Biophysics

Inflammasomes are multiprotein platforms that control caspase-1 activation, which process the inactive precursor forms of the inflammatory cytokines IL-1β and IL-18, leading to an inflammatory type of programmed cell death called pyroptosis. Studying inflammasome-driven processes, such as pyroptosis-induced cell swelling, under controlled conditions remains challenging because the signals that activate pyroptosis also stimulate other signaling pathways. We designed an optogenetic approach using a photo-oligomerizable inflammasome core adapter protein, apoptosis-associated speck-like containing a caspase recruitment domain (ASC), to temporally and quantitatively manipulate inflammasome activation...

Utilising Machine Learning (ML) models to predict dosimetric parameters in pencil beam scanning proton therapy presents a promising and practical approach. The study developed Artificial Neural Network (ANN) models to predict proton beam spot size and relative positional errors using 9000 proton spot data. The irradiation log files as input variables and corresponding scintillation detector measurements as the label values. The ANN models were developed to predict six variables: spot size in the x -axis, y -axis, major axis, minor axis, and relative positional errors in the x -axis and y -axis...

OBJECTIVE: Impact kinematics are widely employed to investigate mechanisms of traumatic brain injury (TBI). However, they are susceptible to noise and artefacts; thus, require data filtering. Few studies have focused on how data filtering affects brain strain most relevant to TBI. Here, we report that impact-induced brain strains are much less sensitive to data filtering than kinematics based on three filtering methods: CFC180, lowpass 200Hz, and a new method called Head Exposure to Acceleration Database in Sport (HEADSport)...

In the field of medical imaging, the fusion of data from diverse modalities plays a pivotal role in advancing our understanding of pathological conditions. Sparse representation (SR), a robust signal modeling technique, has demonstrated noteworthy success in multi-dimensional (MD) medical image fusion. However, a fundamental limitation appearing in existing SR models is their lack of directionality, restricting their efficacy in extracting anatomical details from different imaging modalities. To tackle this issue, we propose a novel directional SR model, termed complex sparse representation (ComSR), specifically designed for medical image fusion...

Identification of seizure sources in the brain is of paramount importance, particularly for drug-resistant epilepsy patients who may require surgical operation. Interictal epileptiform discharges (IEDs), which may or may not be frequent, are known to originate from seizure networks. Delayed responses (DRs) to brain electrical stimulation have been recently discovered. If DRs and IEDs come from the same location and the DRs can be accurately localized, there will be a significant step in identification of the seizure sources...

The accumulation of manganese ions is crucial for scavenging reactive oxygen species and protecting the proteome of Deinococcus radiodurans (Dr). However, metal homeostasis still needs to be tightly regulated to avoid toxicity. DR2539, a dimeric transcription regulator, plays a key role in Dr manganese homeostasis. Despite comprising three well-conserved domains - a DNA-binding domain, a dimerisation domain, and an ancillary domain - the mechanisms underlying both, metal ion activation and DNA recognition remain elusive...

Mechanistic Monte Carlo simulations calculating DNA damage caused by ionizing radiation are highly dependent on the simulation parameters. In the present study, using the Geant4-DNA toolkit, the impact of different parameters on DNA damage induced in a bacterial cell by X- and gamma-ray irradiation was investigated. Three geometry configurations, including the simple (without DNA details), the random (a random multiplication of identical DNA segments), and the fractal (a regular replication of DNA segments using fractal Hilbert curves), were simulated...

Schizophrenia (SZ) has been acknowledged as a highly intricate mental disorder for a long time. In fact, individuals with SZ experience a blurred line between fantasy and reality, leading to a lack of awareness about their condition, which can pose significant challenges during the treatment process. Due to the importance of the issue, timely diagnosis of this illness can not only assist patients and their families in managing the condition but also enable early intervention, which may help prevent its advancement...

Lymphoid restricted membrane protein (LRMP) is a specific regulator of the hyperpolarization-activated cyclic nucleotide-sensitive isoform 4 (HCN4) channel. LRMP prevents cAMP-dependent potentiation of HCN4, but the interaction domains, mechanisms of action, and basis for isoform-specificity remain unknown. Here, we identify the domains of LRMP essential for this regulation, show that LRMP acts by disrupting the intramolecular signal transduction between cyclic nucleotide binding and gating, and demonstrate that multiple unique regions in HCN4 are required for LRMP isoform-specificity...

BACKGROUND: The application of deep learning methods in rapid bone scintigraphy is increasingly promising for minimizing the duration of SPECT examinations. Recent works showed several deep learning models based on simulated data for the synthesis of high-count bone scintigraphy images from low-count counterparts. Few studies have been conducted and validated on real clinical pairs due to the misalignment inherent in multiple scan procedures. PURPOSE: To generate high quality whole-body bone images from 2× and 3× fast scans using deep learning based enhancement method...

BACKGROUND: Motion induced image artifacts have been the focus of many investigations for x-ray computed tomography (CT). Methodologies of combating patient motion include the use of gating devices to optimize the data acquisition, reduction in patient scan time via faster gantry rotation and large detector coverage, and the development of advanced reconstruction and post-processing algorithms to minimize motion artifacts. PURPOSE: Previously proposed approaches are generally "global" in nature in that motion is characterized for the entire image...

The human body exploits its neural mechanisms to optimize actions. Rhythmic movements are optimal when their frequency is close to the natural frequency of the system. In a pendulum, gravity modulates this spontaneous frequency. Participants unconsciously adjust their natural pace when cyclically moving the arm in altered gravity. However, the timescale of this adaptation is unexplored. Participants performed cyclic movements before, during, and after fast transitions between hypergravity levels (1g-3g and 3g-1g) induced by a human centrifuge...

Introduction: Horses are susceptible to oxidative stress during strenuous endurance exercise, leading to muscle fatigue and damage. Mulberry leaf flavonoids (MLFs) possess significant antioxidant properties. However, the antioxidant efficacy of MLFs can be influenced by the extraction process, and their impact on H2 O2 -induced oxidative stress in equine skeletal muscle satellite cells (ESMCs) remains unexplored. Methods: Our study employed three extraction methods to obtain MLFs: ultrasound-assisted extraction (CEP), purification with AB-8 macroporous resin (RP), and n-butanol extraction (NB-EP)...

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In tomato (Solanum lycopersicum), the ripening of fruit is regulated by the selective expression of ripening-related genes, and this procedure is controlled by transcription factors (TFs). In the various plant-specific TF families, the no apical meristem (NAM), Arabidopsis thaliana activating factor 1/2 (ATAF1/2), and cup-shaped cotyledon 2 (CUC2; NAC) TF family stands out and plays a significant function in plant physiological activities, such as fruit ripening (FR). Despite the numerous genes of NAC found in the tomato genome, limited information is available on the effects of NAC members on FR, and there is also a lack of studies on their target genes...

Non-small cell lung cancer (NSCLC), characterized by low survival rates and a high recurrence rate, is a major cause of cancer-related mortality. Aberrant activation of the PI3K/AKT/mTOR signaling pathway is a common driver of NSCLC. Within this study, the inhibitory activity of (+)-anthrabenzoxocinone ((+)-ABX), an oxygenated anthrabenzoxocinone compound derived from Streptomyces, against NSCLC is demonstrated for the first time both in vitro and in vivo. Mechanistically, it is confirmed that the PI3K/AKT/mTOR signaling pathway is targeted and suppressed by (+)-ABX, resulting in the induction of S and G2/M phase arrest, apoptosis, and autophagy in NSCLC cells...

During the past few decades, a wealth of knowledge has been made available for the transcription machinery in bacteria from the structural, functional and mechanistic point of view. However, comparatively little is known about the homooligomerization of the multisubunit M. tuberculosis RNA polymerase (RNAP) enzyme and its functional relevance. While E. coli RNAP has been extensively studied, many aspects of RNAP of the deadly pathogenic M. tuberculosis are still unclear. We used biophysical and biochemical methods to study the oligomerization states of the core and holoenzymes of M...

De novo drug design aims to generate molecules from scratch that possess specific chemical and pharmacological properties. We present a computational approach utilizing interactome-based deep learning for ligand- and structure-based generation of drug-like molecules. This method capitalizes on the unique strengths of both graph neural networks and chemical language models, offering an alternative to the need for application-specific reinforcement, transfer, or few-shot learning. It enables the "zero-shot" construction of compound libraries tailored to possess specific bioactivity, synthesizability, and structural novelty...

Extracellular vesicles (EVs), lipid-enclosed structures released by virtually all life forms, have gained significant attention due to their role in intercellular and interorganismal communication. Despite their recognized importance in disease processes and therapeutic applications, fundamental questions about their primary function remain. Here, we propose a different perspective on the primary function of EVs, arguing that they serve as essential elements providing membrane area for long-distance, contact-dependent cellular communication based on protein-protein interaction...

Among the epimerases specific to alginate, some of them in Azotobacter genera convert β-d-mannuronic acid to α-l-guluronic acid but also have lyase activity to degrade alginate. The remarkable characteristics of these epimerases make it a promising enzyme for tailoring alginates to meet specific demands. Here, we determined the structure of the bifunctional mannuronan C-5 epimerase AlgE3 from Azotobacter chroococcum (AcAlgE3) in complex with several mannuronic acid oligomers as well as in apo form, which allowed us to elucidate the binding manner of each mannuronic acid oligomer, and the structural plasticity, which is dependent on calcium ions...