bluuebunny/crossref_metadata_2025 huggingface dataset:
Activity-Based Protein Profiling Reveals Potential Dasatinib Targets in Gastric Cancer
Authors: Choi Kyoung-Min , Cho Eunji , Bang Geul , Lee Seong-Jae , Kim Boram , Kim Ji-Hee , Park Seo-Gyu , Han Eun Hee , Chung Young-Ho , Kim Jin Young , Kim Eunjung , Kim Jae-Young
Published: December 2020

Dasatinib is a multi-target kinase inhibitor, whose targets include BCR-ABL, SRC family kinases, and various cancer kinases. The elevated SRC activity in gastric cancer (GC) has prompted the need for the therapeutic application of dasatinib in GC. We observed that the efficacy of dasatinib varied with the GC cell lines. The differential effect of dasatinib was not correlated with the basal SRC activity of each cell line. Moreover, the GC cell lines showing the strong antitumor effects of dasatinib were refractory to other SRC inhibitors, i.e., bosutinib and saracatinib, suggesting that unexpected dasatinib’s targets could exist. To profile the targets of dasatinib in GC, we performed activity-based protein profiling (ABPP) via mass spectrometry using a desthiobiotin-ATP probe. We identified 29 and 18 kinases as potential targets in dasatinib-sensitive (SNU-216, MKN-1) and -resistant (SNU-484, SNU-601) cell lines, respectively. The protein–protein interaction mapping of the differential drug targets in dasatinib-sensitive and -resistant GC using the STRING database suggested that dasatinib could target cellular energy homeostasis in the drug-sensitive GC. RNAi screening for identified targets indicated p90RSK could be a novel dasatinib target, which is important for maintaining the viability and motility of GC cells. Further functional validation of dasatinib off-target actions will provide more effective therapeutic options for GC.
D-limonene Inhibits Pentylenetetrazole-Induced Seizure via Adenosine A2A Receptor Modulation on GABAergic Neuronal Activity
Authors: Seo Sowoon , Song Yunjeong , Gu Sun Mi , Min Hyun Kyu , Hong Jin Tae , Cha Hye Jin , Yun Jaesuk
Published: December 2020

Background: Epilepsy is a chronic neurological disorder characterized by the recurrence of seizures. One-third of patients with epilepsy may not respond to antiseizure drugs. Purpose: We aimed to examine whether D-limonene, a cyclic monoterpene, exhibited any antiseizure activity in the pentylenetetrazole (PTZ)-induced kindling mouse model and in vitro. Methods: PTZ kindling mouse model was established by administering PTZ (30 mg/kg) intraperitoneally to mice once every 48 h. We performed immunoblot blots, immunohistochemistry (IHC), and high-performance liquid chromatography (HPLC) analysis after the behavioral study. Results: An acute injection of PTZ (60 mg/kg) induced seizure in mice, while pretreatment with D-limonene inhibited PTZ-induced seizure. Repeated administration of PTZ (30 mg/kg) increased the seizure score gradually in mice, which was reduced in D-limonene (10 mg/kg)-pretreated group. In addition, D-limonene treatment increased glutamate decarboxylase-67 (GAD-67) expression in the hippocampus. Axonal sprouting of hippocampal neurons after kindling was inhibited by D-limonene pretreatment. Moreover, D-limonene reduced the expression levels of Neuronal PAS Domain Protein 4 (Npas4)-induced by PTZ. Furthermore, the adenosine A2A antagonist SCH58261 and ZM241385 inhibited anticonvulsant activity and gamma-aminobutyric acid (GABA)ergic neurotransmission-induced by D-limonene. Conclusion: These results suggest that D-limonene exhibits anticonvulsant activity through modulation of adenosine A2A receptors on GABAergic neuronal function.
Dissection of Molecular Processes and Genetic Architecture Underlying Iron and Zinc Homeostasis for Biofortification: From Model Plants to Common Wheat
Authors: Tong Jingyang , Sun Mengjing , Wang Yue , Zhang Yong , Rasheed Awais , Li Ming , Xia Xianchun , He Zhonghu , Hao Yuanfeng
Published: December 2020

The micronutrients iron (Fe) and zinc (Zn) are not only essential for plant survival and proliferation but are crucial for human health. Increasing Fe and Zn levels in edible parts of plants, known as biofortification, is seen a sustainable approach to alleviate micronutrient deficiency in humans. Wheat, as one of the leading staple foods worldwide, is recognized as a prioritized choice for Fe and Zn biofortification. However, to date, limited molecular and physiological mechanisms have been elucidated for Fe and Zn homeostasis in wheat. The expanding molecular understanding of Fe and Zn homeostasis in model plants is providing invaluable resources to biofortify wheat. Recent advancements in NGS (next generation sequencing) technologies coupled with improved wheat genome assembly and high-throughput genotyping platforms have initiated a revolution in resources and approaches for wheat genetic investigations and breeding. Here, we summarize molecular processes and genes involved in Fe and Zn homeostasis in the model plants Arabidopsis and rice, identify their orthologs in the wheat genome, and relate them to known wheat Fe/Zn QTL (quantitative trait locus/loci) based on physical positions. The current study provides the first inventory of the genes regulating grain Fe and Zn homeostasis in wheat, which will benefit gene discovery and breeding, and thereby accelerate the release of Fe- and Zn-enriched wheats.
Non-Coding RNAs as Blood-Based Biomarkers in Cardiovascular Disease
Authors: Videira Raquel Figuinha , da Costa Martins Paula A. , Falcão-Pires Inês
Published: December 2020

In 2020, cardiovascular diseases (CVDs) remain a leading cause of mortality and morbidity, contributing to the burden of the already overloaded health system. Late or incorrect diagnosis of patients with CVDs compromises treatment efficiency and patient’s outcome. Diagnosis of CVDs could be facilitated by detection of blood-based biomarkers that reliably reflect the current condition of the heart. In the last decade, non-coding RNAs (ncRNAs) present on human biofluids including serum, plasma, and blood have been reported as potential biomarkers for CVDs. This paper reviews recent studies that focus on the use of ncRNAs as biomarkers of CVDs.
Skin Resident γδ T Cell Function and Regulation in Wound Repair
Authors: Munoz Luis D. , Sweeney Michael J. , Jameson Julie M.
Published: December 2020

The skin is a critical barrier that protects against damage and infection. Within the epidermis and dermis reside γδ T cells that play a variety of key roles in wound healing and tissue homeostasis. Skin-resident γδ T cells require T cell receptor (TCR) ligation, costimulation, and cytokine reception to mediate keratinocyte activity and inflammatory responses at the wound site for proper wound repair. While both epidermal and dermal γδ T cells regulate inflammatory responses in wound healing, the timing and factors produced are distinct. In the absence of growth factors, cytokines, and chemokines produced by γδ T cells, wound repair is negatively impacted. This disruption in γδ T cell function is apparent in metabolic diseases such as obesity and type 2 diabetes. This review provides the current state of knowledge on skin γδ T cell activation, regulation, and function in skin homeostasis and repair in mice and humans. As we uncover more about the complex roles played by γδ T cells in wound healing, novel targets can be discovered for future clinical therapies.
LDOC1 as Negative Prognostic Marker for Vulvar Cancer Patients
Authors: Wanka Giulia , Schmoeckel Elisa , Mayr Doris , Fuerst Sophie , Kuhn Christina , Mahner Sven , Knabl Julia , Karsten Maria Margarete , Dannecker Christian , Heidegger Helene H. , Vattai Aurelia , Jeschke Udo , Jueckstock Julia
Published: December 2020

So far, studies about targeted therapies and predictive biomarkers for vulva carcinomas are rare. The leucine zipper downregulated in cancer 1 gene (LDOC1) has been identified in various carcinomas as a tumor-relevant protein influencing patients’ survival and prognosis. Due to the lack of information about LDOC1 and its exact functionality, this study focuses on the expression of LDOC1 in vulvar carcinoma cells and its surrounding immune cells as well as its correlation to clinicopathological characteristics and prognosis. Additionally, a possible regulation of LDOC1 in vulvar cancer cell lines via the NF-κB signaling pathway was analyzed. Vulvar carcinoma sections of 157 patients were immunohistochemically stained and examined regarding LDOC1 expression by using the immunoreactive score (IRS). To characterize LDOC1-positively stained immune cell subpopulations, immunofluorescence double staining was performed. The effect of the NF-κB inhibitor C-DIM 12 (3,3′-[(4-chlorophenyl)methylene]bis[1 H-indole]) on vulvar cancer cell lines A431 and SW 954 was measured according to MTT and BrdU assays. Baseline expression levels of LDOC1 in the vulvar cancer cell lines A431 and SW 954 was analyzed by real-time PCR. LDOC1 was expressed by about 90% of the cancer cells in the cytoplasm and about half of the cells in the nucleus. Cytoplasmatic expression of LDOC1 was associated with decreased ten-year overall survival of the patient, whereas nuclear staining showed a negative association with disease-free survival. Infiltrating immune cells were mainly macrophages followed by regulatory T cells. Incubation with C-DIM 12 decreased the cell viability and proliferation of vulvar cancer cell line A431, but not of cell line SW 954. LDOC1 expression on mRNA level was twice as high in the cell line A431 compared to the cell line SW 954. Overexpression of LDOC1 was associated with unfavorable overall and disease-free survival. Tumor growth could be inhibited by C-DIM 12 in vitro if the expressed LDOC1 level was high enough.
Sleep/Wake Behavior and EEG Signatures of the TgF344-AD Rat Model at the Prodromal Stage
Authors: Kreuzer Matthias , Keating Glenda L. , Fenzl Thomas , Härtner Lorenz , Sinon Christopher G. , Hajjar Ihab , Ciavatta Vincent , Rye David B. , García Paul S.
Published: December 2020

Transgenic modification of the two most common genes (APPsw, PS1ΔE9) related to familial Alzheimer’s disease (AD) in rats has produced a rodent model that develops pathognomonic signs of AD without genetic tau-protein modification. We used 17-month-old AD rats (n = 8) and age-matched controls (AC, n = 7) to evaluate differences in sleep behavior and EEG features during wakefulness (WAKE), non-rapid eye movement sleep (NREM), and rapid eye movement sleep (REM) over 24-h EEG recording (12:12h dark–light cycle). We discovered that AD rats had more sleep–wake transitions and an increased probability of shorter REM and NREM bouts. AD rats also expressed a more uniform distribution of the relative spectral power. Through analysis of information content in the EEG using entropy of difference, AD animals demonstrated less EEG information during WAKE, but more information during NREM. This seems to indicate a limited range of changes in EEG activity that could be caused by an AD-induced change in inhibitory network function as reflected by increased GABAAR-β2 expression but no increase in GAD-67 in AD animals. In conclusion, this transgenic rat model of Alzheimer’s disease demonstrates less obvious EEG features of WAKE during wakefulness and less canonical features of sleep during sleep.
Characterization of AMBN I and II Isoforms and Study of Their Ca2+-Binding Properties
Authors: Vetyskova Veronika , Zouharova Monika , Bednarova Lucie , Vaněk Ondřej , Sázelová Petra , Kašička Václav , Vymetal Jiri , Srp Jaroslav , Rumlová Michaela , Charnavets Tatsiana , Postulkova Klara , Reseland Janne E. , Bousova Kristyna , Vondrasek Jiri
Published: December 2020

Ameloblastin (Ambn) as an intrinsically disordered protein (IDP) stands for an important role in the formation of enamel—the hardest biomineralized tissue commonly formed in vertebrates. The human ameloblastin (AMBN) is expressed in two isoforms: full-length isoform I (AMBN ISO I) and isoform II (AMBN ISO II), which is about 15 amino acid residues shorter than AMBN ISO I. The significant feature of AMBN—its oligomerization ability—is enabled due to a specific sequence encoded by exon 5 present at the N-terminal part in both known isoforms. In this study, we characterized AMBN ISO I and AMBN ISO II by biochemical and biophysical methods to determine their common features and differences. We confirmed that both AMBN ISO I and AMBN ISO II form oligomers in in vitro conditions. Due to an important role of AMBN in biomineralization, we further addressed the calcium (Ca2+)-binding properties of AMBN ISO I and ISO II. The binding properties of AMBN to Ca2+ may explain the role of AMBN in biomineralization and more generally in Ca2+ homeostasis processes.
Spreading of Isolated Ptch Mutant Basal Cell Carcinoma Precursors Is Physiologically Suppressed and Counteracts Tumor Formation in Mice
Authors: Brandes Nadine , Mitkovska Slavica Hristomanova , Botermann Dominik Simon , Maurer Wiebke , Müllen Anna , Scheile Hanna , Zabel Sebastian , Frommhold Anke , Heß Ina , Hahn Heidi , Uhmann Anja
Published: December 2020

Basal cell carcinoma (BCC) originate from Hedgehog/Patched signaling-activated epidermal stem cells. However, the chemically induced tumorigenesis of mice with a CD4Cre-mediated biallelic loss of the Hedgehog signaling repressor Patched also induces BCC formation. Here, we identified the cellular origin of CD4Cre-targeted BCC progenitors as rare Keratin 5+ epidermal cells and show that wildtype Patched offspring of these cells spread over the hair follicle/skin complex with increasing mouse age. Intriguingly, Patched mutant counterparts are undetectable in age-matched untreated skin but are getting traceable upon applying the chemical tumorigenesis protocol. Together, our data show that biallelic Patched depletion in rare Keratin 5+ epidermal cells is not sufficient to drive BCC development, because the spread of these cells is physiologically suppressed. However, bypassing the repression of Patched mutant cells, e.g., by exogenous stimuli, leads to an accumulation of BCC precursor cells and, finally, to tumor development.
Immune Checkpoint Blockade in Advanced Cutaneous Squamous Cell Carcinoma: What Do We Currently Know in 2020?
Authors: Wessely Anja , Steeb Theresa , Leiter Ulrike , Garbe Claus , Berking Carola , Heppt Markus Vincent
Published: December 2020

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer that predominantly arises in chronically sun-damaged skin. Immunosuppression, genetic disorders such as xeroderma pigmentosum (XP), exposure to certain drugs and environmental noxae have been identified as major risk factors. Surgical removal of cSCC is the therapy of choice and mostly curative in early stages. However, a minority of patients develop locally advanced tumors or distant metastases that are still challenging to treat. Immune checkpoint blockade (ICB) targeting CTLA-4, PD-L1 and PD-1 has tremendously changed the field of oncological therapy and especially the treatment of skin cancers as tumors with a high mutational burden. In this review, we focus on the differences between cSCC and cutaneous melanoma (CM) and their implications on therapy, summarize the current evidence on ICB for the treatment of advanced cSCC and discuss the chances and pitfalls of this therapy option for this cancer entity. Furthermore, we focus on special subgroups of interest such as organ transplant recipients, patients with hematologic malignancies, XP and field cancerization.
Structural Perspective of Gliadin Peptides Active in Celiac Disease
Authors: Falcigno Lucia , Calvanese Luisa , Conte Mariangela , Nanayakkara Merlin , Barone Maria Vittoria , D’Auria Gabriella
Published: December 2020

Gluten fragments released in gut of celiac individuals activate the innate or adaptive immune systems. The molecular mechanisms associated with the adaptive response involve a series of immunodominant gluten peptides which are mainly recognized by human leucocyte antigen (HLA)-DQ2.5 and HLA-DQ8. Other peptides, such as A-gliadin P31–43, are not recognized by HLA and trigger innate responses by several routes not yet well detailed. Among the gluten fragments known to be active in Celiac disease, here we focus on the properties of all gluten peptides with known tri-dimensional structure either those locked into HLA-DQ complexes whose crystals were X-ray analyzed or characterized in solution as free forms. The aim of this work was to find the structural reasons why some gluten peptides prompt the adaptive immune systems while others do not, by apparently involving just the innate immune routes. We propose that P31–43 is a non-adaptive prompter because it is not a good ligand for HLA-DQ. Even sharing a similar ability to adopt polyproline II structure with the adaptive ones, the way in which the proline residues are located along the sequence disfavors a productive P31–43-HLA-DQ binding.
New Insights into Immune-Mediated Mechanisms in Parkinson’s Disease
Authors: Tan Jolene Su Yi , Chao Yin Xia , Rötzschke Olaf , Tan Eng-King
Published: December 2020

The immune system has been increasingly recognized as a major contributor in the pathogenesis of Parkinson’s disease (PD). The double-edged nature of the immune system poses a problem in harnessing immunomodulatory therapies to prevent and slow the progression of this debilitating disease. To tackle this conundrum, understanding the mechanisms underlying immune-mediated neuronal death will aid in the identification of neuroprotective strategies to preserve dopaminergic neurons. Specific innate and adaptive immune mediators may directly or indirectly induce dopaminergic neuronal death. Genetic factors, the gut-brain axis and the recent identification of PD-specific T cells may provide novel mechanistic insights on PD pathogenesis. Future studies to address the gaps in the identification of autoantibodies, variability in immunophenotyping studies and the contribution of gut dysbiosis to PD may eventually provide new therapeutic targets for PD.
Geomagnetic Shielding Enhances Radiation Resistance by Promoting DNA Repair Process in Human Bronchial Epithelial Cells
Authors: Xue Xunwen , Ali Yasser F. , Liu Caorui , Hong Zhiqiang , Luo Wanrong , Nie Jing , Li Bingyan , Jiao Yang , Liu Ning-Ang
Published: December 2020

With the advent of long-duration space explorations, ionizing radiation (IR) may pose a constant threat to astronauts without the protection of Earth’s magnetic field, or hypomagnetic field (HMF). However, the potential biological effects of a HMF on the cellular response to IR have not been well characterized so far. In this study, immortalized human bronchial epithelial cells were exposed to X-rays under either a geomagnetic field (GMF, ~50 uT) or HMF (<50 nT) culture condition. A significant increase of the cell survival rate in HMF after radiation was observed by colony formation analysis. The kinetics of DNA double-strand breaks (DSBs), determined by γH2AX foci formation and disappearance, presented a faster decrease of foci-positive cells and a significantly lower mean number of γH2AX foci per nucleus in HMF-cultured cells than in GMF-cultured cells after radiation. In addition, a γH2AX/53BP1 colocalization assay showed an upregulated DSB recovery rate in HMF cultured cells. These findings provided the first evidence that HMF exposure may enhance the cellular DSB repair efficiency upon radiation, and consequently modulate the genotoxic effects of IR.
Cyclodextrin-Based Nanostructure Efficiently Delivers siRNA to Glioblastoma Cells Preferentially via Macropinocytosis
Authors: Manzanares Darío , Pérez-Carrión María Dolores , Jiménez Blanco José Luis , Ortiz Mellet Carmen , García Fernández José Manuel , Ceña Valentín
Published: December 2020

Small interfering ribonucleic acid (siRNA) has the potential to revolutionize therapeutics since it can knockdown very efficiently the target protein. It is starting to be widely used to interfere with cell infection by HIV. However, naked siRNAs are unable to get into the cell, requiring the use of carriers to protect them from degradation and transporting them across the cell membrane. There is no information about which is the most efficient endocytosis route for high siRNA transfection efficiency. One of the most promising carriers to efficiently deliver siRNA are cyclodextrin derivatives. We have used nanocomplexes composed of siRNA and a β-cyclodextrin derivative, AMC6, with a very high transfection efficiency to selectively knockdown clathrin heavy chain, caveolin 1, and p21 Activated Kinase 1 to specifically block clathrin-mediated, caveolin-mediated and macropinocytosis endocytic pathways. The main objective was to identify whether there is a preferential endocytic pathway associated with high siRNA transfection efficiency. We have found that macropinocytosis is the preferential entry pathway for the nanoparticle and its associated siRNA cargo. However, blockade of macropinocytosis does not affect AMC6-mediated transfection efficiency, suggesting that macropinocytosis blockade can be functionally compensated by an increase in clathrin- and caveolin-mediated endocytosis.
Hydroa Vacciniforme and Hydroa Vacciniforme-Like Lymphoproliferative Disorder: A Spectrum of Disease Phenotypes Associated with Ultraviolet Irradiation and Chronic Epstein–Barr Virus Infection
Authors: Chen Chien-Chin , Chang Kung-Chao , Medeiros L Jeffrey , Lee Julia Yu-Yun
Published: December 2020

Hydroa vacciniforme (HV) is a rare form of photosensitivity disorder in children and is frequently associated with Epstein–Barr virus (EBV) infection, whereas HV-like lymphoproliferative disorders (HVLPD) describe a spectrum of EBV-associated T-cell or natural killer (NK)-cell lymphoproliferations with HV-like cutaneous manifestations, including EBV-positive HV, atypical HV, and HV-like lymphoma. Classic HV occurs in childhood with papulovesicules on sun-exposed areas, which is usually induced by sunlight and ultraviolet irradiation, and mostly resolves by early adult life. Unlike classic HV, atypical or severe HV manifests itself as recurrent papulovesicular eruptions in sun-exposed and sun-protected areas associated occasionally with facial edema, fever, lymphadenopathy, oculomucosal lesions, gastrointestinal involvement, and hepatosplenomegaly. Notably, atypical or severe HV may progress to EBV-associated systemic T-cell or natural killer (NK)-cell lymphoma after a chronic course. Although rare in the United States and Europe, atypical or severe HV and HV-like lymphoma are predominantly reported in children from Asia and Latin America with high EBV DNA levels, low numbers of NK cells, and T cell clones in the blood. In comparison with the conservative treatment used for patients with classic HV, systemic therapy such as immunomodulatory agents is recommended as the first-line therapy for patients with atypical or severe HV. This review aims to provide an integrated overview of current evidence and knowledge of HV and HVLPD to elucidate the pathophysiology, practical issues, environmental factors, and the impact of EBV infection.
Different Sensitivity of Control and MICU1- and MICU2-Ablated Trypanosoma cruzi Mitochondrial Calcium Uniporter Complex to Ruthenium-Based Inhibitors
Authors: Bertolini Mayara S. , Docampo Roberto
Published: December 2020

The mitochondrial Ca2+ uptake in trypanosomatids shares biochemical characteristics with that of animals. However, the composition of the mitochondrial Ca2+ uniporter complex (MCUC) in these parasites is quite peculiar, suggesting lineage-specific adaptations. In this work, we compared the inhibitory activity of ruthenium red (RuRed) and Ru360, the most commonly used MCUC inhibitors, with that of the recently described inhibitor Ru265, on Trypanosoma cruzi, the agent of Chagas disease. Ru265 was more potent than Ru360 and RuRed in inhibiting mitochondrial Ca2+ transport in permeabilized cells. When dose-response effects were investigated, an increase in sensitivity for Ru360 and Ru265 was observed in TcMICU1-KO and TcMICU2-KO cells as compared with control cells. In the presence of RuRed, a significant increase in sensitivity was observed only in TcMICU2-KO cells. However, application of Ru265 to intact cells did not affect growth and respiration of epimastigotes, mitochondrial Ca2+ uptake in Rhod-2-labeled intact cells, or attachment to host cells and infection by trypomastigotes, suggesting a low permeability for this compound in trypanosomes.
Regulation of Fetal Genes by Transitions among RNA-Binding Proteins during Liver Development
Authors: Suzuki Toru , Adachi Shungo , Kikuguchi Chisato , Shibata Shinsuke , Nishijima Saori , Kawamoto Yurie , Iizuka Yusuke , Koseki Haruhiko , Okano Hideyuki , Natsume Tohru , Yamamoto Tadashi
Published: December 2020

Transcripts of alpha-fetoprotein (Afp), H19, and insulin-like growth factor 2 (Igf2) genes are highly expressed in mouse fetal liver, but decrease drastically during maturation. While transcriptional regulation of these genes has been well studied, the post-transcriptional regulation of their developmental decrease is poorly understood. Here, we show that shortening of poly(A) tails and subsequent RNA decay are largely responsible for the postnatal decrease of Afp, H19, and Igf2 transcripts in mouse liver. IGF2 mRNA binding protein 1 (IMP1), which regulates stability and translation efficiency of target mRNAs, binds to these fetal liver transcripts. When IMP1 is exogenously expressed in mouse adult liver, fetal liver transcripts show higher expression and possess longer poly(A) tails, suggesting that IMP1 stabilizes them. IMP1 declines concomitantly with fetal liver transcripts as liver matures. Instead, RNA-binding proteins (RBPs) that promote RNA decay, such as cold shock domain containing protein E1 (CSDE1), K-homology domain splicing regulatory protein (KSRP), and CUG-BP1 and ETR3-like factors 1 (CELF1), bind to 3′ regions of fetal liver transcripts. These data suggest that transitions among RBPs associated with fetal liver transcripts shift regulation from stabilization to decay, leading to a postnatal decrease in those fetal transcripts.
Immunostimulatory Effects of Radiotherapy for Local and Systemic Control of Melanoma: A Review
Authors: Takahashi Junko , Nagasawa Shinsuke
Published: December 2020

Recently, modern therapies involving immune checkpoint inhibitors, cytokines, and oncolytic virus have been developed. Because of the limited treatment effect of modern therapy alone, the immunostimulatory effect of radiotherapy attracted increasing attention. The combined use of radiotherapy and modern therapy has been examined clinically and non-clinically, and its effectiveness has been confirmed recently. Because melanomas have high immunogenicity, better therapeutic outcomes are desired when using immunotherapy. However, sufficient therapeutic effects have not yet been achieved. Thus far, radiotherapy has been used only for local control of tumors. Although extremely rare, radiotherapy has also been reported for systemic control, i.e., abscopal effect. This is thought to be due to an antitumor immune response. Therefore, we herein summarize past information on not only the mechanism of immune effects on radiotherapy but also biomarkers reported in case reports on abscopal effects. We also reviewed the animal model suitable for evaluating abscopal effects. These results pave the way for further basic research or clinical studies on new treatment methods for melanoma. Currently, palliative radiation is administered to patients with metastatic melanoma for local control. If it is feasible to provide both systemic and local control, the treatment benefit for the patients is very large.
Autophagy—A Hidden but Important Actor on Oral Cancer Scene
Authors: Alexandra Totan , Marina Imre Melescanu , Daniela Miricescu , Ioana Stanescu Iulia , Maria BencZe , Radu Radulescu , Maria Tancu Ana , Tudor Spinu , Maria Greabu
Published: December 2020

The duration of denture use, oral hygiene, smoking and male sex were identified as risk factors for oral mucosal lesions. As it is well known, all the oral mucosal lesions associated with risk factors have an important degree of malignity. Chronic mechanical irritation can be another cause of oral cancer and it is produced by the constant action of a deleterious agent from the oral cavity. Autophagy represents a complex evolutionary conserved catabolic process in which cells self-digest intracellular organelles in order to regulate their normal turnover and remove the damaged ones with compromised function to further maintain homeostasis. Autophagy is modulated by mTOR kinase and indirectly by PI3K/AKT survival pathway. Due to its dual capacity to either induce cell death or promote cell survival, important evidence pointed that autophagy has a two-faced role in response to chemotherapy in cancer. In conclusion, understanding how to overcome cytoprotective autophagy and how to take advantage of autophagic cell death is critical in order to enhance the cancer cells sensitivity to particular therapeutic agents.
First Insights on Early Host Plants and Dispersal Behavior of Halyomorpha halys (Hemiptera: Pentatomidae) from Overwintering to Crop Colonization
Authors: Bosco Lara , Nardelli Martina , Tavella Luciana
Published: December 2020

Following its first detection in North Italy in 2012, H. halys has become a serious threat in many crops, including hazelnut. The present study aimed at investigating dispersal capacity and behavior in relation to host plants of overwintered adults of H. halys before the colonization of hazelnut crop. Research was carried out in four polyculture areas (from 14 to 50 ha) in north-western Italy in 2018, by using (i) pheromone-baited traps, (ii) visual inspection and beating sheet sampling, and (iii) immunomarking-capture technique. The relative abundance of H. halys was similar between and within the study areas, and the early attractiveness of lures to adults after overwintering was confirmed; the host plants near a pheromone trap (less than 5 m) hosted higher numbers of H. halys than the same plant species far away. Hybrid plane, European spindletree, walnut, oak, and European elder were the first plants on which adult bugs were observed to feed. By immunomarking-capture technique, H. halys showed both short- and long-range dispersal from overwintering sites and/or early host plants to wild and crop plants. Marked adults were found in all zones of each area, irrespective of the distance from the protein treatment. Therefore, H. halys movement patterns depend on the ecosystem features, and plant host distribution and availability. This knowledge together with the interaction between pheromone and early host plants might contribute to the management of post-overwintering adults.
Prediction of Failure in Ceramic Matrix Composites Using Damage-Based Failure Criterion
Authors: Jain Neraj , Koch Dietmar
Published: December 2020

This paper presents a damage-based failure criterion and its implementation in order to predict failure in ceramic matrix composites (CMC) manufactured via filament winding. The material behavior of CMCs is anisotropic and strongly depends on the angle between fiber orientation and loading direction. The inelastic behavior of laminates with different fiber orientations under tension and shear is modeled with the help of continuum damage mechanics. The parameters required for the damage model are obtained from a standard tensile and shear test. An isotropic damage law determines the evolution of damage in thermodynamic space and considers the interaction of damage parameters in different principal material directions. A quadratic damage-based failure criterion inspired by the Tsai-Wu failure criterion is proposed. Failure stress and strain can be predicted with higher accuracy compared to the Tsai-Wu failure criterion in stress- or strain-space. The use of the proposed damage limits allows designing a CMC component based on the microstructural phenomenon of stiffness loss. With the help of results obtained from modeling and experiments, fracture mechanics during the Iosipescu-shear test of CMCs and its capability to determine the shear strength of the material is discussed.
Progressive Collapse Analysis of Intact and Damaged Ships under Unsymmetrical Bending
Authors: Cerik Burak Can , Choung Joonmo
Published: December 2020

This study examined the hull girder strength of intact and damaged ships by adopting the incremental-iterative method for progressive collapse analysis, which was extended to the general case of the unsymmetrical bending of beams with an arbitrary cross-section. The sources of an unsymmetrical loading, including rotation of the loading plane and section asymmetry caused by structural damage, are described. A fast and robust procedure is presented to determine the translation and rotation of the instantaneous neutral axis at each curvature increment when applying Smith’s progressive collapse analysis method. A series of analyses were conducted on a double hull VLCC and a bulk carrier, considering various loading plane angles and damage conditions. The decrease in ultimate strength and the influences of rotation of the instantaneous neutral axis and ship heeling are discussed. The proposed method can be used for a rapid and rational assessment of the hull girder strength under adverse conditions.
Multi-Step-Ahead Forecasting of Wave Conditions Based on a Physics-Based Machine Learning (PBML) Model for Marine Operations
Authors: Wu Mengning , Stefanakos Christos , Gao Zhen
Published: December 2020

Short-term wave forecasts are essential for the execution of marine operations. In this paper, an efficient and reliable physics-based machine learning (PBML) model is proposed to realize the multi-step-ahead forecasting of wave conditions (e.g., significant wave height Hs and peak wave period Tp). In the model, the primary variables in physics-based wave models (i.e., the wind forcing and initial wave boundary condition) are considered as inputs. Meanwhile, a machine learning algorithm (artificial neural network, ANN) is adopted to build an implicit relation between inputs and forecasted outputs of wave conditions. The computational cost of this data-driven model is obviously much lower than that of the differential-equation based physical model. A ten-year (from 2001 to 2010) dataset of every three hours at the North Sea center was used to assess the model performance in a small domain. The result reveals high reliability for one-day-ahead Hs forecasts, while that of Tp is slightly lower due to the weaker implicit relationships between the data. Overall, the PBML model can be conceived as an efficient tool for the multi-step-ahead forecasting of wave conditions, and thus has great potential for furthering assist decision-making during the execution of marine operations.
Approaches to Assessing the Strategic Sustainability of High-Risk Offshore Oil and Gas Projects
Authors: Cherepovitsyn Alexey , Tsvetkova Anna , Komendantova Nadejda
Published: December 2020

In the face of today’s global challenges, oil and gas companies must define long-term priorities and opportunities in implementing complex Arctic offshore projects, taking into account environmental, economic, technological and social aspects. In this regard, ensuring strategic sustainability is the basis for long-term development. The aim of the study is to analyze existing approaches to the concept of “strategic sustainability” of an offshore Arctic oil and gas project and to develop a methodological approach to assessing the strategic sustainability of offshore oil and gas projects. In the theoretical part of the study, the approaches to defining strategic sustainability were reviewed, and their classification was completed, and the most appropriate definition of strategic sustainability for an offshore oil and gas project was chosen. The method of hierarchy analysis was used for strategic sustainability assessment. Specific criteria have been proposed to reflect the technical, geological, investment, social and environmental characteristics important to the offshore oil and gas project. The strategic sustainability of 5 offshore oil and gas projects was analyzed using an expert survey as part of the hierarchy analysis method. Recommendations were made on the development of an offshore project management system to facilitate the emergence of new criteria and improve the quality of the strategic sustainability assessment of offshore projects in the Arctic.
Iron Speciation and Physiological Analysis Indicate that Synechococcus sp. PCC 7002 Reduces Amorphous and Crystalline Iron Forms in Synthetic Seawater Medium
Authors: Hunnestad Annie Vera , Vogel Anne Ilse Maria , Digernes Maria Guadalupe , Ardelan Murat Van , Hohmann-Marriott Martin Frank
Published: December 2020

Cyanobacteria have high iron requirements due to iron-rich photosynthetic machineries. Despite the high concentrations of iron in the Earth’s crust, iron is limiting in many marine environments due to iron’s low solubility. Oxic conditions leave a large portion of the ocean’s iron pool unavailable for biotic uptake, and so the physiochemical properties of iron are hugely important for iron’s bioavailability. Our study is the first to investigate the effect of iron source on iron internalization and extracellular reduction by Synechococcus sp. PCC 7002. The results indicated that the amorphous iron hydrolysis species produced by FeCl3 better support growth in Synechococcus through more efficient iron internalization and a larger degree of extracellular reduction of iron than the crystalline FeO(OH). An analysis of dissolved iron (II) indicated that biogenic reduction took place in cultures of Synechococcus grown on both FeCl3 and FeO(OH).
An Improved Cleaning Protocol for Foraminiferal Calcite from Unconsolidated Core Sediments: HyPerCal—A New Practice for Micropaleontological and Paleoclimatic Proxies
Authors: Zarkogiannis Stergios D. , Kontakiotis George , Gkaniatsa Georgia , Kuppili Venkata S. C. , Marathe Shashidhara , Wanelik Kazimir , Lianou Vasiliki , Besiou Evanggelia , Makri Panayiota , Antonarakou Assimina
Published: December 2020

Paleoclimatic and paleoceanographic studies routinely rely on the usage of foraminiferal calcite through faunal, morphometric and physico-chemical proxies. The application of such proxies presupposes the extraction and cleaning of these biomineralized components from ocean sediments in the most efficient way, a process which is often labor intensive and time consuming. In this respect, in this study we performed a systematic experiment for planktonic foraminiferal specimen cleaning using different chemical treatments and evaluated the resulting data of a Late Quaternary gravity core sample from the Aegean Sea. All cleaning procedures adopted here were made on the basis of their minimum potential bias upon foraminiferal proxies, such as the faunal assemblages, degree of fragmentation, stable isotope composition (δ18O and δ13C) and/or Mg/Ca ratios that are frequently used as proxies for surface-ocean climate parameters (e.g., sea surface temperature, sea surface salinity). Six different protocols were tested, involving washing, sieving, and chemical treatment of the samples with hydrogen peroxide and/or sodium hexametaphosphate (Calgon®). Single species foraminifera shell weighing was combined with high-resolution scanning electron microscopy (SEM) and synchrotron X-ray microtomography (SμCT) of the material processed by each of the cleaning protocols, in order to assess the decontamination degree of specimen’s ultrastructure and interior. It appeared that a good compromise between time and cleaning efficiency is the simultaneous treatment of samples with a mixed hydrogen peroxide and Calgon solution, while the most effective way to almost completely decontaminate the calcareous components from undesirable sedimentary material is a two-step treatment—initially with hydrogen peroxide and subsequently with Calgon solutions.
Purification and Characterization of Two Novel Laccases from Peniophora lycii
Authors: Glazunova Olga A. , Moiseenko Konstantin V. , Savinova Olga S. , Fedorova Tatyana V.
Published: December 2020

Although, currently, more than 100 laccases have been purified from basidiomycete fungi, the majority of these laccases were obtained from fungi of the Polyporales order, and only scarce data are available about the laccases from other fungi. In this article, laccase production by the white-rot basidiomycete fungus Peniophora lycii, belonging to the Russulales order, was investigated. It was shown that, under copper induction, this fungus secreted three different laccase isozymes. Two laccase isozymes—Lac5 and LacA—were purified and their corresponding nucleotide sequences were determined. Both purified laccases were relatively thermostable with periods of half-life at 70 °C of 10 and 8 min for Lac5 and LacA, respectively. The laccases demonstrated the highest activity toward ABTS (97 U·mg−1 for Lac5 and 121 U·mg−1 for LacA at pH 4.5); Lac5 demonstrated the lowest activity toward 2,6-DMP (2.5 U·mg−1 at pH 4.5), while LacA demonstrated this towards gallic acid (1.4 U·mg−1 at pH 4.5). Both Lac5 and LacA were able to efficiently decolorize such dyes as RBBR and Bromcresol Green. Additionally, phylogenetic relationships among laccases of Peniophora spp. were reconstructed, and groups of orthologous genes were determined. Based on these groups, all currently available data about laccases of Peniophora spp. were systematized.
Santiago de Chile through the Eyes of Jane Jacobs. Analysis of the Conditions for Urban Vitality in a Latin American Metropolis
Authors: Fuentes Luis , Miralles-Guasch Carme , Truffello Ricardo , Delclòs-Alió Xavier , Flores Mónica , Rodríguez Sebastián
Published: December 2020

The urban planning ideas proposed by Jane Jacobs in the 1960s remain relevant to this day, promoting a perspective on the relationship between urban morphology and the community that takes into consideration the experiences of the people themselves in the planning of cities. With Jacobs’ ideas in mind, this article seeks to explore the urban territory of Santiago, Chile, and to assess the vitality of its neighborhoods with their diversity of morphological, architectural, and spatial characteristics. The results reveal a spatial reality that differs considerably from typical interpretations of this and other cities across Latin America, characterized by a strong radial center–periphery dynamic interspersed with sub-centers of high vitality, mainly in the form of rural towns and villages that, over time, became absorbed into the urban fabric of Santiago, along with social housing estates located on what used to be the urban periphery.
People Centeredness, Chronic Conditions and Diversity Sensitive eHealth: Exploring Emancipation of the ‘Health Care System’ and the ‘Patient’ in Health Informatics
Authors: Botin Lars , Bertelsen Pernille S. , Kayser Lars , Turner Paul , Villumsen Sidsel , Nøhr Christian
Published: December 2020

Health care systems struggle to consistently deliver integrated high-quality, safe, and patient-centered care to all in an economically sustainable manner. Inequity of access to health care services and variation in diagnostic and treatment outcomes are common. Further, as health care systems become ever more complex, iatrogenesis and counter productivity have emerged as real dangers. In exploring this paradox, this paper considers a subset of those in society living with chronic conditions. Their attributes and circumstances have led to them being marginalized or excluded from ‘end-user’ engagement and/or from their requirements being incorporated into technology supported chronic disease management initiatives. Significantly, these citizens are often the most vulnerable and socially disadvantaged and tend to achieve poorer results and cost more per capita than the ‘average patient’ in their interactions with the health care system. Critically, this paper argues that a truly people-centered technology supported chronic care system can only be designed by understanding and responding to the needs, attributes and capabilities of the most vulnerable in society. This paper suggests innovative ways of supporting interactions with these ‘end-users’ and highlights how reflection on these approaches can contribute to emancipating the health system to move towards more socially inclusive eHealth solutions.
Degradation of Contaminants of Emerging Concern by Electrochemical Oxidation: Coupling of Ultraviolet and Ultrasound Radiations
Authors: Martín de Vidales María J. , Rua Jaime , Montero de Juan José Luis , Fernández-Martínez Francisco , Dos santos-García Antonio J.
Published: December 2020

In this work, we study the electrochemical oxidation of methyl red, a dye present in textile industrial effluents, which is selected as the model for the degradation of Contaminants of Emerging Concern. The influence of the initial pollutant concentration (1–5 mg dm−3), applied current density (2–15 mA cm−2), and the coupling of ultraviolet or ultrasound radiation have been studied using a titanium plate as anode. The results show that electrochemical oxidation is able to efficiently remove methyl red, and the process efficiency decreases with the initial pollutant concentration. At high applied current densities, efficiency drastically decreases due to a less effective mass transfer of the pollutant on the anodic surface. On one hand, the coupling of ultrasound entails an antagonistic effect on the process efficiency, which is probably due to a massive formation of oxidant radicals followed by a fast recombination process. On the other hand, the coupling of ultraviolet radiation increases the process efficiency. Concomitantly to the oxidation processes, titanium electrode produces rising TiO2–anatase nanoparticles, boosting the mineralization process. This new finding sets up a significant improvement over conventional photocatalysis treatments using TiO2–anatase as a catalyst due to synergistic effects coming from the coupling of the electrochemical oxidation and photocatalysis process with Ti anode.
Complex Catalytic Materials Based on the Perovskite-Type Structure for Energy and Environmental Applications
Authors: Andrei Florin , Zăvoianu Rodica , Marcu Ioan-Cezar
Published: December 2020

This review paper focuses on perovskite-type materials as (photo)catalysts for energy and environmental applications. After a short introduction and the description of the structure of inorganic and hybrid organic-inorganic perovskites, the methods of preparation of inorganic perovskites both as powders via chemical routes and as thin films via laser-based techniques are tackled with, for the first, an analysis of the influence of the preparation method on the specific surface area of the material obtained. Then, the (photo)catalytic applications of the perovskites in energy production either in the form of hydrogen via water photodecomposition or by methane combustion, and in the removal of organic pollutants from waste waters, are reviewed.
Bacterial Biofilm Formation Using PCL/Curcumin Electrospun Fibers and Its Potential Use for Biotechnological Applications
Authors: Pompa-Monroy Daniella Alejandra , Figueroa-Marchant Paulina Guadalupe , Dastager Syed G. , Thorat Meghana Namdeo , Iglesias Ana Leticia , Miranda-Soto Valentín , Pérez-González Graciela Lizeth , Villarreal-Gómez Luis Jesús
Published: December 2020

Electrospun nanofibers are used for many applications due to their large surface area, mechanical properties, and bioactivity. Bacterial biofilms are the cause of numerous problems in biomedical devices and in the food industry. On the other hand, these bacterial biofilms can produce interesting metabolites. Hence, the objective of this study is to evaluate the efficiency of poly (Ɛ- caprolactone)/Curcumin (PCL/CUR) nanofibers to promote bacterial biofilm formation. These scaffolds were characterized by scanning electron microscopy (SEM), which showed homogeneous fibers with diameters between 441–557 nm; thermogravimetric analysis and differential scanning calorimetry (TGA and DSC) demonstrated high temperature resilience with degradation temperatures over >350 °C; FTIR and 1H-NMR serve as evidence of CUR incorporation in the PCL fibers. PCL/CUR scaffolds successfully promoted the formation of Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa biofilms. These results will be valuable in the study of controlled harvesting of pathogenic biofilms as well as in metabolites production for biotechnological purposes.