Browse Articles
Discover research articles across all indexed journals
Causal claims, causal assumptions and protected area impact
Hardware-efficient quantum error correction via concatenated bosonic qubits
Artificial photosynthesis directed toward organic synthesis
Remodeling of lipid-foam prototissues by network-wide tension fluctuations induced by active particles
Abstract Recent advances in the field of bottom-up synthetic biology have led to the development of synthetic cells that mimic some features of real cells, such as division, protein synthesis, or DNA replication. Larger assemblies of synthetic cells may be used to form prototissues. However, existing prototissues are limited by their relatively small lateral dimensions or their lack of remodeling ability. Here, we introduce a lipid-based tissue mimetic that can be easily prepared and functionalized, consisting of a millimeter-sized “lipid-foam” with individual micrometer-sized compartments bound by lipid bilayers. We characterize the structural and mechanical properties of the lipid-foam tissue mimetic, and we demonstrate self-healing capabilities enabled by the fluidity of the lipid bilayers. Upon inclusion of bacteria in the tissue compartments, we observe that the tissue mimetic exhibits network-wide tension fluctuations driven by membrane tension generation by the swimming bacteria. Active tension fluctuations facilitate the fluidization and reorganization of the prototissue, providing a versatile platform for understanding and mimicking biological tissues.
Asymmetric rotations slow down diffusion under confinement
Associations of PFAS and OH-PCBs with risk of multiple sclerosis onset and disability worsening
Abstract Exposure to per- and polyfluorinated substances (PFAS) and hydroxylated polychlorinated biphenyls (OH-PCBs) is associated with adverse human health effects, including immunosuppression. It is unknown if these substances can affect the course of autoimmune diseases. This study was based on 907 individuals with multiple sclerosis (MS) and 907 matched controls, where the MS cases were followed longitudinally using the Swedish MS register. We demonstrate sex- and disease-specific differences in serum PFAS concentrations between individuals with MS and controls. Moreover, two OH-PCBs (4-OH-CB187 and 3-OH-CB153) are associated with an increased risk of developing multiple sclerosis, regardless of sex and immigration status. With a clinical follow-up time of up to 18 years, an increase in serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), and perfluorodecanoic acid (PFDA) decreases the risk of confirmed disability worsening in both sexes, as well as perfluoroheptanesulfonic acid (PFHpS) and perfluorononanoic acid (PFNA), only in males with MS. These results show previously unknown associations between OH-PCBs and the risk of developing MS, as well as the inverse associations between PFAS exposure and the risk of disability worsening in MS.
Mass-spectrometry-based proteomics: from single cells to clinical applications
The p3 peptides (Aβ17-40/42) rapidly form amyloid fibrils that cross-seed with full-length Aβ
Abstract The p3 peptides, Aβ17-40/42, are a common alternative cleavage product of the amyloid precursor protein, and are found in diffuse amyloid deposits of Alzheimer’s and Down Syndrome brains. The p3 peptides have been mis-named ‘non-amyloidogenic’. Here we show p340/42 peptides rapidly form amyloid fibrils, with kinetics dominated by secondary nucleation. Importantly, cross-seeding experiments, with full-length Aβ induces a strong nucleation between p3 and Aβ peptides. The cross-seeding interaction is highly specific, and occurs only when the C-terminal residues are matched. We have imaged membrane interactions with p3, and monitored Ca2+ influx and cell viability with p3 peptide. Together this data suggests the N-terminal residues influence, but are not essential for, membrane disruption. Single particle analysis of TEM images indicates p3 peptides can form ring-like annular oligomers. Patch-clamp electrophysiology, shows p342 oligomers are capable of forming large ion-channels across cellular membranes. A role for p3 peptides in disease pathology should be considered as p3 peptides are cytotoxic and cross-seed Aβ fibril formation in vitro.
Author Correction: The RING-finger ubiquitin E3 ligase TaPIR1 targets TaHRP1 for degradation to suppress chloroplast function
Ethylene promotes SMAX1 accumulation to inhibit arbuscular mycorrhiza symbiosis
Abstract Most land plants engage in arbuscular mycorrhiza (AM) symbiosis with Glomeromycotina fungi for better access to mineral nutrients. The plant hormone ethylene suppresses AM development, but a molecular explanation for this phenomenon is lacking. Here we show that ethylene inhibits the expression of many genes required for AM formation in Lotus japonicus. These genes include strigolactone biosynthesis genes, which are needed for fungal activation, and Common Symbiosis genes, which are required for fungal entry into the root. Application of strigolactone analogs and ectopic expression of the Common Symbiosis gene Calcium Calmodulin-dependent Kinase (CCaMK) counteracts the effect of ethylene. Therefore, ethylene likely inhibits AM development by suppressing expression of these genes rather than by inducing defense responses. These same genes are regulated by SUPPRESSOR OF MAX2 1 (SMAX1), a transcriptional repressor that is proteolyzed during karrikin signaling. SMAX1 is required for suppression of AM by ethylene, and SMAX1 abundance in nuclei increases after ethylene application. We conclude that ethylene suppresses AM by promoting accumulation of SMAX1. SMAX1 emerges as a signaling hub that integrates karrikin and ethylene signaling, thereby orchestrating development of a major plant symbiosis with a plant’s physiological state.
Interference-free nanogap pressure sensor array with high spatial resolution for wireless human-machine interfaces applications
SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO
Abstract Cancer genome alterations often lead to vulnerabilities that can be used to selectively target cancer cells. Various inhibitors of such synthetic lethal targets have been approved by the FDA or are in clinical trials, highlighting the potential of this approach1–3. Here we analysed large-scale CRISPR knockout screening data from the Cancer Dependency Map and identified a new synthetic lethal target, PELO, for two independent molecular subtypes of cancer: biallelic deletion of chromosomal region 9p21.3 or microsatellite instability-high (MSI-H). In 9p21.3-deleted cancers, PELO dependency emerges from biallelic deletion of the 9p21.3 gene FOCAD, a stabilizer of the superkiller complex (SKIc). In MSI-H cancers, PELO is required owing to MSI-H-associated mutations in TTC37 (also known as SKIC3), a critical component of the SKIc. We show that both cancer subtypes converge to destabilize the SKIc, which extracts mRNA from stalled ribosomes. In SKIc-deficient cells, PELO depletion induces the unfolded protein response, a stress response to accumulation of misfolded or unfolded nascent polypeptides. Together, our findings indicate PELO as a promising therapeutic target for a large patient population with cancers characterized as MSI-H with deleterious TTC37 mutations or with biallelic 9p21.3 deletions involving FOCAD.
Serum-tolerant polymeric complex for stem-cell transfection and neural differentiation
Unprotected carbon dominates decadal soil carbon increase
Circulating miR-126-3p is a mechanistic biomarker for knee osteoarthritis
Magnetically reshapable 3D multi-electrode arrays of liquid metals for electrophysiological analysis of brain organoids
Abstract To comprehend the volumetric neural connectivity of a brain organoid, it is crucial to monitor the spatiotemporal electrophysiological signals within the organoid, known as intra-organoid signals. However, previous methods risked damaging the three-dimensional (3D) cytoarchitecture of organoids, either through sectioning or inserting rigid needle-like electrodes. Also, the limited numbers of electrodes in fixed positions with non-adjustable electrode shapes were insufficient for examining the complex neural activity throughout the organoid. Herein, we present a magnetically reshapable 3D multi-electrode array (MEA) using direct printing of liquid metals for electrophysiological analysis of brain organoids. The adaptable distribution and the softness of these printed electrodes facilitate the spatiotemporal recording of intra-organoid signals. Furthermore, the unique capability to reshape these soft electrodes within the organoid using magnetic fields allows a single electrode in the MEA to record from multiple points, effectively increasing the recording site density without the need for additional electrodes.