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IRE1 helps mitigate endoplasmic-reticulum stress by cleaving specific mRNAs at a conserved sequence endomotif via regulated IRE1-dependent decay (RIDD). Here the authors discover a more promiscuous IRE1 activity dubbed RIDD lacking endomotif (RIDDLE).
Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.
The plant defense hormone salicylic acid has structural similarity to oxicam-type non-steroidal antiinflammatories. Here the authors show oxicams, as well as endogenous salicylic acid, can alter cellular redox state and immune signaling without affecting the redox status of cysteines in NPR1.
Signals of antimicrobial resistance in pathogen genomes may be detectable before the organism evolves an antimicrobial resistance phenotype. Here, the authors investigate this hypothesis using Mycobacterium tuberculosis data from Peru and identify candidate “pre-resistance” markers.
The hazards of pyroclastic surges remain poorly mitigated globally. Here, the authors show that their destructiveness is amplified by turbulent excursions of dynamic pressure energy that focusses inside the largest eddies and internal gravity waves.
Intravital imaging reveals macrophage-driven de novo induction of cancer stem cells in vivo, and their dramatic enrichment on dissemination through TMEM doorways. These findings provide a mechanism for the validated ability of TMEM doorway density to be prognostic for distant recurrence of metastatic tumors in breast cancer patients.
Here the authors describe the discovery of a class of small molecule splicing modifiers which are orally bioavailable, cross the blood-brain barrier, and lower levels of huntingtin in a mouse model of Huntington’s disease (HD).
Androgen receptor in prostate cancer (PCa) transcriptionally represses multiple genes including MYC. Here, the authors suggest that increased MYC in response to androgen deprivation contributes to castration-resistant PCa, while decreased MYC may contribute to responses to supraphysiological androgen therapy.
Upon intestinal injury, bone marrow derived monocytes are recruited to the damaged site through the bloodstream. Authors here show that peritoneal cavity macrophages directly migrate to the damaged intestine in an ATP and hyaluronan dependent manner, and participate in the restoration of tissue integrity.
Blood microcirculation supplies neurons with oxygen and nutrients, and contributes to clearing their neurotoxic waste. Here, the authors analyse blood flow simulations to establish the physical laws linking the microvascular architecture to the macroscopic transport properties that control oxygen supply and waste clearance.
HfO2 is a promising ferroelectric material for applications in electronics but knowledge on its ferroic and electromechanical response properties is still lacking. Here, the authors demonstrate the peculiar piezoresponse of HfO2, predicting on how to reverse its sign by means of a biaxial strain.
The mechanism of ferroelectric resistance switching is still under debate. Here, the authors propose an interfacial engineering approach to demonstrate its origin and find that it is governed by three independent variables: polarization, barrier change, and initial barrier.
Methods to quantitatively study liquid-liquid phase separation (LLPS) of proteins are lacking. Here the authors report Capillary flow experiments (Capflex) for the quantification of key LLPS parameters; they study Ddx4, the RP3 peptide and the aberrant liquid-to-solid phase transition of α-synuclein.
Anomalously slow seismic velocities in the upper Greenlandic crust reveal soft sedimentary substrates beneath major outlet glaciers. This, together with elevated geothermal heat flux observed at the onset of fast ice flow, has major implications for ice-sheet dynamics.
To accelerate cancer research that correlates biomarkers with clinical endpoints, methods are needed to ascertain outcomes from electronic health records at scale. Here, the authors train natural language processing to extract outcomes for participants in a precision oncology study.
3D brain organoids have been used to investigate human brain development and pathology. Here the authors establish human ventral midbrain organoids coupled with single cell sequencing to study developing and mature dopamine neurons and use silk scaffolding to generate bioengineered brain organoids
Humans have altered plant biogeography by introducing species from one region to another, but an analysis of how naturalized plant species affect the uniqueness of regional floras around the world was missing. This study presents an analysis using data from native and naturalized alien floras in 658 regions, finding strong taxonomic and phylogenetic floristic homogenization overall.
Age-related macular degeneration is characterized by lipid-rich drusen deposits underneath the retinal pigment epithelium (RPE). Here the authors report an in vitro iPSC-RPE model for AMD that recapitulates drusen and RPE atrophy, and identify two drugs that reduce drusen deposits and restore RPE epithelial phenotype.
Though the lunar samples returned by the Apollo and Luna missions have been studied for more than 50 years, scientists are discovering new clues into the early evolution of the Moon by looking through the lens of modern analytical techniques.