bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Changes regarding Working Circumstances during COVID-19 Pandemic upon Patients Evaluated for Thyroid Dysfunction
Authors: Popa Anca , Chereji Aurelia-Ioana , Dodu Monica Angelica , Chereji Ioan , Fitero Andreea , Daina Cristian Marius , Daina Lucia Georgeta , Badau Dana , Neculoiu Daniela Carmen , Domnariu Carmen
Published: August 2022

We evaluated patients who presented with thyroid dysfunction correlated symptoms that started when the Government took important measures to reduce the spread of COVID-19. These measures have influenced the safety of many people’s jobs. Data were collected from 378 patients that were clinically evaluated at the Endocrinology Department, between September 2020 and January 2021. Their health status modifications were statistically analyzed in correlation with their life and work changes. These changes were induced by measures associated with the COVID-19 pandemic. The lifestyle changes correlated with the COVID-19 pandemic have been present in both categories of patients: euthyroid and dysthyroid patients; 87.50% of euthyroid patients physically felt the pandemic-induced changes in their lives. It resulted in changes in lifestyle and job insecurity has a statistically significant influence (p < 0.01) on their state of health. The presence of life/work changes in men is strongly reflected in their state of health (p = 0.0004). Work instability that occurred as a side effect of the COVID-19 pandemic induced symptoms that made many people believe they have an endocrinology disorder.
Analysis of the Nutritional Value of the Diets Presented in Women’s and Sports Magazines before and during the COVID-19 Pandemic
Authors: Głąbska Dominika , Janowska Maria , Bartosz Ewa , Guzek Dominika
Published: August 2022

For consumers, among the most important sources of information related to nutrition are popular journals and magazines, including women’s and sports, but the diets presented there may lead to unhealthy weight-control behaviors. The aim of the study was to assess the nutritional value of regular and low-calorie diets presented in Polish women’s and sports magazines before and during COVID-19 pandemic. The study was based on two popular Polish magazines—one women’s magazine and one sports magazine, which regularly present various types of diets. The nutritional value of all the diets published from January 2014 to May 2022 was analyzed. The total number of included single-day menus was n = 119, while for analysis they were stratified based on: type of magazine (published in the women’s magazine n = 41 and in the sports magazine n = 78), year of publication (before the COVID-19 pandemic n = 78 and during n = 41), and type of diet (regular n = 61 and low-calorie n = 58). The analysis included the energy value and nutritional value. For the type of magazine, the diets published in the sports magazine were characterized by a higher intake of fat (p < 0.0001 for intake in grams and in % of energy) and calcium (p = 0.0330), whereas the diets published in the women’s magazine were characterized by a higher intake of carbohydrates (p = 0.0226 for intake in grams, and p = 0.0002 for intake in % of energy) and fiber (p = 0.0163). For the year of publication, the diets published during the COVID-19 pandemic were characterized by a higher intake of protein (p = 0.0166 for intake in grams), sodium (p = 0.0465), calcium (p < 0.0001), vitamin D (p = 0.0197), vitamin B6 (p = 0.0207), and vitamin B12 (p = 0.0277), whereas the diets published before the COVID-19 pandemic were characterized by a higher intake of carbohydrates (p = 0.0243 for intake in % of energy). For the type of diet, the regular diets were characterized by a higher energy value (p = 0.0020), as well as by a higher intake of fat (p = 0.0162 for intake in grams), carbohydrates (p = 0.0390 for intake in grams), mono- and oligosaccharides (p = 0.0084 for intake in % of energy), fiber (p < 0.0001), magnesium (p = 0.0323), iron (p = 0.0307), and vitamin B6 (p = 0.0204). The nutritional value of the diets presented in the Polish women’s and sports magazines was not justified by the type of magazine or type of diet, associated with the target group, which may cause the following of improperly balanced diets. However, the changes in the typical nutritional value of diets presented in the Polish women’s and sports magazines during the COVID-19 pandemic were justified by some specific needs for the prevention and treatment of COVID-19.
The Impact of Technological Progress and Climate Change on Food Crop Production: Evidence from Sichuan—China
Authors: Chandio Abbas Ali , Nasereldin Yasir A. , Anh Dao Le Trang , Tang Yashuang , Sargani Ghulam Raza , Zhang Huaquan
Published: August 2022

Agriculture is an integral sector in China mandated to feed over 1.3 billion of its people and provide essential inputs for many industries. Sichuan, a central grain-producing province in Southwest China, is a significant supplier of cereals in the country. Yet, it is likely to be threatened by yield damages induced by climate change. Therefore, this study examines the effects of technological progress (via fertilizers usage and mechanization) and climatic changes (via temperature and precipitation) on the productivity of main food crops, such as rice (Oryza sativa), wheat (Triticum aestivum), and maize (Zea mays) in Sichuan province. We employ the generalized method of moments (GMM) model to analyze Sichuan provincial data from 1980 to 2018. Our findings show a positive nexus between fertilizers use and yields of main food crops. Only rice and maize yields are significantly improved by mechanization. Increased average temperature reduces rice and wheat yields significantly. Rainfall is unlikely to have a significant impact on agricultural production. The study suggests that the Chinese government should consider revising its strategies and policies to reduce the impact of climate change on food crop production and increase farmers’ adaptive ability.
Genome-Wide Analysis of the RAV Gene Family in Wheat and Functional Identification of TaRAV1 in Salt Stress
Authors: Luo Yun-Xin , Chen Shou-Kun , Wang Peng-Dan , Peng De , Zhang Xu , Li Hai-Feng , Feng Cui-Zhu
Published: August 2022

RAV transcription factors (TFs) are unique to higher plants and contain both B3 and APETALA2 (AP2) DNA binding domains. Although sets of RAV genes have been identified from several species, little is known about this family in wheat. In this study, 26 RAV genes were identified in the wheat genome. These wheat RAV TFs were phylogenetically clustered into three classes based on their amino acid sequences. A TaRAV gene located on chromosome 1D was cloned and named TaRAV1. TaRAV1 was expressed in roots, stems, leaves, and inflorescences, and its expression was up-regulated by heat while down-regulated by salt, ABA, and GA. Subcellular localization analysis revealed that the TaRAV1 protein was localized in the nucleus. The TaRAV1 protein showed DNA binding activity in the EMSA assay and transcriptional activation activity in yeast cells. Overexpressing TaRAV1 enhanced the salt tolerance of Arabidopsis and upregulated the expression of SOS genes and other stress response genes. Collectively, our data suggest that TaRAV1 functions as a transcription factor and is involved in the salt stress response by regulating gene expression in the SOS pathway.
Real-Time Fluorescence Visualization and Quantitation of Cell Growth and Death in Response to Treatment in 3D Collagen-Based Tumor Model
Authors: Sencha Ludmila M. , Dobrynina Olga E. , Pospelov Anton D. , Guryev Evgenii L. , Peskova Nina N. , Brilkina Anna A. , Cherkasova Elena I. , Balalaeva Irina V.
Published: August 2022

The use of 3D in vitro tumor models has become a common trend in cancer biology studies as well as drug screening and preclinical testing of drug candidates. The transition from 2D to 3D matrix-based cell cultures requires modification of methods for assessing tumor growth. We propose the method for assessing the growth of tumor cells in a collagen hydrogel using macro-scale registration and quantification of the gel epi-fluorescence. The technique does not require gel destruction, can be used for real-time observation of fast (in seconds) cellular responses and demonstrates high agreement with cell counting approaches or measuring total DNA content. The potency of the method was proven in experiments aimed at testing cytotoxic activity of chemotherapeutic drug (cisplatin) and recombinant targeted toxin (DARPin-LoPE) against two different tumor cell lines genetically labelled with fluorescent proteins. Moreover, using fluorescent proteins with sensor properties allows registration of dynamic changes in cells’ metabolism, which was shown for the case of sensor of caspase 3 activity.
Physapruin A Enhances DNA Damage and Inhibits DNA Repair to Suppress Oral Cancer Cell Proliferation
Authors: Yu Tzu-Jung , Yen Ching-Yu , Cheng Yuan-Bin , Yen Chia-Hung , Jeng Jiiang-Huei , Tang Jen-Yang , Chang Hsueh-Wei
Published: August 2022

The selective antiproliferation to oral cancer cells of Physalis peruviana-derived physapruin A (PHA) is rarely reported. Either drug-induced apoptosis and DNA damage or DNA repair suppression may effectively inhibit cancer cell proliferation. This study examined the selective antiproliferation ability of PHA and explored detailed mechanisms of apoptosis, DNA damage, and repair. During an ATP assay, PHA provided high cytotoxicity to two oral cancer cell lines (CAL 27 and Ca9-22) but no cytotoxicity to two non-malignant oral cells (HGF-1 and SG). This selective antiproliferation of PHA was associated with the selective generation of reactive oxygen species (ROS) in oral cancer cells rather than in non-malignant oral cells, as detected by flow cytometry. Moreover, PHA induced other oxidative stresses in oral cancer cells, such as mitochondrial superoxide generation and mitochondrial membrane potential depletion. PHA also demonstrated selective apoptosis in oral cancer cells rather than non-malignant cells in annexin V/7-aminoactinmycin D and caspase 3/7 activity assays. In flow cytometry and immunofluorescence assays, PHA induced γH2AX expressions and increased the γH2AX foci number of DNA damages in oral cancer cells. In contrast, the mRNA expressions for DNA repair signaling, including homologous recombination (HR) and non-homologous end joining (NHEJ)-associated genes, were inhibited by PHA in oral cancer cells. Moreover, the PHA-induced changes were alleviated by the oxidative stress inhibitor N-acetylcysteine. Therefore, PHA generates selective antiproliferation, oxidative stress, and apoptosis associated with DNA damage induction and DNA repair suppression in oral cancer cells.
CDC42-IQGAP Interactions Scrutinized: New Insights into the Binding Properties of the GAP-Related Domain
Authors: Mosaddeghzadeh Niloufar , Pudewell Silke , Bazgir Farhad , Kazemein Jasemi Neda S. , Krumbach Oliver H. F. , Gremer Lothar , Willbold Dieter , Dvorsky Radovan , Ahmadian Mohammad R.
Published: August 2022

The IQ motif-containing GTPase-activating protein (IQGAP) family composes of three highly-related and evolutionarily conserved paralogs (IQGAP1, IQGAP2 and IQGAP3), which fine tune as scaffolding proteins numerous fundamental cellular processes. IQGAP1 is described as an effector of CDC42, although its effector function yet re-mains unclear. Biophysical, biochemical and molecular dynamic simulation studies have proposed that IQGAP RASGAP-related domains (GRDs) bind to the switch regions and the insert helix of CDC42 in a GTP-dependent manner. Our kinetic and equilibrium studies have shown that IQGAP1 GRD binds, in contrast to its C-terminal 794 amino acids (called C794), CDC42 in a nucleotide-independent manner indicating a binding outside the switch regions. To resolve this discrepancy and move beyond the one-sided view of GRD, we carried out affinity measurements and a systematic mutational analysis of the interfacing residues between GRD and CDC42 based on the crystal structure of the IQGAP2 GRD-CDC42Q61L GTP complex. We determined a 100-fold lower affinity of the GRD1 of IQGAP1 and of GRD2 of IQGAP2 for CDC42 mGppNHp in comparison to C794/C795 proteins. Moreover, partial and major mutation of CDC42 switch regions substantially affected C794/C795 binding but only a little GRD1 and remarkably not at all the GRD2 binding. However, we clearly showed that GRD2 contributes to the overall affinity of C795 by using a 11 amino acid mutated GRD variant. Furthermore, the GRD1 binding to the CDC42 was abolished using specific point mutations within the insert helix of CDC42 clearly supporting the notion that CDC42 binding site(s) of IQGAP GRD lies outside the switch regions among others in the insert helix. Collectively, this study provides further evidence for a mechanistic framework model that is based on a multi-step binding process, in which IQGAP GRD might act as a ‘scaffolding domain’ by binding CDC42 irrespective of its nucleotide-bound forms, followed by other IQGAP domains downstream of GRD that act as an effector domain and is in charge for a GTP-dependent interaction with CDC42.
Exosomes in Breast Cancer: Involvement in Tumor Dissemination and Prospects for Liquid Biopsy
Authors: Shefer Aleksei , Yalovaya Alena , Tamkovich Svetlana
Published: August 2022

In women, breast cancer (BC) is the most commonly diagnosed cancer (24.5%) and the leading cause of cancer death (15.5%). Understanding how this heterogeneous disease develops and the confirm mechanisms behind tumor progression is of utmost importance. Exosomes are long-range message vesicles that mediate communication between cells in physiological conditions but also in pathology, such as breast cancer. In recent years, there has been an exponential rise in the scientific studies reporting the change in morphology and cargo of tumor-derived exosomes. Due to the transfer of biologically active molecules, such as RNA (microRNA, long non-coding RNA, mRNA, etc.) and proteins (transcription factors, enzymes, etc.) into recipient cells, these lipid bilayer 30–150 nm vesicles activate numerous signaling pathways that promote tumor development. In this review, we attempt to shed light on exosomes’ involvement in breast cancer pathogenesis (including epithelial-to-mesenchymal transition (EMT), tumor cell proliferation and motility, metastatic processes, angiogenesis stimulation, and immune system repression). Moreover, the potential use of exosomes as promising diagnostic biomarkers for liquid biopsy of breast cancer is also discussed.
A Single Amino Acid Substitution in MIL1 Leads to Activation of Programmed Cell Death and Defense Responses in Rice
Authors: Yan Bowen , Zheng Haoyu , Sang Yuwei , Wang Yan , Sun Jian , Li Fengcheng , Wang Jiayu , Wang Xiaoxue
Published: August 2022

Lesion mimic mutants are an ideal model system for elucidating the molecular mechanisms of programmed cell death and defense responses in rice. In this study, we identified a lesion mimic mutant termed miner infection like 1-1 (mil1-1). The mil1-1 exhibited lesions on the leaves during development, and the chloroplasts of mil1-1 leaves were disrupted. Reactive oxygen species were found to accumulate in mil1-1 leaves. Cell death and DNA fragmentation were observed in mil1-1 leaves, indicating that the cells in the spots of mil1-1 leaves experienced programmed cell death. Most agronomic traits decreased in mil1-1, suggesting that the growth retardation in mil1-1 caused reduced per-plant grain yield. However, the mutation of MIL1 activated the expression of pathogen response genes and enhanced resistance to bacterial blight. The MIL1 gene was cloned using the positional cloning approach. A missense mutation 751 bp downstream of ATG was found in mil1-1. The defects of mil1-1 were able to be rescued by delivering a wild-type MIL1 gene into mil1-1. MIL1 encoded hydroperoxide lyase 3 (OsHPL3), and the expression of OsHPL3 was induced via hormone and abiotic stresses. Our findings provide insights into the roles of MIL1 in regulating programmed cell death, development, yield, and defense responses in rice.
NX210c Peptide Promotes Glutamatergic Receptor-Mediated Synaptic Transmission and Signaling in the Mouse Central Nervous System
Authors: Lemarchant Sighild , Sourioux Mélissa , Le Douce Juliette , Henriques Alexandre , Callizot Noëlle , Hugues Sandrine , Farinelli Mélissa , Godfrin Yann
Published: August 2022

NX210c is a disease-modifying dodecapeptide derived from the subcommissural organ-spondin that is under preclinical and clinical development for the treatment of neurological disorders. Here, using whole-cell patch-clamp recordings, we demonstrate that NX210c increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)- and GluN2A-containing N-methyl-D-aspartate receptor (GluN2A-NMDAR)-mediated excitatory postsynaptic currents in the brain. Accordingly, using extracellular field excitatory postsynaptic potential recordings, an enhancement of synaptic transmission was shown in the presence of NX210c in two different neuronal circuits. Furthermore, the modulation of synaptic transmission and GluN2A-NMDAR-driven signaling by NX210c restored memory in mice chronically treated with the NMDAR antagonist phencyclidine. Overall, by promoting glutamatergic receptor-related neurotransmission and signaling, NX210c represents an innovative therapeutic opportunity for patients suffering from CNS disorders, injuries, and states with crippling synaptic dysfunctions.
Visualizing Conformational Space of Functional Biomolecular Complexes by Deep Manifold Learning
Authors: Wu Zhaolong , Chen Enbo , Zhang Shuwen , Ma Yinping , Mao Youdong
Published: August 2022

The cellular functions are executed by biological macromolecular complexes in nonequilibrium dynamic processes, which exhibit a vast diversity of conformational states. Solving the conformational continuum of important biomolecular complexes at the atomic level is essential to understanding their functional mechanisms and guiding structure-based drug discovery. Here, we introduce a deep manifold learning framework, named AlphaCryo4D, which enables atomic-level cryogenic electron microscopy (cryo-EM) reconstructions that approximately visualize the conformational space of biomolecular complexes of interest. AlphaCryo4D integrates 3D deep residual learning with manifold embedding of pseudo-energy landscapes, which simultaneously improves 3D classification accuracy and reconstruction resolution via an energy-based particle-voting algorithm. In blind assessments using simulated heterogeneous datasets, AlphaCryo4D achieved 3D classification accuracy three times those of alternative methods and reconstructed continuous conformational changes of a 130-kDa protein at sub-3 Å resolution. By applying this approach to analyze several experimental datasets of the proteasome, ribosome and spliceosome, we demonstrate its potential generality in exploring hidden conformational space or transient states of macromolecular complexes that remain hitherto invisible. Integration of this approach with time-resolved cryo-EM further allows visualization of conformational continuum in a nonequilibrium regime at the atomic level, thus potentially enabling therapeutic discovery against highly dynamic biomolecular targets.
Early Changes in Transcriptomic Profiles in Synaptodendrosomes Reveal Aberrant Synaptic Functions in Alzheimer’s Disease
Authors: Qu Xueqi , Lin Li , Yi Wanying , Sun Changyu , Chen Yuewen , Chen Yu
Published: August 2022

Alzheimer’s disease (AD) is one of the most prevalent neurodegenerative disorders characterized by the progressive decline of cognitive functions, and is closely associated with the dysfunction of synapses, which comprise the basic structure that mediates the communication between neurons. Although the protein architecture and machinery for protein translation at synapses are extensively studied, the impact that local changes in the mRNA reservoir have on AD progression is largely unknown. Here, we investigated the changes in transcriptomic profiles in the synaptodendrosomes purified from the cortices of AD mice at ages 3 and 6 months, a stage when early signatures of synaptic dysfunction are revealed. The transcriptomic profiles of synaptodendrosomes showed a greater number of localized differentially expressed genes (DEGs) in 6-month-old AD mice compared with mice 3 months of age. Gene Ontology (GO) analysis showed that these DEGs are majorly enriched in mitochondrial biogenesis and metabolic activity. More specifically, we further identified three representative DEGs in mitochondrial and metabolic pathways—Prnp, Cst3, and Cox6c—that regulate the dendritic spine density and morphology in neurons. Taken together, this study provides insights into the transcriptomic changes in synaptodendrosomes during AD progression, which may facilitate the development of intervention strategies targeting local translation to ameliorate the pathological progression of AD.
Hierarchical Clustering and Target-Independent QSAR for Antileishmanial Oxazole and Oxadiazole Derivatives
Authors: Teles Henrique R. , Ferreira Leonardo L. G. , Valli Marilia , Coelho Fernando , Andricopulo Adriano D.
Published: August 2022

Leishmaniasis is a neglected tropical disease that kills more than 20,000 people each year. The chemotherapy available for the treatment of the disease is limited, and novel approaches to discover novel drugs are urgently needed. Herein, 2D- and 4D-quantitative structure–activity relationship (QSAR) models were developed for a series of oxazole and oxadiazole derivatives that are active against Leishmania infantum, the causative agent of visceral leishmaniasis. A clustering strategy based on structural similarity was applied with molecular fingerprints to divide the complete set of compounds into two groups. Hierarchical clustering was followed by the development of 2D- (R2 = 0.90, R2pred = 0.82) and 4D-QSAR models (R2 = 0.80, R2pred = 0.64), which showed improved statistical robustness and predictive ability.
Reduction of Emphysema Severity by Human Umbilical Cord-Derived Mesenchymal Stem Cells in Mice
Authors: Laiman Vincent , Lee Yueh-Lun , Hou Yu-Wei , Fang Yu-Ting , Chen You-Yin , Lo Yu-Chun , Heriyanto Didik Setyo , Lan Shu-Chi , Chen Chia-Ling , Chen Xiao-Yue , Lee Kang-Yun , Chang Jer-Hwa , Chuang Hsiao-Chi
Published: August 2022

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality in chronic lung disease patients throughout the world. Mesenchymal stem cells (MSCs) have been shown to regulate immunomodulatory, anti-inflammatory, and regenerative responses. However, the effects of human-umbilical-cord-derived mesenchymal stem cells (hUC-MSCs) on the lung pathophysiology of COPD remain unclear. We aimed to investigate the role of hUC-MSCs in emphysema severity and Yes-associated protein (Yap) phosphorylation (p-Yap) in a porcine-pancreatic-elastase (PPE)-induced emphysema model. We observed that the emphysema percentages (normalized to the total lung volume) measured by chest computed tomography (CT) and exercise oxygen desaturation were significantly reduced by hUC-MSCs at 107 cells/kg body weight (BW) via intravenous administration in emphysematous mice (p < 0.05). Consistently, the emphysema index, as assessed by the mean linear intercept (MLI), significantly decreased with hUC-MSC administration at 3 × 106 and 107 cells/kg BW (p < 0.05). Changes in the lymphocytes, monocytes, and splenic cluster of differentiation 4-positive (CD4+) lymphocytes by PPE were significantly reversed by hUC-MSC administration in emphysematous mice (p < 0.05). An increasing neutrophil/lymphocyte ratio was reduced by hUC-MSCs at 3 × 106 and 107 cells/kg BW (p < 0.05). The higher levels of tumor necrosis factor (TNF)-α, keratinocyte chemoattractant (KC), and lactate dehydrogenase (LDH) in bronchoalveolar lavage fluid (BALF) were significantly decreased by hUC-MSC administration (p < 0.05). A decreasing p-Yap/Yap ratio in type II alveolar epithelial cells (AECII) of mice with PPE-induced emphysema was significantly increased by hUC-MSCs (p < 0.05). In conclusion, the administration of hUC-MSCs improved multiple pathophysiological features of mice with PPE-induced emphysema. The effectiveness of the treatment of pulmonary emphysema with hUC-MSCs provides an essential and significant foundation for future clinical studies of MSCs in COPD patients.
Genetic Mining of Newly Isolated Salmophages for Phage Therapy
Authors: Gendre Julia , Ansaldi Mireille , Olivenza David R. , Denis Yann , Casadesús Josep , Ginet Nicolas
Published: August 2022

Salmonella enterica, a Gram-negative zoonotic bacterium, is mainly a food-borne pathogen and the main cause of diarrhea in humans worldwide. The main reservoirs are found in poultry farms, but they are also found in wild birds. The development of antibiotic resistance in S. enterica species raises concerns about the future of efficient therapies against this pathogen and revives the interest in bacteriophages as a useful therapy against bacterial infections. Here, we aimed to decipher and functionally annotate 10 new Salmonella phage genomes isolated in Spain in the light of phage therapy. We designed a bioinformatic pipeline using available building blocks to de novo assemble genomes and perform syntaxic annotation. We then used genome-wide analyses for taxonomic annotation enabled by vContact2 and VICTOR. We were also particularly interested in improving functional annotation using remote homologies detection and comparisons with the recently published phage-specific PHROG protein database. Finally, we searched for useful functions for phage therapy, such as systems encoded by the phage to circumvent cellular defenses with a particular focus on anti-CRISPR proteins. We, thus, were able to genetically characterize nine virulent phages and one temperate phage and identify putative functions relevant to the formulation of phage cocktails for Salmonella biocontrol.
Size and Methylation Index of Cell-Free and Cell-Surface-Bound DNA in Blood of Breast Cancer Patients in the Contest of Liquid Biopsy
Authors: Tamkovich Svetlana , Tupikin Alexey , Kozyakov Anton , Laktionov Pavel
Published: August 2022

Aberrantly methylated circulating DNA (cirDNA) has proven to be a good cancer marker, but its detection is limited by low concentrations, fragmentation, and insufficiency. Since the methylated cirDNA was shown to be more stable in circulation than the unmethylated one and was shown to bind with the blood cell surface, we studied the concentration, representation, and fragmentation of tumor-derived methylated DNA in cell-free and cell-surface-associated DNA. We found that long DNA fragments (more than 10 kb) are mainly associated with the surface of blood cells. However, in plasma short DNA fragments (100–1000 bp) were also found along with long DNA fragments. Isolation of short fragments after separation of cirDNA in 6% PAGE followed by quantitative PCR (L1 element) has shown that short DNA fragments in healthy females represent 22% versus 0.5–4.4% in breast cancer patients. The methylated form of the RARβ2 gene was detected only in long DNA fragments by Real-time TaqMan PCR of bisulfite-converted DNA. The methylation index of cirDNA from healthy women was estimated at 0%, 9%, and 7% in plasma, PBS-EDTA, and trypsin eluates from the surface of blood cells, respectively. The methylation index of breast cancer patients’ DNA was found to be 33%, 15%, and 61% in the same fractions confirming the overrepresentation of methylated DNA in csbDNA.
Functional Expression of Choline Transporters in Microglia and Their Regulation of Microglial M1/M2 Polarization
Authors: Okada Toshio , Muto Eisuke , Yamanaka Tsuyoshi , Uchino Hiroyuki , Inazu Masato
Published: August 2022

Background: Microglia are key cells of the immune system in the central nervous system and are suggested to be deeply involved in the development of neurodegenerative diseases. It is well known that microglia have functional plasticity, with an inflammatory M1 phenotype and an anti-inflammatory M2 phenotype. Inhibition of choline transport in macrophages has been reported to suppress the secretion of inflammatory cytokines. However, the role of the choline transport system in regulating microglial M1/M2 polarization has not been fully elucidated to date. In this study, we investigated the mechanism of choline uptake in microglia, and its association with microglial M1/M2 polarization. Methods: The immortalized mouse microglial cell line SIM-A9 was used for [3H]choline uptake and expression analysis of choline transporters. The association between the choline uptake system and the M1/M2 polarization of microglia was also analyzed. Results: Choline transporter-like protein (CTL) 1 and CTL2 were highly expressed in SIM-A9 cells, and CTL1 and CTL2 were localized in the plasma membrane and mitochondria, respectively. Functional analysis of choline uptake demonstrated the existence of Na+-independent, pH-dependent, and intermediate-affinity choline transport systems. Choline uptake was concentration-dependently inhibited by hemicholinium-3 (HC-3), an inhibitor of choline uptake, and increased by lipopolysaccharide (LPS) and interleukin-4 (IL-4). Expression of the mRNA of M1 microglia markers IL-1β and IL-6 was increased by LPS, and their effects were suppressed by choline deprivation and HC-3. In contrast, mRNA expression of the M2 microglial marker arginase-1 (Arg-1) was increased by IL-4, and the effect was enhanced by choline deprivation and HC-3. Conclusions: Our results suggest that inhibition of CTL1-mediated choline uptake in microglia preferentially induces M2 microglia polarization, which is a potential therapeutic approach for inflammatory brain diseases.
Alterations of Mitochondrial Structure in Methamphetamine Toxicity
Authors: Lenzi Paola , Biagioni Francesca , Busceti Carla L. , Lazzeri Gloria , Polzella Maico , Frati Alessandro , Ferrucci Michela , Fornai Francesco
Published: August 2022

Recent evidence shows that methamphetamine (METH) produces mitochondrial alterations that contribute to neurotoxicity. Nonetheless, most of these studies focus on mitochondrial activity, whereas mitochondrial morphology remains poorly investigated. In fact, morphological evidence about the fine structure of mitochondria during METH toxicity is not available. Thus, in the present study we analyzed dose-dependent mitochondrial structural alterations during METH exposure. Light and transmission electron microscopy were used, along with ultrastructural stoichiometry of catecholamine cells following various doses of METH. In the first part of the study cell death and cell degeneration were assessed and they were correlated with mitochondrial alterations observed using light microscopy. In the second part of the study, ultrastructural evidence of specific mitochondrial alterations of crests, inner and outer membranes and matrix were quantified, along with in situ alterations of mitochondrial proteins. Neurodegeneration induced by METH correlates significantly with specific mitochondrial damage, which allows definition of a scoring system for mitochondrial integrity. In turn, mitochondrial alterations are concomitant with a decrease in fission/mitophagy protein Fis1 and DRP1 and an increase in Pink1 and Parkin in situ, at the mitochondrial level. These findings provide structural evidence that mitochondria represent both direct and indirect targets of METH-induced toxicity.
Moving towards the End of Gender Differences in the Habits of Use and Consumption of Mobile Video Games
Authors: Rodriguez-Barcenilla Eduardo , Ortega-Mohedano Félix
Published: August 2022

The world of video games has become one of the most important entertainment niches for society. In the last decade it has surpassed in turnover audio-visual markets such as cinema and music, driving the development of a new form of communication. The increase in the number of female gamers has highlighted the need to discover differences and similarities between players, both in habits and motivations. We present a study based on a survey procedure for the completion of a questionnaire that aimed to cover the age range of 18 to 30 years of Spanish youngsters and that reached a total of 711 valid responses. The results showed that there were no significant differences in terms of hours spent playing video games between the two genders, although there were motivational differences in the reasons for playing, specifically in terms of competition and challenge. The discussion of the results was carried out by means of a comparative statistical analysis of means to confirm the hypotheses and meet the objectives. Despite the existence of significant differences between genders, these were not as notable as might be expected. When it comes to gaming, as we have detected in our study, there were some consumption habits with differentiated gender patterns; however, in relevant indicators such as hours of consumption, increase in lockdown consumption, and spending, there were no significant differences. The gender gap that existed a few years ago between video gamers is becoming progressively narrower.
Prediction and Privacy Scheme for Traffic Flow Estimation on the Highway Road Network
Authors: Akallouch Mohammed , Akallouch Oussama , Fardousse Khalid , Bouhoute Afaf , Berrada Ismail
Published: August 2022

Accurate and timely traffic information is a vital element in intelligent transportation systems and urban management, which is vitally important for road users and government agencies. However, existing traffic prediction approaches are primarily based on standard machine learning which requires sharing direct raw information to the global server for model training. Further, user information may contain sensitive personal information, and sharing of direct raw data may lead to leakage of user private data and risks of exposure. In the face of the above challenges, in this work, we introduce a new hybrid framework that leverages Federated Learning with Local Differential Privacy to share model updates rather than directly sharing raw data among users. Our FL-LDP approach is designed to coordinate users to train the model collaboratively without compromising data privacy. We evaluate our scheme using a real-world public dataset and we implement different deep neural networks. We perform a comprehensive evaluation of our approach with state-of-the-art models. The prediction results of the experiment confirm that the proposed scheme is capable of building performance accurate traffic predictions, improving privacy preservation, and preventing data recovery attacks.
Mapping Thriving at Work as a Growing Concept: Review and Directions for Future Studies
Authors: Abid Ghulam , Contreras Francoise
Published: August 2022

This study aims to provide a bibliometric analysis of the literature on thriving at work in psychology and business/management produced between 2001 and 2021, using the Web of Science (WoS) database. The analyses allowed us to identify, through 190 documents, the emergence of the concept of thriving at work and its development. The main research variables related to this concept and its methodology were identified. Likewise, the most influential authors, the most cited articles, the more frequently cited journals, and the countries contributing to developing this construct are analyzed. In addition, an analysis of co-citation, co-occurrences, and bibliographic coupling was conducted. Finally, content analysis of the most popular keywords and the co-citation of cited references are conducted. These analyses allow the identification of the main developments in the topic of thriving at work. The theoretical and practical implications of this bibliometric analysis are discussed.
Nectar Dynamics and Pollinators Preference in Sunflower
Authors: Bergonzoli Simone , Romano Elio , Beni Claudio , Latterini Francesco , Lo Scalzo Roberto , Scarfone Antonio
Published: August 2022

Nectar is a complex biochemical substance secreted with particular rhythm by flower nectaries. Nectar is the base of a mutualism in which pollinators consume nectar, as food source, and are involuntarily responsible for the transport of pollen and pollination. The dynamics and temporal patterns of nectar secretion are still not fully understood as well as the environmental and climatic factors influencing its production. The quantity and quality of nectar found in standing crops at flowering influence the mutualistic relationship with pollinators and their foraging behavior. This situation is even more significant considering the reduction in undisturbed environments, the loss of soil quality, the spread of monoculture agricultural management and the use of self-fertile hybrids. The objects of the study are understanding the relationship among soil properties and nectar quality, comparing the nectar composition in a sunflower hybrid variety and evaluate pollinator preferences in selecting nectar sources among hybrid and non-hybrid varieties. For these purposes, two different experimental tests were established. Results highlighted that fertilization strategy influenced crop biomass development, determined soil characteristics and nectar composition in Sunflower. However, when comparing nectar composition of hybrid and non-hybrid varieties of sunflower, no significant differences were found. Despite this, the analysis of number of visits on the two treatments showed statistically significant differences. This research provides further understanding of the very complex relationship among soil, crop and nectar to support the definition of agricultural management strategies and reach the optimal nectar composition level for pollinators in agricultural crops.
Hydrodynamic Analysis of a Novel Modular Floating Structure System Integrated with Floating Artificial Reefs and Wave Energy Converters
Authors: Li Yanwei , Ren Nianxin , Li Xiang , Ou Jinping
Published: August 2022

A novel modular floating structure (MFS) system moored by tension legs was proposed, which is composed of hexagonal floating modules, floating artificial reefs and wave energy converters (WECs). The integration of floating artificial reefs and WECs into the MFS can improve the marine environment and produce considerable electricity. The effects of both wave characteristics and the module quantity on the hydrodynamic responses of the MFS system were studied in depth, based on a time-domain numerical model. Both the modules’ hydrodynamic interaction effect and the connectors’ mechanical coupling effect were considered. The results indicate that floating artificial reefs combined with WECs can effectively reduce wave loads and convert wave energy into electricity for the MFS system. More modules involved in the MFS system could significantly reduce motion response and produced more wave energy output, which indicates that the MFS system is suitable for large-scale expansion. The effect of different power take-off (PTO) damping coefficients on the WECs’ performance was further investigated, and the optimal damping coefficient was recommended for the MFS system. Finally, the main extreme responses of the MFS system were further investigated, and its safety was checked thoroughly. One survival strategy was proposed, which could efficiently reduce extreme connector loads by more than 50%.
Reference Genes Selection of Gymnosporangium yamadae during the Interaction with Apple Leaves
Authors: Shao Chenxi , Lao Wenhao , Liang Yingmei
Published: August 2022

Apple rust disease caused by Gymnosporangium yamadae is the one of the major threats to the development of the apple industry in China, but the pathogenic molecular mechanism of the disease remains unclear. It is imperative to screen out appropriate reference genes during the interaction between G. yamadae and apple leaves to analyze the gene expression patterns during the pathogenesis of G. yamadae. ACT, EF1, EF2, GAPDH, 40S, 60S, α-TUB, β-TUB and UBCE3 were selected as candidate reference genes based on the transcriptomic dataset of G. yamadae. The expression levels were tested by real-time quantitative PCR during time-course infection of apple leaves and the expression stabilities were evaluated by △Ct method as well as by three software (NormFinder, geNorm and BestKeeper) and one web-based analysis software (RefFinder). The expression stability of the candidate reference genes was further validated by using the effector candidate gene Cluster-3395.48660 as the target gene in RT-qPCR. According to the results by △Ct and BestKeeper, 40S, EF2 and EF1 were the most stable reference genes, while EF1, EF2 and GAPDH were the most stable reference genes based on the NormFinder analysis result. The geNorm recommended the most stable genes EF1, EF2 and α-TUB as reference genes. Comprehensive analysis results of the RefFinder indicated EF1, EF2 and α-TUB were the most suitable genes. Based on these results, EF1, EF2 and α-TUB were considered as reference genes for analyzing the gene expression profiles of Cluster-3395.48660 in different infection stages, and the results were consistent with the transcriptome data. All the results suggest that the combination of EF1, EF2 and α-TUB proved to be acceptable reference genes during the interaction between G. yamadae and apple leaves.
Combining T2Bacteria and T2Candida Panels for Diagnosing Intra-Abdominal Infections: A Prospective Multicenter Study
Authors: Krifors Anders , Ullberg Måns , Castegren Markus , Petersson Johan , Sparrelid Ernesto , Özenci Volkan , Blennow Ola
Published: August 2022

The T2Bacteria panel is a direct-from-blood assay that delivers rapid results, targeting E. coli, S. aureus, K. pneumoniae, A. baumanii, P. aeruginosa, and E. faecium (ESKAPE pathogens). In this study, T2Bacteria and T2Candida (targeting C. albicans/C. tropicalis, C. glabrata/C. krusei, and C. parapsilosis) were evaluated in parallel with blood cultures in 101 consecutive surgical patients with suspected intra-abdominal infection admitted to the intensive care unit or high dependency unit. Fifteen patients had bacteremia, with T2Bacteria correctly identifying all on-panel (n = 8) pathogens. T2Bacteria was positive in 19 additional patients, 11 of whom had supportive cultures from other normally sterile sites (newly inserted drains, perioperative cultures or blood cultures) within seven days. Six of these eleven patients (55%) received broad-spectrum antibiotics at the sampling time. T2Candida identified the two cases of blood-culture-positive candidemia and was positive in seven additional patients, three of whom were confirmed to have intra-abdominal candidiasis. Of four patients with concurrent T2Bacteria and T2Candida positivity, only one patient had positive blood cultures (candidemia), while three out of four patients had supporting microbiological evidence of a mixed infection. T2Bacteria and T2Candida were fast and accurate in diagnosing on-panel bloodstream infections, and T2Bacteria was able to detect culture-negative intra-abdominal infections.
Animal Histoplasmosis in Europe: Review of the Literature and Molecular Typing of the Etiological Agents
Authors: Wilmes Dunja , Mayer Ursula , Wohlsein Peter , Suntz Michael , Gerkrath Jasmin , Schulze Christoph , Holst Ina , von Bomhard Wolf , Rickerts Volker
Published: August 2022

Histoplasmosis has been previously diagnosed in animals from Europe. The aim of this study is to review the literature on these reports, to analyze cases diagnosed at our laboratory (2000–2022) and to improve molecular typing of Histoplasma capsulatum directly from tissue to study the molecular epidemiology of Histoplasma capsulatum causing animal infections in Europe. Including 15 cases studied in our laboratory, we identified 39 cases of animal histoplasmosis between 1968 and 2022. They were diagnosed mostly in superficial tissue biopsies from cats and badgers from Central Europe. Using phylogenetic analyses of six partial genes, we were able to classify eight of the etiological agents as belonging to a highly supported lineage within the Eurasian clade. This study confirms the occurrence of autochthonous histoplasmosis in animals in Central Europe and proposes the addition of new loci to the MLST scheme to study the molecular epidemiology of histoplasmosis using either formalin-fixed paraffin-embedded tissue and fresh or cadaveric biopsies.
Melatonin-Induced Inhibition of Shiraia Hypocrellin A Biosynthesis Is Mediated by Hydrogen Peroxide and Nitric Oxide
Authors: Wang Wenjuan , Huang Qunyan , Wang Yue , Li Xinping , Wang Jianwen , Zheng Liping
Published: August 2022

Melatonin (MLT), an evolutionarily conserved pleiotropic molecule, is implicated in numerous physiological processes in plants and animals. However, the effects of MLT on microbes have seldom been reported. In this study, we examined the influence of exogenous MLT on the growth and hypocrellin biosynthesis of bambusicolous fungus Shiraia sp. S9. Hypocrellin A (HA) is a photoactivated and photoinduced perylenequinone (PQ) toxin in Shiraia. Exogenous MLT at 100.00 μM not only decreased fungal conidiation and spore germination but inhibited HA contents significantly in fungal cultures under a light/dark (24 h:24 h) shift. MLT treatment was associated with higher activity of antioxidant enzymes (superoxide dismutase, catalase and peroxidase) and a marked decline in reactive oxygen species (ROS) production in the mycelia. Moreover, MLT induced endogenous nitric oxide (NO) production during the culture. The NO donor sodium nitroprusside (SNP) potentiated MLT-induced inhibition of O2− production, but NO scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) enhanced O2− production, whereas MLT-induced NO level was increased by the ROS scavenger vitamin C (Vc). The changes in NO and H2O2 were proved to be involved in the MLT-induced downregulation of the expressions of HA biosynthetic genes, leading to the suppression of HA production. This study provides new insight into the regulatory roles of MLT on fungal secondary metabolism activities and a basis for understanding self-resistance in phototoxin-producing fungi.
Exploring Awareness and Public Perception towards the Importance of Visual Aesthetics for Preservation of Permanent Forest Reserve (PFR) in Malaysia
Authors: Mundher Riyadh , Abu Bakar Shamsul , Maulan Suhardi , Mohd Yusof Mohd Johari , Osman Syuhaily , Al-Sharaa Ammar , Gao Hangyu
Published: August 2022

Malaysia has suffered a significant loss of forest cover over the years, mainly due to logging and land clearance for agriculture activities. Although the forest legislation has long been established and continuously enforced, it was not inclusive enough to protect the local natural resources. This study aims to identify public perception and awareness regarding values and essential aspects that affect the preservation of permanent forest reserves (PFR) in Malaysia. In particular, this study investigated the values of visual aesthetics to promote the preservation of Malaysian PFR within the existing legal framework. Results from the survey revealed that the public strongly perceived ecology and research education as the two most important aspects of preserving Malaysian PFR. The study also confirmed that visual aesthetics are considered a crucial aspect of forest classification and preservation beyond people’s health, safety, recreational, and economy. Interm of PFR functions, aesthetic is aslo the third most important factors after protection and research/education.
Special Issue Editorial: Mountains under Pressure
Authors: Marchant Robert A. , Cuni-Sanchez Aida
Published: August 2022

Mountains are highly significant regions in the context of climate change and sustainable development; they are situated at the intersection of accelerated climate warming, changes in moisture regime and support a large population that depends on mountains for their livelihoods, either directly or indirectly (Adler et al [...]