bluuebunny/crossref_metadata_2025 huggingface dataset:
The Potential of Amaranth as a Basic Raw Material for the Production of Pasta for a Vegan Diet
Authors: Beitane Ilze , Marisheva Alla
Published: March 2023

The growing public interest in vegan products due to their association with health creates a need for new nutritious products that could cover nutritional deficiencies in the vegan diet. This study aimed to evaluate the potential of amaranth pasta and amaranth pasta blends with buckwheat or oat flour for a vegan diet to provide the limiting nutrients. Different types of pasta were developed in the current study—pasta from amaranth flour, and pasta samples from amaranth flour partly substituted with buckwheat or oat flour. The nutritional and energetic value, sugars, fatty acids, amino acids, and iron content were determined for all samples. All developed pasta samples can be evaluated as products with increased nutritional value, which provide more than 15% protein of the total energy with a sufficient content of lysine, methionine, and threonine; the iron content in the samples covered over 30% of the daily reference intake for iron; and the content of unsaturated fatty acids was above 70% of the total fat content. More nutritious pasta for a vegan diet can be obtained by substituting amaranth flour with buckwheat or oat flour. By improving the technology of amaranth pasta developed to obtain instant pasta, it would be possible to develop disaster food with high nutritional value.
Improving Many-to-Many Neural Machine Translation via Selective and Aligned Online Data Augmentation
Authors: Zhang Weitai , Dai Lirong , Liu Junhua , Wang Shijin
Published: March 2023

Multilingual neural machine translation (MNMT) models are theoretically attractive for low- and zero-resource language pairs with the impact of cross-lingual knowledge transfer. Existing approaches mainly focus on English-centric directions and always underperform compared to their pivot-based counterparts for non-English directions. In this work, we aim to build a many-to-many MNMT system with an emphasis on the quality of non-English directions by exploring selective and aligned online data augmentation algorithms. Based on our findings showing that the augmented synthetic samples are not “the more, the better” we propose selective online back-translation (SOBT) and thoroughly study different selection criteria to pick suitable samples for training. Furthermore, we boost SOBT with cross-lingual online substitution (CLOS) to align token representations and encourage transfer learning. Our intuition is based on the hypothesis that a universal cross-lingual representation leads to a better multilingual translation performance, especially for non-English directions. Comparing to previous state-of-the-art many-to-many MNMT models and conventional pivot-based methods, experiments on IWSLT2014 and OPUS-100 translation benchmarks show that our approach achieves a competitive or even better performance on English-centric directions and achieves up to ∼12 BLEU for non-English directions. All of our models and codes are publicly available.
The Aura of the Object and the Work of Art: A Critical Analysis of Walter Benjamin’s Theory in the Context of Contemporary Art and Culture
Authors: Vassilev Kiril
Published: March 2023

This text is a critical interpretation of Walter Benjamin’s theory in the context of the contemporary situation in art and culture. Benjamin’s innovative method of analysis and key concepts in art theory and their simultaneous research and political function are carefully reconstructed. This critical analysis is centered on the main concept of Benjamin’s philosophical aesthetics, the concept of ‘aura’. This analysis shows how Benjamin mixes and replaces the aura of the work of art with the aura of the historical object. Benjamin’s main thesis about the loss of the aura of the work of art in the age of its technical reproducibility is disputed. Technical reproducibility does not take away the aura of the work of art, but separates its aura from the aura of the historical object. Auraticness is inherent in every work insofar as it is a work of art. The aura of the historical object does not disappear in modernity either. With the emergence of historical and aesthetic consciousness, of the historical and art museum, the almost mechanical production of auratic objects began in modernity. As a result of the critical analysis of the concept of “aura”, the main binary oppositions that frame Benjamin’s theory of art—art with aura/art without aura; art with cult value/art without cult value; aestheticization of politics/politicization of art—are questioned. At the end of this text, the key lines of analysis proposed by Benjamin in an attempt to make sense of the radical changes in art since the beginning of the 20th century are used to outline the contemporary situation in art and the changes in perception with which it is associated.
Picturing, Pledges and Other Scripted Acts: Performance (In) Art
Authors: Beech Dave
Published: March 2023

This essay re-examines several examples of non-performance based artworks from the perspective and history of performance art. For instance, the photomontages I produced as an undergrad art student were based on repeated acts of stealing posters from their public sites on the street between my house and the college. Later, while working collaboratively with Mark Hutchinson in Manchester and London, we made photograms and paintings of scenes that we enacted on the street (striking a match, taking a flag for a walk). Years later, as a solo artist again, I produced a body of work in the form of slide presentations that consisted of photographs of me dressed in homemade costumes that cast me as a monster. In my work with the Freee art collective, we used slogans, our own bodies, costumes and props to give material reality to slogans that we treated as scripts. We wrote manifestos and staged events in which participants read. So, while the forms of my work are image based, the rationale is typically tied to the techniques and values of performance.
What Causes the Arabian Gulf Significant Summer Sea Surface Temperature Warming Trend?
Authors: Alawad Kamal A. , Al-Subhi Abdullah M. , Alsaafani Mohammed A. , Alraddadi Turki M.
Published: March 2023

The present study investigated the significant sea surface temperature (SST) warming trend during the summer season over the Arabian Gulf (AG) and its links with the large-scale atmospheric driver, namely, the Atlantic multidecadal oscillation (AMO), from 1900 to 2021. The link between the AMO and the AGs oceanic circulations has received little scientific attention. It has been found that there is a significant spatial positive trend, with a maximum of up to 0.6 °C per decade over the far northern end, while the time series trend shows a significant shift after 1995, with an average value of about 0.36 °C per decade. The spatial trend in the AG is eight times and four times higher than the global value from 1980 to 2005 using HadISST and OISST, respectively. The AMOs significant role in the AGs SST significant warming trend has been confirmed by the spatial and temporal correlation coefficient, which is above 0.50 and 0.48, respectively, with statistical significance at the 99% level. The underlying mechanisms that explained the AMO-related AGs SST decadal variability can be explained as follows: when the AMO is in a positive phase, the surface northwesterly wind weakens, leading to (1) less advection of the relatively cold air masses from Southern Europe to the AG and surrounding areas, (2) less evaporation, and thus less surface cooling (3); thus, this enhances the water masses stratification and decreases the upwelling process, and vice versa occurs for the negative phase. For the air temperature, the positive AMO phase coincides with the occurrence of warm air masses covering all of the Arabian Peninsula, North Africa, and Southern Europe. These processes prove that the AMO is a possible candidate for the AGs SST decadal variability, hence enabling a better evaluation of future climate scenarios for this important region. Our results provide initial insights into the AMO-driven spatiotemporal variability in the SST over the AG and prove that the relation is nonstationary over time. Further analyses are required to explore whether the impacts of the AMO are extended to other oceanic variables such as evaporation rate, heat transport, etc.
Assessment of Natural Radioactivity and Radon Exhalation in Peruvian Gold Mine Tailings to Produce a Geopolymer Cement
Authors: Liza Rafael , Pereyra Patrizia , Rau Jose , Guzman Maribel , Sajo-Bohus Laszlo , Palacios Daniel
Published: March 2023

Mining generates significant amounts of waste that can represent a source of contamination for areas close to the extraction area, generating a negative impact both on the environment and the health of people. This study aims to evaluate the radiological risk derived from exposure to natural radionuclides contained in tailings from Peruvian gold mines and to establish whether the tailings can be used as raw materials in building materials. The mine tailings come from a mining project in the northern highlands of Peru. Radon exhalation was measured using Rad7 in a closed chamber and activity concentration of 226Ra, 232Th, and 40K radioisotopes by gamma spectrometry using NaI 3” × 3” detector. Maximum activity concentrations measured for 226Ra and 232Th were 15.38 Bq kg−1 and 11.9 Bq kg−1, respectively; meanwhile, activity concentration for 40K ranged from 182.7 Bq kg−1 to 770.8 Bq kg−1. All activity concentrations were below the worldwide average except for 40K. The radon exhalation rate varied from 2.8 to 7.2 mBq kg−1 h−1. The gamma index (Iγ), and radiological parameters, including the Radium equivalent activity (Raeq), and the external hazard index (Hex), being below the recommended levels by UNSCEAR, ensure the safe use of these mines tailing to produce a geopolymer cement.
Seasonal Characteristics of Fine Particulate Carbonaceous Species in Taiyuan, North China
Authors: Li Wenbo , Zhao Xinya , Guo Fengbo , Liu Kankan
Published: March 2023

To characterize seasonal carbonaceous aerosol pollution in Taiyuan, a typical city in North China that mainly relies heavily on coal, a total of 124 PM2.5 samples were collected from August 2018 to the next May. The annual mean PM2.5 concentration was 83.8 ± 48.5 μg m−3, with a seasonal rank of winter (117.4 ± 47.6 μg m−3) > spring (79.2 ± 34.3 μg m−3) > fall (67.3 ± 34.7 μg m−3) > summer (31.8 ± 6.5 μg m−3), suggesting that fine particulate pollution was still serious in cold seasons. Organic carbon (OC) and elemental carbon (EC) showed similar seasonal patterns with PM2.5. The mean concentration values of OC in summer, fall, winter, and spring were 5.1 ± 0.9, 11.8 ± 6.4, 22.1 ± 14.9, and 12.2 ± 6.7 μg m−3, respectively. The mean concentration values of EC in summer, fall, winter, and spring were 1.5 ± 0.3, 2.5 ± 1.6, 4.4 ± 2.8, and 2.4 ± 1.5 μg m−3, respectively. The proportion of total carbon aerosol (TCA) was about 31.7%, 33.8%, 30.0%, and 27.0% in PM2.5 in summer, fall, winter, and spring, respectively. The good correlation between OC vs. EC and the high value of OC/EC suggests that coal and biomass combustion were the main emissions in cold seasons, aggravated by adverse meteorological conditions and the dustpan-shaped terrain. The mean annual secondary organic carbon (SOC) concentration was 6.1 ± 7.1μg m−3, representing 38.7% of the OC content. The present results presented the serious carbonaceous particulate pollution, which might affect haze pollution in cold seasons.
High Wet Deposition of Black Carbon over the Sichuan Basin of China
Authors: Zhou Yu , Zhang Xiaolin , Wang Yuanzhi
Published: March 2023

The wet deposition flux of black carbon (BC) over the Sichuan Basin is studied on the basis of the MERRA-2 data from 1981 to 2020, aiming at investigating high BC wet deposition flux in China in terms of long-term spatial-temporal trends and influences of BC column mass density and precipitation. In China, the largest BC wet deposition flux with a regionally-averaged value of 1.00 × 10−2 μg m−2 s−1 over the Sichuan Basin is observed, especially in the western and southern regions of the Basin with values as high as 2.20 × 10−2 μg m−2 s−1. The seasonality of BC wet deposition flux over the Sichuan Basin depicts maximum levels in autumn, moderate levels in spring and winter, and minimum levels in summer. The monthly mean BC wet deposition flux varies almost twofold, ranging from the lowest average value of 8.05 × 10−3 μg m−2 s−1 in July to the highest 1.28 × 10−2 μg m−2 s−1 in October. This study suggests that BC column mass density and precipitation are two significant factors affecting high BC wet deposition flux, whereas BC wet deposition flux is more related to BC column mass density than to precipitation over the Sichuan Basin.
Quantum-Inspired Fully Complex-Valued Neutral Network for Sentiment Analysis
Authors: Lai Wei , Shi Jinjing , Chang Yan
Published: March 2023

Most of the existing quantum-inspired models are based on amplitude-phase embedding to model natural language, which maps words into Hilbert space. In quantum-computing theory, the vectors corresponding to quantum states are all complex values, so there is a gap between these two areas. Presently, complex-valued neural networks have been studied, but their practical applications are few, let alone in the downstream tasks of natural language processing such as sentiment analysis and language modeling. In fact, the complex-valued neural network can use the imaginary part information to embed hidden information and can express more complex information, which is suitable for modeling complex natural language. Meanwhile, quantum-inspired models are defined in Hilbert space, which is also a complex space. So it is natural to construct quantum-inspired models based on complex-valued neural networks. Therefore, we propose a new quantum-inspired model for NLP, ComplexQNN, which contains a complex-valued embedding layer, a quantum encoding layer, and a measurement layer. The modules of ComplexQNN are fully based on complex-valued neural networks. It is more in line with quantum-computing theory and easier to transfer to quantum computers in the future to achieve exponential acceleration. We conducted experiments on six sentiment-classification datasets comparing with five classical models (TextCNN, GRU, ELMo, BERT, and RoBERTa). The results show that our model has improved by 10% in accuracy metric compared with TextCNN and GRU, and has competitive experimental results with ELMo, BERT, and RoBERTa.
A Data-Driven LiFePO4 Battery Capacity Estimation Method Based on Cloud Charging Data from Electric Vehicles
Authors: Zhou Xingyu , Han Xuebing , Wang Yanan , Lu Languang , Ouyang Minggao
Published: March 2023

The accuracy of capacity estimation is of great importance to the safe, efficient, and reliable operation of battery systems. In recent years, data-driven methods have emerged as promising alternatives to capacity estimation due to higher estimation accuracy. Despite significant progress, data-driven methods are mainly developed by experimental data under well-controlled charge–discharge processes, which are seldom available for practical battery health monitoring under realistic conditions due to uncertainties in environmental and operational conditions. In this paper, a novel method to estimate the capacity of large-format LiFePO4 batteries based on real data from electric vehicles is proposed. A comprehensive dataset consisting of 85 vehicles that has been running for around one year under diverse nominal conditions derived from a cloud platform is generated. A classification and aggregation capacity prediction method is developed, combining a battery aging experiment with big data analysis on cloud data. Based on degradation mechanisms, IC curve features are extracted, and a linear regression model is established to realize high-precision estimation for slow-charging data with constant-current charging. The selected features are highly correlated with capacity (Pearson correlation coefficient < 0.85 for all vehicles), and the MSE of the capacity estimation results is less than 1 Ah. On the basis of protocol analysis and mechanism studies, a feature set including internal resistance, temperature, and statistical characteristics of the voltage curve is constructed, and a neural network (NN) model is established for multi-stage variable-current fast-charging data. Finally, the above two models are integrated to achieve capacity prediction under complex and changeable realistic working conditions, and the relative error of the capacity estimation method is less than 0.8%. An aging experiment using the battery, which is the same as those equipped in the vehicles in the dataset, is carried out to verify the methods. To the best of the authors’ knowledge, our study is the first to verify a capacity estimation model derived from field data using an aging experiment of the same type of battery.
Fondillón Wine Adulteration by Addition of Other Monastrell Wines
Authors: Issa-Issa Hanán , Hernández Francisca , López-Lluch David , Uysal Reyhan Selin , Carbonell-Barrachina Ángel A.
Published: March 2023

Authenticity and traceability are two issues of great importance to quality and food safety in the food industry. For wine producers and authorities, it is essential to know how to detect adulterations because wine is one of the alcoholic beverages most prone to adulteration, as indicated by the European Commission. Fondillón is one of the most important naturally sweet Spanish wines and is certainly the core of the Alicante PDO. Fondillón is a wine that is prone to be adulteration due to its limited production and high price. The aim of this study was to identify potential markers of Fondillón adulteration by mixing it with other Monastrell wines. The experimental results showed that Fondillón is characterized by high concentrations of acetic acid, furfural, benzaldehyde, vitispirane, and TDN and low concentrations of citric, tartaric, and malic acids; a low total phenolic content; and low values of antioxidant activity.
Exploratory Study on Chemosensory Event-Related Potentials in Long COVID-19 and Mild Cognitive Impairment: A Common Pathway?
Authors: Invitto Sara , Boscolo-Rizzo Paolo , Fantin Francesco , Bonifati Domenico Marco , de Filippis Cosimo , Emanuelli Enzo , Frezza Daniele , Giopato Federico , Caggiula Marcella , Schito Andrea , Ciccarese Vincenzo , Spinato Giacomo
Published: March 2023

People affected by the Long COVID-19 (LC) syndrome often show clinical manifestations that are similar to those observed in patients with mild cognitive impairments (MCI), such as olfactory dysfunction (OD), brain fog, and cognitive and attentional diseases. This study aimed to investigate the chemosensory-evoked related potentials (CSERP) in LC and MCI to understand if there is a common pathway for the similarity of symptoms associated with these disorders. Eighteen LC patients (mean age 53; s.d. = 7), 12 patients diagnosed with MCI (mean age 67; s.d. = 6), and 10 healthy control subjects (mean age 66; s.d. = 5, 7) were recruited for this exploratory study. All of them performed a chemosensory event-related potentials (CSERP) task with the administration of trigeminal stimulations (e.g., the odorants cinnamaldehyde and eucalyptus). Study results highlighted that MCI and LC showed reduced N1 amplitude, particularly in the left frontoparietal network, involved in working memory and attentional deficits, and a reduction of P3 latency in LC. This study lays the foundations for evaluating aspects of LC as a process that could trigger long-term functional alterations, and CSERPs could be considered valid biomarkers for assessing the progress of OD and an indicator of other impairments (e.g., attentional and cognitive impairments), as they occur in MCI.
Calumenin, a Ca2+ Binding Protein, Is Required for Dauer Formation in Caenorhabditis elegans
Authors: Lee Kyung Eun , Cho Jeong Hoon , Song Hyun-Ok
Published: March 2023

Caenorhabditis elegans can adapt and survive in dynamically changing environments by the smart and delicate switching of molecular plasticity. C. elegans dauer diapause is a form of phenotypic and developmental plasticity that induces reversible developmental arrest upon environmental cues. An ER (endoplasmic reticulum)-resident Ca2+ binding protein, calumenin has been reported to function in a variety of malignant diseases in vertebrates and in the process of muscle contraction–relaxation. In C. elegans, CALU-1 is known to function in Ca2+-regulated behaviors (pharyngeal pumping and defecation) and cuticle formation. The cuticles of dauer larvae are morphologically distinct from those of larvae that develop in favorable conditions. The structure of the dauer cuticle is thicker and more highly reinforced than that of other larval stages to protect dauer larvae from various environmental insults. Since the calu-1(tm1783) mutant exhibited abnormal cuticle structures such as highly deformed annuli and alae, we investigated whether CALU-1 is involved in dauer formation or not. Ascaroside pheromone (ascr#2) and crude daumone were used under starvation conditions to analyze the rate of dauer formation in the calu-1(tm1783) mutant. Surprisingly, the dauer ratio of the calu-1(tm1783) mutant was extremely low compared to that of the wild type. In fact, the calu-1(tm1783) mutants were mostly unable to enter diapause. We also found that calu-1 is expressed in body-wall muscle and AIA interneurons at the dauer stage. Taken together, our results suggest that CALU-1 is required for normal entry into diapause in C. elegans.
Antineoplastic Nature of WWOX in Glioblastoma Is Mainly a Consequence of Reduced Cell Viability and Invasion
Authors: Kałuzińska-Kołat Żaneta , Kośla Katarzyna , Kołat Damian , Płuciennik Elżbieta , Bednarek Andrzej K.
Published: March 2023

Following the discovery of WWOX, research has moved in many directions, including the role of this putative tumor suppressor in the central nervous system and related diseases. The task of determining the nature of WWOX in glioblastoma (GBM) is still considered to be at the initial stage; however, the influence of this gene on the GBM malignant phenotype has already been reported. Because most of the available in vitro research does not consider several cellular GBM models or a wide range of investigated biological assays, the present study aimed to determine the main processes by which WWOX exhibits anticancer properties in GBM, while taking into account the phenotypic heterogeneity between cell lines. Ectopic WWOX overexpression was studied in T98G, DBTRG-05MG, U251MG, and U87MG cell lines that were compared with the use of assays investigating cell viability, proliferation, apoptosis, adhesion, clonogenicity, three-dimensional and anchorage-independent growth, and invasiveness. Observations presenting the antineoplastic properties of WWOX were consistent for T98G, U251MG, and U87MG. Increased proliferation and tumor growth were noted in WWOX-overexpressing DBTRG-05MG cells. A possible explanation for this, arrived at via bioinformatics tools, was linked to the TARDBP transcription factor and expression differences of USP25 and CPNE2 that regulate EGFR surface abundance. Collectively, and despite various cell line-specific circumstances, WWOX exhibits its anticancer nature mainly via a reduction of cell viability and invasiveness of glioblastoma.
Advances in Viral Aquatic Animal Disease Knowledge: The Molecular Methods’ Contribution
Authors: Volpe Enrico , Errani Francesca , Mandrioli Luciana , Ciulli Sara
Published: March 2023

Aquaculture is the fastest-growing food-producing sector, with a global production of 122.6 million tonnes in 2020. Nonetheless, aquatic animal production can be hampered by the occurrence of viral diseases. Furthermore, intensive farming conditions and an increasing number of reared fish species have boosted the number of aquatic animals’ pathogens that researchers have to deal with, requiring the quick development of new detection and study methods for novel unknown pathogens. In this respect, the molecular tools have significantly contributed to investigating thoroughly the structural constituents of fish viruses and providing efficient detection methods. For instance, next-generation sequencing has been crucial in reassignment to the correct taxonomic family, the sturgeon nucleo-cytoplasmic large DNA viruses, a group of viruses historically known, but mistakenly considered as iridoviruses. Further methods such as in situ hybridisation allowed objectifying the role played by the pathogen in the determinism of disease, as the cyprinid herpesvirus 2, ostreid herpesvirus 1 and betanodaviruses. Often, a combination of molecular techniques is crucial to understanding the viral role, especially when the virus is detected in a new aquatic animal species. With this paper, the authors would critically revise the scientific literature, dealing with the molecular techniques employed hitherto to study the most relevant finfish and shellfish viral pathogens.
Therapeutic Delivery of Tumor Suppressor miRNAs for Breast Cancer Treatment
Authors: Shinde Sonali S. , Ahmed Sakeel , Malik Jonaid Ahmad , Hani Umme , Khanam Afreen , Ashraf Bhat Faisal , Ahmad Mir Suhail , Ghazwani Mohammed , Wahab Shadma , Haider Nazima , Almehizia Abdulrahman A.
Published: March 2023

The death rate from breast cancer (BC) has dropped due to early detection and sophisticated therapeutic options, yet drug resistance and relapse remain barriers to effective, systematic treatment. Multiple mechanisms underlying miRNAs appear crucial in practically every aspect of cancer progression, including carcinogenesis, metastasis, and drug resistance, as evidenced by the elucidation of drug resistance. Non-coding RNAs called microRNAs (miRNAs) attach to complementary messenger RNAs and degrade them to inhibit the expression and translation to proteins. Evidence suggests that miRNAs play a vital role in developing numerous diseases, including cancer. They affect genes critical for cellular differentiation, proliferation, apoptosis, and metabolism. Recently studies have demonstrated that miRNAs serve as valuable biomarkers for BC. The contrast in the expression of miRNAs in normal tissue cells and tumors suggest that miRNAs are involved in breast cancer. The important aspect behind cancer etiology is the deregulation of miRNAs that can specifically influence cellular physiology. The main objective of this review is to emphasize the role and therapeutic capacity of tumor suppressor miRNAs in BC and the advancement in the delivery system that can deliver miRNAs specifically to cancerous cells. Various approaches are used to deliver these miRNAs to the cancer cells with the help of carrier molecules, like nanoparticles, poly D, L-lactic-co-glycolic acid (PLGA) particles, PEI polymers, modified extracellular vesicles, dendrimers, and liposomes. Additionally, we discuss advanced strategies of TS miRNA delivery techniques such as viral delivery, self-assembled RNA-triple-helix hydrogel drug delivery systems, and hyaluronic acid/protamine sulfate inter-polyelectrolyte complexes. Subsequently, we discuss challenges and prospects on TS miRNA therapeutic delivery in BC management so that miRNAs will become a routine technique in developing individualized patient profiles.
Neurobiology of Aggression—Review of Recent Findings and Relationship with Alcohol and Trauma
Authors: Fritz Michael , Soravia Sarah-Maria , Dudeck Manuela , Malli Layal , Fakhoury Marc
Published: March 2023

Aggression can be conceptualized as any behavior, physical or verbal, that involves attacking another person or animal with the intent of causing harm, pain or injury. Because of its high prevalence worldwide, aggression has remained a central clinical and public safety issue. Aggression can be caused by several risk factors, including biological and psychological, such as genetics and mental health disorders, and socioeconomic such as education, employment, financial status, and neighborhood. Research over the past few decades has also proposed a link between alcohol consumption and aggressive behaviors. Alcohol consumption can escalate aggressive behavior in humans, often leading to domestic violence or serious crimes. Converging lines of evidence have also shown that trauma and posttraumatic stress disorder (PTSD) could have a tremendous impact on behavior associated with both alcohol use problems and violence. However, although the link between trauma, alcohol, and aggression is well documented, the underlying neurobiological mechanisms and their impact on behavior have not been properly discussed. This article provides an overview of recent advances in understanding the translational neurobiological basis of aggression and its intricate links to alcoholism and trauma, focusing on behavior. It does so by shedding light from several perspectives, including in vivo imaging, genes, receptors, and neurotransmitters and their influence on human and animal behavior.
Nanobodies Selectively Binding to the Idiotype of a Dengue Virus Neutralizing Antibody Do Not Necessarily Mimic the Viral Epitope
Authors: Poggianella Monica , Bernedo Robert , Oloketuyi Sandra , de Marco Ario
Published: March 2023

Vaccination against dengue virus is challenged by the fact that a generic immune response can induce antibody-dependent-enhancement (ADE) in secondary infections. Only some antibodies targeting a quaternary epitope formed by the dimerization of the virus protein E possess sufficient neutralizing capacity. Therefore, the immunization with anti-idiotypic antibodies of neutralizing antibodies might represent a safe vaccination strategy. Starting from a large pre-immune library, we succeeded in isolating a wide set of anti-idiotypic nanobodies characterized by selective and strong binding to the paratope of the neutralizing antibody 1C10. However, the mice immunized with such constructs did not produce effective antibodies, despite at least some of them eliciting an immune response selective for the nanobody variable regions. The results suggest that complex conformational epitopes might be difficult to be recreated by anti-idiotypic structures. The selection process of the anti-idiotypic candidates might be optimized by applying epitope mapping and modeling approaches aimed at identifying the key residues that is necessary to bind to trigger selective immune response.
Feasibility of Transport of 26 Biologically Active Ultrashort Peptides via LAT and PEPT Family Transporters
Authors: Khavinson Vladimir Khatskelevich , Linkova Natalia Sergeevna , Rudskoy Andrey Ivanovich , Petukhov Michael Gennadievich
Published: March 2023

The aim of this work is to verify the possibility of transport of 26 biologically active ultrashort peptides (USPs) into cells via LAT and PEPT family transporters. Molecular modeling and computer-assisted docking of peptide ligands revealed that the size and structure of ligand-binding sites of the amino acid transporters LAT1, LAT2, and of the peptide transporter PEPT1 are sufficient for the transport of the 26 biologically active di-, tri-, and tetra-peptides. Comparative analysis of the binding of all possible di- and tri-peptides (8400 compounds) at the binding sites of the LAT and PEPT family transporters has been carried out. The 26 biologically active USPs systematically showed higher binding scores to LAT1, LAT2, and PEPT1, as compared with di- and tri-peptides, for which no biological activity has been established. This indicates an important possible role which LAT and PEPT family transporters may play in a variety of biological activities of the 26 biologically active peptides under investigation in this study. Most of the 26 studied USPs were found to bind to the LAT1, LAT2, and PEPT1 transporters more efficiently than the known substrates or inhibitors of these transporters. Peptides ED, DS, DR, EDR, EDG, AEDR, AEDL, KEDP, and KEDG, and peptoids DS7 and KE17 with negatively charged Asp− or Glu− amino acid residues at the N-terminus and neutral or positively charged residues at the C-terminus of the peptide are found to be the most effective ligands of the transporters under investigation. It can be assumed that the antitumor effect of the KE, EW, EDG, and AEDG peptides could be associated with their ability to inhibit the LAT1, LAT2, and PEPT1 amino acid transporters. The data obtained lead to new prospects for further study of the mechanisms of transport of USP-based drugs into the cell and design of new antitumor drugs.
Genome-Wide Identification and Expression Analysis of Rosa roxburghii Autophagy-Related Genes in Response to Top-Rot Disease
Authors: Luo Kaisha , Li Jiaohong , Lu Min , An Huaming , Wu Xiaomao
Published: March 2023

Autophagy is a highly conserved process in eukaryotes that degrades and recycles damaged cells in plants and is involved in plant growth, development, senescence, and resistance to external stress. Top-rot disease (TRD) in Rosa roxburghii fruits caused by Colletotrichum fructicola often leads to huge yield losses. However, little information is available about the autophagy underlying the defense response to TRD. Here, we identified a total of 40 R. roxburghii autophagy-related genes (RrATGs), which were highly homologous to Arabidopsis thaliana ATGs. Transcriptomic data show that RrATGs were involved in the development and ripening processes of R. roxburghii fruits. Gene expression patterns in fruits with different degrees of TRD occurrence suggest that several members of the RrATGs family responded to TRD, of which RrATG18e was significantly up-regulated at the initial infection stage of C. fructicola. Furthermore, exogenous calcium (Ca2+) significantly promoted the mRNA accumulation of RrATG18e and fruit resistance to TRD, suggesting that this gene might be involved in the calcium-mediated TRD defense response. This study provided a better understanding of R. roxburghii autophagy-related genes and their potential roles in disease resistance.
Ablation of GPR56 Causes β-Cell Dysfunction by ATP Loss through Mistargeting of Mitochondrial VDAC1 to the Plasma Membrane
Authors: Mohammad Al-Amily Israa , Sjögren Marie , Duner Pontus , Tariq Mohammad , Wollheim Claes B. , Salehi Albert
Published: March 2023

The activation of G Protein-Coupled Receptor 56 (GPR56), also referred to as Adhesion G-Protein-Coupled Ceceptor G1 (ADGRG1), by Collagen Type III (Coll III) prompts cell growth, proliferation, and survival, among other attributes. We investigated the signaling cascades mediating this functional effect in relation to the mitochondrial outer membrane voltage-dependent anion Channel-1 (VDAC1) expression in pancreatic β-cells. GPR56KD attenuated the Coll III-induced suppression of P70S6K, JNK, AKT, NFκB, STAT3, and STAT5 phosphorylation/activity in INS-1 cells cultured at 20 mM glucose (glucotoxicity) for 72 h. GPR56-KD also increased Chrebp, Txnip, and Vdac1 while decreasing Vdac2 mRNA expression. In GPR56-KD islet β-cells, Vdac1 was co-localized with SNAP-25, demonstrating its plasma membrane translocation. This resulted in ATP loss, reduced cAMP production and impaired glucose-stimulated insulin secretion (GSIS) in INS-1 and human EndoC βH1 cells. The latter defects were reversed by an acute inhibition of VDAC1 with an antibody or the VDAC1 inhibitor VBIT-4. We demonstrate that Coll III potentiates GSIS by increasing cAMP and preserving β-cell functionality under glucotoxic conditions in a GPR56-dependent manner by attenuating the inflammatory response. These results emphasize GPR56 and VDAC1 as drug targets in conditions with impaired β-cell function.
The Association between Infant Colic and the Multi-Omic Composition of Human Milk
Authors: Chandran Desirae , Warren Kaitlyn , McKeone Daniel , Hicks Steven D.
Published: March 2023

Infant colic is a common condition with unclear biologic underpinnings and limited treatment options. We hypothesized that complex molecular networks within human milk (i.e., microbes, micro-ribonucleic acids (miRNAs), cytokines) would contribute to colic risk, while controlling for medical, social, and nutritional variables. This hypothesis was tested in a cohort of 182 breastfed infants, assessed with a modified Infant Colic Scale at 1 month. RNA sequencing was used to interrogate microbial and miRNA features. Luminex assays were used to measure growth factors and cytokines. Milk from mothers of infants with colic (n = 28) displayed higher levels of Staphylococcus (adj. p = 0.038, d = 0.30), miR-224-3p (adj. p = 0.023, d = 0.33), miR-125b-5p (adj. p = 0.028, d = 0.29), let-7a-5p (adj. p = 0.028, d = 0.27), and miR-205-5p (adj. p = 0.029, d = 0.26) compared to milk from non-colic mother–infant dyads (n = 154). Colic symptom severity was directly associated with milk hepatocyte growth factor levels (R = 0.21, p = 0.025). A regression model involving let-7a-5p, miR-29a-3p, and Lactobacillus accurately modeled colic risk (X2 = 16.7, p = 0.001). Molecular factors within human milk may impact colic risk, and provide support for a dysbiotic/inflammatory model of colic pathophysiology.
LncRNA and circRNA in Patients with Non-Alcoholic Fatty Liver Disease: A Systematic Review
Authors: Zeng Qingmin , Liu Chang-Hai , Wu Dongbo , Jiang Wei , Zhang Nannan , Tang Hong
Published: March 2023

Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease worldwide. Early identification and prompt treatment are critical to optimize patient management and improve long-term prognosis. Long non-coding RNA (lncRNA) and circular RNA (circRNA) are recently emerging non-coding RNAs, and are highly stable and easily detected in the circulation, representing a promising non-invasive approach for predicting NAFLD. A literature search of the Pubmed, Embase, Web of Science, and Cochrane Library databases was performed and 36 eligible studies were retrieved, including 18 on NAFLD, 13 on nonalcoholic steatohepatitis (NASH), and 11 on fibrosis and/or cirrhosis. Dynamic changes in lncRNA expression were associated with the occurrence and progression of NAFLD, among which lncRNA NEAT1, MEG3, and MALAT1 exhibited great potential as biomarkers for NAFLD. Moreover, mitochondria-located circRNA SCAR can drive metaflammation and its inhibition might be a promising therapeutic target for NASH. In this systematic review, we highlight the great potential of lncRNA/circRNA for early diagnosis and progression assessment of NAFLD. To further verify their clinical value, large-cohort studies incorporating lncRNA and circRNA expression both in liver tissue and blood should be conducted. Additionally, detailed studies on the functional mechanisms of NEAT1, MEG3, and MALAT1 will be essential for elucidating their roles in diagnosing and treating NAFLD, NASH, and fibrosis.
Glaucoma and Myopia: Diagnostic Challenges
Authors: Sun Michelle T. , Tran Matthew , Singh Kuldev , Chang Robert , Wang Huaizhou , Sun Yang
Published: March 2023

The rising global prevalence of myopia is a growing concern for clinicians, as it predisposes patients to severe ocular pathologies including glaucoma. High myopia can be associated with clinical features that resemble glaucomatous damage, which make an accurate glaucoma diagnosis challenging, particularly among patients with normal intraocular pressures. These patients may also present with established visual field defects which can mimic glaucoma, and standard imaging technology is less useful in disease detection and monitoring due to the lack of normative data for these anatomically unique eyes. Progression over time remains the most critical factor in facilitating the detection of early glaucomatous changes, and thus careful longitudinal follow-up of high-risk myopic patients is the most important aspect of management. Here, we review our current understanding of the complex relationship between myopia and glaucoma, and the diagnostic challenges and limitations of current testing protocols including visual field, intraocular pressure, and imaging. Furthermore, we discuss the clinical findings of two highly myopic patients with suspected glaucoma.
Design and Assembly of a Biofactory for (2S)-Naringenin Production in Escherichia coli: Effects of Oxygen Transfer on Yield and Gene Expression
Authors: Parra Daza Laura E. , Suarez Medina Lina , Tafur Rangel Albert E. , Fernández-Niño Miguel , Mejía-Manzano Luis Alberto , González-Valdez José , Reyes Luis H. , González Barrios Andrés Fernando
Published: March 2023

The molecule (2S)-naringenin is a scaffold molecule with several nutraceutical properties. Currently, (2S)-naringenin is obtained through chemical synthesis and plant isolation. However, these methods have several drawbacks. Thus, heterologous biosynthesis has emerged as a viable alternative to its production. Recently, (2S)-naringenin production studies in Escherichia coli have used different tools to increase its yield up to 588 mg/L. In this study, we designed and assembled a bio-factory for (2S)-naringenin production. Firstly, we used several parametrized algorithms to identify the shortest pathway for producing (2S)-naringenin in E. coli, selecting the genes phenylalanine ammonia lipase (pal), 4-coumarate: CoA ligase (4cl), chalcone synthase (chs), and chalcone isomerase (chi) for the biosynthetic pathway. Then, we evaluated the effect of oxygen transfer on the production of (2S)-naringenin at flask (50 mL) and bench (4 L culture) scales. At the flask scale, the agitation rate varied between 50 rpm and 250 rpm. At the bench scale, the dissolved oxygen was kept constant at 5% DO (dissolved oxygen) and 40% DO, obtaining the highest (2S)-naringenin titer (3.11 ± 0.14 g/L). Using genome-scale modeling, gene expression analysis (RT-qPCR) of oxygen-sensitive genes was obtained.
Nuclear Calcium in Cardiac (Patho)Physiology: Small Compartment, Big Impact
Authors: Kiessling Mara , Djalinac Nataša , Voglhuber Julia , Ljubojevic-Holzer Senka
Published: March 2023

The nucleus of a cardiomyocyte has been increasingly recognized as a morphologically distinct and partially independent calcium (Ca2+) signaling microdomain, with its own Ca2+-regulatory mechanisms and important effects on cardiac gene expression. In this review, we (1) provide a comprehensive overview of the current state of research on the dynamics and regulation of nuclear Ca2+ signaling in cardiomyocytes, (2) address the role of nuclear Ca2+ in the development and progression of cardiac pathologies, such as heart failure and atrial fibrillation, and (3) discuss novel aspects of experimental methods to investigate nuclear Ca2+ handling and its downstream effects in the heart. Finally, we highlight current challenges and limitations and recommend future directions for addressing key open questions.
Transcriptional and Epigenetic Alterations in the Progression of Non-Alcoholic Fatty Liver Disease and Biomarkers Helping to Diagnose Non-Alcoholic Steatohepatitis
Authors: Zhu Yalan , Zhang He , Jiang Pengjun , Xie Chengxia , Luo Yao , Chen Jie
Published: March 2023

Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions from simple steatosis (non-alcoholic fatty liver (NAFL)) to non-alcoholic steatohepatitis (NASH), and its global prevalence continues to rise. NASH, the progressive form of NAFLD, has higher risks of liver and non-liver related adverse outcomes compared with those patients with NAFL alone. Therefore, the present study aimed to explore the mechanisms in the progression of NAFLD and to develop a model to diagnose NASH based on the transcriptome and epigenome. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) among the three groups (normal, NAFL, and NASH) were identified, and the functional analysis revealed that the development of NAFLD was primarily related to the oxidoreductase-related activity, PPAR signaling pathway, tight junction, and pathogenic Escherichia coli infection. The logistic regression (LR) model, consisting of ApoF, THOP1, and BICC1, outperformed the other five models. With the highest AUC (0.8819, 95%CI: 0.8128–0.9511) and a sensitivity of 97.87%, as well as a specificity of 64.71%, the LR model was determined as the diagnostic model, which can differentiate NASH from NAFL. In conclusion, several potential mechanisms were screened out based on the transcriptome and epigenome, and a diagnostic model was built to help patient stratification for NAFLD populations.
Bioimpedance Analysis as Early Predictor for Clot Formation Inside a Blood-Perfused Test Chamber: Proof of Concept Using an In Vitro Test-Circuit
Authors: Türkmen Muhammet , Lauwigi Tobias , Fechter Tamara , Gries Fabienne , Fischbach Anna , Gries Thomas , Rossaint Rolf , Bleilevens Christian , Winnersbach Patrick
Published: March 2023

Clot formation inside a membrane oxygenator (MO) due to blood-to-foreign surface interaction represents a frequent complication during extracorporeal membrane oxygenation. Since current standard monitoring methods of coagulation status inside the MO fail to detect clot formation at an early stage, reliable sensors for early clot detection are in demand to reduce associated complications and adverse events. Bioimpedance analysis offers a monitoring concept by integrating sensor fibers into the MO. Herein, the feasibility of clot detection via bioimpedance analysis is evaluated. A custom-made test chamber with integrated titanium fibers acting as sensors was perfused with heparinized human whole blood in an in vitro test circuit until clot formation occurred. The clot detection capability of bioimpedance analysis was directly compared to the pressure difference across the test chamber (ΔP-TC), analogous to the measurement across MOs (ΔP-MO), the clinical gold standard for clot detection. We found that bioimpedance measurement increased significantly 8 min prior to a significant increase in ΔP-TC, indicating fulminant clot formation. Experiments without clot formation resulted in a lack of increase in bioimpedance or ΔP-TC. This study shows that clot detection via bioimpedance analysis under flow conditions in a blood-perfused test chamber is generally feasible, thus paving the way for further investigation.
Surface Plasmon Resonance (SPR) Sensor for Cancer Biomarker Detection
Authors: Das Sreyashi , Devireddy Ram , Gartia Manas Ranjan
Published: March 2023

A biomarker is a physiological observable marker that acts as a stand-in and, in the best-case scenario, forecasts a clinically significant outcome. Diagnostic biomarkers are more convenient and cost-effective than directly measuring the ultimate clinical outcome. Cancer is among the most prominent global health problems and a major cause of morbidity and death globally. Therefore, cancer biomarker assays that are trustworthy, consistent, precise, and verified are desperately needed. Biomarker-based tumor detection holds a lot of promise for improving disease knowledge at the molecular scale and early detection and surveillance. In contrast to conventional approaches, surface plasmon resonance (SPR) allows for the quick and less invasive screening of a variety of circulating indicators, such as circulating tumor DNA (ctDNA), microRNA (miRNA), circulating tumor cells (CTCs), lipids, and proteins. With several advantages, the SPR technique is a particularly beneficial choice for the point-of-care identification of biomarkers. As a result, it enables the timely detection of tumor markers, which could be used to track cancer development and suppress the relapse of malignant tumors. This review emphasizes advancements in SPR biosensing technologies for cancer detection.