1 ChromEMT: Visualizing 3D chromatin structure and compaction in interphase and mitotic cells
Horng D. Ou, Sébastien Phan, Thomas J. Deerinck, Andrea Thor, Mark H. Ellisman, Clodagh C. O’Shea
The chromatin structure of DNA determines genome compaction and activity in the nucleus. On the basis of in vitro structures and electron microscopy (EM) studies, the hierarchical model is that 11-nanometer DNA-nucleosome polymers fold into 30- and subsequently into 120- and 300- to 700-nanometer fibers and mitotic chromosomes. To visualize chromatin in situ, we identified a fluorescent dye that stains DNA with an osmiophilic polymer and selectively enhances its contrast in EM. Using ChromEMT (ChromEM tomography), we reveal the ultrastructure and three-dimensional (3D) organization of individual chromatin polymers, megabase domains, and mitotic chromosomes. We show that chromatin is a disordered 5- to 24-nanometer-diameter curvilinear chain that is packed together at different 3D concentration distributions in interphase and mitosis. Chromatin chains have many different particle arrangements and bend at various lengths to achieve structural compaction and high packing densities.
2 Reconfiguration of DNA molecular arrays driven by information relay
Jie Song（宋杰，上海交大）, Zhe Li, Pengfei Wang, Travis Meyer, Chengde Mao（毛成德，美国普渡大学）, Yonggang Ke（柯永刚，美国埃默里大学）
Information relay at the molecular level is an essential phenomenon in numerous chemical and biological processes, such as intricate signaling cascades. One key challenge in synthetic molecular self-assembly is to construct artificial structures that imitate these complex behaviors in controllable systems. We demonstrated prescribed, long-range information relay in an artificial molecular array assembled from modular DNA structural units. The dynamic DNA molecular array exhibits transformations with programmable initiation, propagation, and regulation. The transformation of the array can be initiated at selected units and then propagated, without addition of extra triggers, to neighboring units and eventually the entire array. The specific information pathways by which this transformation occurs can be controlled by altering the design of individual units and the arrays.
3 Second-scale nuclear spin coherence time of ultracold 23Na40K molecules
Jee Woo Park, Zoe Z. Yan, Huanqian Loh, Sebastian A. Will, Martin W. Zwierlein
Coherence, the stability of the relative phase between quantum states, is central to quantum mechanics and its applications. For ultracold dipolar molecules at sub-microkelvin temperatures, internal states with robust coherence are predicted to offer rich prospects for quantum many-body physics and quantum information processing. We report the observation of stable coherence between nuclear spin states of ultracold fermionic sodium-potassium (NaK) molecules in the singlet rovibrational ground state. Ramsey spectroscopy reveals coherence times on the scale of 1 second; this enables high-resolution spectroscopy of the molecular gas. Collisional shifts are shown to be absent down to the 100-millihertz level. This work opens the door to the use of molecules as a versatile quantum memory and for precision measurements on dipolar quantum matter.
（导读 魏甜甜） 本研究观察到处于振转基态的超冷NaK分子的核自旋态间具有稳定的相干性。Ramsey光谱揭示了相干时间在1秒量级，这使得测量分子气体的高分辨率光谱成为可能。这项工作为一些研究方向带来了新的机会，比如将分子用作通用量子存储器，对偶极量子物质进行精密测量等。
4 Spectral narrowing of x-ray pulses for precision spectroscopy with nuclear resonances
K. P. Heeg, A. Kaldun, C. Strohm…T. Pfeifer, J. Evers
Spectroscopy of nuclear resonances offers a wide range of applications due to the remarkable energy resolution afforded by their narrow linewidths. However, progress toward higher resolution is inhibited at modern x-ray sources because they deliver only a tiny fraction of the photons on resonance, with the remainder contributing to an off-resonant background. We devised an experimental setup that uses the fast mechanical motion of a resonant target to manipulate the spectrum of a given x-ray pulse and to redistribute off-resonant spectral intensity onto the resonance. As a consequence, the resonant pulse brilliance is increased while the off-resonant background is reduced. Because our method is compatible with existing and upcoming pulsed x-ray sources, we anticipate that this approach will find applications that require ultranarrow x-ray resonances.
5 Tough adhesives for diverse wet surfaces
J. Li1,, A. D. Celiz, J. Yang…Z. Suo, D. J. Mooney
Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields but has proven to be extremely challenging. Existing adhesives are cytotoxic, adhere weakly to tissues, or cannot be used in wet environments. We report a bioinspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energies on wet surfaces as compared with those of existing adhesives. Adhesion occurs within minutes, independent of blood exposure and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings, and tissue repair.
6 Synthesis of FeH5: A layered structure with atomic hydrogen slabs
C. M. Pépin, G. Geneste, A. Dewaele, M. Mezouar, P. Loubeyre
High pressure promotes the formation of polyhydrides with unusually high hydrogen-to-metal ratios. These polyhydrides have complex hydrogenic sublattices. We synthesized iron pentahydride (FeH5) by a direct reaction between iron and H2 above 130 gigapascals in a laser-heated diamond anvil cell. FeH5 exhibits a structure built of atomic hydrogen only. It consists of intercalated layers of quasicubic FeH3 units and four-plane slabs of thin atomic hydrogen. The distribution of the valence electron density indicates a bonding between hydrogen and iron atoms but none between hydrogen atoms, presenting a two-dimensional metallic character. The discovery of FeH5 suggests a low-pressure path to make materials that approach bulk dense atomic hydrogen.
7 Direct optical lithography of functional inorganic nanomaterials
Yuanyuan Wang, Igor Fedin, Hao Zhang, Dmitri V. Talapin
Photolithography is an important manufacturing process that relies on using photoresists, typically polymer formulations, that change solubility when illuminated with ultraviolet light. Here, we introduce a general chemical approach for photoresist-free, direct optical lithography of functional inorganic nanomaterials. The patterned materials can be metals, semiconductors, oxides, magnetic, or rare earth compositions. No organic impurities are present in the patterned layers, which helps achieve good electronic and optical properties. The conductivity, carrier mobility, dielectric, and luminescence properties of optically patterned layers are on par with the properties of state-of-the-art solution-processed materials. The ability to directly pattern all-inorganic layers by using a light exposure dose comparable with that of organic photoresists provides an alternate route for thin-film device manufacturing.
8 Atomic-layered Au clusters on α-MoC as catalysts for the low-temperature water-gas shift reaction
Siyu Yao, Xiao Zhang, Wu Zhou…José A. Rodriguez, Ding Ma
The water-gas shift (WGS) reaction (where carbon monoxide plus water yields dihydrogen and carbon dioxide) is an essential process for hydrogen generation and carbon monoxide removal in various energy-related chemical operations. This equilibrium-limited reaction is favored at a low working temperature. Potential application in fuel cells also requires a WGS catalyst to be highly active, stable, and energy-efficient and to match the working temperature of on-site hydrogen generation and consumption units. We synthesized layered gold (Au) clusters on a molybdenum carbide (α-MoC) substrate to create an interfacial catalyst system for the ultralow-temperature WGS reaction. Water was activated over α-MoC at 303 kelvin, whereas carbon monoxide adsorbed on adjacent Au sites was apt to react with surface hydroxyl groups formed from water splitting, leading to a high WGS activity at low temperatures.
9 Seismic evidence for partial melting at the root of major hot spot plumes
Kaiqing Yuan, Barbara Romanowicz
Ultralow-velocity zones are localized regions of extreme material properties detected seismologically at the base of Earth's mantle. Their nature and role in mantle dynamics are poorly understood. We used shear waves diffracted at the core-mantle boundary to illuminate the root of the Iceland plume from different directions. Through waveform modeling, we detected a large ultralow-velocity zone and constrained its shape to be axisymmetric to a very good first order. We thus attribute it to partial melting of a locally thickened, denser- and hotter-than-average layer, reflecting dynamics and elevated temperatures within the plume root. Such structures are few and far apart, and they may be characteristic of the roots of some of the broad mantle plumes tomographically imaged within the large low-shear-velocity provinces in the lower mantle.
10 Nanocrystalline copper films are never flat
Xiaopu Zhang, Jian Han, John J. Plombon, Adrian P. Sutton, David J. Srolovitz, John J. Boland
We used scanning tunneling microscopy to study low-angle grain boundaries at the surface of nearly planar copper nanocrystalline (111) films. The presence of grain boundaries and their emergence at the film surface create valleys composed of dissociated edge dislocations and ridges where partial dislocations have recombined. Geometric analysis and simulations indicated that valleys and ridges were created by an out-of-plane grain rotation driven by reduction of grain boundary energy. These results suggest that in general, it is impossible to form flat two-dimensional nanocrystalline films of copper and other metals exhibiting small stacking fault energies and/or large elastic anisotropy, which induce a large anisotropy in the dislocation-line energy.
11 Control of species-dependent cortico-motoneuronal connections underlying manual dexterity
Zirong Gu, John Kalamboglas, Shin Yoshioka…John H. Martin, Yutaka Yoshida
Superior manual dexterity in higher primates emerged together with the appearance of cortico-motoneuronal (CM) connections during the evolution of the mammalian corticospinal (CS) system. Previously thought to be specific to higher primates, we identified transient CM connections in early postnatal mice, which are eventually eliminated by Sema6D-PlexA1 signaling. PlexA1 mutant mice maintain CM connections into adulthood and exhibit superior manual dexterity as compared with that of controls. Last, differing PlexA1 expression in layer 5 of the motor cortex, which is strong in wild-type mice but weak in humans, may be explained by FEZF2-mediated cis-regulatory elements that are found only in higher primates. Thus, species-dependent regulation of PlexA1 expression may have been crucial in the evolution of mammalian CS systems that improved fine motor control in higher primates.
12 Eutrophication will increase during the 21st century as a result of precipitation changes
E. Sinha, A. M. Michalak, V. Balaji
Eutrophication, or excessive nutrient enrichment, threatens water resources across the globe. We show that climate change–induced precipitation changes alone will substantially increase (19 ± 14%) riverine total nitrogen loading within the continental United States by the end of the century for the “business-as-usual” scenario. The impacts, driven by projected increases in both total and extreme precipitation, will be especially strong for the Northeast and the corn belt of the United States. Offsetting this increase would require a 33 ± 24% reduction in nitrogen inputs, representing a massive management challenge. Globally, changes in precipitation are especially likely to also exacerbate eutrophication in India, China, and Southeast Asia. It is therefore imperative that water quality management strategies account for the impact of projected future changes in precipitation on nitrogen loading.
（导读 刘威尔）本研究通过情景模拟预测发现，标准情景下气候变化引发的降水量上升将导致本世纪末美国大陆的河流总氮负荷增加19 ± 14%，而抵消这一变化将需要减少33 ± 24%的氮投入。全球尺度上，降水变化还可能加剧印度、中国和东南亚地区的水体富营养化，水资源质量管理策略亟需对此作出响应。
13 Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade
Dung T. Le, Jennifer N. Durham, Kellie N. Smith…Robert A. Anders, Luis A. Diaz Jr.
The genomes of cancers deficient in mismatch repair contain exceptionally high numbers of somatic mutations. In a proof-of-concept study, we previously showed that colorectal cancers with mismatch repair deficiency were sensitive to immune checkpoint blockade with antibodies to programmed death receptor–1 (PD-1). We have now expanded this study to evaluate the efficacy of PD-1 blockade in patients with advanced mismatch repair–deficient cancers across 12 different tumor types. Objective radiographic responses were observed in 53% of patients, and complete responses were achieved in 21% of patients. Responses were durable, with median progression-free survival and overall survival still not reached. Functional analysis in a responding patient demonstrated rapid in vivo expansion of neoantigen-specific T cell clones that were reactive to mutant neopeptides found in the tumor. These data support the hypothesis that the large proportion of mutant neoantigens in mismatch repair–deficient cancers make them sensitive to immune checkpoint blockade, regardless of the cancers’ tissue of origin.
（导读 郭思瑶）错配修复功能缺乏的肿瘤基因组中包含非常多的体细胞突变。之前的研究发现错配修复功能缺乏的结肠癌对程序性死亡受体1 (PD-1)的抗体免疫检查点阻断敏感。科研人员利用这一发现评估病人体内12种肿瘤PD-1阻断功效。结果表明21%的病人实现了完全响应。错配修复缺陷有望成为预测多种实体瘤治疗结果的生物标记。
14 CAT-tailing as a fail-safe mechanism for efficient degradation of stalled nascent polypeptides
Kamena K. Kostova, Kelsey L. Hickey, Beatriz A. Osuna…David E. Weinberg, Jonathan S. Weissman
Ribosome stalling leads to recruitment of the ribosome quality control complex (RQC), which targets the partially synthesized polypeptide for proteasomal degradation through the action of the ubiquitin ligase Ltn1p. A second core RQC component, Rqc2p, modifies the nascent polypeptide by adding a carboxyl-terminal alanine and threonine (CAT) tail through a noncanonical elongation reaction. Here we examined the role of CAT-tailing in nascent-chain degradation in budding yeast. We found that Ltn1p efficiently accessed only nascent-chain lysines immediately proximal to the ribosome exit tunnel. For substrates without Ltn1p-accessible lysines, CAT-tailing enabled degradation by exposing lysines sequestered in the ribosome exit tunnel. Thus, CAT-tails do not serve as a degron, but rather provide a fail-safe mechanism that expands the range of RQC-degradable substrates.
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