bluuebunny/crossref_metadata_2025 huggingface dataset:
Severe COVID-19 Patients Show an Increase in Soluble TNFR1 and ADAM17, with a Relationship to Mortality
Authors: Palacios Yadira , Ruiz Andy , Ramón-Luing Lucero A. , Ocaña-Guzman Ranferi , Barreto-Rodriguez Omar , Sánchez-Monciváis Anahí , Tecuatzi-Cadena Brenda , Regalado-García Ana G. , Pineda-Gudiño Rey David , García-Martínez Alicia , Juárez-Hernández Fortunato , Farias-Contreras Juan Pablo , Fricke-Galindo Ingrid , Pérez-Rubio Gloria , Falfán-Valencia Ramcés , Buendia-Roldan Ivette , Medina-Quero Karen , Chavez-Galan Leslie
Published: August 2021

Overproduction of inflammatory cytokines is a keystone event in COVID-19 pathogenesis; TNF and its receptors (TNFR1 and TNFR2) are critical pro-inflammatory molecules. ADAM17 releases the soluble (sol) forms of TNF, TNFR1, and TNFR2. This study evaluated TNF, TNFRs, and ADAM17 at the protein, transcriptional, and gene levels in COVID-19 patients with different levels of disease severity. In total, 102 patients were divided into mild, moderate, and severe condition groups. A group of healthy donors (HD; n = 25) was included. Our data showed that solTNFR1 and solTNFR2 were elevated among the COVID-19 patients (p < 0.0001), without increasing the transcriptional level. Only solTNFR1 was higher in the severe group as compared to the mildly ill (p < 0.01), and the level was higher in COVID-19 patients who died than those that survived (p < 0.0001). The solTNFR1 level had a discrete negative correlation with C-reactive protein (p = 0.006, Rho = −0.33). The solADAM17 level was higher in severe as compared to mild disease conditions (p < 0.01), as well as in COVID-19 patients who died as compared to those that survived (p < 0.001). Additionally, a potential association between polymorphism TNFRSF1A:rs767455 and a severe degree of disease was suggested. These data suggest that solTNFR1 and solADAM17 are increased in severe conditions. solTNFR1 should be considered a potential target in the development of new therapeutic options.
Melatonin and Myo-Inositol: Supporting Reproduction from the Oocyte to Birth
Authors: Russo Michele , Forte Gianpiero , Montanino Oliva Mario , Laganà Antonio Simone , Unfer Vittorio
Published: August 2021

Human pregnancy is a sequence of events finely tuned by several molecular interactions that come with a new birth. The precise interlocking of these events affecting the reproductive system guarantees safe embryo formation and fetal development. In this scenario, melatonin and myo-inositol seem to be pivotal not only in the physiology of the reproduction process, but also in the promotion of positive gestational outcomes. Evidence demonstrates that melatonin, beyond the role of circadian rhythm management, is a key controller of human reproductive functions. Similarly, as the most representative member of the inositol’s family, myo-inositol is essential in ensuring correct advancing of reproductive cellular events. The molecular crosstalk mediated by these two species is directly regulated by their availability in the human body. To date, biological implications of unbalanced amounts of melatonin and myo-inositol in each pregnancy step are growing the idea that these molecules actively contribute to reduce negative outcomes and improve the fertilization rate. Clinical data suggest that melatonin and myo-inositol may constitute an optimal dietary supplementation to sustain safe human gestation and a new potential way to prevent pregnancy-associated pathologies.
Cytotoxicity Study of UV-Laser-Irradiated PLLA Surfaces Subjected to Bio-Ceramisation: A New Way towards Implant Surface Modification
Authors: Szustakiewicz Konrad , Kryszak Bartłomiej , Dzienny Paulina , Poźniak Błażej , Tikhomirov Marta , Hoppe Viktoria , Szymczyk-Ziółkowska Patrycja , Tylus Włodzimierz , Grzymajło Michał , Gadomska-Gajadhur Agnieszka , Antończak Arkadiusz J.
Published: August 2021

In this research we subjected samples of poly(L-lactide) (PLLA) extruded film to ultraviolet (193 nm ArF excimer laser) radiation below the ablation threshold. The modified film was immersed in Simulated Body Fluid (SBF) at 37 °C for 1 day or 7 days to obtain a layer of apatite ceramic (CaP) coating on the modified PLLA surface. The samples were characterized by means of optical profilometry, which indicated an increase in average roughness (Ra) from 25 nm for the unmodified PLLA to over 580 nm for irradiated PLLA incubated in SBF for 1 day. At the same time, the water contact angle decreased from 78° for neat PLLA to 35° for irradiated PLLA incubated in SBF, which suggests its higher hydrophilicity. The obtained materials were investigated by means of cell response fibroblasts (3T3) and macrophage-like cells (RAW 264.7). Properties of the obtained composites were compared to the unmodified PLLA film as well as to the UV-laser irradiated PLLA. The activation of the PLLA surface by laser irradiation led to a distinct increase in cytotoxicity, while the treatment with SBF and the deposition of apatite ceramic had only a limited preventive effect on this harmful impact and depended on the cell type. Fibroblasts were found to have good tolerance for the irradiated and ceramic-covered PLLA, but macrophages seem to interact with the substrate leading to the release of cytotoxic products.
Therapeutic Potential of Jasmonic Acid and Its Derivatives
Authors: Jarocka-Karpowicz Iwona , Markowska Agnieszka
Published: August 2021

A modern method of therapeutic use of natural compounds that would protect the body are jasmonates. The main representatives of jasmonate compounds include jasmonic acid and its derivatives, mainly methyl jasmonate. Extracts from plants rich in jasmonic compounds show a broad spectrum of activity, i.e., anti-cancer, anti-inflammatory and cosmetic. Studies of the biological activity of jasmonic acid and its derivatives in mammals are based on their structural similarity to prostaglandins and the compounds can be used as natural therapeutics for inflammation. Jasmonates also constitute a potential group of anti-cancer drugs that can be used alone or in combination with other known chemotherapeutic agents. Moreover, due to their ability to stimulate exfoliation of the epidermis, remove discoloration, regulate the function of the sebaceous glands and reduce the visible signs of aging, they are considered for possible use in cosmetics and dermatology. The paper presents a review of literature data on the biological activity of jasmonates that may be helpful in treatment and prevention.
Angiopoietin-like Proteins in Colorectal Cancer—A Literature Review
Authors: Zajkowska Monika , Mroczko Barbara
Published: August 2021

Colorectal cancer (CRC) is one of the most common types of malignancy, with an annual incidence of about 10% of the total number of new cases. Despite well-developed screening tests, mortality from this type of cancer remains unchanged. Therefore, it is important to search for more accurate markers that are useful in the detection of colorectal cancer (especially in its early stages), and treatment. Angiopoietin-like proteins (ANGPTLs) are a family of eight proteins with a diversity of applications, including pro- and anti-angiogenic properties. Consequently, we performed an extensive search of the literature, pertaining to our investigation, via the MEDLINE/PubMed database. Based on the available literature, we summarize that some of those proteins are characterized by increased or decreased concentrations during the course of CRC. We can also assume that some ANGPTLs can inhibit the development of CRC, while others induce its progress. Moreover, some factors are dependent on the stage or histological type of the tumor, the presence of hypoxia, or metastases. Most importantly, some ANGPTLs can be useful in anti-cancer therapy. Therefore, further studies on ANGPTLs as potential markers of CRC should be continued.
Clavibacter michiganensis Downregulates Photosynthesis and Modifies Monolignols Metabolism Revealing a Crosstalk with Tomato Immune Responses
Authors: Tsitsekian Dikran , Daras Gerasimos , Karamanou Konstantina , Templalexis Dimitris , Koudounas Konstantinos , Malliarakis Dimitris , Koufakis Theologos , Chatzopoulos Dimitris , Goumas Dimitris , Ntoukakis Vardis , Hatzopoulos Polydefkis , Rigas Stamatis
Published: August 2021

The gram-positive pathogenic bacterium Clavibacter michiganensis subsp. michiganensis (Cmm) causes bacterial canker disease in tomato, affecting crop yield and fruit quality. To understand how tomato plants respond, the dynamic expression profile of host genes was analyzed upon Cmm infection. Symptoms of bacterial canker became evident from the third day. As the disease progressed, the bacterial population increased in planta, reaching the highest level at six days and remained constant till the twelfth day post inoculation. These two time points were selected for transcriptomics. A progressive down-regulation of key genes encoding for components of the photosynthetic apparatus was observed. Two temporally separated defense responses were observed, which were to an extent interdependent. During the primary response, genes of the phenylpropanoid pathway were diverted towards the synthesis of monolignols away from S-lignin. In dicots, lignin polymers mainly consist of G- and S-units, playing an important role in defense. The twist towards G-lignin enrichment is consistent with previous findings, highlighting a response to generate an early protective barrier and to achieve a tight interplay between lignin recomposition and the primary defense response mechanism. Upon progression of Cmm infection, the temporal deactivation of phenylpropanoids coincided with the upregulation of genes that belong in a secondary response mechanism, supporting an elegant reprogramming of the host transcriptome to establish a robust defense apparatus and suppress pathogen invasion. This high-throughput analysis reveals a dynamic reorganization of plant defense mechanisms upon bacterial infection to implement an array of barriers preventing pathogen invasion and spread.
Freeze-Dried Secretome (Lyosecretome) from Mesenchymal Stem/Stromal Cells Promotes the Osteoinductive and Osteoconductive Properties of Titanium Cages
Authors: Bari Elia , Tartara Fulvio , Cofano Fabio , di Perna Giuseppe , Garbossa Diego , Perteghella Sara , Sorlini Marzio , Mandracchia Delia , Giovannelli Lorella , Gaetani Paolo , Torre Maria Luisa , Segale Lorena
Published: August 2021

Titanium is one of the most frequently used materials in bone regeneration due to its good biocompatibility, excellent mechanical properties, and great osteogenic performance. However, osseointegration with host tissue is often not definite, which may cause implant failure at times. The present study investigates the capacity of the mesenchymal stem cell (MSC)-secretome, formulated as a ready-to-use and freeze-dried medicinal product (the Lyosecretome), to promote the osteoinductive and osteoconductive properties of titanium cages. In vitro tests were conducted using adipose tissue-derived MSCs seeded on titanium cages with or without Lyosecretome. After 14 days, in the presence of Lyosecretome, significant cell proliferation improvement was observed. Scanning electron microscopy revealed the cytocompatibility of titanium cages: the seeded MSCs showed a spread morphology and an initial formation of filopodia. After 7 days, in the presence of Lyosecretome, more frequent and complex cellular processes forming bridges across the porous surface of the scaffold were revealed. Also, after 14 and 28 days of culturing in osteogenic medium, the amount of mineralized matrix detected by alizarin red was significantly higher when Lyosecretome was used. Finally, improved osteogenesis with Lyosecretome was confirmed by confocal analysis after 28 and 56 days of treatment, and demonstrating the production by osteoblast-differentiated MSCs of osteocalcin, a specific bone matrix protein.
The Effect of Chronic Iloperidone Treatment on Cytochrome P450 Expression and Activity in the Rat Liver: Involvement of Neuroendocrine Mechanisms
Authors: Danek Przemysław J. , Kuban Wojciech , Daniel Władysława A.
Published: August 2021

In order to achieve a desired therapeutic effect in schizophrenia patients and to maintain their mental wellbeing, pharmacological therapy needs to be continued for a long time, usually from the onset of symptoms and for the rest of the patients’ lives. The aim of our present research is to find out the in vivo effect of chronic treatment with atypical neuroleptic iloperidone on the expression and activity of cytochrome P450 (CYP) in rat liver. Male Wistar rats received a once-daily intraperitoneal injection of iloperidone (1 mg/kg) for a period of two weeks. Twenty-four hours after the last dose, livers were excised to study cytochrome P450 expression (mRNA and protein) and activity, pituitaries were isolated to determine growth hormone-releasing hormone (GHRH), and blood was collected for measuring serum concentrations of hormones and interleukin. The results showed a broad spectrum of changes in the expression and activity of liver CYP enzymes, which are important for drug metabolism (CYP1A, CYP2B, CYP2C, and CYP3A) and xenobiotic toxicity (CYP2E1). Iloperidone decreased the expression and activity of CYP1A2, CP2B1/2, CYP2C11, and CYP3A1/2 enzymes but increased that of CYP2E1. The CYP2C6 enzyme remained unchanged. At the same time, the level of GHRH, GH, and corticosterone decreased while that of T3 increased, with no changes in IL-2 and IL-6. The presented results indicate neuroendocrine regulation of the investigated CYP enzymes during chronic iloperidone treatment and suggest a possibility of pharmacokinetic/metabolic interactions produced by the neuroleptic during prolonged combined treatment with drugs that are substrates of iloperidone-affected CYP enzymes.
Inhibition of Very Long Chain Fatty Acids Synthesis Mediates PI3P Homeostasis at Endosomal Compartments
Authors: Ito Yoko , Esnay Nicolas , Fougère Louise , Platre Matthieu Pierre , Cordelières Fabrice , Jaillais Yvon , Boutté Yohann
Published: August 2021

A main characteristic of sphingolipids is the presence of a very long chain fatty acid (VLCFA) whose function in cellular processes is not yet fully understood. VLCFAs of sphingolipids are involved in the intracellular traffic to the vacuole and the maturation of early endosomes into late endosomes is one of the major pathways for vacuolar traffic. Additionally, the anionic phospholipid phosphatidylinositol-3-phosphate (PtdIns (3)P or PI3P) is involved in protein sorting and recruitment of small GTPase effectors at late endosomes/multivesicular bodies (MVBs) during vacuolar trafficking. In contrast to animal cells, PI3P mainly localizes to late endosomes in plant cells and to a minor extent to a discrete sub-domain of the plant’s early endosome (EE)/trans-Golgi network (TGN) where the endosomal maturation occurs. However, the mechanisms that control the relative levels of PI3P between TGN and MVBs are unknown. Using metazachlor, an inhibitor of VLCFA synthesis, we found that VLCFAs are involved in the TGN/MVB distribution of PI3P. This effect is independent from either synthesis of PI3P by PI3-kinase or degradation of PI(3,5)P2 into PI3P by the SUPPRESSOR OF ACTIN1 (SAC1) phosphatase. Using high-resolution live cell imaging microscopy, we detected transient associations between TGNs and MVBs but VLCFAs are not involved in those interactions. Nonetheless, our results suggest that PI3P might be transferable from TGN to MVBs and that VLCFAs act in this process.
NGS Analysis Confirms Common TP53 and RB1 Mutations, and Suggests MYC Amplification in Ocular Adnexal Sebaceous Carcinomas
Authors: Peterson Cornelia , Moore Robert , Hicks Jessica L. , Morsberger Laura A. , De Marzo Angelo M. , Zou Ying , Eberhart Charles G. , Campbell Ashley A.
Published: August 2021

Ocular adnexal (OA) sebaceous carcinomas generally demonstrate more aggressive clinical and histopathological phenotypes than extraocular cases, but the molecular drivers implicated in their oncogenesis remain poorly defined. A retrospective review of surgical and ocular pathology archives identified eleven primary resection specimens of OA sebaceous carcinomas with adequate tissue for molecular analysis; two extraocular cases were also examined. Next-generation sequencing was used to evaluate mutations and copy number changes in a large panel of cancer-associated genes. Fluorescence in situ hybridization (FISH) confirmed MYC copy number gain in select cases, and immunohistochemistry to evaluate MYC protein expression. The commonest mutations occurred in TP53 (10/13) and RB1 (7/13). Additional mutations in clinically actionable genes, or mutations with a frequency of at least 25%, included the NF1 (3/12), PMS2 (4/12), ROS1 (3/12), KMT2C (4/12), MNX1 (6/12), NOTCH1 (4/12), PCLO (3/12), and PTPRT (3/12) loci. Low level copy number gain suggestive of amplification of the MYC locus was seen in two cases, and confirmed using FISH. MYC protein expression, as assessed by immunohistochemistry, was present in almost all sebaceous carcinoma cases. Our findings support the concept that alterations in TP53 and RB1 are the commonest alterations in sebaceous carcinoma, and suggest that MYC may contribute to the oncogenesis of these tumors.
Promising Anticancer Activity of [Bis(1,8-quinolato)palladium (II)] Alone and in Combination
Authors: Alam Md , Moni Mohammad , Yu Jun , Beale Philip , Turner Peter , Proschogo Nick , Rahman Mohammad , Hossain M. , Huq Fazlul
Published: August 2021

Due to similar coordination chemistry of palladium and platinum, a large number of palladium compounds as well have been investigated for their anticancer activity. In the present study, we describe synthesis, characterization, and anticancer activity of palladium complex [Bis(1,8-quinolato)palladium (II)], coded as NH3 against seven different cancer cell lines. NH3 is found to have higher antitumor activity than cisplatin against both parent ovarian A2780 cell line and cisplatin-resistant cell lines. Also, NH3 has the lower IC50 value in HT-29 colorectal cancer cell line. The higher antitumor activity of NH3 is due to the presence of bulky 8-Hydroxyquinoline ligand, thus reducing its reactivity. Proteomic study has identified significantly expressed proteins which have been validated through bioinformatics. NH3 has been found to be less toxic than cisplatin at 2.5 mg/kg and 5 mg/kg dosages on mice models. Binary combinations of NH3 with curcumin and epigallocatechin gallate (EGCG) have demonstrated dose and sequence-dependent synergism in ovarian and colorectal cancer models. All of the preclinical studies indicate promising therapeutic potential of NH3 [Bis(1,8-quinolato)palladium (II)] as an anticancer drug.
Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis
Authors: Aykul Senem , Maust Jordan , Thamilselvan Vijayalakshmi , Floer Monique , Martinez-Hackert Erik
Published: August 2021

Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia. The latter, also known as adipogenesis, is a process by which multipotent precursors differentiate to form mature adipocytes. This process is directed by developmental cues that include members of the TGF-β family. Our goal here was to elucidate, using the 3T3-L1 adipogenesis model, how TGF-β family growth factors and inhibitors regulate adipocyte development. We show that ligands of the Activin and TGF-β families, several ligand traps, and the SMAD1/5/8 signaling inhibitor LDN-193189 profoundly suppressed 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands engaged the same mechanism of action involving the simultaneous activation of SMAD2/3 and inhibition of SMAD1/5/8 signaling. This effect was rescued by the SMAD2/3 signaling inhibitor SB-431542. By contrast, although LDN-193189 also suppressed SMAD1/5/8 signaling and adipogenesis, its effect could not be rescued by SB-431542. Collectively, these findings reveal the fundamental role of SMAD1/5/8 for 3T3-L1 adipogenesis, and potentially identify a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 inhibition in adipogenic precursors.
Trace Amine-Associated Receptor 1 (TAAR1) Is a Positive Prognosticator for Epithelial Ovarian Cancer
Authors: Vogelsang Tilman L. R. , Vattai Aurelia , Schmoeckel Elisa , Kaltofen Till , Chelariu-Raicu Anca , Zheng Mingjun , Mahner Sven , Mayr Doris , Jeschke Udo , Trillsch Fabian
Published: August 2021

Trace amine-associated receptor 1 (TAAR1) is a Gαs- protein coupled receptor that plays an important role in the regulation of the immune system and neurotransmission in the CNS. In ovarian cancer cell lines, stimulation of TAAR1 via 3-iodothyronamine (T1AM) reduces cell viability and induces cell death and DNA damage. Aim of this study was to evaluate the prognostic value of TAAR1 on overall survival of ovarian carcinoma patients and the correlation of TAAR1 expression with clinical parameters. Ovarian cancer tissue of n = 156 patients who were diagnosed with epithelial ovarian cancer (serous, n = 110 (high-grade, n = 80; low-grade, n = 24; unknown, n = 6); clear cell, n = 12; endometrioid, n = 21; mucinous, n = 13), and who underwent surgery at the Department of Obstetrics and Gynecology, University Hospital of the Ludwig-Maximilians University Munich, Germany between 1990 and 2002, were analyzed. The tissue was stained immunohistochemically with anti-TAAR1 and evaluated with the semiquantitative immunoreactive score (IRS). TAAR1 expression was correlated with grading, FIGO and TNM-classification, and analyzed via the Spearman’s rank correlation coefficient. Further statistical analysis was obtained using nonparametric Kruskal-Wallis rank-sum test and Mann-Whitney-U-test. This study shows that high TAAR1 expression is a positive prognosticator for overall survival in ovarian cancer patients and is significantly enhanced in low-grade serous carcinomas compared to high-grade serous carcinomas. The influence of TAAR1 as a positive prognosticator on overall survival indicates a potential prognostic relevance of signal transduction of thyroid hormone derivatives in epithelial ovarian cancer. Further studies are required to evaluate TAAR1 and its role in the development of ovarian cancer.
Benefits and Biosafety of Use of 3D-Printing Technology for Titanium Biomedical Implants: A Pilot Study in the Rabbit Model
Authors: Ng Sabrina Livia , Das Subhabrata , Ting Yen-Peng , Wong Raymond Chung Wen , Chanchareonsook Nattharee
Published: August 2021

Background: Titanium has been used in osteosynthesis for decades and its compatibility and safety is unquestioned. Studies have shown that there is release and collection of titanium in the organ systems with little note of toxicity. The gold standard is considered to be titanium osteosynthesis plate produced by milling methods. The use of customized titanium plates produced with 3D printing, specifically direct metal laser sintering, have found increasing use in recent years. It is unknown how much titanium is released in these printed titanium implants, which is known to be potentially porous, depending on the heat settings of the printer. We hypothesize that the amount of titanium released in printed titanium implants may be potentially more or equal compared to the gold standard, which is the implant produced by milling. Methods: We studied the biosafety of this technology and its products by measuring serum and organ titanium levels after implantation of 3D-printed versus traditionally fabrication titanium plates and screws in a pilot study using the rabbit model. A total of nine rabbits were used, with three each in the control, milled and printed titanium group. The animals were euthanized after six months. Serum and organs of the reticuloendothelial system were harvested, digested and assayed for titanium levels. Results: Organ and serum titanium levels were significantly higher in rabbit subjects implanted with titanium implants (milled and printed) compared to the control group. However, there was no significant difference in organ and serum titanium levels of subjects implanted with milled and traditionally fabricated titanium implants. Conclusions: The biosafety of use of 3D-printed titanium implants and traditionally fabricated titanium implants are comparable. With this in mind, 3D-printed custom implants can not only replace, but will very possibly surpass traditionally fabricated titanium implants in the mode and extent of use.
Populating Web-Scale Knowledge Graphs Using Distantly Supervised Relation Extraction and Validation
Authors: Dash Sarthak , Glass Michael R. , Gliozzo Alfio , Canim Mustafa , Rossiello Gaetano
Published: August 2021

In this paper, we propose a fully automated system to extend knowledge graphs using external information from web-scale corpora. The designed system leverages a deep-learning-based technology for relation extraction that can be trained by a distantly supervised approach. In addition, the system uses a deep learning approach for knowledge base completion by utilizing the global structure information of the induced KG to further refine the confidence of the newly discovered relations. The designed system does not require any effort for adaptation to new languages and domains as it does not use any hand-labeled data, NLP analytics, and inference rules. Our experiments, performed on a popular academic benchmark, demonstrate that the suggested system boosts the performance of relation extraction by a wide margin, reporting error reductions of 50%, resulting in relative improvement of up to 100%. Furthermore, a web-scale experiment conducted to extend DBPedia with knowledge from Common Crawl shows that our system is not only scalable but also does not require any adaptation cost, while yielding a substantial accuracy gain.
Enhanced Flexible Pavement Performance Using Treated Compared to Untreated Aggregate Bases: A Comparative Case Study in the Southern United States
Authors: Souliman Mena I. , GC Hemant , Mohammed Zabi
Published: August 2021

One of the important aspects of highway design is aggregates. Aggregates strength and consistency has an effect on pavement structure’s overall performance. The consistency of the base material near the site of the construction doesn’t always match the requirements of pavement construction and carrying quality aggregate raises the cost of construction. Stabilizing agents such as asphalt cement, lime, fly ash were used to improve the strength of these materials in order to make greater use of locally available materials. Layer materials present in the pavements and the structure of them influence pavement performance. The compressive strain and the tensile strain in the layer of subgrade and asphalt layer respectively are influenced by the stiffness of the base layer. The important aspects causing rutting and fatigue cracking are compressive strain in the top region of the subgrade layer and tensile strain at the bottom of the asphalt layer, respectively. In this research study, field performance (cracking, rutting, and surface roughness) of pavement sections with untreated and treated bases were collated to assess the impact of the stabilizing agents. The treated sections performed well significantly compared to the untreated sections in terms of pavement surface roughness and fatigue cracking. The treated sections performed higher than the untreated sections in terms of the cumulative average values of all 3 distresses with fatigue cracking averaging 5 times lower than the untreated sections. The combined IRI and rutting of treated sections averaged about 1.5 times and 0.11 inches smaller, respectively than those of untreated sections.
Barium Titanium Oxynitride from Ammonia-Free Nitridation of Reduced BaTiO3
Authors: Guo Hua , Jaworski Aleksander , Chen Zheng , Lu Can , Slabon Adam , Häussermann Ulrich
Published: August 2021

We investigated the nitridation of reduced BaTiO3, BaTiO2.60H0.08, corresponding to an oxyhydride with a large concentration of O defects (>10%). The material is readily nitrided under flowing N2 gas at temperatures between 400 and 450 °C to yield oxynitrides BaTiO2.6Nx (x = 0.2−0.22) with a slightly tetragonally distorted perovskite structure, a ≈ 4.01 and c ≈ 4.02 Å, and Ti partially remaining in the oxidation state III. The tetragonal structure was confirmed from Raman spectroscopy. 14N MAS NMR spectroscopy shows a single resonance at 270 ppm, which is typical for perovskite transition metal oxynitrides. However, largely different signal intensity for materials with very similar N content suggests N/O/vacancy ordering when prolonging nitridation times to hours. Diffuse reflectance UV-VIS spectroscopy shows a reduction of the intrinsic band gap to 2.4–2.45 eV compared to BaTiO3 (~3.2 eV). Mott-Schottky measurements confirm n-type conductivity and reveal a slight negative shift of the conduction band edge from –0.59 V (BaTiO3) to ~–0.65 eV.
Transcriptional Profiles of Diploid Mutant Apis mellifera Embryos after Knockout of csd by CRISPR/Cas9
Authors: Wang Xiuxiu , Lin Yan , Liang Liqiang , Geng Haiyang , Zhang Meng , Nie Hongyi , Su Songkun
Published: August 2021

In honey bees, complementary sex determiner (csd) is the primary signal of sex determination. Its allelic composition is heterozygous in females, and hemizygous or homozygous in males. To explore the transcriptome differences after sex differentiation between males and females, with genetic differences excluded, csd in fertilized embryos was knocked out by CRISPR/Cas9. The diploid mutant males at 24 h, 48 h, 72 h, and 96 h after egg laying (AEL) and the mock-treated females derived from the same fertilized queen were investigated through RNA-seq. Mutations were detected in the target sequence in diploid mutants. The diploid mutant drones had typical male morphological characteristics and gonads. Transcriptome analysis showed that several female-biased genes, such as worker-enriched antennal (Wat), vitellogenin (Vg), and some venom-related genes, were down-regulated in the diploid mutant males. In contrast, some male-biased genes, such as takeout and apolipophorin-III-like protein (A4), had higher expressions in the diploid mutant males. Weighted gene co-expression network analysis (WGCNA) indicated that there might be interactions between csd and fruitless (fru), feminizer (fem) and hexamerin 70c (hex70c), transformer-2 (tra2) and troponin T (TpnT). The information provided by this study will benefit further research on the sex dimorphism and development of honey bees and other insects in Hymenoptera.
Two Novel Variants in YARS2 Gene Are Responsible for an Extended MLASA Phenotype with Pancreatic Insufficiency
Authors: Carreño-Gago Lidia , Juárez-Flores Diana Luz , Grau Josep Maria , Ramón Javier , Lozano Ester , Vila-Julià Ferran , Martí Ramon , Garrabou Glòria , Garcia-Arumí Elena
Published: August 2021

Pathogenic variants in the mitochondrial tyrosyl-tRNA synthetase gene (YARS2) were associated with myopathy, lactic acidosis, and sideroblastic anemia (MLASA). However, patients can present mitochondrial myopathy, with exercise intolerance and muscle weakness, leading from mild to lethal phenotypes. Genes implicated in mtDNA replication were studied by Next Generation Sequencing (NGS) and whole exome sequence with the TruSeq Rapid Exome kit (Illumina, San Diego, CA, USA). Mitochondrial protein translation was studied following the Sasarman and Shoubridge protocol and oxygen consumption rates with Agilent Seahorse XF24 Analyzer Mitostress Test, (Agilent, Santa Clara, CA, USA). We report two siblings with two novel compound heterozygous pathogenic variants in YARS2 gene: a single nucleotide deletion in exon 1, c.314delG (p.(Gly105Alafs*4)), which creates a premature stop codon in the amino acid 109, and a single nucleotide change in exon 5 c.1391T>C (p.(Ile464Thr)), that cause a missense variant in amino acid 464. We demonstrate the pathogenicity of these new variants associated with reduced YARS2 mRNA transcript, reduced mitochondrial protein translation and dysfunctional organelle function. These pathogenic variants are responsible for late onset MLASA, herein accompanied by pancreatic insufficiency, observed in both brothers, clinically considered as Pearson’s syndrome. Molecular study of YARS2 gene should be considered in patients presenting Pearson’s syndrome characteristics and MLASA related phenotypes.
Impact of Idarucizumab and Andexanet Alfa on DOAC Plasma Concentration and ClotPro® Clotting Time: An Ex Vivo Spiking Study in A Cohort of Trauma Patients
Authors: Oberladstätter Daniel , Schlimp Christoph J. , Zipperle Johannes , Osuchowski Marcin F. , Voelckel Wolfgang , Grottke Oliver , Schöchl Herbert
Published: August 2021

Specific antagonists have been developed for the reversal of direct oral anticoagulants (DOAC). We investigated the impact of these reversal agents on the plasma concentration and visco-elastic test results of dabigatran and factor Xa inhibitors. After baseline measurements of dabigatran, the plasma concentration, and the visco-elastic ClotPro® ecarin clotting time (ECA-CT), we added the reversal agent Idarucizumab in vitro and these two analyses were repeated. Likewise, the baseline plasma concentration of apixaban, edoxaban, and rivaroxaban as well as ClotPro® Russell’s viper venom test clotting time (RVV-CT) were measured and reanalyzed following Andexanet alfa spiking. We analyzed fifty blood samples from 37 patients and 10 healthy volunteers. Idarucizumab decreased the measured dabigatran plasma concentration from 323.9 ± 185.4 ng/mL to 5.9 ± 2.3 ng/mL and ECA-CT from 706.2 ± 344.6 s to 70.6 ± 20.2 s, (all, p < 0.001). Andexanet alfa decreased the apixaban concentration from 165.1 ± 65.5 ng/mL to 9.8 ± 8.1 ng/mL, edoxaban from 152.4 ± 79.0 ng/mL to 36.4 ± 19.2 ng/mL, and rivaroxaban from 153.2 ± 111.8 ng/mL to 18.1 ± 9.1 ng/mL (all p < 0.001). Andexanet alfa shortened the RVV-CT of patients with apixaban from 239.2 ± 71.7 s to 151.1 ± 30.2 s, edoxaban from 288.2 ± 65.0 s to 122.7 ± 37.1 s, and rivaroxaban from 225.9 ± 49.3 s to 103.7 ± 12.1 s (all p < 0.001). In vitro spiking of dabigatran-containing blood with Idarucizumab substantially reduced the plasma concentration and ecarin-test clotting time. Andexanet alfa lowered the concentration of the investigated factor Xa-inhibitors but did not normalize the RVV-CT. In healthy volunteers’ blood, Idarucizumab spiking had no impact on ECA-CT. Andexanet alfa spiking of non-anticoagulated blood prolonged RVV-CT (p = 0.001), potentially as a consequence of a competitive antagonism with human factor Xa.
Genetic Variants in PGE2 Receptors Modulate the Risk of Nephrosclerosis and Clinical Outcomes in These Patients
Authors: González Luz María , Robles Nicolás Roberto , Mota-Zamorano Sonia , Valdivielso José Manuel , López-Gómez Juan , Gervasini Guillermo
Published: August 2021

Prostaglandin E2 (PGE2) is a major actor mediating renal injury. We aimed to determine genetic variability in the genes coding for its receptors (PTGER1-4) and study associations with nephrosclerosis risk and clinical outcomes. We identified 96 tag-SNPs capturing global variability in PTGER1-4 and screened 1209 nephrosclerosis patients and controls. The effect of these variants was evaluated by multivariate regression analyses. Two PTGER3 SNPs, rs11209730 and rs10399704, remained significant in a backward elimination regression model with other non-genetic variables (OR = 1.45 (1.07–1.95), p = 0.016 and OR = 0.71 (0.51–0.99), p = 0.041, respectively). In the nephrosclerosis patients, a proximal region of PTGER3 was tagged as relevant for eGFR (p values for identified SNPs ranged from 0.0003 to 0.038). Two consecutive PTGER3 SNPs, rs2284362 and rs2284363, significantly decreased systolic (p = 0.005 and p = 0.0005), diastolic (p = 0.039 and p = 0.005), and pulse pressure values (p = 0.038 and 0.014). Patients were followed for a median of 47 months (7–54) to evaluate cardiovascular (CV) risk. Cox regression analysis showed that carriers of the PTGER1rs2241360 T variant had better CV event-free survival than wild-type individuals (p = 0.029). In addition, PTGER3rs7533733 GG carriers had lower event-free survival than AA/AG patients (p = 0.011). Our results indicate that genetic variability in PGE2 receptors, particularly EP3, may be clinically relevant for nephrosclerosis and its associated CV risk.
The Multiscale Monitoring of Peatland Ecosystem Carbon Cycling in the Middle Taiga Zone of Western Siberia: The Mukhrino Bog Case Study
Authors: Dyukarev Egor , Zarov Evgeny , Alekseychik Pavel , Nijp Jelmer , Filippova Nina , Mammarella Ivan , Filippov Ilya , Bleuten Wladimir , Khoroshavin Vitaly , Ganasevich Galina , Meshcheryakova Anastasiya , Vesala Timo , Lapshina Elena
Published: August 2021

The peatlands of the West Siberian Lowlands, comprising the largest pristine peatland area of the world, have not previously been covered by continuous measurement and monitoring programs. The response of peatlands to climate change occurs over several decades. This paper summarizes the results of peatland carbon balance studies collected over ten years at the Mukhrino field station (Mukhrino FS, MFS) operating in the Middle Taiga Zone of Western Siberia. A multiscale approach was applied for the investigations of peatland carbon cycling. Carbon dioxide fluxes at the local scale studied using the chamber method showed net accumulation with rates from 110, to 57.8 gC m−2 at the Sphagnum hollow site. Net CO2 fluxes at the pine-dwarf shrubs-Sphagnum ridge varied from negative (−32.1 gC m−2 in 2019) to positive (13.4 gC m−2 in 2017). The cumulative May-August net ecosystem exchange (NEE) from eddy-covariance (EC) measurements at the ecosystem scale was −202 gC m−2 in 2015, due to the impact of photosynthesis of pine trees which was not registered by the chamber method. The net annual accumulation of carbon in the live part of mosses was estimated at 24–190 gC m−2 depending on the Sphagnum moss species. Long-term carbon accumulation rates obtained by radiocarbon analysis ranged from 28.5 to 57.2 gC m−2 yr−1, with local extremes of up to 176.2 gC m−2 yr−1. The obtained estimates of various carbon fluxes using EC and chamber methods, the accounting for Sphagnum growth and decomposition, and long-term peat accumulation provided information about the functioning of the peatland ecosystems at different spatial and temporal scales. Multiscale carbon flux monitoring reveals useful new information for forecasting the response of northern peatland carbon cycles to climatic changes.
Did Solid Surfaces Enable the Origin of Life?
Authors: Gözen İrep
Published: August 2021

In this perspective article, I discuss whether and how solid surfaces could have played a key role in the formation of membranous primitive cells on the early Earth. I argue why surface energy could have been used by prebiotic amphiphile assemblies for unique morphological transformations, and present recent experimental findings showing the surface-dependent formation and behavior of sophisticated lipid membrane structures. Finally, I discuss the possible unique contributions of such surface-adhered architectures to the transition from prebiotic matter to living systems.
Calculation of Mass Transfer and Cell-Specific Consumption Rates to Improve Cell Viability in Bioink Tissue Constructs
Authors: Pössl Axel , Hartzke David , Schlupp Peggy , Runkel Frank E.
Published: August 2021

Biofabrication methods such as extrusion-based bioprinting allow the manufacture of cell-laden structures for cell therapy, but it is important to provide a sufficient number of embedded cells for the replacement of lost functional tissues. To address this issue, we investigated mass transfer rates across a bioink hydrogel for the essential nutrients glucose and glutamine, their metabolites lactate and ammonia, the electron acceptor oxygen, and the model protein bovine serum albumin. Diffusion coefficients were calculated for these substances at two temperatures. We could confirm that diffusion depends on the molecular volume of the substances if the bioink has a high content of polymers. The analysis of pancreatic 1.1B4 β-cells revealed that the nitrogen source glutamine is a limiting nutrient for homeostasis during cultivation. Taking the consumption rates of 1.1B4 β-cells into account during cultivation, we were able to calculate the cell numbers that can be adequately supplied by the cell culture medium and nutrients in the blood using a model tissue construct. For blood-like conditions, a maximum of ~106 cells·mL−1 was suitable for the cell-laden construct, as a function of the diffused substrate and cell consumption rate for a given geometry. We found that oxygen and glutamine were the limiting nutrients in our model.
Evaluation Approach of Fracture Behavior for Asphalt Concrete with Different Aggregate Gradations and Testing Temperatures Using Acoustic Emission Monitoring
Authors: Fu Liuxu , Jiao Yubo , Chen Xianhua , Zhang Mengsu
Published: August 2021

Different aggregate gradations of asphalt concrete possess dissimilar skeleton structures, leading to diverse macroscopic and mechanical characteristics. Acoustic emission (AE) technology can realize real-time monitoring of the whole damage evolution process of materials. The objective of the present investigation was to demonstrate the fracture characteristics of asphalt concrete with three types of aggregate gradations, including dense-graded asphalt concrete (AC), stone mastic asphalt (SMA), and open-graded friction course (OGFC) under indirect tensile load on account of the acoustic emission (AE) technique. The Marshall compaction method was used to prepare specimens, and the indirect tensile test (IDT) and AE monitoring were conducted simultaneously at different temperatures. The corresponding AE parameters containing energy, cumulative energy, count, and cumulative count were adopted to characterize the fracture process of asphalt concrete with different aggregate gradations. The impact of temperature on the damage characteristics of asphalt concrete was also assessed. Test results indicated that the AE parameters could effectively classify the damage stages of asphalt concrete, and specimens with different aggregate gradations exhibited different AE characteristics during failure processes. The combination of AE parameters and cumulative AE parameters can accurately characterize the damage characteristics of asphalt concrete. SMA specimens possessed the best overall performance among these three types of asphalt concrete in terms of the variations in energy and cumulative energy at different temperatures. The findings obtained in this study can provide a practical AE-based evaluation approach for demonstrating the fracture mechanism of asphalt concrete with different aggregate gradations.
An MMF3 Criterion Based Multi-Scale Strategy for the Failure Analysis of Plain-Woven Fabric Composites and Its Validation in the Open-Hole Compression Tests
Authors: Zhou Rui , Gao Weicheng , Liu Wei
Published: August 2021

A modified micromechanics failure criterion (MMF3) based multi-scale analysis strategy was proposed in this article to analyze the failure behaviors of the plain-woven fabric composites. The finite-element (FE) representative unit cell (RUC) models of different scales were first established, and the RUC based stress transformation methods were developed. The micro-scale strengths of the constituents in the unidirectional laminate were achieved based on the tested macro-scale strengths. Under the micro-scale strength invariance hypothesis, the meso-scale strengths of the fiber tows from the plain-woven fabric composites were back-calculated first and were then validated and corrected with the assistance of tested strengths of the fabric laminates. With the micro-scale RUC and the calculated meso-scale strengths of the fiber tows, the micro-scale strengths of the constituents suitable for the plain-woven fabric composites were determined. The multi-scale analysis procedure for the plain-woven fabric composites was then established in providing a more direct failure observation at the constituent level. Open-hole compression specimens were tested according to the ASTM standard D6484, and the failure of the open-hole fabric laminate was simulated with the proposed multi-scale strategy. The numerical predictions were in good agreement with the experimental results, and the feasibility of the multi-scale strategy was validated.
Structural and Phase Transformations and Physical and Mechanical Properties of Cu-Al-Ni Shape Memory Alloys Subjected to Severe Plastic Deformation and Annealing
Authors: Svirid Alexey E. , Pushin Vladimir G. , Kuranova Natalia N. , Makarov Vladimir V. , Ustyugov Yuri M.
Published: August 2021

Using the methods of electron microscopy and X-ray analysis in combination with measurements of the electrical resistance and magnetic susceptibility, the authors have obtained data on the peculiar features of pre-martensitic states and martensitic transformations, as well as subsequent decomposition, in the alloys with shape memory effect of Cu–14wt%Al–3wt%Ni and Cu–13.5wt%Al–3.5wt%Ni. For the first time, we established the microstructure, phase composition, mechanical properties, and microhardness of the alloys obtained in the nanocrystalline state as a result of severe plastic deformation under high pressure torsion and subsequent annealing. A crystallographic model of the martensite nucleation and the rearrangements β1→β1′ and β1→γ1′ are proposed based on the analysis of the observed tweed contrast and diffuse scattering in the austenite and the internal defects in the substructure of the martensite.
Conversion of Bivalve Shells to Monocalcium and Tricalcium Phosphates: An Approach to Recycle Seafood Wastes
Authors: Seesanong Somkiat , Boonchom Banjong , Chaiseeda Kittichai , Boonmee Wimonmat , Laohavisuti Nongnuch
Published: August 2021

The search for sustainable resources remains a subject of global interest and the conversion of the abundantly available bivalve shell wastes to advanced materials is an intriguing method. By grinding, calcium carbonate (CaCO3) powder was obtained from each shell of bivalves (cockle, mussel, and oyster) as revealed by FTIR and XRD results. Each individual shell powder was reacted with H3PO4 and H2O to prepare Ca(H2PO4)2·H2O giving an anorthic crystal structure. The calcination of the mixture of each shell powder and its produced Ca(H2PO4)2·H2O, at 900 °C for 3 h, resulted in rhombohedral crystal β-Ca3(PO4)2 powder. The FTIR and XRD data of the CaCO3, Ca(H2PO4)2·H2O, and Ca3(PO4)2 prepared from each shell powder are quite similar, showing no impurities. The thermal behaviors of CaCO3 and Ca(H2PO4)2·H2O produced from each shell were slightly different. However, particle sizes and morphologies of the same products obtained from different shells were slightly different—but those are significantly different for the kind of the obtained products. Overall, the products (CaCO3, Ca(H2PO4)2·H2O, and Ca3(PO4)2) were obtained from the bivalve shell wastes by a rapidly simple, environmentally benign, and low-cost approach, which shows huge potential in many industries providing both economic and ecological benefits.