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- ArticleChang CJ, Barr DB, Ryan PB, Panuwet P, Smarr MM, Liu K, Kannan K, Yakimavets V, Tan Y, Ly V, Marsit CJ, Jones DP, Corwin EJ, Dunlop AL, Liang D.Environ Int. 2022 01;158:106964.BACKGROUND: Prenatal exposures to per- and polyfluoroalkyl substances (PFAS) have been linked to reduced fetal growth. However, the detailed molecular mechanisms remain largely unknown. This study aims to investigate biological pathways and intermediate biomarkers underlying the association between serum PFAS and fetal growth using high-resolution metabolomics in a cohort of pregnant African American women in the Atlanta area, Georgia.
METHODS: Serum perfluorohexane sulfonic acid (PFHxS), perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and perfluorononanoic acid (PFNA) measurements and untargeted serum metabolomics profiling were conducted in 313 pregnant African American women at 8-14 weeks gestation. Multiple linear regression models were applied to assess the associations of PFAS with birth weight and small-for-gestational age (SGA) birth. A high-resolution metabolomics workflow including metabolome-wide association study, pathway enrichment analysis, and chemical annotation and confirmation with a meet-in-the-middle approach was performed to characterize the biological pathways and intermediate biomarkers of the PFAS-fetal growth relationship.
RESULTS: Each log2-unit increase in serum PFNA concentration was significantly associated with higher odds of SGA birth (OR = 1.32, 95% CI 1.07, 1.63); similar but borderline significant associations were found in PFOA (OR = 1.20, 95% CI 0.94, 1.49) with SGA. Among 25,516 metabolic features extracted from the serum samples, we successfully annotated and confirmed 10 overlapping metabolites associated with both PFAS and fetal growth endpoints, including glycine, taurine, uric acid, ferulic acid, 2-hexyl-3-phenyl-2-propenal, unsaturated fatty acid C18:1, androgenic hormone conjugate, parent bile acid, and bile acid-glycine conjugate. Also, we identified 21 overlapping metabolic pathways from pathway enrichment analyses. These overlapping metabolites and pathways were closely related to amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism perturbations.
CONCLUSION: In this cohort of pregnant African American women, higher serum concentrations of PFOA and PFNA were associated with reduced fetal growth. Perturbations of biological pathways involved in amino acid, lipid and fatty acid, bile acid, and androgenic hormone metabolism were associated with PFAS exposures and reduced fetal growth, and uric acid was shown to be a potential intermediate biomarker. Our results provide opportunities for future studies to develop early detection and intervention for PFAS-induced fetal growth restriction. - ArticleAuer A, Walther LM, Jendryczko D, Auer L, Wirtz PH.Psychoneuroendocrinology. 2024 Apr;162:106964.BACKGROUND & OBJECTIVES: Existing research indicates that not only own stress leads to physiological stress reactions, but also observing stress in others. So far, a standardized paradigm to reliably induce physiological stress contagion based on direct face-to-face stress observation compared to an active placebo-stress observing control condition is lacking. Here, we tested a standardized randomized placebo-controlled experimental paradigm to investigate physiological reactivity to direct stress observation and characterized the stress contagion response of the major endocrine stress systems, including full reactivity kinetics.
METHODS: Healthy young male participants were randomly assigned to (1) undergo an adapted version of the Trier Social Stress Test ("TSST participants", n = 20), (2) observe it ("stress observers", n = 36), or (3) observe a corresponding placebo-stress control condition ("placebo-stress observers", n = 30). We repeatedly assessed heart rate, salivary alpha-amylase, salivary cortisol, and salivary aldosterone.
RESULTS: Stress observers exhibited greater physiological reactivity to stress observation as compared to placebo-stress observers to placebo-stress observation in heart rate, salivary alpha-amylase, and cortisol (p's ≤ .027), but not in aldosterone. We observed similar reactivity kinetics in TSST participants and stress observers but less pronounced in stress observers.
DISCUSSION: Extending previous literature, our findings indicate that independent of secondary effects of the observation setting, direct observation of stress in other individuals induces activation of the hypothalamus-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis. Moreover, the physiological stress contagion response resembles the physiological reactivity to first-hand stress but is less pronounced. Potential implications of physiological stress contagion regarding health, cognition, or behavior, as well as modulating factors need to be further elucidated. - ArticleShi Y, Tang J, Zhi S, Jiang R, Huang Q, Sun L, Wang Z, Wu Y.Bioorg Chem. 2024 01;142:106964.Necroptosis is one of the modes of cell death, and its occurrence and development are associated with the development of numerous diseases. To prevent the progression of necroptosis, it is crucial to inhibit the phosphorylation of three proteins: receptor-interacting protein kinase 1 (RIP1), RIP3, and mixed lineage kinase domain-like protein (MLKL). Through virtual and experimental screening approaches, we have identified 8 small molecular inhibitors with potent antinecroptotic activity and binding affinity to RIP1. Among these compounds, SY-1 demonstrated the most remarkable antinecroptotic activity (EC50 = 105.6 ± 9.6 nM) and binding affinity (RIP1 Kd = 49 nM). It effectively blocked necroptosis and impeded the formation of necrosomes by inhibiting the phosphorylations of the RIP1/RIP3/MLKL pathway triggered by TSZ (TNFα, Smac mimetic and Z-VAD-fmk). Furthermore, SY-1 exhibited a protective effect against tumor necrosis factor (TNF)-induced hypothermia in mice and significantly improved the survival rate (100 %, 30 mg/kg) of mice with systemic inflammatory response syndrome (SIRS) in a dose-dependent manner. Pharmacokinetic parameters of SY-1 were also collected in vitro and in vivo. These results strongly suggest that SY-1 and its derivatives warrant further investigation for their potential therapeutic applications.
- ArticleLai A, Macdonald PM.Biophys Chem. 2023 04;295:106964.The effects of two cationic peptides on phospholipid lateral diffusion in binary mixtures of POPC with various anionic phospholipids were measured via 31P CODEX NMR. Large unilamellar vesicles composed of POPC/POPG (70/30 mol/mol), or POPC/DOPS (70/30 mol/mol), or POPC/TOCL (85/15 mol/mol), or POPC/DOPA (50/50 mol/mol) were exposed to either polylysine (pLYS, N = 134 monomers) or KL-14 (KKLL KKAKK LLKKL), a model amphipathic helical peptide, in an amount corresponding to 80% neutralization of the anionic phospholipid charge by the cationic lysine residues. In the absence of added peptide, phospholipid lateral diffusion coefficients (all measured at 10 °C) increased with increasing reduced temperature (T-Tm). The POPC/DOPA mixture was an exception to this generalization, in that lateral diffusion for both components was far slower than any other mixture investigated, an effect attributed to intermolecular hydrogen bonding. The addition of pLYS or KL-14 decreased lateral diffusion in the POPC/DOPS LUV, but had minimal effects in the POPC/POPG LUV, indicating that ease of access of the cationic peptide residues to the anionic phospholipid groups was important. Both cationic peptides produced the opposite effect in the POPC/DOPA case, in that lateral diffusion increased significantly in their presence, with KL-14 being most effective. This latter observation was interpreted in terms of the electrostatic / H-bond model proposed by Kooijman et al. [Journal of Biological Chemistry, 282:11356-11,364, 2007] to describe the mechanism of interaction between the phosphomonoester head group of PA and the tertiary amine of lysine.
- ArticleRouger-Gaudichon J, Cousin E, Jakobczyk H, Debaize L, Rio AG, Forestier A, Arnaud MP, Villacreces A, Praloran V, Jacamo R, Galibert MD, Troadec MB, Gandemer V.Leuk Res. 2022 12;123:106964.Acute lymphoblastic leukemias (ALL) are the most frequent cancer in children and derive most often from B-cell precursors. Current survival rates roughly reach 90% at 10 years from diagnosis. However, 15-20% of children still relapse with a significant risk of death. Our previous work showed that the transmembrane protein CD9 plays a major role in lymphoblasts migration into sanctuary sites, especially in testis, through the activation of RAC1 signaling upon blasts stimulation with C-X-C chemokine ligand 12 (CXCL12). Here, we identified common factors shared by the bone marrow and extramedullary niches which could upregulate CD9 expression and function. We found that low oxygen levels enhance CD9 expression both at mRNA and protein levels. We further determined that Hypoxia Inducible Factor 1α (HIF1α), the master transcription factor involved in hypoxia response, binds directly CD9 promoter and induce CD9 transcription. We also showed that CD9 protein is crucial for leukemic cell adhesion and migration at low oxygen levels, possibly through its action on RAC1 signaling. Mouse xenograft experiments indicate that HIF1α signaling pathway promotes ALL cells engraftment in a CD9-dependent manner. The present work increments our understanding of CD9 implication in ALL pathogenesis.
- ArticleLang J, Jeschke S, Müller RM, Herziger B, Bertsche T, Neininger MP, Bertsche A.Epilepsy Res. 2022 08;184:106964.PROBLEM: Many studies focus on knowledge and attitudes of unaffected people towards epilepsy and people with epilepsy (PWE). The perspective of PWE themselves is much less explored.
METHODS: We invited PWE in Germany to answer a questionnaire on their knowledge and attitudes towards epilepsy and PWE.
RESULTS: The questionnaire was completed by 230 PWE (median age: 40 years; min./max.: 19/83; 66 % female). Of PWE, 22 % thought that PWE are more helpful, and 10 % thought that PWE are friendlier than other people. Nevertheless, reservations about relationships and friendships with other PWE existed: of the participants, only 74 % would definitely go on a date with another PWE, and 90 % would definitely include another PWE they liked into their circle of friends. Swimming was judged as more dangerous for PWE than for healthy people by 71 % of PWE. Of PWE, 86 % correctly assumed it was not useful to hold a person having a seizure to the ground. Putting a solid object in the mouth was considered not useful by 85 % of PWE. Of PWE, 20 % would definitely administer an available emergency medication if another PWE had a seizure. For 67 % of PWE, certain preconditions should have to be fulfilled such as an available document with instructions. Of PWE, 11 % stated they would not administer an available emergency medication if another PWE had a seizure.
CONCLUSION: Although positive attitudes of PWE towards other PWE exist, we also found some reservations calling for psychosocial support. Most PWE had sufficient knowledge about risks of certain activities and about measures to be taken during a seizure. Nevertheless, a small group of PWE showed knowledge gaps. Thus, educational support still seems essential. - ArticleNguyen P, Le LK, Ananthapavan J, Gao L, Dunstan DW, Moodie M.Prev Med. 2022 03;156:106964.AIMS: METHODS: RESULTS: We identified nine articles (conducted in Australia (n = 5), Europe (n = 3) and China (n = 1)); three reported healthcare costs associated with excessive sedentary time, whilst six were economic evaluations of interventions targeting sedentary behaviour. Healthcare costs associated with excessive sedentary time as reported in cost of illness studies were substantial; however, none explored non-health sector costs. In contrast, all full economics evaluations adopted a societal perspective; however, costs included differed depending on the intervention context. One sedentary behaviour intervention in children was cost-saving. The five interventions targeting occupational sitting time of adults in office workplaces were cost-effective. Physical environmental changes such as sit-stand desks, active workstations etc., were the key cost driver.
CONCLUSIONS: Sedentary behaviour is likely associated with excess healthcare costs, although future research should also explore costs across other sectors. Cost-effectiveness evidence of sedentary behaviour reduction interventions in workplaces is limited but consistent. Key gaps relate to the economic credentials of interventions targeting children, and modelling of long-term health benefits of interventions. - ArticleLe TP, Iwamoto DK, Samee AA.Addict Behav. 2021 09;120:106964.While research suggests that sexism is associated with college women's hazardous alcohol use, few studies have investigated the psychological factors that underlie the association between sexism and alcohol-related problems. Thus, the purpose of the present study was to examine the direct and indirect effect of gender-relevant sociocultural factors, including sexism, self-objectification, and empowerment, on college women's alcohol-related problems through drinking to cope. 450 women attending a large public university completed a cross-sectional survey that assessed these gender-relevant sociocultural factors and alcohol-related outcomes. Controlling for Greek membership, perceived drinking norms, and alcohol use, sexism and empowerment were both directly associated with alcohol-related problems, while sexism, self-objectification, and empowerment were indirectly associated with alcohol-related problems through the mechanism of drinking to cope. The results of this study highlight the importance of taking into account gender-relevant risk factors for women's alcohol-related problems, as well as the role of psychological processes such as drinking to cope. Pathways for intervention on both individual and systemic levels are discussed.
- ArticleCannavale CN, Keye SA, Rosok L, Martell S, Holthaus TA, Reeser G, Raine LB, Mullen SP, Cohen NJ, Hillman CH, Hammond BR, Renzi-Hammond L, Khan NA.Contemp Clin Trials. 2022 11;122:106964.Lutein and zeaxanthin (L + Z) are carotenoids that accumulate in neural tissue and potentially confer benefits to cognition. Whereas cross-sectional studies have revealed positive associations between macular carotenoids (MC) and cognition, no studies have investigated whether L + Z supplementation impacts MC and cognition in childhood. Accordingly, the Integrated Childhood Ocular Nutrition Study aims to investigate the impact of L + Z supplementation over 9-months on academic abilities, attentional control, memory, and MC among preadolescent children. Children 8-10 years (N = 288) will enroll in a 9-month double-blind, placebo-controlled, randomized trial. The study is registered and approved as a clinical trial on the U.S. National Library of Medicine http://ClinicalTrials.gov registry (NCT05177679). Participants will be randomized into an active (10 mg lutein+2 mg zeaxanthin) or waitlist placebo-controlled group. Primary outcomes include hippocampal-dependent memory, attentional inhibition, and academic achievement using a spatial reconstruction task, an Eriksen flanker task, and the Kaufman Test of Academic and Educational Achievement 3rd edition, respectively. Secondary outcomes include event-related brain potentials of attentional resource allocation and information processing speed (i.e., P3/P300 amplitude and latency) recorded during the flanker task. Macular pigment optical density (MPOD) will be assessed using heterochromatic flicker photometry. Cognitive assessments will be completed prior to and after completion of the supplementation period. MPOD will be quantified prior to, at the mid-point of (4-5 months), and after (9 months) the supplementation period. It is hypothesized that L + Z supplementation will improve cognition and academic achievement. Further, benefits for cognition and achievement are anticipated to be mediated by increases in MC among treatment group participants.
- ArticleJia X, Zhang S, Tang Z, Xue K, Chen J, Manickam S, Lin Z, Sun X, Zhu Z.Ultrason Sonochem. 2024 Aug;108:106964.Hydrodynamic cavitation (HC) has emerged as a promising technology for water disinfection. Interestingly, when subjected to specific cavitation pressures, jet pump cavitation reactors (JPCRs) exhibit effective water treatment capabilities. This study investigated the cavitation flow and vorticty transport in a JPCR with various area ratios by utilizing computational fluid dynamics. The results reveal that cavitation is more likely to occur within the JPCR as the area ratio becomes smaller. While as the area ratio decreases, the limit flow ratio also decreases, leading to a reduced operational range for the JPCR. During the cavitation inception stage, only a few bubbles with limited travel distances are generated at the throat inlet. A stable cavitation layer developed between the throat and downstream wall during the limited cavitation stage. In this phase, the primary flow carried the bubbles towards the outlet. In addition, it was found that the vortex stretching, compression expansion, and baroclinic torque terms primarily influence the vorticity transport equation in this context. This work may provide a reference value to the design of JPCRs for water treatment.
- ArticleHuang J, Zhu T, Rong R, You M, Ji D, Li H.Int Immunopharmacol. 2020 Nov;88:106964.Mitochondria play a critical role in triggering immune response. Although recent evidence indicates that autophagy/mitophagy can suppress inflammation via regulation of mitochondrial homeostasis, limited information is available regarding physiological regulation of mitochondria-controlled inflammation. In this study, we investigated FUN14 domain containing 1 (FUNDC1)-mediated mitophagy in the regulation of interleukin-1β (IL-1β) in vitro and in vivo, wild-type FUNDC1 and its mitophagy defective Y18A/L21A mutant were analyzed in bone marrow-derived macrophages (BMDMs)for their effects on IL-1β expression and mitochondrial damage. The current study identified that LPS plus nigericin stimulation induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation, which was detected by IL-1β expression. Moreover, FUNDC1-mediated mitophagy promoted the alleviation of intracellular reactive oxygen species (ROS). IL-1β production was suppressed by the overexpression of wild-type FUNDC1, but not the Y18A/L21A mutant. Our results suggest that FUNDC1 suppresses LPS plus nigericin-mediated IL-1β production through its regulatory effect on mitophagy, which will greatly promote the understanding of mitophagy-related protein in the regulation of immune response.
- ArticleGayathri SL, Bhakat M, Mohanty TK.Microb Pathog. 2024 Nov;196:106964.Mastitis is a global concern in the dairy sector, demanding innovative solutions for effective management for quality lifetime milk production. In this study, infrared thermography (IRT) as a non-invasive technology was integrated into routine farm activities for continuous health monitoring of animals. For 30 days, we systematically monitored the udder health status in 40 Sahiwal cows (160 quarters), employing IRT along with the California Mastitis Test (CMT). We also assessed somatic cell count (SCC), microbial identification, and milk quality parameters of representative samples. The thermal imaging data was analyzed, considering both backward propagation from the 0th day to the -10th day and forward propagation from the 0th day to the +10th day. Our findings revealed that on the 0th day, the mean temperatures of the udder surface skin temperature (USST) and teat skin surface temperature (TSST) exhibited differences (p < 0.05) between the quarters affected by sub-clinical mastitis (SCM) and clinical mastitis (CM) in comparison to the healthy quarters, with the highest degree of difference observed. The observed temperature differences between CM and SCM quarters compared to healthy ranged from 1.8 to 3.62 °C and 0.98 to 3.23 °C for USST, and from 1.68 to 3.16 °C and 0.56 to 2.32 °C for TSST, respectively. Furthermore, our observations indicated that both udder and teat quarters responded differently to mastitis. A temperature rise of 1.37 °C in SCM quarters and 1.75 °C in CM quarters was observed between the -10th and -8th day relative to day 0, with the increase being more pronounced in the morning hours. Also, a notable temperature surge occurred during the -2nd and -1st days relative to the 0th day. The log10SCC values and milk quality parameters significantly differed (p < 0.05) between mastitis-affected and healthy samples. In addition, Staphylococcus spp. was identified as the predominant mastitis-causing pathogen in the bacteriological identification conducted in this study. Therefore, IRT efficiently assesses the initiation point of udder infection in Sahiwal cows, aiding in effective udder health management.
- ArticleRicci P, Sion L, Capezzuto F, Cipriano G, D'Onghia G, Libralato S, Maiorano P, Tursi A, Carlucci R.Data Brief. 2021 Jun;36:106964.The ecological roles of the species in the food web are studied through the Ecopath with Ecosim modelling approach. In this modelling approach, the food web is described by means of functional groups, each representing a species, a life stage of a species, or a group of species with similar trophic, ecological and physiological features. Links between the groups are formally described by a set of linear equations, informed with ecological and fishing data. Here, the data input collected to implement 3 Ecopath models in the Northern Ionian Sea (Central Mediterranean Sea) from 1995 to 2015 are reported. This dataset applied to study the ecological roles of the demersal Chondrichthyes in the study area could be useful to explore different fishing management scenarios. A large dataset of over 300 taxa is shown detailing the ecological inputs, such as Biomass (kg km-2), Production and Consumption rates (y-1), Diet information (weight in %), and fishing data represented by Landings and Discards (t km-2 y-1). In particular, the fishery data described the catches of trawls, longlines, passive nets, other gears and purse seine. In addition, a description of the aggregation method of the species is shown.
- ArticleXu M, Liu X, Zhou X, Qin Y, Yang L, Wen S, Qiu Y, Chen S, Tang R, Guo Y, Liu M, Sun Y.Pharmacol Res. 2023 Nov;197:106964.Hypoxia is a key feature of tumor microenvironment that contributes to the development of breast cancer stem cells (BCSCs) with strong self-renewal properties. However, the specific mechanism underlying hypoxia in BCSC induction is not completely understood. Herein, we provide evidence that a novel hypoxia-specific circSTT3A is significantly upregulated in clinical breast cancer (BC) tissues, and is closely related to the clinical stage and poor prognosis of patients with BC. The study revealed that hypoxia-inducible factor 1 alpha (HIF1α)-regulated circSTT3A has a remarkable effect on mammosphere formation in breast cancer cells. Mechanistically, circSTT3A directly interacts with nucleotide-binding domain of heat shock protein 70 (HSP70), thereby facilitating the recruitment of phosphoglycerate kinase 1 (PGK1) via its substrate-binding domain, which reduces the ubiquitination and increases the stability of PGK1. The enhanced levels of PGK1 catalyze 1,3-diphosphoglycerate (1,3-BPG) into 3-phosphoglycerate (3-PG) leading to 3-PG accumulation and increased serine synthesis, S-adenosylmethionine (SAM) accumulation, and trimethylation of histone H3 lysine 4 (H3K4me3). The activation of the H3K4me3 contributes to BCSCs by increasing the transcriptional level of stemness-related factors. Especially, our work reveals that either loss of circSTT3A or PGK1 substantially suppresses tumor initiation and tumor growth, which dramatically increases the sensitivity of tumors to doxorubicin (DOX) in mice. Injection of PGK1-silenced spheroids with 3-PG can significantly reverse tumor initiation and growth in mice, thereby increasing tumor resistance to DOX. In conclusion, our study sheds light on the functional role of hypoxia in the maintenance of BCSCs via circSTT3A/HSP70/PGK1-mediated serine synthesis, which provides new insights into metabolic reprogramming, tumor initiation and growth. Our findings suggest that targeting circSTT3A alone or in combination with chemotherapy has potential clinical value for BC management.
- ArticleLi D, Zhang C, Zhang S, Wang H, Chen W, Zhang C.Ultrasonics. 2023 Jul;132:106964.Terahertz elastic waves travelling in piezoelectric semiconductors (PSs) with the deformation-polarization-carrier coupling have a huge potential application in elastic wave-based devices. To reveal wave propagation characteristics of terahertz elastic waves in rod-like PS structures, we present three typical rod models based on the Hamilton principle and the linearization of the nonlinear current, which are extensions of the classical, Love, and Mindlin-Herrmann rod models for elastic media to those for PS materials. Using the derived equations, the analytical dispersion relations of the elastic longitudinal waves propagating in an n-type PS rod are obtained, which can be reduced to those for piezoelectric and elastic rods by sequentially dropping the corresponding electron- and piezoelectricity-related terms. The Mindlin-Herrmann rod model is more accurate for analysis of terahertz elastic longitudinal wave in rod-like PS structures. The effects of the interaction between the piezoelectricity and semiconducting properties on the dispersion behaviors of terahertz elastic longitudinal waves are investigated in detail. Numerical results show that both phase and group velocities have a 50%-60% reduction in the terahertz range in comparison with those in the low frequency range, and the effective tuning range of the initial electron concentration is different for longitudinal waves with different frequencies. It lays the theoretical foundations for the design of terahertz elastic wave-based devices.
- ArticlePeltola ME, Trébuchon A, Lagarde S, Scavarda D, Carron R, Metsähonkala L, Lauronen L, Lépine A, Villeneuve N, Bartolomei F.Epilepsy Behav. 2020 04;105:106964.PURPOSE: In this study, we aimed to improve our knowledge of insular epilepsy by studying anatomoelectroclinical correlations in pure insular-onset epilepsy and characterizing differences between anterior and posterior insular-onset seizures.
METHODS: Patients in whom seizure-onset zone was confined to the insula and peri-insular sulcus were selected from 301 consecutive presurgical stereo-electroencephalography (EEG) recordings performed between years 2010 and 2017 in two epilepsy centers. Ictal-onset zone in stereo-EEG was delineated visually and quantitatively using epileptogenic index method. Seizure characteristics were reanalyzed, and anatomoelectroclinical correlations were assessed. Characteristics of posterior and anterior insular-onset seizures were compared.
RESULTS: Eleven insular cases were identified, five of them with an anterior insular seizure onset and six with a posterior one. Nonpainful somatosensory symptoms and autonomic symptoms were the most common symptoms (73% of patients) followed by speech-related symptoms (55%) and ipsilateral eye blinking (45%). Six patients had seizures restricted to somatosensory or viscerosensory symptoms. In all patients, seizures progressed to motor symptoms. Somatosensory symptoms did not differentiate anterior from posterior insular seizures. However, hyperkinetic signs, speech modifications, and viscerosensory symptoms were related to an anterior insular seizure-onset zone. Pain, asymmetric tonic, focal clonic, and tonic symptoms were more frequent in patients with a posterior insular seizure onset.
CONCLUSIONS: Seizure semiology is heterogeneous in pure insular-onset epilepsy. Differences between the anterior and posterior insular seizures reflect the functional organization of the insula. Particularly, the different types of motor symptoms may help to distinguish anterior from posterior insular seizure onset. - ArticleNajafi A, Jolly MK, George JT.iScience. 2023 Jul 21;26(7):106964.The Epithelial-to-Mesenchymal Transition (EMT) is a hallmark of cancer metastasis and morbidity. EMT is a non-binary process, and cells can be stably arrested en route to EMT in an intermediate hybrid state associated with enhanced tumor aggressiveness and worse patient outcomes. Understanding EMT progression in detail will provide fundamental insights into the mechanisms underlying metastasis. Despite increasingly available single-cell RNA sequencing (scRNA-seq) data that enable in-depth analyses of EMT at the single-cell resolution, current inferential approaches are limited to bulk microarray data. There is thus a great need for computational frameworks to systematically infer and predict the timing and distribution of EMT-related states at single-cell resolution. Here, we develop a computational framework for reliable inference and prediction of EMT-related trajectories from scRNA-seq data. Our model can be utilized across a variety of applications to predict the timing and distribution of EMT from single-cell sequencing data.
- ArticleAi H, Song D, Wang X.Comput Biol Med. 2023 06;159:106964.BACKGROUND: Intratumor heterogeneity (ITH) plays a crucial role in tumor progression, relapse, immune evasion, and drug resistance. Existing ITH quantification methods based on a single molecular level are inadequate to capture ITH evolving from genotype to phenotype.
METHODS: We designed a set of information entropy (IE)-based algorithms for quantifying ITH at the genome (somatic copy number alterations and mutations), mRNA, microRNA (miRNA), long non-coding RNA (lncRNA), protein, and epigenome level, respectively. We evaluated the performance of these algorithms by analyzing the correlations between their ITH scores and ITH-associated molecular and clinical features in 33 TCGA cancer types. Moreover, we evaluated the correlations between the ITH measures at different molecular levels by Spearman correlation and clustering analysis.
RESULTS: The IE-based ITH measures had significant correlations with unfavorable prognosis, tumor progression, genomic instability, antitumor immunosuppression, and drug resistance. The mRNA ITH showed stronger correlations with the miRNA, lncRNA, and epigenome ITH than with the genome ITH, supporting the regulatory relationships of miRNA, lncRNA, and DNA methylation towards mRNA. The protein-level ITH displayed stronger correlations with the transcriptome-level ITH than with the genome-level ITH, supporting the central dogma of molecular biology. Clustering analysis based on the ITH scores identified four subtypes of pan-cancer showing significantly different prognosis. Finally, the ITH integrating the seven ITH measures displayed more prominent properties of ITH than that at a single level.
CONCLUSIONS: This analysis provides landscapes of ITH at various molecular levels. Combining the ITH observation from different molecule levels will improve personalized management for cancer patients. - ArticleShoman N, Solomonova E, Akimov A, Rylkova O, Mansurova I.Aquat Toxicol. 2024 Jul;272:106964.According to the results of the experimental study, the main regularities of changes in morphological, structural-functional and fluorescent indices of P. cordatum were established when zinc oxide nanoparticles ZnO NPs (0.3-6.4 mg L-1) and Zn in form of salt (0.09-0.4 mg L-1) were added to the medium. The studied pollutants have cytotoxic (growth inhibition, development of oxidative stress, destruction of cytoplasmic organelles, disorganization of mitochondria) and genotoxic (changes in the morphology of nuclei, chromatin condensation) effects on microalgae, affecting almost all aspects of cell functioning. Despite the similar mechanism of action of zinc sulfate and ZnO NPs on P. cordatum cells, the negative effect of ZnO NPs is also due to the inhibition of photosynthetic activity of cells (significant decrease in the maximum quantum yield of photosynthesis and electron transport rate), reduction of chlorophyll concentration from 3.5 to 1.8 pg cell-1, as well as mechanical effect on cells: deformation and damage of cell membranes, aggregation of NPs on the cell surface. Apoptosis-like signs of cell death upon exposure to zinc sulfate and ZnO NPs were identified by flow cytometry and laser scanning confocal microscopy methods: changes in cell morphology, cytoplasm retraction, development of oxidative stress, deformation of nuclei, and disorganization of mitochondria. It was shown that the first signs of cell apoptosis appear at 0.02 mg L-1 Zn and 0.6 mg L-1 ZnO NPs after 72 h of exposure. At higher concentrations of pollutants, a dose-dependent decrease in algal enzymatic activity (up to 5 times relative to control) and mitochondrial membrane potential (up to 4 times relative to control), and an increase in the production of reactive oxygen species (up to 4-5 times relative to control) were observed. The results of the presented study contribute to the disclosure of fundamental mechanisms of toxic effects of pollutants and prediction of ways of phototrophic microorganisms reaction to this impact.
- ArticleTsabaris C, Eleftheriou G, Tsiaras K, Triantafyllou G.J Environ Radioact. 2022 Oct;251-252:106964.A coupled hydrodynamic/lagrangian particle drift model was applied to obtain the distribution of key radionuclides that are dispersed at the surface water (upper 100 m) of Eastern Mediterranean Sea, in case of an accident of Nuclear Power Plant at Akkuyu. The model was applied to simulate the dispersion of key artificial radionuclide concentration, in case of a hypothetical accident to assess issues related to sea health and potential hazards. The released radionuclide was found to have a favorable westward direction, following the prevailing currents. The variability of the predicted pattern is interpreted according to the near surface circulation patterns in the study area. The dispersion of key radionuclides (137Cs, 238Pu and 131I) was studied in a spatial and temporal manner at the neighboring coasts of the location of the NPP. Furthermore, the fate of the plume was predicted for each month after the accident date close to the areas of Akkuyu, namely Cyprus, Rhodes Island, North Cretan coast, Cyclades and Syrian Coast. The annual study revealed that the radioactive plume is present with high concentration (maximum values of 1200 Bq m-3 for the long lived isotopes and 600 Bq m-3 for 131I) in the location of the plant for short period of time (1-2 months), while the other areas are affected during the whole year with low level of activity concentration (20-50 Bqm-3). The ERICA Assessment Tool was also used to evaluate dose rates to common marine biota at the studied areas.