bluuebunny/crossref_metadata_2025 huggingface dataset:
Weighted Consensus Segmentations
Authors: Saker Halima , Machné Rainer , Fallmann Jörg , Murray Douglas B. , Shahin Ahmad M. , Stadler Peter F.
Published: February 2021

The problem of segmenting linearly ordered data is frequently encountered in time-series analysis, computational biology, and natural language processing. Segmentations obtained independently from replicate data sets or from the same data with different methods or parameter settings pose the problem of computing an aggregate or consensus segmentation. This Segmentation Aggregation problem amounts to finding a segmentation that minimizes the sum of distances to the input segmentations. It is again a segmentation problem and can be solved by dynamic programming. The aim of this contribution is (1) to gain a better mathematical understanding of the Segmentation Aggregation problem and its solutions and (2) to demonstrate that consensus segmentations have useful applications. Extending previously known results we show that for a large class of distance functions only breakpoints present in at least one input segmentation appear in the consensus segmentation. Furthermore, we derive a bound on the size of consensus segments. As show-case applications, we investigate a yeast transcriptome and show that consensus segments provide a robust means of identifying transcriptomic units. This approach is particularly suited for dense transcriptomes with polycistronic transcripts, operons, or a lack of separation between transcripts. As a second application, we demonstrate that consensus segmentations can be used to robustly identify growth regimes from sets of replicate growth curves.
In Vitro Hair Dermal Papilla Cells Induction by Fagraea berteroana, a Tree of the Marquesan Cosmetopoeia (French Polynesia)
Authors: Hughes Kristelle , Ho Raimana , Chazaud Claire , Hermitte Stéphanie , Greff Stéphane , Butaud Jean-François , Filaire Edith , Ranouille Edwige , Berthon Jean-Yves , Raharivelomanana Phila
Published: February 2021

Fagraea berteroana is a tree used in traditional medicine in various islands of the South Pacific. Here, we studied its hair growth-inducing properties as suggested by one of its Marquesan ethno-uses in haircare. The ethyl acetate extract of the fruits of F. berteroana (FEAE) and four resulting fractions (FEAE-F0, FEAE-F1, FEAE-F2, and FEAE-F3) were tested on hair follicle dermal papilla cells to determine their cell proliferative activity. Furthermore, RT-qPCR analysis enabled gene modulation analysis, while immunostaining of the β-catenin protein was used to follow protein regulation. We found that the plant extracts induced a controlled, dose-dependent cell proliferation. FEAE-F0 simultaneously down-regulated Bone Morphogenetic Protein 2 (BMP2) mRNA expression and upregulated Cyclin-D1 (CCND1) gene expression, which suggests an involvement in the regulation of the Wnt and Transforming Growth Factor beta (TGFβ) pathways that control the hair cycle. FEAE-F0 exhibited a 1.34-fold increase of nuclear β-catenin protein. This is indicative of an active hair growth state. Thus, we conclude that FEAE-F0 could be an innovative candidate in hair care, which opens interesting leads to promote the Marquesan cosmetopoeia.
Flash-Based Security Primitives: Evolution, Challenges and Future Directions
Authors: Gordon Holden , Edmonds Jack , Ghandali Soroor , Yan Wei , Karimian Nima , Tehranipoor Fatemeh
Published: February 2021

Over the last two decades, hardware security has gained increasing attention in academia and industry. Flash memory has been given a spotlight in recent years, with the question of whether or not it can prove useful in a security role. Because of inherent process variation in the characteristics of flash memory modules, they can provide a unique fingerprint for a device and have thus been proposed as locations for hardware security primitives. These primitives include physical unclonable functions (PUFs), true random number generators (TRNGs), and integrated circuit (IC) counterfeit detection. In this paper, we evaluate the efficacy of flash memory-based security primitives and categorize them based on the process variations they exploit, as well as other features. We also compare and evaluate flash-based security primitives in order to identify drawbacks and essential design considerations. Finally, we describe new directions, challenges of research, and possible security vulnerabilities for flash-based security primitives that we believe would benefit from further exploration.
Shear-Wave Elastography—Diagnostic Value in Children with Chronic Autoimmune Thyroiditis
Authors: Cepeha Cristina Mihaela , Paul Corina , Borlea Andreea , Fofiu Renata , Borcan Florin , Dehelean Cristina Adriana , Ivan Viviana , Stoian Dana
Published: February 2021

Chronic autoimmune thyroiditis (CAT) is the most common thyroid disorder in the pediatric population. Ultrasound evaluation may suggest the diagnosis. Additionally, shear-wave elastography (SWE) proved to be a valuable additional diagnosis tool in adults with CAT by assessing thyroid stiffness (TS). This study aims to assess its use also in detecting children with CAT. The study group consisted of 50 children with confirmed diagnosis of CAT, who were compared to the control group, consisting of 50 children with no thyroid pathology and with an adult group of 50 subjects with CAT. The evaluation included, besides bioimmunochemical evaluation, also thyroid ultrasound evaluation and elastography measurements in the same session (Aixplorer Mach 30, Supersonic imagine, France). The mean TS values were significantly lower for children in the CAT group compared to adults with CAT (15.51 ± 4.76 kPa vs. 20.96 ± 6.31 kPa; p < 0.0001) and higher compared to the healthy aged matched controls (15.51 ± 4.76 kPa vs. 10.41 ± 2.01 kPa; p < 0.0001). SWE elastography definitely seems a promising technique in the evaluation of children with autoimmune thyroid pathology.
Social Aspects of Tourism Policy in the European Union. The Example of Poland and Slovakia
Authors: Panasiuk Aleksander , Wszendybył-Skulska Ewa
Published: February 2021

Since the beginning of the 21st century, the European Union tourism policy has been increasingly focused on initiatives in the field of social tourism, which are one of the ways of achieving sustainable development in the European tourism economy. Most of the research projects that have so far been conducted in the field have focused on the benefits for its participants (subjective one: Children and youths, seniors, disabled people, people (families) with low incomes and/or unemployed, big families). However, there is a lack of research on the analysis of the place of social aspects of tourism in the general socio-economic policy of the state and, in a detailed aspect, in the sectoral policy represented by tourism policy, as well as its potential impact on the development of the national economy and meeting tourism needs of the society. The authors tried to fill this research gap in this study. The aim of the study is to differentiate the issues related to the social aspects of tourism policy from the entire socio-economic policy pursued in the European Union and selected member states (Poland and Slovakia). The article is of a theoretical–analytical–conceptual nature. Empirical research, due to the nature of its issues, was conducted with the use of qualitative research methods. The results of the conducted research showed that activities in the field of social tourism policy are conditioned by organizational solutions for the entities that undertake them, as well as economic ones, especially in the field of financing. Moreover, they made it possible to propose the concept of a model social tourism policy with an indication of its place in the European policy on the basis of the past and future EU financial perspectives.
Earnings Management in Frontier Market: Do Institutional Settings Matter?
Authors: Martens Wil , Yapa Prem , Safari Maryam
Published: February 2021

We analyse whether differences in earnings management practices in frontier countries can be explained by institutional settings, considering their diverse corporate governance environments, legal regimes, and accounting standards. Across 22 frontier market countries from 2000–2017, we find that financial disclosure, legal environments, and the number of analysts following to be correlated with reduced levels of earnings management (EM). The impact of wealth, GDP growth, firm size, and the use of Big-4 auditors were also associated with reduced EM. Contrary to developed markets and novel to this study, higher levels of societal trust failed to show significance in its ability to constrain EM, suggesting informal institutions are less influential as control monitors. Findings herein verify that the factors that moderate EM are not universally applicable, and help highlight international differences in the management of earnings.
#Mathathome during the COVID-19 Pandemic: Exploring and Reimagining Resources and Social Supports for Parents
Authors: Harper Frances K. , Rosenberg Joshua M. , Comperry Sara , Howell Kay , Womble Sierra
Published: February 2021

During the COVID-19 pandemic, schools abruptly transitioned to emergency remote instruction. Consequently, expectations for parental involvement in school mathematics rose to unprecedented levels. We sought to understand the experiences of parents to reimagine possibilities for engagement in mathematics during and beyond the pandemic. Leveraging data from tweets using #mathathome and survey responses from parents, we identified who supported continued mathematics learning at home and explored the nature of the mathematics taught there. We found that Twitter and survey data sources described two largely distinct groups of those supporting parents to continue mathematics education at home, but similar findings emerged from analyses of each data source, suggesting that themes were common among different groups. Namely, we saw a commitment to continued mathematics learning and engagement with a range of mathematics topics. These topics mostly focused on elementary-level content, especially counting, through everyday activities/objects and mathematical sense-making. Most parents used resources provided by the school alongside resources they identified and provided on their own. School responses to emergency remote instruction were mostly asynchronous, and parents expressed a need for more opportunities to interact directly with their children’s teachers. We discuss what the mathematics education community might learn from these experiences to support parental engagement during and beyond periods of remote emergency instruction.
Status of Life Cycle Assessment (LCA) in Africa
Authors: Karkour Selim , Rachid Safa , Maaoui Mariem , Lin Chia-Chun , Itsubo Norihiro
Published: February 2021

Life cycle assessment (LCA) has received attention as a tool to evaluate the environmental impacts of products and services. In the last 20 years, research on the topic has increased, and now more than 25,000 articles are related to LCA in scientific journals databases such as the Scopus database; however, the concept is relatively new in Africa, where the number of networks has been highlighted to be very low when compared to the other regions. This paper focuses on a review of life cycle assessments conducted in Africa over the last 20 years. It aims at highlighting the current research gap for African LCA. A total of 199 papers were found for the whole continent; this number is lower than that for both Japan and Germany (more than 400 articles each) and nearly equal to developing countries such as Thailand. Agriculture is the sector which received the most attention, representing 53 articles, followed by electricity and energy (60 articles for the two sectors). South Africa (43), Egypt (23), and Tunisia (19) were the countries where most of the research was conducted. Even if the number of articles related to LCA have increased in recent years, many steps still remain. For example, establishing a specific life cycle inventory (LCI) database for African countries or a targeted ideal life cycle impact assessment (LCIA) method. Several African key sectors could also be assessed further.
Numerical Analysis of Air Vortex Interaction with Porous Screen
Authors: An Xudong , Jiang Lin , Hassanipour Fatemeh
Published: February 2021

In many industrial applications, a permeable mesh (porous screen) is used to control the unsteady (most commonly vortex) flows. Vortex flows are known to display intriguing behavior while propagating through porous screens. This numerical study aims to investigate the effects of physical properties such as porosity, Reynolds number, inlet flow dimension, and distance to the screen on the flow behavior. The simulation model includes a piston-cylinder vortex ring generator and a permeable mesh constructed by evenly arranged rods. Two methods of user-defined function and moving mesh have been applied to model the vortex ring generation. The results show the formation, evolution, and characteristics of the vortical rings under various conditions. The results for vorticity contours and the kinetic energy dissipation indicate that the physical properties alter the flow behavior in various ways while propagating through the porous screens. The numerical model, cross-validated with the experimental results, provides a better understanding of the fluid–solid interactions of vortex flows and porous screens.
In Vitro Genotoxicity Assessment of Functional Ingredients: Betaine, Choline, and Taurine
Authors: Sanz-Serrano Julen , Vettorazzi Ariane , Muruzabal Damian , Azqueta Amaya , López de Cerain Adela
Published: February 2021

This article focuses on a complete in vitro genotoxicity assessment of three nutrients widely used as functional ingredients in the European market: betaine, choline, and taurine. The European Food Safety Authority (EFSA) tiered approach for food additives in concordance with the safety assessment of chemicals in food developed by Food and Agriculture Organization/World Health Organization (FAO/WHO) was followed; the miniaturized Ames test in Salmonella typhimurium TA97a, TA98, TA100, TA102, and TA1535 strains (following the principles of Organization for Economic Co-operation and Development (OECD) 471), and the micronucleus test (OECD 487) in TK6 cells were performed. In addition, the in vitro standard and enzyme-modified (human 8-oxoguanine DNA glycosylase 1 (hOGG), endonuclease III (EndoIII), human alkyladenine DNA glycosylase (hAAG)) comet assay (S9−/S9+) was conducted in order to assess the potential premutagenic lesions in TK6 cells. None of the compounds produced any signs of genotoxicity in any of the conditions tested. This article increases the limited evidence available and complements the EFSA recommendations for the in vitro genotoxicity testing of nutrients.
Trust and Trustworthiness in Corrupted Economic Environments
Authors: Becchetti Leonardo , Corazzini Luca , Pelligra Vittorio
Published: February 2021

We use an original variant of the standard trust game to study the effects of corruption on trust and trustworthiness. In this game, both the trustor and the trustee know that part of the surplus they can generate may be captured by a third “corrupted” player under different expected costs of audit and prosecution. We find a slightly higher trustor’s giving in the presence of corruption, matched by a significant excess of reciprocity from the trustee. Both the trustor and the trustee expect, on average, corruption to act as a tax, inelastic to changes in the probability of corruption prosecution. Expectations are correct for the inelasticity assumption and for the actual value of the “corruption tax”. Our experimental findings lead to the rejection of four standard hypotheses based on purely self-regarding preferences. We discuss how the apparently paradoxical excess reciprocity effect is consistent with the cultural role of heroes in history, where examples of commendable giving have been used to stimulate emulation of ordinary people. Our results suggest that the excess reciprocity component of the trustee makes the trustor’s excess giving a rational and effective strategy.
Epigenetics: New Insights into Mammary Gland Biology
Authors: Ivanova Elitsa , Le Guillou Sandrine , Hue-Beauvais Cathy , Le Provost Fabienne
Published: February 2021

The mammary gland undergoes important anatomical and physiological changes from embryogenesis through puberty, pregnancy, lactation and involution. These steps are under the control of a complex network of molecular factors, in which epigenetic mechanisms play a role that is increasingly well described. Recently, studies investigating epigenetic modifications and their impacts on gene expression in the mammary gland have been performed at different physiological stages and in different mammary cell types. This has led to the establishment of a role for epigenetic marks in milk component biosynthesis. This review aims to summarize the available knowledge regarding the involvement of the four main molecular mechanisms in epigenetics: DNA methylation, histone modifications, polycomb protein activity and non-coding RNA functions.
Molecular Characterization and Phylogenetic Analysis of MADS-Box Gene VroAGL11 Associated with Stenospermocarpic Seedlessness in Muscadine Grapes
Authors: Rahman M Atikur , Balasubramani Subramani P , Basha Sheikh M
Published: February 2021

Reduced expression of MADS-box gene AGAMOUS-LIKE11 (VviAGL11) is responsible for stenospermocarpic seedlessness in bunch grapes. This study is aimed to characterize the VviAGL11 orthologous gene (VroAGL11) in native muscadine grapes (Vitis rotundifolia) at the molecular level and analyze its divergence from other plants. The VroAGL11 transcripts were found in all muscadine cultivars tested and highly expressed in berries while barely detectable in leaves. RT-PCR and sequencing of predicted ORFs from diverse grape species showed that AGL11 transcripts were conservatively spliced. The encoded VroAGL11 protein contains highly conserved MADS-MEF2-like domain, MADS domain, K box, putative phosphorylation site and two sumoylation motifs. The muscadine VroAGL11 proteins are almost identical (99%) to that of seeded bunch cultivar, Chardonnay, except in one amino acid (A79G), but differs from mutant protein of seedless bunch grape, Sultanina, in two amino acids, R197L and T210A. Phylogenetic analysis showed that AGL11 gene of muscadine and other Vitis species formed a separate clade than that of other eudicots and monocots. Muscadine grape cultivar “Jane Bell” containing the highest percentage of seed content in berry (7.2% of berry weight) had the highest VroAGL11 expression, but almost none to nominal expression in seedless cultivars Fry Seedless (muscadine) and Reliance Seedless (bunch). These findings suggest that VroAGL11 gene controls the seed morphogenesis in muscadine grapes like in bunch grape and can be manipulated to induce stenospermocarpic seedlessness using gene editing technology.
Numerical Modeling of Venturi Flume
Authors: Heyrani Mehdi , Mohammadian Abdolmajid , Nistor Ioan , Dursun Omerul Faruk
Published: February 2021

In order to measure flow rate in open channels, including irrigation channels, hydraulic structures are used with a relatively high degree of reliance. Venturi flumes are among the most common and efficient type, and they can measure discharge using only the water level at a specific point within the converging section and an empirical discharge relationship. There have been a limited number of attempts to simulate a venturi flume using computational fluid dynamics (CFD) tools to improve the accuracy of the readings and empirical formula. In this study, simulations on different flumes were carried out using a total of seven different models, including the standard k–ε, RNG k–ε, realizable k–ε, k–ω, and k–ω SST models. Furthermore, large-eddy simulation (LES) and detached eddy simulation (DES) were performed. Comparison of the simulated results with physical test data shows that among the turbulence models, the k–ε model provides the most accurate results, followed by the dynamic k LES model when compared to the physical experimental data. The overall margin of error was around 2–3%, meaning that the simulation model can be reliably used to estimate the discharge in the channel. In different cross-sections within the flume, the k–ε model provides the lowest percentage of error, i.e., 1.93%. This shows that the water surface data are well calculated by the model, as the water surface profiles also follow the same vertical curvilinear path as the experimental data.
SARS–CoV-2 Immuno-Pathogenesis and Potential for Diverse Vaccines and Therapies: Opportunities and Challenges
Authors: McGill Andrew , Khalil Roukiah , Dutta Rinku , Green Ryan , Howell Mark , Mohapatra Subhra , Mohapatra Shyam
Published: February 2021

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is a novel coronavirus that emerged from Wuhan, China in late 2019 causing coronavirus disease-19 (COVID-19). SARS-CoV-2 infection begins by attaching to angiotensin-converting enzyme 2 receptor (ACE2) via the spike glycoprotein, followed by cleavage by TMPRSS2, revealing the viral fusion domain. Other presumptive receptors for SARS-CoV-2 attachment include CD147, neuropilin-1 (NRP1), and Myeloid C-lectin like receptor (CLR), each of which might play a role in the systemic viral spread. The pathology of SARS-CoV-2 infection ranges from asymptomatic to severe acute respiratory distress syndrome, often displaying a cytokine storm syndrome, which can be life-threatening. Despite progress made, the detailed mechanisms underlying SARS-CoV-2 interaction with the host immune system remain unclear and are an area of very active research. The process’s key players include viral non-structural proteins and open reading frame products, which have been implicated in immune antagonism. The dysregulation of the innate immune system results in reduced adaptive immune responses characterized by rapidly diminishing antibody titers. Several treatment options for COVID-19 are emerging, with immunotherapies, peptide therapies, and nucleic acid vaccines showing promise. This review discusses the advances in the immunopathology of SARS-CoV-2, vaccines and therapies under investigation to counter the effects of this virus, as well as viral variants.
A Cross-Sectional Community Readiness Assessment for Implementing School-Based Comprehensive Sexuality Education in Islamabad, Pakistan
Authors: Ahmed Furqan , Ahmad Ghufran , Paff Katharina , Samkange-Zeeb Florence , Brand Tilman
Published: February 2021

Evidence indicates that school-based sexuality education empowers children and adolescents with the skills, values, and attitudes that will enable them to appreciate their health and well-being, nourish respectful social and sexual relationships, understand their rights, and to make informed choices. Owing to organized community resistance and prevalent misconceptions, promoting sexual and reproductive health has been challenging, especially in conservative settings like Pakistan. This study aimed at systematically exploring communities’ perceptions regarding implementing school-based comprehensive sexuality education by conducting a cross-sectional community readiness assessment in Islamabad, Pakistan. A total of 35 semi-structured interviews were conducted with community key informants. Following the guidelines of the community readiness handbook, the interviews were transcribed and scored by two independent raters. The results indicate that, overall, the Islamabad community is at stage two of community readiness, the denial/resistance stage. Individual dimension scores indicate that knowledge of efforts, resources for efforts, knowledge about the issue, and leadership dimensions are at the denial/resistance stage. Only community climate was rated at stage three of community readiness, the vague awareness stage. This indicates that, for promoting sexuality education in the Pakistani context, it is essential to tackle resistance by sensitizing the community and the stakeholders through awareness campaigns.
Human Health Risk Assessment on the Consumption of Apples Growing in Urbanized Areas: Case of Kharkiv, Ukraine
Authors: Medvedeva Yuliia , Kucher Anatolii , Lipsa Joanna , Hełdak Maria
Published: February 2021

This study aims to determine the safety of consumption of plant products grown in Kharkiv, Ukraine. Kharkiv, as well as many other post-Soviet cities, is environmentally characterized by the widespread growing of edible plants—from industrial areas to school gardens—as well as the presence of a significant number of nature management conflicts, the location of heavy industry, the prevalence of obsolete environmentally unfriendly transport, etc. The article presents the results of the study of apple samples taken in different functional zones of Kharkiv city, Ukraine. The results of the study showed that the maximum levels of heavy metals were exceeded in apple samples from all sampling sites: Pb—from 11.47 to 38.86 times; Cd—from 1.76 to 5.68 times (of the norms of the FAO and EU). The most polluted were samples from the residential areas, which is partly due to significant land pollution from various types of waste. Levels of hazard index (HI) differ by age groups: from 24.37 to 70.11 HI (children group, 1–6 years); from 10.28 to 29.59 HI (children group, 7–16 years); from 0.88 to 2.53 HI (adult group, 18–65 years). Non-carcinogenic risks can be related to disorders of the immune system, blood, urinoexcretory, and nervous systems as well as problems in the functioning of liver and kidneys. The total carcinogenic risk of eating apples exceeds the permissible level.
12-Week Exercise Training of Knee Joint and Squat Movement Improves Gait Ability in Older Women
Authors: Choi Myungsoo , Ahn Nayoung , Park Jusik , Kim Kijin
Published: February 2021

This study analyzed the effects of an exercise training program consisting of a knee joint complex exercise device (leg-link system) with digitally controlled active motion function and squat movement on physical fitness and gait ability of elderly women aged 70 or above. Fifty four (54) elderly women aged 70 or above were divided into three groups as control group (n = 18), aerobic training group (n = 18), and combined training group with resistance and aerobic exercise (n = 18). Health-related physical fitness, gait ability-related physical fitness, and the temporal and spatial parameters of gait ability were compared. The health-related physical fitness after the 12-week training was not significantly altered in control group, whereas combined training group showed significant increase in all factors (p < 0.05) and aerobic training group showed significant increase (p < 0.05) only in the physical efficiency index. The gait ability-related physical fitness and all items of the temporal and spatial parameters of gait were found to have significantly increased (p < 0.05) in combined training group after the 12-week exercise training; however, in aerobic training group, only the factors related to muscular endurance and balance showed significant increase (p < 0.05). This study suggested that the exercise training consisting of knee joint complex exercise with digitally controlled active motion function and squat exercise for strengthening lower extremities and core muscles had positive effects on enhancing the ambulatory competence in elderly women.
Graphene-Based Composites as Catalysts for the Degradation of Pharmaceuticals
Authors: Olatunde Olalekan C. , Onwudiwe Damian C.
Published: February 2021

The incessant release of pharmaceuticals into the aquatic environment continues to be a subject of increasing concern. This is because of the growing demand for potable water sources and the potential health hazards which these pollutants pose to aquatic animals and humans. The inability of conventional water treatment systems to remove these compounds creates the need for new treatment systems in order to deal with these class of compounds. This review focuses on advanced oxidation processes that employ graphene-based composites as catalysts for the degradation of pharmaceuticals. These composites have been identified to possess enhanced catalytic activity due to increased surface area and reduced charge carrier recombination. The techniques employed in synthesizing these composites have been explored and five different advanced oxidation processes—direct degradation process, chemical oxidation process, photocatalysis, electrocatalyis processes and sonocatalytic/sono-photocatalytic processes—have been studied in terms of their enhanced catalytic activity. Finally, a comparative analysis of the processes that employ graphene-based composites was done in terms of process efficiency, reaction rate, mineralization efficiency and time required to achieve 90% degradation.
Editorial for the Special Issue “Squamous Cell Cancer of the Head and Neck—Time to Arrive in the 21st Century of Oncology”
Authors: Perner Sven , Idel Christian
Published: February 2021

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common cancer worldwide [...]
Evaluation of the Influence of Adalimumab on the Expression Profile of Leptin-Related Genes and Proteins in Keratinocytes Treated with Lipopolysaccharide A
Authors: Grabarek Beniamin Oskar , Kasela Tomasz , Adwent Iwona , Zawidlak-Węgrzyńska Barbara , Brus Ryszard
Published: February 2021

Psoriasis is a disease with a proinflammatory base, in which an increased expression of leptin, tumor necrosis factor alpha (TNF-α), interleukin (IL) IL-12/23, IL-6, is observed. A drug used in the treatment of psoriasis of moderate and acute strength is the monoclonal antibody anti-TNF–adalimumab. The goal of this study was to evaluate the influence of adalimumab on changes in the expression profile of leptin-related genes in human keratinocyte cells exposed to lipopolysaccharide A and analyze if adalimumab acts via leptin pathways. The evaluation of changes of the pattern of genes connected with leptin and proteins coded by them was marked in a culture of human keratinocytes (HaCaT) exposed to 1 µg/mL lipopolysaccharide A (LPS) for 8 h in order to induce the inflammatory process, then to 8 µg/mL of adalimumab for 2.8 and 24 h in comparison with the control (cells not treated with the substances). The techniques used were mRNA microarray, Real-Time Quantitative Reverse Transcription Reaction (RTqPCR), Enzyme-Linked Immunosorbent Assay (ELISA), as well as transfections of HaCaT culture with leptin small interfering RNA (siRNA) in order to see whether adalimumab works through pathways dependent on leptin. A statistically lower expression of leptin and its receptors was observed under the influence of the drug, independent of the exposition time of keratinocytes to adalimumab. In the cells transfected with leptin siRNA, a lower concentration of JAK2 and STAT3 proteins was observed, which confirms that adalimumab works through pathways dependent on leptin. Adalimumab has a modulatory effect on the gene expression pattern and the proteins coded by them connected with leptin in keratinocytes treated with LPS in vitro.
Tryptophan Metabolites and Aryl Hydrocarbon Receptor in Severe Acute Respiratory Syndrome, Coronavirus-2 (SARS-CoV-2) Pathophysiology
Authors: Anderson George , Carbone Annalucia , Mazzoccoli Gianluigi
Published: February 2021

The metabolism of tryptophan is intimately associated with the differential regulation of diverse physiological processes, including in the regulation of responses to severe acute respiratory syndrome, coronavirus-2 (SARS-CoV-2) infection that underpins the COVID-19 pandemic. Two important products of tryptophan metabolism, viz kynurenine and interleukin (IL)4-inducible1 (IL41)-driven indole 3 pyruvate (I3P), activate the aryl hydrocarbon receptor (AhR), thereby altering the nature of immune responses to SARS-CoV-2 infection. AhR activation dysregulates the initial pro-inflammatory cytokines production driven by neutrophils, macrophages, and mast cells, whilst AhR activation suppresses the endogenous antiviral responses of natural killer cells and CD8+ T cells. Such immune responses become further dysregulated by the increased and prolonged pro-inflammatory cytokine suppression of pineal melatonin production coupled to increased gut dysbiosis and gut permeability. The suppression of pineal melatonin and gut microbiome-derived butyrate, coupled to an increase in circulating lipopolysaccharide (LPS) further dysregulates the immune response. The AhR mediates its effects via alterations in the regulation of mitochondrial function in immune cells. The increased risk of severe/fatal SARS-CoV-2 infection by high risk conditions, such as elderly age, obesity, and diabetes are mediated by these conditions having expression levels of melatonin, AhR, butyrate, and LPS that are closer to those driven by SARS-CoV-2 infection. This has a number of future research and treatment implications, including the utilization of melatonin and nutraceuticals that inhibit the AhR, including the polyphenols, epigallocatechin gallate (EGCG), and resveratrol.
Portrait of Cancer Stem Cells on Colorectal Cancer: Molecular Biomarkers, Signaling Pathways and miRNAome
Authors: Angius Andrea , Scanu Antonio Mario , Arru Caterina , Muroni Maria Rosaria , Rallo Vincenzo , Deiana Giulia , Ninniri Maria Chiara , Carru Ciriaco , Porcu Alberto , Pira Giovanna , Uva Paolo , Cossu-Rocca Paolo , De Miglio Maria Rosaria
Published: February 2021

Colorectal cancer (CRC) is a leading cause of cancer death worldwide, and about 20% is metastatic at diagnosis and untreatable. Increasing evidence suggests that the heterogeneous nature of CRC is related to colorectal cancer stem cells (CCSCs), a small cells population with stemness behaviors and responsible for tumor progression, recurrence, and therapy resistance. Growing knowledge of stem cells (SCs) biology has rapidly improved uncovering the molecular mechanisms and possible crosstalk/feedback loops between signaling pathways that directly influence intestinal homeostasis and tumorigenesis. The generation of CCSCs is probably connected to genetic changes in members of signaling pathways, which control self-renewal and pluripotency in SCs and then establish function and phenotype of CCSCs. Particularly, various deregulated CCSC-related miRNAs have been reported to modulate stemness features, controlling CCSCs functions such as regulation of cell cycle genes expression, epithelial-mesenchymal transition, metastasization, and drug-resistance mechanisms. Primarily, CCSC-related miRNAs work by regulating mainly signal pathways known to be involved in CCSCs biology. This review intends to summarize the epigenetic findings linked to miRNAome in the maintenance and regulation of CCSCs, including their relationships with different signaling pathways, which should help to identify specific diagnostic, prognostic, and predictive biomarkers for CRC, but also develop innovative CCSCs-targeted therapies.
Small and Simple, yet Sturdy: Conformationally Constrained Peptides with Remarkable Properties
Authors: Bozovičar Krištof , Bratkovič Tomaž
Published: February 2021

The sheer size and vast chemical space (i.e., diverse repertoire and spatial distribution of functional groups) underlie peptides’ ability to engage in specific interactions with targets of various structures. However, the inherent flexibility of the peptide chain negatively affects binding affinity and metabolic stability, thereby severely limiting the use of peptides as medicines. Imposing conformational constraints to the peptide chain offers to solve these problems but typically requires laborious structure optimization. Alternatively, libraries of constrained peptides with randomized modules can be screened for specific functions. Here, we present the properties of conformationally constrained peptides and review rigidification chemistries/strategies, as well as synthetic and enzymatic methods of producing macrocyclic peptides. Furthermore, we discuss the in vitro molecular evolution methods for the development of constrained peptides with pre-defined functions. Finally, we briefly present applications of selected constrained peptides to illustrate their exceptional properties as drug candidates, molecular recognition probes, and minimalist catalysts.
Na+/H+ Exchangers Involve in Regulating the pH-Sensitive Ion Channels in Mouse Sperm
Authors: Kang Hang , Liu Min , Zhang Wei , Huang Rong-Zu , Zhao Na , Chen Chen , Zeng Xu-Hui
Published: February 2021

Sperm-specific K+ ion channel (KSper) and Ca2+ ion channel (CatSper), whose elimination causes male infertility in mice, determine the membrane potential and Ca2+ influx, respectively. KSper and CatSper can be activated by cytosolic alkalization, which occurs during sperm going through the alkaline environment of the female reproductive tract. However, which intracellular pH (pHi) regulator functionally couples to the activation of KSper/CatSper remains obscure. Although Na+/H+ exchangers (NHEs) have been implicated to mediate pHi in sperm, there is a lack of direct evidence confirming the functional coupling between NHEs and KSper/CatSper. Here, 5-(N,N-dimethyl)-amiloride (DMA), an NHEs inhibitor that firstly proved not to affect KSper/CatSper directly, was chosen to examine NHEs function on KSper/CatSper in mouse sperm. The results of patch clamping recordings showed that, when extracellular pH was at the physiological level of 7.4, DMA application caused KSper inhibition and the depolarization of membrane potential when pipette solutions were not pH-buffered. In contrast, these effects were minimized when pipette solutions were pH-buffered, indicating that they solely resulted from pHi acidification caused by NHEs inhibition. Similarly, DMA treatment reduced CatSper current and intracellular Ca2+, effects also dependent on the buffer capacity of pH in pipette solutions. The impairment of sperm motility was also observed after DMA incubation. These results manifested that NHEs activity is coupled to the activation of KSper/CatSper under physiological conditions.
Roles of microRNAs in Gastrointestinal Cancer Stem Cell Resistance and Therapeutic Development
Authors: Hwang Ga-Ram , Yuen John G. , Ju Jingfang
Published: February 2021

Resistance to cancer treatment is one of the major challenges currently faced when treating gastrointestinal (GI) cancers. A major contributing factor to this resistance is the presence of cancer stem cells (CSCs) in GI cancers (e.g., colorectal, pancreatic, gastric, liver cancer). Non-coding RNAs, such as microRNAs (miRNAs), have been found to regulate several key targets that are responsible for cancer stemness, and function as oncogenic miRNAs (oncomiRs) or tumor suppressor miRNAs. As a result, several miRNAs have been found to alter, or be altered by, the expression of CSC-defining markers and their related pathways. These miRNAs can be utilized to affect stemness in multiple ways, including directly targeting CSCs and enhancing the efficacy of cancer therapeutics. This review highlights current studies regarding the roles of miRNAs in GI CSCs, and efforts towards the development of cancer therapeutics.
Abundance of Entomopathogenic Fungi in Leaf Litter and Soil Layers in Forested Habitats in Poland
Authors: Majchrowska-Safaryan Anna , Tkaczuk Cezary
Published: February 2021

This study aims to determine the species composition and density of colony-forming units (CFU) of entomopathogenic fungi (EPF) in leaf litter at different depths of the top layer of forest soils depending on the type of forest (coniferous, deciduous and mixed forest), and the date of sampling (spring, autumn). In each type of forest, leaf litter and soil were collected using a soil stick from four depths of soil: 0–5, 5–10, 10–15 and 15–20 cm. Entomopathogenic fungi were isolated by a soil or litter dilution plating method on a selective medium. Four fungal genera were found: Beauveria spp., Cordyceps spp., Metarhizium spp., and Lecanicillium spp. The density of EPF was usually higher in leaf litter than in the layers of soil below, and the most frequently isolated species from both environments were Beauveria spp. among soil samples from all forest types; Beauveria spp. were most abundant in the top layer (0–5 cm), and their density of CFUs gradually decreased deeper into the soil profile.
Resistance to Bt Maize by Western Corn Rootworm: Effects of Pest Biology, the Pest–Crop Interaction and the Agricultural Landscape on Resistance
Authors: Gassmann Aaron
Published: February 2021

The western corn rootworm, Diabrotica virgifera virgifera LeConte, is among the most serious pests of maize in the United States. Since 2003, transgenic maize that produces insecticidal toxins from the bacterium Bacillus thuringiensis (Bt) has been used to manage western corn rootworm by killing rootworm larvae, which feed on maize roots. In 2009, the first cases of field-evolved resistance to Bt maize were documented. These cases occurred in Iowa and involved maize that produced Bt toxin Cry3Bb1. Since then, resistance has expanded to include other geographies and additional Bt toxins, with some rootworm populations displaying resistance to all commercially available Bt traits. Factors that contributed to field-evolved resistance likely included non-recessive inheritance of resistance, minimal fitness costs of resistance and limited adult dispersal. Additionally, because maize is the primary agricultural crop on which rootworm larvae can survive, continuous maize cultivation, in particular continuous cultivation of Bt maize, appears to be another key factor facilitating resistance evolution. More diversified management of rootworm larvae, including rotating fields out of maize production and using soil-applied insecticide with non-Bt maize, in addition to planting refuges of non-Bt maize, should help to delay the evolution of resistance to current and future transgenic traits.
Evolved Resistance to Placental Invasion Secondarily Confers Increased Survival in Melanoma Patients
Authors: Suhail Yasir , Afzal Junaid , Kshitiz
Published: February 2021

Mammals exhibit large differences in rates of cancer malignancy, even though the tumor formation rates may be similar. In placental mammals, rates of malignancy correlate with the extent of placental invasion. Our Evolved Levels of Invasibility (ELI) framework links these two phenomena identifying genes that potentially confer resistance in stromal fibroblasts to limit invasion, from trophoblasts in the endometrium, and from disseminating melanoma in the skin. Herein, using patient data from The Cancer Genome Atlas (TCGA), we report that these anti-invasive genes may be crucial in melanoma progression in human patients, and that their loss is correlated with increased cancer spread and lowered survival. Our results suggest that, surprisingly, these anti-invasive genes, which have lower expression in humans compared to species with non-invasive placentation, may potentially prevent stromal invasion, while a further reduction in their levels increases the malignancy and lethality of melanoma. Our work links evolution, comparative biology, and cancer progression across tissues, indicating new avenues for using evolutionary medicine to prognosticate and treat human cancers.
Electrospun Poly(butylene-adipate-co-terephthalate)/Nano-hyDroxyapatite/Graphene Nanoribbon Scaffolds Improved the In Vivo Osteogenesis of the Neoformed Bone
Authors: Vasconcellos Luana Marotta Reis , Santana-Melo Gabriela F. , Silva Edmundo , Pereira Vanessa Fernandes , Araújo Juliani Caroline Ribeiro , Silva André Diniz Rosa , Furtado André S. A. , Elias Conceição de Maria Vaz , Viana Bartolomeu Cruz , Marciano Fernanda Roberta , Lobo Anderson Oliveira
Published: February 2021

Electrospun ultrathin fibrous scaffold filed with synthetic nanohydroxyapatite (nHAp) and graphene nanoribbons (GNR) has bioactive and osteoconductive properties and is a plausible strategy to improve bone regeneration. Poly(butylene-adipate-co-terephthalate) (PBAT) has been studied as fibrous scaffolds due to its low crystallinity, faster biodegradability, and good mechanical properties; however, its potential for in vivo applications remains underexplored. We proposed the application of electrospun PBAT with high contents of incorporated nHAp and nHAp/GNR nanoparticles as bone grafts. Ultrathin PBAT, PBAT/nHAp, and PBAT/nHAp/GNR fibers were produced using an electrospinning apparatus. The produced fibers were characterized morphologically and structurally using scanning electron (SEM) and high-resolution transmission electron (TEM) microscopies, respectively. Mechanical properties were analyzed using a texturometer. All scaffolds were implanted into critical tibia defects in rats and analyzed after two weeks using radiography, microcomputed tomography, histological, histomorphometric, and biomechanical analyses. The results showed through SEM and high-resolution TEM characterized the average diameters of the fibers (ranged from 0.208 µm ± 0.035 to 0.388 µm ± 0.087) and nHAp (crystallite around 0.28, 0.34, and 0.69 nm) and nHAp/GNR (200–300 nm) nanoparticles distribution into PBAT matrices. Ultrathin fibers were obtained, and the incorporated nHAp and nHAp/GNR nanoparticles were well distributed into PBAT matrices. The addition of nHAp and nHAp/GNR nanoparticles improved the elastic modulus of the ultrathin fibers compared to neat PBAT. High loads of nHAp/GNR (PBATnH5G group) improved the in vivo lamellar bone formation promoting greater radiographic density, trabecular number and stiffness in the defect area 2 weeks after implantation than control and PBAT groups.
Breaking-Wave Induced Transient Pore Pressure in a Sandy Seabed: Flume Modeling and Observations
Authors: Li Changfei , Gao Fuping , Yang Lijing
Published: February 2021

Previous studies on wave-induced pore pressure in a porous seabed mainly focused on non-breaking regular waves, e.g., Airy linear waves or Stokes non-linear waves. In this study, breaking-wave induced pore pressure response in a sandy seabed was physically simulated with a large wave flume. The breaking-wave was generated by superimposing a series of longer waves onto the foregoing shorter waves at a specified location. Water surface elevations and the corresponding pore pressure in the process of wave breaking were measured simultaneously at three typical locations, i.e., at the rear, just at, and in front of the wave breaking location. Based on test results, characterization parameters are proposed for the wave surface elevations and the corresponding pore-pressures. Flume observations indicate that the wave height was greatly diminished during wave breaking, which further affected the pore-pressure responses. Moreover, the measured values of the characteristic time parameters for the breaking-wave induced pore-pressure are larger than those for the free surface elevation of breaking-waves. Under the action of incipient-breaking or broken waves, the measured values of the amplitude of transient pore-pressures are generally smaller than the predicted results with the analytical solution by Yamamoto et al. (1978) for non-breaking regular waves with equivalent values of characteristic wave height and wave period.