miR-146a is a significant brake on autoimmunity, myeloproliferation, and cancer in mice

Excessive or inappropriate activation of the immune system can be deleterious to the organism, warranting multiple molecular mechanisms to control and properly terminate immune responses. MicroRNAs (miRNAs), ~22-nt-long noncoding RNAs, have recently emerged as key posttranscriptional regulators, controlling diverse biological processes, including responses to non-self. In this study, we examine the biological role of miR-146a using genetically engineered mice and show that targeted deletion of this gene, whose expression is strongly up-regulated after immune cell maturation and/or activation, results in several immune defects. Collectively, our findings suggest that miR-146a plays a key role as a molecular brake on inflammation, myeloid cell proliferation, and oncogenic transformation

Toward on-sky adaptive optics control using reinforcement learning Model-based policy optimization for adaptive optics

Context. The direct imaging of potentially habitable exoplanets is one prime science case for the next generation of high contrast imaging instruments on ground-based, extremely large telescopes. To reach this demanding science goal, the instruments are equipped with eXtreme Adaptive Optics (XAO) systems which will control thousands of actuators at a framerate of kilohertz to several kilohertz. Most of the habitable exoplanets are located at small angular separations from their host stars, where the current control laws of XAO systems leave strong residuals. Aims. Current AO control strategies such as static matrix-based wavefront reconstruction and integrator control suffer from a temporal delay error and are sensitive to mis-registration, that is, to dynamic variations of the control system geometry. We aim to produce control methods that cope with these limitations, provide a significantly improved AO correction, and, therefore, reduce the residual flux in the coronagraphic point spread function (PSF). Methods. We extend previous work in reinforcement learning for AO. The improved method, called the Policy Optimization for Adaptive Optics (PO4AO), learns a dynamics model and optimizes a control neural network, called a policy. We introduce the method and study it through numerical simulations of XAO with Pyramid wavefront sensor (PWFS) for the 8-m and 40-m telescope aperture cases. We further implemented PO4AO and carried out experiments in a laboratory environment using Magellan Adaptive Optics eXtreme system (MagAO-X) at the Steward laboratory. Results. PO4AO provides the desired performance by improving the coronagraphic contrast in numerical simulations by factors of 3-5 within the control region of deformable mirror and PWFS, both in simulation and in the laboratory. The presented method is also quick to train, that is, on timescales of typically 5-10 s, and the inference time is sufficiently small (Peer reviewe

Toward on-sky adaptive optics control using reinforcement learning Model-based policy optimization for adaptive optics

Context. The direct imaging of potentially habitable exoplanets is one prime science case for the next generation of high contrast imaging instruments on ground-based, extremely large telescopes. To reach this demanding science goal, the instruments are equipped with eXtreme Adaptive Optics (XAO) systems which will control thousands of actuators at a framerate of kilohertz to several kilohertz. Most of the habitable exoplanets are located at small angular separations from their host stars, where the current control laws of XAO systems leave strong residuals. Aims. Current AO control strategies such as static matrix-based wavefront reconstruction and integrator control suffer from a temporal delay error and are sensitive to mis-registration, that is, to dynamic variations of the control system geometry. We aim to produce control methods that cope with these limitations, provide a significantly improved AO correction, and, therefore, reduce the residual flux in the coronagraphic point spread function (PSF). Methods. We extend previous work in reinforcement learning for AO. The improved method, called the Policy Optimization for Adaptive Optics (PO4AO), learns a dynamics model and optimizes a control neural network, called a policy. We introduce the method and study it through numerical simulations of XAO with Pyramid wavefront sensor (PWFS) for the 8-m and 40-m telescope aperture cases. We further implemented PO4AO and carried out experiments in a laboratory environment using Magellan Adaptive Optics eXtreme system (MagAO-X) at the Steward laboratory. Results. PO4AO provides the desired performance by improving the coronagraphic contrast in numerical simulations by factors of 3-5 within the control region of deformable mirror and PWFS, both in simulation and in the laboratory. The presented method is also quick to train, that is, on timescales of typically 5-10 s, and the inference time is sufficiently small (Peer reviewe

Nearly a decade-long repeatable seasonal diversity patterns of bacterioplankton communities in the eutrophic Lake Donghu (Wuhan, China).

Uncovering which environmental factors govern community diversity patterns and how ecological processes drive community turnover are key questions related to understand the community assembly. However, the ecological mechanisms regulating long-term variations of bacterioplankton communities in lake ecosystems remain poorly understood. Here we present nearly a decade-long study of bacterioplankton communities from the eutrophic Lake Donghu (Wuhan, China) using 16S rRNA gene amplicon sequencing with MiSeq platform. We found strong repeatable seasonal diversity patterns in terms of both common (detected in more than 50% samples) and dominant (relative abundance >1%) bacterial taxa turnover. Moreover, community composition tracked the seasonal temperature gradient, indicating that temperature is a key environmental factor controlling observed diversity patterns. Total phosphorus also contributed significantly to the seasonal shifts in bacterioplankton composition. However, any spatial pattern of bacterioplankton communities across the main lake areas within season was overwhelmed by their temporal variabilities. Phylogenetic analysis further indicated that 75%-82% of community turnover was governed by homogeneous selection due to consistent environmental conditions within seasons, suggesting that the microbial communities in Lake Donghu are mainly controlled by niche-based processes. Therefore, dominant niches available within seasons might be occupied by similar combinations of bacterial taxa with modest dispersal rates throughout different lake areas

What traits are carried on mobile genetic elements, and why?

Although similar to any other organism, prokaryotes can transfer genes vertically from mother cell to daughter cell, they can also exchange certain genes horizontally. Genes can move within and between genomes at fast rates because of mobile genetic elements (MGEs). Although mobile elements are fundamentally self-interested entities, and thus replicate for their own gain, they frequently carry genes beneficial for their hosts and/or the neighbours of their hosts. Many genes that are carried by mobile elements code for traits that are expressed outside of the cell. Such traits are involved in bacterial sociality, such as the production of public goods, which benefit a cell's neighbours, or the production of bacteriocins, which harm a cell's neighbours. In this study we review the patterns that are emerging in the types of genes carried by mobile elements, and discuss the evolutionary and ecological conditions under which mobile elements evolve to carry their peculiar mix of parasitic, beneficial and cooperative genes

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Effects of Simulated Microgravity on Embryonic Stem Cells

There have been many studies on the biological effects of simulated microgravity (SMG) on differentiated cells or adult stem cells. However, there has been no systematic study on the effects of SMG on embryonic stem (ES) cells. In this study, we investigated various effects (including cell proliferation, cell cycle distribution, cell differentiation, cell adhesion, apoptosis, genomic integrity and DNA damage repair) of SMG on mouse embryonic stem (mES) cells. Mouse ES cells cultured under SMG condition had a significantly reduced total cell number compared with cells cultured under 1 g gravity (1G) condition. However, there was no significant difference in cell cycle distribution between SMG and 1G culture conditions, indicating that cell proliferation was not impaired significantly by SMG and was not a major factor contributing to the total cell number reduction. In contrast, a lower adhesion rate cultured under SMG condition contributed to the lower cell number in SMG. Our results also revealed that SMG alone could not induce DNA damage in mES cells while it could affect the repair of radiation-induced DNA lesions of mES cells. Taken together, mES cells were sensitive to SMG and the major alterations in cellular events were cell number expansion, adhesion rate decrease, increased apoptosis and delayed DNA repair progression, which are distinct from the responses of other types of cells to SMG

High-Throughput Top-Down Fabrication of Uniform Magnetic Particles

Ion Beam Aperture Array Lithography was applied to top-down fabrication of large dense (108–109 particles/cm2) arrays of uniform micron-scale particles at rates hundreds of times faster than electron beam lithography. In this process, a large array of helium ion beamlets is formed when a stencil mask containing an array of circular openings is illuminated by a broad beam of energetic (5–8 keV) ions, and is used to write arrays of specific repetitive patterns. A commercial 5-micrometer metal mesh was used as a stencil mask; the mesh size was adjusted by shrinking the stencil openings using conformal sputter-deposition of copper. Thermal evaporation from multiple sources was utilized to form magnetic particles of varied size and thickness, including alternating layers of gold and permalloy. Evaporation of permalloy layers in the presence of a magnetic field allowed creation of particles with uniform magnetic properties and pre-determined magnetization direction. The magnetic properties of the resulting particles were characterized by Vibrating Sample Magnetometry. Since the orientation of the particles on the substrate before release into suspension is known, the orientation-dependent magnetic properties of the particles could be determined