bluuebunny/crossref_metadata_2025 huggingface dataset:
Brain Activity during Visual and Auditory Word Rhyming Tasks in Cantonese–Mandarin–English Trilinguals
Authors: Wu Yujia , Ma Jingwen , Cai Lei , Wang Zengjian , Fan Miao , Chu Jianping , Zhang Yue , Li Xiuhong
Published: December 2020

It is unclear whether the brain activity during phonological processing of second languages (L2) is similar to that of the first language (L1) in trilingual individuals, especially when the L1 is logographic, and the L2s are logographic and alphabetic, respectively. To explore this issue, this study examined brain activity during visual and auditory word rhyming tasks in Cantonese–Mandarin–English trilinguals. Thirty Chinese college students whose L1 was Cantonese and L2s were Mandarin and English were recruited. Functional magnetic resonance imaging (fMRI) was conducted while subjects performed visual and auditory word rhyming tasks in three languages (Cantonese, Mandarin, and English). The results revealed that in Cantonese–Mandarin–English trilinguals, whose L1 is logographic and the orthography of their L2 is the same as L1—i.e., Mandarin and Cantonese, which share the same set of Chinese characters—the brain regions for the phonological processing of L2 are different from those of L1; when the orthography of L2 is quite different from L1, i.e., English and Cantonese who belong to different writing systems, the brain regions for the phonological processing of L2 are similar to those of L1. A significant interaction effect was observed between language and modality in bilateral lingual gyri. Regions of interest (ROI) analysis at lingual gyri revealed greater activation of this region when using English than Cantonese and Mandarin in visual tasks.
Hemispheric Asymmetries in Electroencephalogram Oscillations for Long-Term Memory Retrieval in Healthy Individuals
Authors: Jawed Soyiba , Amin Hafeez Ullah , Malik Aamir Saeed , Faye Ibrahima
Published: December 2020

The hemispherical encoding retrieval asymmetry (HERA) model, established in 1991, suggests that the involvement of the right prefrontal cortex (PFC) in the encoding process is less than that of the left PFC. The HERA model was previously validated for episodic memory in subjects with brain traumas or injuries. In this study, a revised HERA model is used to investigate long-term memory retrieval from newly learned video-based content for healthy individuals using electroencephalography. The model was tested for long-term memory retrieval in two retrieval sessions: (1) recent long-term memory (recorded 30 min after learning) and (2) remote long-term memory (recorded two months after learning). The results show that long-term memory retrieval in healthy individuals for the frontal region (theta and delta band) satisfies the revised HERA asymmetry model.
Epigenetics in Breast Cancer Therapy—New Strategies and Future Nanomedicine Perspectives
Authors: Buocikova Verona , Rios-Mondragon Ivan , Pilalis Eleftherios , Chatziioannou Aristotelis , Miklikova Svetlana , Mego Michal , Pajuste Karlis , Rucins Martins , Yamani Naouale El , Longhin Eleonora Marta , Sobolev Arkadij , Freixanet Muriel , Puntes Victor , Plotniece Aiva , Dusinska Maria , Cimpan Mihaela Roxana , Gabelova Alena , Smolkova Bozena
Published: December 2020

Epigenetic dysregulation has been recognized as a critical factor contributing to the development of resistance against standard chemotherapy and to breast cancer progression via epithelial-to-mesenchymal transition. Although the efficacy of the first-generation epigenetic drugs (epi-drugs) in solid tumor management has been disappointing, there is an increasing body of evidence showing that epigenome modulation, in synergy with other therapeutic approaches, could play an important role in cancer treatment, reversing acquired therapy resistance. However, the epigenetic therapy of solid malignancies is not straightforward. The emergence of nanotechnologies applied to medicine has brought new opportunities to advance the targeted delivery of epi-drugs while improving their stability and solubility, and minimizing off-target effects. Furthermore, the omics technologies, as powerful molecular epidemiology screening tools, enable new diagnostic and prognostic epigenetic biomarker identification, allowing for patient stratification and tailored management. In combination with new-generation epi-drugs, nanomedicine can help to overcome low therapeutic efficacy in treatment-resistant tumors. This review provides an overview of ongoing clinical trials focusing on combination therapies employing epi-drugs for breast cancer treatment and summarizes the latest nano-based targeted delivery approaches for epi-drugs. Moreover, it highlights the current limitations and obstacles associated with applying these experimental strategies in the clinics.
Long-Term Neurodevelopmental Outcome of Children after in Utero Exposure to Chemotherapy
Authors: Korakiti Anna-Maria , Zografos Eleni , van Gerwen Mathilde , Amant Frédéric , Dimopoulos Meletios-Athanasios , Zagouri Flora
Published: December 2020

Pregnancy-related cancer management represents a real challenge for both the patients and the physicians. The long-term neurodevelopmental outcome of children in utero exposed to chemotherapeutic agents has only recently been addressed. This review aims to systematically integrate and highlight all existing data from the literature regarding the effect of prenatal exposure to chemotherapy on fetal brain growth and child development. All eligible studies are based on validated neurodevelopmental testing scales (e.g., Bayley Scales of Infant Development, Wechsler Preschool and Primary Scale of Intelligence) and/or well-defined questionnaires. Our systematic review including 17 studies demonstrates that no major consequences on the neurodevelopment of children after in utero exposure to anti-cancer drugs have been reported; nevertheless, longer and more thorough follow-up with large-scale multicenter prospective studies is certainly required in order to draw firm conclusions.
Long Noncoding RNA E2F4as Promotes Progression and Predicts Patient Prognosis in Human Ovarian Cancer
Authors: Park Sun-Ae , Kim Lee Kyung , Kim Young Tae , Heo Tae-Hwe , Kim Hee Jung
Published: December 2020

(1) Background: LncRNAs could be a promising biomarker to predict the prognosis of various cancers. The significance of E2F4antisense lncRNA remains unclear in cancer. In this study, we examined the expression level of E2F4as in the serum of ovarian cancer patients and the functional role of E2F4as. (2) Methods: Serum samples were obtained from 108 OC patients and 32 normal patients to measure the expression of E2F4as in the serum. Ovarian cancer cells were used to investigate the role of E2F4as in cell proliferation, invasion, migration and apoptosis, and the expression of E2F4as was knocked down using RNA interference. In addition, E2F4as knockdown cell lines were used in in vivo experiments. (3) Results: The expression of E2F4as was significantly higher in the serum of OC patients than in that of control patients (p < 0.05). The knockdown of E2F4as in ovarian cancer cells led to a decrease in cell proliferation, invasion and migration and an increase in apoptosis. E2F4as knockdown also reduced the expression of epithelium–mesenchymal metastasis (EMT) genes. (4) Conclusion: These findings highlight the clinical significance of E2F4as in predicting the prognosis of OC patients and suggest its potential in promoting tumour aggressiveness by the regulation of EMT-related mechanisms.
Detection of Structural Variants in Circulating Cell-Free DNA from Sarcoma Patients Using Next Generation Sequencing
Authors: Mc Connell Lauren , Gazdova Jana , Beck Katja , Srivastava Shambhavi , Harewood Louise , Stewart JP , Hübschmann Daniel , Stenzinger Albrecht , Glimm Hanno , Heilig Christoph E. , Fröhling Stefan , Gonzalez David
Published: December 2020

Circulating tumour DNA (ctDNA) analysis using next generation sequencing (NGS) is being implemented in clinical practice for treatment stratification and disease monitoring. However, using ctDNA to detect structural variants, a common occurrence in sarcoma, can be challenging. Here, we use a sarcoma-specific targeted NGS panel to identify translocations and copy number variants in a cohort of 12 tissue specimens and matched circulating cell-free DNA (cfDNA) from soft tissue sarcoma patients, including alveolar rhabdomyosarcoma (n = 2), Ewing’s Sarcoma (n = 2), synovial sarcoma (n = 2), extraskeletal myxoid chondrosarcoma (n = 1), clear cell sarcoma (n = 1), undifferentiated round cell sarcoma (n = 1), myxoid liposarcoma (n = 1), alveolar soft part cell sarcoma (n = 1) and dedifferentiated liposarcoma (n = 1). Structural variants were detected in 11/12 (91.6%) and 6/12 (50%) of tissue and plasma samples, respectively. Structural variants were detected in cfDNA at variant allele frequencies >0.2% with an average sequencing depth of 1026×. The results from this cohort show clinical potential for using NGS in ctDNA to aid in the diagnosis and clinical monitoring of sarcomas and warrant additional studies in larger cohorts.
Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer
Authors: Villalobos-Ayala Krystal , Ortiz Rivera Ivannie , Alvarez Ciara , Husain Kazim , DeLoach DeVon , Krystal Gerald , Hibbs Margaret L. , Jiang Kun , Ghansah Tomar
Published: December 2020

Pancreatic cancer (PC) has an extremely poor prognosis due to the expansion of immunosuppressive myeloid-derived suppressor cells (MDSC) and tumor-associated macrophages (TAM) in the inflammatory tumor microenvironment (TME), which halts the recruitment of effector immune cells and renders immunotherapy ineffective. Thus, the identification of new molecular targets that can modulate the immunosuppressive TME is warranted for PC intervention. Src Homology-2 (SH2) domain-containing Inositol 5′-Phosphatase-1 (SHIP-1) is a lipid signaling protein and a regulator of myeloid cell development and function. Herein, we used the bioflavonoid apigenin (API) to reduce inflammation in different PC models. Wild type mice harboring heterotopic or orthotopic PC were treated with API, which induced SHIP-1 expression, reduced inflammatory tumor-derived factors (TDF), increased the proportion of tumoricidal macrophages and enhanced anti-tumor immune responses, resulting in a reduction in tumor burden compared to vehicle-treated PC mice. In contrast, SHIP-1-deficient mice exhibited an increased tumor burden and displayed augmented proportions of pro-tumor macrophages. These results provide further support for the importance of SHIP-1 expression in promoting pro-tumor macrophage development in the pancreatic TME. Our findings suggest that agents augmenting SHIP-1 expression may provide novel therapeutic options for the treatment of PC.
A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer
Authors: Oshi Masanori , Tokumaru Yoshihisa , Patel Ankit , Yan Li , Matsuyama Ryusei , Endo Itaru , Katz Matthew H.G. , Takabe Kazuaki
Published: December 2020

Pathologically complete (R0) resection is essential for prolonged survival in pancreatic cancer. Survival depends not only on surgical technique, but also on cancer biology. A biomarker to predict survival is a critical need in pancreatic treatment. We hypothesized that this 4-gene score, which was reported to reflect cell proliferation, is a translatable predictive biomarker for pancreatic cancer. A total of 954 pancreatic cancer patients from multiple cohorts were analyzed and validated. Pancreatic cancer had the 10th highest median score of 32 cancers in The Cancer Genome Atlas (TCGA) cohort. The four-gene score significantly correlated with pathological grade and MKI67 expression. The high four-gene score enriched cell proliferation-related and cancer aggressiveness-related gene sets. The high score was associated with activation of KRAS, p53, transforming growth factor (TGF)-β, and E2F pathways, and with high alteration rate of KRAS and CDKN2A genes. The high score was also significantly associated with reduced CD8+ T cell infiltration of tumors, but with high levels of interferon-γ and cytolytic activity in tumors. The four-gene score correlated with the area under the curve of irinotecan and sorafenib in primary pancreatic cancer, and with paclitaxel and doxorubicin in metastatic pancreatic cancer. The high four-gene score was associated with significantly fewer R0 resections and worse survival. The novelty of the study is in the application of the four-gene score to pancreatic cancer, rather than the bioinformatics technique itself. Future analyses of inoperable lesions are expected to clarify the utility of our score as a predictive biomarker of systemic treatments.
Evaluation of Clinicopathological and Molecular Parameters on Disease Recurrence of Papillary Thyroid Cancer Patient: A Retrospective Observational Study
Authors: Sorrenti Salvatore , Carbotta Giovanni , Di Matteo Filippo Maria , Catania Antonio , Pironi Daniele , Tartaglia Francesco , Tarroni Danilo , Gagliardi Federica , Tripodi Domenico , Watanabe Mikiko , Mariani Stefania , D’Armiento Eleonora , Fallahi Poupak , Sindoni Alessandro , De Vito Corrado , Antonelli Alessandro , Ulisse Salvatore , Baldini Enke
Published: December 2020

The American Joint Committee on Cancer has revised the Tumor-Node-Metastasis (TNM) staging system for papillary thyroid cancer (PTC) patients. We examined the impact of this new classification (TNM-8) on patient stratification and estimated the prognostic value of clinicopathological features for the disease-free interval (DFI) in a cohort of 1148 PTC patients. Kaplan–Meier analyses showed that all clinicopathological parameters analyzed, except age and multifocality, were associated significantly with DFI. Cox regression identified tall cell PTC variant and stage as independent risk factors for DFI. When the stage was replaced with age, tumor size, and lymph node (LN) metastases in the set of covariates, the lateral LN metastases stood out as the strongest independent predictor of DFI, followed by tall cell variant and age. A noteworthy result emerging from these analyzes is that regression models had lower Akaike and Bayesian information criterions if variables were categorized based on the TNM-7. In addition, we examined data from a different PTC patient cohort, acquired from The Cancer Genome Atlas database, to verify whether the DFI prediction could be enhanced by further clinicopathological and molecular parameters. However, none of these was found to be a significant predictor of DFI in the Cox model.
Targeting Wnt Signaling for Gastrointestinal Cancer Therapy: Present and Evolving Views
Authors: Kim Moon Jong , Huang Yuanjian , Park Jae-Il
Published: December 2020

Wnt signaling governs tissue development, homeostasis, and regeneration. However, aberrant activation of Wnt promotes tumorigenesis. Despite the ongoing efforts to manipulate Wnt signaling, therapeutic targeting of Wnt signaling remains challenging. In this review, we provide an overview of current clinical trials to target Wnt signaling, with a major focus on gastrointestinal cancers. In addition, we discuss the caveats and alternative strategies for therapeutically targeting Wnt signaling for cancer treatment.
Single-Cell RNA Sequencing of a Postmenopausal Normal Breast Tissue Identifies Multiple Cell Types That Contribute to Breast Cancer
Authors: Peng Sen , Hebert Lora L. , Eschbacher Jennifer M. , Kim Suwon
Published: December 2020

The human breast is composed of diverse cell types. Studies have delineated mammary epithelial cells, but the other cell types in the breast have scarcely been characterized. In order to gain insight into the cellular composition of the tissue, we performed droplet-mediated RNA sequencing of 3193 single cells isolated from a postmenopausal breast tissue without enriching for epithelial cells. Unbiased clustering analysis identified 10 distinct cell clusters, seven of which were nonepithelial devoid of cytokeratin expression. The remaining three cell clusters expressed cytokeratins (CKs), representing breast epithelial cells; Cluster 2 and Cluster 7 cells expressed luminal and basal CKs, respectively, whereas Cluster 9 cells expressed both luminal and basal CKs, as well as other CKs of unknown specificity. To assess which cell type(s) potentially contributes to breast cancer, we used the differential gene expression signature of each cell cluster to derive gene set variation analysis (GSVA) scores and classified breast tumors in The Cancer Gene Atlas (TGGA) dataset (n = 1100) by assigning the highest GSVA scoring cell cluster number for each tumor. The results showed that five clusters (Clusters 2, 3, 7, 8, and 9) could categorize >85% of breast tumors collectively. Notably, Cluster 2 (luminal epithelial) and Cluster 3 (fibroblast) tumors were equally prevalent in the luminal breast cancer subtypes, whereas Cluster 7 (basal epithelial) and Cluster 9 (other epithelial) tumors were present primarily in the triple-negative breast cancer (TNBC) subtype. Cluster 8 (immune) tumors were present in all subtypes, indicating that immune cells may contribute to breast cancer regardless of the subtypes. Cluster 9 tumors were significantly associated with poor patient survival in TNBC, suggesting that this epithelial cell type may give rise to an aggressive TNBC subset.
Enhanced Malignant Phenotypes of Glioblastoma Cells Surviving NPe6-Mediated Photodynamic Therapy are Regulated via ERK1/2 Activation
Authors: Kobayashi Tatsuya , Miyazaki Makoto , Sasaki Nobuyoshi , Yamamuro Shun , Uchida Eita , Kawauchi Daisuke , Takahashi Masamichi , Otsuka Yohei , Kumagai Kosuke , Takeuchi Satoru , Toyooka Terushige , Otani Naoki , Wada Kojiro , Narita Yoshitaka , Yamaguchi Hideki , Muragaki Yoshihiro , Kawamata Takakazu , Mori Kentaro , Ichimura Koichi , Tomiyama Arata
Published: December 2020

To manage refractory and invasive glioblastomas (GBM)s, photodynamic therapy (PDT) using talaporfin sodium (NPe6) (NPe6-PDT) was recently approved in clinical practice. However, the molecular machineries regulating resistance against NPe6-PDT in GBMs and mechanisms underlying the changes in GBM phenotypes following NPe6-PDT remain unknown. Herein, we established an in vitro NPe6-mediated PDT model using human GBM cell lines. NPe6-PDT induced GBM cell death in a NPe6 dose-dependent manner. However, this NPe6-PDT-induced GBM cell death was not completely blocked by the pan-caspase inhibitor, suggesting NPe6-PDT induces both caspase-dependent and -independent cell death. Moreover, treatment with poly (ADP-ribose) polymerase inhibitor blocked NPe6-PDT-triggered caspase-independent GBM cell death. Next, it was also revealed resistance to re-NPe6-PDT of GBM cells and GBM stem cells survived following NPe6-PDT (NPe6-PDT-R cells), as well as migration and invasion of NPe6-PDT-R cells were enhanced. Immunoblotting of NPe6-PDT-R cells to assess the behavior of the proteins that are known to be stress-induced revealed that only ERK1/2 activation exhibited the same trend as migration. Importantly, treatment with the MEK1/2 inhibitor trametinib reversed resistance against re-NPe6-PDT and suppressed the enhanced migration and invasion of NPe6-PDT-R cells. Overall, enhanced ERK1/2 activation is suggested as a key regulator of elevated malignant phenotypes of GBM cells surviving NPe6-PDT and is therefore considered as a potential therapeutic target against GBM.
Production of 5-Hydroxymethylfurfural from Direct Conversion of Cellulose Using Heteropolyacid/Nb2O5 as Catalyst
Authors: Nogueira Jéssica Siqueira Mancilha , Santana Vinícius Tomaz , Henrique Paulo Vitor , Aguiar Leandro Gonçalves de , Silva João Paulo Alves , Mussatto Solange I. , Carneiro Livia Melo
Published: December 2020

This study aimed to select the best reaction conditions to produce 5-hydroxymethylfurfural (HMF) from cellulose using heterogeneous catalyst based on a heteropolyacid (H3PW12O40—HPW) and Nb2O5. Initially, the influence of the temperature (160 or 200 °C), acetone:water ratio (50:50 or 75:25 v/v), cellulose load (5% or 10% w/v) and catalyst concentration (1% or 5% w/v) on HMF production from cellulose was evaluated through a Taguchi’s L16 screening experimental design. Afterwards, the main variables affecting this process, namely the temperature (160–240 °C) and acetone:water ratio (60:40–90:10 v/v), were optimized using a central composite rotatable design. Next, a kinetic study on HMF production from cellulose was carried out. Finally, HMF production from cellulose obtained from different biomass sources was evaluated. It was found that the reaction conditions able to result in maximum HMF yield, i.e., around 20%, were 200 °C, acetone:water ratio of 75:25 (v/v), 10% w/v of cellulose, and 5% w/v of catalyst concentration. The kinetic study revealed that the Langmuir–Hinshelwood–Hougen–Watson approach fit to the experimental data. Under the optimized conditions, the catalyst HPW/Nb2O5 was also effective in converting different sources of cellulose into HMF.
Modeling of Degradation of Diazo Dye in Swirl-Flow Photocatalytic Reactor: Response Surface Approach
Authors: Jadaa Waleed , Prakash Anand , Ray Ajay K.
Published: December 2020

Photocatalytic degradation of Direct Blue 15 (DB15), an azo dye, was studied using a swirl-flow monolithic reactor under UV irradiation. The degradation reactions were carried out to investigate effects of initial dye concentration, catalyst loading, and light intensity at an optimal pH. The experiments were designed and mathematically modelled by CCD-RSM (central composite design-response surface methodology) approach. It was found that the selected parameters significantly affect DB15 degradation. In terms of the linear term, catalyst loading and light intensity had a synergistic effect, while dye concentration registered the opposite effect. Strong interaction was observed between catalyst loading and both light intensity and initial dye concentration compared with the interaction of light intensity and initial dye concentration. Based on the experimental results, a quadratic model was developed to predict the percentage removal of DB15. The predicted values of the model were in good agreement with the experimental values (R2 = 0.987), indicating the model fits well for the parameter space for which experiments were performed. According to diagnostic plots, the model credibility was valid because its residuals were distributed normally and exhibited a random pattern based on their examination versus the predicted values. The results revealed that the initial dye concentration and catalyst concentration have a significant effect on the mineralization time.
Ring-Opening of Epoxides with Amines for Synthesis of β-Amino Alcohols in a Continuous-Flow Biocatalysis System
Authors: Du Li-Hua , Xue Miao , Yang Meng-Jie , Pan Yue , Zheng Ling-Yan , Ou Zhi-Min , Luo Xi-Ping
Published: December 2020

An efficient method for the preparation of β-amino alcohols catalyzed by lipase TL IM from Thermomyces lanuginosus in a continuous-flow reactor was developed. The eco-friendly biocatalyst combined with continuous-flow reaction technology displayed high efficiency in the synthesis of β-amino alcohols. The benign reaction conditions (35 °C) and short residence time (20 min), together with the use of low cost and readily available starting materials, make this synthetic approach a promising alternative to current β-amino alcohol synthesis.
Biocatalysis in the Swiss Manufacturing Environment
Authors: Hecht Katrin , Meyer Hans-Peter , Wohlgemuth Roland , Buller Rebecca
Published: December 2020

Biocatalysis has undergone a remarkable transition in the last two decades, from being considered a niche technology to playing a much more relevant role in organic synthesis today. Advances in molecular biology and bioinformatics, and the decreasing costs for gene synthesis and sequencing contribute to the growing success of engineered biocatalysts in industrial applications. However, the incorporation of biocatalytic process steps in new or established manufacturing routes is not always straightforward. To realize the full synthetic potential of biocatalysis for the sustainable manufacture of chemical building blocks, it is therefore important to regularly analyze the success factors and existing hurdles for the implementation of enzymes in large scale small molecule synthesis. Building on our previous analysis of biocatalysis in the Swiss manufacturing environment, we present a follow-up study on how the industrial biocatalysis situation in Switzerland has evolved in the last four years. Considering the current industrial landscape, we record recent advances in biocatalysis in Switzerland as well as give suggestions where enzymatic transformations may be valuably employed to address some of the societal challenges we face today, particularly in the context of the current Coronavirus disease 2019 (COVID-19) pandemic.
Role of HMGB1/TLR4 Axis in Ischemia/Reperfusion-Impaired Extracellular Glutamate Clearance in Primary Astrocytes
Authors: Lin Chia-Ho , Chen Han-Yu , Wei Kai-Che
Published: December 2020

(1) Background: Abnormal accumulation of extracellular glutamate can occur as dysfunction of astrocytic glutamate transporters, which has been linked to ischemic brain injury. Excessive extracellular glutamate-induced abnormal excitotoxicity is the major cause of secondary neuronal damage after cerebral ischemia/reperfusion. However, the definite mechanism of impaired astrocytic glutamate reuptake remains unclear. (2) Methods: We investigated the mechanism of the HMGB1/TLR4 axis in extracellular glutamate clearance in primary astrocytes exposed to ischemia/reperfusion by using OGD/R (oxygen-glucose deprivation/reoxygenation) model. (3) Results: OGD/R insult activated the HMGB1/TLR4 axis for reducing the activity of glutamate clearance by inhibiting GLAST (glutamate aspartate transporter) expression in primary astrocytes. Interestingly, OGD/R-untreated astrocytes showed impairment of glutamate clearance after exposure to exogenous HMGB1 or conditioned medium from OGD/R-treated astrocytes culture. Inhibition of HMGB1 or TLR4 effectively prevented impaired glutamate clearance, which was induced by OGD/R, exogenous HMGB1, or conditioned medium from OGD/R-treated astrocytes. Furthermore, glycyrrhizic acid attenuated OGD/R-induced impairment of astrocytic glutamate clearance mediated by the HMGB1-TLR4 axis. (4) Conclusion: The HMGB1/TLR4 axis is a potential target for the treatment of post-ischemic excitotoxicity caused by GLAST dysfunction in astrocytes.
Dynamics of Whole-Genome Contacts of Nucleoli in Drosophila Cells Suggests a Role for rDNA Genes in Global Epigenetic Regulation
Authors: Tchurikov Nickolai A. , Klushevskaya Elena S. , Fedoseeva Daria M. , Alembekov Ildar R. , Kravatskaya Galina I. , Chechetkin Vladimir R. , Kravatsky Yuri V. , Kretova Olga V.
Published: December 2020

Chromosomes are organized into 3D structures that are important for the regulation of gene expression and differentiation. Important role in formation of inter-chromosome contacts play rDNA clusters that make up nucleoli. In the course of differentiation, heterochromatization of rDNA units in mouse cells is coupled with the repression or activation of different genes. Furthermore, the nucleoli of human cells shape the direct contacts with genes that are involved in differentiation and cancer. Here, we identified and categorized the genes located in the regions where rDNA clusters make frequent contacts. Using a 4C approach, we demonstrate that in Drosophila S2 cells, rDNA clusters form contacts with genes that are involved in chromosome organization and differentiation. Heat shock treatment induces changes in the contacts between nucleoli and hundreds of genes controlling morphogenesis. We show that nucleoli form contacts with regions that are enriched with active or repressive histone marks and where small non-coding RNAs are mapped. These data indicate that rDNA contacts are involved in the repression and activation of gene expression and that rDNA clusters orchestrate large groups of Drosophila genes involved in differentiation.
Soluble CD5 and CD6: Lymphocytic Class I Scavenger Receptors as Immunotherapeutic Agents
Authors: Velasco-de Andrés María , Casadó-Llombart Sergi , Català Cristina , Leyton-Pereira Alejandra , Lozano Francisco , Aranda Fernando
Published: December 2020

CD5 and CD6 are closely related signal-transducing class I scavenger receptors mainly expressed on lymphocytes. Both receptors are involved in the modulation of the activation and differentiation cell processes triggered by clonotypic antigen-specific receptors present on T and B cells (TCR and BCR, respectively). To serve such a relevant immunomodulatory function, the extracellular region of CD5 and CD6 interacts with soluble and/or cell-bound endogenous counterreceptors but also microbial-associated molecular patterns (MAMPs). Evidence from genetically-modified mouse models indicates that the absence or blockade of CD5- and CD6-mediated signals results in dysregulated immune responses, which may be deleterious or advantageous in some pathological conditions, such as infection, cancer or autoimmunity. Bench to bedside translation from transgenic data is constrained by ethical concerns which can be overcome by exogenous administration of soluble proteins acting as decoy receptors and leading to transient “functional knockdown”. This review gathers information currently available on the therapeutic efficacy of soluble CD5 and CD6 receptor infusion in different experimental models of disease. The existing proof-of-concept warrants the interest of soluble CD5 and CD6 as safe and efficient immunotherapeutic agents in diverse and relevant pathological conditions.
MRE11 Is Crucial for Malaria Parasite Transmission and Its Absence Affects Expression of Interconnected Networks of Key Genes Essential for Life
Authors: Guttery David S. , Ramaprasad Abhinay , Ferguson David J. P. , Zeeshan Mohammad , Pandey Rajan , Brady Declan , Holder Anthony A. , Pain Arnab , Tewari Rita
Published: December 2020

The meiotic recombination 11 protein (MRE11) plays a key role in DNA damage response and maintenance of genome stability. However, little is known about its function during development of the malaria parasite Plasmodium. Here, we present a functional, ultrastructural and transcriptomic analysis of Plasmodium parasites lacking MRE11 during its life cycle in both mammalian and mosquito vector hosts. Genetic disruption of Plasmodium berghei mre11 (PbMRE11) results in significant retardation of oocyst development in the mosquito midgut associated with cytoplasmic and nuclear degeneration, along with concomitant ablation of sporogony and subsequent parasite transmission. Further, absence of PbMRE11 results in significant transcriptional downregulation of genes involved in key interconnected biological processes that are fundamental to all eukaryotic life including ribonucleoprotein biogenesis, spliceosome function and iron–sulfur cluster assembly. Overall, our study provides a comprehensive functional analysis of MRE11′s role in Plasmodium development during the mosquito stages and offers a potential target for therapeutic intervention during malaria parasite transmission.
Hypoxia Dictates Metabolic Rewiring of Tumors: Implications for Chemoresistance
Authors: Belisario Dimas Carolina , Kopecka Joanna , Pasino Martina , Akman Muhlis , De Smaele Enrico , Donadelli Massimo , Riganti Chiara
Published: December 2020

Hypoxia is a condition commonly observed in the core of solid tumors. The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. These events favor tumor progression and chemoresistance. The increase in glucose and amino acid uptake, glycolytic flux, and lactate production; the alterations in glutamine metabolism, tricarboxylic acid cycle, and oxidative phosphorylation; the high levels of mitochondrial reactive oxygen species; the modulation of both fatty acid synthesis and oxidation are hallmarks of the metabolic rewiring induced by hypoxia. This review discusses how metabolic-dependent factors (e.g., increased acidification of tumor microenvironment coupled with intracellular alkalinization, and reduced mitochondrial metabolism), and metabolic-independent factors (e.g., increased expression of drug efflux transporters, stemness maintenance, and epithelial-mesenchymal transition) cooperate in determining chemoresistance in hypoxia. Specific metabolic modifiers, however, can reverse the metabolic phenotype of hypoxic tumor areas that are more chemoresistant into the phenotype typical of chemosensitive cells. We propose these metabolic modifiers, able to reverse the hypoxia-induced metabolic rewiring, as potential chemosensitizer agents against hypoxic and refractory tumor cells.
NKCC1, an Elusive Molecular Target in Brain Development: Making Sense of the Existing Data
Authors: Virtanen Mari A. , Uvarov Pavel , Hübner Christian A. , Kaila Kai
Published: December 2020

Ionotropic GABA transmission is mediated by anion (mainly Cl−)-permeable GABAA receptors (GABAARs). In immature neurons, GABA exerts depolarizing and sometimes functionally excitatory actions, based on active uptake of Cl− by the Na-K-2Cl cotransporter NKCC1. While functional evidence firmly shows NKCC1-mediated ion transport in immature and diseased neurons, molecular detection of NKCC1 in the brain has turned out to be extremely difficult. In this review, we describe the highly inconsistent data that are available on the cell type-specific expression patterns of the NKCC1 mRNA and protein in the CNS. We discuss the major technical caveats, including a lack of knock-out-controlled immunohistochemistry in the forebrain, possible effects of alternative splicing on the binding of antibodies and RNA probes, and the wide expression of NKCC1 in different cell types, which make whole-tissue analyses of NKCC1 useless for studying its neuronal expression. We also review novel single-cell RNAseq data showing that most of the NKCC1 in the adult CNS may, in fact, be expressed in non-neuronal cells, especially in glia. As future directions, we suggest single-cell NKCC1 mRNA and protein analyses and the use of genetically tagged endogenous proteins or systematically designed novel antibodies, together with proper knock-out controls, for the visualization of endogenous NKCC1 in distinct brain cell types and their subcellular compartments.
Evaluating a Standardized Transition of Care Process for Pediatric Inflammatory Bowel Disease Patients
Authors: Shearer Jennifer Lynne , Perry Sharon , Lidyard Nicole , Apperson-Hensen Carolyn , DeLozier Sarah , Burkhart Kimberly , Katz Jeffry , Moses Jonathan
Published: December 2020

To reduce lapses in care for pediatric inflammatory bowel disease (IBD) patients approaching adulthood, a health maintenance transition visit (HMV) was developed to supplement standard medical care (SMV). Our aim was to assess the effect of the HMV on transition readiness. A retrospective chart review was conducted at a single center with demographics and clinical data from HMV and SMV visits. Effectiveness of the HMV was assessed by the patient health questionanaire-9 (PHQ-9) and transition readiness assessment questionnaire (TRAQ) scores. A total of 140 patients, 80% Caucasian and 59% male completed an HMV. The mean age was 18 ± 2 years old, and 93% of patients reported inactive or mild disease. Patients who completed at least 1 prior HMV scored significantly higher on the TRAQ when transferring to adult care compared to patients transferred at their first HMV visit (92 vs. 83, p < 0.05). Of patients with no prior depression diagnosis, 36% had a positive screen for depression. A significant relationship was identified between disease status and PHQ-9 (p < 0.05). This study demonstrated a structured HMV increased transition readiness and quantified the significant under-diagnosis of depression in this population, emphasizing the importance of screening. These results indicate depression may affect patients’ transition preparedness.
Microstructural Analysis and Tribological Behavior of AMDRY 1371 (Mo–NiCrFeBSiC) Atmospheric Plasma Spray Deposited Thin Coatings
Authors: Paleu Cornelia Cîrlan , Munteanu Corneliu , Istrate Bogdan , Bhaumik Shubrajit , Vizureanu Petrică , Bălţatu Mădălina Simona , Paleu Viorel
Published: December 2020

Water treatment plants include a set of pumping stations, and their mechanical components experience various wear modes. In order to combat wear, the mechanical components of the pumps are coated with various types of wear resistant coatings. In this research, AMDRY 1371 (Mo–NiCrFeBSiC) coatings were deposited with the atmospheric plasma spray (APS) method on parallelepipedal steel samples manufactured from a worn sleeve of a multistage vertical irrigation pump. In order to find an optimum thickness of AMDRY 1371 coatings, the samples were coated with five, seven and nine passes (counted as return passes of the APS gun). Mechanical properties of the coating (microhardness and Young’s modulus) were determined by micro-indentation tests. An AMSLER tribometer was used to investigate the wear resistance and wear modes of the coated samples in dry conditions. A mean coefficient of friction (CoF) of around 0.3 was found for all the samples, but its evolution during the one hour of the test and also the final wear volumes and wear rates depended on the thickness of the coating. To estimate the roughness of the surfaces and the wear volumes, measurements were carried out on a Taylor Hobson profilometer. In order to understand the nature and evolution of wear of coatings of various thicknesses, the unworn and worn surfaces of the coated samples were analyzed by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). The wear modes of the coatings were studied, emphasizing the coating removal process for each sample. According to our results, for each dry friction application, there is an optimum value of the thickness of the coating, depending on the running conditions.
Effect of Choice of Solvent on Crystallization Pathway of Paracetamol: An Experimental and Theoretical Case Study
Authors: Chewle Surahit , Emmerling Franziska , Weber Marcus
Published: December 2020

The choice of solvents influences crystalline solid formed during the crystallization of active pharmaceutical ingredients (API). The underlying effects are not always well understood because of the complexity of the systems. Theoretical models are often insufficient to describe this phenomenon. In this study, the crystallization behavior of the model drug paracetamol in different solvents was studied based on experimental and molecular dynamics data. The crystallization process was followed in situ using time-resolved Raman spectroscopy. Molecular dynamics with simulated annealing algorithm was used for an atomistic understanding of the underlying processes. The experimental and theoretical data indicate that paracetamol molecules adopt a particular geometry in a given solvent predefining the crystallization of certain polymorphs.
Crystal Structure and Thermal Studies of Coordination Compounds
Authors: Bartyzel Agata , Cristóvão Beata , Łyszczek Reanata
Published: December 2020

In recent decades, coordination compounds have been of great interest, thanks to their fascinating structures and functional properties [...]
Chemical-Physical Characterization of a Binary Mixture of a Twist Bend Nematic Liquid Crystal with a Smectogen
Authors: Aouini Abir , Nobili Maurizio , Chauveau Edouard , Dieudonné-George Philippe , Damême Gauthier , Stoenescu Daniel , Dozov Ivan , Blanc Christophe
Published: December 2020

Nematic twist-bend phases (NTB) are new types of nematic liquid crystalline phases with attractive properties for future electro-optic applications. However, most of these states are monotropic or are stable only in a narrow high temperature range. They are often destabilized under moderate cooling, and only a few single compounds have shown to give room temperature NTB phases. Mixtures of twist-bend nematic liquid crystals with simple nematogens have shown to strongly lower the nematic to NTB phase transition temperature. Here, we examined the behaviour of new types of mixtures with the dimeric liquid crystal [4′,4′-(heptane-1,7-diyl)bis(([1′,1″-biphenyl]4″-carbo-nitrile))] (CB7CB). This now well-known twist-bend nematic liquid crystal presents a nematic twist-bend phase below T ≈ 104 °C. Mixtures with other monomeric alkyl or alkoxy -biphenylcarbonitriles liquid crystals that display a smectic A (SmA) phase also strongly reduce this temperature. The most interesting smectogen is 4′-Octyl-4-biphenylcarbonitrile (8CB), for which a long-term metastable NTB phase is found at room and lower temperatures. This paper presents the complete phase diagram of the corresponding binary system and a detailed investigation of its thermal, optical, dielectric, and elastic properties.
Disturbed Eating Behaviors in Youth with Type 1 Diabetes: An Exploratory Study about Challenges in Diagnosis
Authors: Calcaterra Valeria , Mazzoni Chiara , Ballardini Donatella , Tomba Elena , Zuccotti Gian Vincenzo , Mameli Chiara , De Giuseppe Rachele , Cena Hellas
Published: December 2020

Background: Disordered eating behaviors (DEBs), including diagnosable eating disorders, are quite common and can interfere with optimal type 1 diabetes (T1DM) management. We explored DEBs prevalence in youth with T1DM, proposing news diagnostic subscales, to represent the clinical dimensions associated with feeding and eating disorders (ED); Methods: additionally to SCOFF questionnaire and Diabetes Eating Problem Survey–Revised (DEPS-R), four subscales combined from the original DEPS-R questionnaire were administered to 40 youths with T1DM (15.0 ± 2.6); Results: females showed higher scores than males in DEPS-R original factor 2 (“preoccupations with thinness/weight”, p = 0.024) and in DEPS-R proposed “restriction” factor (p = 0.009). SCOFF scores was correlated with original DEPS-R factors 1 (“maladaptive eating habits”) and 2 (p < 0.001) and with the newly proposed DEPS-R factors: restriction, disinhibition, compensatory behaviors, diabetes management (all p < 0.02). Diabetes management was the only factor related to glycated hemoglobin level (p = 0.006). Patients with high DEPS-R score (≥20) scored higher than patients with low (<20) DEPS-R score in DEPS-R original factors 1 (p < 0.001) and 2 (p = 0.002) as well as in the proposed factors including restriction, disinhibition, diabetes management (all p < 0.02); Conclusions: the complicated nature of DEBs calls for the development target specific questionnaires to be used as screening tools to detect cases of DEBs and exclude non cases. Early recognition of DEBs in adolescents with T1DM is essential for effective prevention and successful treatment.
Diagnostics in Pleural Disease
Authors: Sundaralingam Anand , Bedawi Eihab O. , Rahman Najib M.
Published: December 2020

Pleural disease diagnostics represent a sprawling topic that has enjoyed a renaissance in recent years from humble beginnings. Whilst pleural patients are heterogeneous as a population and in the aetiology of the disease with which they present, we provide an overview of the typical diagnostic approach. Pleural fluid analysis is the cornerstone of the diagnostic pathway; however, it has many shortcomings. Strong cases have been made for more invasive upfront investigations, including image-guided biopsies or local anaesthetic thoracoscopy, in selected populations. Imaging can guide the diagnostic process as well as act as a vehicle to facilitate therapies, and this is never truer than with the recent advances in thoracic ultrasound.
Sensorless Voltage Observer for a Current-Fed High Step-Up DC-DC Converter Using Extended Kalman Filter
Authors: Haadi Karim , Rajaei Amirhossein , Shahparasti Mahdi , Rahideh Akbar
Published: December 2020

In high voltage applications, sensorless voltage control techniques can reduce the cost and increase the reliability of DC-DC converters. In this paper, a sensorless voltage observer for a current fed Cockcroft-Walton voltage multiplier is designed. The first step is to derive the converter model. Since any inaccuracy in the derived model can result in a discrepancy between the observed voltage and the actual output voltage, an accurate model is derived, which incorporates the influential elements. Then, two voltage observers based on the extended Kalman filter (EKF) are designed and used to estimate the output voltage, transformer magnetizing current and inductor current for two different configurations of the high step-up DC-DC converter. Experimental and simulation results of the system show the efficiency of the observers. The proposed observers represent good precision as the main parasitic parameters are considered in the converter model.
Vertical Round Buoyant Jets and Fountains in a Linearly, Density-Stratified Fluid
Authors: Papanicolaou Panos N. , Stamoulis George C.
Published: December 2020

Turbulent round buoyant jets and fountains issuing vertically into a linearly density-stratified calm ambient have been investigated in a series of laboratory experiments. The terminal (steady-state) height of rise and the mean elevation of subsequent horizontal spreading have been measured in positively buoyant jets (at source level), including pure momentum jets and plumes, as well in momentum-driven negatively buoyant jets (fountains). The results from experiments confirmed the asymptotic analysis that was based on dimensional arguments. The normalized terminal height and spreading elevation with respect to the elevation of injection of momentum-driven (positively) buoyant jets and fountains attained the same asymptotic values. The numerical results from the solution of entrainment equations, using an improved entrainment coefficient function, confirmed the results related to buoyancy dominant flows (plumes), while their predictions in momentum-driven flows were quite low if compared to measurements.
Active Edible Polysaccharide-Based Coating for Preservation of Fresh Figs (Ficus carica L.)
Authors: Paolucci Marina , Di Stasio Michele , Sorrentino Alida , La Cara Francesco , Volpe Maria Grazia
Published: December 2020

Fresh figs are very sensitive to microbial spoilage, even in cold storage conditions. Thus, fresh figs are high perishable products during postharvest with microbiological decay that induces an unpleasant taste and smell due to rot, and suitable conservation methods must therefore be applied. The fruit usually is consumed fresh locally, dried, or preserved longer term in other transformed forms. A sustainable approach to extend the shelf-life of figs can be constituted by application of an edible coating able to maintain the quality of the fruit during storage. A comparison between fresh figs in a commercial preservation system, with the figs preserved in an edible coating, and an active edible coating to preserve their quality characteristics was carried out. The coating efficacy was enhanced with the addition of pomegranate peel extract at two different concentrations. The inclusion of a component with high antioxidant activity in an edible coating proved to be an excellent method for preserving the quality of this highly perishable fruit. The application of natural products, obtained from renewable sources, represents a simple and economic strategy, but also a tool capable of preserving the quality of the fruit during the postharvest storage, which is often consumed in production areas due to shelf-life problems.