Steinlindahl3973

In Golden Syrian hamsters challenged with Beta or Delta strains, the vaccine candidate reduced the viral loads in nasal turbinates and lung tissues, accompanied by significant weight gain and relieved inflammation in the lungs. In rhesus macaque challenged with prototype SARS-CoV-2, the vaccine candidate decreased viral shedding in throat, anal, blood swabs over time, reduced viral loads of bronchus and lung tissue, and effectively relieved the lung pathological inflammatory response. EN460 in vitro Together, our data demonstrated the broadly neutralizing activity and efficacy of the variant vaccine against both prototype and current VOCs of SARS-CoV-2, justifying further clinical development.Visually nonidentifiable pathological symptoms at an early stage are a major limitation in agricultural plantations. Thickness reduction in palisade parenchyma (PP) and spongy parenchyma (SP) layers is one of the most common symptoms that occur at the early stage of leaf diseases, particularly in apple and persimmon. To visualize variations in PP and SP thickness, we used optical coherence tomography (OCT)-based imaging and analyzed the acquired datasets to determine the threshold parameters for pre-identifying and estimating persimmon and apple leaf abnormalities using an intensity-based depth profiling algorithm. The algorithm identified morphological differences between healthy, apparently-healthy, and infected leaves by applying a threshold in depth profiling to classify them. The qualitative and quantitative results revealed changes and abnormalities in leaf morphology in addition to disease incubation in both apple and persimmon leaves. These can be used to examine how initial symptoms are influenced by disease growth. Thus, these datasets confirm the significance of OCT in identifying disease symptoms nondestructively and providing a benchmark dataset to the agriculture community for future reference.In the olfactory system, the olfactory cortex sends glutamatergic projections back to the first stage of olfactory processing, the olfactory bulb (OB). Such corticofugal excitatory circuits - a canonical circuit motif described in all sensory systems- dynamically adjust early sensory processing. Here, we uncover a corticofugal inhibitory feedback to OB, originating from a subpopulation of GABAergic neurons in the anterior olfactory cortex and innervating both local and output OB neurons. In vivo imaging and network modeling showed that optogenetic activation of cortical GABAergic projections drives a net subtractive inhibition of both spontaneous and odor-evoked activity in local as well as output neurons. In output neurons, stimulation of cortical GABAergic feedback enhances separation of population odor responses in tufted cells, but not mitral cells. Targeted pharmacogenetic silencing of cortical GABAergic axon terminals impaired discrimination of similar odor mixtures. Thus, corticofugal GABAergic projections represent an additional circuit motif in cortical feedback control of sensory processing.2D material hydrogels have recently sparked tremendous interest owing to their potential in diverse applications. However, research on the emerging 2D MXene hydrogels is still in its infancy. Herein, we show a universal 4D printing technology for manufacturing MXene hydrogels with customizable geometries, which suits a family of MXenes such as Nb2CTx, Ti3C2Tx, and Mo2Ti2C3Tx. The obtained MXene hydrogels offer 3D porous architectures, large specific surface areas, high electrical conductivities, and satisfying mechanical properties. Consequently, ultrahigh capacitance (3.32 F cm-2 (10 mV s-1) and 233 F g-1 (10 V s-1)) and mass loading/thickness-independent rate capabilities are achieved. The further 4D-printed Ti3C2Tx hydrogel micro-supercapacitors showcase great low-temperature tolerance (down to -20 °C) and deliver high energy and power densities up to 93 μWh cm-2 and 7 mW cm-2, respectively, surpassing most state-of-the-art devices. This work brings new insights into MXene hydrogel manufacturing and expands the range of their potential applications.The primate neocortex exerts high cognitive ability and strong information processing capacity. Here, we establish a single-cell RNA sequencing dataset of 133,454 macaque visual cortical cells. It covers major cortical cell classes including 25 excitatory neuron types, 37 inhibitory neuron types and all glial cell types. We identified layer-specific markers including HPCAL1 and NXPH4, and also identified two cell types, an NPY-expressing excitatory neuron type that expresses the dopamine receptor D3 gene; and a primate specific activity-dependent OSTN + sensory neuron type. Comparisons of our dataset with humans and mice show that the gene expression profiles differ between species in relation to genes that are implicated in the synaptic plasticity and neuromodulation of excitatory neurons. The comparisons also revealed that glutamatergic neurons may be more diverse across species than GABAergic neurons and non-neuronal cells. These findings pave the way for understanding how the primary cortex fulfills the high-cognitive functions.Developing active single-atom-catalyst (SAC) for alkaline hydrogen evolution reaction (HER) is a promising solution to lower the green hydrogen cost. However, the correlations are not clear between the chemical environments around the active-sites and their desired catalytic activity. Here we study a group of SACs prepared by anchoring platinum atoms on NiFe-layered-double-hydroxide. While maintaining the homogeneity of the Pt-SACs, various axial ligands (-F, -Cl, -Br, -I, -OH) are employed via a facile irradiation-impregnation procedure, enabling us to discover definite chemical-environments/performance correlations. Owing to its high first-electron-affinity, chloride chelated Pt-SAC exhibits optimized bindings with hydrogen and hydroxide, which favor the sluggish water dissociation and further promote the alkaline HER. Specifically, it shows high mass-activity of 30.6 A mgPt-1 and turnover frequency of 30.3  H2 s-1 at 100 mV overpotential, which are significantly higher than those of the state-of-the-art Pt-SACs and commercial Pt/C catalyst. Moreover, high energy efficiency of 80% is obtained for the alkaline water electrolyser assembled using the above catalyst under practical-relevant conditions.Seasonal influenza outbreaks, especially in high-risk groups such as the elderly, represent an important public health problem. Prevailing inadequate efficacy of seasonal vaccines is a crucial bottleneck. Understanding the immunological and molecular mechanisms underpinning differential influenza vaccine responsiveness is essential to improve vaccination strategies. Here we show comprehensive characterization of the immune response of randomly selected elderly participants (≥ 65 years), immunized with the adjuvanted influenza vaccine Fluad. In-depth analyses by serology, multi-parametric flow cytometry, multiplex and transcriptome analysis, coupled to bioinformatics and mathematical modelling, reveal distinguishing immunological and molecular features between responders and non-responders defined by vaccine-induced seroconversion. Non-responders are specifically characterized by multiple suppressive immune mechanisms. The generated comprehensive high dimensional dataset enables the identification of putative mechanisms and nodes responsible for vaccine non-responsiveness independently of confounding age-related effects, with the potential to facilitate development of tailored vaccination strategies for the elderly.Enterotoxigenic E. coli (ETEC) produce heat-labile (LT) and/or heat-stable (ST) enterotoxins, and commonly cause diarrhea in resource-poor regions. ETEC have been linked repeatedly to sequelae in children including enteropathy, malnutrition, and growth impairment. Although cellular actions of ETEC enterotoxins leading to diarrhea are well-established, their contributions to sequelae remain unclear. LT increases cellular cAMP to activate protein kinase A (PKA) that phosphorylates ion channels driving intestinal export of salt and water resulting in diarrhea. As PKA also modulates transcription of many genes, we interrogated transcriptional profiles of LT-treated intestinal epithelia. Here we show that LT significantly alters intestinal epithelial gene expression directing biogenesis of the brush border, the major site for nutrient absorption, suppresses transcription factors HNF4 and SMAD4 critical to enterocyte differentiation, and profoundly disrupts microvillus architecture and essential nutrient transport. In addition, ETEC-challenged neonatal mice exhibit substantial brush border derangement that is prevented by maternal vaccination with LT. Finally, mice repeatedly challenged with toxigenic ETEC exhibit impaired growth recapitulating the multiplicative impact of recurring ETEC infections in children. These findings highlight impacts of ETEC enterotoxins beyond acute diarrheal illness and may inform approaches to prevent major sequelae of these common infections including malnutrition that impact millions of children.Toll-like Receptor 3 (TLR3) initiates a potent anti-viral immune response by binding to double-stranded RNA ligands. Previous crystallographic studies showed that TLR3 forms a homodimer when bound to a 46-base pair RNA ligand. However, this short RNA fails to initiate a robust immune response. To obtain structural insights into the length dependency of TLR3 ligands, we determine the cryo-electron microscopy structure of full-length TLR3 in a complex with a synthetic RNA ligand with an average length of ~400 base pairs. In the structure, the dimeric TLR3 units are clustered along the double-stranded RNA helix in a highly organized and cooperative fashion with a uniform inter-dimer spacing of 103 angstroms. The intracellular and transmembrane domains are dispensable for the clustering because their deletion does not interfere with the cluster formation. Our structural observation suggests that ligand-induced clustering of TLR3 dimers triggers the ordered assembly of intracellular signaling adaptors and initiates a robust innate immune response.Understanding exotic forms of magnetism in quantum spin systems is an emergent topic of modern condensed matter physics. Quantum dynamics can be described by particle-like carriers of information, known-as quasiparticles that appear from the collective behaviour of the underlying system. Spinon excitations, governing the excitations of quantum spin-systems, have been accurately calculated and precisely verified experimentally for the antiferromagnetic chain model. However, identification and characterization of novel quasiparticles emerging from the topological excitations of the spin system having periodic exchange interactions are yet to be obtained. Here, we report the identification of emergent composite excitations of the novel quasiparticles doublons and quartons in spin-1/2 trimer-chain antiferromagnet Na2Cu3Ge4O12 (having periodic intrachain exchange interactions J1-J1-J2) and its topologically protected quantum 1/3 magnetization-plateau state. The characteristic energies, dispersion relations, and dynamical structure factor of neutron scattering as well as macroscopic quantum 1/3 magnetization-plateau state are in good agreement with the state-of-the-art dynamical density matrix renormalization group calculations.