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Interdecadal modulation of Ningaloo Niño/Niña strength in the Southeast Indian Ocean by the Atlantic Multidecadal Oscillation
The TaCLE24b peptide signaling cascade modulates lateral root development and drought tolerance in wheat
Correlated states controlled by a tunable van Hove singularity in moiré WSe2 bilayers
Abstract Twisted transition metal dichalcogenide (TMD) bilayers have enabled the discovery of superconductivity, ferromagnetism, correlated insulators, and a series of new topological phases of matter. However, the connection between these electronic phases of matter and the underlying band structure singularities has remained largely unexplored. Here, combining magnetic circular dichroism and exciton sensing measurements, we investigate the influence of a van Hove singularity (vHS) on the correlated phases in bilayer WSe2 with twist angle between 2 and 3 degrees. By tuning the vHS across the Fermi level using electric and magnetic fields, we observe Stoner ferromagnetism below moiré lattice filling one and Chern insulators at filling one. The experimental observations are supported by the continuum model band structure calculations. Our results highlight the prospect of engineering electronic phases of matter in moiré materials by tunable van Hove singularities.
Functional proteoform group deconvolution reveals a broader spectrum of ibrutinib off-targets
Abstract Proteome-wide profiling has revealed that targeted drugs can have complex protein interaction landscapes. However, it’s a challenge to profile drug targets while systematically accounting for the dynamic protein variations that produce populations of multiple proteoforms. We address this problem by combining thermal proteome profiling (TPP) with functional proteoform group detection to refine the target landscape of ibrutinib. In addition to known targets, we implicate additional specific functional proteoform groups linking ibrutinib to mechanisms in immunomodulation and cellular processes like Golgi trafficking, endosomal trafficking, and glycosylation. Further, we identify variability in functional proteoform group profiles in a CLL cohort, linked to treatment status and ex vivo response and resistance. This offers deeper insights into the impacts of functional proteoform groups in a clinical treatment setting and suggests complex biological effects linked to off-target engagement. These results provide a framework for interpreting clinically observed off-target processes and adverse events, highlighting the importance of functional proteoform group-level deconvolution in understanding drug interactions and their functional impacts with potential applications in precision medicine.
A column-like organization for ocular dominance in mouse visual cortex
Abstract The columnar organization of response properties is a fundamental feature of the mammalian visual cortex. However, columns have not been observed universally across all mammalian species. Here, we report the discovery of clusters of ipsilateral eye preferring neurons in layer 4 of the mouse primary visual cortex. These clusters extend into layer 2/3 and upper layer 5, forming a column-like pattern for ocular dominance. Our observation of such structures in this minute cortical area sets a new boundary condition for models explaining the emergence of functional organizations in the neocortex.
Suppression of endothelial ceramide de novo biosynthesis by Nogo-B contributes to cardiometabolic diseases
A single-cell atlas to map sex-specific gene-expression changes in blood upon neurodegeneration
Abstract The clinical course and treatment of neurodegenerative disease are complicated by immune-system interference and chronic inflammatory processes, which remain incompletely understood. Mapping immune signatures in larger human cohorts through single-cell gene expression profiling supports our understanding of observed peripheral changes in neurodegeneration. Here, we employ single-cell gene expression profiling of over 909k peripheral blood mononuclear cells (PBMCs) from 121 healthy individuals, 48 patients with mild cognitive impairment (MCI), 46 with Parkinson’s disease (PD), 27 with Alzheimer’s disease (AD), and 15 with both PD and MCI. The dataset is interactively accessible through a freely available website (https://www.ccb.uni-saarland.de/adrcsc). In this work, we identify disease-associated changes in blood cell type composition and the gene expression in a sex-specific manner, offering insights into peripheral and solid tissue signatures in AD and PD.
Attenuated growth factor signaling during cell death initiation sensitizes membranes towards peroxidation
Abstract Cell death programs such as apoptosis and ferroptosis are associated with aberrant redox homeostasis linked to lipid metabolism and membrane function. Evidence for cross-talk between these programs is emerging. Here, we show that cytotoxic stress channels polyunsaturated fatty acids via lysophospholipid acyltransferase 12 into phospholipids that become susceptible to peroxidation under additional redox stress. This reprogramming is associated with altered acyl-CoA synthetase isoenzyme expression and caused by a decrease in growth factor receptor tyrosine kinase (RTK)-phosphatidylinositol-3-kinase signaling, resulting in suppressed fatty acid biosynthesis, for specific stressors via impaired Akt-SREBP1 activation. The reduced availability of de novo synthesized fatty acids favors the channeling of polyunsaturated fatty acids into phospholipids. Growth factor withdrawal by serum starvation mimics this phenotype, whereas RTK ligands counteract it. We conclude that attenuated RTK signaling during cell death initiation increases cells’ susceptibility to oxidative membrane damage at the interface of apoptosis and alternative cell death programs.
Assessing the climate benefits of afforestation in the Canadian Northern Boreal and Southern Arctic
Abstract Afforestation greatly influences several earth system processes, making it essential to understand these effects to accurately assess its potential for climate change mitigation. Although our understanding of forest-climate system interactions has improved, significant knowledge gaps remain, preventing definitive assessments of afforestation's net climate benefits. In this review, focusing on the Canadian northern boreal and southern arctic, we identify these gaps and synthesize existing knowledge. The review highlights regional realities, Earth's climatic history, uncertainties in biogeochemical (BGC) and biogeophysical (BGP) changes following afforestation, and limitations in current assessment methodologies, emphasizing the need to reconcile these uncertainties before drawing firm conclusions about the climate benefits of afforestation. Finally, we propose an assessment framework which considers multiple forcing components, temporal analysis, future climatic contexts, and implementation details. We hope that the research gaps and assessment framework discussed in this review inform afforestation policy in Canada and other circumpolar nations.
Local halide heterogeneity drives surface wrinkling in mixed-halide wide-bandgap perovskites
Abstract Compositional heterogeneity in wide-bandgap (1.8 − 2.1 eV) mixed-halide perovskites is a key bottleneck in the processing of high-quality solution-processed thin films and prevents their application in efficient multijunction solar cells. Notably, mixed-cation (formamidinium-methylammonium) wide-bandgap perovskite films are prone to form micrometer-scale wrinkles which can interfere with the smooth surfaces ideal for multijunction devices. Here, we study the formation dynamics of wrinkled mixed-halide perovskite films and its impact on the local composition and optoelectronic properties. We use in situ X-ray scattering during perovskite film formation to show that crystallization of bromide-rich perovskites precedes that of mixed-halide phases in wrinkled films cast using an antisolvent-based process. Using nanoscopic X-ray fluorescence and hyperspectral photoluminescence imaging, we also demonstrate the formation of iodide- and bromide-rich phases in the wrinkled domains. This intrinsic spatial halide segregation results in an increased local bandgap variation and Urbach energy. Morphological disorder and compositional heterogeneity also aggravate the formation of sub-bandgap electronic defects, reducing photostability and accelerating light-induced segregation of iodide and bromide ions in thin films and solar cells.
A stereodynamic probe of Pt(II) molecular hinge for chiroptical sensing of cryptochiral compounds
The structure and stability of Fe4+xS3 and its potential to form a Martian inner core
Abstract Seismic, geodetic and cosmochemical evidence point to Mars having a sulfur-rich liquid core. Due to the similarity between estimates of the core’s sulfur content and the iron–iron sulfide eutectic composition at core conditions, it has been concluded that temperatures are too high for Mars to have an inner core. Recent low density estimates for the core, however, appear consistent with sulfur contents that are higher than the eutectic composition, leading to the possibility that an inner core could form from a high-pressure iron sulfide phase. Here we report the crystal structure of a phase with the formula Fe 4+x S 3 , the iron content of which increases with temperature, approaching the stoichiometry Fe 5 S 3 under Martian inner core conditions. We show that Fe 4+x S 3 has a higher density than the liquid Martian core and that a Fe 4+x S 3 inner core would crystalize if temperatures fall below 1960 (±105) K at the center of Mars.
Synthetic short mRNA prevents metastasis via innate-adaptive immunity
Synchrony between midbrain gene transcription and dopamine terminal regulation is modulated by chronic alcohol drinking
Abstract Alcohol use disorder is marked by disrupted behavioral and emotional states which persist into abstinence. The enduring synaptic alterations that remain despite the absence of alcohol are of interest for interventions to prevent relapse. Here, 28 male rhesus macaques underwent over 20 months of alcohol drinking interspersed with three 30-day forced abstinence periods. After the last abstinence period, we paired direct sub-second dopamine monitoring via ex vivo voltammetry in nucleus accumbens core with RNA-sequencing of the ventral tegmental area. We found persistent augmentation of dopamine transporter function, kappa opioid receptor sensitivity, and putative dynorphin release – all inhibitory regulators which act to decrease extracellular dopamine. Surprisingly, though transcript expression was not altered, the relationship between gene expression and functional readouts of these encoded proteins was highly dynamic and altered by drinking history. These results outline the long-lasting synaptic impact of alcohol use and suggest that assessment of transcript-function relationships is critical for the rational design of precision therapeutics.
RH3 enhances antiviral defense by facilitating small RNA loading into Argonaute 2 at endoplasmic reticulum–chloroplast membrane contact sites
KAT6B overexpression rescues embryonic lethality in homozygous null KAT6A mice restoring vitality and normal lifespan
Abstract Closely related genes typically display common essential functions but also functional diversification, ensuring retention of both genes throughout evolution. The histone lysine acetyltransferases KAT6A (MOZ) and KAT6B (QKF/MORF), sharing identical protein domain structure, are mutually exclusive catalytic subunits of a multiprotein complex. Mutations in either KAT6A or KAT6B result in congenital intellectual disability disorders in human patients. In mice, loss of function of either gene results in distinct, severe phenotypic consequences. Here we show that, surprisingly, 4-fold overexpression of Kat6b rescues all previously described developmental defects in Kat6a mutant mice, including rescuing the absence of hematopoietic stem cells. Kat6b restores acetylation at histone H3 lysines 9 and 23 and reverses critical gene expression anomalies in Kat6a mutant mice. Our data suggest that the target gene specificity of KAT6A can be substituted by the related paralogue KAT6B, despite differences in amino acid sequence, if KAT6B is expressed at sufficiently high levels.
Broad-spectrum capture of hundreds of per- and polyfluoroalkyl substances from fluorochemical wastewater
Abstract Hundreds of per- and polyfluoroalkyl substances (PFAS) are present in fluorochemical production effluents, and existing adsorption devices are inadequate to address this PFAS challenge given their extreme structural diversity. Here, we achieve the broad-spectrum capture of 107 PFAS from fluorochemical effluents using a treatment-train strategy that combines Zn-based electrocoagulation (EC) with anion-exchange resin (AER) beds. The “zero-carbon” adsorbent, zinc hydroxide flocs generated insitu by Zn-based EC, bulk removes PFAS with log K ow > 4 through a semi-micellar adsorption mechanism similar to mineral flotation and achieves adsorption capacities at the optimal level of all reported adsorbents. Technical-economic analysis and life-cycle environmental impact show that coupling Zn-based EC reduces the cost by an order-of-magnitude and the carbon-footprint by 70% compared to AER beds alone. It is also observed that iodinated PFAS, with some fluorine atoms are replaced by iodine atoms, exhibit significantly improved adsorption selectivity, which may shed light on designing environmentally-friendly fluorochemicals.