurs by the subsequently acting individual terpene synthases. Our findings expand basic biosynthetic understanding and structural diversity of unusual C16-terpenoids.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"35 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321402","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration 微生物衍生代谢物对神经退行性病变产生影响的机制

IF 8.6 1区生物学

Cell Chemical Biology Pub Date : 2024-09-25 DOI: 10.1016/j.chembiol.2024.08.014

Lara Kern, Ignacio Mastandrea, Anna Melekhova, Eran Elinav

{"title":"Mechanisms by which microbiome-derived metabolites exert their impacts on neurodegeneration","authors":"Lara Kern, Ignacio Mastandrea, Anna Melekhova, Eran Elinav","doi":"10.1016/j.chembiol.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.chembiol.2024.08.014","url":null,"abstract":"Recent developments in microbiome research suggest that the gut microbiome may remotely modulate central and peripheral neuronal processes, ranging from early brain development to age-related changes. Dysbiotic microbiome configurations have been increasingly associated with neurological disorders, such as neurodegeneration, but causal understanding of these associations remains limited. Most mechanisms explaining how the microbiome may induce such remote neuronal effects involve microbially modulated metabolites that influx into the ‘sterile’ host. Some metabolites are able to cross the blood-brain barrier (BBB) to reach the central nervous system, where they can impact a variety of cells and processes. Alternatively, metabolites may directly signal to peripheral nerves to act as neurotransmitters or exert modulatory functions, or impact immune responses, which, in turn, modulate neuronal function and associated disease propensity. Herein, we review the current knowledge highlighting microbiome-modulated metabolite impacts on neuronal disease, while discussing unknowns, controversies and prospects impacting this rapidly evolving research field.","PeriodicalId":265,"journal":{"name":"Cell Chemical Biology","volume":"22 1","pages":""},"PeriodicalIF":8.6,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The next Nobel Prize in chemistry or in physiology or medicine 下一个诺贝尔化学奖、生理学奖或医学奖

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.013

Cigall Kadoch, Jason M. Sheltzer, Hang Yin

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The best of both worlds: Chemigenetic fluorescent sensors for biological imaging 两全其美：用于生物成像的化学基因荧光传感器

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.002

Kelvin K. Tsao , Shosei Imai , Michael Chang , Saaya Hario , Takuya Terai , Robert E. Campbell

引用次数: 0

RNA and condensates: Disease implications and therapeutic opportunities RNA 和凝结物：疾病影响和治疗机会

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.08.009

Tina W. Han , Bede Portz , Richard A. Young , Ann Boija , Isaac A. Klein

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The physiological and pathological roles of RNA modifications in T cells T 细胞中 RNA 修饰的生理和病理作用

IF 6.6 1区生物学

Cell Chemical Biology Pub Date : 2024-09-19 DOI: 10.1016/j.chembiol.2024.06.003

引用次数: 0