bluuebunny/crossref_metadata_2025 huggingface dataset:
Revisiting the Monism and Dualism Dichotomy: What does the South African Constitution of 1996 and the Practice by the Courts tell us about the Reception of SADC Community Law (Treaty Law) in South Africa?
Authors: Phooko Moses Retselisistoe
Published: February 2021

The jurisprudence of the (suspended) SADC Tribunal shows that the Tribunal was prepared to utilise the principles of democracy, human rights and the rule of law contained in the Treaty of the Southern African Development Community (SADC Treaty) to ensure that SADC member states fulfil their treaty obligations. The decisions rendered by the SADC Tribunal and the participation of the South African former President in a process that halted the functioning of the Tribunal have brought interesting legal developments in the South African legal system in so far as the reception and application of SADC community law in South African municipal law is concerned. The argument presented in this article is that the recent seemingly monist approach by the courts represents a major shift from a prescribed procedure provided for in the Constitution of South Africa, 1996 (the Constitution). The practice by the courts further ignores the dualist nature of South Africa's legal system. The main question presented in this discourse is whether a departure by the courts from a constitutionally mandated procedure of domesticating SADC community law into municipal law signifies a new and settled norm which entails that South Africa now follows a hybrid system (i.e. monism and dualism) of treaty incorporation? In light of this possible legal uncertainty, I propose that South Africa adopts a harmonisation theory to address the legal gap created by the courts.
Lecture about Electronic Microtonal Music at the Theremin Center Electronic Studio of the Moscow Conservatory in March 2004
Authors:   “Composers’ Concordance” concert organization, Pehrson Joseph
Published: February 2021

Joseph Pehrson is a well-known New York-based composer. He studied at the Eastman School of Music and the University of Michigan. He has been active in promoting contemporary music in New York, having been a co-director of the “Composers’ Concordance” concert organization from 1984 to 2011. Pehrson has written music in various styles, including neoclassical and avant-garde, microtonal music. The latter includes electronic compositions with and without solo instruments, which he wrote in the decade of the 2000s. He has delved very deeply into microtonal theory and has written compositions for various unusual and non-standard microtonal scales, such as the 21-note to the octave scale. The following is a transcript of Joseph Pehrson’s presentation at the Theremin Center, which was the Moscow Conservatory’s electronic studio in the 1990s and 2000s.
An Interview with Composers Pamela Madsen and Eric Dries from Los Angeles
Authors:   Moscow State P.I. Tchaikovsky Conservatory, Rovner Anton А.
Published: February 2021

Dear readers of the journal “ICONI”! We are offering you an interview with two innovative American composers residing in California, Pamela Madsen and Eric Dries. They demonstrate the rich context of new trends in American music encompassing the serial Uptown School and the experimental Downtown School, as well as their connections to contemporary European music. The composers describe the styles of their respective musical compositions and their versatile musical activities, including teaching at the California State University at Fullerton, performing and organizing concerts of contemporary music.
This Must Surely be the Way to Happiness!: Divergent “bite-size wisdoms” about Happiness in inspirational internet memes
Authors: De Paola Jennifer , Hakoköngäs Eemeli
Published: February 2021

The present study explores the contents and functions of inspirational memes addressing happiness in two cultural contexts, Finnish and Italian. Inspirational memes are understood as a mode of present-day folk wisdom conveying advice that can be easily memorized, shared and applied in everyday life. The material consists of 709 memes collected from Instagram and Facebook in 2019 (N=353 in Finnish; N=356 in Italian). The theoretical background of the study draws from social representation theory. The analysis shows that the contents and functions of inspirational memes addressing happiness are similar in the Finnish and Italian contexts. Five common themes were identified: “the self”, “the others”, “the life goal”, “the here & now”, and “the pointless search”. Furthermore, the social representation of happiness within the material is organized around a fundamental dichotomy: on the one hand, happiness can be built, and detailed advice is dispensed on how this can be achieved; on the other hand, building happiness is represented as an unattainable goal, and supporting this view is the idea that happiness is found in the moment. The dichotomy implies a social representation that emphasizes internal factors of the individual and plays down the role of external circumstances in achieving happiness.
Some Die Young
Authors: Silow Kallenberg Kim
Published: February 2021

This is an ethnographic and an autoethnographic study based on qualitative interviews as well as memories and experiences of the author. It focuses on two men that were childhood friends of the author and who both died prematurely. Marcus died in November 2013 while he was under psychiatric care due to auditory hallucinations and anxiety. Noel died little over a year later, in January 2015, from an overdose of heroin. The aim of the article is to analyse the narratives of women and is concerned with understanding the loss of a son, a brother, or a former boyfriend or friend due to substance abuse or mental health problems. The empirical cases analysed in this text are women’s understandings of the deaths of Marcus and Noel – two young men who were close to them in different ways. Their narratives about the men, their memories, and their rationalisations for what happened to them are analysed.   The analysis shows that when the women talk about, and try to explain, the male lives that led up to the death, a limited number of narratives are available. Narratives about absent and/or abusive fathers, narratives about mothers who fail in providing the expected care, and narratives about shortcomings in psychiatric services and community support are dominant in the analysed material. In relation to these available narratives, the story follows the making of a protest masculinity in which elements such as rock star dreams, violence, drug use, and talk of legalising drugs have a place. Together they form an overarching narrative about protest masculinity; i.e. ways to act in reaction to a perceived alienation or subordination by acting out in ways associated with masculinity.
Men Can/Can Men Change?
Authors: Nilsson Gabriella , Gunnarsson David
Published: February 2021

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KLF2 Inhibits Chicken Preadipocyte Differentiation at Least in Part via Directly Repressing PPARγ Transcript Variant 1 Expression
Authors: Cui Tingting , Huang Jiaxin , Sun Yingning , Ning Bolin , Mu Fang , You Xin , Guo Yaqi , Li Hui , Wang Ning
Published: February 2021

Peroxisome proliferator-activated receptor gamma (PPARγ) is the master regulatory factor of preadipocyte differentiation. As a result of alternative splicing and alternative promoter usage, PPARγ gene generates multiple transcript variants encoding two protein isoforms. Krüppel-like factor 2 (KLF2) plays a negative role in preadipocyte differentiation. However, its underlying mechanism remains incompletely understood. Here, we demonstrated that KLF2 inhibited the P1 promoter activity of the chicken PPARγ gene. Bioinformatics analysis showed that the P1 promoter harbored a conserved putative KLF2 binding site, and mutation analysis showed that the KLF2 binding site was required for the KLF2-mediated transcription inhibition of the P1 promoter. ChIP, EMSA, and reporter gene assays showed that KLF2 could directly bind to the P1 promoter regardless of methylation status and reduced the P1 promoter activity. Consistently, histone modification analysis showed that H3K9me2 was enriched and H3K27ac was depleted in the P1 promoter upon KLF2 overexpression in ICP1 cells. Furthermore, gene expression analysis showed that KLF2 overexpression reduced the endogenous expression of PPARγ transcript variant 1 (PPARγ1), which is driven by the P1 promoter, in DF1 and ICP1 cells, and that the inhibition of ICP1 cell differentiation by KLF2 overexpression was accompanied by the downregulation of PPARγ1 expression. Taken together, our results demonstrated that KLF2 inhibits chicken preadipocyte differentiation at least inpart via direct downregulation of PPARγ1 expression.
ZnO Nanowires/N719 Dye With Different Aspect Ratio as a Possible Photoelectrode for Dye-Sensitized Solar Cells
Authors: Portillo-Cortez Karina , Martínez Ana , Bizarro Monserrat , García-Sánchez Mario F. , Güell Frank , Dutt Ateet , Santana Guillermo
Published: February 2021

The vapor-liquid-solid (VLS) process was applied to fabricate zinc oxide nanowires (ZnO NWs) with a different aspect ratio (AR), morphological, and optical properties. The ZnO NWs were grown on a system that contains a quartz substrate with transparent conductive oxide (TCO) thin film followed by an Al-doped ZnO (AZO) seed layer; both films were grown by magnetron sputtering at room temperature. It was found that the ZnO NWs presented high crystalline quality and vertical orientation from different structural and morphological characterizations. Also, NWs showed a good density distribution of 69 NWs/μm2 with a different AR that offers their capability to be used as possible photoelectrode (anode) in potential future device applications. The samples optical properties were studied using various techniques such as photoluminescence (PL), absorption, and transmittance before and after sensitization with N719 dye. The results demonstrated that NW with 30 nm diameter had the best characteristics as feasible photoelectrode (anode) (high absorption, minimum recombination, high crystallinity). Also, the present samples optical properties were found to be improved due to the existence of N719 dye and Au nanoparticles on the tip of NWs. NWs grown in this work can be used in different photonic and optoelectronic applications.
Lansoprazole-Based Colorimetric Chemosensor for Efficient Binding and Sensing of Carbonate Ion: Spectroscopy and DFT Studies
Authors: Darroudi Mahdieh , Mohammadi Ziarani Ghodsi , Bahar Shahriyar , Ghasemi Jahan B. , Badiei Alireza
Published: February 2021

The new benzimidazole based receptor Lansoprazole has been used to detect carbonate anion by naked-eye and Uv-Vis spectroscopy. This receptor revealed visual changes with CO32- anion in ethanol. No detectable color changes were observed upon the addition of any other tested anions. The lansoprazole chemosensor selectively recognizes CO32- ion over the other interference anions in the ethanol, followed by deprotonation and reflected 1:1 complex formation between the receptor and the carbonate ion. Lansoprazole exhibits splendid selectivity toward carbonate ion via a visible color change from colorless to yellow with a detection limit of 57 μM. The binding mode of CO32- to receptor L is supported by Density Functional Theory calculation. Moreover, this receptor shows a practical visible colorimetric test strip for the detection of carbonate ions. The transition states calculation demonstrates the occurrence of reaction from L to L-CO32- after overcoming an energy barrier of 10.1 kcal/mol, and there is considerable interaction energy between L and CO32- (94.9 kJ/mol), both of which confirmed that receptor L has high sensitivity and selectivity to the carbonate ion. The theoretical studies were performed to acquire an electronic description of the complexation mechanism by CO32- as well as to study bonding and structure in the complex. The optimized structures and binding mechanisms were supported with a high correlation and agreement by spectroscopy and DFT calculations.
Adhesion of Staphylococcus aureus to Candida albicans During Co-Infection Promotes Bacterial Dissemination Through the Host Immune Response
Authors: Van Dyck Katrien , Viela Felipe , Mathelié-Guinlet Marion , Demuyser Liesbeth , Hauben Esther , Jabra-Rizk Mary Ann , Vande Velde Greetje , Dufrêne Yves F. , Krom Bastiaan P. , Van Dijck Patrick
Published: February 2021

Interspecies interactions greatly influence the virulence, drug tolerance and ultimately the outcome of polymicrobial biofilm infections. A synergistic interaction is observed between the fungus Candida albicans and the bacterium Staphylococcus aureus. These species are both normal commensals of most healthy humans and co-exist in several niches of the host. However, under certain circumstances, they can cause hospital-acquired infections with high morbidity and mortality rates. Using a mouse model of oral co-infection, we previously showed that an oral infection with C. albicans predisposes to a secondary systemic infection with S. aureus. Here, we unraveled this intriguing mechanism of bacterial dissemination. Using static and dynamic adhesion assays in combination with single-cell force spectroscopy, we identified C. albicans Als1 and Als3 adhesins as the molecular players involved in the interaction with S. aureus and in subsequent bacterial dissemination. Remarkably, we identified the host immune response as a key element required for bacterial dissemination. We found that the level of immunosuppression of the host plays a critical yet paradoxical role in this process. In addition, secretion of candidalysin, the C. albicans peptide responsible for immune activation and cell damage, is required for C. albicans colonization and subsequent bacterial dissemination. The physical interaction with C. albicans enhances bacterial uptake by phagocytic immune cells, thereby enabling an opportunity to disseminate.
Casting a Wider Net on Ocean NETs
Authors: Cox Emily , Boettcher Miranda , Spence Elspeth , Bellamy Rob
Published: February 2021

Societal issues involving policies and publics are generally understudied in research on ocean-based Negative Emission Technologies (NETs), yet will be crucial if novel techniques are ever to function at scale. Public attitudes are vital for emerging technologies: publics influence political mandates, help determine the degree of uptake by market actors, and are key to realizing broader ambitions for robust decision-making and responsible incentivization. Discourses surrounding ocean NETs will also have fundamental effects on how governance for the techniques emerges, shaping how they are defined as an object of governance, who is assigned the authority to govern, and what instruments are deemed appropriate. This Perspective brings together key insights on the societal dimensions of ocean NETs, drawing on existing work on public acceptability, policy assessment, governance, and discourse. Ocean iron fertilization is the only ocean NET on which there exists considerable social science research thus far, and we show that much evidence points against its social desirability. Taken in conjunction with considerable natural science uncertainties, this leads us to question whether further research is actually necessary in order to rule out ocean iron fertilization as an option. For other ocean NETs, there is a need for further research into social dimensions, yet research on analogous technologies shows that ocean interventions will likely evoke strong risk perceptions, and evidence suggests that the majority of ocean NETs may face a greater public acceptability challenge than terrestrial NETs. Ocean NETs also raise complex challenges around governance, which pose questions well-beyond the remit of the natural sciences and engineering. Using a conceptual exploration of the ways in which different types of discourse may shape emerging ocean NETs governance, we show that the very idea of ocean NETs is likely to set the stage for a whole new range of contested futures.
2D Graphene-TiO2 Composite and Its Photocatalytic Application in Water Pollutants
Authors: Zhou Xin , Zhang Xian , Wang Yuemei , Wu Zhen
Published: February 2021

To solve the global water shortages and serious water pollution problems, research on semiconductor photocatalysts has generated significant research attention. The degradation of pollutants by titanium dioxide (TiO2) exceeds other semiconductor materials. However, its wide bandgap restricts the photocatalytic reaction under visible light. The large specific surface area and good thermal conductivity of graphene yielded an effective graphene-TiO2 catalyst combination effective under visible light. 2D graphene-TiO2 composites (2D-GTC) have shown promise, so a study of the preparation methods, mechanism and catalytic effect of different pollutants on this material was undertaken. In this current review, the characteristics of different graphene and TiO2 composites and their preparation methods, as well as the effects of different synthesis methods on the catalyst are introduced. The reaction mechanism of 2D-GTC catalysts, the degradation effects of different pollutants in water are all reviewed.
Outdoor Atmospheric Microbial Diversity Is Associated With Urban Landscape Structure and Differs From Indoor-Transit Systems as Revealed by Mobile Monitoring and Three-Dimensional Spatial Analysis
Authors: Stewart Justin D. , Kremer Peleg , Shakya Kabindra M. , Conway Meghan , Saad Alexander
Published: February 2021

Microbes are abundant inhabitants of the near-surface atmosphere in urban areas. The distribution of microbial communities may benefit or hinder human wellbeing and ecosystem function. Surveys of airborne microbial diversity are uncommon in both natural and built environments and those that investigate diversity are stationary in the city, thus missing continuous exposure to microbes that covary with three-dimensional urban structure. Individuals in cities are generally mobile and would be exposed to diverse urban structures outdoors and within indoor-transit systems in a day. We used mobile monitoring of microbial diversity and geographic information system spatial analysis, across Philadelphia, Pennsylvania, USA in outdoor and indoor-transit (subways and train cars) environments. This study identifies to the role of the three-dimensional urban landscape in structuring atmospheric microbiomes and employs mobile monitoring over ~1,920 kilometers to measure continuous biodiversity. We found more diverse communities outdoors that significantly differ from indoor-transit air in microbial community structure, function, likely source environment, and potentially pathogenic fraction of the community. Variation in the structure of the urban landscape was associated with diversity and function of the near-surface atmospheric microbiome in outdoor samples.
Circ_0065149 Alleviates Oxidized Low-Density Lipoprotein-Induced Apoptosis and Inflammation in Atherosclerosis by Targeting miR-330-5p
Authors: Li Dan , Jin Wen , Sun Li , Wu Jiawei , Hu Hao , Ma Likun
Published: February 2021

Background

Atherosclerosis is a risk factor for cardiovascular diseases. However, the roles of Circular RNAs (circRNAs) in atherosclerosis is unknown. Our study aimed to explore the effects of circ_0065149 in the pathogenesis of atherosclerosis.

Methods

The expression of circ_0065149 ox-LDL-induced in human umbilical vein endothelial cells (HUVECs) was assessed by RT-PCR. Cell viability, lactate dehydrogenase leakage, apoptosis, invasion, and migration were assessed in HUVECs. Dual luciferase reporter system was carried out to determine the interaction between miR-330-5p and circ_0065149.

Results

Our results showed that circ_0065149 was significantly lower in the ox-LDL-induced HUVECs. Overexpression of circ_0065149 promoted the cell viability and inhibited the apoptosis of ox-LDL-induced HUVECs. Overexpression of circ_0065149 also promoted the migration and invasion of ox-LDL-induced HUVECs. The expression of miR-330-5p was inhibited by overexpression of circ_0065149. Furthermore, circ_0065149 overexpression significantly inhibited the expressions of nuclear NF-κBp65 and suppressed the production of TNF-α, IL-6, and IL-1β in ox-LDL-induced HUVECs, which was rescued by the miR-330-5p mimic.

Conclusion

These findings suggest that circ_0065149 plays an important role in the proliferation, apoptosis, and inflammatory response of HUVECs via targeting miR-330-5p.
Apurinic/Apyrimidinic Endonuclease 1 Restricts the Internalization of Bacteria Into Human Intestinal Epithelial Cells Through the Inhibition of Rac1
Authors: den Hartog Gerco , Butcher Lindsay D. , Ablack Amber L. , Pace Laura A. , Ablack Jailal N. G. , Xiong Richard , Das Soumita , Stappenbeck Thaddeus S. , Eckmann Lars , Ernst Peter B. , Crowe Sheila E.
Published: February 2021

Pathogenic intestinal bacteria lead to significant disease in humans. Here we investigated the role of the multifunctional protein, Apurinic/apyrimidinic endonuclease 1 (APE1), in regulating the internalization of bacteria into the intestinal epithelium. Intestinal tumor-cell lines and primary human epithelial cells were infected withSalmonella entericaserovar Typhimurium or adherent-invasiveEscherichia coli. The effects of APE1 inhibition on bacterial internalization, the regulation of Rho GTPase Rac1 as well as the epithelial cell barrier function were assessed. Increased numbers of bacteria were present in APE1-deficient colonic tumor cell lines and primary epithelial cells. Activation of Rac1 was augmented following infection but negatively regulated by APE1. Pharmacological inhibition of Rac1 reversed the increase in intracellular bacteria in APE1-deficient cells whereas overexpression of constitutively active Rac1 augmented the numbers in APE1-competent cells. Enhanced numbers of intracellular bacteria resulted in the loss of barrier function and a delay in its recovery. Our data demonstrate that APE1 inhibits the internalization of invasive bacteria into human intestinal epithelial cells through its ability to negatively regulate Rac1. This activity also protects epithelial cell barrier function.
Gamma/Delta T Cells in the Course of Healthy Human Pregnancy: Cytotoxic Potential and the Tendency of CD8 Expression Make CD56+ γδT Cells a Unique Lymphocyte Subset
Authors: Nörenberg Jasper , Jaksó Pál , Barakonyi Alíz
Published: February 2021

To date, pregnancy is an immunological paradox. The semi-allogenic fetus must be accepted by the maternal immune system, while defense against pathogens and immune surveillance cannot be compromised. Gamma/delta T cells are believed to play an important role in this immunological puzzle. In this study, we analyzed peripheral blood CD56+ γδT cells from pregnant women (1st, 2nd, and 3rdtrimester) and non-pregnant women by multicolor flow cytometry. Interestingly, γδT cells represent almost half of CD3+/CD56+ cells. Among γδT cells, the CD56+ population expands in the 2ndand 3rdtrimester. CD56+ γδT cells maintained a predominantly CD4–/CD8– or CD8+ phenotype, while CD56– γδT cells were in similar rates CD4–/CD8– or CD4+ during pregnancy. Investigation of the lysosomal degranulation marker CD107a revealed a preserved elevated rate of potentially cytotoxic CD56+ γδT cells in pregnancy, while their cytotoxic strength was reduced. Furthermore, CD56+ γδT cells continuously showed a higher prevalence of PD-1 expression. CD56+ γδT cells’ rate of PD-1 increased in the 1sttrimester and decreased hereafter back to normal level. We correlated the cytotoxic potential and the expression of the inhibitory immune checkpoint PD-1 and were able to demonstrate that highly cytotoxic cells within this CD56+ γδT population tend to express PD-1, which might allow the inhibition of these cells after binding its ligand in the placenta. These findings should support the understanding of the complex processes, which ensure the maintenance of pregnancy.
Extracellular Vesicles as Inflammatory Drivers in NAFLD
Authors: Srinivas Akshatha N. , Suresh Diwakar , Santhekadur Prasanna K. , Suvarna Deepak , Kumar Divya P.
Published: February 2021

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent chronic liver disease in most parts of the world affecting one-third of the western population and a growing cause for end-stage liver diseases such as hepatocellular carcinoma (HCC). Majorly driven by obesity and diabetes mellitus, NAFLD is more of a multifactorial disease affected by extra-hepatic organ crosstalk. Non-alcoholic fatty liver (NAFL) progressed to non-alcoholic steatohepatitis (NASH) predisposes multiple complications such as fibrosis, cirrhosis, and HCC. Although the complete pathogenic mechanisms of this disease are not understood, inflammation is considered as a key driver to the onset of NASH. Lipotoxicity, inflammatory cytokines, chemokines, and intestinal dysbiosis trigger both hepatic and systemic inflammatory cascades simultaneously activating immune responses. Over a few years, extracellular vesicles studied extensively concerning the pathobiology of NAFLD indicated it as a key modulator in the setting of immune-mediated inflammation. Exosomes and microvesicles, the two main types of extracellular vesicles are secreted by an array of most mammalian cells, which are involved mainly in cell-cell communication that are unique to cell type. Various bioactive cargoes containing extracellular vesicles derived from both hepatic and extrahepatic milieu showed critical implications in driving steatosis to NASH reaffirming inflammation as the primary contributor to the whole process. In this mini-review, we provide brief insights into the inflammatory mediators of NASH with special emphasis on extracellular vesicles that acts as drivers of inflammation in NAFLD.
Cellular CARD11 Inhibits the Fusogenic Activity of Newcastle Disease Virus via CBM Signalosome-Mediated Furin Reduction in Chicken Fibroblasts
Authors: Wang Wenbin , Wei Qiaolin , Hao Qiqi , Zhang Yajie , Li Yongshan , Bi Youkun , Jin Zhongyuan , Liu Haijin , Liu Xuelan , Yang Zengqi , Xiao Sa
Published: February 2021

Newcastle disease virus (NDV) causes an infectious disease that poses a major threat to poultry health. Our previous study identified a chicken brain-specific caspase recruitment domain-containing protein 11 (CARD11) that was upregulated in chicken neurons and inhibited NDV replication. This raises the question of whether CARD11 plays a role in inhibiting viruses in non-neural cells. Here, chicken fibroblasts were used as a non-neural cell model to investigate the role. CARD11 expression was not significantly upregulated by either velogenic or lentogenic NDV infection in chicken fibroblasts. Viral replication was decreased in DF-1 cells stably overexpressing CARD11, while viral growth was significantly increased in the CARD11-knockdown DF-1 cell line. Moreover, CARD11 colocalized with the viral P protein and aggregated around the fibroblast nucleus, suggesting that an interaction existed between CARD11 and the viral P protein; this interaction was further examined by suppressing viral RNA polymerase activity by using a minigenome assay. Viral replication was inhibited by CARD11 in fibroblasts, and this result was consistent with our previous report in chicken neurons. Importantly, CARD11 was observed to reduce the syncytia induced by either velogenic virus infection or viral haemagglutinin-neuraminidase (HN) and F cotransfection in fibroblasts. We found that CARD11 inhibited the expression of the host protease furin, which is essential for cleavage of the viral F protein to trigger fusogenic activity. Furthermore, the CARD11-Bcl10-MALT1 (CBM) signalosome was found to suppress furin expression, which resulted in a reduction in the cleavage efficiency of the viral F protein to further inhibit viral syncytia. Taken together, our findings mainly demonstrated a novel CARD11 inhibitory mechanism for viral fusogenic activity in chicken fibroblasts, and this mechanism explains the antiviral roles of this molecule in NDV pathogenesis.
Gut Microbiota Profile in Pediatric Patients With Inflammatory Bowel Disease: A Systematic Review
Authors: Zhuang Xiaojun , Liu Caiguang , Zhan Shukai , Tian Zhenyi , Li Na , Mao Ren , Zeng Zhirong , Chen Minhu
Published: February 2021

Background and Aim: Accumulating evidence have implicated gut microbiota alterations in pediatric and adult patients with inflammatory bowel disease (IBD); however, the results of different studies are often inconsistent and even contradictory. It is believed that early changes in new-onset and treatment-naïve pediatric patients are more informative. We performed a systematic review to investigate the gut microbiota profiles in pediatric IBD and identify specific microbiota biomarkers associated with this disorder.

Methods: Electronic databases were searched from inception to 31 July 2020 for studies that observed gut microbiota alterations in pediatric patients with IBD. Study quality was assessed using the Newcastle–Ottawa scale.

Results: A total of 41 original studies investigating gut microbiota profiles in pediatric patients with IBD were included in this review. Several studies have reported a decrease in α-diversity and an overall difference in β-diversity. Although no specific gut microbiota alterations were consistently reported, a gain in Enterococcus and a significant decrease in Anaerostipes, Blautia, Coprococcus, Faecalibacterium, Roseburia, Ruminococcus, and Lachnospira were found in the majority of the included articles. Moreover, there is insufficient data to show specific microbiota bacteria associated with disease activity, location, and behavior in pediatric IBD.

Conclusions: This systematic review identified evidence for differences in the abundance of some bacteria in pediatric patients with IBD when compared to patients without IBD; however, no clear overall conclusion could be drawn from the included studies due to inconsistent results and heterogeneous methodologies. Further studies with large samples that follow more rigorous and standardized methodologies are needed.
Patagonin-CRISP: Antimicrobial Activity and Source of Antimicrobial Molecules in Duvernoy’s Gland Secretion (Philodryas patagoniensis Snake)
Authors: Badari Juliana Cuoco , Díaz-Roa Andrea , Teixeira Rocha Marisa Maria , Mendonça Ronaldo Zucatelli , Silva Junior Pedro Ismael da
Published: February 2021

Snake venom contains a variety of toxins with a range of biological activity, among these toxins cysteine-rich secreted proteins (CRISPs) can be found. The proteins of this family have masses of 20–30 kDa and display homologous amino acid sequences containing 16 cysteine residues, forming eight disulfide bonds. Some of these proteins have been explored, characterized, and described in terms of their activity; however, little is known about their range of activities. A search for new antimicrobial molecules is ongoing, as the number of microbial strains resistant to available antibiotics is increasing. We identified antimicrobial activity in the secretion of Duvernoy's gland of the rear-fanged Philodryas patagoniensis. Fractions of this venom were subjected to reverse-phase high performance liquid chromatography and analyzed to determine their antimicrobial activity with a liquid broth inhibition assay. One of the fractions presented activity against a Gram-negative bacterium and a filamentous fungus. This fraction was analyzed with LC-MS/MS, and a protein of 24,848.8 Da was identified. Database searches allowed us to identify it as a CRISP due to the presence of some unique fragments in the molecule. We called it patagonin-CRISP, as the same protein in the venom of P. patagoniensis had previously been characterized as having a different biological activity. Patagonin-CRISP presented activity at very low concentrations and showed no cytotoxic activity. This is the first time that antimicrobial activity has been identified for P. patagoniensis venom or for a CRISP family protein.
Inonotus obliquus Polysaccharide Ameliorates Azoxymethane/Dextran Sulfate Sodium-Induced Colitis-Associated Cancer in Mice via Activation of the NLRP3 Inflammasome
Authors: Li Jiawei , Qu Chao , Li Fangfang , Chen Yifang , Zheng Jinjuan , Xiao Yao , Jin Quanxin , Jin Guihua , Huang Xuezhu , Jin Dan
Published: February 2021

Inonotus obliquus polysaccharide (IOP), the primary constituent of the parasitic fungus Inonotus obliquus, has anti-tumor, anti-inflammatory, anti-oxidation effects. However, the roles of IOP on colitis-associated cancer (CAC) are still unclear. Herein, we tested the efficacy of IOP using a mouse model of CAC induced by azoxymethane and dextran sulfate sodium (AOM/DSS). We confirmed that intragastric administration of IOP decreased CAC-induced body weight loss, colon tissue damage, colon shortening, and expression of proinflammatory mediators. Meanwhile, IOP treatment increased in expression of the NLRP3 inflammasome, IL-1β, and IL-18 in the colon of CAC mice. Moreover, in vitro, IOP inhibited the proliferation of SW620 colorectal cancer cells. Finally, overexpression of NLRP3 with plasmid transfection could further enhance the activation of NLRP3 inflammasome by IOP. Taken together, these results suggest that IOP suppresses the development of CAC, possibly by activation of the NLRP3 inflammasome, and reveal that IOP may be a therapeutic drug candidate for CAC.
Involvement of Circulating Exosomal MicroRNAs in Jian-Pi-Yi-Shen Formula Protection Against Adenine-Induced Chronic Kidney Disease
Authors: Liu Xinhui , Liu Siqi , Luo Denggui , Huang Shiying , Wang Fochang , Zhang Bing , Chen Yulian , Zheng Lin , Lu Jiandong , Li Shunmin
Published: February 2021

Jian-Pi-Yi-Shen formula (JPYSF) is a traditional Chinese medicine (TCM) formula used in clinic to treat chronic kidney disease (CKD) for decades. However, the mechanisms of JPYSF in treating CKD have not been fully elucidated. The aim of the present study was to test the renoprotective effect of JPYSF on CKD rat model and investigate the potential mechanism from the perspective of serum exosomal microRNAs (miRNAs). CKD rat model was induced by feeding Sprague-Dawley rats a diet containing 0.75% w/w adenine for four weeks. The rats in the treatment group were given 10.89 g/kg JPYSF by gavage every day, starting from the 3rd week of the adenine-containing diet for six weeks. Serum biochemistry and histopathology were used to evaluate the renoprotective effects of JPYSF. Serum exosomes were isolated by ExoQuick-TC PLUS exosomes extraction kit and were identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot. Exosomal miRNAs profiling was analyzed by small RNA sequencing. The results showed that JPYSF treatment significantly lowered serum creatinine and blood urea nitrogen levels and alleviated renal pathological injury in CKD rats. Furthermore, serum exosomes were successfully isolated and identified. Small RNA sequencing revealed that 4 exosomal miRNAs (miR-192-5p, miR-194-5p, miR-802-5p, and miR-143-3p) were significantly downregulated in the CKD group and were markedly upregulated after JPYSF treatment. At last, miR-192-5p was identified as the most relevant miRNA for CKD diagnosis and JPYSF treatment. In conclusion, JPYSF protects kidney from adenine-induced CKD, which may be associated with modulation of exosomal miRNAs.
In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway
Authors: Zeng Mengnan , Ren Yingjie , Zhang Beibei , Wang Shengchao , Liu Meng , Jia Jufang , Guo Pengli , Zhang Qinqin , Zheng Xiaoke , Feng Weisheng
Published: February 2021

Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ERβ, and antagonising ERβ decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ERβ. However, after antagonizing ERβ, the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ERβ. In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ERβ-STAT3 signaling. Our findings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L.
Co-Therapy of Pegylated G-CSF and Ghrelin for Enhancing Survival After Exposure to Lethal Radiation
Authors: Kiang Juliann G. , Zhai Min , Lin Bin , Smith Joan T. , Anderson Marsha N. , Jiang Suping
Published: February 2021

Exposure to ionizing radiation (radiation injury, RI) in nuclear-related episode is evident to be life-threatening. RI occurs at levels of organs, tissues, cytosols, or nucleus. Their mechanisms are still not fully understood. FDA approves pegylated granulocyte colony-stimulating factor (Neulasta™, Peg-G-CSF) for acute hematopoietic syndrome and has been shown to save lives after lethal RI. We aimed to test whether Ghrelin enhanced Peg-G-CSF’s efficacy to save more lives after lethal RI. B6D2F1/J female mice were used for the study. They received 9.5 Gy (LD50/30 at 0.4 Gy/min) emitted from the60Co-γ-photon radiation facility. Peg-G-CSF was injected subcutaneously at 1 mg/kg once on days 1, 8, and 15 after irradiation. Ghrelin contains 28 amino acid and is a hunger peptide that has been shown to stimulate food intake, promote intestinal epithelial cell proliferation, elevates immunity, inhibits brain hemorrhage, and increases stress-coping. Ghrelin was injected subcutaneously at 113 μg/kg once on days 1, 2, and 3 after irradiation. Survival, body weight, water consumption, hematology, spleen weight, splenocytes, bone marrow cells, and histology of bone marrow and ileum were performed. We observed that radiation resulted in 30-days survival by 30%. RI decreased their body weights and water consumption volumes. On the 30th day post-RI, platelets and WBCs such as basophils, eosinophils, monocytes, lymphocytes, neutrophils and leukocytes were still significantly decreased in surviving mice. Likewise, their RBC, hemoglobin, hematocrit, and splenocytes remained low; splenomegaly was found in these mice. Bone marrow in surviving RI animals maintained low cellularity with high counts of fat cells and low counts of megakaryocytes. Meanwhile, ileum histology displayed injury. However, mice co-treated with both drugs 24 h after RI resulted in 30-days survival by 45% above the vehicle group. Additionally, the body-weight loss was mitigated, the acute radiation syndrome was reduced. This co-therapy significantly increased neutrophils, eosinophils, leukocytes, and platelets in circulation, inhibited splenomegaly, and increased bone marrow cells. Histopathological analysis showed significant improvement on bone marrow cellularity and ileum morphology. In conclusion, the results provide a proof of concept and suggest that the co-therapy of Peg-G-CSF and Ghrelin is efficacious to ameliorate RI.
The Underlying Mechanism of Modulation of Transient Receptor Potential Melastatin 3 by protons
Authors: Hossain Saad Md Zubayer , Xiang Liuruimin , Liao Yan-Shin , Reznikov Leah R. , Du Jianyang
Published: February 2021

Transient receptor potential melastatin 3 channel (TRPM3) is a calcium-permeable nonselective cation channel that plays an important role in modulating glucose homeostasis in the pancreatic beta cells. However, how TRPM3 is regulated under physiological and pathological conditions is poorly understood. In this study, we found that both intracellular and extracellular protons block TRPM3 through its binding sites in the pore region. We demonstrated that external protons block TRPM3 with an inhibitory pH50 of 5.5. whereas internal protons inhibit TRPM3 with an inhibitory pH50 of 6.9. We identified three titratable residues, D1059, D1062, and D1073, at the vestibule of the channel pore that contributes to pH sensitivity. The mutation of D1073Q reduced TRPM3 current by low external pH 5.5 from 62 ± 3% in wildtype to 25 ± 6.0% in D1073Q mutant. These results indicate that D1073 is essential for pH sensitivity. In addition, we found that a single mutation of D1059 or D1062 enhanced pH sensitivity. In summary, our findings identify molecular determinants respionsible for the pH regulation of TRPM3. The inhibition of TRPM3 by protons may indicate an endogenous mechanism governing TRPM3 gating and its physiological/pathological functions.
Proarrhythmic Electrical Remodeling by Noncardiomyocytes at Interfaces With Cardiomyocytes Under Oxidative Stress
Authors: Zhao Yali , Iyer Shankar , Tavanaei Maryam , Nguyen Nicole T. , Lin Andrew , Nguyen Thao P.
Published: February 2021

Life-threatening ventricular arrhythmias, typically arising from interfaces between fibrosis and surviving cardiomyocytes, are feared sequelae of structurally remodeled hearts under oxidative stress. Incomplete understanding of the proarrhythmic electrical remodeling by fibrosis limits the development of novel antiarrhythmic strategies. To define the mechanistic determinants of the proarrhythmia in electrical crosstalk between cardiomyocytes and noncardiomyocytes, we developed a novel in vitro model of interface between neonatal rat ventricular cardiomyocytes (NRVMs) and controls [NRVMs or connexin43 (Cx43)-deficient HeLa cells] vs. Cx43+ noncardiomyocytes [aged rat ventricular myofibroblasts (ARVFs) or HeLaCx43 cells]. We performed high-speed voltage-sensitive optical imaging at baseline and following acute H2O2 exposure. In NRVM-NRVM and NRVM-HeLa controls, no arrhythmias occurred under either experimental condition. In the NRVM-ARVF and NRVM-HeLaCx43 groups, Cx43+ noncardiomyocytes enabled passive decremental propagation of electrical impulses and impaired NRVM activation and repolarization, thereby slowing conduction and prolonging action potential duration. Following H2O2 exposure, arrhythmia triggers, automaticity, and non-reentrant and reentrant arrhythmias emerged. This study reveals that myofibroblasts (which generate cardiac fibrosis) and other noncardiomyocytes can induce not only structural remodeling but also electrical remodeling and that electrical remodeling by noncardiomyocytes can be particularly arrhythmogenic in the presence of an oxidative burst. Synergistic electrical remodeling between H2O2 and noncardiomyocytes may account for the clinical arrhythmogenicity of myofibroblasts at fibrotic interfaces with cardiomyocytes in ischemic/non-ischemic cardiomyopathies. Understanding the enhanced arrhythmogenicity of synergistic electrical remodeling by H2O2 and noncardiomyocytes may guide novel safe-by-design antiarrhythmic strategies for next-generation iatrogenic interfaces between surviving native cardiomyocytes and exogenous stem cells or engineered tissues in cardiac regenerative therapies.
Assessing Intervention Effects in Sentence Processing: Object Relatives vs. Subject Control
Authors: Delgado João , Raposo Ana , Santos Ana Lúcia
Published: February 2021

Object relative clauses are harder to process than subject relative clauses. UnderGrillo’s (2009)Generalized Minimality framework, complexity effects of object relatives are construed as intervention effects, which result from an interaction between locality constraints on movement (Relativized Minimality) and the sentence processing system. Specifically, intervention of the subject DP in the movement dependency is expected to generate a minimality violation whenever processing limitations render the moved object underspecified, resulting in compromised comprehension. In the present study, assuming Generalized Minimality, we compared the processing of object relatives with the processing of subject control in ditransitives, which, like object relatives, instantiates a syntactic dependency across an intervening DP. This comparison is justified by the current debate on whether Control should be analyzed as movement: if control involves movement of the controller DP, as proposed byHornstein (1999), a parallel between the processing of object relatives and subject control in ditransitives may be anticipated on the basis of intervention. In addition, we explored whether general cognitive factors contribute to complexity effects ascribed to movement across a DP. Sixty-nine adult speakers of European Portuguese read sentences and answered comprehension probes in a self-paced reading task with moving-window display, comprising four experimental conditions:Subject Relatives;Object Relatives;Subject Control;Object Control. Furthermore, participants performed four supplementary tasks, serving as measures of resistance to interference, lexical knowledge, working memory capacity and lexical access ability. The results from the reading task showed that whereas object relatives were harder to process than subject relatives, subject control was not harder to process than object control, arguing against recent movement accounts of control. Furthermore, we found that whereas object relative complexity effects assessed by response times to comprehension probes interacted with Reading Span, object relative complexity effects assessed by comprehension accuracy and reading times did not interact with any of the supplementary tasks. We discuss these results in light of Generalized Minimality and the hypothesis of modularity in syntactic processing (Caplan and Waters, 1999).
Self-Reported Voluntary Blame-Taking: Kinship Before Friendship and No Effect of Incentives
Authors: Schneider Teresa , Sauerland Melanie , Merckelbach Harald , Puschke Jens , Cohrs J. Christopher
Published: February 2021

Inspired by theories of prosocial behavior, we tested the effect of relationship status and incentives on intended voluntary blame-taking in two experiments (Experiment 2 was pre-registered). Participants (NE1 = 211 and NE2 = 232) imagined a close family member, a close friend, or an acquaintance and read a scenario that described this person committing a minor traffic offense. The person offered either a monetary, social, or no incentive for taking the blame. Participants indicated their willingness to take the blame and reasons for and against blame-taking. Overall, a sizable proportion of participants indicated to be willing to take the blame (E1: 57.8%; E2: 34.9%). Blame-taking rates were higher for family members than close friends or acquaintances in both experiments, as expected. Unexpectedly, there was no difference between a close friend and an acquaintance in Experiment 2. Social incentives did not have an effect on voluntary blame-taking in either experiment. Neither did we find an interaction between relationship status and incentives. The results highlight the importance of kin relationships in the context of voluntary blame-taking.