bluuebunny/crossref_metadata_2025 huggingface dataset:
Algerian Workers’ Exposure to Mycotoxins—A Biomonitoring Study
Authors: Mendes Marta I. , Cunha Sara C. , Rebai Iméne , Fernandes José O.
Published: August 2023

Mycotoxins, produced by fungi as secondary metabolites, have the potential to induce both short-term and long-term toxic consequences in animals and humans. The present study aimed to determine multi-mycotoxin levels in Algerian workers using urine as the target. A method based on a QuEChERS (quick, easy, cheap, effective, rugged, and safe) extraction procedure followed by liquid chromatography–tandem mass spectrometry (LC-MS/MS) was optimized and validated for the determination of eleven mycotoxins in 96 urine samples. Different sorbents were tested to be used in the dispersive solid-phase extraction (d-SPE) cleanup step of QuEChERS. The final method was fit-for-purpose and showed good analytical performance in terms of specificity, linearity, and precision. All samples contained at least two mycotoxins, and toxin-2 (T-2) was the most common, being found in 92.7% of the samples, followed by zearalenone (ZEN) in 90.6% of positive samples, and ochratoxin A (OTA) in 86.4%. T-2 levels ranged from 0.3 μg/L to 36.3 μg/L, while OTA ranged from 0.3 μg/L to 3.5 μg/L, and ZEN ranged from 7.6 μg/L to 126.8 μg/L. This was the first mycotoxin biomonitoring study carried out in the Algerian population. The findings highlight the need for accurate data for better risk assessment and for the development of better regulation to manage mycotoxin contamination in this country.
Flourishing and Self-Control in Adolescence: The Role of Perceived Parenting
Authors: Mirandi Maria , Lis Adriana , Mazzeschi Claudia , Li Jian-Bin , Salmi Luciana Pagano , Delvecchio Elisa
Published: August 2023

Self-control is the ability to control thoughts, emotions, and impulses to pursuit of long-term goals. Adolescents with high self-control experience higher flourishing levels. The latter refers to the fulfillment of needs for competence, relationship, and self-acceptance, as well as the possession of psychological capital such as flow and commitment. High levels of self-control also seem to be linked to a positive relationship with parents, which is crucial in adolescent flourishing. However, few studies investigated the association between flourishing, self-control, and perceived parenting in adolescence. The aim of this study was to investigate how the ability to exert self-control and the need to perceive and preserve a responsive relationship with parents would facilitate adolescents’ experience of higher flourishing levels. The relationships among self-control, adolescents’ perception of some paternal and maternal dimensions (closeness, communication, and parents’ peer approval), and flourishing were analyzed in a sample of 335 Italian adolescents. Self-control was positively correlated with flourishing and the adolescent’s perception of maternal and paternal dimensions. The PROCESS model showed that perceived maternal and paternal dimensions mediate the relationship between self-control and flourishing. These findings show the importance of self-control and parenting dimensions in promoting flourishing during adolescence.
Meaningful Work, Well-Being, and Health: Enacting a Eudaimonic Vision
Authors: Soren Andrew , Ryff Carol D.
Published: August 2023

Work is one of the most enduring and consequential life domains regarding how meaning and purpose impact health and well-being. This review first examines scientific findings from the MIDUS (Midlife in the U.S.) national longitudinal study that have linked work to well-being and health. Most have focused on adverse work or work conditions as influences on poor health, with a few recent findings investigating links to purpose and other aspects of eudaimonic well-being. Organizational scholarship is then selectively reviewed to show how meaningful work is often linked to motivation, performance, and commitment. Paradoxically, meaning can also lead to the exploitation and erosion of health and well-being when managed without regard for decent working conditions. Recent workplace phenomena known as the Great Resignation and Quiet Quitting underscore the societal consequences of work without meaning or adequate working conditions. Both the scientific and organizational literature are enriched by a vision of meaningful work rooted in Aristotle’s writings about virtue, ethics, and the realization of potential. Evidence-based practices tied to these eudaimonic ideals are examined at multiple levels, including the societal context (public policy), organizational conditions (culture, human resource practices, leadership), and individual strategies to find meaning, engagement, and fulfillment in work. A concluding section highlights strengths and omissions in the scientific and organizational literature and, going forward, calls for greater interplay among researchers, practitioners, and policymakers in enacting eudaimonic ideals.
Race, Poverty, and Foster Care Placement in the United States: Longitudinal and Cross-Sectional Perspectives
Authors: Wulczyn Fred , Zhou Xiaomeng , McClanahan Jamie , Huhr Scott , Hislop Kristen , Moore Forrest , Rhodes Emily
Published: August 2023

Although the connections between race, poverty, and foster care placement seem obvious, the link has not in fact been studied extensively. To address this gap, we view poverty and placement through longitudinal and cross-sectional lenses to more accurately capture how changes in poverty rates relate to changes in placement frequency. The longitudinal study examines the relationship between poverty rate changes and changes in the placement of Black and White children between 2000 and 2015. The cross-sectional study extends the longitudinal analysis by using a richer measure of socio-ecological diversity and more recent foster care data. Using Poisson regression models, we assess the extent to which changes in race-differentiated child poverty rates are correlated with Black and White child placement frequencies and placement disparities. Regardless of whether one looks longitudinally or cross-sectionally, we find that Black children are placed in foster care more often than White children. Higher White child poverty rates are associated with substantially reduced placement differences; however, higher Black child poverty rates are associated with relatively small changes in placement disparity. Black and White child placement rates are more similar in counties with the fewest socio-ecological assets.
Unraveling Depressive Symptomatology and Risk Factors in a Changing World
Authors: Sousa Rute Dinis , Henriques Ana Rita , Caldas de Almeida José , Canhão Helena , Rodrigues Ana Maria
Published: August 2023

Background: This study aimed to examine the prevalence and factors associated with symptoms of depression during the third wave of the COVID-19 pandemic. Methods: A representative sample of Portuguese adults was included in this populational survey, conducted between 25 March and 31 July 2021, with participants completing a structured questionnaire via phone interview. The symptoms of depression were measured using the Portuguese version of the Hospital Anxiety and Depression Scale (HADS). Multivariate logistic regression analyses were used to examine the association between sociodemographic, health, and lifestyle factors and depression levels (normal, mild, or moderate/severe). Results: The estimated prevalence of depression symptoms among participants was 24%. Participants who were women, were in older age groups, had multimorbidity, lived in isolated Portuguese regions such as islands and Alentejo, and were retired or unemployed more frequently reported depression symptoms. Economic hardship was also found to be associated with an increased frequency of mild or moderate-to-severe depression. In contrast, higher levels of education, regular alcohol intake, and regular exercise were associated with a lower frequency of depression symptoms. Conclusions: These findings highlight that during the third wave of the COVID-19 pandemic, a high proportion of Portuguese adults reported depression symptoms, particularly the COVID-19-vulnerable strata such seniors, patients with multimorbidity, and people in economic hardship. On the other hand, citizens who performed regular physical exercise reported lower depressive symptomology. Our work contributes to improving the planning of mental health promotion after the COVID-19 pandemic and future emergencies.
Differences in the Quality of Life of Patients Recently Diagnosed with Crohn’s Disease and Ulcerative Colitis
Authors: Bernabéu Juan Purificación , Cabezos Sirvent Paula , Sempere Robles Laura , van-der Hofstadt Gomis Ana , Rodríguez Marín Jesús , van-der Hofstadt Román Carlos J.
Published: August 2023

Inflammatory bowel diseases (IBD) are chronic diseases, encompassing Crohn’s disease (CD) and ulcerative colitis (UC). An IBD diagnosis has an impact on the quality of life of patients; this impact can be different according to the type of disease. Objective: This study aimed to analyze the differences in the impact on quality of life in the early stages after diagnosis in patients with CD and UC. Patients and methods: This was an observational, multi-center, and cross-sectional study, with the participation of 156 patients recently diagnosed with IBD (<6 months) from 4 hospitals from the Health Council of the Valencian Community. The patients were assessed through the use of the Inflammatory Bowel Disease Questionnaire (IBDQ-32), which measures the quality of life when living with IBD. Results: The sample was composed of 80 patients with CD (51.0%) and 76 patients with a UC diagnosis. The mean age was 42.3 ± 16.2. The CD patients were more affected (42.5%) in their general quality of life than the UC patients (17.1%) (p = 0.001). In the dimensions of the IBDQ-32, the patients with CD showed significant differences in the systemic, emotional, and social spheres. The bowel dimension scores were similar in both groups. Conclusions: The patients who were recently diagnosed with CD were more affected regarding their quality of life as compared to those who were diagnosed with UC. Psychological care must be considered to mitigate the impact of an IBD diagnosis.
Molecular Changes in the Brain of the Wintering Calidris pusilla in the Mangroves of the Amazon River Estuary
Authors: Pereira Patrick Douglas Corrêa , Henrique Ediely Pereira , da Costa Emanuel Ramos , Falcão Anderson de Jesus , de Melo Mauro André Damasceno , Schneider Maria Paula Cruz , Burbano Rommel Mario Rodriguez , Diniz Daniel Guerreiro , Magalhães Nara Gyzely de Morais , Sherry David Francis , Diniz Cristovam Wanderley Picanço , Guerreiro-Diniz Cristovam
Published: August 2023

Migrant birds prepare differently to fly north for breeding in the spring and for the flight to lower latitudes during autumn, avoiding the cold and food shortages of the Northern Hemisphere’s harsh winter. The molecular events associated with these fundamental stages in the life history of migrants include the differential gene expression in different tissues. Semipalmated sandpipers (Calidris pusilla) are Arctic-breeding shorebirds that migrate to the coast of South America during the non-breeding season. In a previous study, we demonstrated that between the beginning and the end of the wintering period, substantial glial changes and neurogenesis occur in the brain of C. pusilla. These changes follow the epic journey of the autumn migration when a 5-day non-stop transatlantic flight towards the coast of South America and the subsequent preparation for the long-distance flight of the spring migration takes place. Here, we tested the hypothesis that the differential gene expressions observed in the brains of individuals captured in the autumn and spring windows are consistent with the previously described cellular changes. We searched for differential gene expressions in the brain of the semipalmated sandpiper, of recently arrived birds (RA) from the autumnal migration, and that of individuals in the premigratory period (PM) in the spring. All individuals were collected in the tropical coastal of northern Brazil in the mangrove region of the Amazon River estuary. We generated a de novo neurotranscriptome for C. pusilla individuals and compared the gene expressions across libraries. To that end, we mapped an RNA-Seq that reads to the C. pusilla neurotranscriptome in four brain samples of each group and found that the differential gene expressions in newly arrived and premigratory birds were related with neurogenesis, metabolic pathways (ketone body biosynthetic and the catabolic and lipid biosynthetic processes), and glial changes (astrocyte-dopaminergic neuron signaling, astrocyte differentiation, astrocyte cell migration, and astrocyte activation involved in immune response), as well as genes related to the immune response to virus infections (Type I Interferons), inflammatory cytokines (IL-6, IL-1β, TNF, and NF-κB), NLRP3 inflammasome, anti-inflammatory cytokines (IL-10), and cell death pathways (pyroptosis- and caspase-related changes).
A Comparative Multi-Frequency EPR Study of Dipolar Interaction in Tetra-Heme Cytochromes
Authors: Hagen Wilfred R. , Louro Ricardo O.
Published: August 2023

Distances between Fe ions in multiheme cytochromes are sufficiently short to make the intramolecular dipole-dipole interaction between hemes probable. In the analysis of EPR data from cytochromes, this interaction has thus far been ignored under the assumption that spectra are the simple sum of non-interacting components. Here, we use a recently developed low-frequency broadband EPR spectrometer to establish the extent of dipolar interaction in the example cytochromes, characterize its spectral signatures, and identify present limitations in the analysis. Broadband EPR spectra of Shewanella oneidensis MR-1 small tetraheme cytochrome (STC) have been collected over the frequency range of 0.45 to 13.11 GHz, and they have been compared to similar data from Desulfovibrio vulgaris Hildenborough cytochrome c3. The two cases are representative examples of two very different heme topologies and corresponding electron-transfer properties in tetraheme proteins. While in cytochrome c3, the six Fe-Fe distances can be sorted into two well-separated groups, those in STC are diffuse. Since the onset of dipolar interaction between Fe-Fe pairs is already observed in the X-band, the g values are determined in the simulation of the 13.11 GHz spectrum. Low-frequency spectra are analyzed with the inclusion of dipolar interaction based on available structural data on mutual distances and orientations between all hemes. In this procedure, all 24 possible assignments of individual heme spectra to heme topologies are sampled. The 24 configurations can be reduced to a few, but inspection falls short of a unique assignment, due to a remaining lack of understanding of the fine details of these complex spectra. In general, the EPR analysis suggests the four-heme system in c3 to be more rigid than that in STC, which is proposed to be related to different physiological roles in electron transfer.
Platelet-Derived Extracellular Vesicles as Lipid Carriers in Severe Allergic Inflammation
Authors: Couto-Rodriguez Alba , Villaseñor Alma , Pablo-Torres Carmela , Obeso David , Rey-Stolle María Fernanda , Peinado Héctor , Bueno José Luis , Reaño-Martos Mar , Iglesias Cadarso Alfredo , Gomez-Casado Cristina , Barbas Coral , Barber Domingo , Escribese María M. , Izquierdo Elena
Published: August 2023

The resolution of inflammation is a complex process that is critical for removing inflammatory cells and restoring tissue function. The dysregulation of these mechanisms leads to chronic inflammatory disorders. Platelets, essential cells for preserving homeostasis, are thought to play a role in inflammation as they are a source of immunomodulatory factors. Our aim was to identify key metabolites carried by platelet-derived extracellular vesicles (PL-EVs) in a model of allergic inflammation. PL-EVs were isolated by serial ultracentrifugation using platelet-rich plasma samples obtained from platelet apheresis from severely (n = 6) and mildly (n = 6) allergic patients and non-allergic individuals used as controls (n = 8). PL-EVs were analysed by a multiplatform approach using liquid and gas chromatography coupled to mass spectrometry (LC-MS and GC-MS, respectively). PL-EVs obtained from severely and mildly allergic patients and control individuals presented comparable particle concentrations and sizes with similar protein concentrations. Strikingly, PL-EVs differed in their lipid and metabolic content according to the severity of inflammation. L-carnitine, ceramide (Cer (d18:0/24:0)), and several triglycerides, all of which seem to be involved in apoptosis and regulatory T functions, were higher in PL-EVs from patients with mild allergic inflammation than in those with severe inflammation. In contrast, PL-EVs obtained from patients with severe allergic inflammation showed an alteration in the arachidonic acid pathway. This study demonstrates that PL-EVs carry specific lipids and metabolites according to the degree of inflammation in allergic patients and propose novel perspectives for characterising the progression of allergic inflammation.
Practical Use of Immortalized Cells in Medicine: Current Advances and Future Perspectives
Authors: Voloshin Nikita , Tyurin-Kuzmin Pyotr , Karagyaur Maxim , Akopyan Zhanna , Kulebyakin Konstantin
Published: August 2023

In modern science, immortalized cells are not only a convenient tool in fundamental research, but they are also increasingly used in practical medicine. This happens due to their advantages compared to the primary cells, such as the possibility to produce larger amounts of cells and to use them for longer periods of time, the convenience of genetic modification, the absence of donor-to-donor variability when comparing the results of different experiments, etc. On the other hand, immortalization comes with drawbacks: possibilities of malignant transformation and/or major phenotype change due to genetic modification itself or upon long-term cultivation appear. At first glance, such issues are huge hurdles in the way of immortalized cells translation into medicine. However, there are certain ways to overcome such barriers that we describe in this review. We determined four major areas of usage of immortalized cells for practical medicinal purposes, and each has its own means to negate the drawbacks associated with immortalization. Moreover, here we describe specific fields of application of immortalized cells in which these problems are of much lesser concern, for example, in some cases where the possibility of malignant growth is not there at all. In general, we can conclude that immortalized cells have their niches in certain areas of practical medicine where they can successfully compete with other therapeutic approaches, and more preclinical and clinical trials with them should be expected.
Characterization of the Molecular Events Underlying the Establishment of Axillary Meristem Region in Pepper
Authors: Wang Haoran , Liu Sujun , Ma Shijie , Wang Yun , Yang Hanyu , Liu Jiankun , Li Mingxuan , Cui Xiangyun , Liang Sun , Cheng Qing , Shen Huolin
Published: August 2023

Plant architecture is a major motif of plant diversity, and shoot branching patterns primarily determine the aerial architecture of plants. In this study, we identified an inbred pepper line with fewer lateral branches, 20C1734, which was free of lateral branches at the middle and upper nodes of the main stem with smooth and flat leaf axils. Successive leaf axil sections confirmed that in normal pepper plants, for either node n, Pn (Primordium n) < 1 cm and Pn+1 < 1 cm were the critical periods between the identification of axillary meristems and the establishment of the region, whereas Pn+3 < 1 cm was fully developed and formed a completely new organ. In 20C1734, the normal axillary meristematic tissue region establishment and meristematic cell identity confirmation could not be performed on the axils without axillary buds. Comparative transcriptome analysis revealed that “auxin-activated signaling pathway”, “response to auxin”, “response to abscisic acid”, “auxin biosynthetic process”, and the biosynthesis of the terms/pathways, such as “secondary metabolites”, were differentially enriched in different types of leaf axils at critical periods of axillary meristem development. The accuracy of RNA-seq was verified using RT-PCR for some genes in the pathway. Several differentially expressed genes (DEGs) related to endogenous phytohormones were targeted, including several genes of the PINs family. The endogenous hormone assay showed extremely high levels of IAA and ABA in leaf axils without axillary buds. ABA content in particular was unusually high. At the same time, there is no regular change in IAA level in this type of leaf axils (normal leaf axils will be accompanied by AM formation and IAA content will be low). Based on this, we speculated that the contents of endogenous hormones IAA and ABA in 20C1734 plant increased sharply, which led to the abnormal expression of genes in related pathways, which affected the formation of Ams in leaf axils in the middle and late vegetative growth period, and finally, nodes without axillary buds and side branches appeared.
The Potent and Selective Histamine H3 Receptor Antagonist E169 Counteracts Cognitive Deficits and Mitigates Disturbances in the PI3K/AKT/GSK-3β Signaling Pathway in MK801-Induced Amnesia in Mice
Authors: Abdalla Sabna , Eissa Nermin , Jayaprakash Petrilla , Beiram Rami , Kuder Kamil J. , Łażewska Dorota , Kieć-Kononowicz Katarzyna , Sadek Bassem
Published: August 2023

The role of histamine H3 receptors (H3Rs) in memory and the prospective of H3R antagonists in pharmacological control of neurodegenerative disorders, e.g., Alzheimer’s disease (AD), is well-accepted. Therefore, the procognitive effects of acute systemic administration of H3R antagonist E169 (2.5–10 mg/kg, i.p.) on MK801-induced amnesia in C57BL/6J mice using the novel object recognition test (NORT) were evaluated. E169 (5 mg) provided a significant memory-improving effect on MK801-induced short- and long-term memory impairments in NORT. The E169 (5 mg)-provided effects were comparable to those observed with the reference phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 and were abrogated with the H3R agonist (R)-α-methylhistamine (RAMH). Additionally, our results demonstrate that E169 ameliorated MK801-induced memory deficits by antagonism of H3Rs and by modulation of the level of disturbance in the expression of PI3K, Akt, and GSK-3β proteins, signifying that E169 mitigated the Akt-mTOR signaling pathway in the hippocampus of tested mice. Moreover, the results observed revealed that E169 (2.5–10 mg/kg, i.p.) did not alter anxiety levels and locomotor activity of animals in open field tests, demonstrating that performances improved following acute systemic administration with E169 in NORT are unrelated to changes in emotional response or in spontaneous locomotor activity. In summary, these obtained results suggest the potential of H3R antagonists such as E169, with good in silico physicochemical properties and stable retained key interactions in docking studies at H3R, in simultaneously modulating disturbed brain neurotransmitters and the imbalanced Akt-mTOR signaling pathway related to neurodegenerative disorders, e.g., AD.
Recent Advances in the Development of Pyrazole Derivatives as Anticancer Agents
Authors: Zhang Yingqian , Wu Chenyuan , Zhang Nana , Fan Rui , Ye Yang , Xu Jun
Published: August 2023

Pyrazole derivatives, as a class of heterocyclic compounds, possess unique chemical structures that confer them with a broad spectrum of pharmacological activities. They have been extensively explored for designing potent and selective anticancer agents. In recent years, numerous pyrazole derivatives have been synthesized and evaluated for their anticancer potential against various cancer cell lines. Structure–activity relationship studies have shown that appropriate substitution on different positions of the pyrazole ring can significantly enhance anticancer efficacy and tumor selectivity. It is noteworthy that many pyrazole derivatives have demonstrated multiple mechanisms of anticancer action by interacting with various targets including tubulin, EGFR, CDK, BTK, and DNA. Therefore, this review summarizes the current understanding on the structural features of pyrazole derivatives and their structure-activity relationships with different targets, aiming to facilitate the development of potential pyrazole-based anticancer drugs. We focus on the latest research advances in anticancer activities of pyrazole compounds reported from 2018 to present.
Purine Metabolism and Pyrimidine Metabolism Alteration Is a Potential Mechanism of BDE-47-Induced Apoptosis in Marine Rotifer Brachionus plicatilis
Authors: Cao Sai , Wang Jiayi , You Xinye , Zhou Bin , Wang You , Zhou Zhongyuan
Published: August 2023

This present study was conducted to provide evidence and an explanation for the apoptosis that occurs in the marine rotifer Brachionus plicatilis when facing 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) stress. Metabolomics analysis showed that aminoacyl-tRNA biosynthesis, valine, leucine and isoleucine biosynthesis, and arginine biosynthesis were the top three sensitive pathways to BDE-47 exposure, which resulted in the reduction in the amino acid pool level. Pyrimidine metabolism and purine metabolism pathways were also significantly influenced, and the purine and pyrimidine content were obviously reduced in the low (0.02 mg/L) and middle (0.1 mg/L) concentration groups while increased in the high (0.5 mg/L) concentration group, evidencing the disorder of nucleotide synthesis and decomposition in B. plicatilis. The biochemical detection of the key enzymes in purine metabolism and pyrimidine metabolism showed the downregulation of Glutamine Synthetase (GS) protein expression and the elevation of Xanthine Oxidase (XOD) activity, which suggested the impaired DNA repair and ROS overproduction. The content of DNA damage biomarker (8-OHdG) increased in treatment groups, and the p53 signaling pathway was found to be activated, as indicated by the elevation of the p53 protein expression and Bax/Bcl-2 ratio. The ROS scavenger (N-acetyl-L-cysteine, NAC) addition effectively alleviated not only ROS overproduction but also DNA damage as well as the activation of apoptosis. The combined results backed up the speculation that purine metabolism and pyrimidine metabolism alteration play a pivotal role in BDE-47-induced ROS overproduction and DNA damage, and the consequent activation of the p53 signaling pathway led to the observed apoptosis in B. plicatilis.
Molecular and Genomic Analysis of the Virulence Factors and Potential Transmission of Hybrid Enteropathogenic and Enterotoxigenic Escherichia coli (EPEC/ETEC) Strains Isolated in South Korea
Authors: Lee Woojung , Sung Soohyun , Ha Jina , Kim Eiseul , An Eun Sook , Kim Seung Hwan , Kim Soon Han , Kim Hae-Yeong
Published: August 2023

Hybrid strains Escherichia coli acquires genetic characteristics from multiple pathotypes and is speculated to be more virulent; however, understanding their pathogenicity is elusive. Here, we performed genome-based characterization of the hybrid of enteropathogenic (EPEC) and enterotoxigenic E. coli (ETEC), the strains that cause diarrhea and mortality in children. The virulence genes in the strains isolated from different sources in the South Korea were identified, and their phylogenetic positions were analyzed. The EPEC/ETEC hybrid strains harbored eae and est encoding E. coli attaching and effacing lesions and heat-stable enterotoxins of EPEC and ETEC, respectively. Genome-wide phylogeny revealed that all hybrids (n = 6) were closely related to EPEC strains, implying the potential acquisition of ETEC virulence genes during ETEC/EPEC hybrid emergence. The hybrids represented diverse serotypes (O153:H19 (n = 3), O49:H10 (n = 2), and O71:H19 (n = 1)) and sequence types (ST546, n = 4; ST785, n = 2). Furthermore, heat-stable toxin-encoding plasmids possessing estA and various other virulence genes and transporters, including nleH2, hlyA, hlyB, hlyC, hlyD, espC, espP, phage endopeptidase Rz, and phage holin, were identified. These findings provide insights into understanding the pathogenicity of EPEC/ETEC hybrid strains and may aid in comparative studies, virulence characterization, and understanding evolutionary biology.
Improved Theory of the Effective Dipole Moments and Absolute Line Strengths of the XY2 Asymmetric Top Molecules in the X2B1 Doublet Electronic States
Authors: Ulenikov Oleg , Bekhtereva Elena , Gromova Olga , Kakaulin Aleksei , Sydow Christian , Bauerecker Sigurd
Published: August 2023

A new effective dipole moment model for the XY2 (C2v−symmetry) molecule in a doublet electronic state is derived that includes (as special cases) all currently known models of effective dipole moments for such types of molecules, and allows us to take into account the influence of spin–rotation interactions on the effective dipole moment operator that were not considered in the preceding studies. Necessary for the analysis of absolute line strengths, the matrix elements of this dipole moment operator are derived. A comparison with the previous analog models is made and discussed. The efficiency of the obtained results is illustrated, which have been applied to a set of the “forbidden” ΔKa=2 transitions of the ν3 band of the OClO free radical molecule.
Signaling Pathways Leading to mTOR Activation Downstream Cytokine Receptors in Lymphocytes in Health and Disease
Authors: Fallone Lucie , Walzer Thierry , Marçais Antoine
Published: August 2023

CD8+ T cells and Natural Killer (NK) cells are cytotoxic lymphocytes important in the response to intracellular pathogens and cancer. Their activity depends on the integration of a large set of intracellular and environmental cues, including antigenic signals, cytokine stimulation and nutrient availability. This integration is achieved by signaling hubs, such as the mechanistic target of rapamycin (mTOR). mTOR is a conserved protein kinase that controls cellular growth and metabolism in eukaryotic cells and, therefore, is essential for lymphocyte development and maturation. However, our current understanding of mTOR signaling comes mostly from studies performed in transformed cell lines, which constitute a poor model for comprehending metabolic pathway regulation. Therefore, it is only quite recently that the regulation of mTOR in primary cells has been assessed. Here, we review the signaling pathways leading to mTOR activation in CD8+ T and NK cells, focusing on activation by cytokines. We also discuss how this knowledge can contribute to immunotherapy development, particularly for cancer treatment.
Structural Analysis of Plasmodium falciparum Hexokinase Provides Novel Information about Catalysis Due to a Plasmodium-Specific Insertion
Authors: Dillenberger Melissa , Werner Anke-Dorothee , Velten Ann-Sophie , Rahlfs Stefan , Becker Katja , Fritz-Wolf Karin
Published: August 2023

The protozoan parasite Plasmodium falciparum is the causative pathogen of the most severe form of malaria, for which novel strategies for treatment are urgently required. The primary energy supply for intraerythrocytic stages of Plasmodium is the production of ATP via glycolysis. Due to the parasite’s strong dependence on this pathway and the significant structural differences of its glycolytic enzymes compared to its human counterpart, glycolysis is considered a potential drug target. In this study, we provide the first three-dimensional protein structure of P. falciparum hexokinase (PfHK) containing novel information about the mechanisms of PfHK. We identified for the first time a Plasmodium-specific insertion that lines the active site. Moreover, we propose that this insertion plays a role in ATP binding. Residues of the insertion further seem to affect the tetrameric interface and therefore suggest a special way of communication among the different monomers. In addition, we confirmed that PfHK is targeted and affected by oxidative posttranslational modifications (oxPTMs). Both S-glutathionylation and S-nitrosation revealed an inhibitory effect on the enzymatic activity of PfHK.
A Novel KCNH2 S981fs Mutation Identified by Whole-Exome Sequencing Is Associated with Type 2 Long QT Syndrome
Authors: Cheng Yu-Wen , Wu Chia-Tung , Chang Chi-Jen , Yeh Yung-Hsin , Chang Gwo-Jyh , Tsai Hsin-Yi , Hsu Lung-An
Published: August 2023

KCNH2 loss-of-function mutations cause long QT syndrome type 2 (LQT2), an inherited cardiac disorder associated with life-threatening ventricular arrhythmia. Through whole-exome sequencing, we discovered a novel AGCGACAC deletion (S981fs) in the hERG gene of an LQT2 patient. Using a heterologous expression system and patch clamping, we found that the mutant K channel had reduced cell surface expression and lower current amplitude compared to the wild type. However, functional expression was restored by lowering temperature and using potassium channel inhibitors or openers (E4031, cisapride, nicorandil). Co-immunoprecipitation experiments confirmed the assembly of mutant proteins with wild-type hERG. Confocal imaging showed decreased hERG distribution on the cell membrane in cells expressing S981fs. Notably, treatment with G418 significantly increased hERG current in wild-type/S981fs heterozygotes. In conclusion, our study identifies a novel hERG mutation leading to impaired Kv11.1 function due to trafficking and nonsense-mediated RNA decay defects. These findings shed light on the mechanisms underlying LQT2 and offer potential therapeutic avenues.
Circulating Neurofilament Light Chain Levels Increase with Age and Are Associated with Worse Physical Function and Body Composition in Men but Not in Women
Authors: Capo Xavier , Galmes-Panades Aina Maria , Navas-Enamorado Cayetano , Ortega-Moral Ana , Marín Silvia , Cascante Marta , Sánchez-Polo Andrés , Masmiquel Luis , Torrens-Mas Margalida , Gonzalez-Freire Marta
Published: August 2023

This study aimed to assess the relationship between age-related changes in Neurofilament Light Chain (NFL), a marker of neuronal function, and various factors including muscle function, body composition, and metabolomic markers. The study included 40 participants, aged 20 to 85 years. NFL levels were measured, and muscle function, body composition, and metabolomic markers were assessed. NFL levels increased significantly with age, particularly in men. Negative correlations were found between NFL levels and measures of muscle function, such as grip strength, walking speed, and chair test performance, indicating a decline in muscle performance with increasing NFL. These associations were more pronounced in men. NFL levels also negatively correlated with muscle quality in men, as measured by 50 kHz phase angle. In terms of body composition, NFL was positively correlated with markers of fat mass and negatively correlated with markers of muscle mass, predominantly in men. Metabolomic analysis revealed significant associations between NFL levels and specific metabolites, with gender-dependent relationships observed. This study provides insights into the relationship between circulating serum NFL, muscle function, and aging. Our findings hint at circulating NFL as a potential early marker of age-associated neurodegenerative processes, especially in men.
Red Blood Cell Deformability Is Expressed by a Set of Interrelated Membrane Proteins
Authors: Barshtein Gregory , Gural Alexander , Arbell Dan , Barkan Refael , Livshits Leonid , Pajic-Lijakovic Ivana , Yedgar Saul
Published: August 2023

Red blood cell (RBC) deformability, expressing their ability to change their shape, allows them to minimize their resistance to flow and optimize oxygen delivery to the tissues. RBC with reduced deformability may lead to increased vascular resistance, capillary occlusion, and impaired perfusion and oxygen delivery. A reduction in deformability, as occurs during RBC physiological aging and under blood storage, is implicated in the pathophysiology of diverse conditions with circulatory disorders and anemias. The change in RBC deformability is associated with metabolic and structural alterations, mostly uncharacterized. To bridge this gap, we analyzed the membrane protein levels, using mass spectroscopy, of RBC with varying deformability determined by image analysis. In total, 752 membrane proteins were identified. However, deformability was positively correlated with the level of only fourteen proteins, with a highly significant inter-correlation between them. These proteins are involved in membrane rafting and/or the membrane–cytoskeleton linkage. These findings suggest that the reduction of deformability is a programmed (not arbitrary) process of remodeling and shedding of membrane fragments, possibly mirroring the formation of extracellular vesicles. The highly significant inter-correlation between the deformability-expressing proteins infers that the cell deformability can be assessed by determining the level of a few, possibly one, of them.
Expression Levels of the Tnni3k Gene in the Heart Are Highly Associated with Cardiac and Glucose Metabolism-Related Phenotypes and Functional Pathways
Authors: Gu Qingqing , Orgil Buyan-Ochir , Bajpai Akhilesh Kumar , Chen Yufeng , Ashbrook David G. , Starlard-Davenport Athena , Towbin Jeffrey A. , Lebeche Djamel , Purevjav Enkhsaikhan , Sheng Hongzhuan , Lu Lu
Published: August 2023

Background: Troponin-I interacting kinase encoded by the TNNI3K gene is expressed in nuclei and Z-discs of cardiomyocytes. Mutations in TNNI3K were identified in patients with cardiac conduction diseases, arrhythmias, and cardiomyopathy. Methods: We performed cardiac gene expression, whole genome sequencing (WGS), and cardiac function analysis in 40 strains of BXD recombinant inbred mice derived from C57BL/6J (B6) and DBA/2J (D2) strains. Expression quantitative trait loci (eQTLs) mapping and gene enrichment analysis was performed, followed by validation of candidate Tnni3k-regulatory genes. Results: WGS identified compound splicing and missense T659I Tnni3k variants in the D2 parent and some BXD strains (D allele) and these strains had significantly lower Tnni3k expression than those carrying wild-type Tnni3k (B allele). Expression levels of Tnni3k significantly correlated with multiple cardiac (heart rate, wall thickness, PR duration, and T amplitude) and metabolic (glucose levels and insulin resistance) phenotypes in BXDs. A significant cis-eQTL on chromosome 3 was identified for the regulation of Tnni3k expression. Furthermore, Tnni3k-correlated genes were primarily involved in cardiac and glucose metabolism-related functions and pathways. Genes Nodal, Gnas, Nfkb1, Bmpr2, Bmp7, Smad7, Acvr1b, Acvr2b, Chrd, Tgfb3, Irs1, and Ppp1cb were differentially expressed between the B and D alleles. Conclusions: Compound splicing and T659I Tnni3k variants reduce cardiac Tnni3k expression and Tnni3k levels are associated with cardiac and glucose metabolism-related phenotypes.
Molecular Advances on Cannabinoid and Endocannabinoid Research
Authors: Meccariello Rosaria
Published: August 2023

Since ancient times, cannabis has been used for recreational and medical purposes [...]
Suaeda salsa NRT1.1 Is Involved in the Regulation of Tolerance to Salt Stress in Transgenic Arabidopsis
Authors: Xiong Yi , Wang Saisai , Cui Cuijie , Wu Xiaoyan , Zhu Jianbo
Published: August 2023

Like other abiotic stresses, salt stress has become a major factor that restricts the growth, distribution and yield of crops. Research has shown that increasing the nitrogen content in soil can improve the salt tolerance of plants and nitrate transporter (NRT) is the primary nitrogen transporter in plants. Suaeda salsa (L.) Pall is a strong halophyte that can grow normally at a salt concentration of 200 mM. The salt stress transcriptome database of S. salsa was found to contain four putative genes that were homologous to NRT, including SsNRT1.1A, SsNRT1.1B, SsNRT1.1C and SsNRT1.1D. The cDNA of SsNRT1.1s was predicted to contain open reading frames of 1791, 1782, 1755 and 1746 bp, respectively. Sequence alignment and structural analysis showed that the SsNRT1.1 amino acids were inducible by salt and have conserved MFS and PTR2 domains. Subcellular localization showed they are on the endoplasmic reticulum. Overexpression of SsNRT1.1 genes in transgenic Arabidopsis improves its salt tolerance and SsNRT1.1C was more effective than others. We constructed a salt-stressed yeast cDNA library and used yeast two-hybrid and BiFC technology to find out that SsHINT1 and SsNRT1.1C have a protein interaction relationship. Overexpression of SsHINT1 in transgenic Arabidopsis also improves salt tolerance and the expressions of Na+ and K+ were increased and reduced, respectively. But the K+/Liratio was up-regulated 11.1-fold compared with the wild type. Thus, these results provide evidence that SsNRT1.1C through protein interactions with SsHINT1 increases the K+/Na+ ratio to improve salt tolerance and this signaling may be controlled by the salt overly sensitive (SOS) pathway.
Osteoblast-Derived Matrix Vesicles Exhibit Exosomal Traits and a Unique Subset of microRNA: Their Caveolae-Dependent Endocytosis Results in Reduced Osteogenic Differentiation
Authors: Skelton Anne M. , Cohen D. Joshua , Boyan Barbara D. , Schwartz Zvi
Published: August 2023

Matrix vesicles (MVs) are nano-sized extracellular vesicles that are anchored in the extracellular matrix (ECM). In addition to playing a role in biomineralization, osteoblast-derived MVs were recently suggested to have regulatory duties. The aims of this study were to establish the characteristics of osteoblast-derived MVs in the context of extracellular vesicles like exosomes, assess their role in modulating osteoblast differentiation, and examine their mechanism of uptake. MVs were isolated from the ECM of MG63 human osteoblast-like cell cultures and characterized via enzyme activity, transmission electron microscopy, nanoparticle tracking analysis, Western blot, and small RNA sequencing. Osteoblasts were treated with MVs from two different culture conditions (growth media [GM]; osteogenic media [OM]) to evaluate their effects on the differentiation and production of inflammatory markers and on macrophage polarization. MV endocytosis was assessed using a lipophilic, fluorescent dye and confocal microscopy with the role of caveolae determined using methyl-β-cyclodextrin. MVs exhibited a four-fold enrichment in alkaline phosphatase specific activity compared to plasma membranes; were 50–150 nm in diameter; possessed exosomal markers CD63, CD81, and CD9 and endosomal markers ALIX, TSG101, and HSP70; and were selectively enriched in microRNA linked to an anti-osteogenic effect and to M2 macrophage polarization. Treatment with GM or OM MVs decreased osteoblast differentiation. Osteoblasts endocytosed MVs using a mechanism that involves caveolae. These results support the hypothesis that osteoblasts produce MVs that participate in the regulation of osteogenesis.
Isolation and Identification of a Novel Anti-Dry Eye Peptide from Tilapia Skin Peptides Based on In Silico, In Vitro, and In Vivo Approaches
Authors: Zeng Jian , Lin Cuixian , Zhang Shilin , Yin Haowen , Deng Kaishu , Yang Zhiyou , Zhang Yongping , Liu You , Hu Chuanyin , Zhao Yun-Tao
Published: August 2023

Tilapia skin is a great source of collagen. Here, we aimed to isolate and identify the peptides responsible for combating dry eye disease (DED) in tilapia skin peptides (TSP). In vitro cell DED model was used to screen anti-DED peptides from TSP via Sephadex G-25 chromatography, LC/MS/MS, and in silico methods. The anti-DED activity of the screened peptide was further verified in the mice DED model. TSP was divided into five fractions (TSP-I, TSP-II, TSP-III, TSP-IV, and TSP-V), and TSP-II exerted an effective effect for anti-DED. A total of 131 peptides were identified using LC/MS/MS in TSP-II, and NGGPSGPR (NGG) was screened as a potential anti-DED fragment in TSP-II via in silico methods. In vitro, NGG restored cell viability and inhibited the expression level of Cyclooxygenase-2 (COX-2) protein in Human corneal epithelial cells (HCECs) induced by NaCl. In vivo, NGG increased tear production, decreased tear ferning score, prevented corneal epithelial thinning, alleviated conjunctival goblet cell loss, and inhibited the apoptosis of corneal epithelial cells in DED mice. Overall, NGG, as an anti-DED peptide, was successfully identified from TSP, and it may be devoted to functional food ingredients or medicine for DED.
XAANTAL1 Reveals an Additional Level of Flowering Regulation in the Shoot Apical Meristem in Response to Light and Increased Temperature in Arabidopsis
Authors: Rodríguez-Bolaños Mónica , Martínez Tania , Juárez Saray , Quiroz Stella , Domínguez Andrea , Garay-Arroyo Adriana , Sanchez María de la Paz , Álvarez-Buylla Elena R. , García-Ponce Berenice
Published: August 2023

Light and photoperiod are environmental signals that regulate flowering transition. In plants like Arabidopsis thaliana, this regulation relies on CONSTANS, a transcription factor that is negatively posttranslational regulated by phytochrome B during the morning, while it is stabilized by PHYA and cryptochromes 1/2 at the end of daylight hours. CO induces the expression of FT, whose protein travels from the leaves to the apical meristem, where it binds to FD to regulate some flowering genes. Although PHYB delays flowering, we show that light and PHYB positively regulate XAANTAL1 and other flowering genes in the shoot apices. Also, the genetic data indicate that XAL1 and FD participate in the same signaling pathway in flowering promotion when plants are grown under a long-day photoperiod at 22 °C. By contrast, XAL1 functions independently of FD or PIF4 to induce flowering at higher temperatures (27 °C), even under long days. Furthermore, XAL1 directly binds to FD, SOC1, LFY, and AP1 promoters. Our findings lead us to propose that light and temperature influence the floral network at the meristem level in a partially independent way of the signaling generated from the leaves.
Prognostic Implication of Plasma Metabolites in Gastric Cancer
Authors: Cao Kang , Lyu Yanping , Chen Jingwen , He Chenzhou , Lyu Xuejie , Zhang Yuling , Chen Liangping , Jiang Yu , Xiang Jianjun , Liu Baoying , Wu Chuancheng
Published: August 2023

Gastric cancer (GC) typically carries a poor prognosis as it is often diagnosed at a late stage. Altered metabolism has been found to impact cancer outcomes and affect patients’ quality of life, and the role of metabolites in gastric cancer prognosis has not been sufficiently understood. We aimed to establish a prognostic prediction model for GC patients based on a metabolism-associated signature and identify the unique role of metabolites in the prognosis of GC. Thus, we conducted untargeted metabolomics to detect the plasma metabolites of 218 patients with gastric adenocarcinoma and explored the metabolites related to the survival of patients with gastric cancer. Firstly, we divided patients into two groups based on the cutoff value of the abundance of each of the 60 metabolites and compared the differences using Kaplan–Meier (K-M) survival analysis. As a result, 23 metabolites associated with gastric cancer survival were identified. To establish a risk score model, we performed LASSO regression and Cox regression analysis on the 60 metabolites and identified 8 metabolites as an independent prognostic factor. Furthermore, a nomogram incorporating clinical parameters and the metabolic signature was constructed to help individualize outcome predictions. The results of the ROC curve and nomogram plot showed good predictive performance of metabolic risk features. Finally, we performed pathway analysis on the 24 metabolites identified in the two parts, and the results indicated that purine metabolism and arachidonic acid metabolism play important roles in gastric cancer prognosis. Our study highlights the important role of metabolites in the progression of gastric cancer and newly identified metabolites could be potential biomarkers or therapeutic targets for gastric cancer patients.