bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of High Voltage Electrical Discharge on the Physicochemical Properties and the Microbiological Safety of Rose Hip Nectars
Authors: Tiban Nela Nedić , Šimović Mirela , Polović Martina , Šarić Antonija , Tomac Ivana , Matić Petra , Jakobek Lidija
Published: February 2022

Although neglected as an industrial raw material, rose hip has been important for both nutritional and medical purposes for centuries. The main goal of this study was to propose a rapid and inexpensive non-thermal technique such as high voltage electrical discharge (HVED) to preserve valuable rose hip bioactive compounds, towards the development of high-quality products, including low-calorie products. The objective of this work was to evaluate the effects of HVED on the physicochemical properties and the microbiological safety of rose hip nectar formulations and, for comparison, on a pasteurised sample. Physicochemical analysis proved that rose hip pulp and the prepared nectars were valuable sources of polyphenols and ascorbic acid with high antioxidant activity. The HVED technique had minimal effects on the quality characteristics of the nectars under the different process conditions (50, 100 Hz; 10, 15, 20 min). In addition, the pasteurised nectar showed the greatest loss of ascorbic acid (54%) and phenolic compounds (40%). The microbiological quality of nectars was examined immediately after preparation/treatment and after 6 and 12 days of storage at 4 °C. In addition to the pasteurised sample, HVED-treated rose hip nectar prepared from microwave-blanched puree with extended shelf life had satisfactory microbiological safety after storage.
Asymptotic Analysis of Low Energy Extremals with Γ-Convergence in Variable Exponent Lebesgue Spaces
Authors: Siddique Adil , Shekhovtsov Andrii , Bashir Zia , Sałabun Wojciech
Published: February 2022

In many physical models, internal energy will run out without external energy sources. Therefore, finding optimal energy sources and studying their behavior are essential issues. In this article, we study the following variational problem: Gϵ∗=sup∫ΩG(u)ϵq(x)dx:∥∇u∥Lp(.)≤ϵ,u=0 on ∂Ω, with the help of Γ-convergence, where G:R→R is upper semicontinuous, non zero in the L1 sense, 0≤G(u)≤c|u|q(.), Ω is a bounded open subset of Rn, n≥3, 1<p(.)<n, and p(.)≤q(.)≤p∗(.). For special choices of G, we can study Bernoulli’s free-boundary and plasma problems in variable exponent Lebesgue spaces.
Reverse Minkowski Inequalities Pertaining to New Weighted Generalized Fractional Integral Operators
Authors: Liko Rozana , Mohammed Pshtiwan Othman , Kashuri Artion , Hamed Y. S.
Published: February 2022

In this paper, we obtain reverse Minkowski inequalities pertaining to new weighted generalized fractional integral operators. Moreover, we derive several important special cases for suitable choices of functions. In order to demonstrate the efficiency of our main results, we offer many concrete examples as applications.
Effectiveness of Video-Assisted Thoracoscopic Surgery with Bullectomy and Partial Pleurectomy in the Treatment of Primary Spontaneous Pneumothorax—A Retrospective Long-Term Single-Center Analysis
Authors: Fung Stephen , Ashmawy Hany , Safi Sami-Alexander , Schauer Matthias , Krieg Andreas , Schauer Anja , Kivilis Marius , Ziayee Farid , Rehders Alexander , Dizdar Levent , Knoefel Wolfram-Trudo
Published: February 2022

Background: Video-assisted thoracoscopic surgery (VATS) with bullectomy and partial pleurectomy (VBPP) is an increasingly used and well-established surgical treatment for primary spontaneous pneumothorax (PSP). However, reports on its effectiveness and long-term outcomes are limited. The aim of this study was to assess and compare long-term recurrence rates following VBPP and chest tube (CT) treatment and to identify potential risk factors for disease recurrence in patients with PSP. Methods: A total of 116 patients treated either by VBPP or CT were included in this study. Long-term recurrence rates and associations between clinical parameters and recurrence of pneumothorax were analyzed. Results: Sixty-two patients (53.4%) underwent VBPP, whereas 54 (46.6%) patients underwent CT treatment only. During a median follow-up period of 76.5 months, VBPP patients experienced a significantly lower recurrence rate compared to CT patients (6/62 vs. 35/54; p < 0.0001). CT treatment (VBPP vs. CT; p < 0.001) and a large initial pneumothorax size (Collins < 4 vs. Collins ≥ 4; p = 0.018) were independent risk factors for pneumothorax recurrence. Conclusion: VBPP is an effective and safe surgical treatment for PSP. Therefore, patients with a large pneumothorax size might benefit from VBPP, as they are at high risk for disease recurrence.
Traditional Craft Training and Demonstration in Museums
Authors: Ringas Christodoulos , Tasiopoulou Eleana , Kaplanidi Danae , Partarakis Nikolaos , Zabulis Xenophon , Zidianakis Emmanouil , Patakos Andreas , Patsiouras Nikolaos , Karuzaki Effie , Foukarakis Michalis , Adami Ilia , Cadi Nedjma , Baka Evangelia , Thalmann Nadia Magnenat , Makrygiannis Dimitrios , Glushkova Alina , Manitsaris Sotirios , Nitti Vito , Panesse Lucia
Published: February 2022

This work regards the representation of handicrafts for craft training and demonstration in the environment of an ethnographic heritage museum. The craft of mastic cultivation is chosen as a use case. This paper presents the process of representation and presentation of this craft, following an articulated pipeline approach for data collection, annotation, and semantic representation. The outcomes were used to implement an exhibition that targets the presentation of craft context and craft training, through interactive experiences, mobile applications, and a hands-on training where users reenact the gestures of a mastic cultivator. Preliminary evaluation results show high acceptance for the installation and increased user interest.
Grapevine Response to Stress Generated by Excessive Temperatures during the Budburst
Authors: Tombesi Sergio , Sabbatini Paolo , Frioni Tommaso , Grisafi Francesca , Barone Federico , Zani Paolo , Palliotti Alberto , Poni Stefano
Published: February 2022

At springtime, the formation of stem somatic traits (stem elongation and leaf growth) and reproductive activity (flowering and fruit set) occur simultaneously. They are all competing carbon sinks, with an extremely high demand for carbohydrates. The shoot growth rate is strongly related to environmental temperature, which, according to climate change scenarios, is expected to increase also in extremes. Our hypothesis was that the increase in temperature during budburst could increase the vegetative carbon sink strength reducing the carbon stock available for the reproductive activity jeopardizing flowering of the next year. In our experiment, we artificially conditioned grapevine budburst by exposing the growing shoots to different temperature regimes. Higher temperatures during the spring vegetative growth favored shoot stem extension at the detriment of shoot leaf area. This caused a reduction in vine CO2 assimilation, which, combined with the competition of the growing vegetative organs, affected the concurrent reproductive activity, with carry-over effects on the following year, resulting in a limited flower initiation in dormant buds. These results suggest that the increase in springtime temperature can alter canopy development and vine physiology, resulting in the reduction in reproductive activity with an economical negative impact on grapevine productivity.
Physiological, Biochemical, and Agronomic Trait Responses of Nigella sativa Genotypes to Water Stress
Authors: Bayati Pedram , Karimmojeni Hassan , Razmjoo Jamshid , Pucci Mariachiara , Abate Giulia , Baldwin Timothy C. , Mastinu Andrea
Published: February 2022

Water stress may affect the growth, physiology, morphology, biochemistry, and productivity of Nigella sativa (black cumin), a medicinal and aromatic plant. Measuring these parameters under various irrigation regimes could provide useful information for successful genotype selection and breeding. Therefore, these agronomically significant features were evaluated in ten black cumin genotypes (Afghanistan, Pakistan, Syria, India, Arak, Isfahan, Semirom, Shahreza, Shahrekord, and Mashhad) under three irrigation regimes (40% (I1), 60% (I2), and 80% (I3) of permissible moisture discharge) during the 2017 to 2018 growing seasons. Water stress was shown to increase the levels of carotenoids (Cars), proline, total soluble carbohydrates (TSC), malondialdehyde (MDA), hydrogen peroxide (H2O2), catalase (CAT), and ascorbate peroxidase (APX) activities but reduced the relative water content (RWC) and chlorophyll content. The highest increases in Cars, TSC, proline, CAT, and APX were noted in the Arak, Isfahan, Semirom, Shahreza, Shahrekord, and Mashhad genotypes under the I3 water regime, respectively. At the same time, the lowest decrease was observed in chlorophyll, H2O2, and relative water content (RWC) in Semirom. According to the stress susceptibility index, the most resistant genotypes were Shahrekord under I2 and Semirom under I3. These data demonstrate that the irrigation regimes affected the physiological, biochemical, and morphological features of black cumin both qualitatively and quantitatively, although the impact varied depending upon the genotype, irrigation regime, and traits. As such, the results presented represent valuable information with which to inform future selection and breeding programs for drought-tolerant black cumin. This is of particular significance considering global climate change.
Biological and Agronomic Traits of the Main Halophytes Widespread in the Mediterranean Region as Potential New Vegetable Crops
Authors: Lombardi Tiziana , Bertacchi Andrea , Pistelli Laura , Pardossi Alberto , Pecchia Susanna , Toffanin Annita , Sanmartin Chiara
Published: February 2022

Salinity is one of the oldest and most serious environmental problems in the world. The increasingly widespread salinization of soils and water resources represents a growing threat to agriculture around the world. A strategy to cope with this problem is to cultivate salt-tolerant crops and, therefore, it is necessary to identify plant species that are naturally adapted to high-salinity conditions. In this review, we focus our attention on some plant species that can be considered among the most representative halophytes of the Mediterranean region; they can be potential resources, such as new or relatively new vegetable crops, to produce raw or minimally processed (or ready-to-eat) products, considering their nutritional properties and nutraceuticals. The main biological and agronomic characteristics of these species and the potential health risks due to mycotoxigenic fungi have been analyzed and summarized in a dedicated section. The objective of this review is to illustrate the main biological and agronomical characteristics of the most common halophytic species in the Mediterranean area, which could expand the range of leafy vegetables on the market.
Determinants of Evapotranspiration in Urban Rain Gardens: A Case Study with Lysimeters under Temperate Climate
Authors: Ouédraogo Ahmeda Assann , Berthier Emmanuel , Durand Brigitte , Gromaire Marie-Christine
Published: February 2022

Accurate evaluation of evapotranspiration (ET) flux is an important issue in sustainable urban drainage systems that target not only flow rate limitations, but also aim at the restoration of natural water balances. This is especially true in context where infiltration possibilities are limited. However, its assessment suffers from insufficient understanding. In this study, ET in 1 m3 pilot rain gardens were studied from eight lysimeters monitored for three years in Paris (France). Daily ET was calculated for each lysimeter based on a mass balance approach and the related uncertainties were assessed at ±0.42 to 0.58 mm. Results showed that for these lysimeters, ET is the major term in water budget (61 to 90% of the precipitations) with maximum values reaching 8–12 mm. Furthermore, the major determinants of ET are the existence or not of an internal water storage and the atmospheric factors. The vegetation type is a secondary determinant, with little difference between herbaceous and shrub configurations, maximum ET for spontaneous vegetation, and minimal values when vegetation was regularly removed. Shading of lysimeters by surroundings buildings is also important, leading to lower values. Finally, ET of lysimeters is higher than tested reference values (evaporimeter, FAO-56, and local Météo-France equations).
Psychometric Properties and Measurement Invariance by Gender of the Abbreviated Three-Item Version of the Satisfaction with Life Scale in a Colombian Sample
Authors: Espejo Begoña , Martín-Carbonell Marta , Checa Irene
Published: February 2022

(1) Background: The need to offer brief scales with items that can be answered with few response options is increasingly important in order to be able to access a broad range of the population. The three-item version of Diener’s Satisfaction with Life Scale has recently been proposed. The objective of this study is to study the psychometric properties of the three-item version of this Scale with five response options, as well as the measurement invariance by gender, in a Colombian sample; (2) Methods: A confirmatory factor model of the three items of the scale together with the Flourishing Scale has been tested, and the measurement invariance by gender of the model has been studied. The results offer a very satisfactory fit of the model, showing good evidence of construct and criterion validity, good indicators of reliability and measurement invariance by gender; (4) Conclusions: The three-item version of the Life Satisfaction Scale, previously adapted to the Colombian population with five response options, is presented as a valid and reliable measurement tool. In future studies, it would be convenient to study the test–retest reliability, as well as its psychometric properties in different samples and at a cross-cultural level.
The Bidirectional Relationship between Posttraumatic Stress Symptoms and Social Support in a 9/11-Exposed Cohort: A Longitudinal Cross-Lagged Analysis
Authors: Liu Sze Yan , Li Jiehui , Leon Lydia F. , Schwarzer Ralf , Cone James E.
Published: February 2022

Research on the longitudinal relationship between posttraumatic stress disorder (PTSD) and social support among survivors of large-scale trauma is limited. This study assessed bidirectional relationships between PTSD and perceived social support in a large sample of the 9/11-exposed cohort over a 14-year follow-up. We used data from 23,165 World Trade Center Health Registry (WTCHR) enrollees who were exposed to the 9/11 attacks and participated in the first four WTCHR surveys (Wave 1 (2003–2004) to Wave 4 (2015–2016)). PTSD symptoms were measured using the 17-item PTSD Checklist. Perceived social support was measured using the five-item version of the Modified Social Support Survey. We used a cross-lagged panel analysis and found an inverse relationship between PTSD symptoms and social support. PTSD at Wave 2 (W2) predicted less social support at Wave 3 (W3) (β = −0.10, p < 0.01), and PTSD at W3 predicted less social support at W4 (β = −0.05, p < 0.01). Conversely, social support at W3 buffered PTSD symptoms at W4 (β = −0.03, p < 0.05). Sub-analyses by types of perceived social support suggest greater effects of PTSD on emotional support than tangible support and in community members than rescue/recovery workers. Our findings suggest a bidirectional effect between PTSD symptoms and social support in a longitudinal study of 9/11-exposed populations.
Couple Conflict and Intimate Partner Violence during the Early Lockdown of the Pandemic: The Good, the Bad, or Is It Just the Same in a North Carolina, Low-Resource Population?
Authors: Langhinrichsen-Rohling Jennifer , Schroeder Grace E. , Langhinrichsen-Rohling Ryan A. , Mennicke Annelise , Harris Yu-Jay , Sullivan Sharon , Gray Glori , Cramer Robert J.
Published: February 2022

The COVID-19 pandemic has forced couples to navigate illness-related stressors and unique public health responses, including extended lockdowns. This study focused on under-resourced North Carolina residents (n = 107) who self-reported changes in relationship conflict (Increased, Decreased, Stayed the Same) and intimate partner violence (IPV) during the pandemic. We expected high rates of increased conflict and IPV since the start of the pandemic. We then sought to determine the associations between dyadic changes in conflict and reports of IPV and pandemic-related experiences and responses. Participants completed a brief online survey assessing their demographics, COVID-19 exposure/stressors, and pandemic responses. As expected, reports of increased couple conflict were related to difficulties getting needed social support, loss of health insurance, more fear and worry, stress, pain, and greater use of alcohol and/or illicit drugs, related to the coronavirus. Participants reporting increased conflict were also more likely to be unemployed. Conversely, reports of decreased conflict were associated with being ill from the virus (48.9%), having health insurance, and working part time. Substantial amounts of IPV were reported (62.2% of the sample); however, increased conflict and IPV were unrelated. Those reporting No IPV were less likely to be receiving public assistance but more likely to have home responsibilities due to the virus. They also reported increased social interactions and less use of alcohol than those reporting IPV perpetration. Findings highlight key associations among pandemic experiences and responses, IPV, and couple functioning in an under-resourced sample. Efforts to facilitate coping, resilience, and tolerating uncertainty may facilitate cooperative and safe couple functioning throughout the pandemic.
Household Air Pollution and High Blood Pressure: A Secondary Analysis of the 2016 Albania Demographic Health and Survey Dataset
Authors: Abba Mustapha S. , Nduka Chidozie U. , Anjorin Seun , Uthman Olalekan A.
Published: February 2022

Background: Hypertension is a significant public health problem in low- and middle-income countries (LMICs). This study aimed to examine the association between household air pollution (HAP) and blood pressure using data from the 2016 Albania Demographic Health and Survey (DHS). Methods: We computed the odds ratio (OR) for the prevalence of hypertension between respondents exposed to clean fuels (e.g., electricity, liquid petroleum gas, natural gas, and biogas) and respondents exposed to polluting fuel (e.g., kerosene, coal/lignite, charcoal, wood, straw/shrubs/grass, and animal dung). Result: The results show that participants exposed to household polluting fuels in Albania were 17% more likely to develop hypertension than those not exposed to household air pollution (OR = 1.17, 95% CI 1.10 to 1.24). Subgroup analysis revealed that the odds of hypertension were more significant among women (OR = 1.22, 95% CI 1.13 to 1.31), rural residents (OR = 1.12, 95% CI 1.04 to 1.22), and participants aged >24 years (OR = 1.35, 95% CI 1.12 to 1.62) who were exposed to household polluting fuels compared to their counterparts who were not exposed. In summary, the results of the study show significant associations between household air pollution and hypertension risk overall, especially among women, rural dwellers, and people aged >24 years in Albania. Conclusion: In this study, an association between household air pollution and the risk of hypertension was found, particularly among low-income households, those with no education, women, and those who live in rural areas.
Policy and Behavior: Comparisons between Twitter Discussions about the US Tobacco 21 Law and Other Age-Related Behaviors
Authors: Dobbs Page D. , Colditz Jason B. , Shields Shelby , Meadows Anna , Primack Brian A.
Published: February 2022

To combat the e-cigarette epidemic among young audiences, a federal law was passed in the US that raised the minimum legal sales age of tobacco to 21 years (commonly known as Tobacco 21). Little is known about sentiment toward this law. Thus, the purpose of our study was to systematically explore trends about Tobacco 21 discussions and comparisons to other age-restriction behaviors on Twitter. Twitter data (n = 4628) were collected from September to December of 2019 that were related to Tobacco 21. A random subsample of identified tweets was used to develop a codebook. Two trained coders independently coded all data, with strong inter-rater reliability (κ = 0.71 to 0.93) found for all content categories. Associations between sentiment and content categories were calculated using χ2 analyses. Among relevant tweets (n = 955), the most common theme—the disjunction between ages for military enlistment and tobacco use—was found in 17.8% of all tweets. Anti-policy sentiment was strongly associated with the age of military enlistment, alcohol, voting, and adulthood (p < 0.001 for all). Opposition to Tobacco 21 propagates on social media because the US federal law does not exempt military members. However, the e-cigarette epidemic may have fueled some support for this law.
The Effect of the Supervisor–Student Relationship on Academic Procrastination: The Chain-Mediating Role of Academic Self-Efficacy and Learning Adaptation
Authors: Wang Qinglin , Xin Zhaoyang , Zhang Hang , Du Jing , Wang Minghui
Published: February 2022

This study used a sample of 818 postgraduate students across several universities in China, to explore the effect of the supervisor–student relationship on procrastination in postgraduates, and the mediating roles played by the postgraduates’ academic self-efficacy and learning adaptation. The study employs multiple scales and finds that: (1) the relationship between postgraduates and their supervisors is significantly and negatively correlated with academic procrastination; (2) the academic self-efficacy of postgraduates plays an independent intermediary role in the connection between the supervisor–student relationship and academic procrastination; (3) the learning adaptation of postgraduates also plays an independent intermediary role in the connection between the supervisor–student relationship and academic procrastination; (4) the academic self-efficacy and learning adaptation of postgraduates shows a chain-mediating effect in the connection between the supervisor–student relationship and academic procrastination. Ultimately, the supervisor–student relationship is an important factor that can directly affect academic procrastination, even if postgraduate students display academic self-efficacy and learning adaptation.
Epigenetic Studies in the Male APP/BIN1/COPS5 Triple-Transgenic Mouse Model of Alzheimer’s Disease
Authors: Martínez-Iglesias Olaia , Naidoo Vinogran , Carrera Iván , Cacabelos Ramón
Published: February 2022

Alzheimer’s Disease (AD) is a major health problem worldwide. The lack of efficacy of existing therapies for AD is because of diagnosis at late stages of the disease, limited knowledge of biomarkers, and molecular mechanisms of AD pathology, as well as conventional drugs that are focused on symptomatic rather than mechanistic features of the disease. The connection between epigenetics and AD, however, may be useful for the development of novel therapeutics or diagnostic biomarkers for AD. The aim of this study was to investigate a pathogenic role for epigenetics and other biomarkers in the male APP/BIN1/COPS5 triple-transgenic (3xTg) mouse model of AD. In the APP/BIN1/COPS5 3xTg-AD mouse hippocampus, sirtuin expression and activity decreased, HDAC3 expression and activity increased, PSEN1 mRNA levels were unchanged, PSEN2 and APOE expression was reduced, and levels of the pro-inflammatory marker IL-6 increased; levels of pro-inflammatory COX-2 and TNFα and apoptotic (NOS3) markers increased slightly, but these were non-significant. In fixed mouse-brain slices, immunoreactivity for CD11b and β-amyloid immunostaining increased. APP/BIN1/COPS5 3xTg-AD mice are a suitable model for evaluating epigenetic changes in AD, the discovery of new epigenetic-related biomarkers for AD diagnosis, and new epidrugs for the treatment of this neurodegenerative disease.
Lighting from Top and Side Enhances Photosynthesis and Plant Performance by Improving Light Usage Efficiency
Authors: Yang Jingli , Song Jinnan , Jeong Byoung Ryong
Published: February 2022

Light is a critical environmental factor that influences plant growth and development, ranging from seed germination to flowering and fruiting. This study was carried out to explore how the optimal combination of various lighting directions increases the light usage efficiency and influences the plant morphophysiology, by investigating the plant growth parameters, leaf anatomy, epidermal morphology, stomatal properties, chlorophyll content, key physiological changes, and correlated gene expressions. In closed-type plant growth chambers, rooted cuttings of two chrysanthemum (Chrysanthemum morifolium Ramat.) cultivars, “Pearl Egg” and “Gaya Glory”, were subjected to a 10-h photoperiod with 600 μmol∙m−2·s−1 photosynthetic photon flux density (PPFD) provided by light-emitting diodes (LEDs) in each light-direction combination (top (1/1) (T), top (1/2) + side (1/2) (TS), top (1/2) + bottom (1/2) (TB), side (1/2) + bottom (1/2) (SB), and top (1/3) + side (1/3) + bottom (1/3) (TSB)). The TS lighting significantly enhanced the morphophysiological performance, compared to the other lighting direction combinations. Notably, the excellent branch formation and earlier flowering were induced by the TS lighting in both “Pearl Egg” and “Gaya Glory” plants.
The Interplay between Autonomic Nervous System and Inflammation across Systemic Autoimmune Diseases
Authors: Bellocchi Chiara , Carandina Angelica , Montinaro Beatrice , Targetti Elena , Furlan Ludovico , Rodrigues Gabriel Dias , Tobaldini Eleonora , Montano Nicola
Published: February 2022

The autonomic nervous system (ANS) and the immune system are deeply interrelated. The ANS regulates both innate and adaptive immunity through the sympathetic and parasympathetic branches, and an imbalance in this system can determine an altered inflammatory response as typically observed in chronic conditions such as systemic autoimmune diseases. Rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis all show a dysfunction of the ANS that is mutually related to the increase in inflammation and cardiovascular risk. Moreover, an interaction between ANS and the gut microbiota has direct effects on inflammation homeostasis. Recently vagal stimulation techniques have emerged as an unprecedented possibility to reduce ANS dysfunction, especially in chronic diseases characterized by pain and a decreased quality of life as well as in chronic inflammation.
Secondary Structure of Influenza A Virus Genomic Segment 8 RNA Folded in a Cellular Environment
Authors: Szutkowska Barbara , Wieczorek Klaudia , Kierzek Ryszard , Zmora Pawel , Peterson Jake M. , Moss Walter N. , Mathews David H. , Kierzek Elzbieta
Published: February 2022

Influenza A virus (IAV) is a member of the single-stranded RNA (ssRNA) family of viruses. The most recent global pandemic caused by the SARS-CoV-2 virus has shown the major threat that RNA viruses can pose to humanity. In comparison, influenza has an even higher pandemic potential as a result of its high rate of mutations within its relatively short (<13 kbp) genome, as well as its capability to undergo genetic reassortment. In light of this threat, and the fact that RNA structure is connected to a broad range of known biological functions, deeper investigation of viral RNA (vRNA) structures is of high interest. Here, for the first time, we propose a secondary structure for segment 8 vRNA (vRNA8) of A/California/04/2009 (H1N1) formed in the presence of cellular and viral components. This structure shows similarities with prior in vitro experiments. Additionally, we determined the location of several well-defined, conserved structural motifs of vRNA8 within IAV strains with possible functionality. These RNA motifs appear to fold independently of regional nucleoprotein (NP)-binding affinity, but a low or uneven distribution of NP in each motif region is noted. This research also highlights several accessible sites for oligonucleotide tools and small molecules in vRNA8 in a cellular environment that might be a target for influenza A virus inhibition on the RNA level.
A New Family of Transcriptional Regulators Activating Biosynthetic Gene Clusters for Secondary Metabolites
Authors: Novakova Renata , Mingyar Erik , Feckova Lubomira , Homerova Dagmar , Csolleiova Dominika , Rezuchova Bronislava , Sevcikova Beatrica , Javorova Rachel , Kormanec Jan
Published: February 2022

We previously identified the aur1 biosynthetic gene cluster (BGC) in Streptomyceslavendulae subsp. lavendulae CCM 3239 (formerly Streptomycesaureofaciens CCM 3239), which is responsible for the production of the unusual angucycline-like antibiotic auricin. Auricin is produced in a narrow interval of the growth phase after entering the stationary phase, after which it is degraded due to its instability at the high pH values reached after the production phase. The complex regulation of auricin BGC is responsible for this specific production by several regulators, including the key activator Aur1P, which belongs to the family of atypical response regulators. The aur1P gene forms an operon with the downstream aur1O gene, which encodes an unknown protein without any conserved domain. Homologous aur1O genes have been found in several BGCs, which are mainly responsible for the production of angucycline antibiotics. Deletion of the aur1O gene led to a dramatic reduction in auricin production. Transcription from the previously characterized Aur1P-dependent biosynthetic aur1Ap promoter was similarly reduced in the S. lavendulaeaur1O mutant strain. The aur1O-specific coactivation of the aur1Ap promoter was demonstrated in a heterologous system using a luciferase reporter gene. In addition, the interaction between Aur1O and Aur1P has been demonstrated by a bacterial two-hybrid system. These results suggest that Aur1O is a specific coactivator of this key auricin-specific positive regulator Aur1P. Bioinformatics analysis of Aur1O and its homologues in other BGCs revealed that they represent a new family of transcriptional coactivators involved in the regulation of secondary metabolite biosynthesis. However, they are divided into two distinct sequence-specific subclasses, each of which is likely to interact with a different family of positive regulators.
Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations
Authors: Valenti Sofia , del Valle Luis Javier , Romanini Michela , Mitjana Meritxell , Puiggalí Jordi , Tamarit Josep Lluís , Macovez Roberto
Published: February 2022

Amorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we employ differential scanning calorimetry and broadband dielectric spectroscopy to investigate dispersions of a small-molecule drug (the Nordazepam anxiolytic) in biodegradable polylactide, both in the form of solvent-cast films and electrospun microfibres. We show that the dispersion of the same small-molecule compound can have opposite (plasticizing or antiplasticizing) effects on the segmental mobility of a biopolymer depending on preparation method, temperature, and polymer enantiomerism. We compare two different chiral forms of the polymer, namely, the enantiomeric pure, semicrystalline L-polymer (PLLA), and a random, fully amorphous copolymer containing both L and D monomers (PDLLA), both of which have lower glass transition temperature (Tg) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher Tg, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their Tg by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the Tg of fully amorphous films. The structural relaxation time of the samples similarly depends on chemical composition and morphology. Most mixtures displayed a single structural relaxation, as expected for homogeneous samples. In the PLLA microfibres, the presence of crystalline domains increases the structural relaxation time of the amorphous fraction, while the presence of the drug lowers the structural relaxation time of the (partially stretched) chains in the microfibres, increasing chain mobility well above that of the fully amorphous polymer matrix. Even fully amorphous homogeneous mixtures exhibit two distinct Johari–Goldstein relaxation processes, one for each chemical component. Our findings have important implications for the interpretation of the Johari–Goldstein process as well as for the physical stability and mechanical properties of microfibres with small-molecule additives.
The Ism between Endothelial Cilia and Endothelial Nanotubules Is an Evolving Concept in the Genesis of the BBB
Authors: Mentor Shireen , Fisher David
Published: February 2022

The blood–brain barrier (BBB) is fundamental in maintaining central nervous system (CNS) homeostasis by regulating the chemical environment of the underlying brain parenchyma. Brain endothelial cells (BECs) constitute the anatomical and functional basis of the BBB. Communication between adjacent BECs is critical for establishing BBB integrity, and knowledge of its nanoscopic landscape will contribute to our understanding of how juxtaposed zones of tight-junction protein interactions between BECs are aligned. The review discusses and critiques types of nanostructures contributing to the process of BBB genesis. We further critically evaluate earlier findings in light of novel high-resolution electron microscopy descriptions of nanoscopic tubules. One such phenotypic structure is BEC cytoplasmic projections, which, early in the literature, is postulated as brain capillary endothelial cilia, and is evaluated and compared to the recently discovered nanotubules (NTs) formed in the paracellular spaces between BECs during barrier-genesis. The review attempts to elucidate a myriad of unique topographical ultrastructures that have been reported to be associated with the development of the BBB, viz., structures ranging from cilia to BEC tunneling nanotubules (TUNTs) and BEC tethering nanotubules (TENTs).
Underestimated Properties of Nanosized Amorphous Titanium Dioxide
Authors: Wiśniewski Marek , Roszek Katarzyna
Published: February 2022

Titanium dioxide is one of the best described photosensitive materials used in photocatalysis, solar cells, self-cleaning coatings, and sunscreens. The scientific and industrial attention has been focused on the highly photoactive crystalline phase of titanium dioxide (TiO2). It is commonly accepted that the smaller TiO2 particles, the higher photoactivity they present. Therefore, titanium dioxide nanoparticles are massively produced and widely used in everyday products. The amorphous phase of titanium dioxide has been treated with neglect, as the lack of its photocatalytic properties is assumed in advance. In this work, the complex experimental proof of the UV-protective properties of the nano-sized amorphous TiO2 phase is reported. Amorphous n-TiO2 is characterized by photocatalytic inactivity and, as a consequence, low cytotoxicity to fibroblast cells. When exposed to UV radiation, cells with amorphous TiO2 better survive under stress conditions. Thus, we postulate that amorphous n-TiO2 will be more beneficial and completely safe for cosmetic applications. Moreover, the results from in situ FTIR studies let us correlate the low toxicity of amorphous samples with low ability to form hydroperoxo surface species.
Integrated Metabolomics and Lipidomics Reveal High Accumulation of Glycerophospholipids in Human Astrocytes under the Lipotoxic Effect of Palmitic Acid and Tibolone Protection
Authors: Cabezas Ricardo , Martin-Jiménez Cynthia , Zuluaga Martha , Pinzón Andrés , Barreto George E. , González Janneth
Published: February 2022

Lipotoxicity is a metabolic condition resulting from the accumulation of free fatty acids in non-adipose tissues which involves a series of pathological responses triggered after chronic exposure to high levels of fatty acids, severely detrimental to cellular homeostasis and viability. In brain, lipotoxicity affects both neurons and other cell types, notably astrocytes, leading to neurodegenerative processes, such as Alzheimer (AD) and Parkinson diseases (PD). In this study, we performed for the first time, a whole lipidomic characterization of Normal Human Astrocytes cultures exposed to toxic concentrations of palmitic acid and the protective compound tibolone, to establish and identify the set of potential metabolites that are modulated under these experimental treatments. The study covered 3843 features involved in the exo- and endo-metabolome extracts obtained from astrocytes with the mentioned treatments. Through multivariate statistical analysis such as PCA (principal component analysis), partial least squares (PLS-DA), clustering analysis, and machine learning enrichment analysis, it was possible to determine the specific metabolites that were affected by palmitic acid insult, such as phosphoethanolamines, phosphoserines phosphocholines and glycerophosphocholines, with their respective metabolic pathways impact. Moreover, our results suggest the importance of tibolone in the generation of neuroprotective metabolites by astrocytes and may be relevant to the development of neurodegenerative processes.
The Role of Synovial Membrane in the Development of a Potential In Vitro Model of Osteoarthritis
Authors: Harvanova Denisa , Matejova Jana , Slovinska Lucia , Lacko Marek , Gulova Slavomira , Fecskeova Livia Kolesar , Janockova Jana , Spakova Timea , Rosocha Jan
Published: February 2022

There is a lack of in vitro models able to plausibly represent the inflammation microenvironment of knee osteoarthritis (OA). We analyzed the molecules released from OA tissues (synovial membrane, cartilage, infrapatellar fat pad) and investigated whether the stimulation of human synovial fibroblasts (SFs), with synthetic cytokines (IL-1β and TNF-α or IFN-γ) or conditioned media (CM) from OA tissues, influence the SFs’ response, in the sense of pro-inflammatory cytokines, chemokines, growth factors, and degradative enzymes modulation. Human SFs were obtained from OA synovial membranes. SFs and their CM were analyzed for biomarkers, proliferation rate, protein profile and gene expression, before and after stimulation. Real-time PCR and multiplex assays quantified OA-related gene expression and biomolecule production. Unlike other activators, CM from OA synovial membrane (CM-SM), significantly up-regulated all genes of interest (IL-6, IL-8, MMP-1, MMP-3, RANTES, MCP-1, TSG-6, YKL-40) in SFs. Multiplex immunoassay analysis showed that levels of OA-related cytokines (IL-6, IL-8, MCP 1, IL-1Ra), chemokine (RANTES) and growth factor (VEGF), produced by CM-SM stimulated SFs, increased significantly compared to non-stimulated SFs. Molecules released from the SM from OA patients induces OA-like changes in vitro, in specific OA synovial populations (SFs). These findings promote the use and establish a compelling in vitro model that simulates the versatility and complexity of the OA disease. This model, in the future, will allow us to study new cell therapies or test drugs by reducing or avoiding animal models.
Augmentation of Transcriptomic Data for Improved Classification of Patients with Respiratory Diseases of Viral Origin
Authors: Kircher Magdalena , Chludzinski Elisa , Krepel Jessica , Saremi Babak , Beineke Andreas , Jung Klaus
Published: February 2022

To better understand the molecular basis of respiratory diseases of viral origin, high-throughput gene-expression data are frequently taken by means of DNA microarray or RNA-seq technology. Such data can also be useful to classify infected individuals by molecular signatures in the form of machine-learning models with genes as predictor variables. Early diagnosis of patients by molecular signatures could also contribute to better treatments. An approach that has rarely been considered for machine-learning models in the context of transcriptomics is data augmentation. For other data types it has been shown that augmentation can improve classification accuracy and prevent overfitting. Here, we compare three strategies for data augmentation of DNA microarray and RNA-seq data from two selected studies on respiratory diseases of viral origin. The first study involves samples of patients with either viral or bacterial origin of the respiratory disease, the second study involves patients with either SARS-CoV-2 or another respiratory virus as disease origin. Specifically, we reanalyze these public datasets to study whether patient classification by transcriptomic signatures can be improved when adding artificial data for training of the machine-learning models. Our comparison reveals that augmentation of transcriptomic data can improve the classification accuracy and that fewer genes are necessary as explanatory variables in the final models. We also report genes from our signatures that overlap with signatures presented in the original publications of our example data. Due to strict selection criteria, the molecular role of these genes in the context of respiratory infectious diseases is underlined.
Alzheimer’s Disease Seen through the Eye: Ocular Alterations and Neurodegeneration
Authors: Romaus-Sanjurjo Daniel , Regueiro Uxía , López-López Maite , Vázquez-Vázquez Laura , Ouro Alberto , Lema Isabel , Sobrino Tomás
Published: February 2022

Alzheimer’s Disease (AD) is one of the main neurodegenerative diseases worldwide. Unfortunately, AD shares many similarities with other dementias at early stages, which impedes an accurate premortem diagnosis. Therefore, it is urgent to find biomarkers to allow for early diagnosis of the disease. There is increasing scientific evidence highlighting the similarities between the eye and other structures of the CNS, suggesting that knowledge acquired in eye research could be useful for research and diagnosis of AD. For example, the retina and optic nerve are considered part of the central nervous system, and their damage can result in retrograde and anterograde axon degeneration, as well as abnormal protein aggregation. In the anterior eye segment, the aqueous humor and tear film may be comparable to the cerebrospinal fluid. Both fluids are enriched with molecules that can be potential neurodegenerative biomarkers. Indeed, the pathophysiology of AD, characterized by cerebral deposits of amyloid-beta (Aβ) and tau protein, is also present in the eyes of AD patients, besides numerous structural and functional changes observed in the structure of the eyes. Therefore, all this evidence suggests that ocular changes have the potential to be used as either predictive values for AD assessment or as diagnostic tools.
Editorial of Special Issue “Inflammasomes and Inflammation”
Authors: Yi Young-Su
Published: February 2022

Although inflammation is a host-protective mechanism from infection and cellular danger signals, chronic inflammation is a major risk factor for various human diseases [...]
Cancer Stem Cells in Ovarian Cancer—A Source of Tumor Success and a Challenging Target for Novel Therapies
Authors: Wilczyński Jacek R , Wilczyński Miłosz , Paradowska Edyta
Published: February 2022

Ovarian cancer is the most lethal neoplasm of the female genital organs. Despite indisputable progress in the treatment of ovarian cancer, the problems of chemo-resistance and recurrent disease are the main obstacles for successful therapy. One of the main reasons for this is the presence of a specific cell population of cancer stem cells. The aim of this review is to show the most contemporary knowledge concerning the biology of ovarian cancer stem cells (OCSCs) and their impact on chemo-resistance and prognosis in ovarian cancer patients, as well as to present the treatment options targeted exclusively on the OCSCs. The review presents data concerning the role of cancer stem cells in general and then concentrates on OCSCs. The surface and intracellular OCSCs markers and their meaning both for cancer biology and clinical prognosis, signaling pathways specifically activated in OCSCs, the genetic and epigenetic regulation of OCSCs function including the recent studies on the non-coding RNA regulation, cooperation between OCSCs and the tumor microenvironment (ovarian cancer niche) including very specific environment such as ascites fluid, the role of shear stress, autophagy and metabolic changes for the function of OCSCs, and finally mechanisms of OCSCs escape from immune surveillance, are described and discussed extensively. The possibilities of anti-OCSCs therapy both in experimental settings and in clinical trials are presented, including the recent II phase clinical trials and immunotherapy. OCSCs are a unique population of cancer cells showing a great plasticity, self-renewal potential and resistance against anti-cancer treatment. They are responsible for the progression and recurrence of the tumor. Several completed and ongoing clinical trials have tested different anti-OCSCs drugs which, however, have shown unsatisfactory efficacy in most cases. We propose a novel approach to ovarian cancer diagnosis and therapy.
Serum Metabolic Profiling Identifies Key Differences between Patients with Single-Ventricle Heart Disease and Healthy Controls
Authors: Pires da Silva Julie , Pietra Ashley E. , Baybayon-Grandgeorge Angela N. , Garcia Anastacia M.
Published: February 2022

There are growing numbers of infants and children living with single-ventricle congenital heart disease (SV). However, cardiac dysfunction and, ultimately, heart failure (HF) are common in the SV population and the ability to predict the progression to HF in SV patients has been limited, primarily due to an incomplete understanding of the disease pathogenesis. Here, we tested the hypothesis that non-invasive circulating metabolomic profiles can serve as novel biomarkers in the SV population. We performed systematic metabolomic and pathway analyses on a subset of pediatric SV non-failing (SVNF) and failing (SVHF) serum samples, compared with samples from biventricular non-failing (BVNF) controls. We determined that serum metabolite panels were sufficient to discriminate SVHF subjects from BVNF subjects, as well as SVHF subjects from SVNF subjects. Many of the identified significantly dysregulated metabolites were amino acids, energetic intermediates and nucleotides. Specifically, we identified pyruvate, palmitoylcarnitine, 2-oxoglutarate and GTP as promising circulating biomarkers that could be used for SV risk stratification, monitoring response to therapy and even as novel targets of therapeutic intervention in a population with few other options.