| | Cancer: Antibodies regulate antitumour immunity
Boosting the T cells that mediate anticancer immune responses is a therapeutic goal. But T cells do not work alone — B cells and the antibodies they produce can both trigger and suppress the response.
| Palaeontology: Dinosaur up in the air
A new feathered dinosaur from China, belonging to an obscure and strange carnivorous group, bears a seemingly bony wrist structure that may have had a role in flight.
| Sequential cancer mutations in cultured human intestinal stem cells
Using the CRISPR/Cas9 system, up to four frequently occurring colorectal cancer mutations were introduced alone or in combination into stem cell organoids derived from human small intestinal or colon tissue, allowing an in-depth investigation of the contribution of these mutations to cancer progression.
| Neurons for hunger and thirst transmit a negative-valence teaching signal
Cell-type-specific electrical activity manipulations and deep-brain imaging in mice of neuronal populations associated with homeostasis of nutrient or fluid intake reveals that learning is conditioned by a negative-valence signal from the hunger-mediating AGRP neurons and also from the thirst-mediating neurons in the subfornical organ.
| An enigmatic plant-eating theropod from the Late Jurassic period of Chile
A new dinosaur from the Late Jurassic period of Chile (about 150 million years ago) has been discovered and identified as a primitive kind of theropod that, unusually, was herbivore.
| Immunosuppressive plasma cells impede T-cell-dependent immunogenic chemotherapy
IgA plasmocytes are shown to promote resistance to the immunogenic chemotherapeutic oxaliplatin in prostate cancer mouse models by inhibiting activation of cytotoxic T cells; immunosuppressive plasma cells, which are also found in human-therapy-resistant prostate cancer, are generated in response to TGFβ, and their functionality depends on PD-L1 expression and IL-10 secretion.
| A bizarre Jurassic maniraptoran theropod with preserved evidence of membranous wings
A recently discovered fossil belonging to the Scansoriopterygidae, a group of bizarre dinosaurs closely related to birds, represents a new scansoriopterygid species and preserves evidence of a membranous aerodynamic surface very different from a classic avian wing.
| The Xist lncRNA interacts directly with SHARP to silence transcription through HDAC3
The mechanisms by which Xist, a long non-coding RNA, silences one X chromosome in female mammals are unknown; here a mass spectrometry-based approach is developed to identify several proteins that interact directly with Xist, including the transcriptional repressor SHARP that is required for transcriptional silencing through the histone deacetylase HDAC3.
| Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles
Structures of actin-like ParM filaments at near-atomic resolution and their arrangements into doublets reveal how subunits and filaments come together to segregate low-copy-number plasmid R1 in Escherichia coli, producing the simplest known mitotic machinery.
| Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity
Naturally occurring tumour-binding IgG antibodies are shown to initiate the rejection of allogeneic tumours, whereby Fc-receptor-mediated uptake of tumour immune complexes into dendritic cells activates tumour-reactive T cells, and intra-tumoral injection of allogeneic IgG together with dendritic cell adjuvants induces systemic T-cell-mediated antitumour responses.
| Th17 cells transdifferentiate into regulatory T cells during resolution of inflammation
Analysis of a mouse model shows that during the course of an immune response, helper T cells undergo functional reprogramming to transdifferentiate into regulatory T cells; this T cell plasticity could possibly be exploited to develop better therapies for restoring immune tolerance in autoimmune diseases.
| | A multilevel multimodal circuit enhances action selection in Drosophila
Combining neural manipulation in freely behaving animals, physiological studies and electron microscopy reconstruction in the Drosophila larva identifies a complex multilsensory circuit involved in the selection of larval escape modes that exhibits a multilevel multimodal convergence architecture.
Tomoko Ohyama, Casey M. Schneider-Mizell, Richard D. Fetter et al. | Structure of the human 80S ribosome
The structure of the human ribosome at high resolution has been solved; by combining single-particle cryo-EM and atomic model building, local resolution of 2.9 Å was achieved within the most stable areas of the structure.
Heena Khatter, Alexander G. Myasnikov, S. Kundhavai Natchiar et al. | | Extended hard-X-ray emission in the inner few parsecs of the Galaxy
A distinct hard-X-ray emission component is reported within the central four parsecs by eight parsecs of the Galaxy; this emission is more sharply peaked toward the Galactic Centre than is the surface brightness of the soft X-ray population, and all the interpretations of this emission pose significant challenges to our understanding of stellar evolution, binary formation and cosmic-ray production in the Galactic Centre.
Kerstin Perez, Charles J. Hailey, Franz E. Bauer et al. | Topological valley transport at bilayer graphene domain walls
The bandgap of bilayer graphene can be tuned with an electric field and topological valley polarized modes have been predicted to exist at its domain boundaries; here, near-field infrared imaging and low-temperature transport measurements reveal such modes in gapped bilayer graphene.
Long Ju, Zhiwen Shi, Nityan Nair et al. | High-mobility three-atom-thick semiconducting films with wafer-scale homogeneity
A new chemical vapour deposition method enables transition-metal dichalcogenide (TMD) monolayers to be grown directly on insulating silicon dioxide wafers, demonstrating the possibility of wafer-scale batch fabrication of high-performance devices with TMD monolayers.
Kibum Kang, Saien Xie, Lujie Huang et al. | Precise interpolar phasing of abrupt climate change during the last ice age
A new ice core from West Antarctica shows that, during the last ice age, abrupt Northern Hemisphere climate variations were followed two centuries later by a response in Antarctica, suggesting an oceanic propagation of the climate signal to the Southern Hemisphere high latitudes.
WAIS Divide Project Members, Christo Buizert, Betty Adrian et al. | Isotopic evidence for biological nitrogen fixation by molybdenum-nitrogenase from 3.2 Gyr
Nitrogen isotope ratios from rocks between 3.2 and 2.75 billion years old are most readily explained by biological nitrogen fixation, most probably using the metal molybdenum as a cofactor, showing that nitrogen fixation is at least 3.2 billion years old and suggesting that molybdenum was available to organisms long before the Great Oxidation Event.
Eva E. Stüeken, Roger Buick, Bradley M. Guy et al. | An epigenome-wide association study of total serum immunoglobulin E concentration
A survey of epigenetic associations between serum immunoglobulin E concentrations indicating allergy and methylation at CpG islands in families and a population sample has revealed associations at 36 loci that harbour genes encoding proteins including eosinophil products and phospholipid inflammatory mediators.
Liming Liang, Saffron A. G. Willis-Owen, Catherine Laprise et al. | A circuit mechanism for differentiating positive and negative associations
Neurons in the basolateral amygdala projecting to canonical fear or reward circuits undergo opposing changes in synaptic strength following fear or reward conditioning, and selectively activating these projection-target-defined neural populations causes either negative or positive reinforcement, respectively.
Praneeth Namburi, Anna Beyeler, Suzuko Yorozu et al. | NIK1-mediated translation suppression functions as a plant antiviral immunity mechanism
A new mechanism that plants use to combat begomoviruses—one of the most pathogenic groups of plant viruses, causing severe disease in major crops worldwide—is uncovered: plants inhibit the transcription of genes associated with the translational apparatus, thus causing a general reduction in protein synthesis.
Cristiane Zorzatto, João Paulo B. Machado, Kênia V. G. Lopes et al. | A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria
Artemisinins are key anti-malarial drugs, but artemisinin resistance has been increasing; this study identifies the molecular target of artemisinins as phosphatidylinositol-3-kinase and increase of the lipid product phosphatidylinositol-3-phosphate induces resistance in Plasmodium falciparum.
Alassane Mbengue, Souvik Bhattacharjee, Trupti Pandharkar et al. | Single-dose attenuated Vesiculovax vaccines protect primates against Ebola Makona virus
Two second-generation attenuated Ebola virus vaccines based on recombinant vesicular stomatitis virus protect macaques against infection with a recent Ebola virus isolate from Guinea.The N1 and N4 rVSV vectors described in this manuscript are the subject of patents licensed to Profectus BioSciences, Inc. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the University of Texas Medical Branch.
Chad E. Mire, Demetrius Matassov, Joan B. Geisbert et al. | Mutant MHC class II epitopes drive therapeutic immune responses to cancer
The authors show that a large fraction of tumour mutations is immunogenic and predominantly recognized by CD4+ T cells; they use these data to design synthetic messenger-RNA-based vaccines specific against tumour mutations, and show that these can reject tumours in mice.
Sebastian Kreiter, Mathias Vormehr, Niels van de Roemer et al. | TP53 loss creates therapeutic vulnerability in colorectal cancer
Genomic deletion of the tumour suppressor TP53 frequently includes other neighbouring genes, such as the POLR2A housekeeping gene that encodes a crucial RNA polymerase II subunit; suppression of POLR2A with α-amanitin or by RNA interference selectively inhibits the tumorigenic potential of cancer cells, and in mouse models of cancer, tumours can be selectively targeted with α-amanitin coupled to antibodies, suggesting new therapeutic approaches for human cancers.
Yunhua Liu, Xinna Zhang, Cecil Han et al. | Structural basis of CpG and inhibitory DNA recognition by Toll-like receptor 9
Crystal structures of three forms of Toll-like receptor (TLR) 9 — unliganded or bound either to immune stimulatory CpG-containing DNA or inhibitory DNA — together reveal the molecular basis of TLR9 activation.
Umeharu Ohto, Takuma Shibata, Hiromi Tanji et al. | The octahaem MccA is a haem c–copper sulfite reductase
Sulfite-reducing microbes couple the reduction of sulfite to the generation of a proton motive force that sustains organismic growth; here, two X-ray crystal structures are solved of MccA, a c-type cytochrome enzyme with eight haem groups that catalyses the six-electron reduction of sulfite to sulfide at a novel haem–copper active site.
Bianca Hermann, Melanie Kern, Luigi La Pietra et al. | | | | |
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