bluuebunny/crossref_metadata_2025 huggingface dataset:
Myricetin as an Antivirulence Compound Interfering with a Morphological Transformation into Coccoid Forms and Potentiating Activity of Antibiotics against Helicobacter pylori
Authors: Krzyżek Paweł , Migdał Paweł , Paluch Emil , Karwańska Magdalena , Wieliczko Alina , Gościniak Grażyna
Published: March 2021

Helicobacter pylori, a gastric pathogen associated with a broad range of stomach diseases, has a high tendency to become resistant to antibiotics. One of the most important factors related to therapeutic failures is its ability to change from a spiral to a coccoid form. Therefore, the main aim of our original article was to determine the influence of myricetin, a natural compound with an antivirulence action, on the morphological transformation of H. pylori and check the potential of myricetin to increase the activity of antibiotics against this pathogen. We observed that sub-minimal inhibitory concentrations (sub-MICs) of this compound have the ability to slow down the process of transformation into coccoid forms and reduce biofilm formation of this bacterium. Using checkerboard assays, we noticed that the exposure of H. pylori to sub-MICs of myricetin enabled a 4–16-fold reduction in MICs of all classically used antibiotics (amoxicillin, clarithromycin, tetracycline, metronidazole, and levofloxacin). Additionally, RT-qPCR studies of genes related to the H. pylori morphogenesis showed a decrease in their expression during exposure to myricetin. This inhibitory effect was more strongly seen for genes involved in the muropeptide monomers shortening (csd3, csd6, csd4, and amiA), suggesting their significant participation in the spiral-to-coccoid transition. To our knowledge, this is the first research showing the ability of any compound to synergistically interact with all five antibiotics against H. pylori and the first one showing the capacity of a natural substance to interfere with the morphological transition of H. pylori from spiral to coccoid forms.
Excision of Oxidatively Generated Guanine Lesions by Competitive DNA Repair Pathways
Authors: Shafirovich Vladimir , Geacintov Nicholas E.
Published: March 2021

The base and nucleotide excision repair pathways (BER and NER, respectively) are two major mechanisms that remove DNA lesions formed by the reactions of genotoxic intermediates with cellular DNA. It is generally believed that small non-bulky oxidatively generated DNA base modifications are removed by BER pathways, whereas DNA helix-distorting bulky lesions derived from the attack of chemical carcinogens or UV irradiation are repaired by the NER machinery. However, existing and growing experimental evidence indicates that oxidatively generated DNA lesions can be repaired by competitive BER and NER pathways in human cell extracts and intact human cells. Here, we focus on the interplay and competition of BER and NER pathways in excising oxidatively generated guanine lesions site-specifically positioned in plasmid DNA templates constructed by a gapped-vector technology. These experiments demonstrate a significant enhancement of the NER yields in covalently closed circular DNA plasmids (relative to the same, but linearized form of the same plasmid) harboring certain oxidatively generated guanine lesions. The interplay between the BER and NER pathways that remove oxidatively generated guanine lesions are reviewed and discussed in terms of competitive binding of the BER proteins and the DNA damage-sensing NER factor XPC-RAD23B to these lesions.
Genome Wide Analysis of U-Box E3 Ubiquitin Ligases in Wheat (Triticum aestivum L.)
Authors: Kim Dae Yeon , Lee Yong Jin , Hong Min Jeong , Kim Jae Ho , Seo Yong Weon
Published: March 2021

U-box E3 ligase genes play specific roles in protein degradation by post-translational modification in plant signaling pathways, developmental stages, and stress responses; however, little is known about U-box E3 genes in wheat. We identified 213 U-box E3 genes in wheat based on U-box and other functional domains in their genome sequences. The U-box E3 genes were distributed among 21 chromosomes and most showed high sequence homology with homoeologous U-box E3 genes. Synteny analysis of wheat U-box E3 genes was conducted with other plant species such as Brachypodium distachyon, barley, rice, Triricum uratu, and Aegilops tauschii. A total of 209 RNA-seq samples representing 22 tissue types, from grain, root, leaf, and spike samples across multiple time points, were analyzed for clustering of U-box E3 gene expression during developmental stages, and the genes responded differently in various tissues and developmental stages. In addition, expression analysis of U-box E3 genes under abiotic stress, including drought, heat, and both heat and drought, and cold conditions, was conducted to provide information on U-box E3 gene expression under specific stress conditions. This analysis of U-box E3 genes could provide valuable information to elucidate biological functions for a better understanding of U-box E3 genes in wheat.
Loss of FADD and Caspases Affects the Response of T-Cell Leukemia Jurkat Cells to Anti-Cancer Drugs
Authors: Mrkvová Zuzana , Portešová Michaela , Slaninová Iva
Published: March 2021

Programmed cell death (PCD) pathways play a crucial role in the response of cancer cells to treatment. Their dysregulation is one of the cancer hallmarks and one of the reasons of drug resistance. Here, we studied the significance of the individual members of PCD signaling pathways in response to treatment with common anti-cancer drugs using the T-cell leukemia Jurkat cells with single or double knockouts of necroptosis and/or apoptosis genes. We identified apoptosis as the primary cell death pathway upon anti-cancer drugs treatment. The cells with knocked out either Fas-associated protein with death domain (FADD) or all executioner caspases were resistant. This resistance could be partially overcome by induction of RIP1-dependent necroptosis through TNFR1 activation using combined treatment with TNF-α and smac mimetic (LCL161). RIP1 was essential for cellular response to TNF-α and smac mimetic, but dispensable for the response to anti-cancer drugs. Here, we demonstrated the significance of FADD and executioner caspases in carrying out programmed cell death upon anti-cancer drug treatments and the ability of combined treatment with TNF-α and smac mimetic to partially overcome drug resistance of FADD and/or CASP3/7/6-deficient cells via RIP1-dependent necroptosis. Thus, a combination of TNF-α and smac mimetic could be a suitable strategy for overcoming resistance to therapy in cells unable to trigger apoptosis.
Interleukin-34-CSF1R Signaling Axis Promotes Epithelial Cell Transformation and Breast Tumorigenesis
Authors: Poudel Muna , Kim Garam , Bhattarai Poshan Yugal , Kim Jin-Young , Choi Hong Seok
Published: March 2021

IL-34 has been recently identified as a ligand for CSF1R that regulates various cellular processes including cell proliferation, survival, and differentiation. Although the binding of IL-34 to CSF1R modulates several cancer-driving signaling pathways, little is known about the role of IL-34/CSF1R signaling in breast cancer. Herein, we report that IL-34 induces epithelial cell transformation and breast tumorigenesis through activation of MEK/ERK and JNK/c-Jun pathways. IL-34 increased the phosphorylation of MEK1/2, ERK1/2, JNK1/2, and c-Jun through CSF1R in mouse skin epidermal JB6 C141 cells and human breast cancer MCF7 cells. IL-34 enhanced c-Fos and c-Jun promoter activity, resulting in increased AP-1 transactivation activity in JB6 Cl41 and MCF7 cells. Moreover, PIN1 enhanced IL-34-induced phosphorylation of MEK1/2, ERK1/2, JNK1/2, and c-Jun in JB6 Cl41 and MCF7 cells. Inhibition of PIN1 using juglone prevented the IL-34-induced transformation of JB6 C141 cells. Similarly, silencing of PIN1 reduced the IL-34-induced tumorigenicity of MCF7 cells. Consistent with these results, the synergistic model showed that treatment with juglone suppressed the IL-34-induced growth of tumors formed by 4T1 cells in BALB/c mice. Our study demonstrates the role of IL-34-induced MEK/ERK and JNK/c-Jun cascades in breast cancer and highlights the regulatory role of PIN1 in IL-34-induced breast tumorigenesis.
Ceramide Synthase 2 Null Mice Are Protected from Ovalbumin-Induced Asthma with Higher T Cell Receptor Signal Strength in CD4+ T Cells
Authors: Shin Sun-Hye , Cho Kyung-Ah , Yoon Hee-Soo , Kim So-Yeon , Kim Hee-Yeon , Pewzner-Jung Yael , Jung Sung-Ae , Park Woo-Jae , Futerman Anthony H. , Park Joo-Won
Published: March 2021

(1) Background: six mammalian ceramide synthases (CerS1–6) determine the acyl chain length of sphingolipids (SLs). Although ceramide levels are increased in murine allergic asthma models and in asthmatic patients, the precise role of SLs with specific chain lengths is still unclear. The role of CerS2, which mainly synthesizes C22–C24 ceramides, was investigated in immune responses elicited by airway inflammation using CerS2 null mice. (2) Methods: asthma was induced in wild type (WT) and CerS2 null mice with ovalbumin (OVA), and inflammatory cytokines and CD4 (cluster of differentiation 4)+ T helper (Th) cell profiles were analyzed. We also compared the functional capacity of CD4+ T cells isolated from WT and CerS2 null mice. (3) Results: CerS2 null mice exhibited milder symptoms and lower Th2 responses than WT mice after OVA exposure. CerS2 null CD4+ T cells showed impaired Th2 and increased Th17 responses with concomitant higher T cell receptor (TCR) signal strength after TCR stimulation. Notably, increased Th17 responses of CerS2 null CD4+ T cells appeared only in TCR-mediated, but not in TCR-independent, treatment. (4) Conclusions: altered Th2/Th17 immune response with higher TCR signal strength was observed in CerS2 null CD4+ T cells upon TCR stimulation. CerS2 and very-long chain SLs may be therapeutic targets for Th2-related diseases such as asthma.
Towards Quantitative and Standardized Serological and Neutralization Assays for COVID-19
Authors: Tian Linhua , Elsheikh Elzafir B. , Patrone Paul N. , Kearsley Anthony J. , Gaigalas Adolfas K. , Inwood Sarah , Lin-Gibson Sheng , Esposito Dominic , Wang Lili
Published: March 2021

Quantitative and robust serology assays are critical measurements underpinning global COVID-19 response to diagnostic, surveillance, and vaccine development. Here, we report a proof-of-concept approach for the development of quantitative, multiplexed flow cytometry-based serological and neutralization assays. The serology assays test the IgG and IgM against both the full-length spike antigens and the receptor binding domain (RBD) of the spike antigen. Benchmarking against an RBD-specific SARS-CoV IgG reference standard, the anti-SARS-CoV-2 RBD antibody titer was quantified in the range of 37.6 µg/mL to 31.0 ng/mL. The quantitative assays are highly specific with no correlative cross-reactivity with the spike proteins of MERS, SARS1, OC43 and HKU1 viruses. We further demonstrated good correlation between anti-RBD antibody titers and neutralizing antibody titers. The suite of serology and neutralization assays help to improve measurement confidence and are complementary and foundational for clinical and epidemiologic studies.
Measuring Digital Citizenship: A Comparative Analysis
Authors: Fernández-Prados Juan Sebastián , Lozano-Díaz Antonia , Ainz-Galende Alexandra
Published: March 2021

This paper aims at showing a state of the art about digital citizenship from the methodological point of view when it comes to measuring this construct. The review of the scientific literature offers at least ten definitions and nine different scales of measurement. The comparative and diachronic analysis of the content of the definitions shows us two conceptions of digital citizenship, some more focused on digital competences and others on critical and activist aspects. This paper replicates and compares three scales of measurement of digital citizenship selected for their relevance and administered in a sample of 366 university students, to analyze their psychometric properties and the existing coincidences and divergences between the three. The most outstanding conclusion is that not all of them seem to measure the same construct, due to its diversity of dimensions. An online activism dimension needs to be incorporated if digital citizenship is to be measured. There is an urgent need to agree internationally on a definition of digital citizenship with its corresponding dimensions to elaborate a reliable and valid measuring instrument.
Age-Related Macular Degeneration (AMD): A View to the Future
Authors: Miller Joan W. , D’Anieri Lily L. , Husain Deeba , Miller John B. , Vavvas Demetrios G.
Published: March 2021

Age-related macular degeneration (AMD) is the leading cause of blindness in people over age 50 worldwide, and the third leading cause of blindness overall [...]
Remote Sensing of Narrowing Barrier Islands along the Coast of Pakistan over Past 30 Years
Authors: Kanwal Shamsa , Ding Xiaoli , Sajjad Muhammad , Nazeer Majid , Zia Ibrahim
Published: March 2021

Barrier islands (BIs) are the first line of defense against the sea/wave actions in coastal areas, and assessing their stability is crucial in the context of effective coastal planning. Therefore, this study evaluates the spatial–temporal shoreline changes of the BIs in Pakistan over the past three decades (1989–2018). Satellite data from Landsat missions are used to delineate the shorelines of 19 BIs in Pakistan. After delineating the shorelines from satellite observations, two well-known statistical methods (i.e., end point rate (EPR) and linear regression rate (LRR)) are used to capture the localized changes in the BIs. The results ascertain that nearly all of the BIs have experienced noteworthy erosion during the past three decades. While the mean erosion over all the BIs during the study period is estimated to be >6 m/y, significant spatial heterogeneities among the individual BIs exist. The interdecadal comparison indicates that the highest mean erosion of the BIs occurred during the period 1989–1999 (13.03 ± 0.62 m/y), which gradually reduced over the preceding decades (i.e., 7.76 ± 0.62 m/y during the period 1999–2009 and 3.8 ± 0.7 m/y during the period 2009–2018). Nevertheless, ~65% of the total BIs experienced high erosion (>2 m/y), ~15% experienced moderate (<2 m/y), and ~20% experienced low erosion (<1 m/y) during the period 1989-2018. This situation implies that while ~65% of these BIs need immediate interventions from the concerned authorities, the 15% BIs with moderate erosion might experience high erosion in the wake of rising sea levels and decreasing sediment influx in the near future without proper measures. This depletion of the BIs might not only affect Pakistan but also have regional consequences due to their various services.
Operational Wave Forecast Selection in the Atlantic Ocean Using Random Forests
Authors: Campos Ricardo M. , Costa Mariana O. , Almeida Fabio , Guedes Soares C.
Published: March 2021

The existence of multiple wave forecasts leads to the question of which one should be used in practical ocean engineering applications. Ensemble forecasts have emerged as an important complement to deterministic forecasts, with better performances at mid-to-long ranges; however, they add another option to the variety of wave predictions that are available nowadays. This study developed random forest (RF) postprocessing models to identify the best wave forecast between two National Centers for Environmental Protection (NCEP) products (deterministic and ensemble). The supervised learning classifier was trained using National Data Buoy Center (NDBC) buoy data and the RF model accuracies were analyzed as a function of the forecast time. A careful feature selection was performed by evaluating the impact of the wind and wave variables (inputs) on the RF accuracy. The results showed that the RF models were able to select the best forecast only in the very short range using input information regarding the significant wave height, wave direction and period, and ensemble spread. At forecast day 5 and beyond, the RF models could not determine the best wave forecast with high accuracy; the feature space presented no clear pattern to allow for successful classification. The challenges and limitations of such RF predictions for longer forecast ranges are discussed in order to support future studies in this area.
The Labour Market Effects of International Trade in the Presence of Vertical Product Differentiation: Some Methodological Remarks in Retrospect
Authors: Celi Giuseppe
Published: March 2021

The paper retrospectively analyses the issue of the impact of international trade on developed countries’ labour markets in the 1990s, when the majority of academic opinion denied the role of trade in the misfortunes of unskilled workers. An analytical framework is proposed in which intra-industry trade is explained in terms of countries’ factor endowments and factor intensities of goods. Unlike the traditional Heckscher–Ohlin model of inter-industry trade, the model suggested here is more consistent with stylised facts about North–South trade. The paper also proposes a method for empirically assessing factor substitution effects at the product level. Inferring the factor content of intra-industry trade from the inter-sectoral relationship between factor intensity and average unit values of exports, the paper found that the labour market effects of intra-industry trade add significantly to the estimated factor market impact of trade.
Spillovers of Stock Markets among the BRICS: New Evidence in Time and Frequency Domains before the Outbreak of COVID-19 Pandemic
Authors: Shi Kai
Published: March 2021

We attempted to comprehensively decode the connectedness among the abbreviation of five emerging market countries (BRICS) stock markets between 1 August 2002 and 31 December 2019 not only in time domain but also in frequency domain. A continuously varying spillover index based on forecasting error variance decomposition within a generalized abbreviation of vector-autoregression (VAR) framework was computed. With the help of spectral representation, heterogeneous frequency responses to shocks were separated into frequency-specific spillovers in five different frequency bands to reveal differentiated linkages among BRICS markets. Rolling sample analyses were introduced to allow for multiple changes during the sample period. It is found that return spillovers dominated by the high frequency band (within 1 week) part declined with the drop of frequencies, while volatility spillovers dominated by the low frequency band (above 1 quarter) part grew with the decline in frequencies; the dynamics of spillovers were influenced by crucial systematic risk events, and some similarities implied in the spillover dynamics in different frequency bands were found. From the perspective of identifying systematic risk sources, China’s stock market and Russia’s stock market, respectively, played an influential role for return spillover and volatility spillover across BRICS markets.
Spatial–Temporal Characteristics of Precipitation and Its Relationship with Land Use/Cover Change on the Qinghai-Tibet Plateau, China
Authors: Zhang Bo , Zhou Wei
Published: March 2021

The Qinghai-Tibet Plateau (QTP) is an area sensitive to global climate change, and land use/land cover change (LUCC) plays a vital role in regulating climate system at different temporal and spatial scales. In this study, we analyzed the temporal and spatial trend of precipitation and the characteristics of LUCC on the QTP. Meanwhile, we also used the normalized difference vegetation index (NDVI) as an indicator of LUCC to discuss the relationship between LUCC and precipitation. The results show the following: (1) Annual precipitation showed a fluctuant upward trend at a rate of 11.5 mm/decade in this area from 1967 to 2016; three periods (i.e., 22 years, 12 years, and 2 years) of oscillations in annual precipitation were observed, in which expectant 22 years is the main oscillation period. It was predicted that QTP will still be in the stage of increasing precipitation. (2) The LUCC of the plateau changed apparently from 1980 to 2018. The area of grassland decreased by 9.47%, and the area of unused land increased by 7.25%. From the perspective of spatial distribution, the transfer of grassland to unused land occurred in the western part of the QTP, while the reverse transfer was mainly distributed in the northwestern part of the QTP. (3) NDVI in the northern and southwestern parts of the QTP is positively correlated with precipitation, while negative correlations are mainly distributed in the southeast of the QTP, including parts of Sichuan and Yunnan Province. Our results show that precipitation in the QTP has shown a fluctuating growth trend in recent years, and precipitation and NDVI are mainly positively correlated. Furthermore, we hope that this work can provide a theoretical basis for predicting regional hydrology, climate change, and LUCC research.
Agricultural Land Use Change in Chongqing and the Policy Rationale behind It: A Multiscale Perspective
Authors: Li Lingyue , Qi Zhixin , Xian Shi , Yao Dong
Published: March 2021

Agricultural land resources have been the central issue for the Chinese government in its attempts to secure food and agricultural sustainability. Yet strict land use control does not protect the agricultural land from erosion by urban expansion. Identifying the specific patterns and mechanisms of the agricultural land conversion, thus, is critical for land management and related decision making. Based on the annual nominal 30 m land use/land cover datasets (called CLUD-A), this study goes below the national/regional level to examine agricultural land conversion in Chongqing from a multiscale perspective. At the metropolis and its subdivision’s scales, the volume of the conversion area has been generally increasing, from 122.40 km2 in 1980–1990, 162.26 km2 in 1990–2000, and 706.14 km2 in 2000–2010, to 684.83 km2 in 2010–2015. Such a conversion in the main city area and its surroundings far outweighed that in the rural outskirts, as 68.9% (1990–2000), 92.2% (2000–2010), and 82.7% (2010–2015) of the conversion happened in the former. Moreover, values of Gini coefficients and coefficient of variation (CV) based on the county/district scale (Gini [0.46, 0.64], CV [0.69, 0.99] throughout the four periods) are much lower than those based on the town/village scale (Gini [0.88, 0.94], CV [3.18, 4.47] throughout the four periods), suggesting the uneven extent of spatial distribution of the agricultural land conversion trickles down along with the downscale of administration: the lower the administrative level, the more severe the unbalance. The policy rationale behind this transition is also discussed. This research argues for tangible approaches to a sustainable rural-urban transformation.
Copper(II) Carboxylates with 2,3,4-Trimethoxybenzoate and 2,4,6-Trimethoxybenzoate: Dinuclear Cu(II) Cluster and µ-Aqua-Bridged Cu(II) Chain Molecule
Authors: Mikuriya Masahiro , Yamakawa Chihiro , Tanabe Kensuke , Nukita Raigo , Amabe Yuki , Yoshioka Daisuke , Mitsuhashi Ryoji , Tatehata Ryota , Tanaka Hidekazu , Handa Makoto , Tsuboi Motohiro
Published: March 2021

Copper(II) complexes with 2,3,4-trimethoxybenzoic acid (H234-tmbz) and 2,4,6-trimethoxybenzoic acid (H246-tmbz), [Cu2(234-tmbz)4(H2O)2] (6) and [Cu(246-tmbz)2(µ-H2O)2(H2O)2]n (7), were synthesized and characterized by elemental analysis, infrared and UV-vis spectra and temperature dependence of magnetic susceptibilities (1.9–300 K). The X-ray crystal structures revealed that the former 6 is a dinuclear cluster having syn-syn-bridged Cu2(µ-234-tmbz)4 core with Cu···Cu separation of 2.6009(7) Å, while the latter 7 is a µ-aqua-bridged chain molecule consisting of Cu(246-tmb)2(µ-H2O)2(H2O)2 units with Cu···Cu separation of 4.1420(5) Å. Temperature dependence of magnetic susceptibilities showed that an antiferromagnetic interaction with 2J = −272 cm−1 for 6 and a weak antiferromagnetic interaction with J = −0.21 cm−1 for 7, between the two copper(II) ions. The adsorption isotherm of 6 showed Types I behavior having a 125.4 m2g−1 of specific surface area.
Assessing the Impact of Attendance Modality on the Learning Performance of a Course on Machines and Mechanisms Theory
Authors: Valiente David , Campello-Vicente Héctor , Velasco-Sánchez Emilio , Rodríguez-Mas Fernando , Campillo-Davo Nuria
Published: March 2021

University education approaches related to the field of science, technology, engineering and mathematics (STEM), have generally particularized on teaching activity and learning programs which are commonly understood as reoriented lessons that fuse theoretic concepts interweaved with practical activities. In this context, team work has been widely acknowledged as a means to conduct practical and hands-on lessons, and has been revealed to be successful in the achievement of exercise resolution and design tasks. Besides this, methodologies sustained by ICT resources such as online or blended approaches, have also reported numerous benefits for students’ active learning. However, such benefits have to be fully validated within the particular teaching context, which may facilitate student achievement to a greater or lesser extent. In this work, we analyze the impact of attendance modalities on the learning performance of a STEM-related course on “Machines and Mechanisms Theory”, in which practical lessons are tackled through a team work approach. The validity of the results is reinforced by group testing and statistical tests with a sample of 128 participants. Students were arranged in a test group (online attendance) and in a control group (face-to-face attendance) to proceed with team work during the practical lessons. Thus, the efficacy of distance and in situ methodologies is compared. Moreover, additional variables have also been compared according to the historical record of the course, in regards to previous academic years. Finally, students’ insights about the collaborative side of this program, self-knowledge and satisfaction with the proposal have also been reported by a custom questionnaire. The results demonstrate greater performance and satisfaction amongst participants in the face-to-face modality. Such a modality is prooven to be statistically significant for the final achievement of students in detriment to online attendance.
Global Portfolio Credit Risk Management: The US Banks Post-Crisis Challenge
Authors: Siarka Pawel
Published: March 2021

This paper addresses the problem of modeling credit risk for multi-product and global loan portfolios. The authors presented an improved version of the Basel Committee’s one-factor model for capital requirements calculation. They examined whether latent market factors corresponding to distinct portfolios are always highly correlated within the global portfolio and how this correlation impacts total losses distribution function. Historical losses of top-tier banks (JPMorgan Chace, Bank of America, Citigroup, Wells Fargo, US Bancorp) were analyzed. Furthermore, the estimation of the correlations between latent market factors was conducted, and its impact on the total loss distribution function was assessed. The research was performed based on consolidated financial statements for holding companies - FR Y-9C reports provided by the Federal Reserve Bank of Chicago. To verify the improved model, the authors analyzed two distinct loan portfolios for each bank, i.e., credit cards and commercial and industrial loans. They showed that the correlation between latent market factors could be significantly lower than one and disregarding this conclusion may lead to overestimating total unexpected losses. Hence, capital requirements calculated according to the IRB (Internal Ratings Based Approach) formula as a sum of individual VaR999 estimates may be biased. According to this finding, the enhanced one-factor model seems to be more accurate while calculating unexpected total loss for global portfolios. The authors proved that the active credit risk management process aiming to lower market factors’ correlation results in less volatile total losses. Therefore, financial institutions could be more resistant to macroeconomic downturns.
Key Roles of Dipterocarpaceae, Bark Type Diversity and Tree Size in Lowland Rainforests of Northeast Borneo—Using Functional Traits of Lichens to Distinguish Plots of Old Growth and Regenerating Logged Forests
Authors: Thüs Holger , Wolseley Pat , Carpenter Dan , Eggleton Paul , Reynolds Glen , Vairappan Charles S. , Weerakoon Gothamie , Mrowicki Robert J.
Published: March 2021

Many lowland rainforests in Southeast Asia are severely altered by selective logging and there is a need for rapid assessment methods to identify characteristic communities of old growth forests and to monitor restoration success in regenerating forests. We have studied the effect of logging on the diversity and composition of lichen communities on trunks of trees in lowland rainforests of northeast Borneo dominated by Dipterocarpaceae. Using data from field observations and vouchers collected from plots in disturbed and undisturbed forests, we compared a taxonomy-based and a taxon-free method. Vouchers were identified to genus or genus group and assigned to functional groups based on sets of functional traits. Both datasets allowed the detection of significant differences in lichen communities between disturbed and undisturbed forest plots. Bark type diversity and the proportion of large trees, particularly those belonging to the family Dipterocarpaceae, were the main drivers of lichen community structure. Our results confirm the usefulness of a functional groups approach for the rapid assessment of tropical lowland rainforests in Southeast Asia. A high proportion of Dipterocarpaceae trees is revealed as an essential element for the restoration of near natural lichen communities in lowland rainforests of Southeast Asia.
Structure-Based Virtual Screening: Identification of a Novel NS2B-NS3 Protease Inhibitor with Potent Antiviral Activity against Zika and Dengue Viruses
Authors: Shin Hye Jin , Kim Mi-Hwa , Lee Joo-Youn , Hwang Insu , Yoon Gun Young , Kim Hae Soo , Kwon Young-Chan , Ahn Dae-Gyun , Kim Kyun-Do , Kim Bum-Tae , Kim Seong-Jun , Kim Chonsaeng
Published: March 2021

Zika virus (ZIKV), which is associated with severe diseases in humans, has spread rapidly and globally since its emergence. ZIKV and dengue virus (DENV) are closely related, and antibody-dependent enhancement (ADE) of infection between cocirculating ZIKV and DENV may exacerbate disease. Despite these serious threats, there are currently no approved antiviral drugs against ZIKV and DENV. The NS2B-NS3 viral protease is an attractive antiviral target because it plays a pivotal role in polyprotein cleavage, which is required for viral replication. Thus, we sought to identify novel inhibitors of the NS2B-NS3 protease. To that aim, we performed structure-based virtual screening using 467,000 structurally diverse chemical compounds. Then, a fluorescence-based protease inhibition assay was used to test whether the selected candidates inhibited ZIKV protease activity. Among the 123 candidate inhibitors selected from virtual screening, compound 1 significantly inhibited ZIKV NS2B-NS3 protease activity in vitro. In addition, compound 1 effectively inhibited ZIKV and DENV infection of human cells. Molecular docking analysis suggested that compound 1 binds to the NS2B-NS3 protease of ZIKV and DENV. Thus, compound 1 could be used as a new therapeutic option for the development of more potent antiviral drugs against both ZIKV and DENV, reducing the risks of ADE.
Contribution of Infectious Agents to the Development of Celiac Disease
Authors: Sánchez Daniel , Hoffmanová Iva , Szczepanková Adéla , Hábová Věra , Tlaskalová-Hogenová Helena
Published: March 2021

The ingestion of wheat gliadin (alcohol-soluble proteins, an integral part of wheat gluten) and related proteins induce, in genetically predisposed individuals, celiac disease (CD), which is characterized by immune-mediated impairment of the small intestinal mucosa. The lifelong omission of gluten and related grain proteins, i.e., a gluten-free diet (GFD), is at present the only therapy for CD. Although a GFD usually reduces CD symptoms, it does not entirely restore the small intestinal mucosa to a fully healthy state. Recently, the participation of microbial components in pathogenetic mechanisms of celiac disease was suggested. The present review provides information on infectious diseases associated with CD and the putative role of infections in CD development. Moreover, the involvement of the microbiota as a factor contributing to pathological changes in the intestine is discussed. Attention is paid to the mechanisms by which microbes and their components affect mucosal immunity, including tolerance to food antigens. Modulation of microbiota composition and function and the potential beneficial effects of probiotics in celiac disease are discussed.
Ten-Year Follow-Up of Patients Treated with Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection from a Randomized Controlled Trial and Review of the Literature
Authors: Ooijevaar R. E. , van Nood E. , Goorhuis A. , Terveer E. M. , van Prehn J. , Verspaget H. W. , van Beurden Y. H. , Dijkgraaf M. G. W. , Keller J. J.
Published: March 2021

Fecal microbiota transplantation (FMT) has become a well-established treatment for recurrent Clostridioides difficile infection (rCDI). While short-term outcomes and adverse events relating to FMT have been well documented, there still is a paucity of data with regard to long-term safety. In this report, we describe the long-term follow-up of the prospective cohort of the first randomized controlled trial of FMT for rCDI, and review the existing literature. A total of 34 patients were treated with FMT for rCDI. Seven patients were still alive after a follow-up of more than 10 years and three patients were lost to follow-up. None of the 34 patients had experienced a new-onset autoimmune, gastrointestinal, or malignant disorder during follow-up. We did not find any deterioration or amelioration of pre-existing medical conditions. Furthermore, no deaths directly attributable to FMT could be identified. These findings are in accordance with the data in available literature. In conclusion, no long-term adverse events or complications directly attributable to FMT were found in our prospective cohort. Review of the available literature does not point to long-term risks associated with FMT in this elderly population, provided that carefully screened fecal suspensions are being used. No firm conclusion on the long-term safety of FMT in younger patients could be drawn.
In Vivo Production of RNA Aptamers and Nanoparticles: Problems and Prospects
Authors: Shanaa Ousama Al , Rumyantsev Andrey , Sambuk Elena , Padkina Marina
Published: March 2021

RNA aptamers are becoming increasingly attractive due to their superior properties. This review discusses the early stages of aptamer research, the main developments in this area, and the latest technologies being developed. The review also highlights the advantages of RNA aptamers in comparison to antibodies, considering the great potential of RNA aptamers and their applications in the near future. In addition, it is shown how RNA aptamers can form endless 3-D structures, giving rise to various structural and functional possibilities. Special attention is paid to the Mango, Spinach and Broccoli fluorescent RNA aptamers, and the advantages of split RNA aptamers are discussed. The review focuses on the importance of creating a platform for the synthesis of RNA nanoparticles in vivo and examines yeast, namely Saccharomyces cerevisiae, as a potential model organism for the production of RNA nanoparticles on a large scale.
Nanomaterials in Cementitious Composites: An Update
Authors: Metaxa Zoi S. , Tolkou Athanasia K. , Efstathiou Stefania , Rahdar Abbas , Favvas Evangelos P. , Mitropoulos Athanasios C. , Kyzas George Z.
Published: March 2021

This review is an update about the addition of nanomaterials in cementitious composites in order to improve their performance. The most common used nanomaterials for cementitious materials are carbon nanotubes, nanocellulose, nanographene, graphene oxide, nanosilica and nanoTiO2. All these nanomaterials can improve the physical, mechanical, thermal and electrical properties of cementitious composites, for example increase their compressive and tensile strength, accelerate hydration, decrease porosity and enhance fire resistance. Cement based materials have a very complex nanostructure consisting of hydration products, crystals, unhydrated cement particles and nanoporosity where traditional reinforcement, which is at the macro and micro scale, is not effective. Nanomaterials can reinforce the nanoscale, which wasn’t possible heretofore, enhancing the performance of the cementitious matrix.
Occurrence of Peptide-Peptide Interactions during the Purification of Self-Assembling Peptide f1-8 from a β-Lactoglobulin Tryptic Hydrolysate
Authors: Pimont-Farge Mathilde , Bérubé Amélie , Perreault Véronique , Brisson Guillaume , Suwal Shyam , Pouliot Yves , Doyen Alain
Published: March 2021

Self-assembling peptides have gained attention because of their nanotechnological applications. Previous work demonstrated that the self-assembling peptide f1-8 (Pf1-8) that is generated from the tryptic hydrolysis of β-lactoglobulin can form a hydrogel after several purification steps, including membrane filtration and consecutive washes. This study evaluates the impact of each processing step on peptide profile, purity, and gelation capacity of each fraction to understand the purification process of Pf1-8 and the peptide-peptide interactions involved. We showed that peptide-peptide interactions mainly occurred through electrostatic and hydrophobic interactions, influencing the fraction compositions. Indeed, the purity of Pf1-8 did not correlate with the number of wash steps. In addition to Pf1-8, two other hydrophobic peptides were identified, peptide f15-20, and peptide f41-60. The gelation observed could be induced either through peptide-peptide interactions or through self-assembling, both being driven by non-covalent bond and more specifically hydrophobic interactions.
Spectroscopic Study of the Molecular Structure of the New Hybrid with a Potential Two-Way Antibacterial Effect
Authors: Kowalczuk Dorota , Gładysz Agata , Pitucha Monika , Kamiński Daniel M. , Barańska Agnieszka , Drop Bartłomiej
Published: March 2021

Bacterial strains become resistant to almost all classes of antibiotics, which makes it necessary to look for new substitutes. The non-absorbable ciprofloxacin–biguanide bismuth complex, used locally, may be a good alternative to a conventional therapy. The purpose of this study was to study the structure of the proposed ciprofloxacin (CIP) -bismuth(III)—chlorhexidine (CHX) composite (CIP-Bi-CHX). The spectroscopic techniques such as UV-VIS (ultraviolet-visible) spectroscopy, FTIR (Fourier-transform infrared) spectroscopy and NMR (Nuclear Magnetic Resonance) spectroscopy were used for structure characterization of the hybrid compound. The performed analysis confirmed the presence of the two active components—CIP and CHX and revealed the possible coordination sites of the ligands with bismuth ion in the metallo-organic structure. Spectroscopic study showed that the complexation between Bi(III) and CIP occurs through the carboxylate and ketone groups of the quinolone ring, while CHX combines with the central ion via the biguanide moieties.
Metal-Organic Frameworks as Versatile Heterogeneous Solid Catalysts for Henry Reactions
Authors: Cirujano Francisco G. , Luque Rafael , Dhakshinamoorthy Amarajothi
Published: March 2021

Metal–organic frameworks (MOFs) have become one of the versatile solid materials used for a wide range of applications, such as gas storage, gas separation, proton conductivity, sensors and catalysis. Among these fields, one of the more well-studied areas is the use of MOFs as heterogeneous catalysts for a broad range of organic reactions. In the present review, the employment of MOFs as solid catalysts for the Henry reaction is discussed, and the available literature data from the last decade are grouped. The review is organized with a brief introduction of the importance of Henry reactions and structural properties of MOFs that are suitable for catalysis. The second part of the review discusses the use of MOFs as solid catalysts for the Henry reaction involving metal nodes as active sites, while the third section provides data utilizing basic sites (primary amine, secondary amine, amides and urea-donating sites). While commenting on the catalytic results in these two sections, the advantage of MOFs over other solid catalysts is compared in terms of activity by providing turnover number (TON) values and the structural stability of MOFs during the course of the reaction. The final section provides our views on further directions in this field.
Cannabinoid Receptor Modulation of Neurogenesis: ST14A Striatal Neural Progenitor Cells as a Simplified In Vitro Model
Authors: Cottone Erika , Pomatto Valentina , Rapelli Stefania , Scandiffio Rosaria , Mackie Ken , Bovolin Patrizia
Published: March 2021

The endocannabinoid system (ECS) is involved in the modulation of several basic biological processes, having widespread roles in neurodevelopment, neuromodulation, immune response, energy homeostasis and reproduction. In the adult central nervous system (CNS) the ECS mainly modulates neurotransmitter release, however, a substantial body of evidence has revealed a central role in regulating neurogenesis in developing and adult CNS, also under pathological conditions. Due to the complexity of investigating ECS functions in neural progenitors in vivo, we tested the suitability of the ST14A striatal neural progenitor cell line as a simplified in vitro model to dissect the role and the mechanisms of ECS-regulated neurogenesis, as well as to perform ECS-targeted pharmacological approaches. We report that ST14A cells express various ECS components, supporting the presence of an active ECS. While CB1 and CB2 receptor blockade did not affect ST14A cell number, exogenous administration of the endocannabinoid 2-AG and the synthetic CB2 agonist JWH133 increased ST14A cell proliferation. Phospholipase C (PLC), but not PI3K pharmacological blockade negatively modulated CB2-induced ST14A cell proliferation, suggesting that a PLC pathway is involved in the steps downstream to CB2 activation. On the basis of our results, we propose ST14A neural progenitor cells as a useful in vitro model for studying ECS modulation of neurogenesis, also in prospective in vivo pharmacological studies.
Isolation, Characterization, and Medicinal Potential of Polysaccharides of Morchella esculenta
Authors: Badshah Syed Lal , Riaz Anila , Muhammad Akhtar , Tel Çayan Gülsen , Çayan Fatih , Emin Duru Mehmet , Ahmad Nasir , Emwas Abdul-Hamid , Jaremko Mariusz
Published: March 2021

Mushroom polysaccharides are active medicinal compounds that possess immune-modulatory and anticancer properties. Currently, the mushroom polysaccharides krestin, lentinan, and polysaccharopeptides are used as anticancer drugs. They are an unexplored source of natural products with huge potential in both the medicinal and nutraceutical industries. The northern parts of Pakistan have a rich biodiversity of mushrooms that grow during different seasons of the year. Here we selected an edible Morchella esculenta (true morels) of the Ascomycota group for polysaccharide isolation and characterization. Polysaccharopeptides and polysaccharides from this mushroom were isolated using the green chemistry, hot water treatment method. Fourier transform infrared spectroscopy revealed the sugar nature and possible beta-glucan type structure of these polysaccharides. Antioxidant assays showed that the deproteinized polysaccharides have moderate free radical scavenging activity. These isolated polysaccharides exhibited good acetylcholinesterase (AChE) and butyryl cholinesterase (BChE) inhibition activities. Therefore, these polysaccharides may be valuable for the treatment of Alzheimer’s and Parkinson’s diseases. Further bioassays are needed to discover the true potential of M. esculenta polysaccharides for medicinal purposes.
Insight into Functional Membrane Proteins by Solution NMR: The Human Bcl-2 Protein—A Promising Cancer Drug Target
Authors: Ul Mushtaq Ameeq , Ådén Jörgen , Sparrman Tobias , Hedenström Mattias , Gröbner Gerhard
Published: March 2021

Evasion from programmed cell death (apoptosis) is the main hallmark of cancer and a major cause of resistance to therapy. Many tumors simply ensure survival by over-expressing the cell-protecting (anti-apoptotic) Bcl-2 membrane protein involved in apoptotic regulation. However, the molecular mechanism by which Bcl-2 protein in its mitochondrial outer membrane location protects cells remains elusive due to the absence of structural insight; and current strategies to therapeutically interfere with these Bcl-2 sensitive cancers are limited. Here, we present an NMR-based approach to enable structural insight into Bcl-2 function; an approach also ideal as a fragment-based drug discovery platform for further identification and development of promising molecular Bcl-2 inhibitors. By using solution NMR spectroscopy on fully functional intact human Bcl-2 protein in a membrane-mimicking micellar environment, and constructs with specific functions remaining, we present a strategy for structure determination and specific drug screening of functional subunits of the Bcl-2 protein as targets. Using 19F NMR and a specific fragment library (Bionet) with fluorinated compounds we can successfully identify various binders and validate our strategy in the hunt for novel Bcl-2 selective cancer drug strategies to treat currently incurable Bcl-2 sensitive tumors.
A Highly Efficient and Stable Photocatalyst; N-Doped ZnO/CNT Composite Thin Film Synthesized via Simple Sol-Gel Drop Coating Method
Authors: Elias Md , Uddin Md Nizam , Saha Joyanta Kumar , Hossain Md Awlad , Sarker Dali R. , Akter Sonia , Siddiquey Iqbal A. , Uddin Jamal
Published: March 2021

The thin film of N-doped ZnO/CNT nanocomposite was successfully fabricated on soda lime glass substrate by a simple sol-gel drop-coating method. The structural, morphological, chemical, and optical properties of as prepared samples were characterized by a variety of tools such as X-ray Diffraction (XRD), Field Emission Scanning Electron Microscopy (FE-SEM), Fourier Transform Infrared spectroscopy (FT-IR), and UV-visible spectroscopy. The hexagonal crystalline structure was confirmed from XRD measurement without any other impurity phase detection in samples. The N-doped ZnO/CNT composite showed excellent photo-catalytic activity towards cationic methylene blue (MB) dye degradation with 100% removal rate under UV light irradiation as compared to N-doped ZnO (65%) and pure ZnO (47.36%). The convincing performance has also been observed for the case of visible light irradiation. The enhancement of that photocatalytic activity might be due to narrowing the band gap as well as the reduction of electron–hole pair recombination in ZnO matrix with the incorporation of dopant nitrogen and CNT. It is assumed from the obtained results that N-doped ZnO/CNT nanocomposite thin film can be employed as an economically achievable and ecofriendly method to degrade dye with UV and visible light irradiation. Additionally, density functional theory (DFT) calculations were applied to explore the effect of N-doping on electronic structure of ZnO. The computational study has supported the experimental results of significant band gap contraction, which leads to the maximum absorption towards higher wavelength and no appreciable change of lattice parameters after doping. A conceivable photocatalytic mechanism of N-doped ZnO/CNT nanocomposite has been proposed as well.