Full-length inhibitor protein is the most effective to perturb human dUTPase activity.

It has been demonstrated recently that knockout of the dUTPase enzyme leads to early embryonic lethality in mice. However, to explore the physiological processes arising upon the lack of dUTPase an effective and selective enzyme inhibitor is much needed. A highly specific and strong binding proteinaceous human dUTPase inhibitor described by us recently was a promising starting point to develop a molecular tool to study temporal and conditional dUTPase inhibition in cellulo.

Enhancing retrieval capacity of the predictive brain through dorsolateral prefrontal cortex intervention.

Extracting spatial or temporal patterns across experiences is essential for skill acquisition and predictive processes. The prefrontal cortex plays a central role in regulating competitive cognitive systems, with a particular influence on executive functions, often opposing statistical learning. This regulatory function may account for observed improvements in the acquisition and consolidation of statistical regularities following inhibition of the dorsolateral prefrontal cortex via repetitive transcranial magnetic stimulation.

Mind wandering enhances statistical learning.

The human brain spends 30-50% of its waking hours engaged in mind-wandering (MW), a common phenomenon in which individuals either spontaneously or deliberately shift their attention away from external tasks to task-unrelated internal thoughts. Despite the significant amount of time dedicated to MW, its underlying reasons remain unexplained. Our pre-registered study investigates the potential adaptive aspects of MW, particularly its role in predictive processes measured by statistical learning.

Structure-Atropisomer Stability Relationship in Selective MCL-1 Inhibitors.

Atropisomersm is an emerging feature in recent drug candidates due to the increasing complexity of the targeted protein surfaces. The developability of the drug candidates requires that their atropisomer interconversion is either fast or very slow at ambient temperature therefore the understanding and predictability of the isomerization rate is of great importance. Through a series of selective MCL-1 inhibitors we studied how structural features influence the interconversion of atropisomers.

Emotion dysregulation in adolescents is normalized by ADHD pharmacological treatment.

Background: Attention-deficit/hyperactivity disorder (ADHD) is associated with emotion dysregulation (ED) and in ADHD, beyond ADHD and comorbidity severity, ED confers increased risk for negative outcomes. First- and second-line ADHD pharmacotherapy is effective at ameliorating core symptoms and improving cognitive functioning and accumulating evidence indicates primairly in children and adults, active ADHD pharmacotherapy has beneficial effects on emotional symptoms. Gaps in knowledge remain about whether in adolescents, ADHD pharmacotherapy has beneficial effects on ED or about the extent to which effects are apparent for discontinued/ past ADHD pharmacotherapy.

Understanding the molecular mechanism of fumonisin esterases by kinetic and structural studies.

Fumonisins are sphingolipid-like mycotoxins that cause serious damage by contaminating food and feed. The tricarballylic acid (TCA) units of fumonisin B (FB; accounting for 70 % of fumonisin contamination) can be removed by fumonisin B esterase (FE, EC 3.1.

Functional and structural polypharmacology of indazole-based privileged ligands to tackle the undruggability of membrane transporters.

Despite the significant roles of solute carrier (SLC) and ATP-binding cassette (ABC) transporters in human health and disease, most remain poorly characterized as intrinsic and/or xenobiotic ligands are unknown, rendering them as 'undruggable'. Polypharmacology, defined as the simultaneous engagement of multiple targets by a single ligand, offers a promising avenue for discovering novel lead compounds addressing these emerging pharmacological challenges - a major focus in contemporary medicinal chemistry. While common structural motifs among phylogenetically diverse proteins have been proposed to underlie polypharmacology through the concept of 'multitarget binding sites', a comprehensive analysis of these functional and structural aspects from a medicinal chemistry perspective has yet to be undertaken.

Optimizing lipopeptide bioactivity: The impact of non-ionic surfactant dressing.

The aim of the research is to increase the applicability of lipopeptides as drugs. To this end, non-ionic triblock copolymers, namely poloxamers, were applied. The physico-chemical properties of poloxamers vary depending on the length of the blocks.

Wanting and liking of Facebook functions and their correlation to problematic use.

A key question about social media use is whether it constitutes an addiction. A possible frame of reference to investigate this question is the Incentive Sensitizations Theory (IST), as it provides a solid empirical background to understand the motivational and hedonic aspects of problematic behaviors. A central assumption of IST that addiction-related cues play a pivotal role in addictive behaviors has remained relatively understudied in the context of social media use.

Electronically Nonadiabatic Quenching of Excited States of O by Collisions with O Atoms.

The kinetics of electronically inelastic quenching of O(Δ) and O(Σ) by collisions with O(P) have been investigated using mixed quantum-classical trajectories governed by adiabatic potential energy surfaces and state couplings generated from a recently developed diabatic potential energy matrix (DPEM) for the 14 lowest-energy A' states of O. Using the coherent switching with decay of mixing (CSDM) method, dynamics calculations were performed both with 14 coupled electronic states and with 8 coupled electronical states, and similar results were obtained. The calculated thermal quenching rate coefficients are generally small, but they increase with temperature.

The effect of transcranial direct current stimulation and inhibitory control training on depression and anxiety among post-stroke individuals.

Background: Recent research has highlighted the role of fronto-parietal brain networks and cognitive control in mood disorders. Transcranial direct current stimulation (tDCS) and computer-based cognitive training are used in post-stroke rehabilitation. This study examined the combined effects ofof computer-based inhibitory control training (ICCT) and anodal tDCS on post-stroke depression and anxiety.

Corrigendum: The influence of temperament and perinatal factors on language development: a longitudinal study.

[This corrects the article DOI: 10.3389/fpsyg.2024.

FDA-approved drugs featuring macrocycles or medium-sized rings.

Macrocycles or medium-sized rings offer diverse functionality and stereochemical complexity in a well-organized ring structure, allowing them to fulfill various biochemical functions, resulting in high affinity and selectivity for protein targets, while preserving sufficient bioavailability to reach intracellular compartments. These features have made macrocycles attractive candidates in organic synthesis and drug discovery. Since the 20th century, more than three-score macrocyclic drugs, including radiopharmaceuticals, have been approved by the US Food and Drug Administration (FDA) for treating bacterial and viral infections, cancer, obesity, immunosuppression, inflammatory, and neurological disorders, managing cardiovascular diseases, diabetes, and more.

A 2D cell segmentation protocol for monitoring multiple STAT signaling pathways by fluorescence microscopy.

Microscopic cell segmentation typically requires complex imaging, staining, and computational steps to achieve acceptable consistency. Here, we describe a protocol for the high-fidelity segmentation of the nucleus and cytoplasm in cell culture and apply it to monitor interferon-induced signal transducer and activator of transcription (STAT) signaling. We provide guidelines for sample preparation, image acquisition, and segmentation.

Cytotoxic Activity of Bisphosphonic Derivatives Obtained by the Michaelis-Arbuzov or the Pudovik Reaction.

Methylenebisphosphonic derivatives including hydroxy-methylenebisphosphonic species may be of potential biological activity, and a part of them is used in the treatment of bone diseases. Methylenebisphosphonates may be obtained by the Michaelis-Arbuzov reaction of suitably α-substituted methylphosphonates and trialkyl phosphites or phosphinous esters, while the hydroxy-methylene variations are prepared by the Pudovik reaction of α-oxophosphonates and different >P(O)H reagents, such as diethyl phosphite and diarylphosphine oxides. After converting α-hydroxy-benzylphosphonates and -phosphine oxides to the α-halogeno- and α-sulfonyloxy derivatives, they were utilized in the Michaelis-Arbuzov reaction with trialkyl phosphites and ethyl diphenylphosphinite to afford the corresponding bisphosphonate, bis(phosphine oxide) and phosphonate-phosphine oxide derivatives.

The Synthesis, Crystal Structure, Modification, and Cytotoxic Activity of α-Hydroxy-Alkylphosphonates.

A series of α-hydroxy-alkylphosphonates and α-hydroxy-alkylphosphine oxides were synthesized by the Pudovik reaction of acetaldehyde and acetone with dialkyl phosphites or diarylphosphine oxides. The additions were performed in three different ways: in liquid phase using triethylamine as the catalyst (1), on the surface of AlO/KF solid catalyst (2), or by a MW-assisted NaCO-catalyzed procedure (3). In most of the cases, our methods were more efficient and more robust than those applied in the literature.

Synthesis of Alkyl α-Amino-benzylphosphinates by the Aza-Pudovik Reaction; The Preparation of the Butyl Phenyl--phosphinate Starting P-Reagent.

Butyl phenyl--phosphinate that is not available commercially was prepared from phenyl--phosphinic acid by three methods: by alkylating esterification (i), by microwave-assisted direct esterification (ii), and unexpectedly, by thermal esterification (iii). Considering the green aspects, selectivity and scalability, the thermal variation seemed to be optimal. However, there was need for prolonged heating.

When a Small Amount of Comonomer Is Enough: Tailoring the Critical Solution Temperature of LCST-Type Thermoresponsive Random Copolymers by PEG Methyl Ether Methacrylate with 1100 g/mol Molecular Weight.

Tuning the critical solution temperature (CST) of thermoresponsive polymers is essential to exploit their immense potential in various applications. In the present study, the effect of PEG-methyl ether methacrylate with a higher molecular weight of 1100 g/mol (mPEGMA) as a comonomer was investigated for its suitability for the CST adjustment of LCST-type polymers. Accordingly, a library of mPEGMA-based copolymers was established with varying compositions () using four main comonomers, namely di(ethylene glycol) ethyl ether acrylate, -isopropyl acrylamide and methacrylamide, and mPEGMA, with different CST values (cloud points, , and clearing points, , by turbidimetry).

The Effect of Lipopolysaccharides from on the Size, Density, and Compressibility of Phospholipid Vesicles.

The properties of the large unilamellar vesicles (LUVs) from 1,2-dimyristoyl-sn-glycero-3-phosphatidylcholine (DMPC), modified by lipopolysaccharides (LPS) from sv. Enteritidis, which mimics Gram-negative bacteria, were studied by various physical methods. LPS, in the range of 0/20/50 % / relative to the lipid, had a regulatory role in the structure of the LUVs toward the lower size, low polydispersity, and over-a-month size stability due to the lower negative zeta potential.

An In Vivo Biostability Evaluation of ALD and Parylene-ALD Multilayers as Micro-Packaging Solutions for Small Single-Chip Implants.

Miniaturization of next-generation active neural implants requires novel micro-packaging solutions that can maintain their long-term coating performance in the body. This work presents two thin-film coatings and evaluates their biostability and in vivo performance over a 7-month animal study. To evaluate the coatings on representative surfaces, two silicon microchips with different surface microtopography are used.

Carborane-Decorated Siloles with Highly Efficient Solid-State Emissions - What Drives the Photophysical Properties?

New hybrids were synthesised by linking carboranes and siloles, both of which are known as aggregation-induced emission active units. Although most of the newly synthesised systems do not display notable quantum yield either in solution or in the aggregated state, they emit strongly in the solid-state, and a quantum yield of up to 100 % can be achieved. The tailorable quantum yield can be attributed to the packing of the molecules in the crystal lattice ruled by the carborane and phenyl moieties according to the SC-XRD data.

Redox-Active Bisphosphonate-Based Viologens as Negolytes for Aqueous Organic Flow Batteries.

Viologen derivatives feature two reversible one-electron redox processes and have been extensively utilized in aqueous organic flow batteries (AOFBs). However, the early variant, methyl viologen (MVi), exhibits low stability in aqueous electrolytes, restricting its practical implementation in AOFB technology. In this context, leveraging the tunability of organic molecules, various substituents have been incorporated into the viologen core to achieve better stability, lower redox potential, and improved solubility.

Tissue-specific roles of de novo DNA methyltransferases.

DNA methylation, catalyzed by DNA methyltransferases (DNMT), plays pivotal role in regulating embryonic development, gene expression, adaption to environmental stress, and maintaining genome integrity. DNMT family consists of DNMT1, DNMT3A, DNMT3B, and the enzymatically inactive DNMT3L. DNMT3A and DNMT3B establish novel methylation patterns maintained by DNMT1 during replication.

Stabilizing effect of HP-β-CD on infliximab in liquid formulations and a solid formulation produced by electrospinning.

The development of stable biopharmaceutical formulations, such as monoclonal antibodies, poses a great challenge in the pharmaceutical industry. This study investigated the stabilizing effect of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) in liquid and solid formulations of infliximab during processing and storage. The solid formulation was produced by a scaled-up high-speed electrospinning method, resulting in a product suitable for reconstitution with excellent dissolution properties.