Benchmarking residue-resolution protein coarse-grained models for simulations of biomolecular condensates.

Intracellular liquid-liquid phase separation (LLPS) of proteins and nucleic acids is a fundamental mechanism by which cells compartmentalize their components and perform essential biological functions. Molecular simulations play a crucial role in providing microscopic insights into the physicochemical processes driving this phenomenon. In this study, we systematically compare six state-of-the-art sequence-dependent residue-resolution models to evaluate their performance in reproducing the phase behaviour and material properties of condensates formed by seven variants of the low-complexity domain (LCD) of the hnRNPA1 protein (A1-LCD)-a protein implicated in the pathological liquid-to-solid transition of stress granules.

Mechano-dependent sorbitol accumulation supports biomolecular condensate.

Condensed droplets of protein regulate many cellular functions, yet the physiological conditions regulating their formation remain largely unexplored. Increasing our understanding of these mechanisms is paramount, as failure to control condensate formation and dynamics can lead to many diseases. Here, we provide evidence that matrix stiffening promotes biomolecular condensation in vivo.

DomiRank Centrality reveals structural fragility of complex networks via node dominance.

Determining the key elements of interconnected infrastructure and complex systems is paramount to ensure system functionality and integrity. This work quantifies the dominance of the networks' nodes in their respective neighborhoods, introducing a centrality metric, DomiRank, that integrates local and global topological information via a tunable parameter. We present an analytical formula and an efficient parallelizable algorithm for DomiRank centrality, making it applicable to massive networks.

Mechano-dependent sorbitol accumulation supports biomolecular condensate.

Biomolecular condensates regulate a wide range of cellular functions from signaling to RNA metabolism , yet, the physiologic conditions regulating their formation remain largely unexplored. Biomolecular condensate assembly is tightly regulated by the intracellular environment. Changes in the chemical or physical conditions inside cells can stimulate or inhibit condensate formation .

Location and Concentration of Aromatic-Rich Segments Dictates the Percolating Inter-Molecular Network and Viscoelastic Properties of Ageing Condensates.

Maturation of functional liquid-like biomolecular condensates into solid-like aggregates has been linked to the onset of several neurodegenerative disorders. Low-complexity aromatic-rich kinked segments (LARKS) contained in numerous RNA-binding proteins can promote aggregation by forming inter-protein β-sheet fibrils that accumulate over time and ultimately drive the liquid-to-solid transition of the condensates. Here, atomistic molecular dynamics simulations are combined with sequence-dependent coarse-grained models of various resolutions to investigate the role of LARKS abundance and position within the amino acid sequence in the maturation of condensates.

Time-Dependent Material Properties of Aging Biomolecular Condensates from Different Viscoelasticity Measurements in Molecular Dynamics Simulations.

Biomolecular condensates are important contributors to the internal organization of the cell material. While initially described as liquid-like droplets, the term biomolecular condensates is now used to describe a diversity of condensed phase assemblies with material properties extending from low to high viscous liquids, gels, and even glasses. Because the material properties of condensates are determined by the intrinsic behavior of their molecules, characterizing such properties is integral to rationalizing the molecular mechanisms that dictate their functions and roles in health and disease.

Wound infiltration or transversus abdominis plane block after laparoscopic radical prostatectomy: a randomized clinical trial.

Background: Regional anesthesia techniques are commonly used for postoperative pain management during laparoscopic surgery. Our aim was to compare the analgesic efficacy of pre-incisional subcutaneous wound infiltration (WI) with that of the transversus abdominis plane (TAP) block as part of a multimodal analgesic approach in laparoscopic radical prostatectomy.

Methods: In this prospective, double-blinded, randomized controlled clinical trial, 60 patients were assigned to either TAP or WI group.

Intravenous lidocaine infusion compared to thoracic epidural analgesia in cytoreductive surgery with or without heated intraperitoneal chemotherapy. A retrospective case-cohort study.

Background: Intravenous (IV) lidocaine is a proven analgesic therapy but has not been evaluated in extensive procedures such as cytoreductive surgery (CRS). Our aim was to assess the effectiveness and safety of IV lidocaine in this setting.

Methods: This is a retrospective hybrid case-cohort study investigating analgesic effectiveness and complications of perioperative IV lidocaine at 1.

Detailed dynamics of discrete Gaussian semiflexible chains with arbitrary stiffness along the contour.

We revisit a model of semiflexible Gaussian chains proposed by Winkler et al., solve the dynamics of the discrete description of the model, and derive exact algebraic expressions for some of the most relevant dynamical observables, such as the mean-square displacement of individual monomers, the dynamic structure factor, the end-to-end vector relaxation, and the shear stress relaxation modulus. The mathematical expressions for the dynamic structure factor are verified by comparing them with results from Brownian dynamics simulations, reporting an excellent agreement.

Alternating one-phase and two-phase crystallization mechanisms in octahedral patchy colloids.

Colloidal systems possess unique features to investigate the governing principles behind liquid-to-solid transitions. The phase diagram and crystallization landscape of colloidal particles can be finely tuned by the range, number, and angular distribution of attractive interactions between the constituent particles. In this work, we present a computational study of colloidal patchy particles with high-symmetry bonding-six patches displaying octahedral symmetry-that can crystallize into distinct competing ordered phases: a cubic simple (CS) lattice, a body-centered cubic phase, and two face-centered cubic solids (orientationally ordered and disordered).

Protein structural transitions critically transform the network connectivity and viscoelasticity of RNA-binding protein condensates but RNA can prevent it.

Biomolecular condensates, some of which are liquid-like during health, can age over time becoming gel-like pathological systems. One potential source of loss of liquid-like properties during ageing of RNA-binding protein condensates is the progressive formation of inter-protein β-sheets. To bridge microscopic understanding between accumulation of inter-protein β-sheets over time and the modulation of FUS and hnRNPA1 condensate viscoelasticity, we develop a multiscale simulation approach.

Homogeneous ice nucleation rates for mW and TIP4P/ICE models through Lattice Mold calculations.

Freezing of water is the most common liquid-to-crystal phase transition on Earth; however, despite its critical implications on climate change and cryopreservation among other disciplines, its characterization through experimental and computational techniques remains elusive. In this work, we make use of computer simulations to measure the nucleation rate (J) of water at normal pressure under different supercooling conditions, ranging from 215 to 240 K. We employ two different water models: mW, a coarse-grained potential for water, and TIP4P/ICE, an atomistic nonpolarizable water model that provides one of the most accurate representations of the different ice phases.

Climate Signatures on Lake And Wetland Size Distributions in Arctic Deltas.

Understanding how thermokarst lakes on arctic river deltas will respond to rapid warming is critical for projecting how carbon storage and fluxes will change in those vulnerable environments. Yet, this understanding is currently limited partly due to the complexity of disentangling significant interannual variability from the longer-term surface water signatures on the landscape, using the short summertime window of optical spaceborne observations. Here, we rigorously separate perennial lakes from ephemeral wetlands on 12 arctic deltas and report distinct size distributions and climate trends for the two waterbodies.

The mysterious death of the beer drinking champ: potential role for hyperacute water loading and acute hyponatremia.

Hyponatremia is acute when present for <48 h. Most cases of acute hyponatremia involve both excess free water intake and an at least partial urinary free water excretion defect. By contrast, hyperacute water intoxication may result from a large excess electrolyte-free water intake in such a short time that properly working urinary free water excretion mechanisms cannot cope.

Feasibility and effectiveness of opioid-free anesthesia in cytoreductive surgery with or without heated intraperitoneal chemotherapy.

Background: Opioid-free anesthesia (OFA) provides analgesia minimizing opioids. OFA has not been evaluated in cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy. We aim to evaluate OFA feasibility and effectiveness in CRS.

Intestinal Intervention Strategy Targeting Myeloid Cells to Improve Hepatic Immunity during Hepatocarcinoma Development.

Innate immunity in the tumor microenvironment plays a pivotal role in hepatocarcinoma (HCC) progression. Plant seeds provide serine-type protease inhibitors (SETIs), which can have a significant influence on liver inflammation and macrophage function. To elucidate the influence of SETIs to counter pro-tumorigenic conditions, at the early stages of HCC development, it was used as an established model of diethylnitrosamine/thioacetamide-injured liver fed with a standard diet (STD) or high-fat diet (42%) (HFD).

'RNA modulation of transport properties and stability in phase-separated condensates.

One of the key mechanisms employed by cells to control their spatiotemporal organization is the formation and dissolution of phase-separated condensates. The balance between condensate assembly and disassembly can be critically regulated by the presence of RNA. In this work, we use a chemically-accurate sequence-dependent coarse-grained model for proteins and RNA to unravel the impact of RNA in modulating the transport properties and stability of biomolecular condensates.

Comparison between epidural technique and mid-axillary ultrasound-guided TAP block for postoperative analgesia of laparoscopic radical prostatectomy: a quasi-randomized clinical trial.

Background: Our goal was to evaluate whether TAP block offers the same analgesic pain control compared to epidural technique in laparoscopic radical prostatectomy surgery through the morphine consumption in the first 48 hours.

Methods: In this study, 45 patients were recruited and assigned to either TAP or epidural. The main study outcome was morphine consumption during the first 48 hours after surgery.

Evolution and transformation of early modern cosmological knowledge: a network study.

We investigated the evolution and transformation of scientific knowledge in the early modern period, analyzing more than 350 different editions of textbooks used for teaching astronomy in European universities from the late fifteenth century to mid-seventeenth century. These historical sources constitute the Sphaera Corpus. By examining different semantic relations among individual parts of each edition on record, we built a multiplex network consisting of six layers, as well as the aggregated network built from the superposition of all the layers.

Nephroprotective Effect of Cilastatin against Gentamicin-Induced Renal Injury In Vitro and In Vivo without Altering Its Bactericidal Efficiency.

Gentamicin is a used antibiotic that causes nephrotoxicity in 10-20% of treatment periods, which limits its use considerably. Our results have shown that cilastatin may be a promising therapeutic alternative in toxin-induced acute kidney injury (AKI). Here, we investigated its potential use as a nephroprotector against gentamicin-induced AKI in vitro and in vivo.

Neotropical Melyroidea group cockroaches reveal various degrees of (eu)sociality.

Eusociality in its various degrees represents an animal social system characterised by cooperative brood care, differentiation into castes and generational overlap. The fossil record indicates that eusociality is likely to have originated in hymenopterans and blattodeans during the Cretaceous. In this study, we present findings from surveys in Peruvian (Villa Carmen) and Ecuadorian (Rio Bigal, El Reventador) cloud forests revealing the first extant cockroach species living in complex, structured groups (n = 90-200 individuals, ˃ 20 adults).