V2a neurons are a genetically defined cell class that forms a major excitatory descending pathway from the brainstem reticular formation to the spinal cord. Their activation has been linked to the termination of locomotor activity based on broad optogenetic manipulations. However, because of the difficulties involved in accessing brainstem structures for in vivo cell type-specific recordings, V2a neuron function has never been directly observed during natural behaviors. Here, we imaged the activity of V2a neurons using micro-endoscopy in freely moving mice. We find that as many as half of the V2a neurons are excited at locomotion arrest and with low reliability. Other V2a neurons are inhibited at locomotor arrests and/or activated during other behaviors such as locomotion initiation or stationary grooming. Our results establish that V2a neurons not only drive stops as suggested by bulk optogenetics but also are stratified into subpopulations that likely contribute to diverse motor patterns.Nonreciprocity, the defining characteristic of isolators, circulators, and a wealth of other applications in radio/microwave communications technologies, is generally difficult to achieve as most physical systems incorporate symmetries that prevent the effect. In particular, acoustic waves are an important medium for information transport, but they are inherently symmetric in time. In this work, we report giant nonreciprocity in the transmission of surface acoustic waves (SAWs) on lithium niobate substrate coated with ferromagnet/insulator/ferromagnet (FeGaB/Al2O3/FeGaB) multilayer structure. We exploit this structure with a unique asymmetric band diagram and expand on magnetoelastic coupling theory to show how the magnetic bands couple with acoustic waves only in a single direction. We measure 48.4-dB (power ratio of 169,200) isolation that outperforms current state-of-the-art microwave isolator devices in a previously unidentified acoustic wave system that facilitates unprecedented size, weight, and power reduction. In addition, these results offer a promising platform to study nonreciprocal SAW devices.The biophysical and biochemical properties of live tissues are important in the context of development and disease. Methods for evaluating these properties typically involve destroying the tissue or require specialized technology and complicated analyses. Here, we present a novel, noninvasive methodology for determining the spatial distribution of tissue features within embryos, making use of nondirectionally migrating cells and software we termed „Landscape,” which performs automatized high-throughput three-dimensional image registration. Using the live migrating cells as bioprobes, we identified structures within the zebrafish embryo that affect the distribution of the cells and studied one such structure constituting a physical barrier, which, in turn, influences amoeboid cell polarity. Overall, this work provides a unique approach for detecting tissue properties without interfering with animal’s development. In addition, Landscape allows for integrating data from multiple samples, providing detailed and reliable quantitative evaluation of variable biological phenotypes in different organisms.Here, we selectively target pancreatic ductal adenocarcinoma (PDAC) cells harboring a hemizygous gene essential for cell growth. MYB binding protein 1A (MYBBP1A), encoding a chromatin-bound protein, is hemizygous in most of the PDAC due to a chromosome 17p deletion that also spans TP53 We find that hemizygous MYBBP1A loss in isogenic PDAC cells promotes tumorigenesis but, paradoxically, homozygous MYBBP1A loss is associated with impaired cell growth and decreased tumorigenesis. Poly-adenosine 5′-diphosphate-ribose polymerase 1 (PARP1) interacts with MYBBP1A and displaces it from chromatin. Small molecules, such as olaparib, that trap PARP1 to chromatin are able to evict the minimal pool of chromatin-bound MYBBP1A protein in MYBBP1A hemizygous cells and impair cell growth, greater than its impact on wild-type cells. Our findings reveal how a cell essential gene with one allele lost in cancer cells can be preferentially susceptible to a specific molecular therapy, when compared to wild-type cells.Seasonal fluctuations in food prices reflect interactions between climate and society, measuring the degree to which predictable patterns of crop growth and harvest are offset by storage and trade. Previous research on seasonality in food systems has focused on specific commodities. This study accounts for substitution between items to meet nutritional needs, computing seasonal variation in local food environments using monthly retail prices for 191 items across Ethiopia, Malawi, and Tanzania from 2002 through 2016. We computed over 25,000 least-cost diets meeting nutrient requirements at each market every month and then measured the magnitude and timing of seasonality in diet costs. We found significant intensity in Malawi, Tanzania, and Ethiopia (10.0, 6.3, and 4.0%, respectively), driven primarily by synchronized price rises for nutrient-dense foods. Results provide a metric to map nutritional security, pointing to opportunities for more targeted investments to improve the year-round delivery of nutrients.Chiral spin textures are of considerable interest for applications in spintronics. It has recently been shown that magnetic materials with D2d symmetry can sustain several distinct spin textures. Here, we show, using Lorentz transmission electron microscopy, that single and double chains of antiskyrmions can be generated at room temperature in nanostripes less than 0.5 μm in width formed from the D2d Heusler compound Mn1.4Pt0.9Pd0.1Sn. Typically, truncated helical spin textures are formed in low magnetic fields, whose edges are terminated by half antiskyrmions. These evolve into chains of antiskyrmions with increasing magnetic field. Single chains of these objects are located in the middle of the nanostripes even when the stripes are much wider than the antiskyrmions. Moreover, the chains can even include elliptical Bloch skyrmions depending on details of the applied magnetic field history. These findings make D2d materials special and highly interesting for applications such as magnetic racetrack memory storage devices.Myelin degeneration and white matter loss resulting from oligodendrocyte (OL) death are early events in Alzheimer’s disease (AD) that lead to cognitive deficits; however, the underlying mechanism remains unknown. Here, we find that mature OLs in both AD patients and an AD mouse model undergo NLR family pyrin domain containing 3 (NLRP3)-dependent Gasdermin D-associated inflammatory injury, concomitant with demyelination and axonal degeneration. The mature OL-specific knockdown of dynamin-related protein 1 (Drp1; a mitochondrial fission guanosine triphosphatase) abolishes NLRP3 inflammasome activation, corrects myelin loss, and improves cognitive ability in AD mice. Drp1 hyperactivation in mature OLs induces a glycolytic defect in AD models by inhibiting hexokinase 1 (HK1; a mitochondrial enzyme that initiates glycolysis), which triggers NLRP3-associated inflammation. These findings suggest that OL glycolytic deficiency plays a causal role in AD development. The Drp1-HK1-NLRP3 signaling axis may be a key mechanism and therapeutic target for white matter degeneration in AD.Macrophages are innate immune cells that adhere to the extracellular matrix within tissues. However, how matrix properties regulate their function remains poorly understood. Here, we report that the adhesive microenvironment tunes the macrophage inflammatory response through the transcriptional coactivator YAP. We find that adhesion to soft hydrogels reduces inflammation when compared to adhesion on stiff materials and is associated with reduced YAP expression and nuclear localization. Substrate stiffness and cytoskeletal polymerization, but not adhesive confinement nor contractility, regulate YAP localization. Furthermore, depletion of YAP inhibits macrophage inflammation, whereas overexpression of active YAP increases inflammation. Last, we show in vivo that soft materials reduce expression of inflammatory markers and YAP in surrounding macrophages when compared to stiff materials. Together, our studies identify YAP as a key molecule for controlling inflammation and sensing stiffness in macrophages and may have broad implications in the regulation of macrophages in health and disease.A new generation of rocket propellants for deep space exploration, ionic liquid propellants, with long endurance and high stability, is attracting more and more attention. However, a major defect of ionic liquid propellants that restricts their application is the inadequate hypergolic reactivity between the fuel and the oxidant, and this defect results in local burnout and accidental explosions during the launch process. We propose a visualization model to show the features of structure, density, thermal stability, and hypergolic activity for estimating propellant performances and their application abilities. This propellant materials genome and visualization model greatly improves the efficiency and quality of developing high-performance propellants, which benefits the discovery of new advanced functional molecules in the field of energetic materials.Complex hydroclimate in the United States and Canada has limited identification of possible ongoing changes in streamflow. We address this challenge by classifying 541 stations in the United States and Canada into 15 „hydro-regions,” each with similar seasonal streamflow characteristics. Analysis of seasonal streamflow records at these stations from 1910 to present indicates regionally coherent changes in the frequency of extreme high- and low-flow events. Where changes are significant, these events have, on average, doubled in frequency relative to 1950 to 1969. In hydro-regions influenced by snowmelt runoff, extreme high-flow event frequency has increased despite snowpack depletion by warming winter temperatures. In drought-prone hydro-regions of the western United States and Southeast, extreme low-flow event frequency has increased, particularly during summer and fall. The magnitude and regional consistency of these hydrologic changes warrant attention by watershed stakeholders. The hydro-region framework facilitates quantification and further analyses of these changes to extreme streamflow.

Systemic juvenile idiopathic arthritis (SJIA) confers high risk for macrophage activation syndrome (MAS), a life-threatening cytokine storm driven by interferon (IFN)-γ. SJIA monocytes display IFN-γ hyper-responsiveness, but the molecular basis of this remains unclear. The objective of this study is to identify circulating monocyte and bone marrow macrophage (BMM) polarisation phenotypes in SJIA including molecular features contributing to IFN response.

Bulk RNA-seq was performed on peripheral blood monocytes (n=26 SJIA patients) and single cell (sc) RNA-seq was performed on BMM (n=1). Cultured macrophages were used to define consequences of tripartite motif containing 8 (TRIM8) knockdown on IFN-γ signalling.

Bulk RNA-seq of SJIA monocytes revealed marked transcriptional changes in patients with elevated ferritin levels. We identified substantial overlap with multiple polarisation states but little evidence of IFN-induced signature. Interestingly, among the most highly upregulated genes was TRIM8, a positive regulator of IFN-γ signalling.