Search Results (452)

Poly(ADP-ribose)polymerase 1 (PARP1) is an enzyme that interacts with chromatin during DNA repair and transcription processes; the molecular mechanisms of these processes remain to be determined. Previously, we have shown that PARP1 can bind to and reorganize nucleosomes using two modes of interaction with a mono-nucleosome, which are realized through PARP1 binding to the ends of linker DNA and to the nucleosome core. Here, it is shown that the latter mode of binding induces the reorganization of nucleosome structure and is more stable under the conditions of poly(ADP-ribosyl)ation (PARylation). The initial nucleosome structure is fully recovered after the dissociation of autoPARylated PARP1. The competition between PARP1 and linker histone H1.0 for binding to a nucleosome is mediated by the PARP1-H1.0 interaction and is affected by the length of linker DNA fragments. Longer linkers stabilize H1.0-nucleosome complexes, while shorter linkers facilitate displacement of H1.0 from the chromatosome by PARP1. PARylation removes both H1.0 and PARP1 from the complexes with nucleosomes. The data suggest that the H1.0 displacement from chromatin by PARP1 that is likely modulated by the density of nucleosomes might reduce chromatin compaction and facilitate access of PARP1-dependent DNA repair and transcription factors to nucleosome and inter-nucleosomal DNA. Full article

Background: Functional Neurological Disorder (FND) encompasses a spectrum of symptoms—including motor, cognitive, and seizure-like manifestations—that are not fully explained by structural neurological disease. Accumulating evidence suggests that comorbid psychiatric and somatic conditions significantly influence the clinical course, diagnostic complexity, and treatment response in FND. Objective: This study systematically explores psychiatric and medical comorbidities across major FND subtypes—Functional Cognitive Disorder (FCD), Functional Movement Disorder (FMD), and Psychogenic Non-Epileptic Seizures (PNES)—with an emphasis on subtype-specific patterns and shared vulnerabilities. Methods: We conducted a narrative review of the published literature, guided by systematic principles for transparency, covering both foundational and contemporary sources to examine comorbid conditions in patients with FCD, FMD, PNES, PPPD and general (mixed) FND populations. Relevant studies were identified through structured research and included based on methodological rigor and detailed reporting of comorbidities (PRISMA). Extracted data were organized by subtype and comorbidity type (psychiatric or medical/somatic). Results: Across all FND subtypes, high rates of psychiatric comorbidities were observed, particularly depression, anxiety, PTSD, and dissociative symptoms. FCD was predominantly associated with internalizing symptoms, affective misattribution, and heightened cognitive self-monitoring. FMD demonstrated strong links with trauma, emotional dysregulation, and personality vulnerabilities. PNES was characterized by the highest burden of psychiatric illness, with complex trauma histories and dissociation frequently reported. Somatic comorbidities—such as fibromyalgia, chronic pain, irritable bowel syndrome, and fatigue—were also prevalent across all subtypes, reflecting overlapping mechanisms involving interoception, central sensitization, and functional symptom migration. Conclusions: Comorbid psychiatric and medical conditions are integral to understanding the presentation and management of FND. Subtype-specific patterns underscore the need for individualized diagnostic and therapeutic approaches, while the shared biopsychosocial mechanisms suggest benefits of integrated care models across the FND spectrum. Full article

The present study deals with hydrate formation with binary gaseous mixtures consisting of carbon dioxide mixed with ethane at varying concentrations. Since the production of hydrates is recognised as a stochastic process and also due to the marked influence that experimental apparatuses often have on the results, the continuous updating of the literature with new experimental data is needed. Hydrates were produced and dissociated in excess water and in unstirred conditions. The dissociation values were collected and tabulated. Each test was plotted and compared with the phase boundary equilibrium conditions of pure ethane and pure carbon dioxide hydrates. The results confirmed the lowering of pressures required for hydrate formation with the increase in ethane concentration in the gas mixture. In detail, the dissociation condition for CO₂/C₂H₆ hydrates was tested within the following thermodynamic ranges: 0.1–13 °C and 11.26–36.75 bar for the 25/75 vol% mixture, 0.1–13 °C and 9.74–35.07 bar for the 50/50 vol% mixture and 7.0–12.9 °C and 17.36–30.05 bar for the 75/25 vol% mixture. When 75 vol% ethane was used, the dissociation of hydrates occurred at conditions corresponding to the phase equilibrium of pure ethane hydrates, denoting that the system reached the most favourable thermodynamic conditions possible despite the presence of 25 vol% CO₂. Full article

The SARS-CoV-2 spike (S1) protein facilitates viral entry through binding to angiotensin-converting enzyme 2 (ACE2), but it also contains an Arg–Gly–Asp (RGD) motif that may enable interactions with RGD-binding integrins on ACE2-negative cells. Here, we provide quantitative evidence for this alternative binding pathway using a live-cell, label-free resonant waveguide grating (RWG) biosensor. RWG technology allowed us to monitor real-time adhesion kinetics of live cells to RGD-displaying substrates, as well as cell adhesion to S1-coated surfaces. To characterize the strength of the integrin–S1 interaction, we determined the dissociation constant using two complementary approaches. First, we performed a live-cell competitive binding assay on RGD-displaying surfaces, where varying concentrations of soluble S1 were added to cell suspensions. Second, we recorded the adhesion kinetics of cells on S1-coated surfaces and fitted the data using a kinetic model based on coupled ordinary differential equations. By comparing the results from both methods, we estimate that approximately 33% of the S1 molecules immobilized on the Nb₂O₅ biosensor surface are capable of initiating integrin-mediated adhesion. These findings support the existence of an alternative integrin-dependent entry route for SARS-CoV-2 and highlight the effectiveness of label-free RWG biosensing for quantitatively probing virus–host interactions under physiologically relevant conditions without the need of the isolation of the interaction partners from the cells. Full article

Background and Objectives: Borderline personality disorder (BPD) is a complex psychiatric condition characterized by emotional instability, impulsivity, a fluctuating self-image, and persistent difficulties in maintaining close interpersonal relationships. Among university students, these traits may be associated with social adjustment and academic functioning difficulties. The present study aimed to examine the prevalence of borderline traits within a Romanian student population and to investigate the associations between these traits and interpersonal difficulties encountered in family life, romantic relationships, and academic environments. Materials and Methods: This cross-sectional study included a total of 151 undergraduate students enrolled in higher education institutions across Romania. Data were gathered through an online questionnaire available between March and May 2025. The instrument comprised items addressing socio-demographic characteristics, diagnostic criteria for borderline personality traits according to the DSM, as well as self-reported social behaviour patterns. Statistical analysis was performed using GraphPad Prism 9, version 9.3.1 for Windows, employing Fisher’s exact test and the odds ratio (OR), with a significance threshold set at p < 0.05. Results: Most participants reported experiencing affective instability (71.5%) and distorted self-image (58.9%). Fear of abandonment was present in 29.4% of the respondents, while impulsivity was identified in 37.7%. Borderline personality traits were significantly associated with a range of social difficulties, including relational anxiety, outbursts of anger, peer conflicts, social withdrawal, and dissociative symptoms. Individuals who exhibited impulsivity, self-injurious behaviours, or dissociative episodes demonstrated a markedly increased risk of social dysfunction, with odds ratios ranging from 3 to 10 (p < 0.0001). Conclusions: The findings reveal a high prevalence of borderline traits within the analysed sample, along with statistically significant associations with social and emotional difficulties. These results underscore the importance of implementing psychological screening programs in universities, as well as early intervention strategies focused on the mental well-being of young adults. Establishing a supportive academic environment and fostering collaboration between faculty members and mental health professionals may play a key role in preventing symptom escalation and in promoting healthy personal and relational development. Full article

Cytochrome P450 (CYP450) enzymes play an essential role in the metabolism of drugs, particularly in phase I metabolic reactions. In this article, we present a comprehensive review of fifteen selected enzymes belonging to the CYP450 family. The enzymes included in this analysis are CYP7A1, CYP3A4, CYP3A5, CYP2D6, CYP2E1, CYP2C8, CYP2C18, CYP2C9, CYP2C19, CYP2B6, CYP2A6, CYP2A13, CYP1B1, CYP1A1, and CYP1A2. We examined the influence of natural, polymorphic variations within their primary amino acid sequences on their enzymatic function and mechanisms of action. To begin, we compiled a dataset of naturally occurring polymorphic variants for these enzymes. This was achieved through a detailed analysis of entries in the UniProt database, as well as an extensive review of the current scientific literature. For each variant, we included commentary regarding its potential impact on enzyme activity or drug response, based on evidence observed in in vitro experiments, in vivo studies, or clinical trials. Particular emphasis was placed on how such polymorphisms might alter the metabolism of xenobiotics, thereby potentially affecting pharmacological outcomes. In this respect, the work represents the first comprehensive source in the scientific literature that systematically gathers and organizes data on CYP450 polymorphisms, including an assessment of their potential significance in processes mediated by these enzymes. A more detailed comparison of the polymorphism-related in vitro studies is devoted to CYP3A4, an enzyme that displays the largest fraction of clinically significant polymorphs. Secondly, we aimed to establish possible molecular explanations for why specific polymorphisms exhibit clinically or experimentally observable effects. To explore this, we performed a qualitative structural analysis of the enzymes, focusing on shared structural characteristics among the examined members of the CYP450 family. The results of this analysis demonstrate that there is no single universal mechanism by which polymorphisms influence the function of CYP450 enzymes. Instead, the mechanisms vary and may include alterations in the orientation of the enzyme within the lipid membrane, changes affecting the association or dissociation of substrates and products at the active site, structural stabilization or destabilization of the enzyme’s reactive centers, modifications in the way the enzyme interacts with its ligand, or alterations in the character of the interface involved in contact with its redox partner (electron transfer protein). Furthermore, among the polymorphisms that significantly impact enzyme function, mutations involving the substitution of arginine residues for other amino acids appear to be overrepresented. Full article

Background: Undercover police work is a psychologically high-risk profession that exposes officers to chronic stress, identity conflicts, and moral dilemmas. The aim of the present review is to evaluate the psychological consequences associated with undercover police work, focusing on specific psychopathological risk factors. Methods: A systematic search was conducted in PubMed, PsycINFO, Web of Science, and Scopus databases. Studies were conducted in the United States, the United Kingdom, New Zealand, and Canada. The present systematic review analyzed data from 380 current undercover operatives, 372 former UCOs, 578 officers without undercover experience, and 60 pre-operational agents. Results: From an initial pool of 365 records, 10 studies were identified, of which 6 met the inclusion criteria. The most frequently reported psychological risk factors included anxiety, hypervigilance, identity issues, dissociative symptoms, and substance misuse. These were assessed using validated self-report instruments (e.g., SCL-90), structured interviews, and clinical evaluations. Long-term consequences were more prominent post-deployment, particularly among former UCOs. Conclusions: Undercover work is associated with an elevated risk of mental health problems, especially after the end of operations. Future research should focus on standardizing assessment tools and identifying protective factors. The findings support the development of targeted interventions such as pre-deployment psychological screening, ongoing monitoring, and structured reintegration programs to safeguard UCOs’ well-being. Full article

Background: Crystalline glucosamine sulfate (cGS) claims to be a stabilized form of glucosamine sulfate with a defined crystalline structure intended to enhance chemical stability. It is proposed to offer pharmacokinetic advantages over regular glucosamine sulfate (rGS) which is stabilized with potassium or sodium chloride. However, comparative human bioavailability data are limited. Since both forms dissociate in gastric fluid into constituent ions, the impact of cGS formulation on absorption remains uncertain. This pilot study aimed to compare the bioavailability of cGS and rGS using a randomized, double-blind, crossover design. Methods: Ten healthy adults received a single 1500 mg oral dose of either cGS or rGS with a 7-day washout between interventions. Capillary blood samples were collected over 24 h. Glucosamine and its metabolite concentrations were quantified by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS), and pharmacokinetic parameters—including maximum concentration (C_max), time to reach C_max (T_max), and area under the curve (AUC)—were calculated. Results: Mean AUC_0–24, C_max, T_max, and T_½ values for glucosamine and glucosamine-6-sulfate (GlcN-6-S) were comparable between cGS and rGS. Although the AUC_0–24 for glucosamine was modestly higher with rGS (18,300 ng·h/mL) than with cGS (12,900 ng·h/mL), the difference was not statistically significant (p = 0.136). GlcN-6-S exposure was also similar between formulations (rGS: 50,700 ng·h/mL; cGS: 50,600 ng·h/mL), with a geometric mean ratio of 1.39, a delayed T_max (6–8 h) and longer half-life, consistent with its role as a downstream metabolite. N-acetylglucosamine levels remained stable, indicating potential homeostatic regulation. Conclusions: This pilot study found no significant pharmacokinetic advantage of cGS over rGS. These preliminary findings challenge claims of cGS’ pharmacokinetic superiority, although the small sample size limits definitive conclusions. Larger, adequately powered studies are needed to confirm these results. Full article

Narcotics trafficking is a fundamental part of organized crime, posing significant and evolving challenges for forensic investigations. Addressing these challenges requires rapid, precise, and scientifically validated analytical methods for reliable identification of illicit substances. Over the past five years, forensic drug testing has advanced considerably, improving detection of traditional drugs—such as tetrahydrocannabinol, cocaine, heroin, amphetamine-type stimulants, and lysergic acid diethylamide—as well as emerging new psychoactive substances (NPS), including synthetic cannabinoids (e.g., 5F-MDMB-PICA), cathinones (e.g., α-PVP), potent opioids (e.g., carfentanil), designer psychedelics (e.g., 25I-NBOMe), benzodiazepines (e.g., flualprazolam), and dissociatives (e.g., 3-HO-PCP). Current technologies include colorimetric assays, ambient ionization mass spectrometry, and chromatographic methods coupled with various detectors, all enhancing accuracy and precision. Vibrational spectroscopy techniques, like Raman and Fourier transform infrared spectroscopy, have become essential for non-destructive identification. Additionally, new sensors with disposable electrodes and miniaturized transducers allow ultrasensitive on-site detection of drugs and metabolites. Advanced chemometric algorithms extract maximum information from complex data, enabling faster and more reliable identifications. An important emerging trend is the adoption of green analytical methods—including direct analysis, solvent-free extraction, miniaturized instruments, and eco-friendly chromatographic processes—that reduce environmental impact without sacrificing performance. This review provides a comprehensive overview of innovations over the last five years in forensic drug analysis based on the ScienceDirect database and highlights technological trends shaping the future of forensic toxicology. Full article

This study presents data from Reverse Osmosis (RO) and Nanofiltration (NF) spiral-wound polyamide modules tested in a semi-pilot plant with multicomponent mixtures of Volatile Fatty Acids (VFAs) comprising acetic, propionic, butyric, valeric, and hexanoic acids. A robust method combining film theory and dissociation equilibria was developed to estimate interfacial concentrations, enabling accurate analysis of concentration polarization, real rejection, and effective transmembrane driving force. Concentration polarization strongly affects NF membranes, resulting in real rejections up to 20% higher than apparent values, while its effect is negligible for RO membranes. NF rejections show marked sensitivity to pH and VFA feed concentration: at 20 g/L and highest flux, acetic acid real rejection increases from 80% to 91% as pH rises from 6 to 9. At pH 7, rejections decline with feed concentration, with acetic acid dropping from 55% at 20 g/L to 32% at 63 g/L, at the same flux. These changes correlate with the molecular weight of the acids. Conversely, RO rejections are marginally affected by pH and not influenced by concentration due to dominant steric exclusion. Membrane permeabilities remain unaffected by VFAs and align with pure water values. The data analysis framework is effective and applicable across a wide range of conditions and membranes. Full article

This article presents a mini-review of the available data on the thermodynamics of the complexation of amino acids and peptides with some nucleic bases in a buffer medium. Data on changes in thermodynamic parameters (binding constants, Gibbs energy, enthalpy, entropy) during the complexation of nucleic bases with amino acids and peptides as a function of physicochemical properties are given at T = 298.15 K. The effects of complexation on the volumetric properties of nucleic bases, including apparent molar volumes, standard molar volumes, and limiting molar expansibility, over a temperature range of 288.15 to 313.15 K are considered in detail. Differences in the behavior of amino acids and peptides caused by different modes of coordination with nucleic bases are noted. These manifest in the stoichiometry of the formed complexes, the relationship with the acid dissociation constants of carboxyl and amino groups, enthalpy–entropy compensation in the complexation process, the temperature dependence of the transfer volumes, and the effect of hydrophobicity on volumetric characteristics. Full article

Virus-like particles (VLPs) have the potential to become a versatile carrier platform for vaccination against multiple diseases. In the light of short process development timelines and the demand for reliable and robust processes, metabolic modeling of cell culture processes offers great advantages when coupled with a Quality-by-Design (QbD) development approach. A previous work was able to demonstrate the accurate prediction of HEK293F PiggyBac cell concentration as well as VLP titer and metabolite production with a reduced metabolic model. This work presents the reduced metabolic model for a more productive cell line Sleeping Beauty and emphasizes the need for model re-parameterization when the producer cell line changes. The goal of precise prediction for a fed-batch and continuous HEK293 cultivation can, therefore, be achieved. In terms of decision-making for downstream unit operations, a soft sensor for the prediction of main impurities like proteins and DNA was introduced for the first time for the production of lentiviral vectors with several terms describing the release of impurities like DNA and proteins, growth-related protein production, and enzymatic degradation activity associated with cell dissociation in an accurate manner. The additional information can contribute to a more efficient design phase by reducing experimental effort as well as during cultivation with data-based decision-making. With the aid of real-time process data acquisition through process analytical technology (PAT), its predictive power can be enhanced and lead to more reliable processes. Full article

Background/Objectives: To evaluate the clinical characteristics and diagnostic significance of dissociation between bithermal caloric test and video head impulse test (vHIT) in patients presenting with dizziness. Methods: We retrospectively reviewed 644 patients who underwent bithermal caloric testing and vHIT at a university-affiliated general hospital. Patients were classified into concordant and discordant groups based on test results. The discordant group was further subdivided into those with abnormal caloric test and normal vHIT, and those with normal caloric test and abnormal vHIT. Demographic data, vestibular function test outcomes, and clinical diagnoses were analyzed. Results: Discordant results were observed in 36.5% of patients. Among these, 31.8% had abnormal caloric responses with normal vHIT, and 4.7% had normal caloric responses with abnormal vHIT. Most patients in both discordant subgroups were diagnosed with peripheral vestibular disorders, such as Ménière’s disease and unilateral vestibulopathy. The abnormal caloric/normal vHIT pattern was more common and associated with low-frequency dysfunction. The normal caloric/abnormal vHIT pattern, though less frequent, also involved predominantly peripheral etiologies. Conclusions: Dissociation between caloric and vHIT results is not uncommon and provides important diagnostic insights. Employing both tests in a complementary manner enhances the identification of frequency-specific vestibular deficits and supports more accurate diagnosis and management of vestibular disorders. Full article

Severe Acute Respiratory Syndrome (SARS) represents a significant cause of morbidity and mortality in children under one year of age, a particularly vulnerable population due to immunological and respiratory immaturity. The diverse etiology includes multiple respiratory viruses such as Respiratory Syncytial Virus (RSV), influenza, rhinovirus, and SARS-CoV-2, each with distinct potential to cause severe illness and death. Understanding the specific incidence and lethality by etiological agents in the recent Brazilian context (2024), after the COVID-19 pandemic, is essential to guide surveillance and public health strategies. This study aimed to analyze the risk of incidence and lethality by specific etiology of SARS in children under one year of age hospitalized in Brazil during the year 2024. A descriptive cross-sectional study was performed using secondary data from the 2024 Influenza Epidemiological Surveillance Information System (SIVEP-Gripe), obtained via OpenDataSUS. Reported cases of SARS hospitalized in children <1 year of age in Brazil were included. Distribution by final classification and epidemiological week (EW) was analyzed; the incidence rate by Federative Unit (FU) (cases/100,000 < 1 year) with risk classification (Low/Moderate/High) was assessed; and, for cases with positive viral RT-PCR, the etiological frequency and virus-specific lethality rate (deaths/total cases of etiology ×100), also with risk classification, were extracted. A multivariate logistic regression model was performed for the risk factors of death. A total of 66,170 cases of SARS were reported in children under 1 year old (national incidence: 2663/100,000), with a seasonal peak between April and May. The majority of cases were classified as “SARS due to another respiratory virus” (49.06%) or “unspecified” (37.46%). Among 36,009 cases with positive RT-PCR, RSV (50.06%) and rhinovirus (26.97%) were the most frequent. The overall lethality in RT-PCR-positive cases was 1.28%. Viruses such as parainfluenza 4 (8.57%), influenza B (2.86%), parainfluenza 3 (2.49%), and SARS-CoV-2 (2.47%) had higher lethality. The multivariate model identified parainfluenza 4 (OR = 6.806), chronic kidney disease (OR = 3.820), immunodeficiency (OR = 3.680), Down Syndrome (OR = 3.590), heart disease (OR = 3.129), neurological disease (OR = 2.250), low O₂ saturation (OR = 1.758), SARS-CoV-2 (OR = 1.569) and respiratory distress (OR = 1.390) as risk factors for death. Cough (OR = 0.477) and RSV (OR = 0.736) were associated with a lower chance of death. The model had good calibration (Hosmer–Lemeshow p = 0.693) and overall significance (p < 0.001). SARS represented a substantial burden of hospitalizations, with marked seasonal and geographic patterns. RSV and rhinovirus were the main agents responsible for the volume of confirmed cases but had a relatively low to moderate risk of lethality. In contrast, less frequent viruses such as parainfluenza 4, influenza B, parainfluenza 3, and SARS-CoV-2 were associated with a significantly higher risk of death. These findings highlight the importance of dissociating frequency from lethality and reinforce the need to strengthen etiological surveillance, improve diagnosis, and direct preventive strategies (such as immunizations) considering the specific risk of each pathogen for this vulnerable population. Full article

The NOS1AP gene encodes the nitric oxide synthase 1 adaptor protein (NOS1AP), which binds to neuronal nitric oxide synthase (nNOS) and regulates nitric oxide (NO) production by dissociating nNOS from NMDA receptors (NMDARs). Notably, NOS1AP expression is upregulated upon NMDAR activation; however, there is no available data regarding its production under the receptor inhibition. The NOS1AP gene is also 1 among more than 1000 genes that are presumed to be associated with the development of schizophrenia. Various animal models of this disorder have been developed, some of which are based on the use of NMDAR antagonists such as dizocilpine (MK-801). In this study, we investigated the expression and production of NOS1AP in rats injected with a low dose of dizocilpine (0.1 mg/kg), as well as in SH-SY5Y and HEK293T cell lines treated with varying concentrations of the same compound (10–200 µM). According to our results, neither the expression of the NOS1AP gene nor the production of NOS1AP protein was affected by dizocilpine treatment. Full article