1【生物】A cargo-sorting DNA robot
Anupama J. Thubagere, et.al
Two critical challenges in the design and synthesis of molecular robots are modularity and algorithm simplicity. We demonstrate three modular building blocks for a DNA robot that performs cargo sorting at the molecular level. A simple algorithm encoding recognition between cargos and their destinations allows for a simple robot design: a single-stranded DNA with one leg and two foot domains for walking, and one arm and one hand domain for picking up and dropping off cargos. The robot explores a two-dimensional testing ground on the surface of DNA origami, picks up multiple cargos of two types that are initially at unordered locations, and delivers them to specified destinations until all molecules are sorted into two distinct piles. The robot is designed to perform a random walk without any energy supply. Exploiting this feature, a single robot can repeatedly sort multiple cargos. Localization on DNA origami allows for distinct cargo-sorting tasks to take place simultaneously in one test tube or for multiple robots to collectively perform the same task.
2【生物】Structures of the CRISPR genome integration complex
Addison V. Wright, et.al
CRISPR-Cas systems depend on the Cas1-Cas2 integrase to capture and integrate short foreign DNA fragments into the CRISPR locus, enabling adaptation to new viruses. We present crystal structures of Cas1-Cas2 bound to both donor and target DNA in intermediate and product integration complexes, as well as a cryo–electron microscopy structure of the full CRISPR locus integration complex, including the accessory protein IHF (integration host factor). The structures show unexpectedly that indirect sequence recognition dictates integration site selection by favoring deformation of the repeat and the flanking sequences. IHF binding bends the DNA sharply, bringing an upstream recognition motif into contact with Cas1 to increase both the specificity and efficiency of integration. These results explain how the Cas1-Cas2 CRISPR integrase recognizes a sequence-dependent DNA structure to ensure site-selective CRISPR array expansion during the initial step of bacterial adaptive immunity.
3【材料】Biological fabrication of cellulose fibers with tailored properties
Filipe Natalio, et.al
Cotton is a promising basis for wearable smart textiles. Current approaches that rely on fiber coatings suffer from function loss during wear. We present an approach that allows biological incorporation of exogenous molecules into cotton fibers to tailor the material’s functionality. In vitro model cultures of upland cotton (Gossypium hirsutum) are incubated with 6-carboxyfluorescein–glucose and dysprosium–1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid–glucose, where the glucose moiety acts as a carrier capable of traveling from the vascular connection to the outermost cell layer of the ovule epidermis, becoming incorporated into the cellulose fibers. This yields fibers with unnatural properties such as fluorescence or magnetism. Combining biological systems with the appropriate molecular design offers numerous possibilities to grow functional composite materials and implements a material-farming concept.
4【物理】Observation of coherent elastic neutrino-nucleus scattering
D. Akimov, et.al
The coherent elastic scattering of neutrinos off nuclei has eluded detection for four decades, even though its predicted cross section is by far the largest of all low-energy neutrino couplings. This mode of interaction offers new opportunities to study neutrino properties and leads to a miniaturization of detector size, with potential technological applications. We observed this process at a 6.7σ confidence level, using a low-background, 14.6-kilogram CsI[Na] scintillator exposed to the neutrino emissions from the Spallation Neutron Source at Oak Ridge National Laboratory. Characteristic signatures in energy and time, predicted by the standard model for this process, were observed in high signal-to-background conditions. Improved constraints on nonstandard neutrino interactions with quarks are derived from this initial data set.
5 【生物】DNA sequence–directed shape change of photopatterned hydrogels via high-degree swelling
Angelo Cangialosi, et.al
Shape-changing hydrogels that can bend, twist, or actuate in response to external stimuli are critical to soft robots, programmable matter, and smart medicine. Shape change in hydrogels has been induced by global cues, including temperature, light, or pH. Here we demonstrate that specific DNA molecules can induce 100-fold volumetric hydrogel expansion by successive extension of cross-links. We photopattern up to centimeter-sized gels containing multiple domains that undergo different shape changes in response to different DNA sequences. Experiments and simulations suggest a simple design rule for controlled shape change. Because DNA molecules can be coupled to molecular sensors, amplifiers, and logic circuits, this strategy introduces the possibility of building soft devices that respond to diverse biochemical inputs and autonomously implement chemical control programs.
6 【物理】Highly efficient electrocaloric cooling with electrostatic actuation
Rujun Ma and Ziyang Zhang, et.al
Solid-state refrigeration offers potential advantages over traditional cooling systems, but few devices offer high specific cooling power with a high coefficient of performance (COP) and the ability to be applied directly to surfaces. We developed a cooling device with a high intrinsic thermodynamic efficiency using a flexible electrocaloric (EC) polymer film and an electrostatic actuation mechanism. Reversible electrostatic forces reduce parasitic power consumption and allow efficient heat transfer through good thermal contacts with the heat source or heat sink. The EC device produced a specific cooling power of 2.8 watts per gram and a COP of 13. The new cooling device is more efficient and compact than existing surface-conformable solid-state cooling technologies, opening a path to using the technology for a variety of practical applications.
7【物理】Soft x-ray excitonics
A Moulet and J. B. Bertrand, et.al
The dynamic response of excitons in solids is central to modern condensed-phase physics, material sciences, and photonic technologies. However, study and control have hitherto been limited to photon energies lower than the fundamental band gap. Here we report application of attosecond soft x-ray and attosecond optical pulses to study the dynamics of core-excitons at the L2,3 edge of Si in silicon dioxide (SiO2). This attosecond x-ray absorption near-edge spectroscopy (AXANES) technique enables direct probing of the excitons’ quasiparticle character, tracking of their subfemtosecond relaxation, the measurement of excitonic polarizability, and observation of dark core-excitonic states. Direct measurement and control of core-excitons in solids lay the foundation of x-ray excitonics.
8【材料】Fabrication of fillable microparticles and other complex 3D microstructures
Kevin J. McHugh and Thand D. Nguyen, et.al
Three-dimensional (3D) microstructures created by microfabrication and additive manufacturing have demonstrated value across a number of fields, ranging from biomedicine to microelectronics. However, the techniques used to create these devices each have their own characteristic set of advantages and limitations with regards to resolution, material compatibility, and geometrical constraints that determine the types of microstructures that can be formed. We describe a microfabrication method, termed StampEd Assembly of polymer Layers (SEAL), and create injectable pulsatile drug-delivery microparticles, pH sensors, and 3D microfluidic devices that we could not produce using traditional 3D printing. SEAL allows us to generate microstructures with complex geometry at high resolution, produce fully enclosed internal cavities containing a solid or liquid, and use potentially any thermoplastic material without processing additives.
9【生物】Distinct phases of Polycomb silencing to hold epigenetic memory of cold in Arabidopsis
Hongchun Yang and Scott Berry, et.al
Gene silencing by Polycomb complexes is central to eukaryotic development. Cold-induced epigenetic repression of FLOWERING LOCUS C (FLC) in the plant Arabidopsis provides an opportunity to study initiation and maintenance of Polycomb silencing. Here, we show that a subset of Polycomb repressive complex 2 factors nucleate silencing in a small region within FLC, locally increasing H3K27me3 levels. This nucleation confers a silenced state that is metastably inherited, with memory held in the local chromatin. Metastable memory is then converted to stable epigenetic silencing through separate Polycomb factors, which spread across the locus after cold to enlarge the domain that contains H3K27me3. Polycomb silencing at FLC thus has mechanistically distinct phases, which involve specialization of distinct Polycomb components to deliver first metastable then long-term epigenetic silencing.
10【生物】DNA replication–coupled histone modification maintains Polycomb gene silencing in plants
Danhua Jiang and Frederic Berger
Propagation of patterns of gene expression through the cell cycle requires prompt restoration of epigenetic marks after the twofold dilution caused by DNA replication. Here we show that the transcriptional repressive mark H3K27me3 (histone H3 lysine 27 trimethylation) is restored in replicating plant cells through DNA replication–coupled modification of histone variant H3.1. Plants evolved a mechanism for efficient K27 trimethylation on H3.1, which is essential for inheritance of the silencing memory from mother to daughter cells. We illustrate how this mechanism establishes H3K27me3-mediated silencing during the developmental transition to flowering. Our study reveals a mechanism responsible for transmission of H3K27me3 in plant cells through cell divisions, enabling H3K27me3 to function as an epigenetic mark.
11【生物】Thirst-associated preoptic neurons encode an aversive motivational drive
William E. Allen and Laura A. DeNardo and Michael Z. Chen, et al.
Water deprivation produces a drive to seek and consume water. How neural activity creates this motivation remains poorly understood. We used activity-dependent genetic labeling to characterize neurons activated by water deprivation in the hypothalamic median preoptic nucleus (MnPO). Single-cell transcriptional profiling revealed that dehydration-activated MnPO neurons consist of a single excitatory cell type . After optogenetic activation of these neurons, mice drank water and performed an operant lever-pressing task for water reward with rates that scaled with stimulation frequency. This stimulation was aversive, and instrumentally pausing stimulation could reinforce lever-pressing. Activity of these neurons gradually decreased over the course of an operant session. Thus, the activity of dehydration-activated MnPO neurons establishes a scalable, persistent, and aversive internal state that dynamically controls thirst-motivated behavior.
12【生物】Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine
Leore T. Geller and Michal Berzily-Rokni, et al.
（导读 郭思瑶） 越来越多的证据显示微生物能影响癌症化疗效果。科学家通过研究结肠癌模型发现细菌能够将化疗药物吉西他滨（2′,2′-二氟脱氧胞苷）代谢为不活跃的2′,2′-二氟脱氧尿苷。代谢所需酶为细菌的胞苷脱氨酶（CDDL），主要存在于γ-变形菌中。细菌能引发癌症耐药性，抗生素结合治疗可减少该耐药产生。
Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.
13【生物】A Neolithic expansion, but strong genetic structure, in the independent history of New Guinea
Anders Bergstrom, et al.
New Guinea shows human occupation since ~50 thousand years ago (ka), independent adoption of plant cultivation ~10 ka, and great cultural and linguistic diversity today. We performed genome-wide single-nucleotide polymorphism genotyping on 381 individuals from 85 language groups in Papua New Guinea and find a sharp divide originating 10 to 20 ka between lowland and highland groups and a lack of non–New Guinean admixture in the latter. All highlanders share ancestry within the last 10 thousand years, with major population growth in the same period, suggesting population structure was reshaped following the Neolithic lifestyle transition. However, genetic differentiation between groups in Papua New Guinea is much stronger than in comparable regions in Eurasia, demonstrating that such a transition does not necessarily limit the genetic and linguistic diversity of human societies.
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