bluuebunny/crossref_metadata_2025 huggingface dataset:
Small Molecule Inhibitors Targeting Nuclear Factor κB Activation Markedly Reduce Expression of Interleukin-2, but Not Interferon-γ, Induced by Phorbol Esters and Calcium Ionophores
Authors: Tanaka Yumiko , Nakao Ayaka , Miyake Yasunobu , Higashi Yukina , Tanigaki Riho , Kataoka Takao
Published: December 2021

The T-box transcription factor Eomesodermin (Eomes) promotes the expression of interferon-γ (IFN-γ). We recently reported that the small molecule inhibitors, TPCA-1 and IKK-16, which target nuclear factor κB (NF-κB) activation, moderately reduced Eomes-dependent IFN-γ expression in mouse lymphoma BW5147 cells stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin (IM). In the present study, we investigated the direct effects of NF-κB on IFN-γ expression in mouse lymphoma EL4 cells and primary effector T cells. Eomes strongly promoted IFN-γ expression and the binding of RelA and NFATc2 to the IFN-γ promoter when EL4 cells were stimulated with PMA and IM. Neither TPCA-1 nor IKK-16 reduced IFN-γ expression; however, they markedly decreased interleukin (IL)-2 expression in Eomes-transfected EL4 cells. Moreover, TPCA-1 markedly inhibited the binding of RelA, but not that of Eomes or NFATc2 to the IFN-γ promoter. In effector CD4+ and CD8+ T cells activated with anti-CD3 and anti-CD28 antibodies, IFN-γ expression induced by PMA and A23187 was not markedly decreased by TPCA-1 or IKK-16 under conditions where IL-2 expression was markedly reduced. Therefore, the present results revealed that NF-κB is dispensable for IFN-γ expression induced by PMA and calcium ionophores in EL4 cells expressing Eomes and primary effector T cells.
Neurogenic Inflammation in the Context of Endometriosis—What Do We Know?
Authors: Velho Renata Voltolini , Taube Eliane , Sehouli Jalid , Mechsner Sylvia
Published: December 2021

Endometriosis (EM) is an estrogen-dependent disease characterized by the presence of epithelial, stromal, and smooth muscle cells outside the uterine cavity. It is a chronic and debilitating condition affecting ~10% of women. EM is characterized by infertility and pain, such as dysmenorrhea, chronic pelvic pain, dyspareunia, dysuria, and dyschezia. Although EM was first described in 1860, its aetiology and pathogenesis remain uncertain. Recent evidence demonstrates that the peripheral nervous system plays an important role in the pathophysiology of this disease. Sensory nerves, which surround and innervate endometriotic lesions, not only drive the chronic and debilitating pain associated with EM but also contribute to a growth phenotype by secreting neurotrophic factors and interacting with surrounding immune cells. Here we review the role that peripheral nerves play in driving and maintaining endometriotic lesions. A better understanding of the role of this system, as well as its interactions with immune cells, will unearth novel disease-relevant pathways and targets, providing new therapeutics and better-tailored treatment options.
Cardiac Remodeling and Repair: Recent Approaches, Advancements, and Future Perspective
Authors: Alam Perwez , Maliken Bryan D. , Jones Shannon M. , Ivey Malina J. , Wu Zhichao , Wang Yigang , Kanisicak Onur
Published: December 2021

The limited ability of mammalian adult cardiomyocytes to proliferate following an injury to the heart, such as myocardial infarction, is a major factor that results in adverse fibrotic and myocardial remodeling that ultimately leads to heart failure. The continued high degree of heart failure-associated morbidity and lethality requires the special attention of researchers worldwide to develop efficient therapeutics for cardiac repair. Recently, various strategies and approaches have been developed and tested to extrinsically induce regeneration and restoration of the myocardium after cardiac injury have yielded encouraging results. Nevertheless, these interventions still lack adequate success to be used for clinical interventions. This review highlights and discusses both cell-based and cell-free therapeutic approaches as well as current advancements, major limitations, and future perspectives towards developing an efficient therapeutic method for cardiac repair.
Long-Term Effects of Neural Precursor Cell Transplantation on Secondary Injury Processes and Functional Recovery after Severe Cervical Contusion-Compression Spinal Cord Injury
Authors: Younsi Alexander , Zheng Guoli , Riemann Lennart , Scherer Moritz , Zhang Hao , Tail Mohamed , Hatami Maryam , Skutella Thomas , Unterberg Andreas , Zweckberger Klaus
Published: December 2021

Cervical spinal cord injury (SCI) remains a devastating event without adequate treatment options despite decades of research. In this context, the usefulness of common preclinical SCI models has been criticized. We, therefore, aimed to use a clinically relevant animal model of severe cervical SCI to assess the long-term effects of neural precursor cell (NPC) transplantation on secondary injury processes and functional recovery. To this end, we performed a clip contusion-compression injury at the C6 level in 40 female Wistar rats and a sham surgery in 10 female Wistar rats. NPCs, isolated from the subventricular zone of green fluorescent protein (GFP) expressing transgenic rat embryos, were transplanted ten days after the injury. Functional recovery was assessed weekly, and FluoroGold (FG) retrograde fiber-labeling, as well as manganese-enhanced magnetic resonance imaging (MEMRI), were performed prior to the sacrifice of the animals eight weeks after SCI. After cryosectioning of the spinal cords, immunofluorescence staining was conducted. Results were compared between the treatment groups (NPC, Vehicle, Sham) and statistically analyzed (p < 0.05 was considered significant). Despite the severity of the injury, leading to substantial morbidity and mortality during the experiment, long-term survival of the engrafted NPCs with a predominant differentiation into oligodendrocytes could be observed after eight weeks. While myelination of the injured spinal cord was not significantly improved, NPC treated animals showed a significant increase of intact perilesional motor neurons and preserved spinal tracts compared to untreated Vehicle animals. These findings were associated with enhanced preservation of intact spinal cord tissue. However, reactive astrogliosis and inflammation where not significantly reduced by the NPC-treatment. While differences in the Basso–Beattie–Bresnahan (BBB) score and the Gridwalk test remained insignificant, animals in the NPC group performed significantly better in the more objective CatWalk XT gait analysis, suggesting some beneficial effects of the engrafted NPCs on the functional recovery after severe cervical SCI.
Novel Criteria for Intratumoral Budding with Prognostic Relevance for Colon Cancer and Its Histological Subtypes
Authors: Pour Farid Pantea , Eckstein Markus , Merkel Susanne , Grützmann Robert , Hartmann Arndt , Bruns Volker , Benz Michaela , Schneider-Stock Regine , Geppert Carol I.
Published: December 2021

Peritumoral budding and intratumoral budding (ITB) are important prognostic factors for colorectal cancer patients. Scientists worldwide have investigated the role of budding in tumor progression and its prognosis, but guidelines for reliably identifying tumor buds based on morphology are lacking. In this study, next-generation tissue microarray (ngTMA®) construction was used for tumor bud evaluation, and highly detailed rule-out annotation was used for tumor definition in pancytokeratin-stained tissue sections. Initially, tissues of 245 colon cancer patients were evaluated with high interobserver reliability, and a concordance of 96% was achieved. It was shown that high ITB scores were associated with poor distant metastasis-free survival (p = 0.006 with a cut-off of ≥10 buds). This cut-off was defined as the best maximum value from one of two/three ngTMA® cores (0.6 mm diameter). ITB in 30 cases of mucinous, medullary, and signet ring cell carcinoma was analyzed for the subsequent determination of differences in tumor bud analyses between those subtypes. In conclusion, blinded randomized punched cores in the tumor center can be useful for ITB detection. It can be assumed that this method is suitable for its adoption in clinical routines.
The Role of Topoisomerase II in DNA Repair and Recombination in Arabidopsis thaliana
Authors: Martinez-Garcia Marina , White Charles I. , Franklin F. Chris. H. , Sanchez-Moran Eugenio
Published: December 2021

DNA entanglements and supercoiling arise frequently during normal DNA metabolism. DNA topoisomerases are highly conserved enzymes that resolve the topological problems that these structures create. Topoisomerase II (TOPII) releases topological stress in DNA by removing DNA supercoils through breaking the two DNA strands, passing a DNA duplex through the break and religating the broken strands. TOPII performs key DNA metabolic roles essential for DNA replication, chromosome condensation, heterochromatin metabolism, telomere disentanglement, centromere decatenation, transmission of crossover (CO) interference, interlock resolution and chromosome segregation in several model organisms. In this study, we reveal the endogenous role of Arabidopsis thaliana TOPII in normal root growth and cell cycle, and mitotic DNA repair via homologous recombination. Additionally, we show that the protein is required for meiotic DSB repair progression, but not for CO formation. We propose that TOPII might promote mitotic HR DNA repair by relieving stress needed for HR strand invasion and D-loop formation.
Prenatal Exposure to Triclocarban Impairs ESR1 Signaling and Disrupts Epigenetic Status in Sex-Specific Ways as Well as Dysregulates the Expression of Neurogenesis- and Neurotransmitter-Related Genes in the Postnatal Mouse Brain
Authors: Wnuk Agnieszka , Rzemieniec Joanna , Przepiórska Karolina , Pietrzak Bernadeta Angelika , Maćkowiak Marzena , Kajta Małgorzata
Published: December 2021

Triclocarban is a highly effective and broadly used antimicrobial agent. Humans are continually exposed to triclocarban, but the safety of prenatal exposure to triclocarban in the context of neurodevelopment remains unknown. In this study, we demonstrated for the first time that mice that had been prenatally exposed to environmentally relevant doses of triclocarban had impaired estrogen receptor 1 (ESR1) signaling in the brain. These mice displayed decreased mRNA and protein expression levels of ESR1 as well as hypermethylation of the Esr1 gene in the cerebral cortex. Prenatal exposure to triclocarban also diminished the mRNA expression of Esr2, Gper1, Ahr, Arnt, Cyp19a1, Cyp1a1, and Atg7, and the protein levels of CAR, ARNT, and MAP1LC3AB in female brains and decreased the protein levels of BCL2, ARNT, and MAP1LC3AB in male brains. In addition, exposure to triclocarban caused sex-specific alterations in the methylation levels of global DNA and estrogen receptor genes. Microarray and enrichment analyses showed that, in males, triclocarban dysregulated mainly neurogenesis-related genes, whereas, in females, the compound dysregulated mainly neurotransmitter-related genes. In conclusion, our data identified triclocarban as a neurodevelopmental risk factor that particularly targets ESR1, affects apoptosis and autophagy, and in sex-specific ways disrupts the epigenetic status of brain tissue and dysregulates the postnatal expression of neurogenesis- and neurotransmitter-related genes.
PHA-680626 Is an Effective Inhibitor of the Interaction between Aurora-A and N-Myc
Authors: Boi Dalila , Souvalidou Fani , Capelli Davide , Polverino Federica , Marini Grazia , Montanari Roberta , Pochetti Giorgio , Tramonti Angela , Contestabile Roberto , Trisciuoglio Daniela , Carpinelli Patrizia , Ascanelli Camilla , Lindon Catherine , De Leo Alessandro , Saviano Michele , Di Santo Roberto , Costi Roberta , Guarguaglini Giulia , Paiardini Alessandro
Published: December 2021

Neuroblastoma is a severe childhood disease, accounting for ~10% of all infant cancers. The amplification of the MYCN gene, coding for the N-Myc transcription factor, is an essential marker correlated with tumor progression and poor prognosis. In neuroblastoma cells, the mitotic kinase Aurora-A (AURKA), also frequently overexpressed in cancer, prevents N-Myc degradation by directly binding to a highly conserved N-Myc region. As a result, elevated levels of N-Myc are observed. During recent years, it has been demonstrated that some ATP competitive inhibitors of AURKA also cause essential conformational changes in the structure of the activation loop of the kinase that prevents N-Myc binding, thus impairing the formation of the AURKA/N-Myc complex. In this study, starting from a screening of crystal structures of AURKA in complexes with known inhibitors, we identified additional compounds affecting the conformation of the kinase activation loop. We assessed the ability of such compounds to disrupt the interaction between AURKA and N-Myc in vitro, using Surface Plasmon Resonance competition assays, and in tumor cell lines overexpressing MYCN, by performing Proximity Ligation Assays. Finally, their effects on N-Myc cellular levels and cell viability were investigated. Our results identify PHA-680626 as an amphosteric inhibitor both in vitro and in MYCN overexpressing cell lines, thus expanding the repertoire of known conformational disrupting inhibitors of the AURKA/N-Myc complex and confirming that altering the conformation of the activation loop of AURKA with a small molecule is an effective strategy to destabilize the AURKA/N-Myc interaction in neuroblastoma cancer cells.
Identification of Phytaspase Interactors via the Proximity-Dependent Biotin-Based Identification Approach
Authors: Teplova Anastasia D. , Serebryakova Marina V. , Galiullina Raisa A. , Chichkova Nina V. , Vartapetian Andrey B.
Published: December 2021

Proteolytic enzymes are instrumental in various aspects of plant development, including senescence. This may be due not only to their digestive activity, which enables protein utilization, but also to fulfilling regulatory functions. Indeed, for the largest family of plant serine proteases, subtilisin-like proteases (subtilases), several members of which have been implicated in leaf and plant senescence, both non-specific proteolysis and regulatory protein processing have been documented. Here, we strived to identify the protein partners of phytaspase, a plant subtilase involved in stress-induced programmed cell death that possesses a characteristic aspartate-specific hydrolytic activity and unusual localization dynamics. A proximity-dependent biotin identification approach in Nicotiana benthamiana leaves producing phytaspase fused to a non-specific biotin ligase TurboID was employed. Although the TurboID moiety appeared to be unstable in the apoplast environment, several intracellular candidate protein interactors of phytaspase were identified. These were mainly, though not exclusively, represented by soluble residents of the endoplasmic reticulum, namely endoplasmin, BiP, and calreticulin-3. For calreticultin-3, whose gene is characterized by an enhanced expression in senescing leaves, direct interaction with phytaspase was confirmed in an in vitro binding assay using purified proteins. In addition, an apparent alteration of post-translational modification of calreticultin-3 in phytaspase-overproducing plant cells was observed.
Acetyl-CoA Carboxylase Inhibitor CP640.186 Increases Tubulin Acetylation and Impairs Thrombin-Induced Platelet Aggregation
Authors: Octave Marie , Pirotton Laurence , Ginion Audrey , Robaux Valentine , Lepropre Sophie , Ambroise Jérôme , Bouzin Caroline , Guigas Bruno , Giera Martin , Foretz Marc , Bertrand Luc , Beauloye Christophe , Horman Sandrine
Published: December 2021

Acetyl-CoA carboxylase (ACC) is the first enzyme regulating de novo lipid synthesis via the carboxylation of acetyl-CoA into malonyl-CoA. The inhibition of its activity decreases lipogenesis and, in parallel, increases the acetyl-CoA content, which serves as a substrate for protein acetylation. Several findings support a role for acetylation signaling in coordinating signaling systems that drive platelet cytoskeletal changes and aggregation. Therefore, we investigated the impact of ACC inhibition on tubulin acetylation and platelet functions. Human platelets were incubated 2 h with CP640.186, a pharmacological ACC inhibitor, prior to thrombin stimulation. We have herein demonstrated that CP640.186 treatment does not affect overall platelet lipid content, yet it is associated with increased tubulin acetylation levels, both at the basal state and after thrombin stimulation. This resulted in impaired platelet aggregation. Similar results were obtained using human platelets that were pretreated with tubacin, an inhibitor of tubulin deacetylase HDAC6. In addition, both ACC and HDAC6 inhibitions block key platelet cytoskeleton signaling events, including Rac1 GTPase activation and the phosphorylation of its downstream effector, p21-activated kinase 2 (PAK2). However, neither CP640.186 nor tubacin affects thrombin-induced actin cytoskeleton remodeling, while ACC inhibition results in decreased thrombin-induced reactive oxygen species (ROS) production and extracellular signal-regulated kinase (ERK) phosphorylation. We conclude that when using washed human platelets, ACC inhibition limits tubulin deacetylation upon thrombin stimulation, which in turn impairs platelet aggregation. The mechanism involves a downregulation of the Rac1/PAK2 pathway, being independent of actin cytoskeleton.
Tailoring Silicon Nitride Surface Chemistry for Facilitating Odontogenic Differentiation of Rat Dental Pulp Cells
Authors: Gong Yanan , Honda Yoshitomo , Adachi Tetsuya , Marin Elia , Yoshikawa Kazushi , Pezzotti Giuseppe , Yamamoto Kazuyo
Published: December 2021

Silicon nitride (Si3N4) can facilitate bone formation; hence, it is used as a biomaterial in orthopedics. Nevertheless, its usability for dentistry is unexplored. The aim of the present study was to investigate the effect of Si3N4 granules for the proliferation and odontogenic differentiation of rat dental pulp cells (rDPCs). Four different types of Si3N4 granules were prepared, which underwent different treatments to form pristine as-synthesized Si3N4, chemically treated Si3N4, thermally treated Si3N4, and Si3N4 sintered with 3 wt.% yttrium oxide (Y2O3). rDPCs were cultured on or around the Si3N4 granular beds. Compared with the other three types of Si3N4 granules, the sintered Si3N4 granules significantly promoted cellular attachment, upregulated the expression of odontogenic marker genes (Dentin Matrix Acidic Phosphoprotein 1 and Dentin Sialophosphoprotein) in the early phase, and enhanced the formation of mineralization nodules. Furthermore, the water contact angle of sintered Si3N4 was also greatly increased to 40°. These results suggest that the sintering process for Si3N4 with Y2O3 positively altered the surface properties of pristine as-synthesized Si3N4 granules, thereby facilitating the odontogenic differentiation of rDPCs. Thus, the introduction of a sintering treatment for Si3N4 granules is likely to facilitate their use in the clinical application of dentistry.
Control of TRPM3 Ion Channels by Protein Kinase CK2-Mediated Phosphorylation in Pancreatic β-Cells of the Line INS-1
Authors: Becker Alexander , Götz Claudia , Montenarh Mathias , Philipp Stephan E.
Published: December 2021

In pancreatic β-cells of the line INS-1, glucose uptake and metabolism induce the openings of Ca2+-permeable TRPM3 channels that contribute to the elevation of the intracellular Ca2+ concentration and the fusion of insulin granules with the plasma membrane. Conversely, glucose-induced Ca2+ signals and insulin release are reduced by the activity of the serine/threonine kinase CK2. Therefore, we hypothesized that TRPM3 channels might be regulated by CK2 phosphorylation. We used recombinant TRPM3α2 proteins, native TRPM3 proteins from INS-1 β-cells, and TRPM3-derived oligopeptides to analyze and localize CK2-dependent phosphorylation of TRPM3 channels. The functional consequences of CK2 phosphorylation upon TRPM3-mediated Ca2+ entry were investigated in Fura-2 Ca2+-imaging experiments. Recombinant TRPM3α2 channels expressed in HEK293 cells displayed enhanced Ca2+ entry in the presence of the CK2 inhibitor CX-4945 and their activity was strongly reduced after CK2 overexpression. TRPM3α2 channels were phosphorylated by CK2 in vitro at serine residue 1172. Accordingly, a TRPM3α2 S1172A mutant displayed enhanced Ca2+ entry. The TRPM3-mediated Ca2+ entry in INS-1 β-cells was also strongly increased in the presence of CX-4945 and reduced after overexpression of CK2. Our study shows that CK2-mediated phosphorylation controls TRPM3 channel activity in INS-1 β-cells.
Targeting MicroRNA-485-3p Blocks Alzheimer’s Disease Progression
Authors: Koh Han , Lee SangJoon , Lee Hyo , Min Jae-Woong , Iwatsubo Takeshi , Teunissen Charlotte , Cho Hyun-Jeong , Ryu Jin-Hyeob
Published: December 2021

Alzheimer’s disease (AD) is a form of dementia characterized by progressive memory decline and cognitive dysfunction. With only one FDA-approved therapy, effective treatment strategies for AD are urgently needed. In this study, we found that microRNA-485-3p (miR-485-3p) was overexpressed in the brain tissues, cerebrospinal fluid, and plasma of patients with AD, and its antisense oligonucleotide (ASO) reduced Aβ plaque accumulation, tau pathology development, neuroinflammation, and cognitive decline in a transgenic mouse model of AD. Mechanistically, miR-485-3p ASO enhanced Aβ clearance via CD36-mediated phagocytosis of Aβ in vitro and in vivo. Furthermore, miR-485-3p ASO administration reduced apoptosis, thereby effectively decreasing truncated tau levels. Moreover, miR-485-3p ASO treatment reduced secretion of proinflammatory cytokines, including IL-1β and TNF-α, and eventually relieved cognitive impairment. Collectively, our findings suggest that miR-485-3p is a useful biomarker of the inflammatory pathophysiology of AD and that miR-485-3p ASO represents a potential therapeutic candidate for managing AD pathology and cognitive decline.
Single Co3O4 Nanocubes Electrocatalyzing the Oxygen Evolution Reaction: Nano-Impact Insights into Intrinsic Activity and Support Effects
Authors: Liu Zhibin , Corva Manuel , Amin Hatem M. A. , Blanc Niclas , Linnemann Julia , Tschulik Kristina
Published: December 2021

Single-entity electrochemistry allows for assessing electrocatalytic activities of individual material entities such as nanoparticles (NPs). Thus, it becomes possible to consider intrinsic electrochemical properties of nanocatalysts when researching how activity relates to physical and structural material properties. Conversely, conventional electrochemical techniques provide a normalized sum current referring to a huge ensemble of NPs constituting, along with additives (e.g., binders), a complete catalyst-coated electrode. Accordingly, recording electrocatalytic responses of single NPs avoids interferences of ensemble effects and reduces the complexity of electrocatalytic processes, thus enabling detailed description and modelling. Herein, we present insights into the oxygen evolution catalysis at individual cubic Co3O4 NPs impacting microelectrodes of different support materials. Simulating diffusion at supported nanocubes, measured step current signals can be analyzed, providing edge lengths, corresponding size distributions, and interference-free turnover frequencies. The provided nano-impact investigation of (electro-)catalyst-support effects contradicts assumptions on a low number of highly active sites.
A Review on Electrochemical Sensors and Biosensors Used in Chlorogenic Acid Electroanalysis
Authors: Munteanu Irina Georgiana , Apetrei Constantin
Published: December 2021

Chlorogenic acid (5-O-caffeoylquinic acid) is a phenolic compound from the hydroxycinnamic acid family. Epidemiological, biological, and biochemical studies concur to support the beneficial role of chlorogenic acid in human health, along with other dietary phenolic compounds. Thus, chlorogenic acid has been reported to exert inhibitory effects on carcinogenesis in the large intestine, liver, and tongue, and a protective action on oxidative stress in vivo, together with anti-inflammatory, antidiabetic and antihypertensive activities. It is also claimed to have antifungal, antibacterial and antiviral effects with relatively low toxicity and side effects, alongside properties that do not lead to antimicrobial resistance. Due to its importance, numerous methods for determining chlorogenic acid (CGA), as well as for its derivatives from coffee beans and other plants, were elaborated. The most frequently used methods are infrared spectroscopy, high performance liquid chromatography (HPLC), capillary electrophoresis, liquid chromatography-mass spectrometry and chemiluminescence. Although these methods proved to be efficient for quantifying CGA and its derived products, a number of deficiencies were identified: they are time consuming, laborious, and require expensive instruments. Therefore, electrochemical methods have been developed and used in the determination of CGA in different nutraceuticals or food products. The present review aims to present the main progresses and performance characteristics of electrochemical sensors and biosensors used to detect CGA, as it is reported in a high number of relevant scientific papers published mainly in the last decade.
Metabolome Profiling of Heat Priming Effects, Senescence, and Acclimation of Bread Wheat Induced by High Temperatures at Different Growth Stages
Authors: Matsunaga Sachiko , Yamasaki Yuji , Mega Ryosuke , Toda Yusuke , Akashi Kinya , Tsujimoto Hisashi
Published: December 2021

Our previous study described stage-specific responses of ‘Norin 61’ bread wheat to high temperatures from seedling to tillering (GS1), tillering to flowering (GS2), flowering to full maturity stage (GS3), and seedling to full maturity stage (GS1–3). The grain development phase lengthened in GS1 plants; source tissue decreased in GS2 plants; rapid senescence occurred in GS3 plants; all these effects occurred in GS1–3 plants. The present study quantified 69 flag leaf metabolites during early grain development to reveal the effects of stage-specific high-temperature stress and identify markers that predict grain weight. Heat stresses during GS2 and GS3 showed the largest shifts in metabolite contents compared with the control, followed by GS1–3 and GS1. The GS3 plants accumulated nucleosides related to the nucleotide salvage pathway, beta-alanine, and serotonin. Accumulation of these compounds in GS1 plants was significantly lower than in the control, suggesting that the reduction related to the high-temperature priming effect observed in the phenotype (i.e., inhibition of senescence). The GS2 plants accumulated a large quantity of free amino acids, indicating residual effects of the previous high-temperature treatment and recovery from stress. However, levels in GS1–3 plants tended to be close to those in the control, indicating an acclimation response. Beta-alanine, serotonin, tryptophan, proline, and putrescine are potential molecular markers that predict grain weight due to their correlation with agronomic traits.
Current and Future Advancements of Raman Spectroscopy Techniques in Cancer Nanomedicine
Authors: Canetta Elisabetta
Published: December 2021

Raman scattering is one of the most used spectroscopy and imaging techniques in cancer nanomedicine due to its high spatial resolution, high chemical specificity, and multiplexity modalities. The flexibility of Raman techniques has led, in the past few years, to the rapid development of Raman spectroscopy and imaging for nanodiagnostics, nanotherapy, and nanotheranostics. This review focuses on the applications of spontaneous Raman spectroscopy and bioimaging to cancer nanotheranostics and their coupling to a variety of diagnostic/therapy methods to create nanoparticle-free theranostic systems for cancer diagnostics and therapy. Recent implementations of confocal Raman spectroscopy that led to the development of platforms for monitoring the therapeutic effects of anticancer drugs in vitro and in vivo are also reviewed. Another Raman technique that is largely employed in cancer nanomedicine, due to its ability to enhance the Raman signal, is surface-enhanced Raman spectroscopy (SERS). This review also explores the applications of the different types of SERS, such as SERRS and SORS, to cancer diagnosis through SERS nanoprobes and the detection of small-size biomarkers, such as exosomes. SERS cancer immunotherapy and immuno-SERS (iSERS) microscopy are reviewed.
Comprehensive Analysis of Arabinogalactan Protein-Encoding Genes Reveals the Involvement of Three BrFLA Genes in Pollen Germination in Brassica rapa
Authors: Huang Huiting , Miao Yingjing , Zhang Yuting , Huang Li , Cao Jiashu , Lin Sue
Published: December 2021

Arabinogalactan proteins (AGPs) are a superfamily of hydroxyproline-rich glycoproteins that are massively glycosylated, widely implicated in plant growth and development. No comprehensive analysis of the AGP gene family has been performed in Chinese cabbage (Brassica rapa ssp. chinensis). Here, we identified a total of 293 putative AGP-encoding genes in B. rapa, including 25 classical AGPs, three lysine-rich AGPs, 30 AG-peptides, 36 fasciclin-like AGPs (FLAs), 59 phytocyanin-like AGPs, 33 xylogen-like AGPs, 102 other chimeric AGPs, two non-classical AGPs and three AGP/extensin hybrids. Their protein structures, phylogenetic relationships, chromosomal location and gene duplication status were comprehensively analyzed. Based on RNA sequencing data, we found that 73 AGP genes were differentially expressed in the floral buds of the sterile and fertile plants at least at one developmental stage in B. rapa, suggesting a potential role of AGPs in male reproductive development. We further characterized BrFLA2, BrFLA28 and BrFLA32, three FLA members especially expressed in anthers, pollen grains and pollen tubes. BrFLA2, BrFLA28 and BrFLA32 are indispensable for the proper timing of pollen germination under high relative humidity. Our study greatly extends the repertoire of AGPs in B. rapa and reveals a role for three members of the FLA subfamily in pollen germination.
An Easy Route to Aziridine Ketones and Carbinols
Authors: Strumfs Boriss , Hermane Jekaterina , Belyakov Sergey , Sobolevs Artjoms , Velikijs Kirils , Uljanovs Romans , Trapencieris Peteris , Strumfa Ilze
Published: December 2021

N,N-Dimethylaziridine-2-carboxamides react with organolithium reagents yielding 2-aziridinylketones. The reaction with one equivalent of organolithium compound is selective to amide carbonyl at a low (−78 °C) temperature. These ketones, in reaction with organolithium reagents, give symmetrical and unsymmetrical aziridinyl carbinols. The usage of excess phenyllithium may serve as a special N-Boc-protecting group cleavage method for acid-sensitive substrates.
Evaluation of the Physico-Chemical Properties of Liposomes Assembled from Bioconjugates of Anisic Acid with Phosphatidylcholine
Authors: Pruchnik Hanna , Gliszczyńska Anna , Włoch Aleksandra
Published: December 2021

The aim of this work was the evaluation of the physico-chemical properties of a new type of liposomes that are composed of DPPC and bioconjugates of anisic acid with phosphatidylcholine. In particular, the impact of modified anisic acid phospholipids on the thermotropic parameters of liposomes was determined, which is crucial for using them as potential carriers of active substances in cancer therapies. Their properties were determined using three biophysical methods, namely differential scanning calorimetry (DSC), steady-state fluorimetry and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Moreover, temperature studies of liposomes composed of DPPC and bioconjugates of anisic acid with phosphatidylcholine provided information about the phase transition, fluidity regarding chain order, hydration and dynamics. The DSC results show that the main phase transition peak for conjugates of anisic acid with phosphatidylcholine molecules was broadened and shifted to a lower temperature in a concentration- and structure-dependent manner. The ATR-FTIR results and the results of measurements conducted using fluorescent probes located at different regions in the lipid bilayer are in line with DSC. The results show that the new bioconjugates with phosphatidylcholine have a significant impact on the physico-chemical properties of a membrane and cause a decrease in the temperature of the main phase transition. The consequence of this is greater fluidity of the lipid bilayer.
Impact of Cigarette Smoking on the Expression of Oxidative Stress-Related Genes in Cumulus Cells Retrieved from Healthy Women Undergoing IVF
Authors: Konstantinidou Fani , Budani Maria Cristina , Sarra Annalina , Stuppia Liborio , Tiboni Gian Mario , Gatta Valentina
Published: December 2021

The female reproductive system represents a sensitive target of the harmful effects of cigarette smoke, with folliculogenesis as one of the ovarian processes most affected by this exposure. The aim of this study was to analyze the impact of tobacco smoking on expression of oxidative stress-related genes in cumulus cells (CCs) from smoking and non-smoking women undergoing IVF techniques. Real time PCR technology was used to analyze the gene expression profile of 88 oxidative stress genes enclosed in a 96-well plate array. Statistical significance was assessed by one-way ANOVA. The biological functions and networks/pathways of modulated genes were evidenced by ingenuity pathway analysis software. Promoter methylation analysis was performed by pyrosequencing. Our results showed a down-regulation of 24 genes and an up-regulation of 2 genes (IL6 and SOD2, respectively) involved in defense against oxidative damage, cell cycle regulation, as well as inflammation in CCs from smoking women. IL-6 lower promoter methylation was found in CCs of the smokers group. In conclusion, the disclosed overall downregulation suggests an oxidant-antioxidant imbalance in CCs triggered by cigarette smoking exposure. This evidence adds a piece to the puzzle of the molecular basis of female reproduction and could help underlay the importance of antioxidant treatments for smoking women undergoing IVF protocols.
AS1411 Nucleolin-Specific Binding Aptamers Reduce Pathological Angiogenesis through Inhibition of Nucleolin Phosphorylation
Authors: Iturriaga-Goyon Emilio , Vivanco-Rojas Oscar , Magaña-Guerrero Fátima Sofía , Buentello-Volante Beatriz , Castro-Salas Ilse , Aguayo-Flores José Eduardo , Gracia-Mora Isabel , Rivera-Huerta Marisol , Sánchez-Bartés Francisco , Garfias Yonathan
Published: December 2021

Proliferative retinopathies produces an irreversible type of blindness affecting working age and pediatric population of industrialized countries. Despite the good results of anti-VEGF therapy, intraocular and systemic complications are often associated after its intravitreal use, hence novel therapeutic approaches are needed. The aim of the present study is to test the effect of the AS1411, an antiangiogenic nucleolin-binding aptamer, using in vivo, ex vivo and in vitro models of angiogenesis and propose a mechanistic insight. Our results showed that AS1411 significantly inhibited retinal neovascularization in the oxygen induced retinopathy (OIR) in vivo model, as well as inhibited branch formation in the rat aortic ex vivo assay, and, significantly reduced proliferation, cell migration and tube formation in the HUVEC in vitro model. Importantly, phosphorylated NCL protein was significantly abolished in HUVEC in the presence of AS1411 without affecting NFκB phosphorylation and -21 and 221-angiomiRs, suggesting that the antiangiogenic properties of this molecule are partially mediated by a down regulation in NCL phosphorylation. In sum, this new research further supports the NCL role in the molecular etiology of pathological angiogenesis and identifies AS1411 as a novel anti-angiogenic treatment.
CIDOC2VEC: Extracting Information from Atomized CIDOC-CRM Humanities Knowledge Graphs
Authors: El-Hajj Hassan , Valleriani Matteo
Published: December 2021

The development of the field of digital humanities in recent years has led to the increased use of knowledge graphs within the community. Many digital humanities projects tend to model their data based on CIDOC-CRM ontology, which offers a wide array of classes appropriate for storing humanities and cultural heritage data. The CIDOC-CRM ontology model leads to a knowledge graph structure in which many entities are often linked to each other through chains of relations, which means that relevant information often lies many hops away from their entities. In this paper, we present a method based on graph walks and text processing to extract entity information and provide semantically relevant embeddings. In the process, we were able to generate similarity recommendations as well as explore their underlying data structure. This approach was then demonstrated on the Sphaera Dataset which was modeled according to the CIDOC-CRM data structure.
Body Size Variation in a Social Sweat Bee, Halictus ligatus (Halictidae, Apoidea), across Urban Environments
Authors: Brant Rachel A. , Camilo Gerardo R.
Published: December 2021

High morphological variation is often associated with species longevity, and it is hypothesized that urban-dwelling species may require more plasticity in functional traits such as body size in order to maximize fitness in heterogeneous environments. There has been published research regarding the functional trait diversity of urban bee pollinators. However, no two cities are identical, so the implementation of multi-city studies is vital. Therefore, we compared body size variation in female Halicus ligatus sweat bees from May–October 2016 from three distinct Midwestern United States cities: Chicago, Detroit, and Saint Louis. Additionally, to elucidate potentially influential environmental factors, we assessed the relationship between temperature and measured body size. We collected bees in community gardens and urban farms and measured their head width and intertegular distance as a proxy for overall body size. We utilized an ANCOVA to determine whether body size variation differed significantly across the three surveyed cities. Results indicated that H. ligatus females in Chicago, Detroit, and Saint Louis had significantly different body size ranges. These findings highlight the importance of intraspecific body size variation and support our prediction that bees from different urban environments will have distinct ranges in body size due to local ecological factors affecting their populations. Additionally, we found a significant influence of temperature, though this is probably not the only important ecological characteristic impacting bee body size. Therefore, we also provided a list of predictions for the future study of specific variables that are likely to impact functional trait diversity in urban bees.
Immediate and Delayed Mortality of Four Stored-Product Pests on Concrete Surfaces Treated with Chlorantraniliprole
Authors: Kavallieratos Nickolas G. , Boukouvala Maria C. , Nika Erifili P. , Eleftheriadou Nikoleta , Avtzis Dimitrios N.
Published: December 2021

Chlorantraniliprole is an effective pesticide against a plethora of pests, but its efficacy against stored-product pests is very poorly explored. In this study we treated concrete surfaces with four different doses of chlorantraniliprole (0.01, 0.05, 0.1, and 0.5 mg a.i./cm2) against the red flour beetle, Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) adults and larvae, the lesser grain borer, Rhyzopertha dominica (F.) (Coleoptera: Bostrychidae) adults, the rice weevil, Sitophilus oryzae (L.) (Coleoptera: Curculionidae) adults, and the flour mite, Acarus siro L. (Sarcoptiformes: Acaridae) adults and nymphs, to examine the immediate mortalities after 1, 2, 3, 4, and 5 days of exposure. Additionally, the delayed mortality of the individuals that survived the 5-day exposure was also evaluated after a further 7 days on untreated concrete surfaces. We documented high mortality rates for all tested species and their developmental stages. After 5 days of exposure to 0.5 mg a.i./cm2, T. castaneum larvae and A. siro adults exhibited the highest immediate mortality levels, reaching 96.7% and 92.2%, respectively. Delayed mortality was also very high for all tested species and their developmental stages. Nymphs of A. siro displayed a 96.3% delayed mortality followed by the adults of R. dominica (98.6%) after exposure to 0.5 mg a.i./cm2. All other tested species and their developmental stages reached complete (100.0%) delayed mortality, where even 0.01 mg a.i./cm2 caused ≥86.6% delayed mortality in all species and their developmental stages. Taking into consideration the effectiveness of chlorantraniliprole on this wide range of noxious arthropods, coupled with its low toxicity towards beneficial arthropods and mammals, this pesticide could provide an effective management tool for stored-product pests in storage facilities.
The Adult, Larva, and Pupa of a New Pseudopyrochroa (Coleoptera: Pyrochroidae: Pyrochroinae) from China, with Molecular Phylogenetic Inferences
Authors: Pan Zhao , Duan Jia-Chong , Gao Qi , Young Daniel K.
Published: December 2021

A new species of Pseudopyrochroa Pic, 1906, P. reni Pan & Young, n. sp., is described from the western region of Mt. Qinling, China. Larvae, pupae, and adults were associated using molecular phylogenetic analyses based on mtDNA COI barcode sequences. All three stages are described and illustrated. Additionally, preliminary phylogenetic relationships among five genera and 14 species of Pyrochroidae, including Pseudopyrochroa, are hypothesized based on COI sequence data. The fauna of Pyrochroidae from the Mt. Qinling biodiversity conservation area is discussed.
The Relationship between Alcohol Hangover Severity, Sleep and Cognitive Performance; a Naturalistic Study
Authors: Ayre Elizabeth , Scholey Andrew , White David , Devilly Grant J. , Kaufman Jordy , Verster Joris C. , Allen Corey , Benson Sarah
Published: December 2021

Alcohol hangover (AH) has been associated with poor sleep due to the negative effects of alcohol intoxication on sleep quantity and sleep quality. The aim of the current study was to further explore the relationship between AH severity and sleep using a naturalistic study design. A further aim was to determine whether quantitative aspects of sleep were a mediating influence on the relationship between AH severity and cognitive performance. As part of the naturalistic study design, 99 drinkers were recruited following a night of drinking in an Australian state capital, with breath alcohol concentration (BrAC) measured as participants were leaving the entertainment district. The following morning at home, participants answered online questions regarding their drinking behaviour on the previous evening, current AH symptoms and sleep quality. Participants also completed an online version of the Trail-Making Test B (TMT-B) to assess cognitive performance. The findings reveal the duration of nightly awakenings to be negatively related to six individual AH symptoms as well as overall AH severity. The number of nightly awakenings, sleep quality and total sleep time correlated with four AH symptoms including overall AH severity. Total AH severity accounted for a moderate amount of variance (11%) in the time to complete the TMT-B. These findings confirm that alcohol consumption negatively affects sleep, which is related to higher next-day hangover severity ratings and poorer cognitive performance.
Fatigue Analysis of NiTi Rotary Endodontic Files through Finite Element Simulation: Effect of Root Canal Geometry on Fatigue Life
Authors: Roda-Casanova Victor , Pérez-González Antonio , Zubizarreta-Macho Álvaro , Faus-Matoses Vicente
Published: December 2021

This article describes a numerical procedure for estimating the fatigue life of NiTi endodontic rotary files. An enhanced finite element model reproducing the interaction of the endodontic file rotating inside the root canal was developed, which includes important phenomena that allowed increasing the degree of realism of the simulation. A method based on the critical plane approach was proposed for extracting significant strain results from finite element analysis, which were used in combination with the Coffin–Manson relation to predict the fatigue life of the NiTi rotary files. The proposed procedure is illustrated with several numerical examples in which different combinations of endodontic rotary files and root canal geometries were investigated. By using these analyses, the effect of the radius of curvature and the angle of curvature of the root canal on the fatigue life of the rotary files was analysed. The results confirm the significant influence of the root canal geometry on the fatigue life of the NiTi rotary files and reveal the higher importance of the radius of curvature with respect to the angle of curvature of the root canal.
Intracranial Pressure Patterns and Neurological Outcomes in Out-of-Hospital Cardiac Arrest Survivors after Targeted Temperature Management: A Retrospective Observational Study
Authors: Song Hogul , Kang Changshin , Park Jungsoo , You Yeonho , In Yongnam , Min Jinhong , Jeong Wonjoon , Cho Yongchul , Ahn Hongjoon , Kim Dongil
Published: December 2021

We aimed to investigate intracranial pressure (ICP) changes over time and the neurologic prognosis for out-of-hospital cardiac arrest (OHCA) survivors who received targeted temperature management (TTM). ICP was measured immediately after return of spontaneous circulation (ROSC) (day 1), then at 24 h (day 2), 48 h (day 3), and 72 h (day 4), through connecting a lumbar drain catheter to a manometer or a LiquoGuard machine. Neurological outcomes were determined at 3 months after ROSC, and a poor neurological outcome was defined as Cerebral Performance Category 3–5. Of the 91 patients in this study (males, n = 67, 74%), 51 (56%) had poor neurological outcomes. ICP was significantly higher in the poor outcome group at each time point except day 4. ICP elevation was highest between days 2 and 3 in the good outcome group, and between days 1 and 2 in the poor outcome group. However, there was no difference in total ICP elevation between the poor and good outcome groups (3.0 vs. 3.1; p = 0.476). All OHCA survivors who had received TTM had elevated ICP, regardless of neurologic prognosis. However, the changing pattern of ICP levels differed depending on the neurological outcome.
Copper and Trace Elements in Gallbladder form Patients with Wilson’s Disease Imaged and Determined by Synchrotron X-ray Fluorescence
Authors: Osterode Wolf , Falkenberg Gerald , Wrba Fritz
Published: December 2021

Investigations about suspected tissue alterations and the role of gallbladder in Wilson’s disease (WD)—an inherited genetic disease with impaired copper metabolism—are rare. Therefore, tissue from patients with genetically characterised WD was investigated by microscopic synchrotron X-ray fluorescence (µSRXRF). For two-dimensional imaging and quantification of elements, X-ray spectra were peak-fitted, and the net peak intensities were normalised to the intensity of the incoming monochromatic beam intensity. Concentrations were calculated by fundamental parameter-based program quant and external standardisation. Copper (Cu), zinc (Zn) and iron (Fe) along with sulphur (S) and phosphorus (P) mappings could be demonstrated in a near histological resolution. All these elements were increased compared to gallbladder tissue from controls. Cu and Zn and Fe in WD-GB were mostly found to be enhanced in the epithelium. We documented a significant linear relationship with Cu, Zn and sulphur. Concentrations of Cu/Zn were roughly 1:1 while S/Cu was about 100:1, depending on the selected areas for investigation. The significant linear relationship with Cu, Zn and sulphur let us assume that metallothioneins, which are sulphur-rich proteins, are increased too. Our data let us suggest that the WD gallbladder is the first in the gastrointestinal tract to reabsorb metals to prevent oxidative damage caused by metal toxicity.