bluuebunny/crossref_metadata_2025 huggingface dataset:
A Methodology Based on FT-IR Data Combined with Random Forest Model to Generate Spectralprints for the Characterization of High-Quality Vinegars
Authors: Calle José Luis P. , Ferreiro-González Marta , Ruiz-Rodríguez Ana , Barbero Gerardo F. , Álvarez José Á. , Palma Miguel , Ayuso Jesús
Published: June 2021

Sherry wine vinegar is a Spanish gourmet product under Protected Designation of Origin (PDO). Before a vinegar can be labeled as Sherry vinegar, the product must meet certain requirements as established by its PDO, which, in this case, means that it has been produced following the traditional solera and criadera ageing system. The quality of the vinegar is determined by many factors such as the raw material, the acetification process or the aging system. For this reason, mainly producers, but also consumers, would benefit from the employment of effective analytical tools that allow precisely determining the origin and quality of vinegar. In the present study, a total of 48 Sherry vinegar samples manufactured from three different starting wines (Palomino Fino, Moscatel, and Pedro Ximénez wine) were analyzed by Fourier-transform infrared (FT-IR) spectroscopy. The spectroscopic data were combined with unsupervised exploratory techniques such as hierarchical cluster analysis (HCA) and principal component analysis (PCA), as well as other nonparametric supervised techniques, namely, support vector machine (SVM) and random forest (RF), for the characterization of the samples. The HCA and PCA results present a clear grouping trend of the vinegar samples according to their raw materials. SVM in combination with leave-one-out cross-validation (LOOCV) successfully classified 100% of the samples, according to the type of wine used for their production. The RF method allowed selecting the most important variables to develop the characteristic fingerprint (“spectralprint”) of the vinegar samples according to their starting wine. Furthermore, the RF model reached 100% accuracy for both LOOCV and out-of-bag (OOB) sets.
Improvement of Must Fermentation from Late Harvest cv. Tempranillo Grapes Treated with Pulsed Light
Authors: Escott Carlos , López Carmen , Loira Iris , González Carmen , Bañuelos María Antonia , Tesfaye Wendu , Suárez-Lepe José Antonio , Morata Antonio
Published: June 2021

Pulsed light irradiation is a nonthermal technology currently used for the elimination of pathogens from a diverse range of food products. In the last two decades, the results obtained using PL at laboratory scale are encouraging wine experts to use it in the winemaking industry. PL can reduce native yeast counts significantly, which facilitates the use of starter cultures, reducing SO2 requirements at the same time. In this experimental set up, Tempranillo grapes were subjected to pulsed light treatment, and the fermentative performance of non-Saccharomyces yeasts belonging to the species Schizosaccharomyces pombe, Lachancea thermotolerans, Torulaspora delbrueckii, Metschnikowia pulcherrima and Hanseniaspora vineae was monitored in sequential fermentations against spontaneous fermentation and pure culture fermentation with the species Saccharomyces cerevisiae. The experimental analyses comprised the determination of anthocyanin (High performance liquid chromatography with photodiode array detector—HPLC-DAD), polyphenol index and colour (Ultraviolet-visible spectroscopy—UV-Vis spectrophotometer), fermentation-derived volatiles (Gas chromatography with flame ionization detector—GC-FID), oenological parameters (Fourier transform Infrared spectroscopy—FT-IR) and structural damage of the skin (atomic force microscopy—AFM). The results showed a decrease of 1.2 log CFU/mL yeast counts after pulsed light treatment and more rapid and controlled fermentation kinetics in musts from treated grapes than in untreated samples. The fermentations done with treated grapes allowed starter cultures to better implant in the must, although a larger anthocyanin loss (up to 93%) and an increase in hue values (1 unit) towards more yellow hues were observed for treated grapes. The development of biomass was larger in musts from treated grapes. The profile of volatile compounds and oenological parameters reveals that fermentations carried out with untreated grapes are prone to deviations from native microbiota (e.g., production of lactic acid). Finally, no severe damage on the skin was observed with the AFM on treated grapes.
Influence of Technological Maturity on the Secondary Metabolites of Hemp Concentrate (Cannabis sativa L.)
Authors: Tremlová Bohuslava , Mikulášková Hana Koudelková , Hajduchová Klaudia , Jancikova Simona , Kaczorová Dominika , Ćavar Zeljković Sanja , Dordevic Dani
Published: June 2021

During the last decade, the popularity of hemp products has been rising rapidly. Products containing cannabidiol (CBD) are of predominant interest. Traditional hemp products are frequently enriched by CBD due to their potential therapeutic effects. Cannabidiol occurs naturally in hemp juice together with other biologically active substances, such as terpenes, flavonoids, and stilbenoids. These constituents act synergistically. This study aimed to observe the influence of the hemp plant developmental stage on its chemical composition and antioxidant activity. The hemp plants were analyzed during three vegetative stages, i.e., before, during, and after flowering. The collected samples were evaluated using the following analyses: total polyphenolic content and profile, terpenoid and cannabinoid contents, and ferric reducing antioxidant power. The results revealed statistically significant differences between the samples in almost all set parameters. The optimal period for hemp harvest depends on desirable compounds, i.e., phenolic content is the highest before flowering, while the levels of cannabinoids and terpenoids are the highest during the flowering period.
Effect of Freeze Drying and Simulated Gastrointestinal Digestion on Phenolic Metabolites and Antioxidant Property of the Natal Plum (Carissa macrocarpa)
Authors: Seke Faith , Manhivi Vimbainashe E. , Shoko Tinotenda , Slabbert Retha M. , Sultanbawa Yasmina , Sivakumar Dharini
Published: June 2021

Natal plums (Carissa macrocarpa) are a natural source of bioactive compounds, particularly anthocyanins, and can be consumed as a snack. This study characterized the impact of freeze drying and in vitro gastrointestinal digestion on the phenolic profile, antioxidant capacity, and α-glucosidase activity of the Natal plum (Carissa macrocarpa). The phenolic compounds were quantified using high performance liquid chromatography coupled to a diode-array detector HPLC-DAD and an ultra-performance liquid chromatograph (UPLC) with a Waters Acquity photodiode array detector (PDA) coupled to a Synapt G2 quadrupole time-of-flight (QTOF) mass spectrometer. Cyanidin-3-O-β-sambubioside (Cy-3-Sa) and cyanidin-3-O-glucoside (Cy-3-G) were the dominant anthocyanins in the fresh and freeze-dried Natal plum powder. Freeze drying did not affect the concentrations of both cyanidin compounds compared to the fresh fruit. Both cyanidin compounds, ellagic acid, catechin, epicatechin syringic acid, caffeic acid, luteolin, and quercetin O-glycoside from the ingested freeze-dried Natal plum powder was quite stable in the gastric phase compared to the small intestinal phase. Cyanidin-3-O-β-sambubioside from the ingested Natal plum powder showed bioaccessibility of 32.2% compared to cyanidin-3-O-glucoside (16.3%). The degradation of anthocyanins increased the bioaccessibility of gallic acid, protocatechuic acid, coumaric acid, and ferulic acid significantly, in the small intestinal digesta. The ferric reducing antioxidant power (FRAP), 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) activities, and inhibitory effect of α-glucosidase activity decreased in the small intestinal phase. Indigenous fruits or freeze-dried powders with Cy-3-Sa can be a better source of anthocyanin than Cy-3-G due to higher bioaccessibility in the small intestinal phase.
How Depressing Is Inbreeding? A Meta-Analysis of 30 Years of Research on the Effects of Inbreeding in Livestock
Authors: Doekes Harmen P. , Bijma Piter , Windig Jack J.
Published: June 2021

Inbreeding depression has been widely documented for livestock and other animal and plant populations. Inbreeding is generally expected to have a stronger unfavorable effect on fitness traits than on other traits. Traditionally, the degree of inbreeding depression in livestock has been estimated as the slope of the linear regression of phenotypic values on pedigree-based inbreeding coefficients. With the increasing availability of SNP-data, pedigree inbreeding can now be replaced by SNP-based measures. We performed a meta-analysis of 154 studies, published from 1990 to 2020 on seven livestock species, and compared the degree of inbreeding depression (1) across different trait groups, and (2) across different pedigree-based and SNP-based measures of inbreeding. Across all studies and traits, a 1% increase in pedigree inbreeding was associated with a median decrease in phenotypic value of 0.13% of a trait’s mean, or 0.59% of a trait’s standard deviation. Inbreeding had an unfavorable effect on all sorts of traits and there was no evidence for a stronger effect on primary fitness traits (e.g., reproduction/survival traits) than on other traits (e.g., production traits or morphological traits). p-values of inbreeding depression estimates were smaller for SNP-based inbreeding measures than for pedigree inbreeding, suggesting more power for SNP-based measures. There were no consistent differences in p-values for percentage of homozygous SNPs, inbreeding based on runs of homozygosity (ROH) or inbreeding based on a genomic relationship matrix. The number of studies that directly compares these different measures, however, is limited and comparisons are furthermore complicated by differences in scale and arbitrary definitions of particularly ROH-based inbreeding. To facilitate comparisons across studies in future, we provide the dataset with inbreeding depression estimates of 154 studies and stress the importance of always reporting detailed information (on traits, inbreeding coefficients, and models used) along with inbreeding depression estimates.
Altered Expression of TSPAN32 during B Cell Activation and Systemic Lupus Erythematosus
Authors: Fagone Paolo , Mangano Katia , Di Marco Roberto , Reyes-Castillo Zyanya , Muñoz-Valle José Francisco , Nicoletti Ferdinando
Published: June 2021

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with various clinical features. Autoreactive B cells play a role in disease pathogenesis, through the production of multiple autoantibodies, which form immune complexes and induce the inflammatory response and tissue damage associated with SLE. Recently, tetraspanins, and in particular, TSPAN32, have been recognized to play a central role in immunity, as they are involved in various biological processes, such as the antigen presentation and the activation of lymphocytes. Evidence suggests that tetraspanins could represent in the future a target for therapeutic purposes in patients suffering from autoimmune/immunoinflammatory disorders. In the present study, by performing in silico analyses of high-throughput data, we evaluated the expression levels of TSPAN32 in B cell activation and investigated its modulation in circulating B cells from SLE patients. Our data show that B cell activation is associated with a significant downregulation of TSPAN32. Additionally, significantly lower levels of TSPAN32 were observed in circulating plasmablasts from SLE patients as compared to healthy donor plasmablasts. In addition, type I interferons (IFNs)-related genes were enriched among the genes negatively correlated to TSPAN32, in SLE plasmablasts. Accordingly, IFN-α is able to induce a dose-dependent downregulation of TSPAN32 in B cells. Overall, the data here presented suggest the potential use of TSPAN32 as a diagnostic marker and therapeutic target for the evaluation and management of humoral immune responses in chronic diseases, such as SLE.
Increase in Phloem Area in the Tomato hawaiian skirt Mutant Is Associated with Enhanced Sugar Transport
Authors: Lombardo Fabien , Gramazio Pietro , Ezura Hiroshi
Published: June 2021

The HAWAIIAN SKIRT (HWS) gene has been described in Arabidopsis, rice, tomato and poplar where it seems to perform distinct functions with relatively little overlap. In tomato, alteration of the gene function confers facultative parthenocarpy, thought to be a consequence of changes in the microRNA metabolism. In the rice mutant, improvement in panicle architecture is associated with an increase in grain yield. Knowing that hws tomato fruits show a higher Brix level, it was suspected that vascular bundles might also be altered in this species, in a similar fashion to the rice phenotype. The pedicel structure of the hws-1 line was therefore examined under the microscope and sugar concentrations from phloem exudate were determined in an enzymatic assay. A distinct increase in the phloem area was observed as well as a higher sugar content in mutant phloem exudates, which is hypothesized to contribute to the high Brix level in the mutant fruits. Furthermore, the described phenotype in this study bridges the gap between Arabidopsis and rice phenotypes, suggesting that the modulation of the microRNA metabolism by HWS influences traits of agricultural interest across several species.
A Methodological Framework to Discover Pharmacogenomic Interactions Based on Random Forests
Authors: Fasola Salvatore , Cilluffo Giovanna , Montalbano Laura , Malizia Velia , Ferrante Giuliana , La Grutta Stefania
Published: June 2021

The identification of genomic alterations in tumor tissues, including somatic mutations, deletions, and gene amplifications, produces large amounts of data, which can be correlated with a diversity of therapeutic responses. We aimed to provide a methodological framework to discover pharmacogenomic interactions based on Random Forests. We matched two databases from the Cancer Cell Line Encyclopaedia (CCLE) project, and the Genomics of Drug Sensitivity in Cancer (GDSC) project. For a total of 648 shared cell lines, we considered 48,270 gene alterations from CCLE as input features and the area under the dose-response curve (AUC) for 265 drugs from GDSC as the outcomes. A three-step reduction to 501 alterations was performed, selecting known driver genes and excluding very frequent/infrequent alterations and redundant ones. For each model, we used the concordance correlation coefficient (CCC) for assessing the predictive performance, and permutation importance for assessing the contribution of each alteration. In a reasonable computational time (56 min), we identified 12 compounds whose response was at least fairly sensitive (CCC > 20) to the alteration profiles. Some diversities were found in the sets of influential alterations, providing clues to discover significant drug-gene interactions. The proposed methodological framework can be helpful for mining pharmacogenomic interactions.
Comprehensive Analysis of RNA Expression Correlations between Biofluids and Human Tissues
Authors: Sun Ruya , Cui Chunmei , Zhou Yuan , Cui Qinghua
Published: June 2021

In recent years, biofluid has been considered a promising source of non-invasive biomarkers for health monitoring and disease diagnosis. However, the expression consistency between biofluid and human tissue, which is fundamental to RNA biomarker development, has not been fully evaluated. In this study, we collected expression profiles across 53 human tissues and five main biofluid types. Utilizing the above dataset, we uncovered a globally positive correlation pattern between various biofluids (including blood, urine, bile, saliva and stool) and human tissues. However, significantly varied biofluid–tissue similarity levels and tendencies were observed between mRNA and lncRNA. Moreover, a higher correlation was found between biofluid types and their functionally related and anatomically closer tissues. In particular, a highly specific correlation was discovered between urine and the prostate. The biological sex of the donor was also proved to be an important influencing factor in biofluid–tissue correlation. Moreover, genes enriched in basic biological processes were found to display low variability across biofluid types, while genes enriched in catabolism-associated pathways were identified as highly variable.
Muscle Energy Technique in the Rehabilitative Treatment for Acute and Chronic Non-Specific Neck Pain: A Systematic Review
Authors: Sbardella Silvia , La Russa Chiara , Bernetti Andrea , Mangone Massimiliano , Guarnera Andrea , Pezzi Letizia , Paoloni Marco , Agostini Francesco , Santilli Valter , Saggini Raoul , Paolucci Teresa
Published: June 2021

Background: Non-specific neck pain (NNP) affects 30–50% of the general population, and it often leads to severe disability. Several manual therapy techniques are available to reduce pain and disability and to improve cervical range of motion and functional activities. Muscle Energy Technique (MET) showed more evidence for treating such a disorder. The aim of this current scientific literature analysis was to compare the clinical effects of MET with the other manual or rehabilitative treatments for non-specific acute and chronic neck pain. Methods: The literature search was conducted using the following databases: PubMed, Medline, PEDro, Cochrane Database, and Google Scholar from 2010 to January 2020. Clinical trials about MET were included. The quality of the trials was assessed according to the PEDro scale. Results: Twenty-one papers according to inclusion and exclusion criteria were selected: 15 studies about non-specific acute neck pain and 6 studies about non-specific chronic neck pain. Conclusions: This analysis suggests that the MET approach has a good clinical effect on reducing neck pain in patients with acute neck pain and improves cervical range of motion in patients with chronic neck pain, and is better if combined with a traditional rehabilitative approach. This review’s findings should be considered with caution for physiotherapy practice because of the studies’ methodologic limitations. On the basis of the current available and limited evidence, clinicians could combine MET with traditional physiotherapy and other manual techniques when treating people with non-specific neck pain.
An Examination of COVID-19 Mitigation Efficiency among 23 Countries
Authors: Su Emily Chia-Yu , Hsiao Cheng-Hsing , Chen Yi-Tui , Yu Shih-Heng
Published: June 2021

The purpose of this paper was to compare the relative efficiency of COVID-19 transmission mitigation among 23 selected countries, including 19 countries in the G20, two heavily infected countries (Iran and Spain), and two highly populous countries (Pakistan and Nigeria). The mitigation efficiency for each country was evaluated at each stage by using data envelopment analysis (DEA) tools and changes in mitigation efficiency were analyzed across stages. Pearson correlation tests were conducted between each change to examine the impact of efficiency ranks in the previous stage on subsequent stages. An indicator was developed to judge epidemic stability and was applied to practical cases involving lifting travel restrictions and restarting the economy in some countries. The results showed that Korea and Australia performed with the highest efficiency in preventing the diffusion of COVID-19 for the whole period covering 105 days since the first confirmed case, while the USA ranked at the bottom. China, Japan, Korea, and Australia were judged to have recovered from the attack of COVID-19 due to higher epidemic stability.
Impact of Diabetes on Cardiac Function in Patients with High Blood Pressure
Authors: Soufi Taleb Bendiab Nabila , Ouabdesselam Souhila , Henaoui Latefa , Lopez-Sublet Marilucy , Monsuez Jean-Jacques , Benkhedda Salim
Published: June 2021

Background: Although the combination of high blood pressure (HBP) and type 2 diabetes (T2DM) increases the risk of left ventricular (LV) dysfunction, the impact of T2DM on LV geometry and subclinical dysfunction in hypertensive patients and normal ejection fraction (EF) has been infrequently evaluated. Methods: Hypertensive patients with or without T2DM underwent cardiac echocardiography coupled with LV global longitudinal strain (GLS) assessment. Results: Among 200 patients with HBP (mean age 61.7 ± 9.7 years) and EF > 55%, 93 had associated T2DM. Patients with T2DM had a higher body mass index (29.9 ± 5.1 kg/m2 vs. 29.3 ± 4.7 kg/m2, p = 0.025), higher BP levels (158 ± 23/95 ± 13 vs. 142 ± 33/87 ± 12 mmHg, p = 0.003), a higher LV mass index (115.8 ± 32.4 vs. 112.0 ± 24.7 g/m2, p = 0.004), and higher relative wall thickness (0.51 ± 0.16 vs. 0.46 ± 0.12, p = 0.0001). They had more frequently concentric remodeling (20.4% vs. 16.8%, p < 0.001), concentric hypertrophy (53.7% vs. 48.6%, p < 0.001), elevated filling pressures (25.8 vs. 12.1%, p = 0.0001), indexed left atrial volumes greater than 28 mL/m2 (17.2 vs. 11.2%, p = 0.001), and a reduced GLS less than −18% (74.2 vs. 47.7%, p < 0.0001). After adjustment for BP and BMI, T2DM remains an independent determinant factor for GLS decline (OR = 2.26, 95% CI 1.11–4.61, p = 0.023). Conclusions: Left ventricular geometry and subclinical LV function as assessed with GLS are more impaired in hypertensive patients with than without T2DM. Preventive approaches to control BMI and risk of T2DM in hypertensive patients should be emphasized.
Early Nutritional Education in the Prevention of Childhood Obesity
Authors: Gato-Moreno Mario , Martos-Lirio María F. , Leiva-Gea Isabel , Bernal-López M. Rosa , Vegas-Toro Fernando , Fernández-Tenreiro María C. , López-Siguero Juan P.
Published: June 2021

Early childhood is a critical period for obesity prevention. This randomized controlled study evaluated the effectiveness of an educational intervention preventing obesity in preschool-age children. A nutritional education intervention, with a follow-up session one year later, was conducted with parents of children aged 3 to 4 years of public schools in the province of Málaga. The main outcome variable was the body mass index z-score (zBMI). The prevalence of overweight or obesity was the secondary outcome variable. The sample comprised 261 students (control group = 139). Initial BMI, weight, height-for-age and prevalence of overweight and obesity were similar for both groups. After the first year of the intervention, the zBMI of the intervention group decreased significantly from 0.23 to 0.10 (p = 0.002), and the subgroup of patients with baseline zBMI above the median decreased from 1 to 0.72 (p = 0.001), and in the second year from 1.01 to 0.73 (p = 0.002). The joint prevalence of overweight and obesity increased in the control group (12.2% to 20.1%; p = 0.027), while in the intervention group, there were no significant changes. This preschool educational intervention with parents improved their children’s BMI, especially those with a higher BMI for their age, and favored the prevention of overweight or obesity.
A Nationwide Population-Based Study on the Association between Land Transport Accident and Peripheral Vestibular Disorders
Authors: Lin Herng-Ching , Xirasagar Sudha , Wang Chia-Hui , Cheng Yen-Fu , Liu Tsai-Ching , Yang Tzong-Hann
Published: June 2021

This case–control study aimed to investigate the association of peripheral vestibular disorders (PVD) with subsequent land transport accidents. Data for this study were obtained from Taiwan’s National Health Insurance (NHI) dataset. We retrieved 8704 subjects who were newly found to have land transport accidents as cases. Their diagnosis date was used as their index date. Controls were identified by propensity score matching (one per case, n = 8704 controls) from the NHI dataset with their index date being the date of their first health service claim in 2017. Multiple logistic regressions were performed to calculate the prior PVD odds ratio of cases vs. controls. We found that 2.36% of the sampled patients had been diagnosed with PVD before the index date, 3.37% among cases and 1.36% among controls. Chi-square test revealed that there was a significant association between land transport accident and PVD (p < 0.001). Furthermore, multiple logistic regression analysis suggested that cases were more likely to have had a prior PVD diagnosis when compared to controls (OR = 2.533; 95% CI = 2.041–3.143; p < 0.001). After adjusting for age, gender, hypertension, diabetes, coronary heart disease, and hyperlipidemia, cases had a greater tendency to have a prior diagnosis of PVD than controls (OR = 3.001, 95% CI = 2.410–3.741, p < 0.001). We conclude that patients with PVD are at twofold higher odds for land transport accidents.
Eco Trends, Counseling and Applied Ecology in Community Using Sophia
Authors: Hategan Vasile-Petru
Published: June 2021

The study investigates the current trends that manifest themselves in two areas that have common origins in antiquity, found in the Hellenistic concept of Sophia: present in philosophy, where it expresses the love of wisdom, but also in theology where it represents divine love. Looking at this approach, the Sophia has manifested various orientations, either toward the field of ecology and the environment through the emergence of new concepts, such as ecophilosophy and ecotheology, but also toward the practice applied to the person, through the philosophical counseling or spiritual or pastoral counseling. This paper analyzes the characteristics of the applied trends, ecophilosophy and ecotheology, through their comparative analysis, along with a bibliometric study on papers published on these topics in indexed databases in the last 45 years. The paper presents the openness to innovation, through the emergence of the two concepts analyzed which created methods and tools specific to philosophical or spiritual counseling, and adaptations of these practices to the needs of contemporary society. Therefore, the innovation is sustained by creating a new specialization in community counseling practice, called eco-counseling for community (EC4com), with the new ecological trend, which can be included in the philosophical and spiritual practices applied in communities through individual counseling, for groups or community.
Reproductive Health Risks Associated with Occupational and Environmental Exposure to Pesticides
Authors: Fucic Aleksandra , Duca Radu C. , Galea Karen S. , Maric Tihana , Garcia Kelly , Bloom Michael S. , Andersen Helle R. , Vena John E.
Published: June 2021

A marked reduction in fertility and an increase in adverse reproductive outcomes during the last few decades have been associated with occupational and environmental chemical exposures. Exposure to different types of pesticides may increase the risks of chronic diseases, such as diabetes, cancer, and neurodegenerative disease, but also of reduced fertility and birth defects. Both occupational and environmental exposures to pesticides are important, as many are endocrine disruptors, which means that even very low-dose exposure levels may have measurable biological effects. The aim of this review was to summarize the knowledge collected between 2000 and 2020, to highlight new findings, and to further interpret the mechanisms that may associate pesticides with infertility, abnormal sexual maturation, and pregnancy complications associated with occupational, environmental and transplacental exposures. A summary of current pesticide production and usage legislation is also included in order to elucidate the potential impact on exposure profile differences between countries, which may inform prevention measures. Recommendations for the medical surveillance of occupationally exposed populations, which should be facilitated by the biomonitoring of reduced fertility, is also discussed.
Osteocyte Dysfunction in Joint Homeostasis and Osteoarthritis
Authors: Zhang Lanlan , Wen Chunyi
Published: June 2021

Structural disturbances of the subchondral bone are a hallmark of osteoarthritis (OA), including sclerotic changes, cystic lesions, and osteophyte formation. Osteocytes act as mechanosensory units for the micro-cracks in response to mechanical loading. Once stimulated, osteocytes initiate the reparative process by recruiting bone-resorbing cells and bone-forming cells to maintain bone homeostasis. Osteocyte-expressed sclerostin is known as a negative regulator of bone formation through Wnt signaling and the RANKL pathway. In this review, we will summarize current understandings of osteocytes at the crossroad of allometry and mechanobiology to exploit the relationship between osteocyte morphology and function in the context of joint aging and osteoarthritis. We also aimed to summarize the osteocyte dysfunction and its link with structural and functional disturbances of the osteoarthritic subchondral bone at the molecular level. Compared with normal bones, the osteoarthritic subchondral bone is characterized by a higher bone volume fraction, a larger trabecular bone number in the load-bearing region, and an increase in thickness of pre-existing trabeculae. This may relate to the aberrant expressions of sclerostin, periostin, dentin matrix protein 1, matrix extracellular phosphoglycoprotein, insulin-like growth factor 1, and transforming growth factor-beta, among others. The number of osteocyte lacunae embedded in OA bone is also significantly higher, yet the volume of individual lacuna is relatively smaller, which could suggest abnormal metabolism in association with allometry. The remarkably lower percentage of sclerostin-positive osteocytes, together with clustering of Runx-2 positive pre-osteoblasts, may suggest altered regulation of osteoblast differentiation and osteoblast-osteocyte transformation affected by both signaling molecules and the extracellular matrix. Aberrant osteocyte morphology and function, along with anomalies in molecular signaling mechanisms, might explain in part, if not all, the pre-osteoblast clustering and the uncoupled bone remodeling in OA subchondral bone.
Molecular Pathophysiology of Autosomal Recessive Polycystic Kidney Disease
Authors: Cordido Adrian , Vizoso-Gonzalez Marta , Garcia-Gonzalez Miguel A.
Published: June 2021

Autosomal recessive polycystic kidney disease (ARPKD) is a rare disorder and one of the most severe forms of polycystic kidney disease, leading to end-stage renal disease (ESRD) in childhood. PKHD1 is the gene that is responsible for the vast majority of ARPKD. However, some cases have been related to a new gene that was recently identified (DZIP1L gene), as well as several ciliary genes that can mimic a ARPKD-like phenotypic spectrum. In addition, a number of molecular pathways involved in the ARPKD pathogenesis and progression were elucidated using cellular and animal models. However, the function of the ARPKD proteins and the molecular mechanism of the disease currently remain incompletely understood. Here, we review the clinics, treatment, genetics, and molecular basis of ARPKD, highlighting the most recent findings in the field.
SARS-CoV-2 Infection and Significance of Oral Health Management in the Era of “the New Normal with COVID-19”
Authors: Imai Kenichi , Tanaka Hajime
Published: June 2021

More than a year ago, the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic by the World Health Organization, with the world approaching its fourth wave. During this period, vaccines were developed in a much shorter period than thought possible, with the initiation of the pertinent vaccination. However, oral cavities have come under renewed scrutiny worldwide because saliva, a mixture of salivary secretions, pharyngeal secretions, and gingival crevicular fluid, have not only been shown to contain infective viral loads, mediating the route of SARS-CoV-2 transmission via droplet, aerosol, or contagion, but also used as a sample for viral RNA testing with a usefulness comparable to the nasopharyngeal swab. The oral cavity is an important portal for ingress of SARS-CoV-2, being an entryway to the bronchi, alveoli, and rest of the lower respiratory tract, causing inflammation by viral infection. Moreover, angiotensin-converting enzyme 2, a host receptor for SARS-CoV-2, coupled with proteases responsible for viral entry have been found to be expressed on the tongue and other oral mucosae, suggesting that the oral cavity is the site of virus replication and propagation. Furthermore, there is a possibility that the aspiration of oral bacteria (such as periodontal pathogens) along with saliva into the lower respiratory tract may be a complicating factor for COVID-19 because chronic obstructive pulmonary disease and diabetes are known COVID-19 comorbidities with a greater risk of disease aggravation and higher death rate. These comorbidities have a strong connection to chronic periodontitis and periodontal pathogens, and an oral health management is an effective measure to prevent these comorbidities. In addition, oral bacteria, particularly periodontal pathogens, could be proinflammatory stimulants to respiratory epithelia upon its exposure to aspirated bacteria. Therefore, it may be expected that oral health management not only prevents comorbidities involved in aggravating COVID-19 but also has an effect against COVID-19 progression. This review discusses the significance of oral health management in SARS-CoV-2 infection in the era of “the new normal with COVID-19” and COVID-19 prevention with reference to the hypothetical mechanisms that the authors and the other researchers have proposed.
Unravelling the Complex Denaturant and Thermal-Induced Unfolding Equilibria of Human Phenylalanine Hydroxylase
Authors: Conde-Giménez María , Sancho Javier
Published: June 2021

Human phenylalanine hydroxylase (PAH) is a metabolic enzyme involved in the catabolism of L-Phe in liver. Loss of conformational stability and decreased enzymatic activity in PAH variants result in the autosomal recessive disorder phenylketonuria (PKU), characterized by developmental and psychological problems if not treated early. One current therapeutic approach to treat PKU is based on pharmacological chaperones (PCs), small molecules that can displace the folding equilibrium of unstable PAH variants toward the native state, thereby rescuing the physiological function of the enzyme. Understanding the PAH folding equilibrium is essential to develop new PCs for different forms of the disease. We investigate here the urea and the thermal-induced denaturation of full-length PAH and of a truncated form lacking the regulatory and the tetramerization domains. For either protein construction, two distinct transitions are seen in chemical denaturation followed by fluorescence emission, indicating the accumulation of equilibrium unfolding intermediates where the catalytic domains are partly unfolded and dissociated from each other. According to analytical centrifugation, the chemical denaturation intermediates of either construction are not well-defined species but highly polydisperse ensembles of protein aggregates. On the other hand, each protein construction similarly shows two transitions in thermal denaturation measured by fluorescence or differential scanning calorimetry, also indicating the accumulation of equilibrium unfolding intermediates. The similar temperatures of mid denaturation of the two constructions, together with their apparent lack of response to protein concentration, indicate the catalytic domains are unfolded in the full-length PAH thermal intermediate, where they remain associated. That the catalytic domain unfolds in the first thermal transition is relevant for the choice of PCs identified in high throughput screening of chemical libraries using differential scanning fluorimetry.
Reconfigurable Dual Peptide Tethered Polymer System Offers a Synergistic Solution for Next Generation Dental Adhesives
Authors: Yuca Esra , Xie Sheng-Xue , Song Linyong , Boone Kyle , Kamathewatta Nilan , Woolfolk Sarah K. , Elrod Philip , Spencer Paulette , Tamerler Candan
Published: June 2021

Resin-based composite materials have been widely used in restorative dental materials due to their aesthetic, mechanical, and physical properties. However, they still encounter clinical shortcomings mainly due to recurrent decay that develops at the composite-tooth interface. The low-viscosity adhesive that bonds the composite to the tooth is intended to seal this interface, but the adhesive seal is inherently defective and readily damaged by acids, enzymes, and oral fluids. Bacteria infiltrate the resulting gaps at the composite-tooth interface and bacterial by-products demineralize the tooth and erode the adhesive. These activities lead to wider and deeper gaps that provide an ideal environment for bacteria to proliferate. This complex degradation process mediated by several biological and environmental factors damages the tooth, destroys the adhesive seal, and ultimately, leads to failure of the composite restoration. This paper describes a co-tethered dual peptide-polymer system to address composite-tooth interface vulnerability. The adhesive system incorporates an antimicrobial peptide to inhibit bacterial attack and a hydroxyapatite-binding peptide to promote remineralization of damaged tooth structure. A designer spacer sequence was incorporated into each peptide sequence to not only provide a conjugation site for methacrylate (MA) monomer but also to retain active peptide conformations and enhance the display of the peptides in the material. The resulting MA-antimicrobial peptides and MA-remineralization peptides were copolymerized into dental adhesives formulations. The results on the adhesive system composed of co-tethered peptides demonstrated both strong metabolic inhibition of S. mutans and localized calcium phosphate remineralization. Overall, the result offers a reconfigurable and tunable peptide-polymer hybrid system as next-generation adhesives to address composite-tooth interface vulnerability.
Filamin A Regulates Cardiovascular Remodeling
Authors: Bandaru Sashidar , Ala Chandu , Zhou Alex-Xianghua , Akyürek Levent M.
Published: June 2021

Filamin A (FLNA) is a large actin-binding cytoskeletal protein that is important for cell motility by stabilizing actin networks and integrating them with cell membranes. Interestingly, a C-terminal fragment of FLNA can be cleaved off by calpain to stimulate adaptive angiogenesis by transporting multiple transcription factors into the nucleus. Recently, increasing evidence suggests that FLNA participates in the pathogenesis of cardiovascular and respiratory diseases, in which the interaction of FLNA with transcription factors and/or cell signaling molecules dictate the function of vascular cells. Localized FLNA mutations associate with cardiovascular malformations in humans. A lack of FLNA in experimental animal models disrupts cell migration during embryogenesis and causes anomalies, including heart and vessels, similar to human malformations. More recently, it was shown that FLNA mediates the progression of myocardial infarction and atherosclerosis. Thus, these latest findings identify FLNA as an important novel mediator of cardiovascular development and remodeling, and thus a potential target for therapy. In this update, we summarized the literature on filamin biology with regard to cardiovascular cell function.
Transcriptome Reveals Roles of Lignin-Modifying Enzymes and Abscisic Acid in the Symbiosis of Mycena and Gastrodia elata
Authors: Ren Li-Ying , Zhao Heng , Liu Xiao-Ling , Zong Tong-Kai , Qiao Min , Liu Shu-Yan , Liu Xiao-Yong
Published: June 2021

Gastrodia elata is a well-known medicinal and heterotrophic orchid. Its germination, limited by the impermeability of seed coat lignin and inhibition by abscisic acid (ABA), is triggered by symbiosis with fungi such as Mycena spp. However, the molecular mechanisms of lignin degradation by Mycena and ABA biosynthesis and signaling in G. elata remain unclear. In order to gain insights into these two processes, this study analyzed the transcriptomes of these organisms during their dynamic symbiosis. Among the 25 lignin-modifying enzyme genes in Mycena, two ligninolytic class II peroxidases and two laccases were significantly upregulated, most likely enabling Mycena hyphae to break through the lignin seed coats of G. elata. Genes related to reduced virulence and loss of pathogenicity in Mycena accounted for more than half of annotated genes, presumably contributing to symbiosis. After coculture, upregulated genes outnumbered downregulated genes in G. elata seeds, suggesting slightly increased biological activity, while Mycena hyphae had fewer upregulated than downregulated genes, indicating decreased biological activity. ABA biosynthesis in G. elata was reduced by the downregulated expression of 9-cis-epoxycarotenoid dioxygenase (NCED-2), and ABA signaling was blocked by the downregulated expression of a receptor protein (PYL12-like). This is the first report to describe the role of NCED-2 and PYL12-like in breaking G. elata seed dormancy by reducing the synthesis and blocking the signaling of the germination inhibitor ABA. This study provides a theoretical basis for screening germination fungi to identify effective symbionts and for reducing ABA inhibition of G. elata seed germination.
Studying SARS-CoV-2 with Fluorescence Microscopy
Authors: Putlyaeva Lidia V. , Lukyanov Konstantin A.
Published: June 2021

The COVID-19 pandemic caused by SARS-CoV-2 coronavirus deeply affected the world community. It gave a strong impetus to the development of not only approaches to diagnostics and therapy, but also fundamental research of the molecular biology of this virus. Fluorescence microscopy is a powerful technology enabling detailed investigation of virus–cell interactions in fixed and live samples with high specificity. While spatial resolution of conventional fluorescence microscopy is not sufficient to resolve all virus-related structures, super-resolution fluorescence microscopy can solve this problem. In this paper, we review the use of fluorescence microscopy to study SARS-CoV-2 and related viruses. The prospects for the application of the recently developed advanced methods of fluorescence labeling and microscopy—which in our opinion can provide important information about the molecular biology of SARS-CoV-2—are discussed.
Neuroprotective Function of High Glycolytic Activity in Astrocytes: Common Roles in Stroke and Neurodegenerative Diseases
Authors: Takahashi Shinichi
Published: June 2021

Astrocytes (also, astroglia) consume huge amounts of glucose and produce lactate regardless of sufficient oxygen availability, indicating a high capacity for aerobic glycolysis. Glycolysis in astrocytes is activated in accordance with neuronal excitation and leads to increases in the release of lactate from astrocytes. Although the fate of this lactate remains somewhat controversial, it is believed to fuel neurons as an energy substrate. Besides providing lactate, astrocytic glycolysis plays an important role in neuroprotection. Among the minor pathways of glucose metabolism, glucose flux to the pentose-phosphate pathway (PPP), a major shunt pathway of glycolysis, is attracting research interest. In fact, PPP activity in astrocytes is five to seven times higher than that in neurons. The astrocytic PPP plays a key role in protecting neurons against oxidative stress by providing neurons with a reduced form of glutathione, which is necessary to eliminate reactive oxygen species. Therefore, enhancing astrocytic glycolysis might promote neuronal protection during acute ischemic stroke. Contrariwise, the dysfunction of astrocytic glycolysis and the PPP have been implicated in the pathogenesis of various neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis, since mitochondrial dysfunction and oxidative stress trigger and accelerate disease progression.
Single-Oocyte Gene Expression Suggests That Curcumin Can Protect the Ovarian Reserve by Regulating the PTEN-AKT-FOXO3a Pathway
Authors: Lv Yue , Cao Rui-Can , Liu Hong-Bin , Su Xian-Wei , Lu Gang , Ma Jin-Long , Chan Wai-Yee
Published: June 2021

A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.
A Secure Steganographic Channel Using DNA Sequence Data and a Bio-Inspired XOR Cipher
Authors: Khalifa Amal
Published: June 2021

Secure communication is becoming an urgent need in a digital world where tera bytes of sensitive information are sent back and forth over public networks. In this paper, we combine the power of both encryption and Steganography to build a secure channel of communication between two parties. The proposed method uses DNA sequence data as a cover to hide the secret message. The hiding process is performed in phases that start with a complementary substitution operation followed by a random insertion process. Furthermore, and before the hiding process takes place, the message is encrypted to secure its contents. Here, we propose an XOR cipher that is also based on how DNA data is digitally represented and stored. A fixed-size header is embedded right before the message itself to facilitate the blind extraction process. The experimental results showed an outstanding performance of the proposed technique, in comparison with other methods, in terms of capacity, security, as well as blind extraction.
A Moving Vehicle Height Monitoring Sensor System for Overheight Impact Avoidance
Authors: Chacon Pedro J. , Park Jong-Yoon , Aly Aly M. , Voyiadjis George Z. , Choi Jin-Woo
Published: June 2021

Bridges, overpasses, and road construction sites with reduced vertical clearance lead to collision threats from crossing vehicles that exceed their clearance due to their inherent height or improper loading. These accidents can pose slight or severe physical damage to property and, primarily, damage to involved individuals in these vehicles or their affected components (i.e., collateral damage around and above an overpass or bridge). Furthermore, the resulting consequences may also incur fatalities, injuries, structural damages, and monetary damages. It has severely impacted the repair and/or replacement costs of the affected structures. Such accidents and consequences have been observed at a national level and could be reduced with a proper implementation of an overheight sensing system to prevent them from happening as often. This paper introduces the design, prototype, and implementation of a low power sensor network to monitor and characterize vehicle height and other characteristics in real time, thus alerting overheight vehicles well in advance of a possible collision.