Browse Articles

TRIM23 mediates cGAS-induced autophagy in anti-HSV defense

Multicationic interactions mitigating lattice strain in sodium layered cathodes

Acute regulation of murine adipose tissue lipolysis and insulin resistance by the TGFβ superfamily protein GDF3

Abstract TGFβ superfamily proteins can affect cellular differentiation, thermogenesis, and fibrosis in mammalian adipose tissue. Here we describe a role for Growth Differentiation Factor 3 (GDF3) on mature adipocyte biology. We find inducible GDF3 loss of function in obese adult mice leads to reduced lipolysis, improved glucose tolerance, and reduced glycemic variability. The effects on lipolysis are driven by lower levels of β3-adrenergic receptor, decreased cAMP and PKA signaling. GDF3 is an ALK5, ALK7, ACVR2A and ACVR2B agonist and also a BMPR2 antagonist. Unlike ALK7 or activin E knockouts, acute GDF3 loss of function does not affect body weight or energy balance but significantly improves metabolic health. These results suggest that blocking GDF3 can improve metabolic health independent of body weight and food intake, an intriguing new model for developing anti-diabetic therapies. Together these results provide much-needed clarity to both the molecular pathways involved in GDF3 signaling and its physiological effects.

DiffInvex identifies evolutionary shifts in driver gene repertoires during tumorigenesis and chemotherapy

Nivolumab plus low-dose ipilimumab in hypermutated HER2-negative metastatic breast cancer: a phase II trial (NIMBUS)

The classical-to-quantum crossover in the strain-induced ferroelectric transition in SrTiO3 membranes

Single-molecule visualization of ATP-induced dynamics of the subunit composition of an ECF transporter complex under turnover conditions

Abstract Energy-Coupling Factor (ECF) transporters are ATP-binding cassette (ABC) transporters essential for uptake of vitamins and cofactors in prokaryotes. They have been linked to pathogen virulence and are potential targets for antimicrobials. ECF transporters have been proposed to use a unique transport mechanism where a substrate-translocating subunit (S-component) dynamically associates with and dissociates from an ATP-hydrolyzing motor (ECF module). This model is contentious, because it is based largely on experimental conditions without compartments or continuous bilayers. Here, we used single-molecule spectroscopy to investigate the conformational dynamics of the vitamin B12 transporter ECF-CbrT in membranes under vectorial transport conditions. We observed ATP hydrolysis-dependent dissociation of the S-component CbrT from, and re-association with the ECF module, in absence and presence of vitamin B12 consistent with futile ATP hydrolysis activity. The single-molecule spectroscopy experiments suggest that S-component expulsion from and re-association with the ECF module are an integral part of the translocation mechanism.

Rhythmic radial oxygen loss enhances soil phosphorus bioavailability

GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial

Exciton-phonon coupling and phonon-assisted exciton relaxation dynamics in In1-xGaxP quantum dots

Altermagnetism in the layered intercalated transition metal dichalcogenide CoNb4Se8

Token-Mol 1.0: tokenized drug design with large language models

Thermal spectrometer for superconducting circuits

Abstract Superconducting circuits provide a versatile and controllable platform for studies of fundamental quantum phenomena as well as for quantum technology applications. A conventional technique to read out the state of a quantum circuit or to characterize its properties is based on RF measurement schemes. Here we demonstrate a simple DC measurement of a thermal spectrometer to investigate properties of a superconducting circuit, in this proof-of-concept experiment a coplanar waveguide resonator. A fraction of the microwave photons in the resonator is absorbed by an on-chip bolometer, resulting in a measurable temperature rise. By monitoring the DC signal of the thermometer due to this process, we are able to determine the resonance frequency and the lineshape (quality factor) of the resonator. The demonstrated scheme, which is a simple DC measurement, offers a wide frequency band potentially reaching up to 200 GHz, far exceeding that of the typical RF spectrometer. Moreover, the thermal measurement yields a highly frequency independent reference level of the Lorentzian absorption signal. In the low power regime, the measurement is fully calibration-free. Our technique offers an alternative spectrometer for quantum circuits.

Alternatively spliced mini-exon B in PTPδ regulates excitatory synapses through cell-type-specific trans-synaptic PTPδ-IL1RAP interaction

Coinciding spring and autumn frosts have a limited impact on carbon fluxes in a grassland ecosystem

Co-initiating-system dual-mechanism drives the design of printable entangled polymer multinetworks

High-contrast in vivo fluorescence imaging exploiting wavelengths beyond 1880 nm

A protein language model for exploring viral fitness landscapes

Improving AI models for rare thyroid cancer subtype by text guided diffusion models

OGG1S326C variant frequent in human populations facilitates inflammatory responses due to its extended interaction with DNA substrate

8-oxoguanine (8-oxoGua) is one of the most frequent forms of oxidative DNA base lesions, repaired by 8-oxoguanine DNA glycosylase 1 (OGG1) via base excision repair (BER) pathway to maintain genome fidelity. The human allelic variant hOGG1 S326C , prevalent in Caucasians and Asians, has been regarded as a susceptibility factor for various diseases, yet its pathogenic mechanism remains elusive. In this study, we demonstrate that Ogg1 S326C/S326C mice exhibit increased and sustained airway inflammation compared with wild-type (WT) Ogg1 S326/S326 mice. Mechanistically, in response to inflammatory stimulation, OGG1S326C undergoes reactive oxygen species-induced dimerization, which impairs its base excision function, but prolongs its association with promoter-embedded substrate(s), leading to an increase in NF-κB’ DNA occupancy, subsequently the excessive expression of proinflammatory cytokines and chemokines, and the exacerbated lung inflammation. In contrast, Serine at position 326 in WT -OGG1 is constitutively phosphorylated by CDK4. To fulfill the requirement for its function in transcriptional regulation, the phosphorylated OGG1 needs to undergo dephosphorylation to rescue DNA binding ability. In this scenario, OGG1S326C lacks this phosphorylation site, disrupting this regulatory cycle. Notably, administration of a small molecule inhibitor of OGG1 prevents OGG1S326C from binding to DNA and significantly decreases gene expression and inflammatory responses. Our findings elucidate a molecular basis for the increased disease susceptibility of individuals carrying the hOGG1 S326C variant and propose the therapeutic potential of OGG1 inhibitors in mitigating inflammation-driven pathologies.