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Intermediate evolutionary state of motile sperm and pollen tubes in the extant gymnosperm Cycas revoluta. 现存裸子植物苏铁活动精子和花粉管的中间进化状态。
IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 Epub Date: 2026-01-23 DOI: 10.1073/pnas.2506320123
Yukiho Toyama, Satohiro Okuda, Takamasa Suzuki, Tetsuya Higashiyama

Evolutionary transitions in land plant fertilization from zooidogamy to siphonogamy were characterized by transformations of male reproductive cells. Basal land plants such as bryophytes and pteridophytes have motile sperm, whereas most seed plants have nonmotile sperm, delivered by a pollen tube. Despite being seed plants, gymnosperm cycads and ginkgo uniquely form highly multiflagellated and large motile sperm within pollen tubes. However, the evolutionary state of these male reproductive cells remains unknown. We clarified the gene expression profiles of Cycas revoluta pollen tubes and motile sperm swimming toward female reproductive cells. Male cycad cells expressed fewer genes associated with transcription, translation, and related processes, which is consistent across land plants. We compared the distinctive orthologous groups (OGs) of the genes specifically expressed in sperm and pollen tubes with those in other plants. Cycad pollen tubes shared several OGs with angiosperms but possessed significantly fewer gene copies and lacked cell wall remodeling and plasma membrane-localized receptor genes that contribute to rapid and guided growth. The growth mechanism of cycad pollen tubes might be largely different from angiosperm pollen tubes. In contrast, despite their morphological uniqueness, cycad sperm shared representative OGs with angiosperm sperm cells to the same extent as egg cells. In addition, a sperm-specific histone variant may contribute to transcriptional regulation via chromatin condensation like other male gametes. As an extant gymnosperm that retains zooidogamy with pollen tubes, the cycad represents a molecular intermediate state in the transition from zooidogamy to siphonogamy, providing insight into the evolution of land plant fertilization.

陆地植物受精从兽偶制到虹吸制的进化转变以雄性生殖细胞的转化为特征。陆生植物如苔藓植物和蕨类植物有活动精子,而大多数种子植物有不活动精子,通过花粉管传递。尽管是种子植物,裸子植物苏铁和银杏独特地在花粉管内形成高度多鞭毛和大运动的精子。然而,这些雄性生殖细胞的进化状态仍然未知。我们明确了苏铁花粉管和运动精子向雌性生殖细胞游动的基因表达谱。苏铁雄性细胞表达与转录、翻译和相关过程相关的基因较少,这在陆地植物中是一致的。我们比较了精子和花粉管中特异性表达的基因与其他植物中的基因的不同同源群(OGs)。苏铁花粉管与被子植物共享几个ogg,但基因拷贝数明显较少,缺乏细胞壁重塑和质膜定位受体基因,这些基因有助于快速和引导生长。苏铁花粉管的生长机制可能与被子植物花粉管有很大的不同。相比之下,苏铁精子尽管形态独特,但与被子植物精子细胞有代表性的OGs,其程度与卵细胞相同。此外,精子特异性组蛋白变异可能像其他雄性配子一样通过染色质凝聚参与转录调节。苏铁作为现存的裸子植物,保留了与花粉管的雌雄同体交配,代表了从雌雄同体交配向管胞同体交配过渡的分子中间状态,为陆地植物受精的进化提供了新的思路。
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引用次数: 0
RHOA controls oncogenic B cell receptor signaling in aggressive lymphoma RHOA控制侵袭性淋巴瘤的致瘤性B细胞受体信号
IF 11.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 DOI: 10.1073/pnas.2534531123
Ariana N. Jacobs, Dominique Jahn, Tim Beringer, Sebastian Wolf, Ramesh K. Krishnan, Michael Engelke, Björn Häupl, Silvia Münch, Niklas Dienstbier, Martine Pape, Marion Bodach, Xin Yu, Nazli Serin, Rebecca Wurm-Kuczera, Alena Zindel, Carmen Döbele, Björn Chapuy, Louis M. Staudt, Sebastian Scheich, Thomas Oellerich
Diffuse large B cell lymphoma (DLBCL) is characterized by a variety of specific genetic alterations that impact signaling pathway dependencies and therapeutic outcomes. Among the recurrently mutated genes, we identified RHOA , a member of the small GTPase family, as a selective dependency in DLBCL. Here, we show that RHOA function is essential for the survival of ABC DLBCL cells because it sustains oncogenic B cell receptor (BCR) signaling through maintaining a signaling-permissive conformation of the cortical actin network. This enables the formation of active BCR microclusters at the cell surface, ultimately resulting in constitutive, BCR-driven NF-κB survival signaling. Moreover, we found that RHOA controlled endocytosis of the BCR and thereby the assembly of the endolysosomal My–T–BCR multiprotein complex, a central activator of NF-κB consisting of MYD88, Toll-like receptor 9, and the internalized BCR. The recurrent DLBCL-associated RHOA R5W mutation rendered RHOA constitutively active in its GTP-bound state and changed the conformation of the actin network from primarily filamentous actin to globular actin. This altered actin state led to an increase in BCR microcluster formation, amplification of NF-κB signaling, and resistance to inhibitors targeting chronic active BCR signaling. Hence, our study establishes RHOA and its mutant isoforms as critical regulators of oncogenic BCR signaling in DLBCL.
弥漫性大B细胞淋巴瘤(DLBCL)的特点是各种特定的遗传改变,影响信号通路依赖性和治疗结果。在反复突变的基因中,我们确定了RHOA,一个小GTPase家族的成员,作为DLBCL的选择性依赖。在这里,我们发现RHOA功能对ABC DLBCL细胞的存活至关重要,因为它通过维持皮质肌动蛋白网络的信号许可构象来维持致癌B细胞受体(BCR)信号传导。这使得活跃的BCR微团簇在细胞表面形成,最终形成BCR驱动的NF-κB生存信号。此外,我们发现RHOA控制BCR的内吞作用,从而控制内溶酶体My-T-BCR多蛋白复合物的组装,该复合物是NF-κB的中心激活剂,由MYD88、toll样受体9和内化的BCR组成。复发性dlbcl相关的RHOA R5W突变使RHOA在gtp结合状态下具有组成性活性,并将肌动蛋白网络的构象从主要的丝状肌动蛋白改变为球状肌动蛋白。这种肌动蛋白状态的改变导致BCR微簇形成的增加,NF-κB信号的扩增,以及对靶向慢性活性BCR信号的抑制剂的耐药性。因此,我们的研究确定RHOA及其突变亚型是DLBCL中致癌BCR信号传导的关键调节因子。
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引用次数: 0
Friction-controlled reentrant aging and fluidization in granular materials 颗粒材料的摩擦控制重入老化和流化
IF 11.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 DOI: 10.1073/pnas.2528600123
Ye Yuan, Walter Kob, Hajime Tanaka
Granular materials densify under repeated mechanical perturbations, nonequilibrium dynamics that underlies many natural and industrial processes. Because granular relaxation is governed by frictional contacts and energy dissipation, this aging behavior fundamentally differs from that of thermal glasses despite their apparent similarities. Here, we uncover how friction controls the compaction dynamics of granular packings subjected to quasistatic cyclic shear. Using discrete element simulations, we construct a dynamic state diagram as a function of strain amplitude and friction, revealing a rich interplay among jamming marginality, stabilization, and fluidization. We identify a friction-dependent crossover strain that separates aging and fluidized regimes, showing reentrant, nonmonotonic behavior: Increasing friction first suppresses fluidization but then promotes it through smooth, creep-like rearrangements. This transition is marked by a shift from intermittent, avalanche-like rearrangements to continuous, diffusive motion. Our findings demonstrate that friction exerts a dual role in granular aging—both stabilizing and fluidizing—thereby uncovering the fundamental nonequilibrium mechanisms that govern compaction, rheology, and aging in athermal disordered systems. More broadly, our results reveal a general principle for how friction governs metastability and flow in athermal matter—from granular and frictional colloids to soils and seismic faults—linking microscopic contact mechanics to macroscopic dynamics.
颗粒材料在重复的机械扰动下密度,非平衡动力学是许多自然和工业过程的基础。由于颗粒松弛是由摩擦接触和能量耗散控制的,这种老化行为与热玻璃的老化行为有着根本的不同,尽管它们有明显的相似之处。在这里,我们揭示了摩擦如何控制颗粒填料在准静态循环剪切作用下的压实动力学。利用离散元模拟,我们构建了应变幅值和摩擦的动态状态图,揭示了干扰边际性、稳定化和流化之间丰富的相互作用。我们确定了一个摩擦依赖的交叉应变,分离老化和流化制度,显示出可重入的,非单调的行为:增加摩擦首先抑制流化,但随后通过光滑的,蠕变的重排促进它。这种转变的标志是从间歇性的、雪崩式的重新排列到连续的、扩散的运动。我们的研究结果表明,摩擦在颗粒老化中发挥着双重作用——既稳定又流化——从而揭示了在非热无序系统中控制压实、流变和老化的基本非平衡机制。更广泛地说,我们的研究结果揭示了摩擦如何控制非热物质亚稳态和流动的一般原理——从颗粒状和摩擦胶体到土壤和地震断层——将微观接触力学与宏观动力学联系起来。
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引用次数: 0
Correction for Coste, The Kinship Formula: Inferring the numbers of all kin from any structured population projection model. 修正成本,亲属公式:从任何结构化人口预测模型推断所有亲属的数量。
IF 11.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 DOI: 10.1073/pnas.2535320122
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引用次数: 0
The BK channel-NS1619 agonist complex reveals molecular insights into allosteric activation gating BK通道- ns1619激动剂复合物揭示了变构激活门控的分子见解
IF 11.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 DOI: 10.1073/pnas.2507707123
Naileth Gonzalez-Sanabria, Gustavo F. Contreras, Maximiliano Rojas, Yorley Duarte, Fernando D. Gonzalez-Nilo, Eduardo Perozo, Ramon Latorre
BK channels play essential roles in a wealth of physiological functions, including regulating smooth muscle tone and neurotransmitter release. Its dysfunction, often caused by loss-of-function mutations, can lead to severe phenotypes, including ataxia and sensory impairment. Despite the therapeutic potential of BK channel agonists, the molecular mechanisms by which they stabilize the pore’s open conformation remain unclear. Using cryoelectron microscopy and molecular dynamic simulations, we identified that NS1619, a synthetic benzimidazolone agonist, first described as a BK opener, binds within a pocket formed by the S6/RCK1 linker and the S4 transmembrane segment. Our simulations suggest that agonist binding promotes a twisting motion in the S6 segment, enabling critical interactions with residues K330, K331, and F223. These findings provide a molecular model for the mechanism of NS1619 and suggest that its binding site can accommodate other agonists, highlighting a promising target for therapeutic development.
BK通道在丰富的生理功能中发挥重要作用,包括调节平滑肌张力和神经递质释放。它的功能障碍通常由功能丧失突变引起,可导致严重的表型,包括共济失调和感觉障碍。尽管BK通道激动剂具有治疗潜力,但它们稳定毛孔开放构象的分子机制仍不清楚。通过低温电子显微镜和分子动力学模拟,我们发现NS1619是一种合成苯并咪唑酮激动剂,最初被描述为BK打开剂,结合在S6/RCK1连接体和S4跨膜段形成的口袋内。我们的模拟表明,激动剂的结合促进了S6片段的扭曲运动,使其与残基K330、K331和F223发生关键的相互作用。这些发现为NS1619的机制提供了分子模型,并表明其结合位点可以容纳其他激动剂,突出了治疗开发的有希望的靶点。
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引用次数: 0
In This Issue. 在本期中。
IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 DOI: 10.1073/iti0426123
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引用次数: 0
Correction for Choi et al., Antibody-mediated blockade for galectin-3 binding protein in tumor secretome abrogates PDAC metastasis. 修正Choi等人的结论,抗体介导的阻断肿瘤分泌组中半乳糖凝集素-3结合蛋白可阻断PDAC转移。
IF 11.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 DOI: 10.1073/pnas.2600063123
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引用次数: 0
Disorder-induced stress-flow misalignment in soft glassy materials revealed using multidirectional shear. 用多向剪切技术揭示软玻璃材料中无序诱导的应力-流动失调。
IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 Epub Date: 2026-01-22 DOI: 10.1073/pnas.2521603123
Frédéric Blanc, Guillaume Ovarlez, Adam Trigui, Kirsten Martens, Romain Mari

Controlling the mechanical response of soft glassy materials-such as emulsions, foams, and colloidal suspensions-is key for many industrial processes. While their steady-state flow behavior is reasonably well understood, their response to complex flow histories, as encountered in operations like pumping or mixing, remains poorly known. Using a custom multiaxis shear apparatus that enables arbitrary changes in flow direction, we investigate how shear history influences the mechanical behavior of a model soft glassy system. We uncover a transient shear response orthogonal to the applied shear direction, together with an anisotropic yield surface. These effects point to an underlying anisotropic distribution of internal stresses imprinted by previous deformation. To rationalize this behavior, we use a mesoscopic elastoplastic model, demonstrating that local mechanical disorder governs the emergence of macroscopic stress-flow misalignment. Our findings offer a route to experimentally probe the distribution of local yield stresses in soft glassy materials.

控制软玻璃材料的机械反应,如乳剂、泡沫和胶体悬浮液,是许多工业过程的关键。虽然它们的稳态流动行为已经被很好地理解,但它们对复杂流动历史的反应,如在泵送或混合等操作中遇到的反应,仍然知之甚少。使用定制的多轴剪切装置,可以任意改变流动方向,我们研究剪切历史如何影响模型软玻璃系统的力学行为。我们发现了一个与施加剪切方向正交的瞬态剪切响应,以及一个各向异性屈服面。这些效应表明,由于先前的变形,内应力具有潜在的各向异性分布。为了使这种行为合理化,我们使用了一个细观弹塑性模型,证明了局部力学紊乱控制了宏观应力-流动失调的出现。我们的研究结果为实验探索软玻璃材料中局部屈服应力的分布提供了一条途径。
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引用次数: 0
Neurochemical imaging reveals changes in dopamine dynamics with photoperiod in a seasonally social vole species. 神经化学成像揭示了季节性社会性田鼠物种的多巴胺动态随光周期的变化。
IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 Epub Date: 2026-01-23 DOI: 10.1073/pnas.2509561123
Jaewan Mun, Kelley C Power, Natsumi Komatsu, Sophia A Tomatz, Annaliese K Beery, Markita P Landry

Studying dopamine signaling in nonmodel organisms is crucial for understanding the broad range of behaviors not represented in traditional model systems. However, exploring new species is often hindered by a scarcity of tools suitable for nongenetic models. In this work, we introduce near-infrared catecholamine nanosensors (nIRCats) to investigate dopamine dynamics in meadow voles, a rodent species that exhibits distinct changes in social behavior and neurobiology across photoperiods. We observe increased dopamine release and release site density in voles housed in short photoperiods (which induce a social phenotype), suggesting adaptations linked to environmental changes. Moreover, pharmacological and extracellular manipulations demonstrate that short photoperiod/social voles exhibit heightened responsiveness to dopamine-increasing interventions and resilience against suppressive conditions. These findings highlight a significant association between dopamine signaling and photoperiod-driven changes in social behavior and establish nIRCats as an effective tool for expanding our understanding of dopamine dynamics across nonmodel organisms.

研究非模式生物中的多巴胺信号对于理解传统模式系统中未表示的广泛行为至关重要。然而,对新物种的探索常常因缺乏适合非遗传模型的工具而受阻。在这项工作中,我们引入近红外儿茶酚胺纳米传感器(nIRCats)来研究草甸田鼠的多巴胺动态,草甸田鼠是一种啮齿动物,在光周期内表现出明显的社会行为和神经生物学变化。我们观察到,在短光周期(诱导社会表型)的田鼠中,多巴胺释放和释放位点密度增加,表明适应与环境变化有关。此外,药理学和细胞外操作表明,短光周期/社会性田鼠对多巴胺增加的干预表现出更高的反应性和对抑制条件的恢复能力。这些发现强调了多巴胺信号和光周期驱动的社会行为变化之间的重要关联,并将nIRCats建立为扩展我们对非模式生物多巴胺动力学的理解的有效工具。
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引用次数: 0
Impact of boiling liquid droplets: Vapor entrapment suppression. 沸腾液滴的影响:蒸汽夹持抑制。
IF 9.1 1区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Pub Date : 2026-01-27 Epub Date: 2026-01-23 DOI: 10.1073/pnas.2522654123
Bernardo Palacios-Muñiz, Edgar Ortega-Roano, Yee Li Ellis Fan, Nayoung Kim, Devaraj van der Meer

There hardly is a fluid mechanics phenomenon attracting more attention than the impact of a droplet, due to its undeniable beauty, many applications, and the numerous challenges it poses. One of the crucial factors turns out to be the cushioning effect of the gas surrounding the droplet. This fact, together with the observation that almost all of the relevant literature was done in air, triggers the question what would happen when the liquid was a boiling liquid, i.e., a liquid in thermal equilibrium with its own vapor, as is the case during transport of cryogenic liquids such as liquid hydrogen. To investigate precisely this question, we experimentally generate droplets in thermodynamical equilibrium with their own vapor, even before impact, such that minute energy exchanges of the droplet with its surroundings can trigger phase change. Using a frustrated total internal reflection setup, we make the exciting observation that depending on the impact speed and vapor conditions, the entrapment of vapor can be completely suppressed under boiling liquid conditions. We create a simplified model based on scaling arguments and perform numerical simulations considering both the compressible and condensable properties of the vapor layer that are in very good agreement with our experimental findings. Our results can be of great consequence to the pressures exerted during droplet impact and on an industrial scale may help better understand the loads experienced during sloshing wave impact inside cryogenic liquid containers.

几乎没有一种流体力学现象比液滴的影响更吸引人们的注意,因为它具有不可否认的美丽,许多应用,以及它带来的众多挑战。其中一个关键因素是液滴周围气体的缓冲作用。这一事实,加上几乎所有相关文献都是在空气中进行的观察,引发了这样一个问题:当液体是沸腾液体时,即与自身蒸汽处于热平衡的液体,就像运输液态氢等低温液体时的情况一样,会发生什么?为了精确地研究这个问题,我们通过实验产生了与自身蒸汽处于热力学平衡的液滴,甚至在撞击之前,液滴与周围环境的微小能量交换可以触发相变。利用受挫式全内反射装置,我们得到了令人兴奋的观察结果,即在沸腾液体条件下,取决于撞击速度和蒸汽条件,蒸汽的夹持可以完全抑制。我们建立了一个基于尺度参数的简化模型,并进行了数值模拟,同时考虑了蒸汽层的可压缩性和可冷凝性,这与我们的实验结果非常吻合。我们的研究结果对液滴撞击时施加的压力具有重要意义,并且在工业规模上可能有助于更好地理解低温液体容器内晃动波撞击时所经历的载荷。
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引用次数: 0
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Proceedings of the National Academy of Sciences of the United States of America
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