PLoS Biology最新文献_第10页

Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy. MAPK4协同激活PDK1和AKT可促进肿瘤生长和对治疗的抵抗。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002227

Dong Han, Wei Wang, Julie Heejin Jeon, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang

{"title":"Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy.","authors":"Dong Han, Wei Wang, Julie Heejin Jeon, Tao Shen, Xiangsheng Huang, Ping Yi, Bingning Dong, Feng Yang","doi":"10.1371/journal.pbio.3002227","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002227","url":null,"abstract":"Phosphoinositide-dependent kinase-1 (PDK1) is a master kinase of the protein A, G, and C (AGC) family kinases that play important roles in regulating cancer cell proliferation, survival, and metabolism. Besides phosphorylating/activating AKT at the cell membrane in a PI3K-dependent manner, PDK1 also exhibits constitutive activity on many other AGC kinases for tumor-promoting activity. In the latter case, PDK1 protein levels dominate its activity. We previously reported that MAPK4, an atypical MAPK, can PI3K-independently promote AKT activation and tumor growth. Here, using triple-negative breast cancer (TNBC) cell models, we demonstrate that MAPK4 can also enhance PDK1 protein synthesis, thus phosphorylate/activate PDK1 substrates beyond AKT. This new MAPK4-PDK1 axis alone lacks vigorous tumor-promoting activity but cooperates with our previously reported MAPK4-AKT axis to promote tumor growth. Besides enhancing resistance to PI3K blockade, MAPK4 also promotes cancer cell resistance to the more stringent PI3K and PDK1 co-blockade, a recently proposed therapeutic strategy. Currently, there is no MAPK4 inhibitor to treat MAPK4-high cancers. Based on the concerted action of MAPK4-AKT and MAPK4-PDK1 axis in promoting cancer, we predict and confirm that co-targeting AKT and PDK1 effectively represses MAPK4-induced cancer cell growth, suggesting a potential therapeutic strategy to treat MAPK4-high cancers.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10395914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9941366","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

Planting the seeds for a forest of RNAi pathways. 为RNAi通路的森林播下种子。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3002279

Peter Sarkies

引用次数: 0

FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells. FOXP1在人皮层基底放射状胶质细胞中协调神经发生。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-08-01 DOI: 10.1371/journal.pbio.3001852

Seon Hye E Park, Ashwinikumar Kulkarni, Genevieve Konopka

{"title":"FOXP1 orchestrates neurogenesis in human cortical basal radial glial cells.","authors":"Seon Hye E Park, Ashwinikumar Kulkarni, Genevieve Konopka","doi":"10.1371/journal.pbio.3001852","DOIUrl":"https://doi.org/10.1371/journal.pbio.3001852","url":null,"abstract":"During cortical development, human basal radial glial cells (bRGCs) are highly capable of sustained self-renewal and neurogenesis. Selective pressures on this cell type may have contributed to the evolution of the human neocortex, leading to an increase in cortical size. bRGCs have enriched expression for Forkhead Box P1 (FOXP1), a transcription factor implicated in neurodevelopmental disorders (NDDs) such as autism spectrum disorder. However, the cell type-specific roles of FOXP1 in bRGCs during cortical development remain unexplored. Here, we examine the requirement for FOXP1 gene expression regulation underlying the production of bRGCs using human brain organoids. We examine a developmental time point when FOXP1 expression is highest in the cortical progenitors, and the bRGCs, in particular, begin to actively produce neurons. With the loss of FOXP1, we show a reduction in the number of bRGCs, as well as reduced proliferation and differentiation of the remaining bRGCs, all of which lead to reduced numbers of excitatory cortical neurons over time. Using single-nuclei RNA sequencing and cell trajectory analysis, we uncover a role for FOXP1 in directing cortical progenitor proliferation and differentiation by regulating key signaling pathways related to neurogenesis and NDDs. Together, these results demonstrate that FOXP1 regulates human-specific features in early cortical development.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10431666/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10009593","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

Policy recommendations to ensure that research software is openly accessible and reusable. 确保研究软件可公开获取和重复使用的政策建议。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-07-21 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pbio.3002204

Erin C McKiernan, Lorena Barba, Philip E Bourne, Caitlin Carter, Zach Chandler, Sayeed Choudhury, Stephen Jacobs, Daniel S Katz, Stefanie Lieggi, Beth Plale, Greg Tananbaum

引用次数: 0

Extensive topographic remapping and functional sharpening in the adult rat visual pathway upon first visual experience 首次视觉体验后成年大鼠视觉通路的广泛地形重映射和功能锐化

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-07-21 DOI: 10.1101/2022.06.20.496863

J. Carvalho, Francisca F. Fernandes, N. Shemesh

{"title":"Extensive topographic remapping and functional sharpening in the adult rat visual pathway upon first visual experience","authors":"J. Carvalho, Francisca F. Fernandes, N. Shemesh","doi":"10.1101/2022.06.20.496863","DOIUrl":"https://doi.org/10.1101/2022.06.20.496863","url":null,"abstract":"Understanding the dynamics of stability/plasticity balances during adulthood is pivotal for learning, disease, and recovery from injury. However, the brain-wide topography of sensory remapping remains unknown. Here, using a first-of-its-kind setup for delivering patterned visual stimuli in a rodent Magnetic Resonance Imaging (MRI) scanner, coupled with biologically-inspired computational models, we noninvasively mapped brain-wide properties - receptive fields (RFs) and spatial frequency (SF) tuning curves - that were insofar only available from invasive electrophysiology or optical imaging. We then tracked the RF dynamics in the chronic Visual Deprivation Model (VDM) of plasticity, and found that light exposure progressively promoted a large-scale topographic remapping in adult rats. Upon light exposure, the initially unspecialized visual pathway progressively evidenced sharpened RFs (smaller and more spatially selective) and enhanced spatial frequency tuning curves. Our findings reveal that visual experience following VDM reshapes both structure and function of the visual system and shifts the stability/plasticity balance in adults.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47688211","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

Spatiotemporal dynamics characterise spectral connectivity profiles of continuous speaking and listening. 时空动力学表征了连续说话和倾听的频谱连接概况。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-07-21 DOI: 10.1371/journal.pbio.3002178

Omid Abbasi, Nadine Steingräber, Nikos Chalas, Daniel S Kluger, Joachim Gross

{"title":"Spatiotemporal dynamics characterise spectral connectivity profiles of continuous speaking and listening.","authors":"Omid Abbasi, Nadine Steingräber, Nikos Chalas, Daniel S Kluger, Joachim Gross","doi":"10.1371/journal.pbio.3002178","DOIUrl":"https://doi.org/10.1371/journal.pbio.3002178","url":null,"abstract":"Speech production and perception are fundamental processes of human cognition that both rely on intricate processing mechanisms that are still poorly understood. Here, we study these processes by using magnetoencephalography (MEG) to comprehensively map connectivity of regional brain activity within the brain and to the speech envelope during continuous speaking and listening. Our results reveal not only a partly shared neural substrate for both processes but also a dissociation in space, delay, and frequency. Neural activity in motor and frontal areas is coupled to succeeding speech in delta band (1 to 3 Hz), whereas coupling in the theta range follows speech in temporal areas during speaking. Neural connectivity results showed a separation of bottom-up and top-down signalling in distinct frequency bands during speaking. Here, we show that frequency-specific connectivity channels for bottom-up and top-down signalling support continuous speaking and listening. These findings further shed light on the complex interplay between different brain regions involved in speech production and perception.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10208857","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

Engineering plants for a changing climate. 为气候变化设计植物。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-07-19 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pbio.3002243

Joanna Clarke, Pamela C Ronald

引用次数: 0

Targeting AAV vectors to the central nervous system by engineering capsid-receptor interactions that enable crossing of the blood-brain barrier. 通过设计能穿越血脑屏障的囊膜-受体相互作用，将 AAV 向量瞄准中枢神经系统。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-07-19 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pbio.3002112

Qin Huang, Albert T Chen, Ken Y Chan, Hikari Sorensen, Andrew J Barry, Bahar Azari, Qingxia Zheng, Thomas Beddow, Binhui Zhao, Isabelle G Tobey, Cynthia Moncada-Reid, Fatma-Elzahraa Eid, Christopher J Walkey, M Cecilia Ljungberg, William R Lagor, Jason D Heaney, Yujia A Chan, Benjamin E Deverman

{"title":"Targeting AAV vectors to the central nervous system by engineering capsid-receptor interactions that enable crossing of the blood-brain barrier.","authors":"Qin Huang, Albert T Chen, Ken Y Chan, Hikari Sorensen, Andrew J Barry, Bahar Azari, Qingxia Zheng, Thomas Beddow, Binhui Zhao, Isabelle G Tobey, Cynthia Moncada-Reid, Fatma-Elzahraa Eid, Christopher J Walkey, M Cecilia Ljungberg, William R Lagor, Jason D Heaney, Yujia A Chan, Benjamin E Deverman","doi":"10.1371/journal.pbio.3002112","DOIUrl":"10.1371/journal.pbio.3002112","url":null,"abstract":"Viruses have evolved the ability to bind and enter cells through interactions with a wide variety of cell macromolecules. We engineered peptide-modified adeno-associated virus (AAV) capsids that transduce the brain through the introduction of de novo interactions with 2 proteins expressed on the mouse blood-brain barrier (BBB), LY6A or LY6C1. The in vivo tropisms of these capsids are predictable as they are dependent on the cell- and strain-specific expression of their target protein. This approach generated hundreds of capsids with dramatically enhanced central nervous system (CNS) tropisms within a single round of screening in vitro and secondary validation in vivo thereby reducing the use of animals in comparison to conventional multi-round in vivo selections. The reproducible and quantitative data derived via this method enabled both saturation mutagenesis and machine learning (ML)-guided exploration of the capsid sequence space. Notably, during our validation process, we determined that nearly all published AAV capsids that were selected for their ability to cross the BBB in mice leverage either the LY6A or LY6C1 protein, which are not present in primates. This work demonstrates that AAV capsids can be directly targeted to specific proteins to generate potent gene delivery vectors with known mechanisms of action and predictable tropisms.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10355383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9849786","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

Pan-European study of genotypes and phenotypes in the Arabidopsis relative Cardamine hirsuta reveals how adaptation, demography, and development shape diversity patterns. 对拟南芥近缘植物 Cardamine hirsuta 的基因型和表型的泛欧研究揭示了适应、人口和发展如何形成多样性模式。

IF 9.8 1区生物学

PLoS Biology Pub Date : 2023-07-18 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pbio.3002191

Lukas Baumgarten, Bjorn Pieper, Baoxing Song, Sébastien Mane, Janne Lempe, Jonathan Lamb, Elizabeth L Cooke, Rachita Srivastava, Stefan Strütt, Danijela Žanko, Pedro Gp Casimiro, Asis Hallab, Maria Cartolano, Alexander D Tattersall, Bruno Huettel, Dmitry A Filatov, Pavlos Pavlidis, Barbara Neuffer, Christos Bazakos, Hanno Schaefer, Richard Mott, Xiangchao Gan, Carlos Alonso-Blanco, Stefan Laurent, Miltos Tsiantis

{"title":"Pan-European study of genotypes and phenotypes in the Arabidopsis relative Cardamine hirsuta reveals how adaptation, demography, and development shape diversity patterns.","authors":"Lukas Baumgarten, Bjorn Pieper, Baoxing Song, Sébastien Mane, Janne Lempe, Jonathan Lamb, Elizabeth L Cooke, Rachita Srivastava, Stefan Strütt, Danijela Žanko, Pedro Gp Casimiro, Asis Hallab, Maria Cartolano, Alexander D Tattersall, Bruno Huettel, Dmitry A Filatov, Pavlos Pavlidis, Barbara Neuffer, Christos Bazakos, Hanno Schaefer, Richard Mott, Xiangchao Gan, Carlos Alonso-Blanco, Stefan Laurent, Miltos Tsiantis","doi":"10.1371/journal.pbio.3002191","DOIUrl":"10.1371/journal.pbio.3002191","url":null,"abstract":"We study natural DNA polymorphisms and associated phenotypes in the Arabidopsis relative Cardamine hirsuta. We observed strong genetic differentiation among several ancestry groups and broader distribution of Iberian relict strains in European C. hirsuta compared to Arabidopsis. We found synchronization between vegetative and reproductive development and a pervasive role for heterochronic pathways in shaping C. hirsuta natural variation. A single, fast-cycling ChFRIGIDA allele evolved adaptively allowing range expansion from glacial refugia, unlike Arabidopsis where multiple FRIGIDA haplotypes were involved. The Azores islands, where Arabidopsis is scarce, are a hotspot for C. hirsuta diversity. We identified a quantitative trait locus (QTL) in the heterochronic SPL9 transcription factor as a determinant of an Azorean morphotype. This QTL shows evidence for positive selection, and its distribution mirrors a climate gradient that broadly shaped the Azorean flora. Overall, we establish a framework to explore how the interplay of adaptation, demography, and development shaped diversity patterns of 2 related plant species.","PeriodicalId":20240,"journal":{"name":"PLoS Biology","volume":null,"pages":null},"PeriodicalIF":9.8,"publicationDate":"2023-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10207249","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

How to engineer the unknown: Advancing a quantitative and predictive understanding of plant and soil biology to address climate change. 如何设计未知：促进对植物和土壤生物学的定量和预测性理解，以应对气候变化。

IF 7.8 1区生物学

PLoS Biology Pub Date : 2023-07-17 eCollection Date: 2023-07-01 DOI: 10.1371/journal.pbio.3002190

Simon Alamos, Patrick M Shih

引用次数: 0