Notes

Gonadal mosaicism throughout ARID1B gene brings about rational incapacity as well as dysmorphic features within 3 siblings.
Inflammation is an essential part of immunity against pathogens and tumors but can promote disease if not tightly regulated. Self and non-self-nucleic acids can trigger inflammation, through recognition by the cyclic GMP-AMP (cGAMP) synthetase (cGAS) and subsequent activation of the stimulator of interferon genes (STING) protein. Here, we show that RNADNA hybrids can be detected by cGAS and that the Lysyl-tRNA synthetase (LysRS) inhibits STING activation through two complementary mechanisms. First, LysRS interacts with RNADNA hybrids, delaying recognition by cGAS and impeding cGAMP production. Second, RNADNA hybrids stimulate LysRS-dependent production of diadenosine tetraphosphate (Ap4A) that in turn attenuates STING-dependent signaling. We propose a model whereby these mechanisms cooperate to buffer STING activation. Consequently, modulation of the LysRS-Ap4A axis in vitro or in vivo interferes with inflammatory responses. Thus, altogether, we establish LysRS and Ap4A as pharmacological targets to control STING signaling and treat inflammatory diseases.It is of significance, but still remains a key challenge, to simultaneously enhance the strength and damping capacities in metals, as these two properties are often mutually exclusive. Here, we provide a multidesign strategy for defeating such a conflict by developing a Mg-NiTi composite with a bicontinuous interpenetrating-phase architecture through infiltration of magnesium melt into three-dimensionally printed Nitinol scaffold. The composite exhibits a unique combination of mechanical properties with improved strengths at ambient to elevated temperatures, remarkable damage tolerance, good damping capacities at differing amplitudes, and exceptional energy absorption efficiency, which is unprecedented for magnesium materials. The shape and strength after deformation can even be largely recovered by heat treatment. This study offers a new perspective for the structural and biomedical applications of magnesium.Suprastructures at the colloidal scale must be assembled with precise control over local interactions to accurately mimic biological complexes. The toughest design requirements include breaking the symmetry of assembly in a simple and reversible fashion to unlock functions and properties so far limited to living matter. We demonstrate a simple experimental technique to program magnetic field-induced interactions between metallodielectric patchy particles and isotropic, nonmagnetic "satellite" particles. By controlling the connectivity, composition, and distribution of building blocks, we show the assembly of three-dimensional, multicomponent supraparticles that can dynamically reconfigure in response to change in external field strength. The local arrangement of building blocks and their reconfigurability are governed by a balance of attraction and repulsion between oppositely polarized domains, which we illustrate theoretically and tune experimentally. Tunable, bulk assembly of colloidal matter with predefined symmetry provides a platform to design functional microstructured materials with preprogrammable physical and chemical properties.Exosomes are nanoscale vesicles distinguished by characteristic biophysical and biomolecular features; current analytical approaches, however, remain univariate. Here, we develop a dedicated platform for multiparametric exosome analysis-through simultaneous biophysical and biomolecular evaluation of the same vesicles-directly in clinical biofluids. Termed templated plasmonics for exosomes, the technology leverages in situ growth of gold nanoshells on vesicles to achieve multiselectivity. For biophysical selectivity, the nanoshell formation is templated by and tuned to distinguish exosome dimensions. For biomolecular selectivity, the nanoshell plasmonics locally quenches fluorescent probes only if they are target-bound on the same vesicle. The technology thus achieves multiplexed analysis of diverse exosomal biomarkers (e.g., proteins and microRNAs) but remains unresponsive to nonvesicle biomarkers. When implemented on a microfluidic, smartphone-based sensor, the platform is rapid, sensitive, and wash-free. It not only distinguished biomarker organizational states in native clinical samples but also showed that the exosomal subpopulation could more accurately differentiate patient prognosis.Interaction between dipolar forces, such as permanent magnets, generally leads to the formation of one-dimensional chains and rings. We investigated whether it was possible to let dipoles self-assemble into three-dimensional structures by encapsulating them in a shell with a specific shape. We found that the condition for self-assembly of a three-dimensional crystal is satisfied when the energies of dipoles in the parallel and antiparallel states are equal. Our experiments show that the most regular structures are formed using cylinders and cuboids and not by spheroids. This simple design rule will help the self-assembly community to realize three-dimensional crystals from objects in the micrometer range, which opens up the way toward previously unknown metamaterials.Moist air is lighter than dry air at the same temperature, pressure, and volume because the molecular weight of water is less than that of dry air. We call this the vapor buoyancy effect. Although this effect is well documented, its impact on Earth's climate has been overlooked. Here, we show that the lightness of water vapor helps to stabilize tropical climate by increasing the outgoing longwave radiation (OLR). In the tropical atmosphere, buoyancy is horizontally uniform. Then, the vapor buoyancy in the moist regions must be balanced by warmer temperatures in the dry regions of the tropical atmosphere. These higher temperatures increase tropical OLR. This radiative effect increases with warming, leading to a negative climate feedback. At a near present-day surface temperature, vapor buoyancy is responsible for a radiative effect of 1 W/m2 and a negative climate feedback of about 0.15 W/m2 per kelvin.Carboxysomes, prototypical bacterial microcompartments (BMCs) found in cyanobacteria, are large (~1 GDa) and essential protein complexes that enhance CO2 fixation. While carboxysome biogenesis has been elucidated, the activity dynamics, lifetime, and degradation of these structures have not been investigated, owing to the inability of tracking individual BMCs over time in vivo. We have developed a fluorescence-imaging platform to simultaneously measure carboxysome number, position, and activity over time in a growing cyanobacterial population, allowing individual carboxysomes to be clustered on the basis of activity and spatial dynamics. We have demonstrated both BMC degradation, characterized by abrupt activity loss followed by polar recruitment of the deactivated complex, and a subclass of ultraproductive carboxysomes. Together, our results reveal the BMC life cycle after biogenesis and describe the first method for measuring activity of single BMCs in vivo.Host shifts can lead to ecological speciation and the emergence of new pests and pathogens. However, the mutational events that facilitate the exploitation of novel hosts are poorly understood. Here, we characterize an adaptive walk underpinning the host shift of the aphid Myzus persicae to tobacco, including evolution of mechanisms that overcame tobacco chemical defenses. A series of mutational events added as many as 1.5 million nucleotides to the genome of the tobacco-adapted subspecies, M. p. nicotianae, and yielded profound increases in expression of an enzyme that efficiently detoxifies nicotine, both in aphid gut tissue and in the bacteriocytes housing the obligate aphid symbiont Buchnera aphidicola. This dual evolutionary solution overcame the challenge of preserving fitness of a mutualistic symbiosis during adaptation to a toxic novel host. Our results reveal the intricate processes by which genetic novelty can arise and drive the evolution of key innovations required for ecological adaptation.Carbon is a volatile element that has a considerable influence on the formation and evolution of planetary bodies, although it was previously believed to be depleted in the Moon. We present observations by the lunar orbiter KAGUYA of carbon ions emitted from the Moon. These emissions were distributed over almost the total lunar surface, but amounts were differed with respect to lunar geographical areas. The estimated emission fluxes to space were ~5.0 × 104 per square centimeter per second, which is greater than possible ongoing supplies from the solar wind and micrometeoroids. Our estimates demonstrate that indigenous carbon exists over the entire Moon, supporting the hypothesis of a carbon-containing Moon, where the carbon was embedded at its formation and/or was transported billions of years ago.Fluid commonly flows in response to an external pressure gradient. However, when a tunnel-containing hydrogel is immersed in water, spontaneous flow occurs through the tunnel without any pressure gradient. We confirmed this flow in a wide range of plant- and animal-derived hydrogels. The flow appears to be driven by axial concentration gradients originating from surface activities of the tunnel wall. Those activities include (i) hydrogel-water interaction and (ii) material exchange across the tunnel boundary. Unlike pressure-driven flow, this surface-induced flow has two distinct features incident infrared energy substantially increases flow velocity, and narrower tunnels generate faster flow. Thus, surface activities in hydrogel-lined tunnels may confer kinetic energy on the enclosed fluid, with infrared as an energy source.Cell-cell fusion or syncytialization is fundamental to the reproduction, development, and homeostasis of multicellular organisms. In addition to various cell type-specific fusogenic proteins, cell surface externalization of phosphatidylserine (PS), a universal eat-me signal in apoptotic cells, has been observed in different cell fusion events. Nevertheless, the molecular underpinnings of PS externalization and cellular mechanisms of PS-facilitated cell-cell fusion are unclear. Here, we report that TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), plays an essential role in placental trophoblast fusion by translocating PS to cell surface independent of apoptosis. The placentas from the TMEM16F knockout mice exhibit deficiency in trophoblast syncytialization and placental development, which lead to perinatal lethality. We thus identified a new biological function of TMEM16F CaPLSase in trophoblast fusion and placental development. Our findings provide insight into understanding cell-cell fusion mechanism of other cell types and on mitigating pregnancy complications such as miscarriage, intrauterine growth restriction, and preeclampsia.Human-machine interfaces (HMIs) experience increasing requirements for intuitive and effective manipulation. Current commercialized solutions of glove-based HMI are limited by either detectable motions or the huge cost on fabrication, energy, and computing power. We propose the haptic-feedback smart glove with triboelectric-based finger bending sensors, palm sliding sensor, and piezoelectric mechanical stimulators. The detection of multidirectional bending and sliding events is demonstrated in virtual space using the self-generated triboelectric signals for various degrees of freedom on human hand. We also perform haptic mechanical stimulation via piezoelectric chips to realize the augmented HMI. The smart glove achieves object recognition using machine learning technique, with an accuracy of 96%. Through the integrated demonstration of multidimensional manipulation, haptic feedback, and AI-based object recognition, our glove reveals its potential as a promising solution for low-cost and advanced human-machine interaction, which can benefit diversified areas, including entertainment, home healthcare, sports training, and medical industry.
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