bluuebunny/crossref_metadata_2025 huggingface dataset:
Activating beyond Informing: Action-Oriented Utilization of WeChat by Chinese Environmental NGOs
Authors: Xu Jing , Zhang Huijun
Published: March 2022

Social media has generated new opportunities for non-governmental organizations (NGOs) to inform and educate publics, and more powerfully, it enables NGOs to mobilize people to act. To enhance understanding how social media functions to serve action-oriented communication for organizations, we focused on WeChat, the largest social media in China. We examined an original dataset of 2472 articles posted by 175 environmental NGOs (ENGOs) during a two-month period in 2019 on WeChat. A qualitative content analysis was conducted to identify what actions ENGOs use WeChat to mobilize. We used statistical methods to analyze the effectiveness of ENGOs’ action-oriented utilization of WeChat and the organizational differences in the adoption of action-oriented messages. This study reveals that more than a quarter of the articles were mobilizational in nature. There were three major types of action ENGOs mobilize via WeChat. Though the informational use of WeChat is extensive, users prefer action-oriented messages and the activating strategy is more effective in motivating users to engage. Our analysis indicates that the more participatory people feel, the more likely they are to respond to WeChat messages, and the more they are involved. Our findings have implications for how the adoption of WeChat helps engender new paradigms of citizen participation.
Latent Classes of Polysubstance Use and Associations with HIV Risk and Structural Vulnerabilities among Cisgender Women Who Engage in Street-Based Transactional Sex in Baltimore City
Authors: Beckham Sam Wilson , Glick Jennifer L. , Schneider Kristin E. , Allen Sean T. , Shipp Lillian , White Rebecca Hamilton , Park Ju Nyeong , Sherman Susan G.
Published: March 2022

We describe patterns of polysubstance use and associations with HIV risk-related behaviors among women engaged in street-based transactional sex, an understudied yet important population and area of research. This sample was restricted to cisgender women who reported drug use (n = 244) in the baseline of the longitudinal SAPPHIRE cohort study. Latent class analysis (LCA) was conducted using drug use measures (route of administration (injection/non-injection); type of drug (specific opioids, stimulants)) and selection based on fit statistics and qualitative interpretation of the classes. Polysubstance use was prevalent (89% ≥ 2), and 68% had injected drugs in the past 3 months. A three-class solution was selected: Class 1 (“heroin/cocaine use”, 48.4% of sample), Class 2 (“poly-opioid use”, 21.3%), and Class 3 (“poly-route, polysubstance use”, 30.3%). Class 3 was significantly younger, and Class 2 was disproportionately non-White. Women reported high levels of housing (63%) and food (55%) insecurity, condomless sex with clients (40%), and client-perpetrated violence (35%), with no significant differences by class. Obtaining syringes from syringe services programs differed significantly by class, despite injection behaviors in all classes. Tailored HIV and overdose prevention programming that considers drug use patterns would strengthen their impact.
Impact of Activity Tracker Usage in Combination with a Physical Activity Intervention on Physical and Cognitive Parameters in Healthy Adults Aged 60+: A Randomized Controlled Trial
Authors: Auerswald Tina , Hendker Anna , Ratz Tiara , Lippke Sonia , Pischke Claudia R. , Peters Manuela , Meyer Jochen , Holdt Kai von , Voelcker-Rehage Claudia
Published: March 2022

Regular physical activity (PA) is of central importance for healthy aging and has a well-known impact on helping older adults maintain their cognitive and physical health. Thus, we aimed to compare the effectiveness of two physical activity interventions primarily conducted at home (print-based or web-based vs. web-based plus the use of an activity tracker) on cognitive and physical health parameters in older adults. Data of participants (n = 551, 60–80 years) were analyzed after being randomly allocated to a waitlist control group (CG), a web-based or print-based intervention group (IG) or a web-based intervention group that also included the use of an activity tracker (AG). Measured parameters were grip strength, endurance (two-minute step test), gait speed (four-meter walk test), cognition (Simon task; balanced integration score (BIS), reaction time and accuracy) and physical self-concept (Physical Self-Description Questionnaire (PSDQ)). We found the highest effect sizes in all measured dimensions for AG (grip strength, endurance, gait speed, reaction time, physical self-concept), followed by IG (endurance, gait speed, reaction time, physical self-concept) and CG (endurance, gait speed, BIS). Findings suggest that a combined web-based and activity tracker intervention may improve physical functions, physical self-concept, and cognition in community-dwelling older adults.
Toxic Asset Subsidies and the Early Redemption of TALF Loans
Authors: Wilson Linus
Published: March 2022

This paper develops a formula to numerically estimate the unsubsidized, fair-market value of the toxic assets purchased with Federal Reserve loans. It finds that subsidy rates on these loans were on average 33.9 percent at origination. In contrast, by the 3rd quarter of the 2010, there was on average no subsidy in TALF loans. The theoretical model is used to predict the early redemption of Term Asset-Backed Securities Loan Facility (TALF) loans used to purchase commercial mortgage-backed securities (CMBS). The predictions of the model are strongly supported by the data. In addition, this paper looks at the determinants of early redemption. CMBS originated inside the peak bubble years of 2005–2007 were much less likely to be redeemed early. The giant investment managers, Blackrock and PIMCO, were much more likely to redeem their TALF loans early than smaller investment managers.
Toxic Potential of Cerrado Plants on Different Organisms
Authors: Rocha Jamira Dias , Carneiro Fernanda Melo , Fernandes Amanda Silva , Morais Jéssyca Moreira , Borges Leonardo Luiz , Chen-Chen Lee , de Almeida Luciane Madureira , Bailão Elisa Flávia Luiz Cardoso
Published: March 2022

Cerrado has many compounds that have been used as biopesticides, herbicides, medicines, and others due to their highly toxic potential. Thus, this review aims to present information about the toxicity of Cerrado plants. For this purpose, a review was performed using PubMed, Science Direct, and Web Of Science databases. After applying exclusion criteria, 187 articles published in the last 20 years were selected and analyzed. Detailed information about the extract preparation, part of the plant used, dose/concentration tested, model system, and employed assay was provided for different toxic activities described in the literature, namely cytotoxic, genotoxic, mutagenic, antibacterial, antifungal, antiviral, insecticidal, antiparasitic, and molluscicidal activities. In addition, the steps to execute research on plant toxicity and the more common methods employed were discussed. This review synthesized and organized the available research on the toxic effects of Cerrado plants, which could contribute to the future design of new environmentally safe products.
An Efficient and Universal Protoplast Isolation Protocol Suitable for Transient Gene Expression Analysis and Single-Cell RNA Sequencing
Authors: Wang Juanjuan , Wang Yang , Lü Tianfeng , Yang Xia , Liu Jing , Dong Yang , Wang Yinzheng
Published: March 2022

The recent advent of single-cell RNA sequencing (scRNA-seq) has enabled access to the developmental landscape of a complex organ by monitoring the differentiation trajectory of every specialized cell type at the single-cell level. A main challenge in this endeavor is dissociating plant cells from the rigid cell walls and some species are recalcitrant to such cellular isolation. Here, we describe the establishment of a simple and efficient protocol for protoplast preparation in Chirita pumila, which includes two consecutive digestion processes with different enzymatic buffers. Using this protocol, we generated viable cell suspensions suitable for an array of expression analyses, including scRNA-seq. The universal application of this protocol was further tested by successfully isolating high-quality protoplasts from multiple organs (petals, fruits, tuberous roots, and gynophores) from representative species on the key branches of the angiosperm lineage. This work provides a robust method in plant science, overcoming barriers to isolating protoplasts in diverse plant species and opens a new avenue to study cell type specification, tissue function, and organ diversification in plants.
Comparative Analysis of Transcriptional Responses to Genotoxic and Non-Genotoxic Agents in the Blood Cell Model TK6 and the Liver Model HepaRG
Authors: Kreuzer Katrin , Sprenger Heike , Braeuning Albert
Published: March 2022

Transcript signatures are a promising approach to identify and classify genotoxic and non-genotoxic compounds and are of interest as biomarkers or for future regulatory application. Not much data, however, is yet available about the concordance of transcriptional responses in different cell types or tissues. Here, we analyzed transcriptomic responses to selected genotoxic food contaminants in the human p53-competent lymphoblastoid cell line TK6 using RNA sequencing. Responses to treatment with five genotoxins, as well as with four non-genotoxic liver toxicants, were compared with previously published gene expression data from the human liver cell model HepaRG. A significant overlap of the transcriptomic changes upon genotoxic stress was detectable in TK6 cells, whereas the comparison with the HepaRG model revealed considerable differences, which was confirmed by bioinformatic data mining for cellular upstream regulators or pathways. Taken together, the study presents a transcriptomic signature for genotoxin exposure in the human TK6 blood cell model. The data demonstrate that responses in different cell models have considerable variations. Detection of a transcriptomic genotoxin signature in blood cells indicates that gene expression analyses of blood samples might be a valuable approach to also estimate responses to toxic exposure in target organs such as the liver.
Current Advances in 3D Bioprinting for Cancer Modeling and Personalized Medicine
Authors: Germain Nicolas , Dhayer Melanie , Dekiouk Salim , Marchetti Philippe
Published: March 2022

Tumor cells evolve in a complex and heterogeneous environment composed of different cell types and an extracellular matrix. Current 2D culture methods are very limited in their ability to mimic the cancer cell environment. In recent years, various 3D models of cancer cells have been developed, notably in the form of spheroids/organoids, using scaffold or cancer-on-chip devices. However, these models have the disadvantage of not being able to precisely control the organization of multiple cell types in complex architecture and are sometimes not very reproducible in their production, and this is especially true for spheroids. Three-dimensional bioprinting can produce complex, multi-cellular, and reproducible constructs in which the matrix composition and rigidity can be adapted locally or globally to the tumor model studied. For these reasons, 3D bioprinting seems to be the technique of choice to mimic the tumor microenvironment in vivo as closely as possible. In this review, we discuss different 3D-bioprinting technologies, including bioinks and crosslinkers that can be used for in vitro cancer models and the techniques used to study cells grown in hydrogels; finally, we provide some applications of bioprinted cancer models.
Thrombin-Activated Platelets Protect Vascular Endothelium against Tumor Cell Extravasation by Targeting Endothelial VCAM-1
Authors: Lee Chiou-Mei , Chang Ming-Ling , Chen Ren-Hao , Chen Fan-Wen , Liu Jo-Chuan , Kuo Shun-Li , Peng Hsin-Hsin
Published: March 2022

When activated by thrombin, the platelets release their granular store of factors. These thrombin-activated platelets (TAPLT) have been shown to be capable of ameliorating pro-inflammatory processes. In this study, we tested if TAPLT could also protect the endothelium against tumor-related pro-inflammatory changes that promote angiogenesis and metastasis. Using endothelial cell (EC) models in vitro, we demonstrated that TAPLT protected EC against tumor conditioned medium (TCM)-induced increases of reactive oxygen species (ROS) production, EC permeability and angiogenesis, and inhibited transendothelial migration that was critical for cancer cell extravasation and metastasis. In vivo observations of TAPLT-mediated inhibition of angiogenesis and pulmonary colonization in a BALB/c nude mouse model were consistent with the in vitro findings. Neutralization of vascular cell adhesion molecule-1 (VCAM-1) binding significantly inhibited the ability of TAPLT to interact with EC and abrogated the TAPLT-mediated protection of EC against tumor angiogenesis and metastasis. Taken together, these findings suggest that VCAM-1-mediated linkage to EC is required for TAPLT to confer protection of EC against tumor-induced permeation and angiogenesis, thereby resisting tumor extravasation and metastasis.
Expression of the Chemokine Receptor CCR1 in Burkitt Lymphoma Cell Lines Is Linked to the CD10-Negative Cell Phenotype and Co-Expression of the EBV Latent Genes EBNA2, LMP1, and LMP2
Authors: Zvejniece Laura , Kozireva Svetlana , Rudevica Zanna , Leonciks Ainars , Ehlin-Henriksson Barbro , Kashuba Elena , Kholodnyuk Irina
Published: March 2022

Chemokines and their receptors regulate the migration of immune cells and the dissemination of cancer cells. CCR1, CCR2, CCR3, and CCR5 all belong to a single protein homology cluster and respond to the same inflammatory chemokines. We previously reported that CCR1 and CCR2B are induced upon Epstein-Barr virus (EBV) infection of B cells in vitro. EBV is present in almost all cases of endemic Burkitt lymphoma (BL); however, the contribution of EBV in the pathogenesis of the disease is not fully understood. Here, we analyzed the relation of the expression of CCR1, CCR2, CCR3, and CCR5, the EBV DNA load and expression of EBV latent genes in nine EBV-carrying and four EBV-negative BL cell lines. We revealed that CCR1 is expressed at high mRNA and protein levels in two CD10-negative BL cell lines with co-expression of the EBV latent genes EBNA2, LMP1, and LMP2. Low levels of CCR2 transcripts were found in three BL cell lines. CCR3 and CCR5 transcripts were hardly detectable. Our data suggest that in vivo, CCR1 may be involved in the dissemination of BL cells and in the selection of BL cells with restricted EBV gene expression programs.
The Role of Advanced Glycation End Products and Its Soluble Receptor in Kidney Diseases
Authors: Steenbeke Mieke , Speeckaert Reinhart , Desmedt Stéphanie , Glorieux Griet , Delanghe Joris R. , Speeckaert Marijn M.
Published: March 2022

Patients with chronic kidney disease (CKD) are more prone to oxidative stress and chronic inflammation, which may lead to an increase in the synthesis of advanced glycation end products (AGEs). Because AGEs are mostly removed by healthy kidneys, AGE accumulation is a result of both increased production and decreased kidney clearance. On the other hand, AGEs may potentially hasten decreasing kidney function in CKD patients, and are independently related to all-cause mortality. They are one of the non-traditional risk factors that play a significant role in the underlying processes that lead to excessive cardiovascular disease in CKD patients. When AGEs interact with their cell-bound receptor (RAGE), cell dysfunction is initiated by activating nuclear factor kappa-B (NF-κB), increasing the production and release of inflammatory cytokines. Alterations in the AGE-RAGE system have been related to the development of several chronic kidney diseases. Soluble RAGE (sRAGE) is a decoy receptor that suppresses membrane-bound RAGE activation and AGE-RAGE-related toxicity. sRAGE, and more specifically, the AGE/sRAGE ratio, may be promising tools for predicting the prognosis of kidney diseases. In the present review, we discuss the potential role of AGEs and sRAGE as biomarkers in different kidney pathologies.
Porphyromonas gingivalis W83 Membrane Components Induce Distinct Profiles of Metabolic Genes in Oral Squamous Carcinoma Cells
Authors: Groeger Sabine , Herrmann Jens Martin , Chakraborty Trinad , Domann Eugen , Ruf Sabine , Meyle Joerg
Published: March 2022

Periodontitis, a chronic inflammatory disease is caused by a bacterial biofilm, affecting all periodontal tissues and structures. This chronic disease seems to be associated with cancer since, in general, inflammation intensifies the risk for carcinoma development and progression. Interactions between periodontal pathogens and the host immune response induce the onset of periodontitis and are responsible for its progression, among them Porphyromonas gingivalis (P. gingivalis), a Gram-negative anaerobic rod, capable of expressing a variety of virulence factors that is considered a keystone pathogen in periodontal biofilms. The aim of this study was to investigate the genome-wide impact of P. gingivalis W83 membranes on RNA expression of oral squamous carcinoma cells by transcriptome analysis. Human squamous cell carcinoma cells (SCC-25) were infected for 4 and 24 h with extracts from P. gingivalis W83 membrane, harvested, and RNA was extracted. RNA sequencing was performed, and differential gene expression and enrichment were analyzed using GO, KEGG, and REACTOME. The results of transcriptome analysis were validated using quantitative real-time PCR with selected genes. Differential gene expression analysis resulted in the upregulation of 15 genes and downregulation of 1 gene after 4 h. After 24 h, 61 genes were upregulated and 278 downregulated. GO, KEGG, and REACTONE enrichment analysis revealed a strong metabolic transcriptomic response signature, demonstrating altered gene expressions after 4 h and 24 h that mainly belong to cell metabolic pathways and replication. Real-time PCR of selected genes belonging to immune response, signaling, and metabolism revealed upregulated expression of CCL20, CXCL8, NFkBIA, TNFAIP3, TRAF5, CYP1A1, and NOD2. This work sheds light on the RNA transcriptome of human oral squamous carcinoma cells following stimulation with P. gingivalis membranes and identifies a strong metabolic gene expression response to this periodontal pathogen. The data provide a base for future studies of molecular and cellular interactions between P. gingivalis and oral epithelium to elucidate the basic mechanisms of periodontitis and the development of cancer.
Diversity-Oriented Synthesis Catalyzed by Diethylaminosulfur-Trifluoride—Preparation of New Antitumor Ecdysteroid Derivatives
Authors: Vágvölgyi Máté , Kocsis Endre , Nové Márta , Szemerédi Nikoletta , Spengler Gabriella , Kele Zoltán , Berkecz Róbert , Gáti Tamás , Tóth Gábor , Hunyadi Attila
Published: March 2022

Fluorine represents a privileged building block in pharmaceutical chemistry. Diethylaminosulfur-trifluoride (DAST) is a reagent commonly used for replacement of alcoholic hydroxyl groups with fluorine and is also known to catalyze water elimination and cyclic Beckmann-rearrangement type reactions. In this work we aimed to use DAST for diversity-oriented semisynthetic transformation of natural products bearing multiple hydroxyl groups to prepare new bioactive compounds. Four ecdysteroids, including a new constituent of Cyanotis arachnoidea, were selected as starting materials for DAST-catalyzed transformations. The newly prepared compounds represented combinations of various structural changes DAST was known to catalyze, and a unique cyclopropane ring closure that was found for the first time. Several compounds demonstrated in vitro antitumor properties. A new 17-N-acetylecdysteroid (13) exerted potent antiproliferative activity and no cytotoxicity on drug susceptible and multi-drug resistant mouse T-cell lymphoma cells. Further, compound 13 acted in significant synergism with doxorubicin without detectable direct ABCB1 inhibition. Our results demonstrate that DAST is a versatile tool for diversity-oriented synthesis to expand chemical space towards new bioactive compounds.
Poly(ethylene-Co-vinyl Alcohol)/Titanium Dioxide Nanocomposite: Preparation and Characterization of Properties for Potential Use in Bone Tissue Engineering
Authors: Saeed Waseem Sharaf , Alotaibi Dalal H. , Al-Odayni Abdel-Basit , Haidyrah Ahmed S. , Al-Owais Ahmad Abdulaziz , Khan Rawaiz , De Vera Merry Angelyn Tan , Alrahlah Ali , Aouak Taieb
Published: March 2022

A series of poly(ethylene-co-vinyl alcohol)/titanium dioxide (PEVAL/TiO2) nanocomposites containing 1, 2, 3, 4 and 5 wt% TiO2 were prepared by the solvent casting method. These prepared hybrid materials were characterized by Fourier-transform infrared (FT-IR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and scanning electron microscopy (SEM). The pores and their interconnections inside these nanocomposites were created using naphthalene microparticles used as a porogen after having been extracted by sublimation under a high vacuum at temperatures slightly below the glass transition temperature. A cellular activity test of these hybrid materials was performed on human gingival fibroblast cells (HGFs) in accordance with ISO 10993-5 and ISO 10993-12 standards. The bioviability (cell viability) of HGFs was evaluated after 1, 4 and 7 days using Alamar Blue®. The results were increased cell activity throughout the different culture times and a significant increase in cell activity in all samples from Day 1 to Day 7, and all systems tested showed significantly higher cell viability than the control group on Day 7 (p < 0.002). The adhesion of HGFs to the scaffolds studied by SEM showed that HGFs were successfully cultured on all types of scaffolds.
A Novel Family of Winged-Helix Single-Stranded DNA-Binding Proteins from Archaea
Authors: Huang Can , Liu Xuehui , Chen Yuanyuan , Zhou Junshi , Li Wenqian , Ding Niannian , Huang Li , Chen Jingyu , Zhang Zhenfeng
Published: March 2022

The winged helix superfamily comprises a large number of structurally related nucleic acid-binding proteins. While these proteins are often shown to bind dsDNA, few are known to bind ssDNA. Here, we report the identification and characterization of Sul7s, a novel winged-helix single-stranded DNA binding protein family highly conserved in Sulfolobaceae. Sul7s from Sulfolobus islandicus binds ssDNA with an affinity approximately 15-fold higher than that for dsDNA in vitro. It prefers binding oligo(dT)30 over oligo(dC)30 or a dG-rich 30-nt oligonucleotide, and barely binds oligo(dA)30. Further, binding by Sul7s inhibits DNA strand annealing, but shows little effect on the melting temperature of DNA duplexes. The solution structure of Sul7s determined by NMR shows a winged helix-turn-helix fold, consisting of three α-helices, three β-strands, and two short wings. It interacts with ssDNA via a large positively charged binding surface, presumably resulting in ssDNA deformation. Our results shed significant light on not only non-OB fold single-stranded DNA binding proteins in Archaea, but also the divergence of the winged-helix proteins in both function and structure during evolution.
NAD+ Anabolism Disturbance Causes Glomerular Mesangial Cell Injury in Diabetic Nephropathy
Authors: Li Xue , Li Yankun , Li Fengxia , Chen Qi , Zhao Zhonghua , Liu Xueguang , Zhang Nong , Li Hui
Published: March 2022

The homeostasis of NAD+ anabolism is indispensable for maintaining the NAD+ pool. In mammals, the mainly synthetic pathway of NAD+ is the salvage synthesis, a reaction catalyzed by nicotinamide mononucleotide adenylyltransferase (NAMPT) and nicotinamide mononucleotide adenylyltransferase (NMNATs) successively, converting nicotinamide (NAM) to nicotinamide mononucleotide (NMN) and NMN to NAD+, respectively. However, the relationship between NAD+ anabolism disturbance and diabetic nephropathy (DN) remains elusive. Here our study found that the disruption of NAD+ anabolism homeostasis caused an elevation in both oxidative stress and fibronectin expression, along with a decrease in Sirt1 and an increase in both NF-κB P65 expression and acetylation, culminating in extracellular matrix deposition and globular fibrosis in DN. More importantly, through constitutively overexpressing NMNAT1 or NAMPT in human mesangial cells, we revealed NAD+ levels altered inversely with NMN levels in the context of DN and, further, their changes affect Sirt1/NF-κB P65, thus playing a crucial role in the pathogenesis of DN. Accordingly, FK866, a NAMPT inhibitor, and quercetin, a Sirt1 agonist, have favorable effects on the maintenance of NAD+ homeostasis and renal function in db/db mice. Collectively, our findings suggest that NMN accumulation may provide a causal link between NAD+ anabolism disturbance and diabetic nephropathy (DN) as well as a promising therapeutic target for DN treatment.
BcSOC1 Promotes Bolting and Stem Elongation in Flowering Chinese Cabbage
Authors: Wang Yudan , Huang Xiu , Huang Xinmin , Su Wei , Hao Yanwei , Liu Houcheng , Chen Riyuan , Song Shiwei
Published: March 2022

Flowering Chinese cabbage is one of the most economically important stalk vegetables. However, the molecular mechanisms underlying bolting, which is directly related to stalk quality and yield, in this species remain unknown. Previously, we examined five key stem development stages in flowering Chinese cabbage. Here, we identified a gene, BcSOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1), in flowering Chinese cabbage using transcriptome analysis, whose expression was positively correlated with bolting. Exogenous gibberellin (GA3) and low-temperature treatments significantly upregulated BcSOC1 and promoted early bolting and flowering. Additionally, BcSOC1 overexpression accelerated early flowering and stem elongation in both Arabidopsis and flowering Chinese cabbage, whereas its knockdown dramatically delayed bolting and flowering and inhibited stem elongation in the latter; the inhibition of stem elongation was more notable than delayed flowering. BcSOC1 overexpression also induced cell expansion by upregulating genes encoding cell wall structural proteins, such as BcEXPA11 (cell wall structural proteins and enzymes) and BcXTH3 (xyloglucan endotransglycosidase/hydrolase), upon exogenous GA3 and low-temperature treatments. Moreover, the length of pith cells was correlated with stem height, and BcSOC1 interacted with BcAGL6 (AGAMOUS-LIKE 6) and BcAGL24 (AGAMOUS-LIKE 24). Thus, BcSOC1 plays a vital role in bolting and stem elongation of flowering Chinese cabbage and may play a novel role in regulating stalk development, apart from the conserved function of Arabidopsis SOC1 in flowering alone.
The P2Y2 Receptor C-Terminal Tail Modulates but Is Dispensable for β-Arrestin Recruitment
Authors: Pottie Eline , Storme Jolien , Stove Christophe P.
Published: March 2022

The P2Y2 receptor (P2Y2R) is a G protein-coupled receptor that is activated by extracellular ATP and UTP, to a similar extent. This allows it to play roles in the cell’s response to the (increased) release of these nucleotides, e.g., in response to stress situations, including mechanical stress and oxygen deprivation. However, despite its involvement in important (patho)physiological processes, the intracellular signaling induced by the P2Y2R remains incompletely described. Therefore, this study implemented a NanoBiT® functional complementation assay to shed more light on the recruitment of β-arrestins (βarr1 and βarr2) upon receptor activation. More specifically, upon determination of the optimal configuration in this assay system, the effect of different (receptor) residues/regions on βarr recruitment to the receptor in response to ATP or UTP was estimated. To this end, the linker was shortened, the C-terminal tail was truncated, and phosphorylatable residues in the third intracellular loop of the receptor were mutated, in either singly or multiply adapted constructs. The results showed that none of the introduced adaptations entirely abolished the recruitment of either βarr, although EC50 values differed and time-luminescence profiles appeared to be qualitatively altered. The results hint at the C-terminal tail modulating the interaction with βarr, while not being indispensable.
The Human-Restricted Isoform of the α7 nAChR, CHRFAM7A: A Double-Edged Sword in Neurological and Inflammatory Disorders
Authors: Di Lascio Simona , Fornasari Diego , Benfante Roberta
Published: March 2022

CHRFAM7A is a relatively recent and exclusively human gene arising from the partial duplication of exons 5 to 10 of the α7 neuronal nicotinic acetylcholine receptor subunit (α7 nAChR) encoding gene, CHRNA7. CHRNA7 is related to several disorders that involve cognitive deficits, including neuropsychiatric, neurodegenerative, and inflammatory disorders. In extra-neuronal tissues, α7nAChR plays an important role in proliferation, differentiation, migration, adhesion, cell contact, apoptosis, angiogenesis, and tumor progression, as well as in the modulation of the inflammatory response through the “cholinergic anti-inflammatory pathway”. CHRFAM7A translates the dupα7 protein in a multitude of cell lines and heterologous systems, while maintaining processing and trafficking that are very similar to the full-length form. It does not form functional ion channel receptors alone. In the presence of CHRNA7 gene products, dupα7 can assemble and form heteromeric receptors that, in order to be functional, should include at least two α7 subunits to form the agonist binding site. When incorporated into the receptor, in vitro and in vivo data showed that dupα7 negatively modulated α7 activity, probably due to a reduction in the number of ACh binding sites. Very recent data in the literature report that the presence of the duplicated gene may be responsible for the translational gap in several human diseases. Here, we will review the studies that have been conducted on CHRFAM7A in different pathologies, with the intent of providing evidence regarding when and how the expression of this duplicated gene may be beneficial or detrimental in the pathogenesis, and eventually in the therapeutic response, to CHRNA7-related neurological and non-neurological diseases.
Cardiac Glycosides Increase Temozolomide Anticancer Activity in Therapy Resistant Glioblastoma Cells
Authors: Valluri Anisha , Lawrence Logan , Denning Krista L. , Cuda Jonathan , Zhu Guo-Zhang
Published: March 2022

Glioblastomas (GBMs) are a form of malignant gliomas characterized by a dismal prognosis. Standard treatment for glioblastoma patients is combined maximal surgical removal of the tumor with postoperative radiotherapy and concomitant chemotherapy with Temozolomide (TMZ). Among the histological characteristics that contribute to GBM progression are the rapid proliferation and neo-angiogenetic processes. The Na+/K+-ATPase is a transporter that promotes the migration of cancer cells, and its aberrant expression and activity have been associated with several cancers, including GBM. Using cardiac glycosides, we examined the effects of direct inhibition of the Na+/K+-ATPase in glioblastoma cells in vitro. We found that cardiac glycoside Digoxin is an effective anticancer agent on several glioma cell lines via Na+/K+-ATPase inhibition. Drug cytotoxicity assays showed that Digoxin as monotherapy significantly increased cell death and increased the efficacy of Temozolomide (TMZ) in the glioma cell lines T98G, U-97 MG, and primary GBM cells BNC-6. Additionally, Digoxin exhibited important anti-migratory effects on the highly aggressive and chemotherapy-resistant T98G glioma cell-line, demonstrating a potential therapeutic role for cardiac glycosides.
Flow in Pillow-Plate Channels for High-Speed Turbomachinery Heat Exchangers
Authors: Sundermeier Stephan , Passmann Maximilian , aus der Wiesche Stefan , Kenig Eugeny Y.
Published: March 2022

In numerous turbomachinery applications, e.g., in aero-engines with regenerators for improving specific fuel consumption (SFC), heat exchangers with low-pressure loss are required. Pil low-plate heat exchangers (PPHE) are a novel exchanger type and promising candidates for high-speed flow applications due to their smooth profiles avoiding blunt obstacles in the flow path. This work deals with the overall system behavior and gas dynamics of pillow-plate channels. A pillow-plate channel was placed in the test section of a blow-down wind tunnel working with dry air, and compressible flow phenomena were investigated utilizing conventional and focusing schlieren optics; furthermore, static and total pressure measurements were performed. The experiments supported the assumption that the system behavior can be described through a Fanno–Rayleigh flow model. Since only wavy walls with smooth profiles were involved, linearized gas dynamics was able to cover important flow features within the channel. The effects of the wavy wall structures on pressure drop and Mach number distribution within the flow path were investigated, and a good qualitative agreement with theoretical and numerical predictions was found. The present analysis demonstrates that pressure losses in pillow-plate heat exchangers are rather low, although their strong turbulent mixing enables high convective heat transfer coefficients.
Clinical and Epidemiological Characteristics of Sporotrichosis in a Reference Center of Uruguay
Authors: Cabeza Elisa , Arrillaga Annie , Dalcín Lucía , Carbia Mauricio , Arteta Zaida , Perera Patricia
Published: March 2022

Background: Sporotrichosis is a fungal implantation disease of subacute/ chronic course caused by species of the dimorphic fungus Sporothrix spp. This infection usually develops after traumatic inoculation of contaminated soil, plants or organic material contaminated by Sporothrix spp. conidia into skin or mucosa. The objective of this work is to contribute to the knowledge of sporotrichosis in Uruguay by providing a report of a series of cases diagnosed in a reference center. Methods: We conducted a retrospective, observational, descriptive and cross-sectional study of cases of sporotrichosis diagnosed in the last 38 years. Results: In the period analyzed, 157 cases of sporotrichosis were diagnosed, 152 of those corresponded to male patients. The most frequent clinical presentation was nodular lymphatic in 120 patients. In relation to epidemiological antecedents, 128 patients had been scratched by armadillos during hunting. Conclusions: Sporotrichosis in Uruguay is a sporadic disease with a clear seasonal pattern related to particular social practices, such as hunting armadillos. Related to this practice, the affectation is greater in males and in young adults.
Impact of Immunosuppressive Therapy on the Performance of Latent Tuberculosis Screening Tests in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Authors: Park Chan Hyuk , Park Jung Ho , Jung Yoon Suk
Published: March 2022

Screening for latent tuberculosis infection (LTBI) is mandatory before commencing tumor necrosis factor (TNF)-α inhibitor use. However, the impact of immunosuppressive therapy (IST), including corticosteroids and immunomodulators, on the performance of LTBI screening in patients with inflammatory bowel disease (IBD) has not been fully elucidated. We searched all relevant studies published before November 2021 that examined the performance of interferon γ release assays (IGRAs) and tuberculin skin tests (TSTs) in patients with IBD who received IST, using the Medline, EMBASE, and Cochrane Library databases. We performed meta-analyses of positive or indeterminate rates of IGRA or TST according to IST and calculated the concordance rates between IGRA and TST results. A total of 20 studies with 4045 patients were included in the meta-analysis. The IGRA-positive rate was lower in patients on IST than in those not on IST (odds ratio (OR) (95% confidence interval (CI)) = 0.55 (0.39–0.78)), whereas the IGRA-indeterminate rate was higher in patients on IST than in those not on IST (OR (95% CI) = 2.91 (1.36–6.24)). The TST-positive rate did not differ between the on-IST and not-on-IST groups (OR (95% CI) = 0.87 (0.51–1.50)). The concordance rate between IGRA and TST was 83.3% (95% CI, 78.5–88.1%). The IGRA-negative/TST-positive rate tended to be higher than that the IGRA-positive/TST-negative rate (9.5% vs. 5.8%, respectively), although the difference was not statistically significant. In conclusion, IGRA results were negatively affected by IST in patients with IBD, supporting requirements that IGRA should be performed before initiating IST. The use of both an IGRA and TST in patients with IBD on IST may improve the diagnosis rate of LTBI.
Personalized Management and Treatment of Alzheimer’s Disease
Authors: Cacabelos Ramón , Naidoo Vinogran , Martínez-Iglesias Olaia , Corzo Lola , Cacabelos Natalia , Pego Rocío , Carril Juan C.
Published: March 2022

Alzheimer’s disease (AD) is a priority health problem with a high cost to society and a large consumption of medical and social resources. The management of AD patients is complex and multidisciplinary. Over 90% of patients suffer from concomitant diseases and require personalized therapeutic regimens to reduce adverse drug reactions (ADRs), drug–drug interactions (DDIs), and unnecessary costs. Men and women show substantial differences in their AD-related phenotypes. Genomic, epigenetic, neuroimaging, and biochemical biomarkers are useful for predictive and differential diagnosis. The most frequent concomitant diseases include hypertension (>25%), obesity (>70%), diabetes mellitus type 2 (>25%), hypercholesterolemia (40%), hypertriglyceridemia (20%), metabolic syndrome (20%), hepatobiliary disorder (15%), endocrine/metabolic disorders (>20%), cardiovascular disorder (40%), cerebrovascular disorder (60–90%), neuropsychiatric disorders (60–90%), and cancer (10%). Over 90% of AD patients require multifactorial treatments with risk of ADRs and DDIs. The implementation of pharmacogenetics in clinical practice can help optimize the limited therapeutic resources available to treat AD and personalize the use of anti-dementia drugs, in combination with other medications, for the treatment of concomitant disorders.
The Role of Photo-Cycles in the Modulation of Growth and Biochemical Profile of Microalgae: Part I—Food Interest Compounds
Authors: Sartori Rafaela Basso , Vendruscolo Raquel Guidetti , Ribeiro Stephanie Reis , Furlan Valcenir Júnior Mendes , Wagner Roger , Zepka Leila Queiroz , Jacob-Lopes Eduardo
Published: March 2022

The objective of this work was to evaluate the effect of different photo-cycles on the growth and biochemical profile of Scenedesmus obliquus CPCC05, focusing on food interest compounds. The photo-cycle conditions were separated into three groups: long-term photo-cycles (24:0, 22:2, 20:4, 18:6, 12:12, and 10:14 (h:h)), frequency photo-cycles (2, 4, 8, 12, 24, and 48 times per day (t/d)), and short photo-cycles (0.91:0.09, 0.83:0.17, 0.75:0.25, and 0.50:0.50 (s:s)) of light:dark, respectively. The results showed these microalgae can store enough energy to support cell growth for continuous periods of up to 2 h in the dark, without affecting the productivity of the process. This 2 h, when divided into 2 cycles per day (2 t/d), showed the best growth condition (3700 mg L−1), generation time (14.40 h), and maximum biomass productivity (21.43 mg L h−1). This photo-cycle of 2 t/d was also the best condition for the production of total sterols. However, the values of polyunsaturated fatty acids, lipid content, and amino acids obtained higher yields in the short photo-cycle of 0.75:0.25. Thus, the modulation of light cycles becomes an important tool for boosting and directing the production of target molecules in phototrophic cultures of microalgae.
Changes in mGlu5 Receptor Signaling Are Associated with Associative Learning and Memory Extinction in Mice
Authors: Teleuca Ana Elena , Alemà Giovanni Sebastiano , Casolini Paola , Barberis Ilaria , Ciabattoni Francesco , Orlando Rosamaria , Di Menna Luisa , Iacovelli Luisa , Scioli Maria Rosaria , Nicoletti Ferdinando , Zuena Anna Rita
Published: March 2022

Using an in vivo method for the assessment of polyphosphoinositide (PI) hydrolysis, we examine whether spatial learning and memory extinction cause changes in mGlu5 metabotropic glutamate receptor signaling in the hippocampus and prefrontal cortex. We use the following five groups of mice: (i) naive mice; (ii) control mice exposed to the same environment as learner mice; (iii) leaner mice, trained for four days in a water maze; (iv) mice in which memory extinction was induced by six trials without the platform; (v) mice that spontaneously lost memory. The mGlu5 receptor-mediated PI hydrolysis was significantly reduced in the dorsal hippocampus of learner mice as compared to naive and control mice. The mGlu5 receptor signaling was also reduced in the ventral hippocampus and prefrontal cortex of learner mice, but only with respect to naive mice. Memory extinction was associated with a large up-regulation of mGlu5 receptor-mediated PI hydrolysis in the three brain regions and with increases in mGlu5 receptor and phospholipase-Cβ protein levels in the ventral and dorsal hippocampus, respectively. These findings support a role for mGlu5 receptors in mechanisms underlying spatial learning and suggest that mGlu5 receptors are candidate drug targets for disorders in which cognitive functions are impaired or aversive memories are inappropriately retained.
Experimental and Theoretical Investigations of Three-Ring Ester/Azomethine Materials
Authors: Alamro Fowzia S. , Al-Kadhi Nada S. , Gomha Sobhi M. , Popoola Saheed A. , Khushaim Muna S. , Alhaddad Omaima A. , Ahmed Hoda A.
Published: March 2022

New three-ring ester/azomethine homologues series, (E)-4-((4-hydroxybenzylidene)amino)phenyl 4-(alkoxy)benzoate In, were prepared and their properties were investigated experimentally and theoretically. FT-IR, NMR, and elemental analyses were used to confirm the chemical structures of the synthesized compounds. The mesomorphic activities of the planned homologues were evaluated using differential scanning calorimetry (DSC) and polarized optical microscopy. All of the homologous examined were found to have non-mesomorphic properties. Theoretical calculations using the density functional theory (DFT) were used to validate the experimental data and determine the most stable conformation of the synthesized compounds. All calculated conformers’ thermal properties, dipole moments, and polarizability were discussed. The results show that the terminal alkoxy chain length affects the thermal parameters of the conformers. The correlations between these parameters’ values and the conformer type were demonstrated. The base component was expected to be in two conformers according to the orientation of the N atom of imine-linkage. DFT calculations revealed the more probable of the two possible conformers, and the incorporation of the alkoxy terminal chain in one position affect its geometrical and mesomerphic characteristics.
Optimization of Digital Light Processing Three-Dimensional Printing of the Removable Partial Denture Frameworks; The Role of Build Angle and Support Structure Diameter
Authors: Hussein Mostafa Omran , Hussein Lamis Ahmed
Published: March 2022

The optimal three-dimensional (3D) printing parameters of removable partial denture (RPD) frameworks should be studied to achieve the best accuracy, printing time, and least materials consumed. This study aimed to find the best build angle and support structures’ diameter of the 3D printed (RPD) framework. Sixty (RPD) frameworks (10 in each group) were manufactured by digital light processing (DLP) 3D printing technology at three build angles (110-D, 135-D, and 150-D) and two support structures diameters (thick, L, and thin, S). Six groups were named according to their printing setting as (110-DS, 135-DS, 150-DS, 110-DL, 135-DL, and 150-DL). Frameworks were 3D scanned and compared to the original cast surface using 3D metrology software (Geomagic Control X; 3D Systems, Rock Hill, SC). Both printing time and material consumption were also recorded. Data were tested for the significant difference by one-way analysis of variance (ANOVA) test at (α = 0.05). The correlations between outcome parameters were also calculated. The 110-DL group showed the least accuracy. Significantly, the printing time of the 150-D groups had the lowest time. Material consumption of group 110-DS presented the lowest significantly statistical value. Printing time had a linear correlation with both accuracy and material consumption. Within the study limitations, the 150-degree build angle and thin diameter support structures showed optimal accuracy and time-saving regardless of material consumption.
Peri-Implant Repair Using a Modified Implant Macrogeometry in Diabetic Rats: Biomechanical and Molecular Analyses of Bone-Related Markers
Authors: Sant’Anna Hugo Robertson , Casati Marcio Zaffalon , Mussi Mounir Colares , Cirano Fabiano Ribeiro , Pimentel Suzana Peres , Ribeiro Fernanda Vieira , Corrêa Mônica Grazieli
Published: March 2022

DM has a high prevalence worldwide and exerts a negative influence on bone repair around dental implants. Modifications of the microgeometry of implants have been related to positive results in bone repair. This study assessed, for the first time, the influence of an implant with modified macrodesign based on the presence of a healing chamber in the pattern of peri-implant repair under diabetic conditions. Thirty Wistar rats were assigned to receive one titanium implant in each tibia (Control Implant (conventional macrogeometry) or Test Implant (modified macrogeometry)) according to the following groups: Non-DM + Control Implant; Non-DM + Test Implant; DM + Control Implant; DM + Test Implant. One month from the surgeries, the implants were removed for counter-torque, and the bone tissue surrounding the implants was stored for the mRNA quantification of bone-related markers. Implants located on DM animals presented lower counter-torque values in comparison with Non-DM ones, independently of macrodesign (p < 0.05). Besides, higher biomechanical retention levels were observed in implants with modified macrogeometry than in the controls in both Non-DM and DM groups (p < 0.05). Moreover, the modified macrogeometry upregulated OPN mRNA in comparison with the control group in Non-DM and DM rats (p < 0.05). Peri-implant bone repair may profit from the use of implants with modified macrogeometry in the presence of diabetes mellitus, as they offer higher biomechanical retention and positive modulation of important bone markers in peri-implant bone tissue.