bluuebunny/crossref_metadata_2025 huggingface dataset:
Coupling Coordination Relationship and Driving Mechanism between Urbanization and Ecosystem Service Value in Large Regions: A Case Study of Urban Agglomeration in Yellow River Basin, China
Authors: Zhang Kaili , Liu Tan , Feng Rongrong , Zhang Zhicheng , Liu Kang
Published: July 2021

Mastering the coupling and coordination relationship and driving mechanism of urbanization and ecosystem service value (ESV) is of great significance to ecological protection and regional sustainable development. In this paper, the coupling coordination model, geographic detector and GWR model are used to analyze the spatio-temporal coupling interaction between urbanization and ESV and the spatial differentiation characteristics of influencing factors from 1995 to 2018. The results of the study are as follows: (1) During the study period, cities in the Yellow River Basin experienced accelerated urban expansion, and the ESV of forests, water and wetlands increased, which offset the reduction in ESV due to the expansion of construction land and farmland and grassland. (2) The degree of coupling and coordination between the two gradually improved, but the overall situation showed a low-level coupling and coordination process. Mild coupling coordination gradually increased, reaching an increase of 38.10%; severe imbalance types tended to disappear, decreasing by 52.38%, and coupling subtypes developed from lagging urbanization to ESV backward types. The high-value areas of the coupling coordination degree are distributed in the high-value areas of ESV in the north of the upper reaches, and the low-value areas are distributed in the cities of Henan and Shandong with high urbanization levels in the downstream and most resource-based cities in the middle reaches. (3) In addition, the spatial intensity of the effect of each dominant factor on the degree of coupling coordination is different. Economic growth, technological development, environmental regulations and the proportion of forest land have positive and belt-shaped alienation characteristics for the coupling and coordination of the two, and infrastructure and temperature show negative driving characteristics. Therefore, the coupling and coordination relationship between ESV and urbanization should be clarified to help future urban planning. On the basis of determining the regional environmental carrying capacity and the adjustment direction of the rational planning of land resources, the impact of urban barriers formed by administrative boundaries and natural geographical conditions on the development of urban agglomerations should be broken to achieve the overall high-quality and coordinated development of the basin.
Using Exploratory Spatial Analysis to Understand the Patterns of Adolescents’ Active Transport to School and Contributory Factors
Authors: Chen Long , Moore Antoni B. , Mandic Sandra
Published: July 2021

Active transport to school (ATS) is a convenient way for adolescents to reach their recommended daily physical activity levels. Most previous ATS research examined the factors that promote or hinder ATS, but this research has been of a global (i.e., non-spatial), statistical nature. Geographical Information Science (GIS) is widely applied in analysing human activities, focusing on local spatial phenomena, such as distribution, autocorrelation, and co-association. This study, therefore, applied exploratory spatial analysis methods to ATS and its factors. Kernel Density Estimation (KDE) was used to derive maps of transport mode and ATS factor distribution patterns. The results of KDE were compared to and verified by Local Indicators of Spatial Association (LISA) outputs. The data used in this study was collected from 12 high schools, including 425 adolescents who lived within walkable distance and used ATS or MTS in Dunedin New Zealand. This study identified clusters and spatial autocorrelation, confirming that the adolescents living in the south of the city, who were female, attended girls-only schools, lived in more deprived neighbourhoods, and lived in neighbourhoods with higher intersection density and residential density used more ATS. On the other hand, adolescents who were male, attended boys-only schools, lived in less deprived neighbourhoods, had more vehicles at home, and lived in neighbourhoods with medium level intersection density and residential density used more ATS in the northwest of the city as well as some part of the city centre and southeast of the city. The co-association between spatial patterns of the ATS factors and the ATS usages that this study detected adds to the evidence for autocorrelation underpinning ATS users across the study area.
Extending the IFC Standard to Enable Road Operation and Maintenance Management through OpenBIM
Authors: Ait-Lamallam Sara , Yaagoubi Reda , Sebari Imane , Doukari Omar
Published: July 2021

Open Building Information Modelling (OpenBIM) is a collaborative project management process. Its application to road infrastructures is currently limited. OpenBIM standards for infrastructure are still under development. One of these standards is the Industry Foundation Classes (IFC), which is a data architecture for modelling infrastructure projects. The current and upcoming releases of IFCRoad focus on structuring data for the design and construction phases of an infrastructure’s lifecycle. Semantics of the O&M process phase are not fully integrated within these standards. This paper proposes an extension of the IFC schema to enrich this standard with semantics inherent in the O&M phase of road infrastructures. This extension, based on IFCInfra4OM ontology, allows the OpenBIM process to be fully applied to road infrastructures. Its implementation on a case study relative to the A7 Agadir–Marrakech Highway in Morocco enables, on the one hand, analysis and compliance with O&M management requirements on the basis of a single container: the IFC-BIM-based model. On the other hand, it allows comparison of the OpenBIM process with that of ClosedBIM for the integration of O&M data into BIM for a road infrastructure.
A Multi-Zone Staged Indoor Emergency Evacuation Algorithm Based on Time Equalization
Authors: Han Litao , Gong Cheng , Gu Lei , Qiao Hu , Zhang Aiguo , Liu Mengfan
Published: July 2021

Most of the existing staged evacuation algorithms only consider the impact of crowd density on evacuation partition, but do not take into account the influence of the spatial distribution of occupants and the capacity of exits on the total evacuation time (TET). Therefore, a novel indoor emergency evacuation algorithm based on time equalization is proposed in this paper. All factors affecting TET such as the position and size of each group and the capacity of exits are fully considered in the proposed algorithm, which are uniformly converted into the occupancy time of each exit. An improved Dijkstra algorithm is used to generate evacuation zones according to the proximity relationship and the occupancy time of different exits. The strategy of waiting at the starting point is adopted to ensure that all evacuees are free from congestion during the escape process. In addition, the method of group merging is proposed to further increase the balance among all zones during the partitioning process. The objectives of the proposed algorithm include minimizing the TET of all evacuees, the path length of each escape group, avoiding congestion during the escape process. The experimental results show that the proposed algorithm effectively reduces TET and the path length of groups compared with existing algorithms, which improves the efficiency of evacuation and utilization of all exits and can be applied to the various distribution and density of evacuees.
A Process-Oriented Approach to Identify Evolutions of Sea Surface Temperature Anomalies with a Time-Series of a Raster Dataset
Authors: Li Lianwei , Xu Yangfeng , Xue Cunjin , Fu Yuxuan , Zhang Yuanyu
Published: July 2021

It is important to consider where, when, and how the evolution of sea surface temperature anomalies (SSTA) plays significant roles in regional or global climate changes. In the comparison of where and when, there is a great challenge in clearly describing how SSTA evolves in space and time. In light of the evolution from generation, through development, and to the dissipation of SSTA, this paper proposes a novel approach to identifying an evolution of SSTA in space and time from a time-series of a raster dataset. This method, called PoAIES, includes three key steps. Firstly, a cluster-based method is enhanced to explore spatiotemporal clusters of SSTA, and each cluster of SSTA at a time snapshot is taken as a snapshot object of SSTA. Secondly, the spatiotemporal topologies of snapshot objects of SSTA at successive time snapshots are used to link snapshot objects of SSTA into an evolution object of SSTA, which is called a process object. Here, a linking threshold is automatically determined according to the overlapped areas of the snapshot objects, and only those snapshot objects that meet the specified linking threshold are linked together into a process object. Thirdly, we use a graph-based model to represent a process object of SSTA. A node represents a snapshot object of SSTA, and an edge represents an evolution between two snapshot objects. Using a number of child nodes from an edge’s parent node and a number of parent nodes from the edge’s child node, a type of edge (an evolution relationship) is identified, which shows its development, splitting, merging, or splitting/merging. Finally, an experiment on a simulated dataset is used to demonstrate the effectiveness and the advantages of PoAIES, and a real dataset of satellite-SSTA is used to verify the rationality of PoAIES with the help of ENSO’s relevant knowledge, which may provide new references for global change research.
Identification of Rhythmically Expressed LncRNAs in the Zebrafish Pineal Gland and Testis
Authors: Mishra Shital Kumar , Liu Taole , Wang Han
Published: July 2021

Noncoding RNAs have been known to contribute to a variety of fundamental life processes, such as development, metabolism, and circadian rhythms. However, much remains unrevealed in the huge noncoding RNA datasets, which require further bioinformatic analysis and experimental investigation—and in particular, the coding potential of lncRNAs and the functions of lncRNA-encoded peptides have not been comprehensively studied to date. Through integrating the time-course experimentation with state-of-the-art computational techniques, we studied tens of thousands of zebrafish lncRNAs from our own experiments and from a published study including time-series transcriptome analyses of the testis and the pineal gland. Rhythmicity analysis of these data revealed approximately 700 rhythmically expressed lncRNAs from the pineal gland and the testis, and their GO, COG, and KEGG pathway functions were analyzed. Comparative and conservative analyses determined 14 rhythmically expressed lncRNAs shared between both the pineal gland and the testis, and 15 pineal gland lncRNAs as well as 3 testis lncRNAs conserved among zebrafish, mice, and humans. Further, we computationally analyzed the conserved lncRNA-encoded peptides, and revealed three pineal gland and one testis lncRNA-encoded peptides conserved among these three species, which were further investigated for their three-dimensional (3D) structures and potential functions. Our computational findings provided novel annotations and regulatory mechanisms for hundreds of rhythmically expressed pineal gland and testis lncRNAs in zebrafish, and set the stage for their experimental studies in the near future.
Oral Selective Estrogen Receptor Degraders (SERDs) as a Novel Breast Cancer Therapy: Present and Future from a Clinical Perspective
Authors: Hernando Cristina , Ortega-Morillo Belén , Tapia Marta , Moragón Santiago , Martínez María Teresa , Eroles Pilar , Garrido-Cano Iris , Adam-Artigues Anna , Lluch Ana , Bermejo Begoña , Cejalvo Juan Miguel
Published: July 2021

Estrogen receptor-positive (ER+) is the most common subtype of breast cancer. Endocrine therapy is the fundamental treatment against this entity, by directly or indirectly modifying estrogen production. Recent advances in novel compounds, such as cyclin-dependent kinase 4/6 inhibitors (CDK4/6i), or phosphoinositide 3-kinase (PI3K) inhibitors have improved progression-free survival and overall survival in these patients. However, some patients still develop endocrine resistance after or during endocrine treatment. Different underlying mechanisms have been identified as responsible for endocrine treatment resistance, where ESR1 gene mutations are one of the most studied, outstanding from others such as somatic alterations, microenvironment involvement and epigenetic changes. In this scenario, selective estrogen receptor degraders/downregulators (SERD) are one of the weapons currently in research and development against aromatase inhibitor- or tamoxifen-resistance. The first SERD to be developed and approved for ER+ breast cancer was fulvestrant, demonstrating also interesting activity in ESR1 mutated patients in the second line treatment setting. Recent investigational advances have allowed the development of new oral bioavailable SERDs. This review describes the evolution and ongoing studies in SERDs and new molecules against ER, with the hope that these novel drugs may improve our patients’ future landscape.
LncRNA MORT (ZNF667-AS1) in Cancer—Is There a Possible Role in Gynecological Malignancies?
Authors: Di Fiore Riccardo , Suleiman Sherif , Drago-Ferrante Rosa , Felix Ana , O’Toole Sharon A. , O’Leary John J. , Ward Mark P. , Beirne James , Yordanov Angel , Vasileva-Slaveva Mariela , Subbannayya Yashwanth , Pentimalli Francesca , Giordano Antonio , Calleja-Agius Jean
Published: July 2021

Gynecological cancers (GCs) are currently among the major threats to female health. Moreover, there are different histologic subtypes of these cancers, which are defined as ‘rare’ due to an annual incidence of <6 per 100,000 women. The majority of these tend to be associated with a poor prognosis. Long non-coding RNAs (lncRNAs) play a critical role in the normal development of organisms as well as in tumorigenesis. LncRNAs can be classified into tumor suppressor genes or oncogenes, depending on their function within the cellular context and the signaling pathways in which they are involved. These regulatory RNAs are potential therapeutic targets for cancer due to their tissue and tumor specificity. However, there still needs to be a deeper understanding of the mechanisms by which lncRNAs are involved in the regulation of numerous biological functions in humans, both in normal health and disease. The lncRNA Mortal Obligate RNA Transcript (MORT; alias ZNF667-AS1) has been identified as a tumor-related lncRNA. ZNF667-AS1 gene, located in the human chromosome region 19q13.43, has been shown to be silenced by DNA hypermethylation in several cancers. In this review, we report on the biological functions of ZNF667-AS1 from recent studies and describe the regulatory functions of ZNF667-AS1 in human disease, including cancer. Furthermore, we discuss the emerging insights into the potential role of ZNF667-AS1 as a biomarker and novel therapeutic target in cancer, including GCs (ovarian, cervical, and endometrial cancers).
Biochemical Studies of Mitochondrial Malate: Quinone Oxidoreductase from Toxoplasma gondii
Authors: Acharjee Rajib , Talaam Keith , Hartuti Endah , Matsuo Yuichi , Sakura Takaya , Gloria Bundutidi , Hidano Shinya , Kido Yasutoshi , Mori Mihoko , Shiomi Kazuro , Sekijima Masakazu , Nozaki Tomoyoshi , Umeda Kousuke , Nishikawa Yoshifumi , Hamano Shinjiro , Kita Kiyoshi , Inaoka Daniel
Published: July 2021

Toxoplasma gondii is a protozoan parasite that causes toxoplasmosis and infects almost one-third of the global human population. A lack of effective drugs and vaccines and the emergence of drug resistant parasites highlight the need for the development of new drugs. The mitochondrial electron transport chain (ETC) is an essential pathway for energy metabolism and the survival of T. gondii. In apicomplexan parasites, malate:quinone oxidoreductase (MQO) is a monotopic membrane protein belonging to the ETC and a key member of the tricarboxylic acid cycle, and has recently been suggested to play a role in the fumarate cycle, which is required for the cytosolic purine salvage pathway. In T. gondii, a putative MQO (TgMQO) is expressed in tachyzoite and bradyzoite stages and is considered to be a potential drug target since its orthologue is not conserved in mammalian hosts. As a first step towards the evaluation of TgMQO as a drug target candidate, in this study, we developed a new expression system for TgMQO in FN102(DE3)TAO, a strain deficient in respiratory cytochromes and dependent on an alternative oxidase. This system allowed, for the first time, the expression and purification of a mitochondrial MQO family enzyme, which was used for steady-state kinetics and substrate specificity analyses. Ferulenol, the only known MQO inhibitor, also inhibited TgMQO at IC50 of 0.822 μM, and displayed different inhibition kinetics compared to Plasmodium falciparum MQO. Furthermore, our analysis indicated the presence of a third binding site for ferulenol that is distinct from the ubiquinone and malate sites.
Suppression of Pain in the Late Phase of Chronic Trigeminal Neuropathic Pain Failed to Rescue the Decision-Making Deficits in Rats
Authors: Murugappan Suresh Kanna , Xie Li , Wong Heung Yan , Iqbal Zafar , Lei Zhuogui , Ramkrishnan Aruna Surendran , Li Ying
Published: July 2021

Trigeminal neuropathic pain (TNP) led to vital cognitive functional deficits such as impaired decision-making abilities in a rat gambling task. Chronic TNP caused hypomyelination in the anterior cingulate cortex (ACC) associated with decreased synchronization between ACC spikes and basal lateral amygdala (BLA) theta oscillations. The aim of this study was to investigate the effect of pain suppression on cognitive impairment in the early or late phases of TNP. Blocking afferent signals with a tetrodotoxin (TTX)-ELVAX implanted immediately following nerve lesion suppressed the allodynia and rescued decision-making deficits. In contrast, the TTX used at a later phase could not suppress the allodynia nor rescue decision-making deficits. Intra-ACC administration of riluzole reduced the ACC neural sensitization but failed to restore ACC-BLA spike-field phase synchrony during the late stages of chronic neuropathic pain. Riluzole suppressed allodynia but failed to rescue the decision-making deficits during the late phase of TNP, suggesting that early pain relief is important for recovering from pain-related cognitive impairments. The functional disturbances in ACC neural circuitry may be relevant causes for the deficits in decision making in the chronic TNP state.
Cytokine-Laden Extracellular Vesicles Predict Patient Prognosis after Cerebrovascular Accident
Authors: Fringuello Anthony , Tatman Philip D. , Wroblewski Tadeusz , Thompson John A. , Yu Xiaoli , Lillehei Kevin O. , Kowalski Robert G. , Graner Michael W.
Published: July 2021

Background: A major contributor to disability after hemorrhagic stroke is secondary brain damage induced by the inflammatory response. Following stroke, global increases in numerous cytokines—many associated with worse outcomes—occur within the brain, cerebrospinal fluid, and peripheral blood. Extracellular vesicles (EVs) may traffic inflammatory cytokines from damaged tissue within the brain, as well as peripheral sources, across the blood–brain barrier, and they may be a critical component of post-stroke neuroinflammatory signaling. Methods: We performed a comprehensive analysis of cytokine concentrations bound to plasma EV surfaces and/or sequestered within the vesicles themselves. These concentrations were correlated to patient acute neurological condition by the Glasgow Coma Scale (GCS) and to chronic, long-term outcome via the Glasgow Outcome Scale-Extended (GOS-E). Results: Pro-inflammatory cytokines detected from plasma EVs were correlated to worse outcomes in hemorrhagic stroke patients. Anti-inflammatory cytokines detected within EVs were still correlated to poor outcomes despite their putative neuroprotective properties. Inflammatory cytokines macrophage-derived chemokine (MDC/CCL2), colony stimulating factor 1 (CSF1), interleukin 7 (IL7), and monokine induced by gamma interferon (MIG/CXCL9) were significantly correlated to both negative GCS and GOS-E when bound to plasma EV membranes. Conclusions: These findings correlate plasma-derived EV cytokine content with detrimental outcomes after stroke, highlighting the potential for EVs to provide cytokines with a means of long-range delivery of inflammatory signals that perpetuate neuroinflammation after stroke, thus hindering recovery.
Cross-Recognition of Promoters by the Nine SigB Homologues Present in Streptomyces coelicolor A3(2)
Authors: Sevcikova Beatrica , Rezuchova Bronislava , Mazurakova Vladimira , Homerova Dagmar , Novakova Renata , Feckova Lubomira , Kormanec Jan
Published: July 2021

In contrast to Bacillus subtilis, Streptomyces coelicolor A3(2) contains nine homologues of stress response sigma factor SigB with a major role in differentiation and osmotic stress response. The aim of this study was to further characterize these SigB homologues. We previously established a two-plasmid system to identify promoters recognized by sigma factors and used it to identify promoters recognized by the three SigB homologues, SigF, SigG, and SigH from S. coelicolor A3(2). Here, we used this system to identify 14 promoters recognized by SigB. The promoters were verified in vivo in S. coelicolor A3(2) under osmotic stress conditions in sigB and sigH operon mutants, indicating some cross-recognition of these promoters by these two SigB homologues. This two-plasmid system was used to examine the recognition of all identified SigB-, SigF-, SigG-, and SigH-dependent promoters with all nine SigB homologues. The results confirmed this cross-recognition. Almost all 24 investigated promoters were recognized by two or more SigB homologues and data suggested some distinguishing groups of promoters recognized by these sigma factors. However, analysis of the promoters did not reveal any specific sequence characteristics for these recognition groups. All promoters showed high similarity in the -35 and -10 regions. Immunoblot analysis revealed the presence of SigB under osmotic stress conditions and SigH during morphological differentiation. Together with the phenotypic analysis of sigB and sigH operon mutants in S. coelicolor A3(2), the results suggest a dominant role for SigB in the osmotic stress response and a dual role for SigH in the osmotic stress response and morphological differentiation. These data suggest a complex regulation of the osmotic stress response in relation to morphological differentiation in S. coelicolor A3(2).
Reference Gene Selection for Gene Expression Analyses in Mouse Models of Acute Lung Injury
Authors: Fragoulis Athanassios , Biller Kristina , Fragoulis Stephanie , Lex Dennis , Uhlig Stefan , Reiss Lucy Kathleen
Published: July 2021

qRT-PCR still remains the most widely used method for quantifying gene expression levels, although newer technologies such as next generation sequencing are becoming increasingly popular. A critical, yet often underappreciated, problem when analysing qRT-PCR data is the selection of suitable reference genes. This problem is compounded in situations where up to 25% of all genes may change (e.g., due to leukocyte invasion), as is typically the case in ARDS. Here, we examined 11 widely used reference genes for their suitability in commonly used models of acute lung injury (ALI): ventilator-induced lung injury (VILI), in vivo and ex vivo, lipopolysaccharide plus mechanical ventilation (MV), and hydrochloric acid plus MV. The stability of reference gene expression was determined using the NormFinder, BestKeeper, and geNorm algorithms. We then proceeded with the geNorm results because this is the only algorithm that provides the number of reference genes required to achieve normalisation. We chose interleukin-6 (Il-6) and C-X-C motif ligand 1 (Cxcl-1) as the genes of interest to analyse and demonstrate the impact of inappropriate normalisation. Reference gene stability differed between the ALI models and even within the subgroup of VILI models, no common reference gene index (RGI) could be determined. NormFinder, BestKeeper, and geNorm produced slightly different, but comparable results. Inappropriate normalisation of Il-6 and Cxcl1 gene expression resulted in significant misinterpretation in all four ALI settings. In conclusion, choosing an inappropriate normalisation strategy can introduce different kinds of bias such as gain or loss as well as under- or overestimation of effects, affecting the interpretation of gene expression data.
Histatin-1 Attenuates LPS-Induced Inflammatory Signaling in RAW264.7 Macrophages
Authors: Lee Sang Min , Son Kyung-No , Shah Dhara , Ali Marwan , Balasubramaniam Arun , Shukla Deepak , Aakalu Vinay Kumar
Published: July 2021

Macrophages play a critical role in the inflammatory response to environmental triggers, such as lipopolysaccharide (LPS). Inflammatory signaling through macrophages and the innate immune system are increasingly recognized as important contributors to multiple acute and chronic disease processes. Nitric oxide (NO) is a free radical that plays an important role in immune and inflammatory responses as an important intercellular messenger. In addition, NO has an important role in inflammatory responses in mucosal environments such as the ocular surface. Histatin peptides are well-established antimicrobial and wound healing agents. These peptides are important in multiple biological systems, playing roles in responses to the environment and immunomodulation. Given the importance of macrophages in responses to environmental triggers and pathogens, we investigated the effect of histatin-1 (Hst1) on LPS-induced inflammatory responses and the underlying molecular mechanisms in RAW264.7 (RAW) macrophages. LPS-induced inflammatory signaling, NO production and cytokine production in macrophages were tested in response to treatment with Hst1. Hst1 application significantly reduced LPS-induced NO production, inflammatory cytokine production, and inflammatory signaling through the JNK and NF-kB pathways in RAW cells. These results demonstrate that Hst1 can inhibit LPS-induced inflammatory mediator production and MAPK signaling pathways in macrophages.
Fluorescence Spectroscopic Analysis of ppGpp Binding to cAMP Receptor Protein and Histone-Like Nucleoid Structuring Protein
Authors: Duysak Taner , Tran Thanh Tuyen , Afzal Aqeel Rana , Jung Che-Hun
Published: July 2021

The cyclic AMP receptor protein (CRP) is one of the best-known transcription factors, regulating about 400 genes. The histone-like nucleoid structuring protein (H-NS) is one of the nucleoid-forming proteins and is responsible for DNA packaging and gene repression in prokaryotes. In this study, the binding of ppGpp to CRP and H-NS was determined by fluorescence spectroscopy. CRP from Escherichia coli exhibited intrinsic fluorescence at 341 nm when excited at 280 nm. The fluorescence intensity decreased in the presence of ppGpp. The dissociation constant of 35 ± 3 µM suggests that ppGpp binds to CRP with a similar affinity to cAMP. H-NS also shows intrinsic fluorescence at 329 nm. The fluorescence intensity was decreased by various ligands and the calculated dissociation constant for ppGpp was 80 ± 11 µM, which suggests that the binding site was occupied fully by ppGpp under starvation conditions. This study suggests the modulatory effects of ppGpp in gene expression regulated by CRP and H-NS. The method described here may be applicable to many other proteins.
DNA Dynamics under Periodic Force Effects
Authors: Svidlov Alexander , Drobotenko Mikhail , Basov Alexander , Gerasimenko Eugeny , Malyshko Vadim , Elkina Anna , Baryshev Mikhail , Dzhimak Stepan
Published: July 2021

The sensitivity of DNA to electromagnetic radiation in different ranges differs depending on various factors. The aim of this study was to examine the molecular dynamics of DNA under the influence of external periodic influences with different frequencies. In the present paper, within the framework of a mechanical model without simplifications, we investigated the effect of various frequencies of external periodic action in the range from 1011 s−1 to 108 s−1 on the dynamics of a DNA molecule. It was shown that under the influence of an external periodic force, a DNA molecule can perform oscillatory movements with a specific frequency characteristic of this molecule, which differs from the frequency of the external influence ω. It was found that the frequency of such specific vibrations of a DNA molecule depends on the sequence of nucleotides. Using the developed mathematical model describing the rotational motion of the nitrogenous bases around the sugar–phosphate chain, it is possible to calculate the frequency and amplitude of the oscillations of an individual DNA area. Such calculations can find application in the field of molecular nanotechnology.
Low-Energy Electron Damage to Condensed-Phase DNA and Its Constituents
Authors: Gao Yingxia , Zheng Yi , Sanche Léon
Published: July 2021

The complex physical and chemical reactions between the large number of low-energy (0–30 eV) electrons (LEEs) released by high energy radiation interacting with genetic material can lead to the formation of various DNA lesions such as crosslinks, single strand breaks, base modifications, and cleavage, as well as double strand breaks and other cluster damages. When crosslinks and cluster damages cannot be repaired by the cell, they can cause genetic loss of information, mutations, apoptosis, and promote genomic instability. Through the efforts of many research groups in the past two decades, the study of the interaction between LEEs and DNA under different experimental conditions has unveiled some of the main mechanisms responsible for these damages. In the present review, we focus on experimental investigations in the condensed phase that range from fundamental DNA constituents to oligonucleotides, synthetic duplex DNA, and bacterial (i.e., plasmid) DNA. These targets were irradiated either with LEEs from a monoenergetic-electron or photoelectron source, as sub-monolayer, monolayer, or multilayer films and within clusters or water solutions. Each type of experiment is briefly described, and the observed DNA damages are reported, along with the proposed mechanisms. Defining the role of LEEs within the sequence of events leading to radiobiological lesions contributes to our understanding of the action of radiation on living organisms, over a wide range of initial radiation energies. Applications of the interaction of LEEs with DNA to radiotherapy are briefly summarized.
Cold Atmospheric Plasma Changes the Amino Acid Composition of Solutions and Influences the Anti-Tumor Effect on Melanoma Cells
Authors: Arndt Stephanie , Fadil Fadi , Dettmer Katja , Unger Petra , Boskovic Marko , Samol Claudia , Bosserhoff Anja-Katrin , Zimmermann Julia L. , Gruber Michael , Gronwald Wolfram , Karrer Sigrid
Published: July 2021

Cold Atmospheric Plasma (CAP) is an ionized gas near room temperature. Its anti-tumor effect can be transmitted either by direct treatment or mediated by a plasma-treated solution (PTS), such as treated standard cell culture medium, which contains different amino acids, inorganic salts, vitamins and other substances. Despite extensive research, the active components in PTS and its molecular or cellular mechanisms are not yet fully understood. The purpose of this study was the measurement of the reactive species in PTS and their effect on tumor cells using different plasma modes and treatment durations. The PTS analysis yielded mode- and dose-dependent differences in the production of reactive oxygen and nitrogen species (RONS), and in the decomposition and modification of the amino acids Tyrosine (Tyr) and Tryptophan (Trp). The Trp metabolites Formylkynurenine (FKyn) and Kynurenine (Kyn) were produced in PTS with the 4 kHz (oxygen) mode, inducing apoptosis in Mel Im melanoma cells. Nitrated derivatives of Trp and Tyr were formed in the 8 kHz (nitrogen) mode, elevating the p16 mRNA expression and senescence-associated ß-Galactosidase staining. In conclusion, the plasma mode has a strong impact on the composition of the active components in PTS and affects its anti-tumor mechanism. These findings are of decisive importance for the development of plasma devices and the effectiveness of tumor treatment.
The Role of Supplementation with Natural Compounds in Post-Stroke Patients
Authors: Cichon Natalia , Saluk-Bijak Joanna , Miller Elzbieta , Gorniak Leslaw , Redlicka Justyna , Niwald Marta , Bijak Michal
Published: July 2021

Malnutrition is a serious problem in post-stroke patients. Importantly, it intensifies with hospitalization, and is related to both somatic and psychological reasons, as well as is associated with the insufficient knowledge of people who accompany the patient. Malnutrition is a negative prognostic factor, leading to a reduction in the quality of life. Moreover, this condition significantly extends hospitalization time, increases the frequency of treatment in intensive care units, and negatively affects the effectiveness of rehabilitation. Obtaining growing data on the therapeutic effectiveness of new compounds of natural origin is possible through the use of pharmacodynamic and analytical methods to assess their therapeutic properties. The proper supply of nutrients, as well as compounds of natural origin, is an important element of post-stroke therapy, due to their strong antioxidant, anti-inflammatory, neuroprotective and neuroplasticity enhancing properties. Taking the above into account, in this review we present the current state of knowledge on the benefits of using selected substances of natural origin in patients after cerebral stroke.
Tying Small Changes to Large Outcomes: The Cautious Promise in Incorporating the Microbiome into Immunotherapy
Authors: Chau Justin , Zhang Jun
Published: July 2021

The role of the microbiome in immunology is a rapidly burgeoning topic of study. Given the increasing use of immune checkpoint inhibitor (ICI) therapy in cancers, along with the recognition that carcinogenesis has been linked to dysregulations of the immune system, much attention is now directed at potentiation of ICI efficacy, as well as minimizing the incidence of treatment-associated immune-related adverse events (irAEs). We provide an overview of the major research establishing links between the microbiome to tumorigenesis, chemotherapy and radiation potentiation, and ICI efficacy and irAE development.
A Comprehensive Review on Network Protocol Design for Autonomic Internet of Things
Authors: Sari Riri Fitri , Rosyidi Lukman , Susilo Bambang , Asvial Muhamad
Published: July 2021

The autonomic Internet of Things is the creation of self-management capability in the Internet of Things system by embedding some autonomic properties, with the goal of freeing humans from all detail of the operation and management of the system. At same time, this provides a system to always operate on the best performance. This paper presents a review of the recent studies related to the design of network communication protocol, which can support autonomic Internet of Things. Many of the studies come from the research and development in Wireless Sensor Network protocols, as it becomes one of the key technologies for the Internet of Things. The identified autonomic properties are self-organization, self-optimization, and self-protection. We review some protocols with the objective of energy consumption reduction and energy harvesting awareness, as it can support the self-energy-awareness property. As the result, the protocol designs are mapped according to each autonomic property supported, including protocols for MAC layer, protocols for clustering, protocols for routing, and protocols for security. This can be used to map the advances of communication protocol research for the autonomic Internet of Things and to identify the opportunities for future research.
Assessing the Potential of Inoculative Field Releases of Telenomus remus to Control Spodoptera frugiperda in Ghana
Authors: Agboyi Lakpo Koku , Layodé Babatoundé Ferdinand Rodolphe , Fening Ken Okwae , Beseh Patrick , Clottey Victor Attuquaye , Day Roger , Kenis Marc , Babendreier Dirk
Published: July 2021

In response to the threat caused by the fall armyworm to African maize farmers, we conducted a series of field release studies with the egg parasitoid Telenomus remus in Ghana. Three releases of ≈15,000 individuals each were conducted in maize plots of 0.5 ha each in the major and minor rainy seasons of 2020, and compared to no-release control plots as well as to farmer-managed plots with chemical pest control. No egg mass parasitism was observed directly before the first field release. Egg mass parasitism reached 33% in the T. remus release plot in the major rainy season, while 72–100% of egg masses were parasitized in the minor rainy season, during which pest densities were much lower. However, no significant difference in egg mass parasitism was found among the T. remus release plots, the no-release control plots and the farmer-managed plots. Similarly, no significant decrease in larval numbers or plant damage was found in the T. remus release fields compared to the no-release plots, while lower leaf and tassel damage was observed in farmer-managed plots. Larval parasitism due to other parasitoids reached 18–42% in the major rainy season but was significantly lower in the minor rainy season, with no significant differences among treatments. We did not observe significant differences in cob damage or yield among the three treatments. However, the lack of any significant differences between the release and no-release plots, which may be attributed to parasitoid dispersal during the five weeks of observation, would require further studies to confirm. Interestingly, a single application of Emamectin benzoate did not significantly affect the parasitism rates of T. remus and, thus, merits further investigation in the context of developing IPM strategies against FAW.
Two Complete Mitochondrial Genomes of Mileewinae (Hemiptera: Cicadellidae) and a Phylogenetic Analysis
Authors: Yu Tinghao , Zhang Yalin
Published: July 2021

More studies are using mitochondrial genomes of insects to explore the sequence variability, evolutionary traits, monophyly of groups and phylogenetic relationships. Controversies remain on the classification of the Mileewinae and the phylogenetic relationships between Mileewinae and other subfamilies remain ambiguous. In this study, we present two newly completed mitogenomes of Mileewinae (Mileewa rufivena Cai and Kuoh 1997 and Ujna puerana Yang and Meng 2010) and conduct comparative mitogenomic analyses based on several different factors. These species have quite similar features, including their nucleotide content, codon usage of protein genes and the secondary structure of tRNA. Gene arrangement is identical and conserved, the same as the putative ancestral pattern of insects. All protein-coding genes of U. puerana began with the start codon ATN, while 5 Mileewa species had the abnormal initiation codon TTG in ND5 and ATP8. Moreover, M. rufivena had an intergenic spacer of 17 bp that could not be found in other mileewine species. Phylogenetic analysis based on three datasets (PCG123, PCG12 and AA) with two methods (maximum likelihood and Bayesian inference) recovered the Mileewinae as a monophyletic group with strong support values. All results in our study indicate that Mileewinae has a closer phylogenetic relationship to Typhlocybinae compared to Cicadellinae. Additionally, six species within Mileewini revealed the relationship (U. puerana + (M. ponta + (M. rufivena + M. alara) + (M. albovittata + M. margheritae))) in most of our phylogenetic trees. These results contribute to the study of the taxonomic status and phylogenetic relationships of Mileewinae.
High Post-Procedural Transvalvular Gradient or Delayed Mean Gradient Increase after Transcatheter Aortic Valve Implantation: Incidence, Prognosis and Associated Variables. The FRANCE-2 Registry
Authors: Didier Romain , Benic Clément , Nasr Bahaa , Le Ven Florent , Hannachi Sinda , Eltchaninoff Hélène , Koifman Edward , Donzeau-Gouge Patrick , Fajadet Jean , Leprince Pascal , Leguerrier Alain , Lièvre Michel , Prat Alain , Teiger Emmanuel , Lefevre Thierry , Cuisset Thomas , Le Breton Herve , Auffret Vincent , Iung Bernard , Gilard Martine
Published: July 2021

Mean Gradient (MG) elevation can be detected immediately after transcatheter aortic valve implantation (TAVI) or secondarily during follow-up. Comparisons and interactions between these two parameters and their impact on outcomes have not previously been investigated. This study aimed to identify incidence, influence on prognosis, and parameters associated with immediate high post-procedural mean transvalvular gradient (PPMG) and delayed mean gradient increase (6 to 12 months after TAVI, DMGI) in the FRANCE 2 (French Aortic National CoreValve and Edwards 2) registry. The registry includes all consecutive symptomatic patients with severe aortic stenosis who have undergone TAVI. Three groups were analyzed: (1) PPMG < 20 mmHg without DMGI > 10 mmHg (control); (2) PPMG < 20 mmHg with DMGI > 10 mmHg (Group 1); and (3) PPMG ≥ 20 mmHg (Group 2). From January 2010 to January 2012, 4201 consecutive patients were prospectively enrolled in the registry. Controls comprised 2078 patients. In Group 1(n = 131 patients), DMGI exceeded 10 mmHg in 5.6%, and was not associated with greater 4-years mortality than in controls (32.6% vs. 40.1%, p = 0.27). In Group 2 (n = 144 patients), PPMG was at least 20 mmHg in 6.1% and was associated with higher 4-year mortality (48.7% versus 40.1%, p = 0.005). A total of two-thirds of the patients with PPMG ≥ 20 mmHg had MG < 20 mmHg at 1 year, with mortality similar to the controls (39.2% vs. 40.1%, p = 0.73). Patients with PPMG > 20 mmHg 1 year post-TAVI had higher 4-years mortality than the general population of the registry, unlike patients with MG normalization.
Air Pollutants’ Concentrations Are Associated with Increased Number of RSV Hospitalizations in Polish Children
Authors: Wrotek August , Badyda Artur , Czechowski Piotr O. , Owczarek Tomasz , Dąbrowiecki Piotr , Jackowska Teresa
Published: July 2021

Respiratory syncytial virus (RSV) contributes significantly to pediatric hospitalizations. An association between air pollution and an increased number of RSV cases has been suggested. We sought to evaluate the short-term impact of air pollutants on RSV hospitalizations in Polish children in the period 2010–2019. Daily concentrations of PM10 and PM2.5 (particulate matter with an aerodynamic diameter less than or equal to 10 μm and 2.5 μm, respectively) and nitrogen dioxide (NO2) were analyzed in general regression models (GRM) to establish their influence and full interaction scheme. Significant seasonal and annual periodicity among 53,221 hospitalizations was observed; finally, data from the 2012–2019 RSV high-risk seasons created models for seven agglomerations. The addition of PM2.5, PM10, and NO2 to the basic model for RSV seasonality explained 23% (4.9–31%, univariate model) to 31.4% (8.4–31%, multivariate model) of the variance in RSV hospitalizations. A 10 μg/m3 increase in PM2.5, PM10, and NO2 concentrations was associated with 0.134 (0.087–0.16), 0.097 (0.031–0.087), and 0.212 (0.04–0.29) average increases in hospitalizations, respectively. In the multivariate models, PM2.5, PM10, and NO2 alone, as well as PM2.5–NO2, PM2.5–PM10, and PM10–NO2 interactions, were associated with hospitalizations in some of the locations, while the metaregression showed statistically significant interactions between each of the pollutants, and between the pollutants and the year of the study. The inclusion of PM2.5, PM10, and NO2 in GRM explains a significant number of RSV hospitalizations. The pollutants act alone and interact together in a varied manner. Reducing air contamination might decrease the costs of hospital healthcare.
Characterization and Treatment Responsiveness of Genetically Engineered Ornithine Transcarbamylase-Deficient Pig
Authors: Enosawa Shin , Hsu Huai-Che , Yanagi Yusuke , Matsunari Hitomi , Uchikura Ayuko , Nagashima Hiroshi
Published: July 2021

To develop novel medical technologies, pig disease models are invaluable especially in the final stages of translational research. Recently, we established a genetically engineered ornithine transcarbamylase-deficient (OTCD) pig strain. Here, we report its characterization and treatment responsiveness. OTCD pigs were obtained by mating an OTCD carrier female (OTC-Xc.186_190delXWT) with a wild-type male. Due to the X-linked recessive mode of inheritance, the disease phenotype emerged only in males. Medication with nitrogen-scavenging agents was based on a clinical protocol. OTCD pigs were born smaller than their wild-type and carrier littermates, showing anemia and faltering. Biochemically, high levels of urinary orotic acid and loss of OTC activity were observed. The natural life course of OTCD pigs was characterized by a decrease in arterial percentage saturation of oxygen and body temperature, as well as an increase in blood ammonia levels; the pigs died in 24.0 ± 5.0 h (mean ± SD, n = 6). The established standard medication composed with nitrogen-scavenging agents and transfusion nearly doubled the survival time to 42.4 ± 13.7 h (n = 6). Our OTCD pig model appropriately mimicked the human pathology. Along with established protocols in handling and medication, this is a first step in developing a large animal disease model that is useful for translational research into novel medical technologies, such as cell transplantation and gene therapy, as well as in relation to urea cycle disorder.
Pulmonary Complications in Hematopoietic Stem Cell Transplant Recipients—A Clinician Primer
Authors: Astashchanka Anna , Ryan Joseph , Lin Erica , Nokes Brandon , Jamieson Catriona , Kligerman Seth , Malhotra Atul , Mandel Jess , Joshua Jisha
Published: July 2021

Hematopoietic stem cell transplants (HSCT) are becoming more widespread as a result of optimization of conditioning regimens and prevention of short-term complications with prophylactic antibiotics and antifungals. However, pulmonary complications post-HSCT remain a leading cause of morbidity and mortality and are a challenge to clinicians in both diagnosis and treatment. This comprehensive review provides a primer for non-pulmonary healthcare providers, synthesizing the current evidence behind common infectious and non-infectious post-transplant pulmonary complications based on time (peri-engraftment, early post-transplantation, and late post-transplantation). Utilizing the combination of timing of presentation, clinical symptoms, histopathology, and radiographic findings should increase rates of early diagnosis, treatment, and prognostication of these severe illness states.