Browse Articles

High resolution profiling of cell cycle-dependent protein and phosphorylation abundance changes in non-transformed cells

A greening Earth has reversed the trend of decreasing carbonate weathering under a warming climate

Benchmarking selective capture of trace CO2 from C2H2 using an amine-functionalized adsorbent

2D edge-seeded heteroepitaxy of ultrathin high-κ dielectric CaNb2O6 for 2D field-effect transistors

High-speed computed tomography to visualise the 3D microstructural dynamics of oil uptake in deep-fried foods

Ink formulation of functional nanowires with hyperbranched stabilizers for versatile printing of flexible electronics

Mechanism of ASF1 engagement by CDAN1

Abstract Codanin-1 (CDAN1) is an essential and ubiquitous protein named after congenital dyserythropoietic anemia type I, an autosomal recessive disease that manifests from mutations in CDAN1 or CDIN1 (CDAN1 interacting nuclease 1). CDAN1 interacts with CDIN1 and the paralogous histone H3-H4 chaperones ASF1A (Anti-Silencing Function 1 A) and ASF1B. However, CDAN1 function remains unclear. Here, we analyze CDAN1 complexes using biochemistry, single-particle cryo-EM, and structural predictions. We find that CDAN1 dimerizes and assembles into cytosolic complexes with CDIN1 and multiple copies of ASF1A/B. One CDAN1 can engage two ASF1 through two B-domains commonly found in ASF1 binding partners and two helices that mimic histone H3 binding. We additionally show that ASF1A and ASF1B have different requirements for CDAN1 engagement. Our findings explain how CDAN1 sequesters ASF1A/B by occupying all functional binding sites known to facilitate histone chaperoning and provide molecular-level insights into this enigmatic complex.

A tunable and versatile chemogenetic near-infrared fluorescent reporter

Quantifying cascading power outages during climate extremes considering renewable energy integration

Aggregation induced emission luminogen bacteria hybrid bionic robot for multimodal phototheranostics and immunotherapy

Pd-catalyzed deuteration of aryl halides with deuterium oxide

Ubiquinol-mediated suppression of mitochondria-associated ferroptosis is a targetable function of lactate dehydrogenase B in cancer

Abstract Lactate dehydrogenase B (LDHB) fuels oxidative cancer cell metabolism by converting lactate to pyruvate. This study uncovers LDHB’s role in countering mitochondria-associated ferroptosis independently of lactate’s function as a carbon source. LDHB silencing alters mitochondrial morphology, causes lipid peroxidation, and reduces cancer cell viability, which is potentiated by the ferroptosis inducer RSL3. Unlike LDHA, LDHB acts in parallel with glutathione peroxidase 4 (GPX4) and dihydroorotate dehydrogenase (DHODH) to suppress mitochondria-associated ferroptosis by decreasing the ubiquinone (coenzyme Q, CoQ) to ubiquinol (CoQH2) ratio. Indeed, supplementation with mitoCoQH2 (mitochondria-targeted analogue of CoQH2) suppresses mitochondrial lipid peroxidation and cell death after combined LDHB silencing and RSL3 treatment, consistent with the presence of LDHB in the cell fraction containing the mitochondrial inner membrane. Addressing the underlying molecular mechanism, an in vitro NADH consumption assay with purified human LDHB reveals that LDHB catalyzes the transfer of reducing equivalents from NADH to CoQ and that the efficiency of this reaction increases by the addition of lactate. Finally, radiation therapy induces mitochondrial lipid peroxidation and reduces tumor growth, which is further enhanced when combined with LDHB silencing. Thus, LDHB-mediated lactate oxidation drives the CoQ-dependent suppression of mitochondria-associated ferroptosis, a promising target for combination therapies.

Drosophila ovarian stem cell niche ageing involves coordinated changes in transcription and alternative splicing

Abstract Gene expression (GE) and alternative splicing (AS) contribute to the formation of new interaction networks with potentially significant cellular functions. Here, we investigate ageing in the Drosophila female germline stem cell (GSC) niche and describe functional changes in both GE and AS. The GSC niche comprises three types of support cells, whose ageing transcriptomes reveal differential GE and AS variations related to cell adhesion, cytoskeleton and neural signalling. Because each population show distinctive GE and AS changes, niche cell types possess unique ageing signatures. Depending on the cell population, groups of genes display changes in both GE and AS, revealing a coordinated regulation of transcription and splicing during niche ageing. One such gene is Fasciclin 2, a neural adhesion molecule that we find is essential for niche functioning. Furthermore, genes involved in AS undergo changes in GE and/or AS themselves, providing a mechanistic explanation for the coordination of these two processes during niche ageing. This is the case of the splicing factor Smu1, described here as a key element necessary for ovarian niche homeostasis.

Discovering organic reactions with a machine-learning-powered deciphering of tera-scale mass spectrometry data

Neural signatures of temporal anticipation in human cortex represent event probability density

Abstract Temporal prediction is a fundamental function of neural systems. Recent results show that humans anticipate future events by calculating probability density functions, rather than hazard rates. However, direct neural evidence for this hypothesized mechanism is lacking. We recorded neural activity using magnetoencephalography as participants anticipated auditory and visual events distributed in time. We show that temporal anticipation, measured as reaction times, approximates the event probability density function, but not hazard rate. Temporal anticipation manifests as spatiotemporally patterned activity in three anatomically and functionally distinct parieto-temporal and sensorimotor cortical areas. Each of these areas revealed a marked neural signature of anticipation: Prior to sensory cues, activity in a specific frequency range of neural oscillations, spanning alpha and beta ranges, encodes the event probability density function. These neural signals predicted reaction times to imminent sensory cues. These results demonstrate that supra-modal representations of probability density across cortex underlie the anticipation of future events.

Prioritizing involuntary immobility in climate policy and disaster planning

Abstract Globally, populations are increasingly located in areas at high risk of climate change impacts. Some populations lack the agency to move out of harm’s way, leading to involuntary immobility. The climate risks these populations face are insufficiently addressed in climate policy and disaster planning. While policy and planning should be data-informed, the lack of appropriate data should not limit governments and institutions from taking action to reduce the risk of involuntary immobility. Incorporating involuntary immobility within the broader sustainable development goals of climate action and safe, orderly, and regular migration may substantially reduce the risk of involuntary immobility.

Enhanced RNA-targeting CRISPR-Cas technology in zebrafish

Adaptive damage analysis method for ultimate bearing capacity of steel truss structures with box section

Multi-objective collaborative optimization of active distribution network operation based on improved particle swarm optimization algorithm

Robust control of a compliant manipulator with reduced dynamics and sliding perturbation observer