bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Study on Different Remediation Strategies Applied in Petroleum-Contaminated Soils
Authors: Cui Jia-Qi , He Qing-Sheng , Liu Ming-Hui , Chen Hong , Sun Ming-Bo , Wen Jian-Ping
Published: March 2020

Due to the increasing pollution by petroleum hydrocarbons (PHs), it is an important task to develop eco-friendly and highly efficient methods for remediating petroleum-contaminated soils. In this study, bioremediation technology was applied to remediate PHs contaminated soils, and the bacterial community structure and physicochemical characteristics of the soil treated using different bioremediation regimens were analyzed. Compared with the control condition (S0), the PHs removal efficiency of biostimulation (S2) and bioaugmentation (S3) was increased significantly. Combined biostimulation with bioaugmentation (S4) had the highest PHs removal efficiency, up to 60.14 ± 4.12%. Among all the selected remediation strategies (S1–S4, S1: soil moisture content: 25–30%), the bacterial alpha-diversity was higher than in S0. The genera Acinetobacter, Escherichia-Shigella, Bacteroides, Microbacterium, and Parabacteroides were found to greatly contribute to PHs’ degradation. In the group S4, the PH-degraders and soil enzyme activity were higher than in the other remediation regimens, and these indices gradually decreased in the mid-to-later periods of all remediation tests. Additionally, the abundance of alkB and nah genes was increased by improving the environmental condition of the microorganism communities. Redundancy analysis (RDA) revealed that the total nitrogen (TN) and total phosphorus (TP) had a positive correlation with total PHs degradation. This study offers insights into the microbial community response to environmental factors during bioremediation, which shows a promoting effect in enhancing the efficiency of PHs remediation.
Inter-Rater Reliability of Ergonomic Work Demands for Childcare Workers Using the Observation Instrument TRACK
Authors: Svendsen Malene Jagd , Hendriksen Peter Fjeldstad , Schmidt Kathrine Greby , Stochkendahl Mette Jensen , Rasmussen Charlotte Nørregaard , Holtermann Andreas
Published: March 2020

The aim of this study is to evaluate the inter-rater reliability of a newly developed instrument-TRACK (observaTion woRk demAnds Childcare worK) for observations of ergonomic work demands in childcare work. Two trained raters conducted thirty hours of concurrent observation of fifteen childcare workers in three different day nurseries. Inter-rater reliability of ergonomic work demands was evaluated using Gwet’s Agreement Coefficient (AC1) and interpreted by the Landis and Koch benchmark scale. Twenty ergonomic work demand items were evaluated. Inter-rater reliability was ‘almost perfect’ for nine items (AC1 0.81–1.00), ‘substantial’ for four items (AC1 0.61–0.80), ‘moderate’ for four items (AC1 0.41–0.60), ‘fair’ for two items (AC1 0.21–0.40), and ‘slight’ (AC1 0.00–0.20) for one item. No items had ‘poor’ (AC1 < 0.00) agreement. The instrument is reliable for assessing ergonomic work demands in childcare in real-life settings.
The Effects of Risk Perceptions Related to Particulate Matter on Outdoor Activity Satisfaction in South Korea
Authors: Kim Bomi , Yoon Eun Joo , Kim Songyi , Lee Dong Kun
Published: March 2020

In recent years, the Korean public has become aware of the form of air pollution known as particulate matter, with a consequent growth of public anxiety causing a negative risk perception about outdoor activity. This study aims at determining the causal relationship between risk perceptions about particulate matter and outdoor activity satisfaction in South Korea. An Internet survey was conducted with 412 people, and a structural equation model was used to perform confirmatory factor analysis. The statistically significant results show that the perceived risk of particulate matter is higher when people do not show interest in or trust public opinion or policy on the subject. This increases people’s perceptions of health risks, which in turn lowers their satisfaction with outdoor activity. Although trust levels in public opinion or policy had a positive impact on outdoor activity satisfaction, this was not statistically significant. These results are expected to contribute to risk communication guidelines in public opinion reporting and to the direction of environmental health policies in developing countries with high levels of air pollution, such as particulate matter.
Consumer Understanding of the Date of Minimum Durability of Food in Association with Quality Evaluation of Food Products After Expiration
Authors: Zielińska Dorota , Bilska Beata , Marciniak-Łukasiak Katarzyna , Łepecka Anna , Trząskowska Monika , Neffe-Skocińska Katarzyna , Tomaszewska Marzena , Szydłowska Aleksandra , Kołożyn-Krajewska Danuta
Published: March 2020

Food labelled with a “best before” date has a long shelf life. This study aimed to examine the respondents’ knowledge and understanding regarding the labelling on food products, as well as to assess the microbiological, physico–chemical and the sensory quality of selected durable food products on and after the date specified by the manufacturer. Two methods were used—a survey and laboratory tests. It was found that the majority of respondents have difficulty distinguishing and understanding the terms on the label and that a significant proportion of the respondents consume food products after the “best before” date. Laboratory tests of milk, pasta, mayonnaise and jam confirmed the microbiological safety of the products even six months after the “best before” date. Other features (texture, colour and sensory quality) slightly changed after one month for milk and mayonnaise (the colour had become more yellow) and after three months for pasta (its hardness had decreased) and jam (it had become browner). The possibility of extending the “best before” dates of selected durable foods could be considered, which could allow such products to legally be handed over to public benefit organisations, thereby reducing food wastage.
Glutathione–Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair
Authors: Di Giovanni Emilia , Buonvino Silvia , Amelio Ivano , Melino Sonia
Published: March 2020

The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S agents on the cell growth and differentiation of cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH–garlic conjugates (GSGa) on cMSC compared to other H2S-releasing agents, such as Na2S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell–cell adhesion and commitment to differentiation. These results highlight the effects of H2S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.
mTOR-Related Cell-Clearing Systems in Epileptic Seizures, an Update
Authors: Limanaqi Fiona , Biagioni Francesca , Busceti Carla Letizia , Fabrizi Cinzia , Frati Alessandro , Fornai Francesco
Published: March 2020

Recent evidence suggests that autophagy impairment is implicated in the epileptogenic mechanisms downstream of mTOR hyperactivation. This holds true for a variety of genetic and acquired epileptic syndromes besides malformations of cortical development which are classically known as mTORopathies. Autophagy suppression is sufficient to induce epilepsy in experimental models, while rescuing autophagy prevents epileptogenesis, improves behavioral alterations, and provides neuroprotection in seizure-induced neuronal damage. The implication of autophagy in epileptogenesis and maturation phenomena related to seizure activity is supported by evidence indicating that autophagy is involved in the molecular mechanisms which are implicated in epilepsy. In general, mTOR-dependent autophagy regulates the proliferation and migration of inter-/neuronal cortical progenitors, synapse development, vesicular release, synaptic plasticity, and importantly, synaptic clustering of GABAA receptors and subsequent excitatory/inhibitory balance in the brain. Similar to autophagy, the ubiquitin–proteasome system is regulated downstream of mTOR, and it is implicated in epileptogenesis. Thus, mTOR-dependent cell-clearing systems are now taking center stage in the field of epilepsy. In the present review, we discuss such evidence in a variety of seizure-related disorders and models. This is expected to provide a deeper insight into the molecular mechanisms underlying seizure activity.
Novel Genetically Encoded Bright Positive Calcium Indicator NCaMP7 Based on the mNeonGreen Fluorescent Protein
Authors: Subach Oksana M. , Sotskov Vladimir P. , Plusnin Viktor V. , Gruzdeva Anna M. , Barykina Natalia V. , Ivashkina Olga I. , Anokhin Konstantin V. , Nikolaeva Alena Y. , Korzhenevskiy Dmitry A. , Vlaskina Anna V. , Lazarenko Vladimir A. , Boyko Konstantin M. , Rakitina Tatiana V. , Varizhuk Anna M. , Pozmogova Galina E. , Podgorny Oleg V. , Piatkevich Kiryl D. , Boyden Edward S. , Subach Fedor V.
Published: March 2020

Green fluorescent genetically encoded calcium indicators (GECIs) are the most popular tool for visualization of calcium dynamics in vivo. However, most of them are based on the EGFP protein and have similar molecular brightnesses. The NTnC indicator, which is composed of the mNeonGreen fluorescent protein with the insertion of troponin C, has higher brightness as compared to EGFP-based GECIs, but shows a limited inverted response with an ΔF/F of 1. By insertion of a calmodulin/M13-peptide pair into the mNeonGreen protein, we developed a green GECI called NCaMP7. In vitro, NCaMP7 showed positive response with an ΔF/F of 27 and high affinity (Kd of 125 nM) to calcium ions. NCaMP7 demonstrated a 1.7-fold higher brightness and similar calcium-association/dissociation dynamics compared to the standard GCaMP6s GECI in vitro. According to fluorescence recovery after photobleaching (FRAP) experiments, the NCaMP7 design partially prevented interactions of NCaMP7 with the intracellular environment. The NCaMP7 crystal structure was obtained at 1.75 Å resolution to uncover the molecular basis of its calcium ions sensitivity. The NCaMP7 indicator retained a high and fast response when expressed in cultured HeLa and neuronal cells. Finally, we successfully utilized the NCaMP7 indicator for in vivo visualization of grating-evoked and place-dependent neuronal activity in the visual cortex and the hippocampus of mice using a two-photon microscope and an NVista miniscope, respectively.
Cell-Type Specific Metabolic Response of Cancer Cells to Curcumin
Authors: Mojzeš Anamarija , Tomljanović Marko , Milković Lidija , Novak Kujundžić Renata , Čipak Gašparović Ana , Gall Trošelj Koraljka
Published: March 2020

In order to support uncontrolled proliferation, cancer cells need to adapt to increased energetic and biosynthetic requirements. One such adjustment is aerobic glycolysis or the Warburg effect. It is characterized by increased glucose uptake and lactate production. Curcumin, a natural compound, has been shown to interact with multiple molecules and signaling pathways in cancer cells, including those relevant for cell metabolism. The effect of curcumin and its solvent, ethanol, was explored on four different cancer cell lines, in which the Warburg effect varied. Vital cellular parameters (proliferation, viability) were measured along with the glucose consumption and lactate production. The transcripts of pyruvate kinase 1 and 2 (PKM1, PKM2), serine hydroxymethyltransferase 2 (SHMT2) and phosphoglycerate dehydrogenase (PHGDH) were quantified with RT-qPCR. The amount and intracellular localization of PKM1, PKM2 and signal transducer and activator of transcription 3 (STAT3) proteins were analyzed by Western blot. The response to ethanol and curcumin seemed to be cell-type specific, with respect to all parameters analyzed. High sensitivity to curcumin was present in the cell lines originating from head and neck squamous cell carcinomas: FaDu, Detroit 562 and, especially, Cal27. Very low sensitivity was observed in the colon adenocarcinoma-originating HT-29 cell line, which retained, after exposure to curcumin, a higher levels of lactate production despite decreased glucose consumption. The effects of ethanol were significant.
Altered Growth and Envelope Properties of Polylysogens Containing Bacteriophage Lambda N−cI− Prophages
Authors: Barik Sailen , Mandal Nitai C.
Published: March 2020

The bacterial virus lambda (λ) is a temperate bacteriophage that can lysogenize host Escherichia coli (E. coli) cells. Lysogeny requires λ repressor, the cI gene product, which shuts off transcription of the phage genome. The λ N protein, in contrast, is a transcriptional antiterminator, required for expression of the terminator-distal genes, and thus, λ N mutants are growth-defective. When E. coli is infected with a λ double mutant that is defective in both N and cI (i.e., λN-cI-), at high multiplicities of 50 or more, it forms polylysogens that contain 20–30 copies of the λN-cI- genome integrated in the E. coli chromosome. Early studies revealed that the polylysogens underwent “conversion” to long filamentous cells that form tiny colonies on agar. Here, we report a large set of altered biochemical properties associated with this conversion, documenting an overall degeneration of the bacterial envelope. These properties reverted back to those of nonlysogenic E. coli as the metastable polylysogen spontaneously lost the λN-cI- genomes, suggesting that conversion is a direct result of the multiple copies of the prophage. Preliminary attempts to identify lambda genes that may be responsible for conversion ruled out several candidates, implicating a potentially novel lambda function that awaits further studies.
DROSHA-Dependent miRNA and AIM2 Inflammasome Activation in Idiopathic Pulmonary Fibrosis
Authors: Cho Soo Jung , Lee Mihye , Stout-Delgado Heather W. , Moon Jong-Seok
Published: March 2020

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease. Chronic lung inflammation is linked to the pathogenesis of IPF. DROSHA, a class 2 ribonuclease III enzyme, has an important role in the biogenesis of microRNA (miRNA). The function of miRNAs has been identified in the regulation of the target gene or protein related to inflammatory responses via degradation of mRNA or inhibition of translation. The absent-in-melanoma-2 (AIM2) inflammasome is critical for inflammatory responses against cytosolic double stranded DNA (dsDNA) from pathogen-associated molecular patterns (PAMPs) and self-DNA from danger-associated molecular patterns (DAMPs). The AIM2 inflammasome senses double strand DNA (dsDNA) and interacts with the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which recruits pro-caspase-1 and regulates the maturation and secretion of interleukin (IL)-1β and IL-18. A recent study showed that inflammasome activation contributes to lung inflammation and fibrogenesis during IPF. In the current review, we discuss recent advances in our understanding of the DROSHA–miRNA–AIM2 inflammasome axis in the pathogenesis of IPF.
A Survey of Antimicrobial Resistance Determinants in Category A Select Agents, Exempt Strains, and Near-Neighbor Species
Authors: Taitt Chris R. , Leski Tomasz A. , Chen Amy , Berk Kimberly L. , Dorsey Robert W. , Gregory Michael J. , Sozhamannan Shanmuga , Frey Kenneth G. , Dutt Diane L. , Vora Gary J.
Published: March 2020

A dramatic increase in global antimicrobial resistance (AMR) has been well documented. Of particular concern is the dearth of information regarding the spectrum and prevalence of AMR within Category A Select Agents. Here, we performed a survey of horizontally and vertically transferred AMR determinants among Category A agents and their near neighbors. Microarrays provided broad spectrum screening of 127 Francisella spp., Yersinia spp., and Bacillus spp. strains for the presence/absence of 500+ AMR genes (or families of genes). Detecting a broad variety of AMR genes in each genus, microarray analysis also picked up the presence of an engineered plasmid in a Y. pestis strain. High resolution melt analysis (HRMA) was also used to assess the presence of quinolone resistance-associated mutations in 100 of these strains. Though HRMA was able to detect resistance-causing point mutations in B. anthracis strains, it was not capable of discriminating these point mutations from other nucleotide substitutions (e.g., arising from sequence differences in near neighbors). Though these technologies are well-established, to our knowledge, this is the largest survey of Category A agents and their near-neighbor species for genes covering multiple mechanisms of AMR.
Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value
Authors: Fabisiewicz Anna , Szostakowska-Rodzos Malgorzata , Zaczek Anna J. , Grzybowska Ewa A.
Published: March 2020

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.
The Fate of Th17 Cells is Shaped by Epigenetic Modifications and Remodeled by the Tumor Microenvironment
Authors: Renaude Elodie , Kroemer Marie , Loyon Romain , Binda Delphine , Borg Christophe , Guittaut Michaël , Hervouet Eric , Peixoto Paul
Published: March 2020

Th17 cells represent a subset of CD4+ T cells characterized by the master transcription factor RORγt and the production of IL-17. Epigenetic modifications such as post-translational histone modifications and DNA methylation play a key role in Th17 cell differentiation and high plasticity. Th17 cells are highly recruited in many types of cancer and can be associated with good or bad prognosis. Here, we will review the remodeling of the epigenome induced by the tumor microenvironment, which may explain Th17 cell predominance. We will also discuss the promising treatment perspectives of molecules targeting epigenetic enzymes to remodel a Th17-enriched tumor microenvironment.
Genetic Identification and Transcriptome Analysis of Lintless and Fuzzless Traits in Gossypium arboreum L.
Authors: Liu Xueying , Moncuquet Philippe , Zhu Qian-Hao , Stiller Warwick , Zhang Zhengsheng , Wilson Iain
Published: March 2020

Cotton fibres, as single cells arising from the seed coat, can be classified as lint and fuzz according to their final length. Gossypium arboreum is a cultivated diploid cotton species and a potential donor of the A subgenome of the more widely grown tetraploid cottons. In this study, we performed genetic studies on one lintless and seven fuzzless G. arboreum accessions. Through association and genetic linkage analyses, a recessive locus on Chr06 containing GaHD-1 was found to be the likely gene underlying the lintless trait. GaHD-1 carried a mutation at a splicing acceptor site that resulted in alternative splicing and a deletion of 247 amino acid from the protein. The regions containing GaGIR1 and GaMYB25-like were found to be associated with fuzz development in G. arboreum, with the former being the major contributor. Comparative transcriptome analyses using 0-5 days post-anthesis (dpa) ovules from lintless, fuzzless, and normal fuzzy seed G. arboreum accessions revealed gene modules and hub genes potentially important for lint and fuzz initiation and development. Three significant modules and 26 hub genes associated with lint fibre initiation were detected by weighted gene co-expression network analysis. Similar analyses identified three vital modules and 10 hub genes to be associated with fuzz development. The findings in this study contribute to understanding the complex molecular mechanism(s) regulating fibre initiation and development and indicate that G. arboreum may have fibre developmental pathways different from tetraploid cotton. It also provides candidate genes for further investigation into modifying fibre development in G. arboreum.
Combined Effect of Light and Nutrients on the Micromorphology of the White rot Fungus Cerrena unicolor
Authors: Pawlik Anna , Jaszek Magdalena , Stefaniuk Dawid , Świderska-Burek Urszula , Mazur Andrzej , Wielbo Jerzy , Koper Piotr , Żebracki Kamil , Janusz Grzegorz
Published: March 2020

Light influences developmental pathways in fungi. Recent transcriptomic and biochemical analyses have demonstrated that light influences the metabolism of a white-rot basidiomycete Cerrena unicolor. However, the expression profile of genes involved in the growth and development, or micromorphological observations of the mycelium in response to variable lighting and culturing media, have not performed. We aim to reveal the effect of light and nutrients on C. unicolor growth and a potential relationship between the culture medium and lighting conditions on fungus micromorphological structures. Confocal laser scanning microscopy and scanning electron microscopy were employed for morphological observations of C. unicolor mycelium cultivated in red, blue, green, and white light and darkness on mineral and sawdust media. A comprehensive analysis of C. unicolor differentially expressed genes (DEGs) was employed to find global changes in the expression profiles of genes putatively involved in light-dependent morphogenesis. Both light and nutrients influenced C. unicolor growth and development. Considerable differences in the micromorphology of the mycelia were found, which were partially reflected in the functional groups of DEGs observed in the fungus transcriptomes. A complex cross-interaction of nutritional and environmental signals on C. unicolor growth and morphology was suggested. The results are a promising starting point for further investigations of fungus photobiology.
Genome-Wide Identification of Metal Tolerance Protein Genes in Populus trichocarpa and Their Roles in Response to Various Heavy Metal Stresses
Authors: Gao Yongfeng , Yang Fengming , Liu Jikai , Xie Wang , Zhang Lin , Chen Zihao , Peng Zhuoxi , Ou Yongbin , Yao Yinan
Published: March 2020

Metal tolerance proteins (MTPs) are plant divalent cation transporters that play important roles in plant metal tolerance and homeostasis. Poplar is an ideal candidate for the phytoremediation of heavy metals because of its numerous beneficial attributes. However, the definitive phylogeny and heavy metal transport mechanisms of the MTP family in poplar remain unknown. Here, 22 MTP genes in P. trichocarpa were identified and classified into three major clusters and seven groups according to phylogenetic relationships. An evolutionary analysis suggested that PtrMTP genes had undergone gene expansion through tandem or segmental duplication events. Moreover, all PtrMTPs were predicted to localize in the vacuole and/or cell membrane, and contained typical structural features of the MTP family, cation efflux domain. The temporal and spatial expression pattern analysis results indicated the involvement of PtrMTP genes in poplar developmental control. Under heavy metal stress, most of PtrMTP genes were induced by at least two metal ions in roots, stems or leaves. In addition, PtrMTP8.1, PtrMTP9 and PtrMTP10.4 displayed the ability of Mn transport in yeast cells, and PtrMTP6 could transport Co, Fe and Mn. These findings will provide an important foundation to elucidate the biological functions of PtrMTP genes, and especially their role in regulating heavy metal tolerance in poplar.
Study of Inheritance and Linkage of Virulence Genes in a Selfing Population of a Pakistani Dominant Race of Puccinia striiformis f. sp. tritici
Authors: Mehmood Sajid , Sajid Marina , Husnain Syed Kamil , Zhao Jie , Huang Lili , Kang Zhensheng
Published: March 2020

Wheat stripe rust is a severe threat of almost all wheat-growing regions in the world. Being an obligate biotrophic fungus, Puccinia striiformis f. sp. tritici (PST) produces new virulent races that break the resistance of wheat varieties. In this study, 115 progeny isolates were generated through sexual reproduction on susceptible Himalayan Berberis pseudumbellata using a dominant Pakistani race (574232) of PST. The parental isolate and progeny isolates were characterized using 24 wheat Yr single-gene lines and ten simple sequence repeat (SSR) markers. From the one-hundred-and-fifteen progeny isolates, 25 virulence phenotypes (VPs) and 60 multilocus genotypes were identified. The parental and all progeny isolates were avirulent to Yr5, Yr10, Yr15, Yr24, Yr32, Yr43, YrSp, YrTr1, YrExp2, Yr26, and YrTye and virulent to Yr1, Yr2, Yr6, Yr7, Yr8, Yr9, Yr17, Yr25, Yr27, Yr28, YrA, Yr44, and Yr3. Based on the avirulence/virulence phenotypes, we found that VPs virulent to Yr1, Yr2, Yr9, Yr17, Yr47, and YrA were controlled by one dominant gene; those to YrSp, YrTr1, and Yr10 by two dominant genes; and those to YrExp2 by two complementary dominant genes. The results are useful in breeding stripe rust-resistant wheat varieties and understanding virulence diversity.
N-terminal Backbone Pairing Shifts in CCL5-12AAA14 Dimer Interface: Structural Significance of the FAY Sequence
Authors: Li Jin-Ye , Chen Yi-Chen , Lee Yi-Zong , Huang Chun-Hsiang , Sue Shih-Che
Published: March 2020

CC-type chemokine ligand 5 (CCL5) has been known to regulate immune responses by mediating the chemotaxis of leukocytes. Depending on the environment, CCL5 forms different orders of oligomers to interact with targets and create functional diversity. A recent CCL5 trimer structure revealed that the N-terminal conversed F12-A13-Y14 (12FAY14) sequence is involved in CCL5 aggregation. The CCL5-12AAA14 mutant with two mutations had a deficiency in the formation of high-order oligomers. In the study, we clarify the respective roles of F12 and Y14 through NMR analysis and structural determination of the CCL5-12AAA14 mutant where F12 is involved in the dimer assembly and Y14 is involved in aggregation. The CCL5-12AAA14 structure contains a unique dimer packing. The backbone pairing shifts for one-residue in the N-terminal interface, when compared to the native CCL5 dimer. This difference creates a new structural orientation and leads to the conclusion that F12 confines the native CCL5 dimer configuration. Without F12 anchoring in the position, the interfacial backbone pairing is permitted to slide. Structural plasticity occurs in the N-terminal interaction. This is the first case to report this structural rearrangement through mutagenesis. The study provides a new idea for chemokine engineering and complements the understanding of CCL5 oligomerization and the role of the 12FAY14 sequence.
Extracellular Vesicle-Induced Classical Complement Activation Leads to Retinal Endothelial Cell Damage via MAC Deposition
Authors: Huang Chao , Fisher Kiera P. , Hammer Sandra S. , Busik Julia V.
Published: March 2020

Several studies have suggested that there is a link between membrane attack complex (MAC) deposition in the retina and the progression of diabetic retinopathy (DR). Our recent investigation demonstrated that circulating IgG-laden extracellular vesicles contribute to an increase in retinal vascular permeability in DR through activation of the complement system. However, the mechanism through which extracellular vesicle-induced complement activation contributes to retinal vascular cytolytic damage in DR is not well understood. In this study, we demonstrate that IgG-laden extracellular vesicles in rat plasma activate the classical complement pathway, and in vitro Streptozotocin (STZ)-induced rat diabetic plasma results in MAC deposition and cytolytic damage in human retinal endothelial cells (HRECs). Moreover, removal of the plasma extracellular vesicles reduced the MAC deposition and abrogated cytolytic damage seen in HRECs. Together, the results of this study demonstrate that complement activation by IgG-laden extracellular vesicles in plasma could lead to MAC deposition and contribute to endothelium damage and progression of DR.
Heterogeneity of Circulating Tumor Cells in Breast Cancer: Identifying Metastatic Seeds
Authors: Menyailo Maxim E. , Tretyakova Maria S. , Denisov Evgeny V.
Published: March 2020

Metastasis being the main cause of breast cancer (BC) mortality represents the complex and multistage process. The entrance of tumor cells into the blood vessels and the appearance of circulating tumor cells (CTCs) seeding and colonizing distant tissues and organs are one of the key stages in the metastatic cascade. Like the primary tumor, CTCs are extremely heterogeneous and presented by clusters and individual cells which consist of phenotypically and genetically distinct subpopulations. However, among this diversity, only a small number of CTCs is able to survive in the bloodstream and to form metastases. The identification of the metastasis-initiating CTCs is believed to be a critical issue in developing therapeutic strategies against metastatic disease. In this review, we summarize the available literature addressing morphological, phenotypic and genetic heterogeneity of CTCs and the molecular makeup of specific subpopulations associated with BC metastasis. Special attention is paid to the need for in vitro and in vivo studies to confirm the tumorigenic and metastatic potential of metastasis-associating CTCs. Finally, we consider treatment approaches that could be effective to eradicate metastatic CTCs and to prevent metastasis.
Intra-Molecular Homologous Recombination of Scarless Plasmid
Authors: Liang Yaping , Zhang Yu , Liu Liangwei
Published: March 2020

Although many methods have been reported, plasmid construction compromises transformant efficiency (number of transformants per ng of DNAs) with plasmid accuracy (rate of scarless plasmids). An efficient method is two-step PCR serving DNA amplification. An accurate method is ExnaseII cloning serving homology recombination (HR). We combine DNA amplification and HR to develop an intra-molecular HR by amplifying plasmid DNAs to contain homology 5′- and 3′-terminus and recombining the plasmid DNAs in vitro. An example was to construct plasmid pET20b-AdD. The generality was checked by constructing plasmid pET21a-AdD and pET22b-AdD in parallel. The DNAs having 30-bp homology arms were optimal for intra-molecular HR, and transformation of which created 14.2 transformants/ng and 90% scarless plasmids, more than the two-step PCR and the ExnaseII cloning. Transformant efficiency correlated with the component of nicked circular plasmid DNAs of HR products, indicating nick modification in vivo leads to scar plasmids.
Discovery of 1-Pyrimidinyl-2-Aryl-4,6-Dihydropyrrolo [3,4-d]Imidazole-5(1H)-Carboxamide as a Novel JNK Inhibitor
Authors: Jang Miyoung , Oh Youri , Cho Hyunwook , Yang Songyi , Moon Hyungwoo , Im Daseul , Hah Jung-Mi
Published: March 2020

We designed and synthesized 1-pyrimidinyl-2-aryl-4, 6-dihydropyrrolo [3,4-d] imidazole-5(1H)-carboxamide derivatives as selective inhibitors of c-Jun-N-terminal Kinase 3 (JNK3), a target for the treatment of neurodegenerative diseases. Based on the compounds found in previous studies, a novel scaffold was designed to improve pharmacokinetic characters and activity, and compound 18a, (R)-1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-2-(3,4-dichlorophenyl)-4,6-dihydro pyrrolo [3,4-d]imidazole-5(1H)-carboxamide, showed the highest IC50 value of 2.69 nM. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases, having mild activity against JNK2, RIPK3, and GSK3β, which also known to involve in neuronal apoptosis.
Systematic Review of Polygenic Risk Scores for Type 1 and Type 2 Diabetes
Authors: Padilla-Martínez Felipe , Collin Francois , Kwasniewski Miroslaw , Kretowski Adam
Published: March 2020

Recent studies have led to considerable advances in the identification of genetic variants associated with type 1 and type 2 diabetes. An approach for converting genetic data into a predictive measure of disease susceptibility is to add the risk effects of loci into a polygenic risk score. In order to summarize the recent findings, we conducted a systematic review of studies comparing the accuracy of polygenic risk scores developed during the last two decades. We selected 15 risk scores from three databases (Scopus, Web of Science and PubMed) enrolled in this systematic review. We identified three polygenic risk scores that discriminate between type 1 diabetes patients and healthy people, one that discriminate between type 1 and type 2 diabetes, two that discriminate between type 1 and monogenic diabetes and nine polygenic risk scores that discriminate between type 2 diabetes patients and healthy people. Prediction accuracy of polygenic risk scores was assessed by comparing the area under the curve. The actual benefits, potential obstacles and possible solutions for the implementation of polygenic risk scores in clinical practice were also discussed. Develop strategies to establish the clinical validity of polygenic risk scores by creating a framework for the interpretation of findings and their translation into actual evidence, are the way to demonstrate their utility in medical practice.
Beneficial and Detrimental Effects of Regulatory T Cells in Neurotropic Virus Infections
Authors: Ciurkiewicz Malgorzata , Herder Vanessa , Beineke Andreas
Published: March 2020

Neurotropic viruses infect the central nervous system (CNS) and cause acute or chronic neurologic disabilities. Regulatory T cells (Treg) play a critical role for immune homeostasis, but may inhibit pathogen-specific immunity in infectious disorders. The present review summarizes the current knowledge about Treg in human CNS infections and their animal models. Besides dampening pathogen-induced immunopathology, Treg have the ability to facilitate protective responses by supporting effector T cell trafficking to the infection site and the development of resident memory T cells. Moreover, Treg can reduce virus replication by inducing apoptosis of infected macrophages and attenuate neurotoxic astrogliosis and pro-inflammatory microglial responses. By contrast, detrimental effects of Treg are caused by suppression of antiviral immunity, allowing for virus persistence and latency. Opposing disease outcomes following Treg manipulation in different models might be attributed to differences in technique and timing of intervention, infection route, genetic background, and the host’s age. In addition, mouse models of virus-induced demyelination revealed that Treg are able to reduce autoimmunity and immune-mediated CNS damage in a disease phase-dependent manner. Understanding the unique properties of Treg and their complex interplay with effector cells represents a prerequisite for the development of new therapeutic approaches in neurotropic virus infections.
Liraglutide Suppresses Tau Hyperphosphorylation, Amyloid Beta Accumulation through Regulating Neuronal Insulin Signaling and BACE-1 Activity
Authors: Jantrapirom Salinee , Nimlamool Wutigri , Chattipakorn Nipon , Chattipakorn Siriporn , Temviriyanukul Piya , Inthachat Woorawee , Govitrapong Piyarat , Potikanond Saranyapin
Published: March 2020

Neuronal insulin resistance is a significant feature of Alzheimer’s disease (AD). Accumulated evidence has revealed the possible neuroprotective mechanisms of antidiabetic drugs in AD. Liraglutide, a glucagon-like peptide-1 (GLP-1) analog and an antidiabetic agent, has a benefit in improving a peripheral insulin resistance. However, the neuronal effect of liraglutide on the model of neuronal insulin resistance with Alzheimer’s formation has not been thoroughly investigated. The present study discovered that liraglutide alleviated neuronal insulin resistance and reduced beta-amyloid formation and tau hyperphosphorylation in a human neuroblostoma cell line, SH-SY5Y. Liraglutide could effectively reverse deleterious effects of insulin overstimulation. In particular, the drug reversed the phosphorylation status of insulin receptors and its major downstream signaling molecules including insulin receptor substrate 1 (IRS-1), protein kinase B (AKT), and glycogen synthase kinase 3 beta (GSK-3β). Moreover, liraglutide reduced the activity of beta secretase 1 (BACE-1) enzyme, which then decreased the formation of beta-amyloid in insulin-resistant cells. This indicated that liraglutide can reverse the defect of phosphorylation status of insulin signal transduction but also inhibit the formation of pathogenic Alzheimer’s proteins like Aβ in neuronal cells. We herein provided the possibility that the liraglutide-based therapy may be able to reduce such deleterious effects caused by insulin resistance. In view of the beneficial effects of liraglutide administration, these findings suggest that the use of liraglutide may be a promising therapy for AD with insulin-resistant condition.
How Approaches to Animal Swarm Intelligence Can Improve the Study of Collective Intelligence in Human Teams
Authors: O’Bryan Lisa , Beier Margaret , Salas Eduardo
Published: March 2020

Researchers of team behavior have long been interested in the essential components of effective teamwork. Much existing research focuses on examining correlations between team member traits, team processes, and team outcomes, such as collective intelligence or team performance. However, these approaches are insufficient for providing insight into the dynamic, causal mechanisms through which the components of teamwork interact with one another and impact the emergence of team outcomes. Advances in the field of animal behavior have enabled a precise understanding of the behavioral mechanisms that enable groups to perform feats that surpass the capabilities of the individuals that comprise them. In this manuscript, we highlight how studies of animal swarm intelligence can inform research on collective intelligence in human teams. By improving the ability to obtain precise, time-varying measurements of team behaviors and outcomes and building upon approaches used in studies of swarm intelligence to analyze and model individual and group-level behaviors, researchers can gain insight into the mechanisms underlying the emergence of collective intelligence. Such understanding could inspire targeted interventions to improve team effectiveness and support the development of a comparative framework of group-level intelligence in animal and human groups.
Evaluating the Performance of Islamic Banks Using a Modified Monti-Klein Model
Authors: Sumarti Novriana , Andirasdini Indah G. , Ghaida Nidya I. , Mukhaiyar Utriweni
Published: March 2020

The development of Islamic banking continues to increase in many Muslim (majority) countries. Substituting interest with profit shares in the assets of a given Islamic bank as one of the bases of operation has many interesting implications, one of which is the need for more involved risk and return measures. In this paper, we take a balance sheet analysis-based approach to formulating profit in order to assess the performance of an Islamic bank. Then the implementation of this approach is demonstrated using data provided by Indonesia’s financial services authority, known as the OJK. We develop formulae for the calculation of profit share between funding and financing funds as well as the appropriate rates of return. The resulting figures are then used to construct statistical models for short-term forecasting of the volumes of funding fund from the depositors and financing fund for business people who need funds for their investment projects. The approach we develop is innovative for Islamic banks and would be a welcome addition to their performance assessment toolkit. One of the results of our model indicates an increasing pattern on the equivalent rates of returns for funding and financing funds every year, which is caused by the fact that the reported income from the financing fund seems to have been accumulated from the beginning until the end of year in the Islamic bank.
A General Family of Autoregressive Conditional Duration Models Applied to High-Frequency Financial Data
Authors: Cunha Danúbia R. , Vila Roberto , Saulo Helton , Fernandez Rodrigo N.
Published: March 2020

In this paper, we propose a general family of Birnbaum–Saunders autoregressive conditional duration (BS-ACD) models based on generalized Birnbaum–Saunders (GBS) distributions, denoted by GBS-ACD. We further generalize these GBS-ACD models by using a Box-Cox transformation with a shape parameter λ to the conditional median dynamics and an asymmetric response to shocks; this is denoted by GBS-AACD. We then carry out a Monte Carlo simulation study to evaluate the performance of the GBS-ACD models. Finally, an illustration of the proposed models is made by using New York stock exchange (NYSE) transaction data.
Influence of Process Parameters in Graphene Oxide Obtention on the Properties of Mechanically Strong Alginate Nanocomposites
Authors: Larraza Izaskun , Ugarte Lorena , Fayanas Aintzane , Gabilondo Nagore , Arbelaiz Aitor , Corcuera Maria , Eceiza Arantxa
Published: March 2020

Sodium alginate, a biopolymer extracted from brown algae, has shown great potential for many applications, mainly due to its remarkable biocompatibility and biodegradability. To broaden its fields of applications and improve material characteristics, the use of nanoreinforcements to prepare nanocomposites with enhanced properties, such as carbonaceous structures which could improve thermal and mechanical behavior and confer new functionalities, is being studied. In this work, graphene oxide was obtained from graphite by using modified Hummers’ method and exfoliation was assisted by sonication and centrifugation, and it was later used to prepare sodium alginate/graphene oxide nanocomposites. The effect that different variables, during preparation of graphene oxide, have on the final properties has been studied. Longer oxidation times showed higher degrees of oxidation and thus larger amount of oxygen-containing groups in the structure, whereas longer sonication times and higher centrifugation rates showed more exfoliated graphene sheets with lower sizes. The addition of graphene oxide to a biopolymeric matrix was also studied, considering the effect of processing and content of reinforcement on the material. Materials with reinforcement size-dependent properties were observed, showing nanocomposites with large flake sizes, better thermal stability, and more enhanced mechanical properties, reaching an improvement of 65.3% and 83.3% for tensile strength and Young’s modulus, respectively, for a composite containing 8 wt % of graphene oxide.
Effect of Nb Content on Cyclic Oxidation Behavior of As-Cast Ti-1100 Alloys
Authors: Song Yingjun , Fu Binguo , Dong Tianshun , Li Guolu , Wang Fei , Zhao Xuebo , Liu Jinhai
Published: March 2020

The cyclic oxidation behaviors of the as-cast Ti-1100-xNb (x = 0.5, 1.0, 1.5, 2.0) alloys exposed at 650 °C for up to 100 h were systematically investigated. The aim of this work is to explore the in-depth oxidation mechanism by using the oxidation kinetics and the structure of the oxide products. The oxidation kinetics were determined by thermogravimetrically, and the microstructure and composition of the oxidation scale were studied by using XRD and SEM. The results demonstrate that Nb can significantly improve the oxidation resistance. However, the average weight gains of the alloys decrease firstly and then increase with the increase of Nb content. The oxidation kinetics obeys a parabolic model. The Ti-1100-1.0Nb alloy has the lowest kp value, which is 5.7 × 10−13 g2cm−4s−1. The surface oxidation products are mainly composed of massive or acicular rutile-TiO2, TixO (x = 3, 6), NbO2 and Al2O3. Besides, Al2(MoO4)3 oxide is also presented on the oxidation surface of the Ti-1100-1.5Nb alloys. Ti-1100-1.0Nb alloy shows the best oxidation resistance property revealed by combining weight gains and EDS-SEM element content profiles analysis. The interaction of Nb, O, Ti, and other elements retarded the diffusion of O atoms into the alloys, which improves the oxidation resistance.
Kinetic Model of Incipient Hydride Formation in Zr Clad under Dynamic Oxide Growth Conditions
Authors: Yu Qianran , Reyes Michael , Shah Nachiket , Marian Jaime
Published: March 2020

The formation of elongated zirconium hydride platelets during corrosion of nuclear fuel clad is linked to its premature failure due to embrittlement and delayed hydride cracking. Despite their importance, however, most existing models of hydride nucleation and growth in Zr alloys are phenomenological and lack sufficient physical detail to become predictive under the variety of conditions found in nuclear reactors during operation. Moreover, most models ignore the dynamic nature of clad oxidation, which requires that hydrogen transport and precipitation be considered in a scenario where the oxide layer is continuously growing at the expense of the metal substrate. In this paper, we perform simulations of hydride formation in Zr clads with a moving oxide/metal boundary using a stochastic kinetic diffusion/reaction model parameterized with state-of-the-art defect and solute energetics. Our model uses the solutions of the hydrogen diffusion problem across an increasingly-coarse oxide layer to define boundary conditions for the kinetic simulations of hydrogen penetration, precipitation, and dissolution in the metal clad. Our method captures the spatial dependence of the problem by discretizing all spatial derivatives using a stochastic finite difference scheme. Our results include hydride number densities and size distributions along the radial coordinate of the clad for the first 1.6 h of evolution, providing a quantitative picture of hydride incipient nucleation and growth under clad service conditions.
The Influence of Thermal Residual Stresses on Mechanical Properties of Silicon Nitride-Based Composites
Authors: Dubiel Aleksandra , Grabowski Grzegorz , Goły Marcin , Skrzypek Stanisław
Published: March 2020

In this work, two kinds of silicon nitride-based composites, namely, those with titanium nitride or silicon carbide additives, were sintered using the hot pressing technique (HP). The phase composition, microstructure, and mechanical and elastic properties of the materials were characterized. Three-dimensional geometric models of the composites were created on the basis of microstructure parameters. Using these models, bulk residual thermal stresses were calculated by the finite element method (FEM). Surface stresses were determined using the XRD method of sin2ψ.