Browse Articles

Structures of TGF-β with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling

Abstract Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-β (TGF-β) family of signaling ligands. It is essential for embryonic development, tissue homeostasis and fertility in adults. It functions by enabling binding of the three TGF-β isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-βs and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-β bound both to BG and the signaling receptors, TGFBR1 and TGFBR2. We identify key regions responsible for ligand engagement, which has revealed binding interfaces that differ from those described for the closely related co-receptor of the TGF-β family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-β signal potentiation.

Anger and emotion regulation strategies: a meta-analysis

Immune signature and pathways investigation of adrenal gland diffuse large B-cell lymphoma

KRT7 promotes pancreatic cancer metastasis by remodeling the extracellular matrix niche through FGF2-fibroblast crosstalk

Structural Transformation and Degradation of Cu Oxide Nanocatalysts during Electrochemical CO ₂ Reduction

Photothermal conversion and geochemical characterization of sulfur-rich lignite for non-conventional energy applications

Neuroimaging Model of Visceral Manipulation in an Awake Rat

Reciprocal neuronal connections exist between the internal organs of the body and the nervous system. These projections to and from the viscera play an essential role in maintaining and fine-tuning organ responses in order to sustain homeostasis and allostasis. Functional maps of brain regions participating in this bidirectional communication have been previously studied in awake humans and anesthetized rodents. To further refine the mechanistic understanding of visceral influence on brain states, however, new paradigms that allow for more invasive, and ultimately more informative, measurements and perturbations must be explored. Furthermore, such paradigms should prioritize human translatability. In the current paper, we address these issues by demonstrating the feasibility of nonanesthetized animal imaging during visceral manipulation. More specifically, we used a barostat interfaced with an implanted gastric balloon to cyclically induce distension of a nonanesthetized male rat's stomach during simultaneous blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging. General linear modeling and spatial independent component analysis revealed several regions with BOLD activation temporally coincident with the gastric distension stimulus. The ON–OFF (20–0 mmHg) barostat balloon pressure cycle resulted in widespread BOLD activation of the inferior colliculus, cerebellum, ventral midbrain, and a variety of hippocampal structures. These results suggest that neuroimaging models of gastric manipulation in the nonanesthetized rat are achievable and provide an avenue for more comprehensive studies involving the integration of other neuroscience techniques like electrophysiology.

PIA-A secure and efficient identity authentication scheme in telemedicine via the PUF method

An advanced robotic system incorporating haptic feedback for precision cardiac ablation procedures

Multiple Reaction Pathways for Oxygen Evolution as a Key Factor for the Catalytic Activity of Nickel–Iron (Oxy)Hydroxides

Collaborative optimization of truck scheduling in container terminals using graph theory and DDQN

Combining an improved political optimizer with convolutional neural networks for accurate anterior cruciate ligament tear detection in sports injuries

Behavioral and pathological characteristics of 5xFAD female mice in the early stage

Phasic Dopamine Release in the Nucleus Accumbens Influences REM Sleep Timing

Based on the activity of dopamine (DA) neurons during behavioral states, the DA system has long been thought to be foundational in regulating sleep–wake behavior; over the past decade, advances in circuit manipulation and recording techniques have strengthened this perspective. Recently, several studies have demonstrated that DA release in regions of the limbic system is important in the promotion of REM sleep. Yet how DA dynamics change within bouts of sleep, how these changes are regulated, and whether they influence future state changes remains unclear. To address these questions, in mice of both sexes we used in vivo fiber photometry and inhibitory optogenetics to identify a specific role of DA transients in the nucleus accumbens (NAcc) in state transitions from NREM sleep. We found that DA transients increase their frequency and amplitude over the duration of NREM sleep and that this increase is more pronounced during NREM bouts that transition into REM sleep. Next, we found that DA transients in NREM sleep are influenced by changes in REM sleep pressure. Finally, we show that transient DA release in the NAcc plays a functional role in regulating the timing of REM sleep entrances, as inhibition of midbrain DA neuron terminals in the NAcc prolonged bouts of NREM sleep and decreased the frequency of bouts of REM sleep. These findings demonstrate that DA release in the NAcc is dynamically regulated by sleep pressure and has a functional role in transitions from NREM sleep, particularly those into REM sleep.

Smoking, and to a lesser extent non-combustible nicotine use, is associated with higher levels of alcohol consumption and risky drinking

Abstract This study aimed to estimate differences in alcohol consumption, receipt of alcohol brief intervention, and alcohol reduction attempts by smoking status and use of non-combustible nicotine (including e-cigarettes, nicotine replacement therapy, heated tobacco products, or nicotine pouches). Data were from a representative household survey of adults in England (n = 188,878). Participants who reported former or current smoking scored approximately 1 point higher, on average, on the AUDIT-C (which measures alcohol consumption) than those who had never regularly smoked (B adj=0.97 [95%CI 0.93–1.00] and 0.92 [0.87–0.96], respectively) and had double the odds of risky drinking (AUDIT-C ≥ 5: ORadj=2.04 [1.98–2.10] and 2.03 [1.97–2.10], respectively), while differences for those who did versus did not use non-combustible nicotine use were less pronounced (AUDIT-C: B adj=0.14 [0.08–0.21]; AUDIT-C ≥ 5: ORadj=1.09 [1.04–1.13]). Among participants who engaged in risky drinking, those who smoked (vs. not) were more likely to report receiving alcohol brief interventions, and those attempting to quit smoking (vs. not) were more likely to report alcohol reduction attempts. Overall, combustible and - less so - non-combustible nicotine use is associated with higher levels of alcohol consumption and risky drinking.

Flight testing of drone-delivered automated external defibrillators for simulated out-of-hospital cardiac arrest in suburban Thailand

Enhancement of electric field uniformity using 3-phase circular electrodes in RF heating applications

Weather-driven risk assessment model for two-wheeler road crashes in Uttar Pradesh, India

Robust estimation of the intrinsic dimension of data sets with quantum cognition machine learning

Conceptual design of airborne contra rotating VAWTs for rooftop wind energy

Abstract Co-rotating, counter, and contra-rotating Vertical Axis Wind Turbines (VAWTs) offer higher power yields than singular turbines due to synergetic interactions, making them ideal for rooftop applications. This study focuses on enhancing the efficiency of a Contra-Rotating VAWT (CR-VAWT) using a ducted airborne configuration. A wind gathering device (WGD), optimized via the Taguchi method, is integrated around the CR-VAWT, which is elevated using an oblate spheroid aerostat designed through a force-weight approach. CFD analyses reveal that incorporating the WGD boosts power output by 32% and increases instantaneous torque by 40% during dynamic stall. The WGD enhances flow redirection towards the rotor plane, achieving a 58% power gain at a 10°skew angle. By suppressing blade-tip vortex shedding, the WGD not only improves efficiency but may also reduce noise. This portable system is suitable for rooftops with limited space, requiring fewer turbines to meet energy demands while reducing noise and improving aesthetics. It also allows for integration with other renewable technologies like photovoltaics, promoting sustainability and lowering carbon footprints. A comprehensive implementation framework is presented to support future research on airborne VAWTs.