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Vector-borne pathogens are known to elicit immune response upon mosquito biting the host which is critically linked to the establishment of infection and pathogenesis of disease, yet the impact of the mosquito bite itself is not immunologically well-appreciated. Here the authors characterize the immune response to the mosquito vector Aedes aegypti in a controlled human in vivo challenge model and show the induction of a range of immune pathways and cell types.
Reductive stress, reflected by the elevated intracellular NADH/NAD+ ratio, is associated with multiple human diseases. Here, the authors develop a genetic tool to manipulate the ratios of cellular NADH/NAD+ and NADPH/NADP+, and identify purine biosynthesis as an NADH-sensing pathway to mediate reductive stress.
Here the authors find that the mRNA of GYS2, the liver-specific glycogen synthase, is a substrate of METTL3 and IGF2BP2 and that m6A-mediated regulation of Gys2 mRNA is critical for the maintenance of liver glycogenesis in mammals during growth, such as mice and rats.
Chemotherapy resistance poses a major obstacle in cancer therapy. Here, the authors identify the mTOR pathway as a determinant of chemosensitivity and demonstrate that inhibition of mTOR promotes the persistence of a chemotherapy-resistant cancer-cell subpopulation.
TOPOVIBL and REC114 are required for meiotic DNA double-strand breaks (DSBs). This study shows that TOPOVIBL forms a complex with REC114 and mice carrying mutations that disrupt the interaction show DSB defects with distinct outcomes in males and females.
How does DNA encode shape? Here, via in toto light sheet microscopy and optogenetic control of cellular forces, the authors show that spatially patterned mechanical feedback loops establish the cytoskeletal patterns driving axis elongation tissue flow in Drosophila.
The poor contact at poly(3-hexylthiophene)/perovskite interface has led to unsatisfactory performance in solar cells. To resolve this issue, the authors introduce a molecular bridge to form a charge transport channel, realizing devices with maximum efficiency value of 22.87% and long-term stability.
Fungal infections are often major causes of disease in immune compromised patients and photodynamic therapy offers and attractive treatment. Here, the authors develop stereoisomeric photosensitizers via supramolecular assembly and demonstrate aggregation-induced photodynamic action against fungi.
CRY2 mediates photoperiod-responsive floral initiation in Arabidopsis. Here the authors show that CRY2 also regulates temperature sensitive flowering and that CRY2 can interact with and regulate the splicing factor CIS1 to affect alternative splicing of transcripts that regulate flowering.
The blood vessel wall is a complex multi-layered structure, yet upon injury or infection, neutrophil leukocytes are rapidly migrating from the blood stream to the affected tissues, by a process termed diapedesis. Authors here show that the final steps of diapedesis through the outer pericyte layer is regulated by perivascular mast cells via IL-17A production.
Density functional theory provides a formal map from the electron density to all observables of interest of a many-body system; however, maps for electronic excited states are unknown. Here, the authors demonstrate a data-driven machine learning approach for constructing multistate functionals.
It is known that the T cell co-receptor CD4 greatly enhances the capacity of T cell receptor (TCR) signalling, triggered by the peptide-bound MHC molecule. Here authors show that the mechanistic basis for the enhancement is the co-operative binding of TCR and CD4 to the MHC-peptide complex.
Rhee et al. demonstrates that the potent neuroprotective agent CNTF significantly impacts metabolism of degenerating retinas, thus revealing cellular mechanisms underlying enhanced neuronal viability and providing insight for the ongoing CNTF clinical trials.
Mutations in the chromatin remodeler CHD7 cause CHARGE syndrome, affecting development of several organs including the inner ear. Here, the authors recapitulated pathogenesis of this disease with human inner ear organoids and found that CHD7 is indispensable for proper otic lineage specification and hair cell differentiation.
Pentameric ligand-gated ion channels are modulated by anionic phospholipids. Here, by capturing an open-channel conformation of ELIC, the authors demonstrate the structural details of channel activation and a leaflet-specific mechanism for modulation by phosphatidylglycerol.
The stabilization of low-coordinate boron radicals is challenging, as they tend to form strong chemical bonds. Here the authors report the isolation and structural characterization of a dicoordinate boron radical featuring a π-donating amino and a π-accepting carbene ligand.
Monitoring the aging process in vivo is challenging. Here the authors generate a Glb1+/m‒Glb1-2A-mCherry (GAC) reporter mouse model, where the GAC signal is consistently correlated with established biomarkers of cellular senescence, cardiac hypertrophy and shortened lifespan, which may prove helpful for studies developing anti-aging interventions.
Here, the authors use reproductive mode data with matching phylogenetic data to explore the evolution of reproductive mode, transitions between reproductive modes, and diversification rates in amphibians.
Designing efficient reconfigurable field effect transistors remains a challenge. Here, the authors develop a transistor with three distinct operation modes, realized directly on an industrial 22nm FDSOI platform, demonstrating a reconfigurable analog circuit element with signal follower, phase shifter, and frequency doubler operation.
In this study, the microbiota of multiple body sites from 101 marine fish species from Southern California were sampled and analysed. The authors compared diversity measures while also establishing a method to estimate microbial biomass. Body site is shown to be the strongest driver of microbial diversity and patterns of phylosymbiosis are observed across the gill, skin and hindgut.