bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Catechin on the Formation of Polycyclic Aromatic Hydrocarbons in Camellia oleifera Oil during Thermal Processing
Authors: Pei Wenjun , Wang Jiaqi , Zhang Lu , Guo Yiwen , Cao Minjie , Liu Ruijie , Chang Ming , Wang Xingguo
Published: February 2023

Polycyclic aromatic hydrocarbons (PAHs) in oil are affected by many factors, including temperature, time, and PAHs precursors. Phenolic compounds, as beneficial endogenous components of oil, are often associated with the inhibition of PAHs. However, studies have found that the presence of phenols may lead to increased levels of PAHs. Therefore, this study took Camellia oleifera (C. oleifera) oil as the research object, in order to study the effect of catechin in the formation of PAHs under different heating conditions. The results showed that PAH4 were generated rapidly during the lipid oxidation induction period. When the addition of catechin was >0.02%, more free radicals were quenched than generated, thus inhibiting the generation of PAH4. ESR, FT-IR, and other technologies were employed to prove that when the catechin addition was <0.02%, more free radicals were produced than quenched, causing lipid damage and increasing PAHs intermediates. Moreover, the catechin itself would break and polymerize to form aromatic ring compounds, ultimately leading to the conclusion that phenolic compounds in oil may be involved in the formation of PAHs. This provides suggestions for the flexible processing of phenol-rich oil to balance the retention of beneficial substances, and for the safe control of hazardous substances in real-life applications.
Xanthine Oxidase Inhibitory Peptides from Larimichthys polyactis: Characterization and In Vitro/In Silico Evidence
Authors: Chen Xiaoling , Guan Weiliang , Li Yujin , Zhang Jinjie , Cai Luyun
Published: February 2023

Hyperuricemia is linked to a variety of disorders that can have serious consequences for human health. Peptides that inhibit xanthine oxidase (XO) are expected to be a safe and effective functional ingredient for the treatment or relief of hyperuricemia. The goal of this study was to discover whether papain small yellow croaker hydrolysates (SYCHs) have potent xanthine oxidase inhibitory (XOI) activity. The results showed that compared to the XOI activity of SYCHs (IC50 = 33.40 ± 0.26 mg/mL), peptides with a molecular weight (MW) of less than 3 kDa (UF-3) after ultrafiltration (UF) had stronger XOI activity, which was reduced to IC50 = 25.87 ± 0.16 mg/mL (p < 0.05). Two peptides were identified from UF-3 using nano-high-performance liquid chromatography–tandem mass spectrometry. These two peptides were chemically synthesized and tested for XOI activity in vitro. Trp-Asp-Asp-Met-Glu-Lys-Ile-Trp (WDDMEKIW) (p < 0.05) had the stronger XOI activity (IC50 = 3.16 ± 0.03 mM). The XOI activity IC50 of the other peptide, Ala-Pro-Pro-Glu-Arg-Lys-Tyr-Ser-Val-Trp (APPERKYSVW), was 5.86 ± 0.02 mM. According to amino acid sequence results, the peptides contained at least 50% hydrophobic amino acids, which might be responsible for reducing xanthine oxidase (XO) catalytic activity. Furthermore, the inhibition of the peptides (WDDMEKIW and APPERKYSVW) against XO may depend on their binding to the XO active site. According to molecular docking, certain peptides made from small yellow croaker proteins were able to bind to the XO active site through hydrogen bonds and hydrophobic interactions. The results of this work illuminate SYCHs as a promising functional candidate for the prevention of hyperuricemia.
Bioprocessing to Preserve and Improve Microalgae Nutritional and Functional Potential: Novel Insight and Perspectives
Authors: Verni Michela , Demarinis Chiara , Rizzello Carlo Giuseppe , Pontonio Erica
Published: February 2023

Microalgae are aquatic unicellular microorganisms and, although various species are approved for human consumption, Arthrospira and Chlorella are the most widespread. Several nutritional and functional properties have been bestowed to microalgae principal micro- and macro-nutrients, with antioxidant, immunomodulatory and anticancer being the most common. The many references to their potential as a food of the future is mainly ascribed to the high protein and essential amino acid content, but they are also a source of pigments, lipids, sterols, polysaccharides, vitamins, and phenolic compounds with positive effects on human health. Nevertheless, microalgae use is often hindered by unpleasant color and flavor and several strategies have been sought to minimize such challenges. This review provides an overview of the strategies so far proposed and the main nutritional and functional characteristic of microalgae and the foods made thereof. Processing treatments have been used to enrich microalgae-derived substrates in compounds with antioxidant, antimicrobial, and anti-hypertensive properties. Extraction, microencapsulation, enzymatic treatments, and fermentation are the most common, each with their own pros and cons. Yet, for microalgae to be the food of the future, more effort should be put into finding the right pre-treatments that can allow the use of the whole biomass and be cost-effective while bringing about features that go beyond the mere increase of proteins.
The Influence of Grape Clone and Yeast Strain on Varietal Thiol Concentrations and Sensory Properties of Graševina Wines
Authors: Tomašević Marina , Lukić Katarina , Ćurko Natka , Jagatić Korenika Ana-Marija , Preiner Darko , Tuščić Valentina , Jeromel Ana , Kovačević Ganić Karin
Published: February 2023

Varietal thiol concentration in wine is influenced by numerous factors, of which grape variety and winemaking practices are often highlighted as the most important. Therefore, the aim of this work was to study the effects of grape clone and yeast strain (Saccharomyces and non-Saccharomyces) on the varietal thiols concentrations and sensory characteristics of Graševina (Vitis vinifera L.) white wines. Two grape clones were evaluated (OB-412 and OB-445) along with three different commercial yeast strains (Saccharomyces cerevisiae Lalvin Sensy and Sauvy, and Metschnikowia pulcherrima Flavia). The results showed that the concentration of varietal thiols in Graševina wines amounted up to a total of 226 ng/L. The clone OB-412 was characterized by its significantly higher concentrations, especially of 3-sulfanylhexanol (3SH) and 3-sulfanylhexyl acetate (3SHA). Moreover, alcoholic fermentation with pure S. cerevisiae Sauvy yeasts generally resulted in higher thiol concentrations, while sequential fermentation involving M. pulcherrima positively affected only the 4-methyl-4-sulfanyl-pentan-2-one (4MSP) concentration. Finally, sensory analysis showed that fermentation with pure S. cerevisiae Sauvy yeast also produced more desirable wines. The results suggest that clonal, and especially yeast strain, selections are important modulators of the aroma and sensory properties of wine.
Quantitative Analysis of Oat (Avena sativa L.) and Pea (Pisum sativum L.) Saponins in Plant-Based Food Products by Hydrophilic Interaction Liquid Chromatography Coupled with Mass Spectrometry
Authors: Bljahhina Anastassia , Pismennõi Dmitri , Kriščiunaite Tiina , Kuhtinskaja Maria , Kobrin Eeva-Gerda
Published: February 2023

This work presents the sample extraction methods for solid and liquid sample matrices for simultaneous quantification of oat (Avena sativa L.) and pea (Pisum sativum L.) saponins: avenacoside A, avenacoside B, 26-desglucoavenacoside A, and saponin B and 2,3-dihydro-2,5-dihydroxy-6-methyl-4H-pyran-4-one (DDMP) saponin, respectively. The targeted saponins were identified and quantified using a hydrophilic interaction liquid chromatography with mass spectrometric detection (HILIC-MS) method. The simple and high-throughput extraction procedure was developed for solid oat- and pea-based food samples. In addition, a very simple extraction procedure for liquid samples, without the need to use lyophilisation, was also implemented. Oat seed flour (U-13C-labelled) and soyasaponin Ba were used as internal standards for avenacoside A and saponin B, respectively. Other saponins were relatively quantified based on avenacoside A and saponin B standard responses. The developed method was tested and successfully validated using oat and pea flours, protein concentrates and isolates, as well as their mixtures, and plant-based drinks. With this method, the saponins from oat- and pea-based products were separated and quantified simultaneously within 6 min. The use of respective internal standards derived from U-13C-labelled oat and soyasaponin Ba ensured high accuracy and precision of the proposed method.
Multiple Organic Contaminants Determination Including Multiclass of Pesticides, Polychlorinated Biphenyls, and Brominated Flame Retardants in Portuguese Kiwano Fruits by Gas Chromatography
Authors: Fernandes Virgínia Cruz , Podlasiak Martyna , Vieira Elsa F. , Rodrigues Francisca , Grosso Clara , Moreira Manuela M. , Delerue-Matos Cristina
Published: February 2023

Global production of exotic fruits has been growing steadily over the past decade and expanded beyond the originating countries. The consumption of exotic and new fruits, such as kiwano, has increased due to their beneficial properties for human health. However, these fruits are scarcely studied in terms of chemical safety. As there are no studies on the presence of multiple contaminants in kiwano, an optimized analytical method based on the QuEChERS for the evaluation of 30 multiple contaminants (18 pesticides, 5 polychlorinated biphenyls (PCB), 7 brominated flame retardants) was developed and validated. Under the optimal conditions, satisfactory extraction efficiency was obtained with recoveries ranging from 90% to 122%, excellent sensitivity, with a quantification limit in the range of 0.6 to 7.4 µg kg−1, and good linearity ranging from 0.991 to 0.999. The relative standard deviation for precision studies was less than 15%. The assessment of the matrix effects showed enhancement for all the target compounds. The developed method was validated by analyzing samples collected from Douro Region. PCB 101 was found in trace concentration (5.1 µg kg−1). The study highlights the relevance of including other organic contaminants in monitoring studies in food samples in addition to pesticides.
Effect of Lactose-Reduction in Murciano-Granadina Semi-Hard Goat Cheese on Physicochemical and Sensory Characteristics
Authors: López Ruiz Ángel Luis , Ruiz Morales Francisco de Asís , Ruiz Pérez-Cacho Pilar , Galán-Soldevilla Hortensia
Published: February 2023

Semi-hard pressed goat’s cheese, a traditional matured cheese in Andalusia, has a residual lactose content that may affect people with intolerance to that carbohydrate. Nowadays, lactose-free dairy products are characterized by presenting a scant sensory quality, far removed from their traditional profile for their pronounced sweet and bitter taste and aroma related to Maillard reactions. The aim of this work was to make a cheese with a similar sensory profile to that of the traditional Andalusian one but without lactose. For this purpose, the doses of the enzyme lactase that would be necessary to add to the milk were investigated so that, during the manufacturing of the cheese, there would remain enough lactose for the starter cultures to trigger lactic fermentation and, in turn, to spark the cheese’s own maturity processes. The results show that the combined action of lactase (0.125 g/L, 0.250 g/L, 0.5 g/L, and 1 g/L) and of the lactic bacteria reduces the final content of lactose to below 0.01%, complying with the European Authority of Food Safety’s recommendations for considering the cheeses as being under the denomination “lactose-free”. The physicochemical and sensory values resulting from the different batches of cheese obtained indicate that the lowest dose studied (0.125 g/L) had very similar ones to those of the control cheese.
Curcumin Alleviates Aflatoxin B1-Induced Liver Pyroptosis and Fibrosis by Regulating the JAK2/NLRP3 Signaling Pathway in Ducks
Authors: Cui Yilong , Wang Qi , Zhang Xuliang , Yang Xu , Shi Yun , Li Yanfei , Song Miao
Published: February 2023

Aflatoxin B1 (AFB1) is a serious pollutant in feed and food which causes liver inflammation, fibrosis, and even cirrhosis. The Janus kinase 2 (JAK2)/signal transducers and activators of the transcription 3 (STAT3) signaling pathway is widely involved in inflammatory response and promotes the activation of nod-like receptor protein 3 (NLRP3) inflammasome, thus leading to pyroptosis and fibrosis. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties. However, whether AFB1 exposure leads to the activation of the JAK2/NLRP3 signaling pathway in the liver and whether curcumin can regulate this pathway to influence pyroptosis and fibrosis in the liver remains unclear. In order to clarify these problems, we first treated ducklings with 0, 30, or 60 µg/kg AFB1 for 21 days. We found that AFB1 exposure caused growth inhibition, liver structural and functional damage, and activated JAK2/NLRP3-mediated liver pyroptosis and fibrosis in ducks. Secondly, ducklings were divided into a control group, 60 µg/kg AFB1 group, and 60 µg/kg AFB1 + 500 mg/kg curcumin group. We found that curcumin significantly inhibited the activation of the JAK2/STAT3 pathway and NLRP3 inflammasome, as well as the occurrence of pyroptosis and fibrosis in AFB1-exposed duck livers. These results suggested that curcumin alleviated AFB1-induced liver pyroptosis and fibrosis by regulating the JAK2/NLRP3 signaling pathway in ducks. Curcumin is a potential agent for preventing and treating liver toxicity of AFB1.
The Mushroom Glucans: Molecules of High Biological and Medicinal Importance
Authors: Vetter János
Published: February 2023

Carbohydrates, including polysaccharide macromolecules, are the main constituents of the fungal cell wall. Among these, the homo- or heteropolymeric glucan molecules are decisive, as they not only protect fungal cells but also have broad, positive biological effects on the animal and human bodies. In addition to the beneficial nutritional properties of mushrooms (mineral elements, favorable proteins, low fat and energy content, pleasant aroma, and flavor), they have a high glucan content. Folk medicine (especially in the Far East) used medicinal mushrooms based on previous experience. At the end of the 19th century, but mainly since the middle of the 20th century, progressively more scientific information has been published. Glucans from mushrooms are polysaccharides that contain sugar chains, sometimes of only one kind (glucose), sometimes having several monosaccharide units, and they have two (α and β) anomeric forms (isomers). Their molecular weights range from 104 to 105 Da, and rarely 106 Da. X-ray diffraction studies were the first to determine the triple helix configuration of some glucans. It seems that the existence and integrity of the triple helix structure are criteria for their biological effects. Different glucans can be isolated from different mushroom species, and several glucan fractions can be obtained. The biosynthesis of glucans takes place in the cytoplasm, the processes of initiation and then chain extension take place with the help of the glucan synthase enzyme complex (EC 2.4.1.34), and the sugar units are provided by sugar donor UDPG molecules. The two methods used today for glucan determination are the enzymatic and Congo red methods. True comparisons can only be made using the same method. Congo red dye reacts with the tertiary triple helix structure, and the resulting glucan content better reflects the biological value of glucan molecules. The biological effect of β-glucan molecules is proportional to the integrity of the tertiary structure. The glucan contents of the stipe exceed the values of the caps. The glucan levels of individual fungal taxa (including varieties) differ quantitatively and qualitatively. This review presents in more detail the glucans of lentinan (from Lentinula edodes), pleuran (from Pleurotus ostreatus), grifolan (from Grifola frondose), schizophyllan (from Schizophyllum commune), and krestin (from Trametes versicolor), along with their main biological effects.
Using Laplace Residual Power Series Method in Solving Coupled Fractional Neutron Diffusion Equations with Delayed Neutrons System
Authors: Shqair Mohammed , Ghabar Ibrahim , Burqan Aliaa
Published: February 2023

In this paper, a system of coupled fractional neutron diffusion equations with delayed neutrons was solved efficiently by using a combination of residual power series and Laplace transform techniques, and the anomalous diffusion was considered by taking the non-Gaussian case with different values of fractional parameter α. The Laplace residual power series method (LRPSM) does not require differentiation, conversion, or discretization for the assumed conditions, so the approach is simple and suitable for solving higher-order fractional differential equations. To assure the theoretical results, two different neutron flux initial conditions were presented numerically, where the needed Mathematica codes were performed using essential nuclear reactor cross-section data, and the results for different values of times were tabulated and graphically figured out. Finally, it must be noted that the results align with the Adomian decomposition method.
Design and Performance Analysis of Dry Gas Fishbone Wells for Lower Carbon Footprint
Authors: Ouadi Habib , Laalam Aimen , Hassan Amjed , Chemmakh Abderraouf , Rasouli Vamegh , Mahmoud Mohamed
Published: February 2023

Multilateral well drilling technology has recently assisted the drilling industry in improving borehole contact area and reducing operation time, while maintaining a competitive cost. The most advanced multilateral well drilling method is Fishbone drilling (FbD). This method has been utilized in several hydrocarbon fields worldwide, resulting in high recovery enhancement and reduced carbon emissions from drilling. FbD involves drilling several branches from laterals and can be considered as an alternative method to hydraulic fracturing to increase the stimulated reservoir volume. However, the expected productivity of applying a Fishbone well from one field to another can vary due to various challenges such as Fishbone well design, reservoir lithology, and accessibility. Another challenge is the lack of existing analytical models and the effect of each Fishbone parameter on the cumulative production, as well as the interaction between them. In this paper, analytical and empirical productivity models were modified for FbD in a dry gas reservoir. The modified analytical model showed a higher accuracy with respect to the existing model. It was also compared with the modified empirical model, which proved its higher accuracy. Finally, machine learning algorithms were developed to predict FbD productivity, which showed close results with both analytical and empirical models.
Oleogels as a Fat Substitute in Food: A Current Review
Authors: Silva Roberta Claro da , Ferdaus Md. Jannatul , Foguel Aline , da Silva Thais Lomonaco Teodoro
Published: February 2023

Fats and oils in food give them flavor and texture while promoting satiety. Despite the recommendation to consume predominantly unsaturated lipid sources, its liquid behavior at room temperature makes many industrial applications impossible. Oleogel is a relatively new technology applied as a total or partial replacement for conventional fats directly related to cardiovascular diseases (CVD) and inflammatory processes. Some of the complications in developing oleogels for the food industry are finding structuring agents Generally Recognized as Safe (GRAS), viable economically, and that do not compromise the oleogel palatability; thus, many studies have shown the different possibilities of applications of oleogel in food products. This review presents applied oleogels in foods and recent proposals to circumvent some disadvantages, as reaching consumer demand for healthier products using an easy-to-use and low-cost material can be intriguing for the food industry.
Empirical Law for the Magnetorheological Effect of Nanocomposite Hydrogels with Magnetite Microparticles
Authors: Selzer Lukas , Odenbach Stefan
Published: February 2023

Hydrogels are functional smart materials which can be tailored by modifying their chemical composition. Further functionalization can be achieved by incorporating magnetic particles into the gel matrix. In this study, a hydrogel with magnetite micro-particles is synthesized and characterized by rheological measurements. Inorganic clay is used as the crosslinking agent, which additionally prevents the sedimentation of the micro-particles during the synthesis of the gel. The mass fractions for the magnetite particles in the synthesized gels range from 10% to 60% in the initial state. Rheological measurements are performed in different degrees of swelling using temperature as a stimulus. The influence of a homogeneous magnetic field is analyzed by a step-wise activation and deactivation during dynamic mechanical analysis. For the evaluation of the magnetorheological effect in the steady states a procedure is developed, which takes occurring drift effects into account. Using the magnetic flux density, the particle volume fraction and the storage modulus as independent parameters, a general product approach is deployed for a regression analysis of the dataset. In the end, an empirical law for the magnetorheological effect in nanocomposite hydrogels can be found.
Real and Imagined Places in the Diary of Gabriella Trebits
Authors: Huhák Heléna , Szécsényi András
Published: February 2023

Gabriella Trebits was a prisoner of the Bergen-Belsen concentration camp between November 1944 and April 1945. The spaces present in her diary include both the places of the camp and her typhoid hallucinations. Gabriella described venues through their sensuous dimensions. Since the sensory experiences of everyday life mingled with her visions, her diary became a “textual journey” between real and imagined places. Her narratives helped her to express the difficulties caused by her physical environment and the confusion caused by her hallucinations. As a result, the references to changes in her sensory impressions created a discursive space for the diarist to express her feelings. Since her narrative depicts a suffering and painful condition, we use Joanna Bourke’s concept of pain talk in our analysis. Moreover, the diary demonstrates that it was possible for typhoid patients to connect with their environment despite their isolated situation. Even on the periphery of the camp space, social life persisted. This exploration will not only uncover the narrative strategy of one diarist but also contribute to a deeper understanding of the ways in which tens of thousands died of starvation and diseases―without mass executions or gas chambers―in the Bergen-Belsen concentration camp during the spring of 1945.
Reconstruction of a Comprehensive Interactome and Experimental Data Analysis of FRA10AC1 May Provide Insights into Its Biological Role in Health and Disease
Authors: Sarafidou Theologia , Galliopoulou Eleni , Apostolopoulou Despina , Fragkiadakis Georgios A. , Moschonas Nicholas K.
Published: February 2023

FRA10AC1, the causative gene for the manifestation of the FRA10A fragile site, encodes a well-conserved nuclear protein characterized as a non-core spliceosomal component. Pre-mRNA splicing perturbations have been linked with neurodevelopmental diseases. FRA10AC1 variants have been, recently, causally linked with severe neuropathological and growth retardation phenotypes. To further elucidate the participation of FRA10AC1 in spliceosomal multiprotein complexes and its involvement in neurological phenotypes related to splicing, we exploited protein–protein interaction experimental data and explored network information and information deduced from transcriptomics. We confirmed the direct interaction of FRA10AC1with ESS2, a non-core spliceosomal protein, mapped their interacting domains, and documented their tissue co-localization and physical interaction at the level of intracellular protein stoichiometries. Although FRA10AC1 and SF3B2, a major core spliceosomal protein, were shown to interact under in vitro conditions, the endogenous proteins failed to co-immunoprecipitate. A reconstruction of a comprehensive, strictly binary, protein–protein interaction network of FRA10AC1 revealed dense interconnectivity with many disease-associated spliceosomal components and several non-spliceosomal regulatory proteins. The topological neighborhood of FRA10AC1 depicts an interactome associated with multiple severe monogenic and multifactorial neurodevelopmental diseases mainly referring to spliceosomopathies. Our results suggest that FRA10AC1 involvement in pre-mRNA processing might be strengthened by interconnecting splicing with transcription and mRNA export, and they propose the broader role(s) of FRA10AC1 in cell pathophysiology.
Reference Guided De Novo Genome Assembly of Transformation Pliable Solanum lycopersicum cv. Pusa Ruby
Authors: Vats Sanskriti , Kumar Virender , Mandlik Rushil , Patil Gunvant , Sonah Humira , Roy Joy , Sharma Tilak Raj , Deshmukh Rupesh
Published: February 2023

Solanum lycopersicum cv. Pusa Ruby (PR) is a superior tomato cultivar routinely used as a model tomato variety. Here, we report a reference-guided genome assembly for PR, covering 97.6% of the total single-copy genes in the solanales order. The PR genome contains 34,075 genes and 423,288 variants, out of which 127,131 are intragenic and 1232 are of high impact. The assembly was packaged according to PanSol guidelines (N50 = 60,396,827) with the largest scaffold measuring 85 megabases. The similarity of the PR genome assembly to Heinz1706, M82, and Fla.8924 was measured and the results suggest PR has the lowest affinity towards the hybrid Fla.8924. We then analyzed the regeneration efficiency of PR in comparison to another variety, Pusa Early Dwarf (PED). PR was found to have a high regeneration rate (45.51%) and therefore, we performed allele mining for genes associated with regeneration and found that only AGAMOUS-LIKE15 has a null mutation. Further, allele mining for fruit quality-related genes was also executed. The PR genome has an Ovate mutation leading to round fruit shape, causing economically undesirable fruit cracking. This genomic data can be potentially used for large scale crop improvement programs as well as functional annotation studies.
DNMT3B rs2424913 as a Risk Factor for Congenital Heart Defects in Down Syndrome
Authors: Majstorović Dijana , Barišić Anita , Božović Ivana Babić , Čače Iva Bilić , Čače Neven , Štifanić Mauro , Vraneković Jadranka
Published: February 2023

Impairments of the genes that encode enzymes that are involved in one-carbon metabolism because of the presence of gene polymorphisms can affect the methylation pattern. The altered methylation profiles of the genes involved in cardiogenesis may result in congenital heart defects (CHDs). The aim of this study was to investigate the association between the MTHFR rs1801133, MTHFR rs1801131, MTRR rs1801394, DNMT1 rs2228611, DNMT3A rs1550117, DNMT3B rs1569686, and DNMT3B rs2424913 gene polymorphisms and congenital heart defects in Down syndrome (DS) individuals. The study was conducted on 350 participants, including 134 DS individuals with CHDs (DSCHD+), 124 DS individuals without CHDs (DSCHD−), and 92 individuals with non-syndromic CHD. The genotyping was performed using the PCR–RFLP method. A statistically significant higher frequency of the DNMT3B rs2424913 TT in the DSCHD+ individuals was observed. The DNMT3B rs2424913 TT genotype, as well as the T allele, had significantly higher frequencies in the individuals with DS and atrial septal defects (ASDs) in comparison with the individuals with DS and other CHDs. Furthermore, our results indicate a statistically significant effect of the DNMT3B rs1569686 TT genotype in individuals with non-syndromic CHDs. The results of the study suggest that the DNMT3B rs2424913 TT genotypes may be a possible predisposing factor for CHDs in DS individuals, and especially those with ASDs.
Epigenetic Regulation of β-Globin Genes and the Potential to Treat Hemoglobinopathies through Epigenome Editing
Authors: Fontana Letizia , Alahouzou Zoe , Miccio Annarita , Antoniou Panagiotis
Published: February 2023

Beta-like globin gene expression is developmentally regulated during life by transcription factors, chromatin looping and epigenome modifications of the β-globin locus. Epigenome modifications, such as histone methylation/demethylation and acetylation/deacetylation and DNA methylation, are associated with up- or down-regulation of gene expression. The understanding of these mechanisms and their outcome in gene expression has paved the way to the development of new therapeutic strategies for treating various diseases, such as β-hemoglobinopathies. Histone deacetylase and DNA methyl-transferase inhibitors are currently being tested in clinical trials for hemoglobinopathies patients. However, these approaches are often uncertain, non-specific and their global effect poses serious safety concerns. Epigenome editing is a recently developed and promising tool that consists of a DNA recognition domain (zinc finger, transcription activator-like effector or dead clustered regularly interspaced short palindromic repeats Cas9) fused to the catalytic domain of a chromatin-modifying enzyme. It offers a more specific targeting of disease-related genes (e.g., the ability to reactivate the fetal γ-globin genes and improve the hemoglobinopathy phenotype) and it facilitates the development of scarless gene therapy approaches. Here, we summarize the mechanisms of epigenome regulation of the β-globin locus, and we discuss the application of epigenome editing for the treatment of hemoglobinopathies.
Estimates of Genomic Heritability and the Marker-Derived Gene for Re(Production) Traits in Xinggao Sheep
Authors: Liu Zaixia , Fu Shaoyin , He Xiaolong , Liu Xuewen , Shi Caixia , Dai Lingli , Wang Biao , Chai Yuan , Liu Yongbin , Zhang Wenguang
Published: February 2023

Xinggao sheep are a breed of Chinese domestic sheep that are adapted to the extremely cold climatic features of the Hinggan League in China. The economically vital reproductive trait of ewes (litter size, LS) and productive traits of lambs (birth weight, BWT; weaning weight, WWT; and average daily gain, ADG) are expressed in females and later in life after most of the selection decisions have been made. This study estimated the genetic parameters for four traits to explore the genetic mechanisms underlying the variation, and we performed genome-wide association study (GWAS) tests on a small sample size to identify novel marker trait associations (MTAs) associated with prolificacy and growth. We detected two suggestive significant single-nucleotide polymorphisms (SNPs) associated with LS and eight significant SNPs for BWT, WWT, and ADG. These candidate loci and genes also provide valuable information for further fine-mapping of QTLs and improvement of reproductive and productive traits in sheep.
SERPINF1 Mediates Tumor Progression and Stemness in Glioma
Authors: Song Lairong , Huo Xulei , Li Xiaojie , Xu Xiaoying , Zheng Yi , Li Da , Zhang Junting , Wang Ke , Wang Liang , Wu Zhen
Published: February 2023

Serpin family F member 1 (SERPINF1) reportedly plays multiple roles in various tumors; however, its clinical significance and molecular functions in glioma have been largely understudied. In the present study, we analyzed the prognostic value of SERPINF1 in three independent glioma datasets. Next, we explored the molecular functions and transcriptional regulation of SERPINF1 at the single-cell level. Moreover, in vitro experiments were conducted to evaluate the roles of SERPINF1 in the proliferation, invasion, migration, and stemness of glioma cells. Our results showed that a higher expression of SERPINF1 correlated with a poor overall survival rate in glioma patients (hazard ratio: 4.061 in TCGA, 2.017 in CGGA, and 1.675 in GSE16011, p < 0.001). Besides, SERPINF1 knockdown could suppress the proliferation, invasion, and migration of glioma cells in vitro. In addition, SERPINF1 expression was significantly upregulated in glioma stem cells (GSCs) compared to parental glioma cells. Knocking down SERPINF1 impaired the sphere formation of GSC-A172 and GSC-LN18. Bioinformatics analysis revealed that Notch signaling activation was closely associated with high SERPINF1 expression at the single-cell level. Furthermore, STAT1, CREM, and NR2F2 may participate in the transcriptional regulation of SERPINF1 in glioma. Overall, our results suggest that SERPINF1 may be a candidate prognostic predictor and potential therapeutic target for glioma.
Whole-Genome Sequencing Data Reveal New Loci Affecting Milk Production in German Black Pied Cattle (DSN)
Authors: Korkuć Paula , Neumann Guilherme B. , Hesse Deike , Arends Danny , Reißmann Monika , Rahmatalla Siham , May Katharina , Wolf Manuel J. , König Sven , Brockmann Gudrun A.
Published: February 2023

German Black Pied (DSN) is considered an ancestral population of the Holstein breed. The goal of the current study was to fine-map genomic loci for milk production traits and to provide sequence variants for selection. We studied genome-wide associations for milk-production traits in 2160 DSN cows. Using 11.7 million variants from whole-genome sequencing of 304 representative DSN cattle, we identified 1980 associated variants (−log10(p) ≥ 7.1) in 13 genomic loci on 9 chromosomes. The highest significance was found for the MGST1 region affecting milk fat content (−log10(p) = 11.93, MAF = 0.23, substitution effect of the minor allele (ßMA) = −0.151%). Different from Holstein, DGAT1 was fixed (0.97) for the alanine protein variant for high milk and protein yield. A key gene affecting protein content was CSN1S1 (−log10(p) = 8.47, MAF = 049, ßMA = −0.055%) and the GNG2 region (−log10(p) = 10.48, MAF = 0.34, ßMA = 0.054%). Additionally, we suggest the importance of FGF12 for protein and fat yield, HTR3C for milk yield, TLE4 for milk and protein yield, and TNKS for milk and fat yield. Selection for favored alleles can improve milk yield and composition. With respect to maintaining the dual-purpose type of DSN, unfavored linkage to genes affecting muscularity has to be investigated carefully, before the milk-associated variants can be applied for selection in the small population.
Integrating Whole-Genome Resequencing and RNA Sequencing Data Reveals Selective Sweeps and Differentially Expressed Genes Related to Nervous System Changes in Luxi Gamecocks
Authors: Zhou Jieke , Chang Ying , Li Junying , Bao Haigang , Wu Changxin
Published: February 2023

The Luxi gamecock developed very unique morphological and behavioral features under the special artificial selection of the most famous Chinese gamecocks. There are very few research studies on the genetics and selection of the Luxi gamecock. We used six methods (Fst, Tajima’s D, hapFLK, iHS, XP-EHH, and Runs of homozygosity) to detect selective sweeps in whole-genome resequencing data of 19 Luxi gamecocks compared to other Chinese indigenous chickens. Eleven genes that were highly related to nervous system development (CDH18, SLITRK1, SLITRK6, NDST3, ATP23, LRIG3, IL1RAPL1, GADL1, C5orf22, UGT8, WISP1, and WNT9A) appeared in at least four methods and were regarded as the most significant genes under selection. Differentially expressed gene (DEG) analysis based on the RNA sequencing data of the cerebral cortex and middle brain between six Luxi gamecocks, Tibetan chickens, and white leghorns found that most differentially expressed genes were enriched in pathways with nervous system functions. Genes associated with aggressiveness-related neurotransmitters (SLC4A2, DRD1, DRD2, ADRA2A, and ADRA2B) showed differential expression rates in Luxi gamecocks as well. Combined results showed that most genes in selective sweep regions were also differentially expressed in Luxi gamecocks including the most significant genes (SLITRK6, IL1RAPL1, GADL1, WISP1, and LRIG3). This study provides more insight into molecular mechanisms of the aggressiveness of gamecocks and aims to promote further studies on animal and human aggression.
CoNet: Efficient Network Regression for Survival Analysis in Transcriptome-Wide Association Studies—With Applications to Studies of Breast Cancer
Authors: Han Jiayi , Zhang Liye , Yan Ran , Ju Tao , Jin Xiuyuan , Wang Shukang , Yuan Zhongshang , Ji Jiadong
Published: February 2023

Transcriptome-wide association studies (TWASs) aim to detect associations between genetically predicted gene expression and complex diseases or traits through integrating genome-wide association studies (GWASs) and expression quantitative trait loci (eQTL) mapping studies. Most current TWAS methods analyze one gene at a time, ignoring the correlations between multiple genes. Few of the existing TWAS methods focus on survival outcomes. Here, we propose a novel method, namely a COx proportional hazards model for NEtwork regression in TWAS (CoNet), that is applicable for identifying the association between one given network and the survival time. CoNet considers the general relationship among the predicted gene expression as edges of the network and quantifies it through pointwise mutual information (PMI), which is under a two-stage TWAS. Extensive simulation studies illustrate that CoNet can not only achieve type I error calibration control in testing both the node effect and edge effect, but it can also gain more power compared with currently available methods. In addition, it demonstrates superior performance in real data application, namely utilizing the breast cancer survival data of UK Biobank. CoNet effectively accounts for network structure and can simultaneously identify the potential effecting nodes and edges that are related to survival outcomes in TWAS.
Novel Exon 7 Deletions in TSPAN12 in a Three-Generation FEVR Family: A Case Report and Literature Review
Authors: Jiang Zixuan , Wang Panfeng
Published: February 2023

Familial exudative vitreoretinopathy (FEVR) is a severe clinically and genetically heterogeneous disease that is characterized by vascular disorder. FEVR exhibits strikingly variable clinical phenotypes, ranging from asymptomatic to total blindness. In this case, we present a patient who was first treated as having high myopia and retinopathy but was finally diagnosed with FEVR caused by the heterozygous deletion of exon 7 in TSPAN12 with the aid of whole genome sequencing (WGS). Typical vascular changes, including vascular leakage and an avascular zone in the peripheral retina, were observed in the proband using fundus fluorescein angiography (FFA), and the macular dragging was shown to be progressing in the follow-up visit. Furthermore, the proband showed unreported TSPAN12-related phenotypes of FEVR: ERG (full-field electroretinogram) abnormalities and retinoschisis. Only mild vascular changes were exhibited in the FFA for the other three family members who carried the same deletion of exon 7 in TSPAN12. This case expands our understanding of the phenotype resulting from TSPAN12 mutations and signifies the importance of combining both clinical and molecular analysis approaches to establish a complete diagnosis.
Description of the Three Complete Mitochondrial Genomes of Sitta (S. himalayensis, S. nagaensis, and S. yunnanensis) and Phylogenetic Relationship (Aves: Sittidae)
Authors: Yuan Qingmiao , Guo Qiang , Cao Jing , Luo Xu , Duan Yubao
Published: February 2023

Nuthatches (genus Sitta; family Sittidae) are a passerine genus with a predominantly Nearctic and Eurasian distribution. To understand the phylogenetic position of Sitta and phylogenetic relations within this genus, we sequenced the complete mitochondrial genomes of three Sitta species (S. himalayensis, S. nagaensis, and S. yunnanensis), which were 16,822–16,830 bp in length and consisted of 37 genes and a control region. This study recovered the same gene arrangement found in the mitogenomes of Gallus gallus, which is considered the typical ancestral avian gene order. All tRNAs were predicted to form the typical cloverleaf secondary structures. Bayesian inference and maximum likelihood phylogenetic analyses of sequences of 18 species obtained a well-supported topology. The family Sittidae is the sister group of Troglodytidae, and the genus Sitta can be divided into three major clades. We demonstrated the phylogenetic relationships within the genus Sitta (S. carolinensis + ((S. villosa + S. yunnanensis) + (S. himalayensis + (S. europaea + S. nagaensis)))).
Nanoplastics Toxicity Specific to Liver in Inducing Metabolic Dysfunction—A Comprehensive Review
Authors: Haldar Shoumi , Yhome Nounenuo , Muralidaran Yuvashree , Rajagopal Senthilkumar , Mishra Prabhakar
Published: February 2023

Plastic pollution in the world is widespread and growing. The environment is swamped with nanoplastics (<100 nm), and the health consequences of these less visible pollutants are unknown. Furthermore, there is evidence that microplastics can release nanoplastics by digestive disintegration, implying that macroplastic exposure can cause direct and indirect disease via nanoplastics. The existence and impact of nanoplastics in numerous tissues from invertebrates to larger vertebrates that consume significant amounts of plastics were investigated, and histopathological techniques were utilized to determine physiological reactions and inflammation from the plastics. Nanoplastics enters an organism through the respiratory and gastro-intestinal tract where they accumulate into the liver through blood circulation via absorption, or epidermal infiltration. It is stated that macroplastics can cause damage directly at the site of exposure, whereas nanoplastics can influence the liver, causing subsequent damage to other organs. Multi-organ dysfunction is brought on by liver changes, and nanoplastics can readily enter the gut-liver axis and disturb the gut microflora. By exploring the literature and summarizing the research that has been published to date, this review article reveals the deleterious effect and mechanisms of nanoplastics on the pathophysiological functions of the hepatic system.
TNC Accelerates Hypoxia-Induced Cardiac Injury in a METTL3-Dependent Manner
Authors: Cheng Hao , Li Linnan , Xue Junqiang , Ma Jianying , Ge Junbo
Published: February 2023

Cardiac fibrosis and cardiomyocyte apoptosis are reparative processes after myocardial infarction (MI), which results in cardiac remodeling and heart failure at last. Tenascin-C (TNC) consists of four distinct domains, which is a large multimodular glycoprotein of the extracellular matrix. It is also a key regulator of proliferation and apoptosis in cardiomyocytes. As a significant m6A regulator, METTL3 binds m6A sites in mRNA to control its degradation, maturation, stabilization, and translation. Whether METTL3 regulates the occurrence and development of myocardial infarction through the m6A modification of TNC mRNA deserves our study. Here, we have demonstrated that overexpression of METTL3 aggravated cardiac dysfunction and cardiac fibrosis after 4 weeks after MI. Moreover, we also demonstrated that TNC resulted in cardiac fibrosis and cardiomyocyte apoptosis after MI. Mechanistically, METTL3 led to enhanced m6A levels of TNC mRNA and promoted TNC mRNA stability. Then, we mutated one m6A site “A” to “T”, and the binding ability of METTL3 was reduced. In conclusion, METTL3 is involved in cardiac fibrosis and cardiomyocyte apoptosis by increasing m6A levels of TNC mRNA and may be a promising target for the therapy of cardiac fibrosis after MI.
Considerations of the Genetic Background of Obesity among Patients with Psoriasis
Authors: Czarnecka Anna , Purzycka-Bohdan Dorota , Zabłotna Monika , Bohdan Michał , Nowicki Roman J. , Szczerkowska-Dobosz Aneta
Published: February 2023

Psoriasis comorbidities may emerge from pleiotropic mechanisms, including common proinflammatory pathways, cellular mediators or genetic predisposition. Obesity is considered to be an independent risk factor of psoriasis, which may influence the severity of the disease and its early onset, decrease patients’ quality of life, alter response to psoriasis therapies and affect morbidity by reduced life expectancy due to cardiovascular events. Although novel approaches, including genetic techniques, have provided a wide range of new research, there are still scarce studies elaborating on the common genetic background of psoriasis and obesity. The aim of this study was to present and evaluate a possible common genetic background of psoriasis and concomitant increased body mass based on the review of the available literature.
Elucidation of the Landscape of Alternatively Spliced Genes and Features in the Dorsal Striatum of Aggressive/Aggression-Deprived Mice in the Model of Chronic Social Conflicts
Authors: Babenko Vladimir , Redina Olga , Smagin Dmitry , Kovalenko Irina , Galyamina Anna , Kudryavtseva Natalia
Published: February 2023

Both aggressive and aggression-deprived (AD) individuals represent pathological cases extensively studied in psychiatry and substance abuse disciplines. We employed the animal model of chronic social conflicts curated in our laboratory for over 30 years. In the study, we pursued the task of evaluation of the key events in the dorsal striatum transcriptomes of aggression-experienced mice and AD species, as compared with the controls, using RNA-seq profiling. We evaluated the alternative splicing-mediated transcriptome dynamics based on the RNA-seq data. We confined our attention to the exon skipping (ES) events as the major AS type for animals. We report the concurrent posttranscriptional and posttranslational regulation of the ES events observed in the phosphorylation cycles (in phosphoproteins and their targets) in the neuron-specific genes of the striatum. Strikingly, we found that major neurospecific splicing factors (Nova1, Ptbp1, 2, Mbnl1, 2, and Sam68) related to the alternative splicing regulation of cAMP genes (Darpp-32, Grin1, Ptpn5, Ppp3ca, Pde10a, Prkaca, Psd95, and Adora1) are upregulated specifically in aggressive individuals as compared with the controls and specifically AD animals, assuming intense switching between isoforms in the cAMP-mediated (de)phosphorylation signaling cascade. We found that the coding alternative splicing events were mostly attributed to synaptic plasticity and neural development-related proteins, while the nonsense-mediated decay-associated splicing events are mostly attributed to the mRNA processing of genes, including the spliceosome and splicing factors. In addition, considering the gene families, the transporter (Slc) gene family manifested most of the ES events. We found out that the major molecular systems employing AS for their plasticity are the ‘spliceosome’, ‘chromatin rearrangement complex’, ‘synapse’, and ‘neural development/axonogenesis’ GO categories. Finally, we state that approximately 35% of the exon skipping variants in gene coding regions manifest the noncoding variants subject to nonsense-mediated decay, employed as a homeostasis-mediated expression regulation layer and often associated with the corresponding gene expression alteration.