Search Results (1,607)

Endocytosis plays a complex role in pathogen-host interactions. It serves as a pathway for pathogens to enter the host cell and acts as a part of the immune defense mechanism. Endocytosis involves the formation of lipid membrane vesicles and the reshaping of the cell membrane, a task predominantly managed by proteins containing BAR (Bin1/Amphiphysin/yeast RVS167) domains. Insights into how BAR domains can remodel and reshape cell membranes provide crucial information on infections and can aid the development of treatment. Aiming at deciphering the roles of the BAR dimers in lipid membrane bending and remodeling, we conducted extensive all-atom molecular dynamics simulations and discovered that the presence of helix kinks divides the BAR monomer into two segments—the “arm segment” and the “core segment”—which exhibit distinct movement patterns. Contrary to the prior hypothesis of BAR domains working as a rigid scaffold, we found that it functions in an “Arms-Hands” mode. These findings enhance the understanding of endocytosis, potentially advancing research on pathogen-host interactions and aiding in the identification of new treatment strategies targeting BAR domains. Full article

Individuals with chronic diseases are more vulnerable to environmental inhalation exposures. Although metabolic syndrome (MetS) is increasingly common and is associated with susceptibility to inhalation exposures such as particulate air pollution, the underlying mechanisms remain unclear. In previous studies, we determined that, compared to a healthy mouse model, a mouse model of MetS exhibited increased pulmonary inflammation 24 h after exposure to AgNPs. This exacerbated response was associated with decreases in pulmonary levels of specific specialized pro-resolving mediators (SPMs). Supplementation with specific SPMs that are known to be dysregulated in MetS may alter particulate-induced inflammatory responses and be useful in treatment strategies. Our current study hypothesized that administration of resolvin E1 (RvE1), protectin D1 (PD1), or maresin (MaR1) following AgNP exposure will differentially regulate inflammatory responses. To examine this hypothesis, healthy and MetS mouse models were exposed to either a vehicle (control) or 50 μg of 20 nm AgNPs via oropharyngeal aspiration. They were then treated 24 h post-exposure with either a vehicle (control) or 400 ng of RvE1, PD1, or MaR1 via oropharyngeal aspiration. Endpoints of pulmonary inflammation and toxicity were evaluated three days following AgNP exposure. MetS mice that were exposed to AgNPs and received PBS treatment exhibited significantly exacerbated pulmonary inflammatory responses compared to healthy mice. In mice exposed to AgNPs and treated with RvE1, neutrophil infiltration was reduced in healthy mice and the exacerbated neutrophil levels were decreased in the MetS model. This decreased neutrophilia was associated with decreases in proinflammatory cytokines’ gene and protein expression. Healthy mice treated with PD1 did not demonstrate alterations in AgNP-induced neutrophil levels compared to mice not receiving treat; however, exacerbated neutrophilia was reduced in the MetS model. These PD1 alterations were associated with decreases in proinflammatory cytokines, as well as elevated interleukin-10 (IL-10). Both mouse models receiving MaR1 treatment demonstrated reductions in AgNP-induced neutrophil influx. MaR1 treatment was associated with decreases in proinflammatory cytokines in both models and increases in the resolution inflammatory cytokine IL-10 in both models, which were enhanced in MetS mice. Inflammatory responses to particulate exposure may be treated using specific SPMs, some of which may benefit susceptible subpopulations. Full article

Background/Objectives: Myocardial involvement has been observed in athletes following SARS-CoV-2 infection. It is unclear if these changes are due to myocardial damage per se or to an interruption in training. The aim of this study was to assess cardiac function and structure in elite athletes before and after infection (INFAt) and compare them to a group of healthy controls (CON). Methods: Transthoracic echocardiography was performed in 32 elite athletes, including 16 INFAt (median 21.0 (19.3–21.5) years, 10 male) before (t₀) and 52 days after (t₁) mild SARS-CoV-2 infection and 16 sex-, age- and sports type-matched CON. Left and right ventricular global longitudinal strain (LV/RV GLS), RV free wall longitudinal strain (RV FWS) and left atrial strain (LAS) were assessed by an investigator blinded to patient history. Results: INFAt showed no significant changes in echocardiographic parameters between t₀ and t₁, including LV GLS (−21.8% vs. −21.7%, p = 0.649) and RV GLS (−29.1% vs. −28.7%, p = 0.626). A significant increase was observed in LA reservoir strain (LASr) (35.7% vs. 47.8%, p = 0.012). Compared to CON, INFAt at t₁ had significantly higher RV FWS (−33.0% vs. −28.2%, p = 0.011), LASr (47.8% vs. 30.5%, p < 0.001) and LA contraction strain (−12.8% vs. −4.9%, p = 0.050) values. Conclusions: In elite athletes, mild SARS-CoV-2 infection does not significantly impact LV function when compared to their pre-SARS-CoV-2 status and to healthy controls. However, subtle changes in RV and LA strain may indicate temporary or training-related adaptions. Further research is needed, particularly focusing on athletes with more severe infections or prolonged symptoms. Full article

Aim: Respiratory viruses significantly impact public health, contributing to high morbidity and mortality rates in both children and adults. This study evaluates the distribution and incidence of respiratory tract viruses in our hospital from 2019 to 2022, focusing on changes post-COVID-19 pandemic. Material and Methods: Utilizing molecular methods, we analyzed nasopharyngeal swabs with the FTD Respiratory Pathogens 21 kit and the QIAStat Dx Respiratory Panel kit at Istanbul Faculty of Medicine. A total of 1186 viruses were detected in 2488 samples (47.6% of the total) examined with the FTD Respiratory Pathogens 21 kit between 2019 and 2022. Results: It was determined that the detection rates were 52.8% in 2019, 44.3% in 2020, 50.0% in 2021, and 40.0% in 2022. Notable changes in prevalence were observed for pandemic influenza A (IAV-H1N1pdm2009), parainfluenza virus (PIV)-3, rhinovirus (RV), and respiratory syncytial virus (RSV)-A/B (p < 0.05). RV consistently showed the highest detection rates across all years (17.6% to 7.9%). Additionally, 1276 viruses were detected in 1496 samples using the QIAStat DX kit, with 91.3% positivity in 2021 and 78.6% in 2022, highlighting the kit’s effectiveness in rapid diagnosis. Conclusions: This study enhances understanding of respiratory virus epidemiology during and after the pandemic, emphasizing the need for ongoing surveillance and strategic public health measures to address the evolving landscape of respiratory infections. Full article

Aims. To identify the difference between adult patients with septal defects and paroxysmal atrial fibrillation (AF) and patients without a history of arrhythmia using the left atrial (LA) volume and function parameters, to reveal the parameters associated with AF development. Methods and results. In this prospective study, 81 patients with septal defects and left-to-right shunts were enrolled between 2021 and 2023 and divided into two groups: with paroxysmal AF and without AF. Left atrial function was analyzed based on the indexed left atrial volumes (LAVI and preA-LAVI), ejection fraction (LAEF), expansion index (LAEI), reservoir (LAS-r), conduit (LAS-cd) and contractile (LAS-ct) strain, and stiffness index (LASI) using a Philips CVx3D ultrasound system (Philips, Amsterdam, The Netherlands) and corresponding software. In total, 26 patients with paroxysmal atrial fibrillation (mean age: 59.6 ± 11.7 years, female: 80.8%) and 55 patients with septal defects without any history of arrhythmias (mean age: 44.8 ± 11.6 years, female: 81.8%) were included. All patients were in the NYHA class I or II at baseline. Our findings demonstrated a significant difference between all LA function parameters in the two groups. Upon univariable analysis, the LAVI, preA-LAVI, LASI, LAEF, LAEI, LAS-r, LAS-c, LAS-ct, age, cardiac index, E/A, and RV pressure were found to be associated with AF. The multivariate analysis identified LAVI (OR 1.236, 95% CI 1.022–1.494, p = 0.03), LAS-r (OR 0.723, 95% CI 0.556–0.940, p = 0.02), and LAS-ct (OR 1.518, 95% CI 1.225–1.880, p < 0.001) as independent predictors of AF development. The proposed model demonstrated high sensitivity and specificity with an adjusted classification threshold of 0.38 (AUC: 0.97, 95% CI 0.93–1.00, sensitivity 92% and specificity 92%, p < 0.001). Conclusions. The assessment of LA function using speckle-tracking echocardiography demonstrated significantly different values in the AF group among patients with congenital septal defects. This technique can therefore be implemented in routine clinical management. The key message. Atrial fibrillation development in adult patients with congenital septal defects and a left-to-right shunt is associated with the changes in left atrial function under conditions of an increased preload. Full article

Soil salinization, especially in arid and semi-arid regions, is one of the major abiotic stresses that affect plant growth. To mediate and boost plant tolerance against this abiotic stress, arbuscular mycorrhizal fungi (AMF) symbiosis is commonly thought to be an effective tool. So, the main purpose of this study was to estimate the role of AMF (applied as a consortium of Claroideoglomus etunicatum, Funneliformis mosseae, Rhizophagus fasciculatum, and R. intraradices species) symbiosis in mitigating deleterious salt stress effects on the growth parameters (shoot length (SL), root length (RL), shoot dry weight (SDW), root dry weight (RDW), root surface area (RSA), total root length (TRL), root volume (RV), root diameter (RD), number of nodes and leaves) of Cenchrus ciliaris L. plants through improved accumulations of photosynthetic pigments (chlorophyll _a, chlorophyll _b, total chlorophyll), proline and phenolic compounds. The results of this experiment revealed that the roots of C. ciliaris plants were colonized by AMF under all the applied salinity levels (0, 75, 150, 225, and 300 mM NaCl). However, the rate of colonization was negatively affected by increasing salinity as depicted by the varied colonization structures (mycelium, vesicles, arbuscules and spores) which were highest under non-saline conditions. This association of AMF induced an increase in the growth parameters of the plant which were reduced by salinity stress. The improved shoot/root indices are likely due to enhanced photosynthetic activities as the AMF-treated plants showed increased accumulation of pigments (chlorophyll _a, chlorophyll _b and total chlorophyll), under saline as well as non-saline conditions, compared to non-AMF (N-AMF) plants. Furthermore, the AMF-treated plants also exhibited enhanced accumulation of proline and phenolic compounds. These accumulated metabolites act as protective measures under salinity stress, hence explaining the improved photosynthetic and growth parameters of the plants. These results suggest that AMF could be a good tool for the restoration of salt-affected habitats. However, more research is needed to check the true efficacy of different AMF inoculants under field conditions. Full article

Background: The diagnosis and follow-up of cardiac involvement in Fabry disease constitutes an important challenge for clinicians caring for affected patients. Combining cardiac imaging with laboratory biomarkers appears most appropriate for longitudinal monitoring. Therefore, we examined the use of NT-proBNP and its association with imaging findings in patients with Fabry disease. Methods: We analysed cardiac MRI and echocardiography data, as well as laboratory results, from a single-centre prospective registry. Results: Repetitive follow-ups of 38 patients with Fabry disease, of whom 18 presented with left ventricular hypertrophy (LVH), revealed a correlation of NT-proBNP with left ventricular (LV) interventricular septal thickness, LV maximum wall thickness, LV and right ventricular (RV) mass index and trabecular mass in patients with LVH. Patients without LVH did not exhibit any tangible association between NT-proBNP and the mentioned parameters. Conversely, we could not detect an association of NT-proBNP with impairment of LV or RV ejection fraction or diastolic volume. Conclusions: NT-proBNP plays a pivotal role as a biomarker for cardiac involvement in patients with Fabry disease. Interestingly, in this specific population with mostly preserved ejection fraction, it seems to reflect ventricular hypertrophy rather than ventricular dysfunction or dilatation. While strong associations were found in hypertrophic patients, NT-proBNP’s prognostic value appears limited in non- or pre-hypertrophic stages. Full article

Background and Objectives: Although left ventricular excessive trabeculation (LVET) can cause heart failure, arrhythmia and thromboembolism, limited literature is available on the ECG characteristics of primary LVET with preserved left ventricular function (EF). We aimed to compare the ECG characteristics and cardiac MR (CMR) parameters of LVET individuals with preserved left ventricular EF to a control (C) group, to identify sex-specific differences, and to compare the genetic subgroups of LVET with each other and with a C population. Methods: In our study, we selected 69 LVET individuals (EF > 50%) without any comorbidities and compared them to 69 sex- and age-matched control subjects (42% females in both groups, p = 1.000; mean age LVET-vs-C: 38 ± 14 vs. 38 ± 14 years p = 0.814). We analyzed the pattern and notable parameters of the 12-lead ECG recordings. We determined the volumetric and functional parameters, as well as the muscle mass values of the left and right ventricles (LV, RV) based on the CMR recordings. Based on the genotype, three subgroups were established: pathogenic, variant of uncertain significance and benign. Results: In the LVET group, we found normal but elevated volumetric and muscle mass values and a decreased LV_EF, wider QRS, prolonged QTc, higher RV Sokolow index values and lower T wave amplitude compared to the C. When comparing MR and ECG parameters between genetic subgroups, only the QTc showed a significant difference. Over one-third of the LVET population had arrhythmic episodes and a positive family history. Conclusions: The subclinical morphological and ECG changes and the clinical background of the LVET group indicate the need for follow-up of this population, even with preserved EF. Full article

Jump dynamics in financial markets exhibit significant complexity, often resulting in increased probabilities of subsequent jumps, akin to earthquake aftershocks. This study aims to understand these complexities within a multifractal framework. To do this, we employed the high-frequency intraday data from six major cryptocurrencies (Bitcoin, Ethereum, Litecoin, Dashcoin, EOS, and Ripple) and six major forex markets (Euro, British pound, Canadian dollar, Australian dollar, Swiss franc, and Japanese yen) between 4 August 2019 and 4 October 2023, at 5 min intervals. We began by extracting daily jumps from realized volatility using a MinRV-based approach and then applying Multifractal Detrended Fluctuation Analysis (MFDFA) to those jumps to explore their multifractal characteristics. The results of the MFDFA—especially the fluctuation function, the varying Hurst exponent, and the Renyi exponent—confirm that all of these jump series exhibit significant multifractal properties. However, the range of the Hurst exponent values indicates that Dashcoin has the highest and Litecoin has the lowest multifractal strength. Moreover, all of the jump series show significant persistent behavior and a positive autocorrelation, indicating a higher probability of a positive/negative jump being followed by another positive/negative jump. Additionally, the findings of rolling-window MFDFA with a window length of 250 days reveal persistent behavior most of the time. These findings are useful for market participants, investors, and policymakers in developing portfolio diversification strategies and making important investment decisions, and they could enhance market efficiency and stability. Full article

Trajectory interception is a critical synchronization element in the transportation and manufacturing sectors using robotic platforms. This is usually performed by matching the position and velocity of a target object with the position and velocity of the robot interceptor. However, the synchronization task is exasperated by (i) the proper gain tuning of the controller, (ii) the dynamic response of the robotic platform, (iii) the velocity constraints in the actuators, and (iv) the trajectory profile exhibited by the moving object. This means that the interception time is not controlled, which is critical for energy optimization, resources, and production. This paper proposes a prescribed time trajectory interception algorithm for robot manipulators. The approach uses the finite-time convergence properties of sliding mode control combined with a terminal attractor based on a time base generator. The combined approach guarantees trajectory interception in a prescribed time with robust properties. Simulation studies are conducted using the first three degrees of freedom (DOFs) of a RV-M1 robot under single- and multi-object interception tasks. The results verify the effectiveness of the proposed methodology under different hyperparameter configurations. Full article

Pulmonary embolism (PE) is correlated with serious morbidity and mortality. Efforts have been made to establish and validate mortality predictive scores based mainly on clinical parameters. Patients with PE and traditional indices of echocardiographic right ventricular (RV) dysfunction or pressure overload have a higher probability of a worse outcome. During the last two decades, studies regarding the use of two-dimensional speckle-tracking echocardiography (2DSTE) and its derived indices in the setting of acute PE have been conducted. In this comprehensive review of the literature, we aimed to summarize these studies. Safe conclusions and comparisons among the reviewed studies are prone to statistical errors, mainly because the studies published were heterogenous in design, different 2DSTE-derived parameters were tested, and different clinical outcomes were used as endpoints. Nonetheless, RV strain indices and, more commonly, regional longitudinal strain of the RV free wall have shown a promising correlation with mortality, assisting in the differential diagnosis between PE and other acute or chronic disorders. Full article

Retroviruses integrate into the genomes of infected host cells to form proviruses, a genetic platform for stable viral gene expression. Epigenetic silencing can, however, hamper proviral transcriptional activity. As gammaretroviruses (γRVs) preferentially integrate into active promoter and enhancer sites, the high transcriptional activity of γRVs can be attributed to this integration preference. In addition, long terminal repeats (LTRs) of some γRVs were shown to act as potent promoters by themselves. Here, we investigate the capacity of different γRV LTRs to drive stable expression within a non-preferred epigenomic environment in the context of diverse retroviral vectors. We demonstrate that different γRV LTRs are either rapidly silenced or remain active for long periods of time with a predominantly active proviral population under normal and retargeted integration. As an alternative to the established γRV systems, the feline leukemia virus and koala retrovirus LTRs are able to drive stable, albeit intensity-diverse, transgene expression. Overall, we show that despite the occurrence of rapid silencing events, most γRV LTRs can drive stable expression outside of their preferred chromatin landscape after retrovirus integrations. Full article

Background and Objectives: Diagnosis of myocarditis remains a challenge in clinical practice; however, magnetic resonance imaging (CMRI) can ease the diagnostic approach by providing various parameters. The prevalence of right ventricular involvement in acute myocarditis is suggested to be more frequent than previously hypothesized. In this study, we sought to investigate subclinical RV involvement in patients with acute myocarditis and preserved RV ejection fraction (EF), using CMRI RV speckle-tracking imaging. Materials and Methods: CMRI of 27 patients with acute myocarditis (nine females, age 35.1 ± 12.2 y) was retrospectively analyzed. A control group consisting of CMRI images of 27 healthy individuals was included. Results: No significant differences were found regarding left ventricle (LV) and atrium dimensions. LV ejection fraction was significantly different between groups (56.6 ± 10.6 vs. 62.1 ± 2.6, p < 0.05). No significant differences were present between parameters used for conventional assessment of RV. However, RV strain absolute values were significantly lower in the acute myocarditis group in comparison with that of the control group (18.4 ± 5.4 vs. 21.8 ± 2.8, p = 0.018). Conclusions: Subclinical RV dysfunction detected by CMR-derived strain may be present in patients with acute myocarditis even with preserved RVEF. Full article

A focussed library of pyridyl and 2-hydroxyphenyl chalcones were synthesized and tested for growth inhibitory activity against Mycobacterium tuberculosis H37Rv, and normal and cancer breast cell lines. Pyridyl chalcones bearing lipophilic A-ring, e.g., dichloro-phenyl-(14), pyrene-1-yl (20)- and biphenyl-4-yl (21) moieties were found to be the most potent of the series inhibiting the growth of M. tuberculosis H37Rv with IC₉₀ values ranging from 8.9–28 µM. Aryl chalcones containing a 3-methoxyphenyl A-ring and either p-Br-phenyl (25) or p-Cl-phenyl (26) B-rings showed an IC₉₀ value of 28 µM. Aryl-chalcones were generally less toxic to HepG2 cells compared to pyridyl-chalcones. Dose-dependent antiproliferative activity against MDA468 cells was observed for trimethoxy-phenyl (16) and anthracene-9-yl (19) pyridyl-chalcones with IC₅₀ values of 0.7 and 0.3 µM, respectively. Docking studies revealed that chalone 20 was predicted to bind to the M. tuberculosis protein tyrosine phosphatases B (PtpB) with higher affinity compared to a previously reported PtpB inhibitor. Full article

Motivated by the comovement of realized volatilities (RVs) of agricultural commodity prices, we study whether multi-task forecasting algorithms improve the accuracy of out-of-sample forecasts of 15 agricultural commodities during the sample period from July 2015 to April 2023. We consider alternative multi-task stacking algorithms and variants of the multivariate Lasso estimator. We find evidence of in-sample predictability but scarce evidence that multi-task forecasting improves out-of-sample forecasts relative to a classic univariate heterogeneous autoregressive (HAR)-RV model. This lack of systematic evidence of out-of-sample forecasting gains is corroborated by extensive robustness checks, including an in-depth study of the quantiles of the distributions of the RVs and subsample periods that account for increases in the total spillovers among the RVs. We also study an extended model that features the RVs of energy commodities and precious metals, but our conclusions remain unaffected. Besides offering important lessons for future research, our results are interesting for financial market participants, who rely on accurate forecasts of RVs when solving portfolio optimization and derivatives pricing problems, and policymakers, who need accurate forecasts of RVs when designing policies to mitigate the potential adverse effects of a rise in the RVs of agricultural commodity prices and the concomitant economic and political uncertainty. Full article