bluuebunny/crossref_metadata_2025 huggingface dataset:
YAP/TAZ Signalling in Colorectal Cancer: Lessons from Consensus Molecular Subtypes
Authors: Mouillet-Richard Sophie , Laurent-Puig Pierre
Published: October 2020

Recent advance in the characterization of the heterogeneity of colorectal cancer has led to the definition of a consensus molecular classification within four CMS subgroups, each associated with specific molecular and clinical features. Investigating the signalling pathways that drive colorectal cancer progression in relation to the CMS classification may help design therapeutic strategies tailored for each CMS subtype. The two main effectors of the Hippo pathway YAP and its paralogue TAZ have been intensively scrutinized for their contribution to colon carcinogenesis. Here, we review the knowledge of YAP/TAZ implication in colorectal cancer from the perspective of the CMS framework. We identify gaps in our current understanding and delineate research avenues for future work.
Detection of Pathogenic Isoforms of IKZF1 in Leukemic Cell Lines and Acute Lymphoblastic Leukemia Samples: Identification of a Novel Truncated IKZF1 Transcript in SUP-B15
Authors: Zhao Weiqiang , Li Ying , Yao Chenjiao , Zhang Guojuan , Zhao Kevin , Chen Wei , Ru Peng , Pan Xiaokang , Tu Huolin , Jones Daniel
Published: October 2020

Leukemia-associated alternative splicing of IKZF1 can result in proteins with loss of one to four copies of its N-terminal zinc finger domains (N-ZnF). The best characterized pathogenic splice isoforms, Ik-6 and Ik-8, have been commonly found in BCR-ABL1+ acute lymphoblastic leukemia (ALL) and a subset of BCR-ABL1-like ALL. Infantile and childhood ALL that express these pathogenic IKZF1 isoforms have shown inferior clinical outcomes and can be resistant to tyrosine kinase inhibitors. Using ALL cell lines, we designed and validated a method to detect abnormal IKZF1 transcripts. In the SUP-B15 leukemia cell line, we noted novel IKZF1 transcripts that include both an Ik-6 splice and a transcript with a 14 base pair insertion at the C-terminus. There was also increased IKZF2 protein in SUP-B15 as compared to other ALL lines. Expression of Ik-6 could be suppressed by treatment with the pro-apoptotic type II histone deacetylase inhibitor givinostat. In 17 adult ALL samples, we noted the Ik-6 isoforms in 6 of 15 BCR-ABL1−, and 1 of 2 BCR-ABL1+ cases, with Ik-8 also expressed in one case. Cases with Ik-6 expression showed inferior survival as well as older age at presentation, lower expression of CD10 and more commonly a diploid karyotype.
Targeting CREB in Cancer Therapy: A Key Candidate or One of Many? An Update
Authors: Sapio Luigi , Salzillo Alessia , Ragone Angela , Illiano Michela , Spina Annamaria , Naviglio Silvio
Published: October 2020

Intratumor heterogeneity (ITH) is considered the major disorienting factor in cancer treatment. As a result of stochastic genetic and epigenetic alterations, the appearance of a branched evolutionary shape confers tumor plasticity, causing relapse and unfavorable clinical prognosis. The growing evidence in cancer discovery presents to us “the great paradox” consisting of countless potential targets constantly discovered and a small number of candidates being effective in human patients. Among these, cyclic-AMP response element-binding protein (CREB) has been proposed as proto-oncogene supporting tumor initiation, progression and metastasis. Overexpression and hyperactivation of CREB are frequently observed in cancer, whereas genetic and pharmacological CREB downregulation affects proliferation and apoptosis. Notably, the present review is designed to investigate the feasibility of targeting CREB in cancer therapy. In particular, starting with the latest CREB evidence in cancer pathophysiology, we evaluate the advancement state of CREB inhibitor design, including the histone lysine demethylases JMJD3/UTX inhibitor GSKJ4 that we newly identified as a promising CREB modulator in leukemia cells. Moreover, an accurate analysis of strengths and weaknesses is also conducted to figure out whether CREB can actually represent a therapeutic candidate or just one of the innumerable preclinical cancer targets.
Impact of Preoperative Low Prognostic Nutritional Index and High Intramuscular Adipose Tissue Content on Outcomes of Patients with Oral Squamous Cell Carcinoma
Authors: Yoshimura Takuya , Suzuki Hajime , Takayama Hirotaka , Higashi Shotaro , Hirano Yuka , Tezuka Masahiro , Ishida Takayuki , Ishihata Kiyohide , Nishi Yasuhiro , Nakamura Yasunori , Imamura Yasushi , Nozoe Etsuro , Nakamura Norifumi
Published: October 2020

The impact of preoperative malnutrition and sarcopenia on survival in oral squamous cell carcinoma (OSCC) patients remains controversial. We investigated the effects of the preoperative nutritional status and abnormalities in body composition on the mortality of OSCC patients. A retrospective study involving 103 patients with OSCC was conducted. Disease-specific survival (DSS) according to the preoperative psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC) was evaluated. Univariate and multivariate analyses were performed to determine the predictive performance of the covariates with respect to DSS. The DSS rate in patients with high IMAC and low PMI was significantly lower than that in controls. Multivariate analysis revealed that a low preoperative Prognostic Nutritional Index (PNI) and high IMAC were independent risk factors. We demonstrated that preoperative malnutrition and abnormal body composition, such as preoperative skeletal muscle quality, are associated with DSS in OSCC patients. Our study suggests that the evaluation of preoperative malnutrition and skeletal muscle quality would be useful for predicting mortality in patients with OSCC.
The Long Noncoding RNA LOC441461 (STX17-AS1) Modulates Colorectal Cancer Cell Growth and Motility
Authors: Wang Jui-Ho , Lu Tzung-Ju , Kung Mei-Lang , Yang Yi-Fang , Yeh Chung-Yu , Tu Ya-Ting , Chen Wei-Shone , Tsai Kuo-Wang
Published: October 2020

Colorectal carcinoma (CRC) is one of the most prevalent cancers worldwide and has a high mortality rate. Long noncoding RNAs (lncRNAs) have been noted to play critical roles in cell growth; cell apoptosis; and metastasis in CRC. This study determined that LOC441461 expression was significantly higher in CRC tissues than in adjacent normal mucosa. Pathway enrichment analysis of LOC441461-coexpressed genes revealed that LOC441461 was involved in biological functions related to cancer cell growth and motility. Knockdown of the LOC441461 expression significantly suppressed colon cancer cell growth by impairing cell cycle progression and inducing cell apoptosis. Furthermore, significantly higher LOC441461 expression was discovered in primary colon tumors and metastatic liver tumors than in the corresponding normal mucosa, and LOC441461 knockdown was noted to suppress colon cancer cell motility. Knockdown of LOC441461 expression suppressed the phosphorylation of MLC and LIMK1 through the inhibition of RhoA/ROCK signaling. Overall, LOC441461 was discovered to play an oncogenic role in CRC cell growth and motility through RhoA/ROCK signaling. Our findings provide new insights into the regulation of lncRNAs and their application in the treatment of colon cancer
NGS for (Hemato-) Oncology in Belgium: Evaluation of Laboratory Performance and Feasibility of a National External Quality Assessment Program
Authors: Delcourt Thomas , Vanneste Kevin , Soumali Mohamed Rida , Coucke Wim , Ghislain Vanessa , Hebrant Aline , Van Valckenborgh Els , De Keersmaecker Sigrid C. J. , Roosens Nancy H. , Van De Walle Philippe , Van Den Bulcke Marc , Antoniou Aline
Published: October 2020

Next-generation sequencing (NGS) is being integrated into routine clinical practice in the field of (hemato-) oncology to search for variants with diagnostic, prognostic, or therapeutic value at potentially low allelic frequencies. The complex sequencing workflows used require careful validation and continuous quality control. Participation in external quality assessments (EQA) helps laboratories evaluate their performance and guarantee the validity of tests results with the ultimate goal of ensuring high-quality patient care. Here, we describe three benchmarking trials performed during the period 2017–2018 aiming firstly at establishing the state-of-the-art and secondly setting up a NGS-specific EQA program at the national level in the field of clinical (hemato-) oncology in Belgium. DNA samples derived from cell line mixes and artificially mutated cell lines, designed to carry variants of clinical relevance occurring in solid tumors, hematological malignancies, and BRCA1/BRCA2 genes, were sent to Belgian human genetics, anatomic pathology, and clinical biology laboratories, to be processed following routine practices, together with surveys covering technical aspects of the NGS workflows. Despite the wide variety of platforms and workflows currently applied in routine clinical practice, performance was satisfactory, since participating laboratories identified the targeted variants with success rates ranging between 93.06% and 97.63% depending on the benchmark, and few false negative or repeatability issues were identified. However, variant reporting and interpretation varied, underlining the need for further standardization. Our approach showcases the feasibility of developing and implementing EQA for routine clinical practice in the field of (hemato-) oncology, while highlighting the challenges faced.
Modulation of Immune Infiltration of Ovarian Cancer Tumor Microenvironment by Specific Subpopulations of Fibroblasts
Authors: Wang Ji , Cheng Frank H. C. , Tedrow Jessica , Chang Wennan , Zhang Chi , Mitra Anirban K.
Published: October 2020

Tumor immune infiltration plays a key role in the progression of solid tumors, including ovarian cancer, and immunotherapies are rapidly emerging as effective treatment modalities. However, the role of cancer-associated fibroblasts (CAFs), a predominant stromal constituent, in determining the tumor-immune microenvironment and modulating efficacy of immunotherapies remains poorly understood. We have conducted an extensive bioinformatic analysis of our and other publicly available ovarian cancer datasets (GSE137237, GSE132289 and GSE71340), to determine the correlation of fibroblast subtypes within the tumor microenvironment (TME) with the characteristics of tumor-immune infiltration. We identified (1) four functional modules of CAFs in ovarian cancer that are associated with the TME and metastasis of ovarian cancer, (2) immune-suppressive function of the collagen 1,3,5-expressing CAFs in primary ovarian cancer and omental metastases, and (3) consistent positive correlations between the functional modules of CAFs with anti-immune response genes and negative correlation with pro-immune response genes. Our study identifies a specific fibroblast subtype, fibroblast functional module (FFM)2, in the ovarian cancer tumor microenvironment that can potentially modulate a tumor-promoting immune microenvironment, which may be detrimental toward the effectiveness of ovarian cancer immunotherapies.
Real-World Experience of Pembrolizumab Monotherapy in Patients with Recurrent or Persistent Cervical Cancer: A Korean Multi-Center Retrospective Study (KGOG1041)
Authors: Choi Min Chul , Kim Yong-Man , Lee Jeong-Won , Lee Yong Jae , Suh Dong Hoon , Lee Sung Jong , Lee Taek Sang , Lee Maria , Park Dong Choon , Kim Min Kyu , Lee Jong-Min , Shim Seung-Hyuk , Jeon Seob , Min Kyung Jin , Kim Mi Kyung , Kim Bo Wook , Park Jeong Yeol , Kim Byoung-Gie , Kim Dae Yeon , Kim Moon-Hong , Kim Hyun-Soo , Lee Jung-Yun
Published: October 2020

This study investigated the antitumor activity and safety of pembrolizumab in patients with recurrent cervical cancer in real-world practice. We conducted a multi-center retrospective study of patients with recurrent or persistent cervical cancer treated with pembrolizumab at sixteen institutions in Korea between January 2016 and March 2020. The primary endpoints were the objective response rate (ORR) and safety. Data were available for 117 patients. The median age was 53 years (range, 28–79). Sixty-four (54.7%) patients had an Eastern Cooperative Oncology Group (ECOG) performance status of ≥2. Forty-nine (41.9%) patients were stage ≥III at diagnosis. Eighty-eight (75.2%) patients had squamous cell carcinoma. The median number of prior chemotherapy lines was two (range, 1–6). During the median follow-up of 4.9 months (range, 0.2–35.3), the ORR was 9.4%, with three complete responses and eight partial responses. The median time to response was 2.8 months (range 1.3–13.1), and the median duration of response (DOR) was not reached. In the population of patients with favorable performance status (ECOG ≤1) (n = 53), the ORR was 18.9%, and the median DOR was 8.9 months (range, 7.3–10.4). Adverse events occurred in 55 (47.0%) patients, including eight (6.8%) patients who experienced grade ≥3 events, and two of them were suspicious treatment-related deaths. Pembrolizumab had modest antitumor activity in patients with recurrent cervical cancer comparable to that found in previously reported clinical trials. However, in patients with favorable performance status, pembrolizumab showed effective antitumor activity. Some safety profiles should be carefully monitored during treatment.
Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?
Authors: Stéphan Pierre , Lautraite Raphaëlle , Voisin Allison , Grinberg-Bleyer Yenkel
Published: October 2020

Extensive research in the past decades has highlighted the tight link between immunity and cancer, leading to the development of immunotherapies that have revolutionized cancer care. However, only a fraction of patients display durable responses to these treatments, and a deeper understanding of the cellular and mechanisms orchestrating immune responses to tumors is mandatory for the discovery of novel therapeutic targets. Among the most scrutinized immune cells, Forkhead Box Protein P3 (Foxp3)+ Regulatory T cells (Treg cells) are central inhibitors of protective anti-tumor immunity. These tumor-promoting functions render Treg cells attractive immunotherapy targets, and multiple strategies are being developed to inhibit their recruitment, survival, and function in the tumor microenvironment. In this context, it is critical to decipher the complex and multi-layered molecular mechanisms that shape and stabilize the Treg cell transcriptome. Here, we provide a global view of the transcription factors, and their upstream signaling pathways, involved in the programming of Treg cell homeostasis and functions in cancer. We also evaluate the feasibility and safety of novel therapeutic approaches aiming at targeting specific transcriptional regulators.
Challenges in Combining Immunotherapy with Radiotherapy in Recurrent/Metastatic Head and Neck Cancer
Authors: Plavc Gaber , Jesenko Tanja , Oražem Miha , Strojan Primož
Published: October 2020

Immunotherapy with immune checkpoint inhibitors (ICI) has recently become a standard part of the treatment of recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC), although the response rates are low. Numerous preclinical and clinical studies have now illuminated several mechanisms by which radiotherapy (RT) enhances the effect of ICI. From RT-induced immunogenic cancer cell death to its effect on the tumor microenvironment and vasculature, the involved mechanisms are diverse and intertwined. Moreover, the research of these interactions is challenging because of the thin line between immunostimulatory and the immunosuppressive effect of RT. In the era of active research of immunoradiotherapy combinations, the significance of treatment and host-related factors that were previously seen as being less important is being revealed. The impact of dose and fractionation of RT is now well established, whereas selection of the number and location of the lesions to be irradiated in a multi-metastatic setting is something that is only now beginning to be understood. In addition to spatial factors, the timing of irradiation is as equally important and is heavily dependent on the type of ICI used. Interestingly, using smaller-than-conventional RT fields or even partial tumor volume RT could be beneficial in this setting. Among host-related factors, the role of the microbiome on immunotherapy efficacy must not be overlooked nor can we neglect the role of gut irradiation in a combined RT and ICI setting. In this review we elaborate on synergistic mechanisms of immunoradiotherapy combinations, in addition to important factors to consider in future immunoradiotherapy trial designs in R/M HNSCC.
Self-Regeneration Effect of Three-Way Catalysts during Thermal Aging Procedure
Authors: Alikin Evgeny A. , Denisov Sergey P. , Bubnov Konstantin V. , Vedyagin Aleksey A.
Published: October 2020

One of the most important features of the three-way catalysts is their long-term stability. However, quite often, promising catalytic compositions with excellent activity become deactivated after a relatively short period of exploitation due to various reasons. Therefore, a study on the onboard regeneration of the deactivated three-way catalysts remains its actuality. The present work is mainly focused on the self-regeneration effect of the rhodium-containing component. Aging of the catalysts in the standard and model engine braking regimes revealed the difference in the catalytic performance. Deactivated rhodium species turned to the active state as a result of rapid cooling in air flow from 1200 to 600 °C. The regenerated catalyst shows improved activity towards NOx reduction and, therefore, widened operation window, which indicates higher accessibility of the rhodium species. X-ray diffraction analysis of the aged catalysts does not reveal any noticeable phase changes. Contrary, significant changes in the Rh oxidation state were registered by X-ray photoelectron spectroscopy. The observed effect opens new horizons for the development of the onboard purification systems with prolonged exploitation lifetime.
Carbon Nitride-Perovskite Composites: Evaluation and Optimization of Photocatalytic Hydrogen Evolution in Saccharides Aqueous Solution
Authors: Speltini Andrea , Romani Lidia , Dondi Daniele , Malavasi Lorenzo , Profumo Antonella
Published: October 2020

The application of hybrid photocatalysts made of carbon nitride and lead-free perovskites, namely DMASnBr3/g-C3N4 and PEA2SnBr4/g-C3N4, for the H2 evolution from saccharides aqueous solution is described. The novel composites were tested and compared in terms of hydrogen evolution rate (HER) under simulated solar light, using Pt as a reference co-catalyst, and glucose as a representative sacrificial biomass. The conditions were optimized to maximize H2 generation by a design of experiments involving catalyst amount, glucose concentration and Pt loading. For both materials, such parameters affected significantly H2 photogeneration, with the best performance observed using 0.5 g L−1 catalyst, 0.2 M glucose and 0.5 wt% Pt. Under optimized conditions, DMASnBr3/g-C3N4 showed a 5-fold higher HER compared to PEA2SnBr4/g-C3N4, i.e., 925 µmoles g−1 h−1 and 190 µmoles g−1 h−1, respectively (RSD ≤ 11%, n = 4). The former composite, which affords an HER 15-fold higher in aqueous glucose than in neat water, provided H2 also with no metal co-catalyst (around 140 µmoles g−1 h−1), and it was reusable for at least three photoreactions. Encouraging results were also collected by explorative tests on raw starch solution (around 150 µmoles g−1 h−1).
Photocatalysis for Organic Wastewater Treatment: From the Basis to Current Challenges for Society
Authors: Sinar Mashuri Salma Izati , Ibrahim Mohd Lokman , Kasim Muhd Firdaus , Mastuli Mohd Sufri , Rashid Umer , Abdullah Abdul Halim , Islam Aminul , Asikin Mijan Nurul , Tan Yie Hua , Mansir Nasar , Mohd Kaus Noor Haida , Yun Hin Taufiq-Yap
Published: October 2020

Organic pollutants such as dyes, antibiotics, analgesics, herbicides, pesticides, and stimulants become major sources of water pollution. Several treatments such as absorptions, coagulation, filtration, and oxidations were introduced and experimentally carried out to overcome these problems. Nowadays, an advanced technique by photocatalytic degradation attracts the attention of most researchers due to its interesting and promising mechanism that allows spontaneous and non-spontaneous reactions as they utilized light energy to initiate the reaction. However, only a few numbers of photocatalysts reported were able to completely degrade organic pollutants. In the past decade, the number of preparation techniques of photocatalyst such as doping, morphology manipulation, metal loading, and coupling heterojunction were studied and tested. Thus, in this paper, we reviewed details on the fundamentals, common photocatalyst preparation for coupling heterojunction, morphological effect, and photocatalyst’s characterization techniques. The important variables such as catalyst dosage, pH, and initial concentration of sample pollution, irradiation time by light, temperature system, durability, and stability of the catalyst that potentially affect the efficiency of the process were also discussed. Overall, this paper offers an in-depth perspective of photocatalytic degradation of sample pollutions and its future direction.
Oxidative Hydroxylation of Aryl Boronic Acid Catalyzed by Co-porphyrin Complexes via Blue-Light Irradiation
Authors: Atia Alaa A. , Kimura Masanari
Published: October 2020

Oxidative reactions often require unstable and environmentally harmful oxidants; therefore, the investigation of safer alternatives is urgent. Here, the hydroxylation of aryl boronic acid in the presence of Co-complexes is demonstrated. Tetrakis(4-carboxyphenyl) Co(II)-porphyrin was combined with biodegradable polymers such as chitosan catalyzed hydroxylation of phenyl boronic acids to form phenol derivatives under blue-light irradiation. This catalytic system can be used as an eco-friendly oxidation process that does not release oxidizing agents into the atmosphere.
Systemic Glycosaminoglycan Clearance by HARE/Stabilin-2 Activates Intracellular Signaling
Authors: Weigel Paul H.
Published: October 2020

Scavenger receptors perform essential functions, critical to maintaining mammalian physiologic homeostasis by continuously clearing vast numbers of biomolecules from blood, interstitial fluid and lymph. Stabilin-2 (Stab2) and the Hyaluronic Acid Receptor for Endocytosis (HARE), a proteolytic isoform of Stab2, are important scavenger receptors responsible for the specific binding and internalization (leading to degradation) of 22 discrete molecules, macromolecular complexes and cell types. One-third of these ligands are glycosaminoglycans (GAGs). Full-length Stab2, but not HARE, mediates efficient phagocytosis of apoptotic cells and bacteria via binding to target surface ligands. HARE, the C-terminal half of Stab2, mediates endocytosis of all the known soluble ligands. HA was the first ligand identified, in 1981, prior to receptor purification or cloning. Seven other GAG ligands were subsequently identified: heparin, dermatan sulfate, chondroitin and chondroitin sulfates A, C, D and E. Synthetic dextran sulfate is also a GAG mimic and ligand. HARE signaling during HA endocytosis was first discovered in 2008, and we now know that activation of HARE/Stab2 signaling is stimulated by receptor-mediated endocytosis or phagocytosis of many, but not all, of its ligands. This review focuses on the HARE-mediated GAG activation of intracellular signaling, particularly the Extracellular Signal-Regulated Kinase 1/2 pathway.
The Role of PPARs in Disease
Authors: Wagner Nicole , Wagner Kay-Dietrich
Published: October 2020

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that function as ligand-activated transcription factors. They exist in three isoforms: PPARα, PPARβ/δ, and PPARγ. For all PPARs, lipids are endogenous ligands, linking them directly to metabolism. PPARs form heterodimers with retinoic X receptors, and upon ligand binding, they modulate the gene expression of downstream target genes, depending on the presence of co-repressors or co-activators. This results in a complex, cell type-specific regulation of proliferation, differentiation, and cell survival. PPARs are linked to metabolic disorders and are interesting pharmaceutical targets. PPARα and PPARγ agonists are already in clinical use for the treatment of hyperlipidemia and type 2 diabetes, respectively. More recently, PPARβ/δ activation came into focus as an interesting novel approach for the treatment of metabolic syndrome and associated cardiovascular diseases; however, this has been limited due to the highly controversial function of PPARβ/δ in cancer. This Special Issue of Cells brings together the most recent advances in understanding the various aspects of the action of PPARs, and it provides new insights into our understanding of PPARs, implying also the latest therapeutic perspectives for the utility of PPAR modulation in different disease settings.
Structural Basis of Inhibition of the Pioneer Transcription Factor NF-Y by Suramin
Authors: Nardone Valentina , Chaves-Sanjuan Antonio , Lapi Michela , Airoldi Cristina , Saponaro Andrea , Pasqualato Sebastiano , Dolfini Diletta , Camilloni Carlo , Bernardini Andrea , Gnesutta Nerina , Mantovani Roberto , Nardini Marco
Published: October 2020

NF-Y is a transcription factor (TF) comprising three subunits (NF-YA, NF-YB, NF-YC) that binds with high specificity to the CCAAT sequence, a widespread regulatory element in gene promoters of prosurvival, cell-cycle-promoting, and metabolic genes. Tumor cells undergo “metabolic rewiring” through overexpression of genes involved in such pathways, many of which are under NF-Y control. In addition, NF-YA appears to be overexpressed in many tumor types. Thus, limiting NF-Y activity may represent a desirable anti-cancer strategy, which is an ongoing field of research. With virtual-screening docking simulations on a library of pharmacologically active compounds, we identified suramin as a potential NF-Y inhibitor. We focused on suramin given its high water-solubility that is an important factor for in vitro testing, since NF-Y is sensitive to DMSO. By electrophoretic mobility shift assays (EMSA), isothermal titration calorimetry (ITC), STD NMR, X-ray crystallography, and molecular dynamics (MD) simulations, we showed that suramin binds to the histone fold domains (HFDs) of NF-Y, preventing DNA-binding. Our analyses, provide atomic-level detail on the interaction between suramin and NF-Y and reveal a region of the protein, nearby the suramin-binding site and poorly conserved in other HFD-containing TFs, that may represent a promising starting point for rational design of more specific and potent inhibitors with potential therapeutic applications.
Formation of an RNA Quadruplex-Duplex Hybrid in Living Cells between mRNA of the Epidermal Growth Factor Receptor (EGFR) and a G-Rich Antisense Oligoribonucleotide
Authors: Gudanis Dorota , Kaniowski Damian , Kulik Katarzyna , Baranowski Daniel , Gdaniec Zofia , Nawrot Barbara
Published: October 2020

Antisense DNA oligonucleotides, short interfering RNAs (siRNAs), and CRISPR/Cas9 genetic tools are the most useful therapeutic nucleic acids regulating gene expression based on the antisense specificity towards messenger RNA. Here, we present an effective novel strategy for inhibiting translation based on the antisense-controlled formation of an RNA quadruplex-duplex hybrid (QDH) between a G-rich RNA antisense oligoribonucleotide (Q-ASO) and specific mRNA, comprising two distant G-tracts. We selected epidermal growth factor receptor (EGFR) as a well-established target protein in anticancer therapy. The chemically modified, bi-functional anti-EGFR Q-ASO and a 56-nt long EGFR mRNA fragment, in the presence of potassium ions, were shown to form in vitro very stable parallel G-quadruplex containing a 28-nt long external loop folding to two duplex-stem structure. Besides, the Q-ASOs effectively reduced EGFR mRNA levels compared to the non-modified RNA and DNA antisense oligonucleotides (rASO, dASO). In addition, the hybridization specificity of Q-ASO comprising a covalently attached fluorescent tag was confirmed in living cells by visualization of the G4 green fluorescent species in the presence of other antisense inhibitors under competitive conditions. The results presented here offer novel insights into the potential application of Q-ASOs for the detection and/or alteration of (patho)biological processes through RNA:RNA quadruplex-duplex formation in cellular systems.
Crosstalk Pathway between Trehalose Metabolism and Cytokinin Degradation for the Determination of the Number of Berries per Bunch in Grapes
Authors: Moriyama Ayane , Yamaguchi Chiho , Enoki Shinichi , Aoki Yoshinao , Suzuki Shunji
Published: October 2020

In grapes, the number of flowers per inflorescence determines the compactness of grape bunches. Grape cultivars with tight bunches and thin-skinned berries easily undergo berry splitting, especially in growing areas with heavy rainfall during the grapevine growing season, such as Japan. We report herein that grape cytokinin oxidase/dehydrogenase 5 (VvCKX5) determines the number of berries per inflorescence in grapes. The number of berries per bunch was inversely proportional to the VvCKX5 expression level in juvenile inflorescences among the cultivars tested. VvCKX5 overexpression drastically decreased the number of flower buds per inflorescence in Arabidopsis plants, suggesting that VvCKX5 might be one of the negative regulators of the number of flowers per inflorescence in grapes. Similarly, the overexpression of grape sister of ramose 3 (VvSRA), which encodes trehalose 6-phosphate phosphatase that catalyzes the conversion of trehalose-6-phosphate into trehalose, upregulated AtCKX7 expression in Arabidopsis plants, leading to a decrease in the number of flower buds per Arabidopsis inflorescence. VvCKX5 gene expression was upregulated in grapevine cultured cells and juvenile grape inflorescences treated with trehalose. Finally, injecting trehalose into swelling buds nearing bud break using a microsyringe decreased the number of berries per bunch by half. VvCKX5 overexpression in Arabidopsis plants had no effect on the number of secondary inflorescences from the main inflorescence, and similarly trehalose did not affect pedicel branching on grapevine inflorescences, suggesting that VvCKX5, as well as VvSRA-mediated trehalose metabolism, regulates flower formation but not inflorescence branching. These findings may provide new information on the crosstalk between VvSRA-mediated trehalose metabolism and VvCKX-mediated cytokinin degradation for determining the number of berries per bunch. Furthermore, this study is expected to contribute to the development of innovative cultivation techniques for loosening tight bunches.
A Model Study on the Dynamics of the Amino Acid Content in Micrometeoroids during Atmospheric Entry
Authors: Canepa Carlo
Published: October 2020

A model for the survival of the amino acid content in micrometeorites and its possible transformations upon atmospheric entry is described. Since any organic species released in the atmosphere at high altitudes would exhibit a limited lifetime with respect to the typical timescale for atmospheric mixing (due to the substantial radiation field of the early Sun), only the organic content inside the meteorites could have contributed to prebiotic chemistry. It is thus important to determine both the amino acid loss from meteorites, due to both degassing and chemical degradation, and the extent of the chemical transformation of amino acids subjected to the increased temperature due to friction with the atmosphere. According to the interplay between the potential energy barrier and the pre-exponential factor in rate coefficients, either diffusion or chemical processing might be the dominant process following the rising temperature upon atmospheric entry. The possibility of the elimination of water from glycine to form aminoketene, or CO2 to form methylamine, ultimately driven by gravitational energy, was examined along with the more conventional formation of a peptide bond between two glycine units to afford Gly–Gly. While retention, degassing, and decarboxylation are the fastest processes, each dominating in different ranges of the initial velocity and radius, the formation of either Gly–Gly from bimolecular water elimination or aminoketene from unimolecular water elimination appears to be negligible.
Experimental and Numerical Modeling for Flattening and Rapid Solidification with Crystallization Behavior of Supersonic Ceramic Droplets
Authors: Wang Yu , Chong Nanjing , Bai Yu , Wu Kai , Zhou Jun , Shen Mingguang , Ming You , Liu Qi , Sun Yiwen , Hu Yongbao , Du Xiaojuan , She Zhaobin
Published: October 2020

Successive impingement of droplets after refining in supersonic plasma jet generally yields a submicron-sized lamellar coating with excellent comprehensive properties. Nevertheless, physical insight into the flattening and rapid solidification with crystallization behavior of supersonic impingement of refined droplets is difficult to understand. In this research, the content of refinement droplets reached 90% and displayed the multi-scale distribution of equiaxed grains. The boundary migration of equiaxed grains and anisotropic coalescence was found in the dynamic temperature gradient. Furthermore, an optimized model was established in order to accurately reproduce the multi-physical coupling process of supersonic impingement of single or two refined droplets, which was based on the numerical calculation of nonlinear equations (including the Mass and momentum, energy balance, Cahn–Hilliard, phase-field and orientational field equations). The size distribution and growth orientation of columnar grains within single or two flattened droplets were in good agreement with the experimental results. Epitaxial growth of columnar grains was found in the two-flattened droplet interface during the extremely rapid cooling stage. This optimized model could be an effective method in predicting the flattening and solidification with crystallization behavior of droplets during plasma spraying.
Hydrodynamics and Mass Transfer during the Solution Growth of the K2(Co,Ni)(SO4)2•6H2O Mixed Crystals in the Shapers
Authors: Prostomolotov Anatoly I. , Verezub Nataliya A. , Vasilyeva Natalia A. , Voloshin Alexey E.
Published: October 2020

Mathematical models of the hydrodynamics and mass transfer processes during the mixed crystal growth from low-temperature aqueous solutions have been analyzed. The features of these processes are caused by complex design of the crystallizer with a shaper. Two models of the solution flowing into the shaper have been considered. In the first model, the solution is fed to the central part of the crystal. The second model presents a peripheral solution supply along the shaper perimeter, which allows us to create a swirling flow. The calculation models correspond to laminar and turbulent regimes of solution flow during the growth of K2(Co,Ni)(SO4)2•6H2O mixed crystal from an aqueous solution.
Sexual Dysfunction in Diabetic Women: An Update on Current Knowledge
Authors: Barbagallo Federica , Mongioì Laura , Cannarella Rossella , La Vignera Sandro , Condorelli Rosita , Calogero Aldo
Published: October 2020

Diabetes mellitus (DM) is one of the most common chronic diseases worldwide and its prevalence is expected to increase in the coming years. Therefore, updated knowledge of all diabetic complications and their management is essential for the proper treatment of these patients. Sexual dysfunctions are one of the long-term complications of DM in both genders. However, female sexuality is still a taboo and sexual concerns are often overlooked, underdiagnosed, and untreated. The aim of this review is to summarize the current knowledge on the relationship between sexual function and DM in women. In particular, we evaluated the prevalence, etiology, diagnostic approaches, and current treatment options of female sexual dysfunction (FSD) in diabetic patients.
Diabetology: A New Online Diabetes Journal. What Role Can It Play in a Crowded Field?
Authors: Clifton Peter
Published: October 2020

As a general physician with an interest in endocrinology, more than half of my patients have type 2 diabetes invariably accompanied by obesity, and in almost all cases at least one complication of diabetes [...]
Numerical Modeling of Transcritical and Supercritical Fuel Injections Using a Multi-Component Two-Phase Flow Model
Authors: Ningegowda Bittagowdanahalli Manjegowda , Rahantamialisoa Faniry Nadia Zazaravaka , Pandal Adrian , Jasak Hrvoje , Im Hong Geun , Battistoni Michele
Published: October 2020

In the present numerical study, implicit large eddy simulations (LES) of non-reacting multi-components mixing processes of cryogenic nitrogen and n-dodecane fuel injections under transcritical and supercritical conditions are carried out, using a modified reacting flow solver, originally available in the open source software OpenFOAM®. To this end, the Peng-Robinson (PR) cubic equation of state (EOS) is considered and the solver is modified to account for the real-fluid thermodynamics. At high pressure conditions, the variable transport properties such as dynamic viscosity and thermal conductivity are accurately computed using the Chung transport model. To deal with the multicomponent species mixing, molar averaged homogeneous classical mixing rules are used. For the velocity-pressure coupling, a PIMPLE based compressible algorithm is employed. For both cryogenic and non-cryogenic fuel injections, qualitative and quantitative analyses are performed, and the results show significant effects of the chamber pressure on the mixing processes and entrainment rates. The capability of the proposed numerical model to handle multicomponent species mixing with real-fluid thermophysical properties is demonstrated, in both supercritical and transcritical regimes.
Using Lenses Attached to a Smartphone as a Macroscopic Early Warning Tool in the Illegal Timber Trade, in Particular for CITES-Listed Species
Authors: de Palacios Paloma , G. Esteban Luis , Gasson Peter , García-Fernández Francisco , de Marco Antonio , García-Iruela Alberto , García-Esteban Lydia , González-de-Vega David
Published: October 2020

Wood anatomy is a key discipline as a tool for monitoring the global timber trade, particularly for wood listed in protected species conventions such as Convention on International Trade in Endangered Species of Wild Flora and Fauna (CITES). One of the main barriers to reducing illegal trafficking of protected species is ensuring that customs officials with appropriate training in wood anatomy are equipped with simple tools, at both the origin and destination of shipments, so they can raise an early warning about wood suspected of contravening international treaties and immediately send samples to a specialised laboratory. This work explains how lenses attached to a smartphone, capable of achieving up to 400× magnification using the phone digital zoom, can be used to distinguish features that are not visible with traditional 10× or 12× lenses, enhancing the capacity to view features not typically observable in the field. In softwoods, for example, this method permits determination of the type of axial parenchyma arrangement, whether there are helical thickenings in axial tracheids and whether axial tracheids have organic deposits or contain alternate polygonal pits, and in the rays, if the tracheids are smooth-walled or dentate and if the cross-field pits are window-like. In hardwoods, it allows verification of the presence of tyloses and deposits in vessels, the type of perforation plates and whether the intervascular pitting is scalariform; in the rays it is possible to differentiate the types of ray cells; and in the axial parenchyma, to determine the presence of oil cells. In addition, unlike macroscopic analysis with a conventional magnifying lens, this type of lens can be used with the appropriate mobile application for the biometry of important elements such as ray height and vessel diameter.
Attracting Green Consumers as a Basis for Creating Sustainable Marketing Strategy on the Organic Market—Relevance for Sustainable Agriculture Business Development
Authors: Melović Boban , Cirović Dragana , Backovic-Vulić Tamara , Dudić Branislav , Gubiniova Katarina
Published: October 2020

The aim of this paper was to analyze the main factors that affect green consumers’ choice regarding the purchase of organic agriculture products. The data collected through a survey of 559 green consumers were analyzed using explanatory factor analysis, the Relative Importance Index, and logistic regression. The results point out eleven main factors related to the offerings on the organic agriculture market that predominantly drive green consumers’ purchasing decisions. The Relative Importance Index identified health benefits that stem from a specific way of production as the main purchasing motive. This was also confirmed by the results of logistic regression, which showed that a respondent who buys organic agricultural products on a daily basis is approximately 71.5% less likely to disagree with the claim that organic products are healthier than non-organic, compared to a consumer who purchases organic products several times a week or month. However, as these benefits cannot be empirically confirmed, green consumers look for official labels on the product packaging. In order to assure the product quality, more than half of them find out very important information about producers: whether they have a product quality certificate (69.5%), how many years they are engaged in production (56.2%), and whether they have specific product packaging (54.9%). The Relative Importance Index also revealed that the main purchasing barriers that consumers face are scarce offerings and an insufficient development of the distribution channel, which were ranked in first and second place. The price as a barrier is of less importance. About 30.8% of the respondents are willing to pay up to 20% higher prices for organic food compared to conventional food, while 39.4% of them would pay even up to 40% higher prices. Based on the given results, there are clear suggestions for creating a sustainable marketing strategy for organic agriculture products as the main prerequisite for an increase of healthy food choices and fostering the future development of organic agriculture businesses at the local and global levels.
Safe Food Handling Knowledge and Practices of Street Food Vendors in Polokwane Central Business District
Authors: Marutha Khomotso J. , Chelule Paul K.
Published: October 2020

Street food vending is a common business practice in most South African cities. However, street vended foods may be a source of foodborne illnesses if their handling is not well regulated and executed. This study aimed to investigate the knowledge and practices regarding food safety by street food vendors in the Polokwane central business district. This was a quantitative descriptive study where a structured questionnaire was used to collect self-reported data from street food vendors. A checklist was used to collect observed data from the vending site on vendor practices and status of the vending environment. A total of 312 vendors participated in the study, most being young females aged below 40 years (62%), single (51.2%) with less than six years of trade experience (58.3%). Although the level of knowledge was high, safe food handling practices were mostly inadequate. Most vendors operated their businesses in the open air and tents (66.2%). Vending experience significantly correlated with safe food handling practices (p < 0.05). It is significantly riskier to sell cooked rather than uncooked food in the street. Lack of resources like water and a healthy environment negatively affected food handling practices. Health promotion on food safety is recommended for street vendors.
The Microbial Diversity of Non-Korean Kimchi as Revealed by Viable Counting and Metataxonomic Sequencing
Authors: Maoloni Antonietta , Ferrocino Ilario , Milanović Vesna , Cocolin Luca , Corvaglia Maria Rita , Ottaviani Donatella , Bartolini Chiara , Talevi Giulia , Belleggia Luca , Cardinali Federica , Marabini Rico , Aquilanti Lucia , Osimani Andrea
Published: October 2020

Kimchi is recognized worldwide as the flagship food of Korea. To date, most of the currently available microbiological studies on kimchi deal with Korean manufactures. Moreover, there is a lack of knowledge on the occurrence of eumycetes in kimchi. Given these premises, the present study was aimed at investigating the bacterial and fungal dynamics occurring during the natural fermentation of an artisan non-Korean kimchi manufacture. Lactic acid bacteria were dominant, while Enterobacteriaceae, Pseudomonadaceae, and yeasts progressively decreased during fermentation. Erwinia spp., Pseudomonasveronii, Pseudomonasviridiflava, Rahnellaaquatilis, and Sphingomonas spp. were detected during the first 15 days of fermentation, whereas the last fermentation phase was dominated by Leuconostoc kimchi, together with Weissellasoli. For the mycobiota at the beginning of the fermentation process, Rhizoplaca and Pichia orientalis were the dominant Operational Taxonomic Units (OTUs) in batch 1, whereas in batch 2 Protomyces inundatus prevailed. In the last stage of fermentation, Saccharomyces cerevisiae, Candida sake,Penicillium, and Malassezia were the most abundant taxa in both analyzed batches. The knowledge gained in the present study represents a step forward in the description of the microbial dynamics of kimchi produced outside the region of origin using local ingredients. It will also serve as a starting point for further isolation of kimchi-adapted microorganisms to be assayed as potential starters for the manufacturing of novel vegetable preserves with high quality and functional traits.
Magnetized Particle Motion in γ-Spacetime in a Magnetic Field
Authors: Abdujabbarov Ahmadjon , Rayimbaev Javlon , Atamurotov Farruh , Ahmedov Bobomurat
Published: October 2020

In the present work we explored the dynamics of magnetized particles around the compact object in γ-spacetime in the presence of an external asymptotically-uniform magnetic field. The analysis of the circular orbits of magnetized particles around the compact object in the spacetime of a γ-object immersed in the external magnetic field has shown that the area of stable circular orbits of magnetized particles increases with the increase of γ-parameter. We have also investigated the acceleration of the magnetized particles near the γ-object and shown that the center-of-mass energy of colliding magnetized particles increases with the increase of γ-parameter. Finally, we have applied the obtained results to the astrophysical scenario and shown that the values of γ-parameter in the range of γ∈(0.5,1) can mimic the spin of Kerr black hole up to a≃0.85, while the magnetic interaction can mimic the γ-parameter at γ∈(0.8,1) and spin of a Kerr black hole up to a≃0.3.