首页 > 最新文献

Proceedings of the National Academy of Sciences of the United States of America最新文献

英文 中文
Structural determinants of protein kinase A essential for CFTR channel activation. 对 CFTR 通道激活至关重要的蛋白激酶 A 的结构决定因素。
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-04 DOI: 10.1073/pnas.2407728121
Csaba Mihályi, Iordan Iordanov, Andras Szollosi, László Csanády

Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the anion channel mutated in cystic fibrosis (CF) patients, is activated by the catalytic subunit of protein kinase A (PKA-C). PKA-C activates CFTR both noncatalytically, through binding, and catalytically, through phosphorylation of multiple serines in CFTR's regulatory (R) domain. Here, we identify key molecular determinants of the CFTR/PKA-C interaction essential for these processes. By comparing CFTR current activation in the presence of ATP or an ATP analog unsuitable for phosphotransfer, as well as pseudosubstrate peptides of various lengths, we identify two distinct specific regions of the PKA-C surface which interact with CFTR to cause noncatalytic and catalytic CFTR stimulation, respectively. Whereas the "substrate site" mediates CFTR phosphorylation, a distinct hydrophobic patch (the "docking site") is responsible for noncatalytic CFTR activation, achieved by stabilizing the R domain in a "released" conformation permissive to channel gating. Furthermore, by comparing PKA-C variants with different posttranslational modification patterns, we find that direct membrane tethering of the kinase through its N-terminal myristoyl group is an unappreciated fundamental requirement for CFTR activation: PKA-C demyristoylation abolishes noncatalytic, and profoundly slows catalytic, CFTR stimulation. For the F508del CFTR mutant, present in ~90% of CF patients, maximal activation by demyristoylated PKA-C is reduced by ~10-fold compared to that by myristoylated PKA-C. Finally, in bacterial genera that contain common CF pathogens, we identify virulence factors that demyristoylate PKA-C in vitro, raising the possibility that during recurrent bacterial infections in CF patients, PKA-C demyristoylation may contribute to the exacerbation of lung disease.

囊性纤维化跨膜传导调节器(CFTR)是一种在囊性纤维化(CF)患者中发生突变的阴离子通道,由蛋白激酶 A(PKA-C)的催化亚基激活。PKA-C 通过与 CFTR 的调节(R)结构域中的多个丝氨酸磷酸化,以非催化和催化的方式激活 CFTR。在这里,我们确定了对这些过程至关重要的 CFTR/PKA-C 相互作用的关键分子决定因素。通过比较在 ATP 或不适合磷酸转移的 ATP 类似物以及不同长度的伪底物肽存在下 CFTR 电流的激活情况,我们确定了 PKA-C 表面两个不同的特定区域,它们与 CFTR 相互作用,分别导致非催化性和催化性 CFTR 刺激。当 "底物位点 "介导 CFTR 磷酸化时,一个不同的疏水斑块("对接位点")负责非催化 CFTR 激活,通过将 R 结构域稳定在允许通道门控的 "释放 "构象来实现。此外,通过比较具有不同翻译后修饰模式的 PKA-C 变体,我们发现激酶通过其 N 端肉豆蔻酰基直接拴住膜是 CFTR 激活的一个未被重视的基本要求:PKA-C的肉豆蔻酰化会取消非催化性的CFTR刺激,并大大减缓催化性的CFTR刺激。对于存在于约 90% CF 患者体内的 F508del CFTR 突变体,去肉豆蔻酰化 PKA-C 的最大激活作用比肉豆蔻酰化 PKA-C 的最大激活作用降低了约 10 倍。最后,在含有常见CF病原体的细菌属中,我们发现了能在体外使PKA-C脱肉豆蔻酰化的毒力因子,这就提出了一种可能性,即在CF患者反复感染细菌期间,PKA-C脱肉豆蔻酰化可能会导致肺部疾病恶化。
{"title":"Structural determinants of protein kinase A essential for CFTR channel activation.","authors":"Csaba Mihályi, Iordan Iordanov, Andras Szollosi, László Csanády","doi":"10.1073/pnas.2407728121","DOIUrl":"https://doi.org/10.1073/pnas.2407728121","url":null,"abstract":"<p><p>Cystic Fibrosis Transmembrane Conductance Regulator (CFTR), the anion channel mutated in cystic fibrosis (CF) patients, is activated by the catalytic subunit of protein kinase A (PKA-C). PKA-C activates CFTR both noncatalytically, through binding, and catalytically, through phosphorylation of multiple serines in CFTR's regulatory (R) domain. Here, we identify key molecular determinants of the CFTR/PKA-C interaction essential for these processes. By comparing CFTR current activation in the presence of ATP or an ATP analog unsuitable for phosphotransfer, as well as pseudosubstrate peptides of various lengths, we identify two distinct specific regions of the PKA-C surface which interact with CFTR to cause noncatalytic and catalytic CFTR stimulation, respectively. Whereas the \"substrate site\" mediates CFTR phosphorylation, a distinct hydrophobic patch (the \"docking site\") is responsible for noncatalytic CFTR activation, achieved by stabilizing the R domain in a \"released\" conformation permissive to channel gating. Furthermore, by comparing PKA-C variants with different posttranslational modification patterns, we find that direct membrane tethering of the kinase through its N-terminal myristoyl group is an unappreciated fundamental requirement for CFTR activation: PKA-C demyristoylation abolishes noncatalytic, and profoundly slows catalytic, CFTR stimulation. For the F508del CFTR mutant, present in ~90% of CF patients, maximal activation by demyristoylated PKA-C is reduced by ~10-fold compared to that by myristoylated PKA-C. Finally, in bacterial genera that contain common CF pathogens, we identify virulence factors that demyristoylate PKA-C in vitro, raising the possibility that during recurrent bacterial infections in CF patients, PKA-C demyristoylation may contribute to the exacerbation of lung disease.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Weather deviations linked to undocumented migration and return between Mexico and the United States. 与墨西哥和美国之间无证移民和回返有关的天气变化。
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-04 DOI: 10.1073/pnas.2400524121
Julia Li Zhu, Nancy Chau, Amanda D Rodewald, Filiz Garip

As the world's climate continues to change, human populations are exposed to increasingly severe and extreme weather conditions that can promote migration. Here, we examine how extreme weather influences the likelihood of undocumented migration and return between Mexico and the United States. We used data from 48,313 individuals observed between 1992 and 2018 in 84 Mexican agricultural communities. While controlling for regional and temporal confounding factors, we related individual decisions to migrate to the United States without documents and subsequently return to Mexico with lagged weather deviations from the historical norm during the corn-growing season (May to August). Undocumented migration was most likely from areas experiencing extreme drought, and migrants were less likely to return to their communities of origin when extreme weather persisted. These findings establish the role of weather shocks in undocumented Mexican migration to, and eventual settlement in, the United States. The findings also suggest that extreme weather conditions, which are likely to increase with climate change, promote clandestine mobility across borders and, thus, expose migrants to risks associated with crossing dangerous terrain and relying upon smugglers.

随着世界气候的不断变化,人类面临的恶劣和极端天气条件越来越多,这可能会促进人口迁移。在此,我们研究了极端天气如何影响墨西哥和美国之间的无证移民和返回的可能性。我们使用了 1992 年至 2018 年间在 84 个墨西哥农业社区观察到的 48,313 人的数据。在控制区域和时间混杂因素的同时,我们将个人无证移民美国并随后返回墨西哥的决定与玉米种植季节(5 月至 8 月)滞后天气偏离历史正常值的情况联系起来。无证移民最有可能来自遭遇极端干旱的地区,而当极端天气持续存在时,移民返回原籍社区的可能性较小。这些发现确定了天气冲击在墨西哥无证移民到美国并最终定居美国中的作用。研究结果还表明,极端天气条件(可能会随着气候变化而加剧)会促进跨境秘密流动,从而使移民面临穿越危险地形和依赖偷渡者的风险。
{"title":"Weather deviations linked to undocumented migration and return between Mexico and the United States.","authors":"Julia Li Zhu, Nancy Chau, Amanda D Rodewald, Filiz Garip","doi":"10.1073/pnas.2400524121","DOIUrl":"https://doi.org/10.1073/pnas.2400524121","url":null,"abstract":"<p><p>As the world's climate continues to change, human populations are exposed to increasingly severe and extreme weather conditions that can promote migration. Here, we examine how extreme weather influences the likelihood of undocumented migration and return between Mexico and the United States. We used data from 48,313 individuals observed between 1992 and 2018 in 84 Mexican agricultural communities. While controlling for regional and temporal confounding factors, we related individual decisions to migrate to the United States without documents and subsequently return to Mexico with lagged weather deviations from the historical norm during the corn-growing season (May to August). Undocumented migration was most likely from areas experiencing extreme drought, and migrants were less likely to return to their communities of origin when extreme weather persisted. These findings establish the role of weather shocks in undocumented Mexican migration to, and eventual settlement in, the United States. The findings also suggest that extreme weather conditions, which are likely to increase with climate change, promote clandestine mobility across borders and, thus, expose migrants to risks associated with crossing dangerous terrain and relying upon smugglers.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576625","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer. mRNA 翻译的应激反应调控:癌症中抗氧化酶表达的意义
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-04 DOI: 10.1073/pnas.2317846121
Yeon Soo Kim, Scot R Kimball, Elena Piskounova, Thomas J Begley, Nadine Hempel

From tumorigenesis to advanced metastatic stages, tumor cells encounter stress, ranging from limited nutrient and oxygen supply within the tumor microenvironment to extrinsic and intrinsic oxidative stress. Thus, tumor cells seize regulatory pathways to rapidly adapt to distinct physiologic conditions to promote cellular survival, including manipulation of mRNA translation. While it is now well established that metastatic tumor cells must up-regulate their antioxidant capacity to effectively spread and that regulation of antioxidant enzymes is imperative to disease progression, relatively few studies have assessed how translation and the hijacking of RNA systems contribute to antioxidant responses of tumors. Here, we review the major stress signaling pathways involved in translational regulation and discuss how these are affected by oxidative stress to promote prosurvival changes that manipulate antioxidant enzyme expression. We describe how tumors elicit these adaptive responses and detail how stress-induced translation can be regulated by kinases, RNA-binding proteins, RNA species, and RNA modification systems. We also highlight opportunities for further studies focused on the role of mRNA translation and RNA systems in the regulation of antioxidant enzyme expression, which may be of particular importance in the context of metastatic progression and therapeutic resistance.

从肿瘤发生到晚期转移阶段,肿瘤细胞会遇到各种压力,包括肿瘤微环境中有限的营养和氧气供应,以及外在和内在的氧化压力。因此,肿瘤细胞抓住调节途径,迅速适应不同的生理条件,以促进细胞存活,包括操纵 mRNA 翻译。虽然转移性肿瘤细胞必须上调其抗氧化能力才能有效扩散,而且抗氧化酶的调控对疾病进展至关重要,但评估翻译和 RNA 系统劫持如何促进肿瘤抗氧化反应的研究相对较少。在此,我们回顾了参与翻译调节的主要应激信号通路,并讨论了这些通路如何受到氧化应激的影响,从而促进操纵抗氧化酶表达的促生存变化。我们描述了肿瘤如何引起这些适应性反应,并详细介绍了激酶、RNA 结合蛋白、RNA 物种和 RNA 修饰系统如何调控应激诱导的翻译。我们还强调了进一步研究 mRNA 翻译和 RNA 系统在抗氧化酶表达调控中的作用的机会,这在转移进展和治疗耐药性方面可能尤为重要。
{"title":"Stress response regulation of mRNA translation: Implications for antioxidant enzyme expression in cancer.","authors":"Yeon Soo Kim, Scot R Kimball, Elena Piskounova, Thomas J Begley, Nadine Hempel","doi":"10.1073/pnas.2317846121","DOIUrl":"https://doi.org/10.1073/pnas.2317846121","url":null,"abstract":"<p><p>From tumorigenesis to advanced metastatic stages, tumor cells encounter stress, ranging from limited nutrient and oxygen supply within the tumor microenvironment to extrinsic and intrinsic oxidative stress. Thus, tumor cells seize regulatory pathways to rapidly adapt to distinct physiologic conditions to promote cellular survival, including manipulation of mRNA translation. While it is now well established that metastatic tumor cells must up-regulate their antioxidant capacity to effectively spread and that regulation of antioxidant enzymes is imperative to disease progression, relatively few studies have assessed how translation and the hijacking of RNA systems contribute to antioxidant responses of tumors. Here, we review the major stress signaling pathways involved in translational regulation and discuss how these are affected by oxidative stress to promote prosurvival changes that manipulate antioxidant enzyme expression. We describe how tumors elicit these adaptive responses and detail how stress-induced translation can be regulated by kinases, RNA-binding proteins, RNA species, and RNA modification systems. We also highlight opportunities for further studies focused on the role of mRNA translation and RNA systems in the regulation of antioxidant enzyme expression, which may be of particular importance in the context of metastatic progression and therapeutic resistance.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576592","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Latitudinal patterns in ocean C:N:P reflect phytoplankton acclimation and macromolecular composition. 海洋 C:N:P 的纬度模式反映了浮游植物的适应性和大分子组成。
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-05 DOI: 10.1073/pnas.2404460121
Justin D Liefer, Angelicque E White, Zoe V Finkel, Andrew J Irwin, Mathilde Dugenne, Keisuke Inomura, François Ribalet, E Virginia Armbrust, David M Karl, Matthew H Fyfe, Christopher M Brown, Michael J Follows

The proportions of carbon (C), nitrogen (N), and phosphorus (P) in surface ocean particulate matter deviate greatly from the canonical Redfield Ratio (C:N:P = 106:16:1) in space and time with significant implications for global carbon storage as this matter reaches the deep ocean. Recent work has revealed clear latitudinal patterns in C:N:P, yet the relative importance of ecological, physiological, or biochemical processes in creating these patterns is unclear. We present high-resolution, concurrent measurements of particulate C:N:P, macromolecular composition, environmental conditions, and plankton community composition from a transect spanning a subtropical-subpolar boundary, the North Pacific Transition Zone. We find that the summed contribution of macromolecules to particulate C, N, and P is consistent with, and provides interpretation for, particulate C:N:P patterns. A decline in particulate C:N from the subtropical to subpolar North Pacific largely reflects an increase in the relative contribution of protein compared to carbohydrate and lipid, whereas variation in C:P and N:P correspond to shifts in protein relative to polyphosphate, DNA, and RNA. Possible causes for the corresponding trends in C:N and macromolecular composition include physiological responses and changes in community structure of phytoplankton, which represented approximately 1/3rd of particulate C across the transect. Comparison with culture experiments and an allocation-based model of phytoplankton macromolecular composition suggest that physiological acclimation to changing nutrient supply is the most likely explanation for the latitudinal trend in C:N, offering both a mechanistic interpretation and biochemical basis for large-scale patterns in C:N:P.

表层海洋颗粒物质中碳(C)、氮(N)和磷(P)的比例在空间和时间上与典型的雷德菲尔德比例(C:N:P = 106:16:1)有很大偏差,当这些物质到达深海时,会对全球碳储存产生重大影响。最近的研究揭示了 C:N:P 的明显纬度模式,但生态、生理或生化过程在形成这些模式中的相对重要性尚不清楚。我们在北太平洋过渡带(North Pacific Transition Zone)横断面上对微粒 C:N:P、大分子组成、环境条件和浮游生物群落组成进行了高分辨率的同步测量。我们发现,大分子对微粒 C、N 和 P 的贡献总和与微粒 C:N:P 的模式一致,并为其提供了解释。从亚热带到亚极地北太平洋微粒C:N的下降主要反映了蛋白质相对于碳水化合物和脂质贡献的增加,而C:P和N:P的变化则对应于蛋白质相对于聚磷酸盐、DNA和RNA的变化。造成 C:N 和大分子组成相应变化趋势的可能原因包括浮游植物的生理反应和群落结构变化,浮游植物约占横断面上微粒 C 的 1/3。与培养实验和基于分配的浮游植物大分子组成模型的比较表明,生理适应营养供应的变化是最有可能解释 C:N 纬度趋势的原因,为 C:N:P 的大规模模式提供了机制解释和生物化学基础。
{"title":"Latitudinal patterns in ocean C:N:P reflect phytoplankton acclimation and macromolecular composition.","authors":"Justin D Liefer, Angelicque E White, Zoe V Finkel, Andrew J Irwin, Mathilde Dugenne, Keisuke Inomura, François Ribalet, E Virginia Armbrust, David M Karl, Matthew H Fyfe, Christopher M Brown, Michael J Follows","doi":"10.1073/pnas.2404460121","DOIUrl":"https://doi.org/10.1073/pnas.2404460121","url":null,"abstract":"<p><p>The proportions of carbon (C), nitrogen (N), and phosphorus (P) in surface ocean particulate matter deviate greatly from the canonical Redfield Ratio (C:N:P = 106:16:1) in space and time with significant implications for global carbon storage as this matter reaches the deep ocean. Recent work has revealed clear latitudinal patterns in C:N:P, yet the relative importance of ecological, physiological, or biochemical processes in creating these patterns is unclear. We present high-resolution, concurrent measurements of particulate C:N:P, macromolecular composition, environmental conditions, and plankton community composition from a transect spanning a subtropical-subpolar boundary, the North Pacific Transition Zone. We find that the summed contribution of macromolecules to particulate C, N, and P is consistent with, and provides interpretation for, particulate C:N:P patterns. A decline in particulate C:N from the subtropical to subpolar North Pacific largely reflects an increase in the relative contribution of protein compared to carbohydrate and lipid, whereas variation in C:P and N:P correspond to shifts in protein relative to polyphosphate, DNA, and RNA. Possible causes for the corresponding trends in C:N and macromolecular composition include physiological responses and changes in community structure of phytoplankton, which represented approximately 1/3<sup>rd</sup> of particulate C across the transect. Comparison with culture experiments and an allocation-based model of phytoplankton macromolecular composition suggest that physiological acclimation to changing nutrient supply is the most likely explanation for the latitudinal trend in C:N, offering both a mechanistic interpretation and biochemical basis for large-scale patterns in C:N:P.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Lithium isotope evidence for a plumeworld ocean in the aftermath of the Marinoan snowball Earth. 马里诺雪球地球之后梅花世界海洋的锂同位素证据。
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-05 DOI: 10.1073/pnas.2407419121
Tian Gan, Meng Tian, Xi-Kai Wang, Shijie Wang, Xiao-Ming Liu, Ganqing Jiang, Benjamin C Gill, Morrison Nolan, Alan J Kaufman, Taiyi Luo, Shuhai Xiao

The snowball Earth hypothesis predicts that continental chemical weathering diminished substantially during, but rebounded strongly after, the Marinoan ice age some 635 Mya. Defrosting the planet would result in a plume of fresh glacial meltwater with a different chemical composition from underlying hypersaline seawater, generating both vertical and lateral salinity gradients. Here, we test the plumeworld hypothesis using lithium isotope compositions in the Ediacaran Doushantuo cap dolostone that accumulated in the aftermath of the Marinoan snowball Earth along a proximal-distal (nearshore-offshore) transect in South China. Our data show an overall decreasing δ7Li trend with distance from the shoreline, consistent with the variable mixing of a meltwater plume with high δ7Li (due to incongruent silicate weathering on the continent) and hypersaline seawater with low δ7Li (due to synglacial distillation). The evolution of low δ7Li of synglacial seawater, as opposed to the modern oceans with high δ7Li, was likely driven by weak continental chemical weathering coupled with strong reverse weathering on the seafloor underneath silica-rich oceans. The spatial pattern of δ7Li is also consistent with the development and then collapse of the meltwater plume that occurred at the time scale of cap dolostone accumulation. Therefore, the δ7Li data are consistent with the plumeworld hypothesis, considerably reduced chemical weathering on the continent during the Marinoan snowball Earth, and enhanced reverse weathering on the seafloor of Precambrian oceans.

根据 "滚雪球地球假说 "的预测,在大约 635 万年前的马里诺冰期,大陆化学风化作用大幅减弱,但在冰期过后又出现了强劲的反弹。地球解冻将导致化学成分不同于下层超盐海水的新鲜冰川融水羽流,从而产生垂直和横向的盐度梯度。在这里,我们利用华南近岸-远岸(近岸-离岸)横断面上的埃迪卡拉纪都山头盖白云石中的锂同位素组成来验证梅花世界假说。我们的数据显示,随着距离海岸线的增加,δ7Li总体呈下降趋势,这与具有高δ7Li的融水羽流(由于大陆上不协调的硅酸盐风化)和具有低δ7Li的高盐度海水(由于共冰期蒸馏)的混合变化是一致的。相对于现代海洋的高δ7Li,合成冰期海水的低δ7Li演化可能是由大陆弱化学风化作用和富含二氧化硅海洋下的海底强逆向风化作用共同驱动的。δ7Li的空间模式也与在盖层白云石堆积的时间尺度上发生的融水羽流的发展和崩溃相一致。因此,δ7Li数据与梅花世界假说、马里亚诺雪球地球期间大陆化学风化作用显著减弱以及前寒武纪海洋海底反向风化作用增强相一致。
{"title":"Lithium isotope evidence for a plumeworld ocean in the aftermath of the Marinoan snowball Earth.","authors":"Tian Gan, Meng Tian, Xi-Kai Wang, Shijie Wang, Xiao-Ming Liu, Ganqing Jiang, Benjamin C Gill, Morrison Nolan, Alan J Kaufman, Taiyi Luo, Shuhai Xiao","doi":"10.1073/pnas.2407419121","DOIUrl":"https://doi.org/10.1073/pnas.2407419121","url":null,"abstract":"<p><p>The snowball Earth hypothesis predicts that continental chemical weathering diminished substantially during, but rebounded strongly after, the Marinoan ice age some 635 Mya. Defrosting the planet would result in a plume of fresh glacial meltwater with a different chemical composition from underlying hypersaline seawater, generating both vertical and lateral salinity gradients. Here, we test the plumeworld hypothesis using lithium isotope compositions in the Ediacaran Doushantuo cap dolostone that accumulated in the aftermath of the Marinoan snowball Earth along a proximal-distal (nearshore-offshore) transect in South China. Our data show an overall decreasing δ<sup>7</sup>Li trend with distance from the shoreline, consistent with the variable mixing of a meltwater plume with high δ<sup>7</sup>Li (due to incongruent silicate weathering on the continent) and hypersaline seawater with low δ<sup>7</sup>Li (due to synglacial distillation). The evolution of low δ<sup>7</sup>Li of synglacial seawater, as opposed to the modern oceans with high δ<sup>7</sup>Li, was likely driven by weak continental chemical weathering coupled with strong reverse weathering on the seafloor underneath silica-rich oceans. The spatial pattern of δ<sup>7</sup>Li is also consistent with the development and then collapse of the meltwater plume that occurred at the time scale of cap dolostone accumulation. Therefore, the δ<sup>7</sup>Li data are consistent with the plumeworld hypothesis, considerably reduced chemical weathering on the continent during the Marinoan snowball Earth, and enhanced reverse weathering on the seafloor of Precambrian oceans.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142582717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
CTCF-dependent insulation of Hoxb13 and the heterochronic control of tail length. Hoxb13 的 CTCF 依赖性绝缘和尾长的异时控制
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-05 DOI: 10.1073/pnas.2414865121
Lucille Lopez-Delisle, Jozsef Zakany, Célia Bochaton, Pierre Osteil, Alexandre Mayran, Fabrice Darbellay, Bénédicte Mascrez, Hocine Rekaik, Denis Duboule

Mammalian tail length is controlled by several genetic determinants, among which are Hox13 genes, whose function is to terminate the body axis. Accordingly, the precise timing in the transcriptional activation of these genes may impact upon body length. Unlike other Hox clusters, HoxB lacks posterior genes between Hoxb9 and Hoxb13, two genes separated by a ca. 70 kb large DNA segment containing a high number of CTCF sites, potentially isolating Hoxb13 from the rest of the cluster and thereby delaying its negative impact on trunk extension. We deleted the spacer DNA to induce a potential heterochronic gain of function of Hoxb13 at physiological concentration and observed a shortening of the tail as well as other abnormal phenotypes. These defects were all rescued by inactivating Hoxb13 in-cis with the deletion. A comparable gain of function was observed in mutant Embryonic Stem (ES) cells grown as pseudoembryos in vitro, which allowed us to examine in detail the importance of both the number and the orientation of CTCF sites in the insulating activity of the DNA spacer. A short cassette containing all the CTCF sites was sufficient to insulate Hoxb13 from the rest of HoxB, and additional modifications of this CTCF cassette showed that two CTCF sites in convergent orientations were already capable of importantly delaying Hoxb13 activation in these conditions. We discuss the relative importance of genomic distance versus number and orientation of CTCF sites in preventing Hoxb13 to be activated too early during trunk extension and hence to modulate tail length.

哺乳动物的尾巴长度受多个遗传决定因素控制,其中包括 Hox13 基因,其功能是终止体轴。因此,这些基因转录激活的精确时间可能会影响体长。与其他Hox基因簇不同,HoxB在Hoxb9和Hoxb13之间缺乏后位基因,这两个基因被一个约70 kb的大DNA片段隔开,其中含有大量的CTCF位点,可能将Hoxb13与该基因簇的其他基因隔离开来,从而延迟其对躯干延伸的负面影响。我们删除了间隔 DNA,以诱导 Hoxb13 在生理浓度下的潜在异时功能增益,并观察到尾部缩短以及其他异常表型。通过使 Hoxb13 与缺失基因同向失活,这些缺陷都得到了挽救。在体外生长为假胚胎的突变胚胎干(ES)细胞中观察到了类似的功能增益,这使我们能够详细研究 CTCF 位点的数量和方向在 DNA 间隔的绝缘活性中的重要性。含有所有 CTCF 位点的短盒式片段足以将 Hoxb13 与 HoxB 的其他部分隔离开来,而对该 CTCF 盒式片段的进一步改造表明,在这些条件下,两个方向趋同的 CTCF 位点已经能够显著延迟 Hoxb13 的激活。我们讨论了基因组距离与 CTCF 位点的数量和方向在防止 Hoxb13 在躯干伸展过程中过早被激活从而调节尾长方面的相对重要性。
{"title":"CTCF-dependent insulation of <i>Hoxb13</i> and the heterochronic control of tail length.","authors":"Lucille Lopez-Delisle, Jozsef Zakany, Célia Bochaton, Pierre Osteil, Alexandre Mayran, Fabrice Darbellay, Bénédicte Mascrez, Hocine Rekaik, Denis Duboule","doi":"10.1073/pnas.2414865121","DOIUrl":"https://doi.org/10.1073/pnas.2414865121","url":null,"abstract":"<p><p>Mammalian tail length is controlled by several genetic determinants, among which are <i>Hox13</i> genes, whose function is to terminate the body axis. Accordingly, the precise timing in the transcriptional activation of these genes may impact upon body length. Unlike other <i>Hox</i> clusters, <i>HoxB</i> lacks posterior genes between <i>Hoxb9</i> and <i>Hoxb13</i>, two genes separated by a ca. 70 kb large DNA segment containing a high number of CTCF sites, potentially isolating <i>Hoxb13</i> from the rest of the cluster and thereby delaying its negative impact on trunk extension. We deleted the spacer DNA to induce a potential heterochronic gain of function of <i>Hoxb13</i> at physiological concentration and observed a shortening of the tail as well as other abnormal phenotypes. These defects were all rescued by inactivating <i>Hoxb13</i> in-cis with the deletion. A comparable gain of function was observed in mutant Embryonic Stem (ES) cells grown as pseudoembryos in vitro, which allowed us to examine in detail the importance of both the number and the orientation of CTCF sites in the insulating activity of the DNA spacer. A short cassette containing all the CTCF sites was sufficient to insulate <i>Hoxb13</i> from the rest of <i>HoxB</i>, and additional modifications of this CTCF cassette showed that two CTCF sites in convergent orientations were already capable of importantly delaying <i>Hoxb13</i> activation in these conditions. We discuss the relative importance of genomic distance versus number and orientation of CTCF sites in preventing <i>Hoxb13</i> to be activated too early during trunk extension and hence to modulate tail length.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142584236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Path dependence, stigmergy, and memetic reification in the formation of the 27 Club myth. 27 俱乐部神话形成过程中的路径依赖、僵化和记忆重构。
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-04 DOI: 10.1073/pnas.2413373121
Zackary Okun Dunivin, Patrick Kaminski

The "27 Club" refers to the widespread legend that notable people, particularly musicians, are unusually likely to die at age 27. A 2011 inquiry in The BMJ showed this is not the case, dismissing the 27 Club as a myth. We expand on this discourse by demonstrating that although the existence of the phenomenon cannot be empirically validated, it is real in its consequences. Using Wikipedia data, we show that while age 27 does not hold greater risk of mortality for notable persons, those who died at 27 are as a group exceptionally notable compared to those who died at other young ages. The 27 Club legend originated from a statistically improbable event circa 1970, wherein four superstar musicians died within the span of 2 y all at age 27. This coincidence captured the public imagination such that our fascination with the 27 Club brought itself into being, producing greater interest in those who died at age 27 than would have been otherwise. This demonstrates path dependence in cultural evolution, whereby an effectively random event evolves into a narrative that shapes otherwise unrelated events and thus the way we make and interpret history.

27 俱乐部 "指的是一个广为流传的传说,即知名人士,尤其是音乐家,在 27 岁时死亡的可能性异常高。2011 年《英国医学杂志》(The BMJ)上的一项调查表明,事实并非如此,并将 "27 岁俱乐部 "斥为神话。我们对这一论述进行了扩展,证明虽然这一现象的存在无法通过经验验证,但其后果却是真实存在的。我们利用维基百科的数据表明,虽然 27 岁并不意味着知名人士的死亡风险更大,但与那些在其他年轻年龄死亡的人相比,那些在 27 岁死亡的人作为一个群体格外引人注目。27 岁俱乐部 "的传说源于 1970 年左右发生的一件统计上不可能发生的事件,当时有四位巨星音乐家在两年内相继去世,他们的年龄都是 27 岁。这一巧合吸引了公众的想象力,使我们对 "27 岁俱乐部 "产生了浓厚的兴趣,从而对 27 岁去世的人产生了更大的兴趣。这表明了文化演变的路径依赖性,即一个实际上随机发生的事件演变成了一种叙事,这种叙事塑造了原本毫不相关的事件,进而塑造了我们创造和解释历史的方式。
{"title":"Path dependence, stigmergy, and memetic reification in the formation of the 27 Club myth.","authors":"Zackary Okun Dunivin, Patrick Kaminski","doi":"10.1073/pnas.2413373121","DOIUrl":"https://doi.org/10.1073/pnas.2413373121","url":null,"abstract":"<p><p>The \"27 Club\" refers to the widespread legend that notable people, particularly musicians, are unusually likely to die at age 27. A 2011 inquiry in The BMJ showed this is not the case, dismissing the 27 Club as a myth. We expand on this discourse by demonstrating that although the existence of the phenomenon cannot be empirically validated, it is real in its consequences. Using Wikipedia data, we show that while age 27 does not hold greater risk of mortality for notable persons, those who died at 27 are as a group exceptionally notable compared to those who died at other young ages. The 27 Club legend originated from a statistically improbable event circa 1970, wherein four superstar musicians died within the span of 2 y all at age 27. This coincidence captured the public imagination such that our fascination with the 27 Club brought itself into being, producing greater interest in those who died at age 27 than would have been otherwise. This demonstrates path dependence in cultural evolution, whereby an effectively random event evolves into a narrative that shapes otherwise unrelated events and thus the way we make and interpret history.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
V1 neurons are tuned to perceptual borders in natural scenes. V1 神经元对自然场景中的感知边界进行调谐。
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-04 DOI: 10.1073/pnas.2221623121
Paolo Papale, Wietske Zuiderbaan, Rob R M Teeuwen, Amparo Gilhuis, Matthew W Self, Pieter R Roelfsema, Serge O Dumoulin

The visual system needs to identify perceptually relevant borders to segment complex natural scenes. The primary visual cortex (V1) is thought to extract local borders, and higher visual areas are thought to identify the perceptually relevant borders between objects and the background. To test this conjecture, we used natural images that had been annotated by human observers who marked the perceptually relevant borders. We assessed the effect of perceptual relevance on V1 responses using human neuroimaging, macaque electrophysiology, and computational modeling. We report that perceptually relevant borders elicit stronger responses in the early visual cortex than irrelevant ones, even if simple features, such as contrast and the energy of oriented filters, are matched. Moreover, V1 neurons discriminate perceptually relevant borders surprisingly fast, during the early feedforward-driven activity at a latency of ~50 ms, indicating that they are tuned to the features that characterize them. We also revealed a delayed, contextual effect that enhances the V1 responses that are elicited by perceptually relevant borders at a longer latency. Our results reveal multiple mechanisms that allow V1 neurons to infer the layout of objects in natural images.

视觉系统需要识别与感知相关的边界,以分割复杂的自然场景。初级视觉皮层(V1)被认为能提取局部边界,而高级视觉区域则被认为能识别物体与背景之间的感知相关边界。为了验证这一猜想,我们使用了由人类观察者标注感知相关边界的自然图像。我们利用人类神经影像学、猕猴电生理学和计算模型评估了知觉相关性对 V1 反应的影响。我们发现,即使对比度和定向滤波器能量等简单特征相匹配,知觉相关边界在早期视觉皮层中引起的反应也比无关边界更强。此外,V1神经元分辨知觉相关边界的速度出奇地快,在早期前馈驱动活动中的潜伏期约为50毫秒,这表明它们对边界的特征进行了调整。我们还发现了一种延迟的情境效应,它能在更长的潜伏期内增强由知觉相关边界引起的 V1 反应。我们的研究结果揭示了 V1 神经元推断自然图像中物体布局的多种机制。
{"title":"V1 neurons are tuned to perceptual borders in natural scenes.","authors":"Paolo Papale, Wietske Zuiderbaan, Rob R M Teeuwen, Amparo Gilhuis, Matthew W Self, Pieter R Roelfsema, Serge O Dumoulin","doi":"10.1073/pnas.2221623121","DOIUrl":"https://doi.org/10.1073/pnas.2221623121","url":null,"abstract":"<p><p>The visual system needs to identify perceptually relevant borders to segment complex natural scenes. The primary visual cortex (V1) is thought to extract local borders, and higher visual areas are thought to identify the perceptually relevant borders between objects and the background. To test this conjecture, we used natural images that had been annotated by human observers who marked the perceptually relevant borders. We assessed the effect of perceptual relevance on V1 responses using human neuroimaging, macaque electrophysiology, and computational modeling. We report that perceptually relevant borders elicit stronger responses in the early visual cortex than irrelevant ones, even if simple features, such as contrast and the energy of oriented filters, are matched. Moreover, V1 neurons discriminate perceptually relevant borders surprisingly fast, during the early feedforward-driven activity at a latency of ~50 ms, indicating that they are tuned to the features that characterize them. We also revealed a delayed, contextual effect that enhances the V1 responses that are elicited by perceptually relevant borders at a longer latency. Our results reveal multiple mechanisms that allow V1 neurons to infer the layout of objects in natural images.</p>","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
How to survive enormous amounts of alcohol. 如何在大量酒精中生存
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-11-04 DOI: 10.1073/pnas.2420068121
Rainer Spanagel
{"title":"How to survive enormous amounts of alcohol.","authors":"Rainer Spanagel","doi":"10.1073/pnas.2420068121","DOIUrl":"https://doi.org/10.1073/pnas.2420068121","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142576400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Correction to Supporting Information for Grossman et al., Political partisanship influences behavioral responses to governors' recommendations for COVID-19 prevention in the United States. 对 Grossman 等人的佐证信息的更正,《政治党派性影响对美国州长预防 COVID-19 建议的行为反应》。
IF 9.4 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2024-11-12 Epub Date: 2024-10-31 DOI: 10.1073/pnas.2420903121
{"title":"Correction to Supporting Information for Grossman et al., Political partisanship influences behavioral responses to governors' recommendations for COVID-19 prevention in the United States.","authors":"","doi":"10.1073/pnas.2420903121","DOIUrl":"10.1073/pnas.2420903121","url":null,"abstract":"","PeriodicalId":20548,"journal":{"name":"Proceedings of the National Academy of Sciences of the United States of America","volume":null,"pages":null},"PeriodicalIF":9.4,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
期刊
Proceedings of the National Academy of Sciences of the United States of America
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1