Attosecond spectroscopy of liquid water
Electronic dynamics in liquids are of fundamental importance, but time-resolved experiments have so far remained limited to the femtosecond time scale. We report the extension of attosecond spectroscopy to the liquid phase. We measured time delays of 50 to 70 attoseconds between the photoemission from liquid water and that from gaseous water at photon energies of 21.7 to 31.0 electron volts. These photoemission delays can be decomposed into a photoionization delay sensitive to the local environment...
Thu Aug 20, 2020 20:38
Antibodies targeting the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) present a promising approach to combat the coronavirus disease 2019 (COVID-19) pandemic; however, concerns remain that mutations can yield antibody resistance. We investigated the development of resistance against four antibodies to the spike protein that potently neutralize SARS-CoV-2, individually as well as when combined into cocktails. These antibodies remain effective against spike variants...
Thu Aug 20, 2020 20:38
Understanding the impact of curvature on the self-assembly of elongated microscopic building blocks, such as molecules and proteins, is key to engineering functional materials with predesigned structure. We develop model "banana-shaped" colloidal particles with tunable dimensions and curvature, whose structure and dynamics are accessible at the particle level. By heating initially straight rods made of SU-8 photoresist, we induce a controllable shape deformation that causes the rods to buckle into...
Thu Aug 20, 2020 20:38
Stimulator of interferon genes (STING) links innate immunity to biological processes ranging from antitumor immunity to microbiome homeostasis. Mechanistic understanding of the anticancer potential for STING receptor activation is currently limited by metabolic instability of the natural cyclic dinucleotide (CDN) ligands. From a pathway-targeted cell-based screen, we identified a non-nucleotide, small-molecule STING agonist, termed SR-717, that demonstrates broad interspecies and interallelic specificity....
Thu Aug 20, 2020 20:38
In developed countries, the leading causes of blindness such as diabetic retinopathy are characterized by disorganized vasculature that can become fibrotic. Although many such pathological vessels often naturally regress and spare sight-threatening complications, the underlying mechanisms remain unknown. Here, we used orthogonal approaches in human patients with proliferative diabetic retinopathy and a mouse model of ischemic retinopathies to identify an unconventional role for neutrophils in vascular...
Thu Aug 20, 2020 20:38
Intestinal microbiota have been proposed to induce commensal-specific memory T cells that cross-react with tumor-associated antigens. We identified major histocompatibility complex (MHC) class I–binding epitopes in the tail length tape measure protein (TMP) of a prophage found in the genome of the bacteriophage Enterococcus hirae. Mice bearing E. hirae harboring this prophage mounted a TMP-specific H-2Kb–restricted CD8+ T lymphocyte response upon immunotherapy with cyclophosphamide or anti–PD-1 antibodies....
Thu Aug 20, 2020 20:38
Abrupt climate changes during the last glacial period have been detected in a global array of palaeoclimate records, but our understanding of their absolute timing and regional synchrony is incomplete. Our compilation of 63 published, independently dated speleothem records shows that abrupt warmings in Greenland were associated with synchronous climate changes across the Asian Monsoon, South American Monsoon, and European-Mediterranean regions that occurred within decades. Together with the demonstration...
Thu Aug 20, 2020 20:38
Germinal center (GC) responses potentiate the generation of follicular regulatory T (TFR) cells. However, the molecular cues driving TFR cell formation remain unknown. Here, we show that sclerostin domain-containing protein 1 (SOSTDC1), secreted by a subpopulation of follicular helper T (TFH) cells and T–B cell border–enriched fibroblastic reticular cells, is developmentally required for TFR cell generation. Fate tracking and transcriptome assessment in reporter mice establishes SOSTDC1-expressing...
Thu Aug 20, 2020 20:38
Uromodulin is the most abundant protein in human urine, and it forms filaments that antagonize the adhesion of uropathogens; however, the filament structure and mechanism of protection remain poorly understood. We used cryo–electron tomography to show that the uromodulin filament consists of a zigzag-shaped backbone with laterally protruding arms. N-glycosylation mapping and biophysical assays revealed that uromodulin acts as a multivalent ligand for the bacterial type 1 pilus adhesin, presenting...
Thu Aug 20, 2020 20:38
Oxygenic photosynthesis is the main process that drives life on earth. It starts with the harvesting of solar photons that, after transformation into electronic excitations, lead to charge separation in the reaction centers of photosystems I and II (PSI and PSII). These photosystems are large, modular pigment-protein complexes that work in series to fuel the formation of carbohydrates, concomitantly producing molecular oxygen. Recent advances in cryo–electron microscopy have enabled the determination...
Thu Aug 20, 2020 20:38
Gamma delta () T cells infiltrate most human tumors, but current immunotherapies fail to exploit their in situ major histocompatibility complex–independent tumoricidal potential. Activation of T cells can be elicited by butyrophilin and butyrophilin-like molecules that are structurally similar to the immunosuppressive B7 family members, yet how they regulate and coordinate αβ and T cell responses remains unknown. Here, we report that the butyrophilin BTN3A1 inhibits tumor-reactive αβ T cell receptor...
Thu Aug 20, 2020 20:38
Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled a cohort of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–recovered participants, developed neutralization assays to investigate antibody responses, adapted our high-throughput antibody generation pipeline to rapidly screen more than 1800 antibodies, and established an animal model to test protection. We isolated potent neutralizing antibodies (nAbs) to two epitopes on...
Thu Aug 20, 2020 20:38
Site selectivity and stereocontrol remain major challenges in C–H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)–H bonds to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C–H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and...
Thu Aug 20, 2020 20:38
Versatile chemical transformations of surface functional groups in two-dimensional transition-metal carbides (MXenes) open up a previously unexplored design space for this broad class of functional materials. We introduce a general strategy to install and remove surface groups by performing substitution and elimination reactions in molten inorganic salts. Successful synthesis of MXenes with oxygen, imido, sulfur, chlorine, selenium, bromine, and tellurium surface terminations, as well as bare MXenes...
Thu Aug 20, 2020 20:38
Cytoarchitecture is a basic principle of microstructural brain parcellation. We introduce Julich-Brain, a three-dimensional atlas containing cytoarchitectonic maps of cortical areas and subcortical nuclei. The atlas is probabilistic, which enables it to account for variations between individual brains. Building such an atlas was highly data- and labor-intensive and required the development of nested, interdependent workflows for detecting borders between brain areas, data processing, provenance tracking,...
Thu Aug 20, 2020 20:38
Pulse-like carbon dioxide release to the atmosphere on centennial time scales has only been identified for the most recent glacial and deglacial periods and is thought to be absent during warmer climate conditions. Here, we present a high-resolution carbon dioxide record from 330,000 to 450,000 years before present, revealing pronounced carbon dioxide jumps (CDJ) under cold and warm climate conditions. CDJ come in two varieties that we attribute to invigoration or weakening of the Atlantic meridional...
Thu Aug 20, 2020 20:38
Neutralizing antibodies have become an important tool in treating infectious diseases. Recently, two separate approaches yielded successful antibody treatments for Ebola—one from genetically humanized mice and the other from a human survivor. Here, we describe parallel efforts using both humanized mice and convalescent patients to generate antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, which yielded a large collection of fully human antibodies that...
Thu Aug 20, 2020 20:38
Thu Aug 20, 2020 20:38
Pharmacological activation of the STING (stimulator of interferon genes)–controlled innate immune pathway is a promising therapeutic strategy for cancer. Here we report the identification of MSA-2, an orally available non-nucleotide human STING agonist. In syngeneic mouse tumor models, subcutaneous and oral MSA-2 regimens were well tolerated and stimulated interferon-β secretion in tumors, induced tumor regression with durable antitumor immunity, and synergized with anti–PD-1 therapy. Experimental...
Thu Aug 20, 2020 20:38
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