PLoS Biology最新文献_第4页

A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans. 一种安全机制能够使秀丽隐杆线虫在衰老过程中对蛋白质聚集产生组织特异性抵抗。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-09-14 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002284

Raimund Jung, Marie C Lechler, Ana Fernandez-Villegas, Chyi Wei Chung, Harry C Jones, Yoon Hee Choi, Maximilian A Thompson, Christian Rödelsperger, Waltraud Röseler, Gabriele S Kaminski Schierle, Ralf J Sommer, Della C David

{"title":"A safety mechanism enables tissue-specific resistance to protein aggregation during aging in C. elegans.","authors":"Raimund Jung, Marie C Lechler, Ana Fernandez-Villegas, Chyi Wei Chung, Harry C Jones, Yoon Hee Choi, Maximilian A Thompson, Christian Rödelsperger, Waltraud Röseler, Gabriele S Kaminski Schierle, Ralf J Sommer, Della C David","doi":"10.1371/journal.pbio.3002284","DOIUrl":"10.1371/journal.pbio.3002284","url":null,"abstract":"During aging, proteostasis capacity declines and distinct proteins become unstable and can accumulate as protein aggregates inside and outside of cells. Both in disease and during aging, proteins selectively aggregate in certain tissues and not others. Yet, tissue-specific regulation of cytoplasmic protein aggregation remains poorly understood. Surprisingly, we found that the inhibition of 3 core protein quality control systems, namely chaperones, the proteasome, and macroautophagy, leads to lower levels of age-dependent protein aggregation in Caenorhabditis elegans pharyngeal muscles, but higher levels in body-wall muscles. We describe a novel safety mechanism that selectively targets newly synthesized proteins to suppress their aggregation and associated proteotoxicity. The safety mechanism relies on macroautophagy-independent lysosomal degradation and involves several previously uncharacterized components of the intracellular pathogen response (IPR). We propose that this protective mechanism engages an anti-aggregation machinery targeting aggregating proteins for lysosomal degradation.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 9","pages":"e3002284"},"PeriodicalIF":7.8,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501630/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10283456","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The human fungal pathogen Aspergillus fumigatus can produce the highest known number of meiotic crossovers. 人类真菌病原体烟曲霉可以产生已知数量最高的减数分裂交叉。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-09-14 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002278

Ben Auxier, Alfons J M Debets, Felicia Adelina Stanford, Johanna Rhodes, Frank M Becker, Francisca Reyes Marquez, Reindert Nijland, Paul S Dyer, Matthew C Fisher, Joost van den Heuvel, Eveline Snelders

{"title":"The human fungal pathogen Aspergillus fumigatus can produce the highest known number of meiotic crossovers.","authors":"Ben Auxier, Alfons J M Debets, Felicia Adelina Stanford, Johanna Rhodes, Frank M Becker, Francisca Reyes Marquez, Reindert Nijland, Paul S Dyer, Matthew C Fisher, Joost van den Heuvel, Eveline Snelders","doi":"10.1371/journal.pbio.3002278","DOIUrl":"10.1371/journal.pbio.3002278","url":null,"abstract":"Sexual reproduction involving meiosis is essential in most eukaryotes. This produces offspring with novel genotypes, both by segregation of parental chromosomes as well as crossovers between homologous chromosomes. A sexual cycle for the opportunistic human pathogenic fungus Aspergillus fumigatus is known, but the genetic consequences of meiosis have remained unknown. Among other Aspergilli, it is known that A. flavus has a moderately high recombination rate with an average of 4.2 crossovers per chromosome pair, whereas A. nidulans has in contrast a higher rate with 9.3 crossovers per chromosome pair. Here, we show in a cross between A. fumigatus strains that they produce an average of 29.9 crossovers per chromosome pair and large variation in total map length across additional strain crosses. This rate of crossovers per chromosome is more than twice that seen for any known organism, which we discuss in relation to other genetic model systems. We validate this high rate of crossovers through mapping of resistance to the laboratory antifungal acriflavine by using standing variation in an undescribed ABC efflux transporter. We then demonstrate that this rate of crossovers is sufficient to produce one of the common multidrug resistant haplotypes found in the cyp51A gene (TR34/L98H) in crosses among parents harboring either of 2 nearby genetic variants, possibly explaining the early spread of such haplotypes. Our results suggest that genomic studies in this species should reassess common assumptions about linkage between genetic regions. The finding of an unparalleled crossover rate in A. fumigatus provides opportunities to understand why these rates are not generally higher in other eukaryotes.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 9","pages":"e3002278"},"PeriodicalIF":7.8,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10284327","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","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 novel TOX3-WDR5-ABCG2 signaling axis regulates the progression of colorectal cancer by accelerating stem-like traits and chemoresistance. 一种新的TOX3-WDR5-ABCG2信号轴通过加速干样性状和化疗耐药性来调节结直肠癌癌症的进展。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-09-14 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002256

Jiaojiao Hao, Jinsheng Huang, Chunyu Hua, Yan Zuo, Wendan Yu, Xiaojun Wu, Liren Li, Guoqing Xue, Xinyu Wan, Liyuan Ru, Ziyue Guo, Shilong Han, Wuguo Deng, Fei Lin, Wei Guo

{"title":"A novel TOX3-WDR5-ABCG2 signaling axis regulates the progression of colorectal cancer by accelerating stem-like traits and chemoresistance.","authors":"Jiaojiao Hao, Jinsheng Huang, Chunyu Hua, Yan Zuo, Wendan Yu, Xiaojun Wu, Liren Li, Guoqing Xue, Xinyu Wan, Liyuan Ru, Ziyue Guo, Shilong Han, Wuguo Deng, Fei Lin, Wei Guo","doi":"10.1371/journal.pbio.3002256","DOIUrl":"10.1371/journal.pbio.3002256","url":null,"abstract":"The eradication of cancer stem cells (CSCs) with drug resistance confers the probability of local tumor control after chemotherapy or targeted therapy. As the main drug resistance marker, ABCG2 is also critical for colorectal cancer (CRC) evolution, in particular cancer stem-like traits expansion. Hitherto, the knowledge about the expression regulation of ABCG2, in particular its upstream transcriptional regulatory mechanisms, remains limited in cancer, including CRC. Here, ABCG2 was found to be markedly up-regulated in CRC CSCs (cCSCs) expansion and chemo-resistant CRC tissues and closely associated with CRC recurrence. Mechanistically, TOX3 was identified as a specific transcriptional factor to drive ABCG2 expression and subsequent cCSCs expansion and chemoresistance by binding to -261 to -141 segments of the ABCG2 promoter region. Moreover, we found that TOX3 recruited WDR5 to promote tri-methylation of H3K4 at the ABCG2 promoter in cCSCs, which further confers stem-like traits and chemoresistance to CRC by co-regulating the transcription of ABCG2. In line with this observation, TOX3, WDR5, and ABCG2 showed abnormal activation in chemo-resistant tumor tissues of in situ CRC mouse model and clinical investigation further demonstrated the comprehensive assessment of TOX3, WDR5, and ABCG2 could be a more efficient strategy for survival prediction of CRC patients with recurrence or metastasis. Thus, our study found that TOX3-WDR5/ABCG2 signaling axis plays a critical role in regulating CRC stem-like traits and chemoresistance, and a combination of chemotherapy with WDR5 inhibitors may induce synthetic lethality in ABCG2-deregulated tumors.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 9","pages":"e3002256"},"PeriodicalIF":9.8,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10501593/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10287706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Supporting nonlinear careers to diversify science. 支持非线性职业，使科学多样化。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-09-14 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002291

Anna L Vlasits, Monique L Smith, Maria Maldonado, Simone Brixius-Anderko

引用次数: 0

Wounding the stroma: Docetaxel's role in dormant breast cancer escape. 基质损伤：多西他赛在休眠期乳腺癌症转移中的作用。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-09-13 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002297

Tyler T Cooper, Lynne-Marie Postovit

引用次数: 0

Systematic characterization of photoperiodic gene expression patterns reveals diverse seasonal transcriptional systems in Arabidopsis. 光周期基因表达模式的系统表征揭示了拟南芥中不同的季节性转录系统。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-09-12 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002283

Chun Chung Leung, Daniel A Tarté, Lilijana S Oliver, Qingqing Wang, Joshua M Gendron

{"title":"Systematic characterization of photoperiodic gene expression patterns reveals diverse seasonal transcriptional systems in Arabidopsis.","authors":"Chun Chung Leung, Daniel A Tarté, Lilijana S Oliver, Qingqing Wang, Joshua M Gendron","doi":"10.1371/journal.pbio.3002283","DOIUrl":"10.1371/journal.pbio.3002283","url":null,"abstract":"Photoperiod is an annual cue measured by biological systems to align growth and reproduction with the seasons. In plants, photoperiodic flowering has been intensively studied for over 100 years, but we lack a complete picture of the transcriptional networks and cellular processes that are photoperiodic. We performed a transcriptomics experiment on Arabidopsis plants grown in 3 different photoperiods and found that thousands of genes show photoperiodic alteration in gene expression. Gene clustering, daily expression integral calculations, and cis-element analysis then separate photoperiodic genes into co-expression subgroups that display 19 diverse seasonal expression patterns, opening the possibility that many photoperiod measurement systems work in parallel in Arabidopsis. Then, functional enrichment analysis predicts co-expression of important cellular pathways. To test these predictions, we generated a comprehensive catalog of genes in the phenylpropanoid biosynthesis pathway, overlaid gene expression data, and demonstrated that photoperiod intersects with 2 major phenylpropanoid pathways differentially, controlling flavonoids but not lignin. Finally, we describe the development of a new app that visualizes photoperiod transcriptomic data for the wider community.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 9","pages":"e3002283"},"PeriodicalIF":7.8,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10240137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The genetic identity of neighboring plants in intraspecific mixtures modulates disease susceptibility of both wheat and rice. 种内混合物中相邻植物的遗传特性调节小麦和水稻的疾病易感性。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-09-12 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002287

Rémi Pélissier, Elsa Ballini, Coline Temple, Aurélie Ducasse, Michel Colombo, Julien Frouin, Xiaoping Qin, Huichuan Huang, David Jacques, Fort Florian, Fréville Hélène, Violle Cyrille, Jean-Benoit Morel

{"title":"The genetic identity of neighboring plants in intraspecific mixtures modulates disease susceptibility of both wheat and rice.","authors":"Rémi Pélissier, Elsa Ballini, Coline Temple, Aurélie Ducasse, Michel Colombo, Julien Frouin, Xiaoping Qin, Huichuan Huang, David Jacques, Fort Florian, Fréville Hélène, Violle Cyrille, Jean-Benoit Morel","doi":"10.1371/journal.pbio.3002287","DOIUrl":"10.1371/journal.pbio.3002287","url":null,"abstract":"Mixing crop cultivars has long been considered as a way to control epidemics at the field level and is experiencing a revival of interest in agriculture. Yet, the ability of mixing to control pests is highly variable and often unpredictable in the field. Beyond classical diversity effects such as dispersal barrier generated by genotypic diversity, several understudied processes are involved. Among them is the recently discovered neighbor-modulated susceptibility (NMS), which depicts the phenomenon that susceptibility in a given plant is affected by the presence of another healthy neighboring plant. Despite the putative tremendous importance of NMS for crop science, its occurrence and quantitative contribution to modulating susceptibility in cultivated species remains unknown. Here, in both rice and wheat inoculated in greenhouse conditions with foliar fungal pathogens considered as major threats, using more than 200 pairs of intraspecific genotype mixtures, we experimentally demonstrate the occurrence of NMS in 11% of the mixtures grown in experimental conditions that precluded any epidemics. Thus, the susceptibility of these 2 major crops results from indirect effects originating from neighboring plants. Quite remarkably, the levels of susceptibility modulated by plant-plant interactions can reach those conferred by intrinsic basal immunity. These findings open new avenues to develop more sustainable agricultural practices by engineering less susceptible crop mixtures thanks to emergent but now predictable properties of mixtures.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 9","pages":"e3002287"},"PeriodicalIF":9.8,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10241873","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Taxane chemotherapy induces stromal injury that leads to breast cancer dormancy escape. 紫杉烷化疗诱导间质损伤，导致乳腺癌症休眠逃避。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-09-12 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002275

Ramya Ganesan, Swati S Bhasin, Mojtaba Bakhtiary, Upaasana Krishnan, Nagarjuna R Cheemarla, Beena E Thomas, Manoj K Bhasin, Vikas P Sukhatme

{"title":"Taxane chemotherapy induces stromal injury that leads to breast cancer dormancy escape.","authors":"Ramya Ganesan, Swati S Bhasin, Mojtaba Bakhtiary, Upaasana Krishnan, Nagarjuna R Cheemarla, Beena E Thomas, Manoj K Bhasin, Vikas P Sukhatme","doi":"10.1371/journal.pbio.3002275","DOIUrl":"10.1371/journal.pbio.3002275","url":null,"abstract":"A major cause of cancer recurrence following chemotherapy is cancer dormancy escape. Taxane-based chemotherapy is standard of care in breast cancer treatment aimed at killing proliferating cancer cells. Here, we demonstrate that docetaxel injures stromal cells, which release protumor cytokines, IL-6 and granulocyte colony stimulating factor (G-CSF), that in turn invoke dormant cancer outgrowth both in vitro and in vivo. Single-cell transcriptomics shows a reprogramming of awakened cancer cells including several survival cues such as stemness, chemoresistance in a tumor stromal organoid (TSO) model, as well as an altered tumor microenvironment (TME) with augmented protumor immune signaling in a syngeneic mouse breast cancer model. IL-6 plays a role in cancer cell proliferation, whereas G-CSF mediates tumor immunosuppression. Pathways and differential expression analyses confirmed MEK as the key regulatory molecule in cancer cell outgrowth and survival. Antibody targeting of protumor cytokines (IL-6, G-CSF) or inhibition of cytokine signaling via MEK/ERK pathway using selumetinib prior to docetaxel treatment prevented cancer dormancy outgrowth suggesting a novel therapeutic strategy to prevent cancer recurrence.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 9","pages":"e3002275"},"PeriodicalIF":9.8,"publicationDate":"2023-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497165/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10241872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Applying an evolutionary mismatch framework to understand disease susceptibility. 应用进化错配框架来理解疾病易感性。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-09-11 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002311

Amanda J Lea, Andrew G Clark, Andrew W Dahl, Orrin Devinsky, Angela R Garcia, Christopher D Golden, Joseph Kamau, Thomas S Kraft, Yvonne A L Lim, Dino J Martins, Donald Mogoi, Päivi Pajukanta, George H Perry, Herman Pontzer, Benjamin C Trumble, Samuel S Urlacher, Vivek V Venkataraman, Ian J Wallace, Michael Gurven, Daniel E Lieberman, Julien F Ayroles

{"title":"Applying an evolutionary mismatch framework to understand disease susceptibility.","authors":"Amanda J Lea, Andrew G Clark, Andrew W Dahl, Orrin Devinsky, Angela R Garcia, Christopher D Golden, Joseph Kamau, Thomas S Kraft, Yvonne A L Lim, Dino J Martins, Donald Mogoi, Päivi Pajukanta, George H Perry, Herman Pontzer, Benjamin C Trumble, Samuel S Urlacher, Vivek V Venkataraman, Ian J Wallace, Michael Gurven, Daniel E Lieberman, Julien F Ayroles","doi":"10.1371/journal.pbio.3002311","DOIUrl":"10.1371/journal.pbio.3002311","url":null,"abstract":"Noncommunicable diseases (NCDs) are on the rise worldwide. Obesity, cardiovascular disease, and type 2 diabetes are among a long list of \"lifestyle\" diseases that were rare throughout human history but are now common. The evolutionary mismatch hypothesis posits that humans evolved in environments that radically differ from those we currently experience; consequently, traits that were once advantageous may now be \"mismatched\" and disease causing. At the genetic level, this hypothesis predicts that loci with a history of selection will exhibit \"genotype by environment\" (GxE) interactions, with different health effects in \"ancestral\" versus \"modern\" environments. To identify such loci, we advocate for combining genomic tools in partnership with subsistence-level groups experiencing rapid lifestyle change. In these populations, comparisons of individuals falling on opposite extremes of the \"matched\" to \"mismatched\" spectrum are uniquely possible. More broadly, the work we propose will inform our understanding of environmental and genetic risk factors for NCDs across diverse ancestries and cultures.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":"21 9","pages":"e3002311"},"PeriodicalIF":9.8,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10513379/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10563866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fluctuating temperatures have a surprising effect on disease transmission. 气温的波动对疾病的传播有着惊人的影响。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-09-08 eCollection Date: 2023-09-01 DOI: 10.1371/journal.pbio.3002288

Marta S Shocket

引用次数: 0