bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterisation of the Gut Bacteria of Cultured and Wild Spiny Lobster Panulirus ornatus
Authors: Ooi Mei C. , Trotter Andrew J. , Smith Gregory G. , Bridle Andrew R.
Published: February 2023

The commercial onshore aquaculture of the spiny lobster Panulirus ornatus, while in its infancy, has progressed rapidly from the enabling research that continues at the University of Tasmania. The development of lobster feeds, both fresh and manufactured, has been critical to the success of this emerging aquaculture sector. Fresh feeds derived from mussel represent the gold standard in terms of the growth performance of juvenile lobsters. Nonetheless, concerns regarding availability, sustainability, and potential biosecurity issues of fresh feeds highlight the importance of developing manufactured feeds for lobster aquaculture. Wild lobsters are assumed to have a balanced natural diet that allows for standard growth and development, and as such natural diets are often used as a reference for feed development. Similarly, the gut microbiota associated with a natural diet is assumed to reflect a healthy microbial assemblage. The aim of this study was to compare the microbiota of the hindgut and hepatopancreas of cultured P. ornatus fed with a commercial prawn pellet or mussel to that of wild spiny lobster juveniles. Gut samples were analysed using Oxford Nanopore 16S rRNA gene sequencing. Based on principal coordinate analysis, the gut bacteria of cultured lobsters were different from the wild juveniles. The core microbiota of the hindgut and hepatopancreas libraries were phyla Proteobacteria (Gamma, Alpha) and Bacteroidetes. Vibrio was the most dominant genus in both organs. The differences in bacterial relative abundance were mainly between cultured (pellet-, mussel-fed) and wild lobsters. In conclusion, bacteria in the cultured lobsters had significantly different profiles to that of the wild juveniles, indicating that current onshore aquaculture practices alter the gut microbiota. A number of different feeding and culture practices may be required if the aim of closed culture practices is to attain a gut microbiota in cultured animals that is representative of that found in wild spiny lobsters.
What Is It Like for You? Rethinking Voice Appropriation in Parafictional Identities in Israeli Art
Authors: Goldberg Keren
Published: February 2023

The article focuses on two parafictional figures created by Israeli artists at about the same time in the early 2000s: Oreet Ashery’s Marcus Fisher and Roee Rosen’s Justine Frank. Through a close reading of these case studies, I examine the phenomenon of parafictional characters as extreme cases of voice appropriation. Against the background of rising international concern with cultural appropriation, and of the Israeli sociopolitical context characterized by a multiplicity of often conflicting identities, I argue that such appropriation is, in fact, a basic aesthetic procedure. Using Hannah Arendt’s reading of Immanuel Kant’s aesthetic judgment as political judgment, and her articulation of an “enlarged mentality” as necessary for both aesthetic and political thinking, the article demonstrates how the ability to imagine a position different from your own is inherent for aesthetic representation as well as reception.
An Empirical Study on the Learning Experiences and Outcomes of College Student Club Committee Members Using a Linear Hierarchical Regression Model
Authors: Chen Ming-Kuo , Chien Hsin-Nan , Liu Ruo-Lan
Published: February 2023

This study explored college students’ learning experiences and outcomes as club committee members. Using a linear regression model, it investigated the relevance of personal background variables and club learning experiences to club learning outcomes. This study selected 15 universities and colleges’ student club committee members in TaiwanA total of 1850 questionnaires were distributed, and 1761 valid questionnaires were recovered, with a recovery rate of over 95%. The study findings are as follows: Regarding learning experiences and learning outcomes, the student club committee members was good. According to this study’s linear regression analysis: The personal background of student club committee members and their club learning experience had significant explanatory power on the learning outcomes, with R2 values ranging from 39.6% to 61.1% for each dimension. This indicates that learning from club activities can be an essential pathway to cultivating students’ learning outcomes and a valuable reference for promoting club education in colleges and universities in Taiwan. Higher education practitioners should plan activities or programs for student club leaders with learning outcomes in mind, and design learning programs to meet the needs of student club leaders in each school so that students can achieve higher quality learning outcomes. In addition, this study also found that the assessment indicators of learning outcomes of the CAS of the U.S. can be applied to check the learning outcomes of student clubs in higher education in Taiwan.
Data-Mining Techniques Based Relaying Support for Symmetric-Monopolar-Multi-Terminal VSC-HVDC System
Authors: Pragati Abha , Gadanayak Debadatta Amaresh , Parida Tanmoy , Mishra Manohar
Published: February 2023

Considering the advantage of the ability of data-mining techniques (DMTs) to detect and classify patterns, this paper explores their applicability for the protection of voltage source converter-based high voltage direct current (VSC-HVDC) transmission systems. In spite of the location of fault occurring points such as external/internal, rectifier-substation/inverter-substation, and positive/negative pole of the DC line, the stated approach is capable of accurate fault detection, classification, and location. Initially, the local voltage and current measurements at one end of the HVDC system are used in this work to extract the feature vector. Once the feature vector is retrieved, the DMTs are trained and tested to identify the fault types (internal DC faults, external AC faults, and external DC faults) and fault location in the particular feeder. In the data-mining framework, several state-of-the-art machine learning (ML) models along with one advanced deep learning (DL) model are used for training and testing. The proposed VSC-HVDC relaying system is comprehensively tested on a symmetric-monopolar-multi-terminal VSC-HVDC system and presents heartening results in diverse operating conditions. The results show that the studied deep belief network (DBN) based DL model performs better compared with other ML models in both fault classification and location. The accuracy of fault classification of the DBN is found to be 98.9% in the noiseless condition and 91.8% in the 20 dB noisy condition. Similarly, the DBN-based DMT is found to be effective in fault locations in the HVDC system with a smaller percentage of errors as MSE: 2.116, RMSE: 1.4531, and MAPE: 2.7047. This approach can be used as an effective low-cost relaying support tool for the VSC-HVDC system, as it does not necessitate a communication channel.
On Modified Integral Inequalities for a Generalized Class of Convexity and Applications
Authors: Srivastava Hari Mohan , Tariq Muhammad , Mohammed Pshtiwan Othman , Alrweili Hleil , Al-Sarairah Eman , De La Sen Manuel
Published: February 2023

In this paper, we concentrate on and investigate the idea of a novel family of modified p-convex functions. We elaborate on some of this newly proposed idea’s attractive algebraic characteristics to support it. This is used to study some novel integral inequalities in the frame of the Hermite–Hadamard type. A unique equality is established for differentiable mappings. The Hermite–Hadamard inequality is extended and estimated in a number of new ways with the help of this equality to strengthen the findings. Finally, we investigate and explore some applications for some special functions. We think the approach examined in this work will further pique the interest of curious researchers.
Recent Progress in Solid Electrolytes for All-Solid-State Metal(Li/Na)–Sulfur Batteries
Authors: Bhardwaj Ravindra Kumar , Zitoun David
Published: February 2023

Metal–sulfur batteries, especially lithium/sodium–sulfur (Li/Na-S) batteries, have attracted widespread attention for large-scale energy application due to their superior theoretical energy density, low cost of sulfur compared to conventional lithium-ion battery (LIBs) cathodes and environmental sustainability. Despite these advantages, metal–sulfur batteries face many fundamental challenges which have put them on the back foot. The use of ether-based liquid electrolyte has brought metal–sulfur batteries to a critical stage by causing intermediate polysulfide dissolution which results in poor cycling life and safety concerns. Replacement of the ether-based liquid electrolyte by a solid electrolyte (SEs) has overcome these challenges to a large extent. This review describes the recent development and progress of solid electrolytes for all-solid-state Li/Na-S batteries. This article begins with a basic introduction to metal–sulfur batteries and explains their challenges. We will discuss the drawbacks of the using liquid organic electrolytes and the advantages of replacing liquid electrolytes with solid electrolytes. This article will also explain the fundamental requirements of solid electrolytes in meeting the practical applications of all solid-state metal–sulfur batteries, as well as the electrode–electrolyte interfaces of all solid-state Li/Na-S batteries.
Coating Defects of Lithium-Ion Battery Electrodes and Their Inline Detection and Tracking
Authors: Schoo Alexander , Moschner Robin , Hülsmann Jens , Kwade Arno
Published: February 2023

In order to reduce the cost of lithium-ion batteries, production scrap has to be minimized. The reliable detection of electrode defects allows for a quality control and fast operator reaction in ideal closed control loops and a well-founded decision regarding whether a piece of electrode is scrap. A widely used inline system for defect detection is an optical detection system based on line scan cameras and specialized lighting. The cameras scan the electrode, and brightness differences on the surface are detected and processed inline. The characteristics of the defect image are used for automated classification of the defects based on image features. Furthermore, the detailed detection of defects allows for the identification of causes. This paper describes the working principle of such an inline detection system, the catalog of typical defects, and the image features used to classify them automatically. Furthermore, we propose and discuss causes and effects of the different defect types on the basis of the literature and expert experience. In combination with tracking and tracing, this enables the manufacturer to reduce scrap by detecting defects early in the production chain.
Crystal Group Prediction for Lithiated Manganese Oxides Using Machine Learning
Authors: Prosini Pier Paolo
Published: February 2023

This work aimed to predict the crystal structure of a compound starting only from the knowledge of its chemical composition. The method was developed to select new materials in the field of lithium-ion batteries and tested on Li-Fe-O compounds. For each testing compound, the correspondence with respect to the training compounds was evaluated simply by calculating the Euclidean distance existing between the stoichiometric coefficients of the elements constituting the two compounds. At the compound under test was assigned the crystal structure of the training compound for which the distance value was minimum. The results showed that the model can predict the crystalline group of the test compound with an accuracy higher than 80% and a precision higher than 90%, for a cut-off distance higher than four. The method was then used to predict the crystalline group of manganese-based compounds (Li-Mn-O). The analysis conducted on twenty randomly selected compounds showed an accuracy of 70%. Out of ten valid predictions, nine were true positives, with a precision of 90%.
Cascade of Denoising and Mapping Neural Networks for MRI R2* Relaxometry of Iron-Loaded Liver
Authors: Lu Qiqi , Wang Changqing , Lian Zifeng , Zhang Xinyuan , Yang Wei , Feng Qianjin , Feng Yanqiu
Published: February 2023

MRI of effective transverse relaxation rate (R2*) measurement is a reliable method for liver iron concentration quantification. However, R2* mapping can be degraded by noise, especially in the case of iron overload. This study aimed to develop a deep learning method for MRI R2* relaxometry of an iron-loaded liver using a two-stage cascaded neural network. The proposed method, named CadamNet, combines two convolutional neural networks separately designed for image denoising and parameter mapping into a cascade framework, and the physics-based R2* decay model was incorporated in training the mapping network to enforce data consistency further. CadamNet was trained using simulated liver data with Rician noise, which was constructed from clinical liver data. The performance of CadamNet was quantitatively evaluated on simulated data with varying noise levels as well as clinical liver data and compared with the single-stage parameter mapping network (MappingNet) and two conventional model-based R2* mapping methods. CadamNet consistently achieved high-quality R2* maps and outperformed MappingNet at varying noise levels. Compared with conventional R2* mapping methods, CadamNet yielded R2* maps with lower errors, higher quality, and substantially increased efficiency. In conclusion, the proposed CadamNet enables accurate and efficient iron-loaded liver R2* mapping, especially in the presence of severe noise.
Tau; One Protein, So Many Diseases
Authors: Tabeshmehr Parisa , Eftekharpour Eftekhar
Published: February 2023

Tau, a member of the microtubule-associated proteins, is a known component of the neuronal cytoskeleton; however, in the brain tissue, it is involved in other vital functions beyond maintaining the cellular architecture. The pathologic tau forms aggregates inside the neurons and ultimately forms the neurofibrillary tangles. Intracellular and extracellular accumulation of different tau isoforms, including dimers, oligomers, paired helical filaments and tangles, lead to a highly heterogenous group of diseases named “Tauopathies”. About twenty-six different types of tauopathy diseases have been identified that have different clinical phenotypes or pathophysiological characteristics. Although all these diseases are identified by tau aggregation, they are distinguishable based on the specific tau isoforms, the affected cell types and the brain regions. The neuropathological and phenotypical heterogeneity of these diseases impose significant challenges for discovering new diagnostic and therapeutic strategies. Here, we review the recent literature on tau protein and the pathophysiological mechanisms of tauopathies. This article mainly focuses on physiologic and pathologic tau and aims to summarize the upstream and downstream events and discuss the current diagnostic approaches and therapeutic strategies.
Extracellular Vesicles in Lung Cancer: Bystanders or Main Characters?
Authors: Tinè Mariaenrica , Biondini Davide , Damin Marco , Semenzato Umberto , Bazzan Erica , Turato Graziella
Published: February 2023

Lung cancer still represents the main cause of cancer death worldwide. The poor survival is mainly related to the diagnosis which is often obtained in advanced stages when the disease is unresectable and characterized by the worst prognosis. Only in the last decades have great discoveries led to the development of new therapies targeted to oncogenes and to boost the host immune response against the tumor. Tumor identification and molecular/immunological characterization rely on bioptic samples which represent the gold standard for diagnosis. Nonetheless, less invasive procedures providing small samples will be more and more common in the future. Extracellular vesicles (EV), submicron particles released by any cell type, are candidates for diagnostic and prognostic biomarkers. EV are mediators of intercellular communication and can convey cytokines, miRNAs, antigens, and many other factors of tumorigenesis. This review summarizes the most appealing findings on lung-cancer-related EV, debating the evidence on circulating versus airway EV as potential biomarkers in disease management and the main studies on the role of these particles on lung cancer pathogenesis. Overall, the available results point toward a wide range of possible applications, supported by the promising achievements of genotyping on BAL fluid EV and proteomic analysis on pleural effusion EV. Nonetheless, the study of lung EV is still affected by remarkable methodological issues, especially when in vitro evidence is translated into humans. Whether EV still represent an “information fog” or can be useful in lung cancer management will be discussed, with possible hints on how to improve their usage.
Cumulus Cell Transcriptome after Cumulus-Oocyte Complex Exposure to Nanomolar Cadmium in an In Vitro Animal Model of Prepubertal and Adult Age
Authors: Martino Nicola Antonio , Picardi Ernesto , Ciani Elena , D’Erchia Anna Maria , Bogliolo Luisa , Ariu Federica , Mastrorocco Antonella , Temerario Letizia , Mansi Luigi , Palumbo Valeria , Pesole Graziano , Dell’Aquila Maria Elena
Published: February 2023

Cadmium (Cd), a highly toxic pollutant, impairs oocyte fertilization, through oxidative damage on cumulus cells (CCs). This study analysed the transcriptomic profile of CCs of cumulus-oocyte complexes (COCs) from adult and prepubertal sheep, exposed to Cd nanomolar concentration during in vitro maturation. In both age-groups, CCs of matured oocytes underwent RNA-seq, data analysis and validation. Differentially expressed genes (DEGs) were identified in adult (n = 99 DEGs) and prepubertal (n = 18 DEGs) CCs upon Cd exposure. Transcriptomes of adult CCs clustered separately between Cd-exposed and control samples, whereas prepubertal ones did not as observed by Principal Component Analysis. The transcriptomic signature of Cd-induced CC toxicity was identified by gene annotation and literature search. Genes associated with previous studies on ovarian functions and/or Cd effects were confirmed and new genes were identified, thus implementing the knowledge on their involvement in such processes. Enrichment and validation analysis showed that, in adult CCs, Cd acted as endocrine disruptor on DEGs involved in hormone biosynthesis, cumulus expansion, regulation of cell signalling, growth and differentiation and oocyte maturation, whereas in prepubertal CCs, Cd affected DEGs involved in CC development and viability and CC-oocyte communications. In conclusion, these DEGs could be used as valuable non-invasive biomarkers for oocyte competence.
Added Value of Abnormal Lymph Nodes Detected with FDG-PET/CT in Suspected Vascular Graft Infection
Authors: van Rijsewijk Nick D. , Helthuis Jasper H. G. , Glaudemans Andor W. J. M. , Wouthuyzen-Bakker Marjan , Prakken Niek H. J. , Liesker David J. , Saleem Ben R. , Slart Riemer H. J. A.
Published: February 2023

Vascular graft and endograft infections (VGEI) cause a serious morbidity and mortality burden. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) imaging is frequently used in the diagnostic workup, but the additional value of abnormal (18F-FDG active and/or enlarged) locoregional lymph nodes is unknown. In this retrospective study, the additional diagnostic value of abnormal locoregional lymph nodes on 18F-FDG PET/CT imaging for VGEI was evaluated, including 54 patients with a culture-proven VGEI (defined according to the Management of Aortic Graft Infection [MAGIC] group classification) and 25 patients without VGEI. 18F-FDG PET/CT was qualitatively and quantitatively assessed for tracer uptake and pattern at the location of the vascular graft, and locoregional lymph node uptake and enlargement (>10 mm). 18F-FDG uptake intensity and pattern independently predicted the presence of VGEI by logistic regression (Χ2: 46.19, p < 0.001), with an OR of 7.38 (95% CI [1.65, 32.92], p = 0.009) and 18.32 (95% CI [3.95, 84.88], p < 0.001), respectively. Single visual assessment of abnormal locoregional lymph nodes predicted the presence of VGEI with a sensitivity of 35%, specificity of 96%, PPV of 95%, and NPV of 41%. The visual assessment of abnormal lymph nodes after qualitative assessment of 18F-FDG uptake intensity and pattern at the vascular graft location did not independently predict the presence of VGEI by logistic regression (Χ2: 3.60, p = 0.058; OR: 8.25, 95% CI [0.74, 63.37], p = 0.096). In conclusion, detection of abnormal locoregional lymph nodes on 18F-FDG PET/CT has a high specificity (96%) and PPV (95%) for VGEI. However, it did not add to currently used 18F-FDG PET/CT interpretation criteria.
Inter-Individual Variation in DNA Methylation Patterns across Two Tissues and Leukocytes in Mature Brahman Cattle
Authors: Baker Emilie C. , San Audrey E. , Cilkiz Kubra Z. , Littlejohn Brittni P. , Cardoso Rodolfo C. , Ghaffari Noushin , Long Charles R. , Riggs Penny K. , Randel Ronald D. , Welsh Thomas H. , Riley David G.
Published: February 2023

Quantifying the natural inter-individual variation in DNA methylation patterns is important for identifying its contribution to phenotypic variation, but also for understanding how the environment affects variability, and for incorporation into statistical analyses. The inter-individual variation in DNA methylation patterns in female cattle and the effect that a prenatal stressor has on such variability have yet to be quantified. Thus, the objective of this study was to utilize methylation data from mature Brahman females to quantify the inter-individual variation in DNA methylation. Pregnant Brahman cows were transported for 2 h durations at days 60 ± 5; 80 ± 5; 100 ± 5; 120 ± 5; and 140 ± 5 of gestation. A non-transport group was maintained as a control. Leukocytes, amygdala, and anterior pituitary glands were harvested from eight cows born from the non-transport group (Control) and six from the transport group (PNS) at 5 years of age. The DNA harvested from the anterior pituitary contained the greatest variability in DNA methylation of cytosine-phosphate-guanine (mCpG) sites from both the PNS and Control groups, and the amygdala had the least. Numerous variable mCpG sites were associated with retrotransposable elements and highly repetitive regions of the genome. Some of the genomic features that had high variation in DNA methylation are involved in immune responses, signaling, responses to stimuli, and metabolic processes. The small overlap of highly variable CpG sites and features between tissues and leukocytes supports the role of variable DNA methylation in regulating tissue-specific gene expression. Many of the CpG sites that exhibited high variability in DNA methylation were common between the PNS and Control groups within a tissue, but there was little overlap in genomic features with high variability. The interaction between the prenatal environment and the genome could be responsible for the differences in location of the variable DNA methylation.
The Sensitivity of Tau Tracers for the Discrimination of Alzheimer’s Disease Patients and Healthy Controls by PET
Authors: Mohammadi Zohreh , Alizadeh Hadi , Marton János , Cumming Paul
Published: February 2023

Hyperphosphorylated tau aggregates, also known as neurofibrillary tangles, are a hallmark neuropathological feature of Alzheimer’s disease (AD). Molecular imaging of tau by positron emission tomography (PET) began with the development of [18F]FDDNP, an amyloid β tracer with off-target binding to tau, which obtained regional specificity through the differing distributions of amyloid β and tau in AD brains. A concerted search for more selective and affine tau PET tracers yielded compounds belonging to at least eight structural categories; 18F-flortaucipir, known variously as [18F]-T807, AV-1451, and Tauvid®, emerged as the first tau tracer approved by the American Food and Drug Administration. The various tau tracers differ concerning their selectivity over amyloid β, off-target binding at sites such as monoamine oxidase and neuromelanin, and degree of uptake in white matter. While there have been many reviews of molecular imaging of tau in AD and other conditions, there has been no systematic comparison of the fitness of the various tracers for discriminating between AD patient and healthy control (HC) groups. In this narrative review, we endeavored to compare the binding properties of the various tau tracers in vitro and the effect size (Cohen’s d) for the contrast by PET between AD patients and age-matched HC groups. The available tracers all gave good discrimination, with Cohen’s d generally in the range of two–three in culprit brain regions. Overall, Cohen’s d was higher for AD patient groups with more severe illness. Second-generation tracers, while superior concerning off-target binding, do not have conspicuously higher sensitivity for the discrimination of AD and HC groups. We suppose that available pharmacophores may have converged on a maximal affinity for tau fibrils, which may limit the specific signal imparted in PET studies.
Identification of Novel Coloboma Candidate Genes through Conserved Gene Expression Analyses across Four Vertebrate Species
Authors: Trejo-Reveles Violeta , Owen Nicholas , Ching Chan Brian Ho , Toms Maria , Schoenebeck Jeffrey J. , Moosajee Mariya , Rainger Joe
Published: February 2023

Ocular coloboma (OC) is a failure of complete optic fissure closure during embryonic development and presents as a tissue defect along the proximal–distal axis of the ventral eye. It is classed as part of the clinical spectrum of structural eye malformations with microphthalmia and anophthalmia, collectively abbreviated to MAC. Despite deliberate attempts to identify causative variants in MAC, many patients remain without a genetic diagnosis. To reveal potential candidate genes, we utilised transcriptomes experimentally generated from embryonic eye tissues derived from humans, mice, zebrafish, and chicken at stages coincident with optic fissure closure. Our in-silico analyses found 10 genes with optic fissure-specific enriched expression: ALDH1A3, BMPR1B, EMX2, EPHB3, NID1, NTN1, PAX2, SMOC1, TENM3, and VAX1. In situ hybridization revealed that all 10 genes were broadly expressed ventrally in the developing eye but that only PAX2 and NTN1 were expressed in cells at the edges of the optic fissure margin. Of these conserved optic fissure genes, EMX2, NID1, and EPHB3 have not previously been associated with human MAC cases. Targeted genetic manipulation in zebrafish embryos using CRISPR/Cas9 caused the developmental MAC phenotype for emx2 and ephb3. We analysed available whole genome sequencing datasets from MAC patients and identified a range of variants with plausible causality. In combination, our data suggest that expression of genes involved in ventral eye development is conserved across a range of vertebrate species and that EMX2, NID1, and EPHB3 are candidate loci that warrant further functional analysis in the context of MAC and should be considered for sequencing in cohorts of patients with structural eye malformations.
The Actin Network Interfacing Diverse Integrin-Mediated Adhesions
Authors: Geiger Benjamin , Boujemaa-Paterski Rajaa , Winograd-Katz Sabina E. , Balan Venghateri Jubina , Chung Wen-Lu , Medalia Ohad
Published: February 2023

The interface between the cellular actin network and diverse forms of integrin-mediated cell adhesions displays a unique capacity to serve as accurate chemical and mechanical sensors of the cell’s microenvironment. Focal adhesion-like structures of diverse cell types, podosomes in osteoclasts, and invadopodia of invading cancer cells display distinct morphologies and apparent functions. Yet, all three share a similar composition and mode of coupling between a protrusive structure (the lamellipodium, the core actin bundle of the podosome, and the invadopodia protrusion, respectively), and a nearby adhesion site. Cytoskeletal or external forces, applied to the adhesion sites, trigger a cascade of unfolding and activation of key adhesome components (e.g., talin, vinculin, integrin), which in turn, trigger the assembly of adhesion sites and generation of adhesion-mediated signals that affect cell behavior and fate. The structural and molecular mechanisms underlying the dynamic crosstalk between the actin cytoskeleton and the adhesome network are discussed.
Intracellular Sugar Transporters Facilitate Cellulase Synthesis in Trichoderma reesei Using Lactose
Authors: Wang Haiyan , Pang Ai-Ping , Li Bingzhi , Huo Liujie , Wu Fu-Gen , Lin Fengming
Published: February 2023

Sugar transporters play an important role in the cellulase production of lignocellulose-degrading fungi. Nevertheless, the role and function of these transporters are still unclear. Here we first report intracellular sugar transporters assisting cellulase production in Trichoderma reesei (T. reesei) using lactose. The mRNA levels of sugar transporter genes mfs, gst, and lac1 were substantially upregulated in T. reesei cultivated on lactose, with the most abundant mRNA levels at 24 h as compared to glucose. Moreover, the individual deletion of these sugar transporters significantly inhibited cellulase production, solid cell growth, and sporulation of T. reesei, suggesting they play a supporting role in cellulase production when grown in lactose. Surprisingly, MFS, GST, and LAC1 were mainly localized in the cytoplasm, with MFS and LAC1 in the endoplasmic reticulum (ER), representing the first discovery of intracellular sugar transporters involved in cellulase biosynthesis in lactose culture. The absence of the gene lac1 noticeably inhibited most of the crucial genes related to cellulase production, including cellulase-encoding genes, transcription factors, and sugar transporters, at 24 h, which was fully relieved at 48 h or 72 h, indicating that lac1 affects cellulase production more at the early step. This research advances the understanding of the function of intracellular sugar transporters in fungi, particularly for fungal cellulase production.
Bacterial Quorum-Sensing Peptides as Immune Modulators Present in Systemic Circulation
Authors: De Spiegeleer Anton , Descamps Amélie , Govindarajan Srinath , Coudenys Julie , Van der borght Kevin , Hirmz Hannah , Van Den Noortgate Nele , Elewaut Dirk , De Spiegeleer Bart , Wynendaele Evelien
Published: February 2023

Quorum-sensing peptides (QSPs) are bacterial peptides traditionally considered only as inter-bacterial communication molecules. Recently, their involvement in microbiome–host interactions influencing host diseases such as cancer and sarcopenia were explored. However, it is still unknown to what extent these peptides have the potential to modulate the immune system. In this proof-of-concept study, we screened 89 QSPs for their potential to induce IL-6 and TNFα in murine splenocytes and J774 macrophages. Confirmatory experiments on the positive screening-hits were conducted using murine splenocytes and human PBMCs of different ages. Finally, to investigate the biological relevance of immunomodulatory QSPs, we analysed plasma in a human cohort for the presence of the immunomodulatory QSP Q010. To do this, we used a newly developed UHPLC-MS/MS method. Our findings indicated that specific QSPs activate immune cells in vitro, with Q007, Q010, Q017 and Q212 being the top four screening hits. Q007 and Q010 were affirmed in subsequent confirmatory experiments using murine splenocytes and human PBMCs. Finally, Q010 was detected in human plasma, demonstrating for the first time the presence of an immunomodulatory QSP in human circulation. In conclusion, our data are the first evidence indicating the potential of biologically relevant quorum-sensing peptides to modulate the immune system.
The Associations of Neutrophil–Lymphocyte, Platelet–Lymphocyte, Monocyte–Lymphocyte Ratios and Immune-Inflammation Index with Negative Symptoms in Patients with Schizophrenia
Authors: Šagud Marina , Madžarac Zoran , Nedic Erjavec Gordana , Šimunović Filipčić Ivona , Mikulić Filip Luka , Rogić Dunja , Bradaš Zoran , Bajs Janović Maja , Pivac Nela
Published: February 2023

Neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR) and systemic immune-inflammation index (SII index) are increasingly used as indicators of inflammation in different conditions, including schizophrenia. However, their relationship with negative symptoms, including anhedonia, is largely unknown. Included were 200 patients with schizophrenia and 134 healthy controls (HC), assessed for physical anhedonia (PA), using the Revised Physical Anhedonia Scale (RPAS), and social anhedonia (SA) by the Revised Social Anhedonia Scale (RSAS). Patients were rated by the Positive and Negative Syndrome Scale (PANSS), the Clinical Assessment Interview for Negative Symptoms (CAINS) and the Brief Negative Symptom Scale (BNSS). Most of the negative symptoms were in a weak to moderate positive correlations with blood cell inflammatory ratios, namely, between NLR and MLR with PANSS negative scale, CAINS, and BNSS, and in male patients, between PLR and PANSS negative scale and CAINS. Fewer correlations were detected in females, but also in a positive direction. An exception was SA, given the negative correlation between its severity and the SII index in females, and its presence and higher PLR in males. While different negative symptoms were associated with subclinical inflammation, the relationship between SA and lower inflammatory markers deserves further exploration.
The Role of a Cytokinin Antagonist in the Progression of Clubroot Disease
Authors: Bíbová Jana , Kábrtová Veronika , Večeřová Veronika , Kučerová Zuzana , Hudeček Martin , Plačková Lenka , Novák Ondřej , Strnad Miroslav , Plíhal Ondřej
Published: February 2023

Plasmodiophora brassicae is an obligate biotrophic pathogen causing clubroot disease in cruciferous plants. Infected plant organs are subject to profound morphological changes, the roots form characteristic galls, and the leaves are chlorotic and abscise. The process of gall formation is governed by timely changes in the levels of endogenous plant hormones that occur throughout the entire life cycle of the clubroot pathogen. The homeostasis of two plant hormones, cytokinin and auxin, appears to be crucial for club development. To investigate the role of cytokinin and auxin in gall formation, we used metabolomic and transcriptomic profiling of Arabidopsis thaliana infected with clubroot, focusing on the late stages of the disease, where symptoms were more pronounced. Loss-of-function mutants of three cytokinin receptors, AHK2, AHK3, and CRE1/AHK4, were employed to further study the homeostasis of cytokinin in response to disease progression; ahk double mutants developed characteristic symptoms of the disease, albeit with varying intensity. The most susceptible to clubroot disease was the ahk3 ahk4 double mutant, as revealed by measuring its photosynthetic performance. Quantification of phytohormone levels and pharmacological treatment with the cytokinin antagonist PI-55 showed significant changes in the levels of endogenous cytokinin and auxin, which was manifested by both enhanced and reduced development of disease symptoms in different genotypes.
Molecular Docking and Site-Directed Mutagenesis of GH49 Family Dextranase for the Preparation of High-Degree Polymerization Isomaltooligosaccharide
Authors: Wang Huanyu , Lin Qianru , Liu Mingwang , Ding Wen , Weng Nanhai , Ni Hao , Lu Jing , Lyu Mingsheng , Wang Shujun
Published: February 2023

The high-degree polymerization of isomaltooligosaccharide (IMO) not only effectively promotes the growth and reproduction of Bifidobacterium in the human body but also renders it resistant to rapid degradation by gastric acid and can stimulate insulin secretion. In this study, we chose the engineered strain expressed dextranase (PsDex1711) as the research model and used the AutoDock vina molecular docking technique to dock IMO4, IMO5, and IMO6 with it to obtain mutation sites, and then studied the potential effect of key amino acids in this enzyme on its hydrolysate composition and enzymatic properties by site-directed mutagenesis method. It was found that the yield of IMO4 increased significantly to 62.32% by the mutant enzyme H373A. Saturation mutation depicted that the yield of IMO4 increased to 69.81% by the mutant enzyme H373R, and its neighboring site S374R IMO4 yield was augmented to 64.31%. Analysis of the enzymatic properties of the mutant enzyme revealed that the optimum temperature of H373R decreased from 30 °C to 20 °C, and more than 70% of the enzyme activity was maintained under alkaline conditions. The double-site saturation mutation results showed that the mutant enzyme H373R/N445Y IMO4 yield increased to 68.57%. The results suggest that the 373 sites with basic non-polar amino acids, such as arginine and histidine, affect the catalytic properties of the enzyme. The findings provide an important theoretical basis for the future marketable production of IMO4 and analysis of the structure of dextranase.
Biological and Genetic Mechanisms of COPD, Its Diagnosis, Treatment, and Relationship with Lung Cancer
Authors: Czarnecka-Chrebelska Karolina H. , Mukherjee Debjita , Maryanchik Sofya V. , Rudzinska-Radecka Magdalena
Published: February 2023

Chronic obstructive pulmonary disease (COPD) is one of the most prevalent chronic adult diseases, with significant worldwide morbidity and mortality. Although long-term tobacco smoking is a critical risk factor for this global health problem, its molecular mechanisms remain unclear. Several phenomena are thought to be involved in the evolution of emphysema, including airway inflammation, proteinase/anti-proteinase imbalance, oxidative stress, and genetic/epigenetic modifications. Furthermore, COPD is one main risk for lung cancer (LC), the deadliest form of human tumor; formation and chronic inflammation accompanying COPD can be a potential driver of malignancy maturation (0.8–1.7% of COPD cases develop cancer/per year). Recently, the development of more research based on COPD and lung cancer molecular analysis has provided new light for understanding their pathogenesis, improving the diagnosis and treatments, and elucidating many connections between these diseases. Our review emphasizes the biological factors involved in COPD and lung cancer, the advances in their molecular mechanisms’ research, and the state of the art of diagnosis and treatments. This work combines many biological and genetic elements into a single whole and strongly links COPD with lung tumor features.
Atherosclerosis and Endometriosis: The Role of Diet and Oxidative Stress in a Gender-Specific Disorder
Authors: Cirillo Michela , Argento Flavia Rita , Attanasio Monica , Becatti Matteo , Ladisa Irene , Fiorillo Claudia , Coccia Maria Elisabetta , Fatini Cinzia
Published: February 2023

Background: Accelerated atherosclerosis in patients with endometriosis has been hypothesised, and lifestyle improvement might control cardiovascular risk. We explored cardiometabolic markers and oxidative stress and evaluated the effects of the Mediterranean Diet (MD) in modulating these markers. Methods: In this prospective study, we included 35 women with endometriosis. At baseline (T0) and after 3 (T1) and 6 (T2) months from the start of the diet, we investigated cardiometabolic parameters, lifestyle and oxidative stress. Results: After a 3-month intervention with MD, we observed a significant reduction in total cholesterol (p = 0.01) and LDL-c (p = 0.003). We observed at T1 an increase in B12 and E vitamins, folate and zinc. After 6 months, zinc (p = 0.04) and folate (p = 0.08) increased in comparison to T0. A reduction in homocysteine from T0 to T1 (p = 0.01) was found. After 3 months, an increase in Rapid Assessment of Physical Activity tool 1 (RAPA) (p < 0.001) and RAPA 2 was observed (p = 0.009). We observed high levels of oxidative stress markers at baseline. After 6 months of MD, a significant improvement in lymphocyte Reactive Oxygen Species (ROS) (p < 0.001) and total antioxidant capacity was observed (p = 0.02). Conclusions: The improvement of lifestyle, and in particular the Mediterranean dietary intervention, allowed the improvement of the metabolic and oxidative profile and overall health-related quality of life.
Chimeric Newcastle Disease Virus Vectors Expressing Human IFN-γ Mediate Target Immune Responses and Enable Multifaceted Treatments
Authors: Soliman Rofaida Mostafa , Nishioka Keisuke , Daidoji Tomo , Noyori Osamu , Nakaya Takaaki
Published: February 2023

The therapeutic potential of Newcastle disease virus (NDV) has been reported as both an oncolytic agent and a vaccine vector against many antigens. However, in the individuals already immunized with NDVs, second and subsequent administration does not provide substantial benefits. In this study, two types of recombinant chimeric NDVs using APMV-2 F and HN genes were generated. In rNDV-2HN, the wild-type NDV HN gene was replaced with the APMV-2 HN gene, and in rNDV-2F/2HN, both wild-type F and HN genes were replaced with APMV-2 F and HN genes, respectively. We enhanced the immune responses of these chimeric viruses by inserting the human IFN-γ gene. To examine the escape from NDV antiserum, each virus was treated with diluted NDV antiserum, and HEp-2 cells were infected with these virus particles. The two constructed chimeric viruses indicated notably lower virus-neutralizing titer compared to wild-type NDV and escaped the action of NDV antiserum. These two chimeric viruses infected both respiratory and colon cancer cell lines, indicating their potential as a cancer treatment tool. Chimeric viruses with enhanced immune responses can be considered a novel therapeutic strategy in cancer treatment that can be administered multiple times and used to enhance immune cells interaction.
Brain-Type Creatine Kinase Release from Cultured Osteoclasts Exposed to Neridronate in Children Affected by Osteogenesis Imperfecta Type 1
Authors: Faienza Maria Felicia , Tummolo Albina , Celli Mauro , Finocchiaro Roberto , Piacente Laura , Di Serio Francesca , Nicchia Grazia Paola , Brunetti Giacomina , D’Eufemia Patrizia
Published: February 2023

Brain-type creatine kinase (CK-BB) increases during osteoclastogenesis, with high circulating amounts in type I osteogenesis imperfecta (OI) following treatment with neridronate, a bisphosphonate able to inhibit osteoclast activity and survival. The aim of this study was to demonstrate the correlation between osteoclastogenesis and CK-BB release from OI patients’ osteoclasts treated with different concentrations of neridronate. Our patients showed reduced bone quality, increased levels of CTX I, a marker of bone resorption, and decreased levels of OPG, an inhibitor of osteoclastogenesis. In OI patients, the presence of MCSF and RANKL determined an increased secretion of CK-BB from osteoclasts (p = 0.04) compared with control conditions without these cytokines; interestingly, in the absence of these factors, the secretion of CK-BB is significantly elevated at 3 µmol/L compared with 0.03 and 1 µmol/L (p = 0.007). In healthy donors’ cultures, the higher concentration of CK-BB can be detected following stimulation with 3 µmol/L neridronate compared with the untreated condition both with and without MCSF and RANKL (p = 0.03 and p = 0.006, respectively). Consistently, in osteoclast cultures, neridronate treatment is associated with a decrease in multinucleated TRAP+ cells, together with morphology changes typical of apoptosis. Consistently, in the media of the same osteoclast cultures, we demonstrated a significant increase in caspase-3 levels. In conclusion, our findings support the idea that CK-BB levels increase in the serum of OI-treated patients.
Indole Alkaloids from Psychoactive Mushrooms: Chemical and Pharmacological Potential as Psychotherapeutic Agents
Authors: Plazas Erika , Faraone Nicoletta
Published: February 2023

Neuropsychiatric diseases such as depression, anxiety, and post-traumatic stress represent a substantial long-term challenge for the global health systems because of their rising prevalence, uncertain neuropathology, and lack of effective pharmacological treatments. The approved existing studies constitute a piece of strong evidence whereby psychiatric drugs have shown to have unpleasant side effects and reduction of sustained tolerability, impacting patients’ quality of life. Thus, the implementation of innovative strategies and alternative sources of bioactive molecules for the search for neuropsychiatric agents are required to guarantee the success of more effective drug candidates. Psychotherapeutic use of indole alkaloids derived from magic mushrooms has shown great interest and potential as an alternative to the synthetic drugs currently used on the market. The focus on indole alkaloids is linked to their rich history, their use as pharmaceuticals, and their broad range of biological properties, collectively underscoring the indole heterocycle as significant in drug discovery. In this review, we aim to report the physicochemical and pharmacological characteristics of indole alkaloids, particularly those derived from magic mushrooms, highlighting the promising application of such active ingredients as safe and effective therapeutic agents for the treatment of neuropsychiatric disorders.
Hyperactivation of p21-Activated Kinases in Human Cancer and Therapeutic Sensitivity
Authors: Sankaran Deivendran , Amjesh Revikumar , Paul Aswathy Mary , George Bijesh , Kala Rajat , Saini Sunil , Kumar Rakesh
Published: February 2023

Over the last three decades, p21-activated kinases (PAKs) have emerged as prominent intracellular nodular signaling molecules in cancer cells with a spectrum of cancer-promoting functions ranging from cell survival to anchorage-independent growth to cellular invasiveness. As PAK family members are widely overexpressed and/or hyperactivated in a variety of human tumors, over the years PAKs have also emerged as therapeutic targets, resulting in the development of clinically relevant PAK inhibitors. Over the last two decades, this has been a promising area of active investigation for several academic and pharmaceutical groups. Similar to other kinases, blocking the activity of one PAK family member leads to compensatory activity on the part of other family members. Because PAKs are also activated by stress-causing anticancer drugs, PAKs are components in the rewiring of survival pathways in the action of several therapeutic agents; in turn, they contribute to the development of therapeutic resistance. This, in turn, creates an opportunity to co-target the PAKs to achieve a superior anticancer cellular effect. Here we discuss the role of PAKs and their effector pathways in the modulation of cellular susceptibility to cancer therapeutic agents and therapeutic resistance.