bluuebunny/crossref_metadata_2025 huggingface dataset:
Searching for New Tools to Counteract the Helicobacter pylori Resistance: The Positive Action of Resveratrol Derivatives
Authors: Di Fermo Paola , Di Lodovico Silvia , Amoroso Rosa , De Filippis Barbara , D’Ercole Simonetta , Di Campli Emanuela , Cellini Luigina , Di Giulio Mara
Published: December 2020

The drug-resistance phenomenon in Helicobacter pylori underlines the need of novel strategies to improve the eradication rate including alternative treatments combining antibiotic and non-antibiotic compounds with synergistic action. In this study, the antibacterial (MIC/MBC) and anti-virulence effects (biofilm reduction and swarming motility inhibition) of resveratrol-RSV and new synthetized RSV-phenol derivatives, with a higher bioavailability, alone and combined with levofloxacin-LVX were evaluated against resistant H. pylori clinical strains. The experiments were confirmed in vivo using the Galleria mellonella model. Among the studied RSV derivatives, RSV-3 and RSV-4 possessed higher antibacterial activity with respect to RSV (MICs from 6.25 to 200 µg/mL and from 3.12 to 200 µg/mL, respectively). RSV, RSV-3, and RSV-4 were able to synergize with LVX restoring its effect in two out of seven clinical resistant strains tested for the study. RSV, RSV-3, and RSV-4, alone and with LVX at sub-MIC and sub-synergistic concentrations, significantly reduced the biofilm formation. Moreover, RSV-3 and RSV-4 reduced the H. pylori swarming motility on soft agar. RSV, RSV-3, and RSV-4 were non-toxic for G. mellonella larvae and displayed a protective effect against H. pylori infection. Overall, RSV–phenol derivatives should be considered interesting candidates for innovative therapeutic schemes to tackle the H. pylori antibiotic resistance.
Influence of Low-Pressure Plasma on the Surface Properties of CAD-CAM Leucite-Reinforced Feldspar and Resin Matrix Ceramics
Authors: Sevilla Pablo , Lopez-Suarez Carlos , Pelaez Jesús , Tobar Celia , Rodriguez-Alonso Veronica , Suarez María J.
Published: December 2020

The introduction of new ceramic materials for dental restorations is currently a reality; however, little information is available on their surface treatment for the bonding process. Furthermore, surface treatment with plasma on ceramic materials has been recently introduced, although not many studies are available. The aim of this study was to evaluate the surface properties of a leucite-reinforced feldspar ceramic (LIC) and resin matrix ceramic (RMC) after low-pressure plasma treatment. From each material, 48 discs were prepared and subject to surface treatment. The LIC group was treated by hydrofluoric acid (HF) (LIC-HF), plasma with oxygen (LIC-O2), and plasma with argon (LIC-Ar). The RMC group was treated by sandblasting with alumina (RMC-SB), plasma with oxygen (RMC-O2), and plasma with argon (RMC-Ar). The groups whose surfaces were not subjected to treatment were considered as the control group. Surface wettability and roughness was analyzed. The results showed significant differences among the treatments for both ceramics regarding wettability and roughness. Plasma treatments increased the wettability and had a very low effect on the roughness. Plasma treatments achieved similar values for both surface properties in each ceramic group with no differences between both treatments. Plasma treatment seems to be a promising alternative for ceramic surface treatments since it increased the surface energy of the ceramics analyzed and hardly affects the roughness. Further studies are necessary to evaluate the effect of plasma treatment on the bond strength of ceramics.
Occlusion Effect in Response to Stimulation by Soft Tissue Conduction-Implications
Authors: Geal-Dor Miriam , Adelman Cahtia , Chordekar Shai , Sohmer Haim
Published: December 2020

To gain insight into the broader implications of the occlusion effect (OE—difference between unoccluded and occluded external canal thresholds), the OE in response to pure tones at 0.5, 1.0, 2.0 and 4.0 kHz to two bone conduction sites (mastoid and forehead) and two soft tissue conduction (STC) sites (under the chin and at the neck) were assessed. The OE was present at the soft tissue sites and at the bone conduction sites, with no statistical difference between them. The OE was significantly greater at lower frequencies, and negligible at higher frequencies. It seems that the vibrations induced in the soft tissues (STC) during stimulation at the soft tissue sites are conducted not only to the inner ear and elicit hearing, but also reach the walls of the external canal and initiate air pressures in the occluded canal which drive the tympanic membrane and excite the inner ear, leading to hearing. Use of a stethoscope by the internist to hear intrinsic body sounds (heartbeat, blood flow) serves as a clear demonstration of STC and its relation to hearing.
Highly Sensitive Detection of Zika Virus Nonstructural Protein 1 in Serum Samples by a Two-Site Nanobody ELISA
Authors: Delfin-Riela Triana , Rossotti Martín , Alvez-Rosado Romina , Leizagoyen Carmen , González-Sapienza Gualberto
Published: December 2020

The Zika virus was introduced in Brazil in 2015 and, shortly after, spread all over the Americas. Nowadays, it remains present in more than 80 countries and represents a major threat due to some singularities among other flaviviruses. Due to its easy transmission, high percentage of silent cases, the severity of its associated complications, and the lack of prophylactic methods and effective treatments, it is essential to develop reliable and rapid diagnostic tests for early containment of the infection. Nonstructural protein 1 (NS1), a glycoprotein involved in all flavivirus infections, is secreted since the beginning of the infection into the blood stream and has proven to be a valuable biomarker for the early diagnosis of other flaviviral infections. Here, we describe the development of a highly sensitive nanobody ELISA for the detection of the NS1 protein in serum samples. Nanobodies were selected from a library generated from a llama immunized with Zika NS1 (ZVNS1) by a two-step high-throughput screening geared to identify the most sensitive and specific nanobody pairs. The assay was performed with a sub-ng/mL detection limit in the sera and showed excellent reproducibility and accuracy when validated with serum samples spiked with 0.80, 1.60, or 3.10 ng/mL of ZVNS1. Furthermore, the specificity of the developed ELISA was demonstrated using a panel of flavivirus’ NS1 proteins; this is of extreme relevance in countries endemic for more than one flavivirus. Considering that the nanobody sequences are provided, the assay can be reproduced in any laboratory at low cost, which may help to strengthen the diagnostic capacity of the disease even in low-resource countries.
Carotenoids in Cancer Metastasis—Status Quo and Outlook
Authors: Koklesova Lenka , Liskova Alena , Samec Marek , Zhai Kevin , Abotaleb Mariam , Ashrafizadeh Milad , Brockmueller Aranka , Shakibaei Mehdi , Biringer Kamil , Bugos Ondrej , Najafi Masoud , Golubnitschaja Olga , Büsselberg Dietrich , Kubatka Peter
Published: December 2020

Metastasis represents a major obstacle in cancer treatment and the leading cause of cancer-related deaths. Therefore, the identification of compounds targeting the multi-step and complex process of metastasis could improve outcomes in the management of cancer patients. Carotenoids are naturally occurring pigments with a plethora of biological activities. Carotenoids exert a potent anti-cancer capacity in various cancer models in vitro and in vivo, mediated by the modulation of signaling pathways involved in the migration and invasion of cancer cells and metastatic progression, including key regulators of the epithelial–mesenchymal transition and regulatory molecules, such as matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), urokinase plasminogen activator (uPA) and its receptor (uPAR), hypoxia-inducible factor-1α (HIF-1α), and others. Moreover, carotenoids modulate the expression of genes associated with cancer progression and inflammatory processes as key mediators of the complex process involved in metastasis. Nevertheless, due to the predominantly preclinical nature of the known anti-tumor effects of carotenoids, and unclear results from certain carotenoids in specific cancer types and/or specific parts of the population, a precise analysis of the anti-cancer effects of carotenoids is essential. The identification of carotenoids as effective compounds targeting the complex process of cancer progression could improve the outcomes of advanced cancer patients.
In Vitro Differentiation of Human Placenta-Derived Multipotent Cells into Schwann-Like Cells
Authors: Juan Chung-Hau , Chen Mei-Hsiu , Lin Feng-Hui , Wong Chih-Shung , Chien Chih-Cheng , Chen Ming-Hong
Published: December 2020

Human placenta-derived multipotent stem cells (PDMCs) resembling embryonic stem cells can differentiate into three germ layer cells, including ectodermal lineage cells, such as neurons, astrocytes, and oligodendrocytes. The favorable characteristics of noninvasive cell harvesting include fewer ethical, religious, and legal considerations as well as accessible and limitless supply. Thus, PDMCs are attractive for cell-based therapy. The Schwann cell (SC) is the most common cell type used for tissue engineering such as nerve regeneration. However, the differentiation potential of human PDMCs into SCs has not been demonstrated until now. In this study, we evaluated the potential of PDMCs to differentiate into SC-like cells in a differentiation medium. After induction, PDMCs not only exhibited typical SC spindle-shaped morphology but also expressed SC markers, including S100, GFAP, p75, MBP, and Sox 10, as revealed by immunocytochemistry. Moreover, a reverse transcription-quantitative polymerase chain reaction analysis revealed the elevated gene expression of S100, GFAP, p75, MBP, Sox-10, and Krox-20 after SC induction. A neuroblastoma cell line, SH-SY5Y, was cultured in the conditioned medium (CM) collected from PDMC-differentiated SCs. The growth rate of the SH-SY5Y increased in the CM, indicating the function of PDMC-induced SCs. In conclusion, human PDMCs can be differentiated into SC-like cells and thus are an attractive alternative to SCs for cell-based therapy in the future.
The 10/5 Repeated Jumps Test: Are 10 Repetitions and Three Trials Necessary?
Authors: Stratford Callum , Dos’Santos Thomas , McMahon John J.
Published: December 2020

The purpose of this study was to identify whether ten repetitions and three trials were necessary to achieve stability in peak reactive strength index (RSI) during the 10/5 repeated jumps test (RJT). Twenty-five males, from multiple sports, performed three trials of the RJT on an in-ground force plate, with 90 seconds’ rest between trials. Intraclass correlation coefficients (ICC = 0.916–0.986) and coefficients of variation (CV ≤ 14.5%) were considered acceptable for all variables. Repeated-measures analysis of variance and Freidman’s tests revealed large and significant differences (p ≤ 0.006, η2 = 0.159–0.434, power ≥ 0.859) in ground contact time (GCT), jump height (JH), and subsequently RSI both between trials and repetitions. Pairwise comparisons revealed that repetitions 1–3 produced longer GCTs (p ≤ 0.05, d = 0.41–1.40), lower JHs (p ≤ 0.05, d = 0.31–0.56), and lower RSI values (p ≤ 0.05, d = 0.35–1.24). The shortest GCTs, greatest JHs and greater RSIs occurred between repetitions 7 and 10, with approximately 60% of peak RSIs occurring during these ranges. The sequential estimate technique revealed that seven repetitions were needed to attain stability in mean peak RSI. Non-significant (p = 0.554) and negligible differences (d ≤ 0.09) in the five best RSIs between trials were noted. One trial of the 10/5 RJT is sufficient to evaluate peak RSI in athletes and should reduce data collection time and fatigue.
Role of Natural Killer Cells in Uveal Melanoma
Authors: Javed Asad , Milhem Mohammed
Published: December 2020

Uveal melanoma has a high mortality rate following metastasis to the liver. Despite advances in systemic immune therapy, treatment of metastatic uveal melanoma (MUM) has failed to achieve long term durable responses. Barriers to success with immune therapy include the immune regulatory nature of uveal melanoma as well as the immune tolerant environment of the liver. To adequately harness the anti-tumor potential of the immune system, non-T cell-based approaches need to be explored. Natural Killer (NK) cells possess potent ability to target tumor cells via innate and adaptive responses. In this review, we discuss evidence that highlights the role of NK cell surveillance and targeting of uveal melanoma. We also discuss the repertoire of intra-hepatic NK cells. The human liver has a vast and diverse lymphoid population and NK cells comprise 50% of the hepatic lymphocytes. Hepatic NK cells share a common niche with uveal melanoma micro-metastasis within the liver sinusoids. It is, therefore, crucial to understand and investigate the role of intra-hepatic NK cells in the control or progression of MUM.
Single Cell Detection of the p53 Protein by Mass Cytometry
Authors: Fagerholt Oda Helen Eck , Hellesøy Monica , Gullaksen Stein-Erik , Gjertsen Bjørn Tore
Published: December 2020

Purpose: The p53 protein and its post-translational modifications are distinctly expressed in various normal cell types and malignant cells and are usually detected by immunohistochemistry and flow cytometry in contemporary diagnostics. Here, we describe an approach for simultaneous multiparameter detection of p53, its post-translational modifications and p53 pathway-related signaling proteins in single cells using mass cytometry. Method: We conjugated p53-specific antibodies to metal tags for detection by mass cytometry, allowing the detection of proteins and their post-translational modifications in single cells. We provide an overview of the antibody validation process using relevant biological controls, including cell lines treated in vitro with a stimulus (irradiation) known to induce changes in the expression level of p53. Finally, we present the potential of the method through investigation of primary samples from leukemia patients with distinct TP53 mutational status. Results: The p53 protein can be detected in cell lines and in primary samples by mass cytometry. By combining antibodies for p53-related signaling proteins with a surface marker panel, we show that mass cytometry can be used to decipher the single cell p53 signaling pathway in heterogeneous patient samples. Conclusion: Single cell profiling by mass cytometry allows the investigation of the p53 functionality through examination of relevant downstream signaling proteins in normal and malignant cells. Our work illustrates a novel approach for single cell profiling of p53.
Machine Learning Based Analysis of Human Serum N-glycome Alterations to Follow up Lung Tumor Surgery
Authors: Mészáros Brigitta , Járvás Gábor , Kun Renáta , Szabó Miklós , Csánky Eszter , Abonyi János , Guttman András
Published: December 2020

The human serum N-glycome is a valuable source of biomarkers for malignant diseases, already utilized in multiple studies. In this paper, the N-glycosylation changes in human serum proteins were analyzed after surgical lung tumor resection. Seventeen lung cancer patients were involved in this study and the N-glycosylation pattern of their serum samples was analyzed before and after the surgery using capillary electrophoresis separation with laser-induced fluorescent detection. The relative peak areas of 21 N-glycans were evaluated from the acquired electropherograms using machine learning-based data analysis. Individual glycans as well as their subclasses were taken into account during the course of evaluation. For the data analysis, both discrete (e.g., smoker or not) and continuous (e.g., age of the patient) clinical parameters were compared against the alterations in these 21 N-linked carbohydrate structures. The classification tree analysis resulted in a panel of N-glycans, which could be used to follow up on the effects of lung tumor surgical resection.
Inflammation Is a Mediating Factor in the Association between Lifestyle and Fatigue in Colorectal Cancer Patients
Authors: Wesselink Evertine , van Baar Harm , van Zutphen Moniek , Tibosch Meilissa , Kouwenhoven Ewout A. , Keulen Eric T.P. , Kok Dieuwertje , van Halteren Henk K. , Breukink Stephanie O. , de Wilt Johannes H. W. , Weijenberg Matty P. , Kenkhuis Marlou-Floor , Balvers Michiel G. J. , Witkamp Renger F. , van Duijnhoven Fränzel J. B. , Kampman Ellen , Beijer Sandra , Bours Martijn J. L. , Winkels Renate M.
Published: December 2020

Fatigue is very common among colorectal cancer (CRC) patients. We examined the association between adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) lifestyle recommendations and fatigue among stage I-III CRC patients, and whether inflammation mediated this association. Data from two prospective cohort studies were used. Adherence to the WCRF/AICR recommendations was expressed as a score ranging from 0–7, and assessed shortly after diagnosis. Six months post-diagnosis, fatigue was assessed with the European Organization for Research and Treatment of Cancer quality of life questionnaire C30 (EORTC QLQ-C30), and in a subpopulation, the plasma levels of inflammation markers (IL6, IL8, TNFα, and hsCRP) were assessed. Multiple linear regression analyses were performed to investigate the association between adherence to the WCRF/AICR recommendations and fatigue. To test mediation by inflammation, the PROCESS analytic tool developed by Hayes was used. A higher WCRF/AICR adherence score was associated with less fatigue six months after diagnosis (n = 1417, β −2.22, 95%CI −3.65; −0.78). In the population of analysis for the mediation analyses (n = 551), the total association between lifestyle and fatigue was (β −2.17, 95% CI −4.60; 0.25). A statistically significant indirect association via inflammation was observed (β −0.97, 95% CI −1.92; −0.21), explaining 45% of the total association between lifestyle and fatigue (−0.97/−2.17 × 100). Thus, inflammation is probably one of the underlying mechanisms linking lifestyle to fatigue.
The Collagen-Based Medical Device MD-Tissue Acts as a Mechanical Scaffold Influencing Morpho-Functional Properties of Cultured Human Tenocytes
Authors: Randelli Filippo , Sartori Patrizia , Carlomagno Cristiano , Bedoni Marzia , Menon Alessandra , Vezzoli Elena , Sommariva Michele , Gagliano Nicoletta
Published: December 2020

Mechanotransduction is the ability of cells to translate mechanical stimuli into biochemical signals that can ultimately influence gene expression, cell morphology and cell fate. Tenocytes are responsible for tendon mechanical adaptation converting mechanical stimuli imposed during mechanical loading, thus affecting extracellular matrix homeostasis. Since we previously demonstrated that MD-Tissue, an injectable collagen-based medical compound containing swine-derived collagen as the main component, is able to affect tenocyte properties, the aim of this study was to analyze whether the effects triggered by MD-Tissue were based on mechanotransduction-related mechanisms. For this purpose, MD-Tissue was used to coat Petri dishes and cytochalasin B was used to deprive tenocytes of mechanical stimulation mediated by the actin cytoskeleton. Cell morphology, migration, collagen turnover pathways and the expression of key mechanosensors were analyzed by morphological and molecular methods. Our findings confirm that MD-Tissue affects collagen turnover pathways and favors cell migration and show that the MD-Tissue-induced effect represents a mechanical input involving the mechanotransduction machinery. Overall, MD-Tissue, acting as a mechanical scaffold, could represent an effective medical device for a novel therapeutic, regenerative and rehabilitative approach to favor tendon healing in tendinopathies.
Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction
Authors: Zhao Fuguang , Vakhrusheva Olesya , Markowitsch Sascha D. , Slade Kimberly S. , Tsaur Igor , Cinatl Jindrich , Michaelis Martin , Efferth Thomas , Haferkamp Axel , Juengel Eva
Published: December 2020

Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1–100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.
Hormone Receptor Loss in Breast Cancer: Molecular Mechanisms, Clinical Settings, and Therapeutic Implications
Authors: Zattarin Emma , Leporati Rita , Ligorio Francesca , Lobefaro Riccardo , Vingiani Andrea , Pruneri Giancarlo , Vernieri Claudio
Published: December 2020

Hormone receptor-positive breast cancer (HR+ BC) accounts for approximately 75% of new BC diagnoses. Despite the undisputable progresses obtained in the treatment of HR+ BC in recent years, primary or acquired resistance to endocrine therapies still represents a clinically relevant issue, and is largely responsible for disease recurrence after curative surgery, as well as for disease progression in the metastatic setting. Among the mechanisms causing primary or acquired resistance to endocrine therapies is the loss of estrogen/progesterone receptor expression, which could make BC cells independent of estrogen stimulation and, consequently, resistant to estrogen deprivation or the pharmacological inhibition of estrogen receptors. This review aims at discussing the molecular mechanisms and the clinical implications of HR loss as a result of the therapies used in the neoadjuvant setting or for the treatment of advanced disease in HR+ BC patients.
Cell Sheets Restore Secretory Function in Wounded Mouse Submandibular Glands
Authors: dos Santos Harim T. , Kim Kyungsook , Okano Teruo , Camden Jean M. , Weisman Gary A. , Baker Olga J. , Nam Kihoon
Published: December 2020

Thermoresponsive cell culture plates release cells as confluent living sheets in response to small changes in temperature, with recovered cell sheets retaining functional extracellular matrix proteins and tight junctions, both of which indicate formation of intact and functional tissue. Our recent studies demonstrated that cell sheets are highly effective in promoting mouse submandibular gland (SMG) cell differentiation and recovering tissue integrity. However, these studies were performed only at early time points and extension of the observation period is needed to investigate duration of the cell sheets. Thus, the goal of this study was to demonstrate that treatment of wounded mouse SMG with cell sheets is capable of increasing salivary epithelial integrity over extended time periods. The results indicate that cell sheets promote tissue organization as early as eight days after transplantation and that these effects endure through Day 20. Furthermore, cell sheet transplantation in wounded SMG induces a significant time-dependent enhancement of cell polarization, differentiation and ion transporter expression. Finally, this treatment restored saliva quantity to pre-wounding levels at both eight and twenty days post-surgery and significantly improved saliva quality at twenty days post-surgery. These data indicate that cell sheets engineered with thermoresponsive cell culture plates are useful for salivary gland regeneration and provide evidence for the long-term stability of cell sheets, thereby offering a potential new therapeutic strategy for treating hyposalivation.
Glycosaminoglycan Modification of Decorin Depends on MMP14 Activity and Regulates Collagen Assembly
Authors: Daquinag Alexes C. , Gao Zhanguo , Fussell Cale , Sun Kai , Kolonin Mikhail G.
Published: December 2020

Proper processing of collagens COL1 and COL6 is required for normal function of adipose tissue and skeletal muscle. Proteoglycan decorin (DCN) regulates collagen fiber formation. The amino-terminus of DCN is modified with an O-linked glycosaminoglycan (GAG), the function of which has remained unclear. Previously, non-glycanated DCN (ngDCN) was identified as a marker of adipose stromal cells. Here, we identify MMP14 as the metalloprotease that cleaves DCN to generate ngDCN. We demonstrate that mice ubiquitously lacking DCN GAG (ngDCN mice) have reduced matrix rigidity, enlarged adipocytes, fragile skin, as well as skeletal muscle hypotrophy, fibrosis, and dysfunction. Our results indicate that DCN deglycanation results in reduced intracellular DCN—collagen binding and increased production of truncated COL6 chains, leading to aberrant procollagen processing and extracellular localization. This study reveals that the GAG of DCN functions to regulate collagen assembly in adipose tissue and skeletal muscle and uncovers a new mechanism of matrix dysfunction in obesity and aging.
Cyclin D1 in Cancer: A Molecular Connection for Cell Cycle Control, Adhesion and Invasion in Tumor and Stroma
Authors: Montalto Francesca Ida , De Amicis Francesca
Published: December 2020

Cyclin D1, an important regulator of cell cycle, carries out a central role in the pathogenesis of cancer determining uncontrolled cellular proliferation. In normal cells, Cyclin D1 expression levels are strictly regulated, conversely, in cancer, its activity is intensified in various manners. Different studies demonstrate that CCDN1 gene is amplified in several tumor types considering it as a negative prognostic marker of this pathology. Cyclin D1 is known for its role in the nucleus, but recent clinical studies associate the amount located in the cytoplasmic membrane with tumor invasion and metastasis. Cyclin D1 has also other functions: it governs the expression of specific miRNAs and it plays a crucial role in the tumor-stroma interactions potentiating most of the cancer hallmarks. In the present review, we will summarize the current scientific evidences that highlight the involvement of Cyclin D1 in the pathogenesis of different types of cancer, best of all in breast cancer. We will also focus on recent insights regarding the Cyclin D1 as molecular bridge between cell cycle control, adhesion, invasion, and tumor/stroma/immune-system interplay in cancer.
High Mobility Group Box-1 and Blood–Brain Barrier Disruption
Authors: Nishibori Masahiro , Wang Dengli , Ousaka Daiki , Wake Hidenori
Published: December 2020

Increasing evidence suggests that inflammatory responses are involved in the progression of brain injuries induced by a diverse range of insults, including ischemia, hemorrhage, trauma, epilepsy, and degenerative diseases. During the processes of inflammation, disruption of the blood–brain barrier (BBB) may play a critical role in the enhancement of inflammatory responses and may initiate brain damage because the BBB constitutes an interface between the brain parenchyma and the bloodstream containing blood cells and plasma. The BBB has a distinct structure compared with those in peripheral tissues: it is composed of vascular endothelial cells with tight junctions, numerous pericytes surrounding endothelial cells, astrocytic endfeet, and a basement membrane structure. Under physiological conditions, the BBB should function as an important element in the neurovascular unit (NVU). High mobility group box-1 (HMGB1), a nonhistone nuclear protein, is ubiquitously expressed in almost all kinds of cells. HMGB1 plays important roles in the maintenance of chromatin structure, the regulation of transcription activity, and DNA repair in nuclei. On the other hand, HMGB1 is considered to be a representative damage-associated molecular pattern (DAMP) because it is translocated and released extracellularly from different types of brain cells, including neurons and glia, contributing to the pathophysiology of many diseases in the central nervous system (CNS). The regulation of HMGB1 release or the neutralization of extracellular HMGB1 produces beneficial effects on brain injuries induced by ischemia, hemorrhage, trauma, epilepsy, and Alzheimer’s amyloidpathy in animal models and is associated with improvement of the neurological symptoms. In the present review, we focus on the dynamics of HMGB1 translocation in different disease conditions in the CNS and discuss the functional roles of extracellular HMGB1 in BBB disruption and brain inflammation. There might be common as well as distinct inflammatory processes for each CNS disease. This review will provide novel insights toward an improved understanding of a common pathophysiological process of CNS diseases, namely, BBB disruption mediated by HMGB1. It is proposed that HMGB1 might be an excellent target for the treatment of CNS diseases with BBB disruption.
The Close Relationship between the Golgi Trafficking Machinery and Protein Glycosylation
Authors: Frappaolo Anna , Karimpour-Ghahnavieh Angela , Sechi Stefano , Giansanti Maria Grazia
Published: December 2020

Glycosylation is the most common post-translational modification of proteins; it mediates their correct folding and stability, as well as their transport through the secretory transport. Changes in N- and O-linked glycans have been associated with multiple pathological conditions including congenital disorders of glycosylation, inflammatory diseases and cancer. Glycoprotein glycosylation at the Golgi involves the coordinated action of hundreds of glycosyltransferases and glycosidases, which are maintained at the correct location through retrograde vesicle trafficking between Golgi cisternae. In this review, we describe the molecular machinery involved in vesicle trafficking and tethering at the Golgi apparatus and the effects of mutations in the context of glycan biosynthesis and human diseases.
Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications
Authors: Aurilio Gaetano , Cimadamore Alessia , Mazzucchelli Roberta , Lopez-Beltran Antonio , Verri Elena , Scarpelli Marina , Massari Francesco , Cheng Liang , Santoni Matteo , Montironi Rodolfo
Published: December 2020

Around 80–90% of prostate cancer (PCa) cases are dependent on androgens at initial diagnosis; hence, androgen ablation therapy directed toward a reduction in serum androgens and the inhibition of androgen receptor (AR) is generally the first therapy adopted. However, the patient’s response to androgen ablation therapy is variable, and 20–30% of PCa cases become castration resistant (CRPCa). Several mechanisms can guide treatment resistance to anti-AR molecules. In this regard, AR-dependent and -independent resistance mechanisms can be distinguished within the AR pathway. In this article, we investigate the multitude of AR signaling aspects, encompassing the biological structure of AR, current AR-targeted therapies, mechanisms driving resistance to AR, and AR crosstalk with other pathways, in an attempt to provide a comprehensive review for the PCa research community. We also summarize the new anti-AR drugs approved in non-metastatic castration-resistant PCa, in the castration-sensitive setting, and combination therapies with other drugs.
The Role of Protein Disorder in Nuclear Transport and in Its Subversion by Viruses
Authors: Wubben Jacinta M. , Atkinson Sarah C. , Borg Natalie A.
Published: December 2020

The transport of host proteins into and out of the nucleus is key to host function. However, nuclear transport is restricted by nuclear pores that perforate the nuclear envelope. Protein intrinsic disorder is an inherent feature of this selective transport barrier and is also a feature of the nuclear transport receptors that facilitate the active nuclear transport of cargo, and the nuclear transport signals on the cargo itself. Furthermore, intrinsic disorder is an inherent feature of viral proteins and viral strategies to disrupt host nucleocytoplasmic transport to benefit their replication. In this review, we highlight the role that intrinsic disorder plays in the nuclear transport of host and viral proteins. We also describe viral subversion mechanisms of the host nuclear transport machinery in which intrinsic disorder is a feature. Finally, we discuss nuclear import and export as therapeutic targets for viral infectious disease.
Ca2+ Dyshomeostasis Disrupts Neuronal and Synaptic Function in Alzheimer’s Disease
Authors: McDaid John , Mustaly-Kalimi Sarah , Stutzmann Grace E.
Published: December 2020

Ca2+ homeostasis is essential for multiple neuronal functions and thus, Ca2+ dyshomeostasis can lead to widespread impairment of cellular and synaptic signaling, subsequently contributing to dementia and Alzheimer’s disease (AD). While numerous studies implicate Ca2+ mishandling in AD, the cellular basis for loss of cognitive function remains under investigation. The process of synaptic degradation and degeneration in AD is slow, and constitutes a series of maladaptive processes each contributing to a further destabilization of the Ca2+ homeostatic machinery. Ca2+ homeostasis involves precise maintenance of cytosolic Ca2+ levels, despite extracellular influx via multiple synaptic Ca2+ channels, and intracellular release via organelles such as the endoplasmic reticulum (ER) via ryanodine receptor (RyRs) and IP3R, lysosomes via transient receptor potential mucolipin channel (TRPML) and two pore channel (TPC), and mitochondria via the permeability transition pore (PTP). Furthermore, functioning of these organelles relies upon regulated inter-organelle Ca2+ handling, with aberrant signaling resulting in synaptic dysfunction, protein mishandling, oxidative stress and defective bioenergetics, among other consequences consistent with AD. With few effective treatments currently available to mitigate AD, the past few years have seen a significant increase in the study of synaptic and cellular mechanisms as drivers of AD, including Ca2+ dyshomeostasis. Here, we detail some key findings and discuss implications for future AD treatments.
The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
Authors: Rybalka Emma , Timpani Cara , Debruin Danielle , Bagaric Ryan , Campelj Dean , Hayes Alan
Published: December 2020

Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcome measures selected: the myostatin inhibition story, thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models have failed to translate into clinical benefit to patients have been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.
Long-Term Rainfall Trends and Their Variability in Mainland Portugal in the Last 106 Years
Authors: Portela Maria Manuela , Espinosa Luis Angel , Zelenakova Martina
Published: December 2020

This study addresses the long-term rainfall trends, their temporal variability and uncertainty over mainland Portugal, a small country on the most western European coast. The study was based on monthly, seasonal and annual rainfall series spanning for a period of 106 years, between October 1913 and September 2019 (herein after referred to as global period), at 532 rain gauges evenly distributed over the country (c.a. 6 rain gauges per 1000 km2). To understand the rainfall behavior over time, an initial sub-period with 55 years and a final sub-period with 51 years were also analyzed along with the global period. The trends identification and the assessment of their magnitude were derived using the nonparametric Mann-Kendall (MK) test coupled with the Sen’s slope estimator method. The results showed that after the initial sub-period with prevailing increasing rainfall, the trends were almost exclusively decreasing. They were also so pronounced that they counterbalanced the initial rainfall increase and resulted in equally decreasing trends for the global period. The study also shows that approximately from the late 1960s on, the rainy season pattern has changed, with the last months prior to the dry season showing a sustained decrease of their relative contributions to the annual rainfalls. Overall, the results support the hypothesis of less uncertainty on the pronounced decrease of rainfall over mainland Portugal in recent years, which is expected to continue. They also show that the asymmetry between a less wet North, yet still wet, and an arid South is becoming much more marked.
Thermal Stability of Rare Earth-PYSZ Thermal Barrier Coating with High-Resolution Transmission Electron Microscopy
Authors: Mahalingam Savisha , Manap Abreeza , Yunus Salmi Mohd , Afandi Nurfanizan
Published: December 2020

Durability of a thermal barrier coating (TBC) depends strongly on the type of mixed oxide in the thermally grown oxide (TGO) of a TBC. This study aims on discovering the effect of thermal stability in the TGO area containing mixed oxides. Two different bondcoats were studied using high-resolution transmission electron microscopy: high-velocity oxygen fuel (HVOF) and air-plasma spray (APS), under isothermal and thermal cyclic tests at 1400 °C. The HVOF bondcoats were intact until 1079 cycles. In comparison, APS failed at the early stage of thermal cycling at 10 cycles. The phase transformation of topcoat from tetragonal to the undesired monoclinic was observed, leading to TBC failure. The results showed that the presence of transient aluminas found in HVOF bondcoat helps in the slow growth of α-Al2O3. In contrast, the APS bondcoat does not contain transient aluminas and transforms quickly to α-Al2O3 along with spinel and other oxides. This fast growth of mixed oxides causes stress at the interface (topcoat and TGO) and severely affects the TBC durability leading to early failure. Therefore, the mixed oxide with transient aluminas slows down the quick transformation into alpha-aluminas, which provides high thermal stability for a high TBC durability.
Investigating Hydrogen Separation in a Novel Rotating Carbon Nanotube–Carbon Nanocone Setup Using Molecular Dynamics Simulations
Authors: Muraru Sorin , Muraru Sebastian , Ionita Mariana
Published: December 2020

Hydrogen fuel cells rely on the purity of the hydrogen gas for maintaining a high performance. This study investigates a novel nanostructure design for its effectiveness in separating H2 molecules from a mixture of gases containing H2, CH4, CO2, N2, CO and H2O molecules using Molecular Dynamics simulations. Based on an open-ended (28, 0) rotating carbon nanotube with one carbon nanocone at each of its two extremes, this device is predicted through Molecular Dynamics simulations to be able to separate hydrogen from a gas mixture contained within. The nanocones were placed with their tips inside the nanotube and the size of the open channel created between the two was controlled to find a configuration that allows hydrogen to pass while restricting the other gases. Although in need of optimization, we find it capable of high selectivity and highlight captivating gas behavior insights to help advance rational gas separation device development.
Introducing Compounds: An Interdisciplinary Open Access Journal
Authors: Mejuto Juan C.
Published: December 2020

Almost 10 years have passed since the International Year of Chemistry was celebrated [...]
Development and Investigation of SiC and SiC-Based Devices
Authors: Lebedev Alexander A.
Published: December 2020

The modern development of the nuclear industry, nuclear energy, and aerospace technology is in dire need of the development of a new generation of electronics capable of operating at elevated levels of radiation and high temperatures and in chemically active environments [...]
Contact Resistance Parallel Model for Edge-Contacted 2D Material Back-Gate FET
Authors: Cai Fei , Deng Guangsheng , Li Xiangxiang , Lin Fujiang
Published: December 2020

Because 2D materials have adjust band gap, high mobility ratio, bipolar, anisotropy and flexibility characters, they have become the new direction for FET’s channel materials. According to the characteristics of the layers of 2D materials, the current transport characteristics can be improved by using the edge-contacted electrode. Moreover, the research on the current transfer mechanism between channel layers is the basis of the practical application of 2D transistors. In the research, the 2D material-MoS2 is used as the channel material, the back-gate transistors with different layers are prepared by dry etching and edge-contacted electrode structure. We also discuss the current transport mechanism of channel and established the channel resistance parallel transport model. The parallel model and TLM are used to analyze the contact resistance of the edge-contacted structure, and the total resistance, total contact resistance, and single-layer contact resistance of different layers are calculated. The parallel model is verified by dc test data. The number of channel layers is closely related to contact resistance, total resistance, and mobility. In addition, the of single MoS2 is about 7.27 kΩ·um. This contact resistance parallel model can also be applied to other 2D materials edge-contacted FET.
Some Algorithms for Computing Short-Length Linear Convolution
Authors: Cariow Aleksandr , Paplinski Janusz P.
Published: December 2020

In this article, we propose a set of efficient algorithmic solutions for computing short linear convolutions focused on hardware implementation in VLSI. We consider convolutions for sequences of length N= 2, 3, 4, 5, 6, 7, and 8. Hardwired units that implement these algorithms can be used as building blocks when designing VLSI -based accelerators for more complex data processing systems. The proposed algorithms are focused on fully parallel hardware implementation, but compared to the naive approach to fully parallel hardware implementation, they require from 25% to about 60% less, depending on the length N and hardware multipliers. Since the multiplier takes up a much larger area on the chip than the adder and consumes more power, the proposed algorithms are resource-efficient and energy-efficient in terms of their hardware implementation.
Steroid-Induced Iatrogenic Adrenal Insufficiency in Children: A Literature Review
Authors: Akahoshi Shogo , Hasegawa Yukihiro
Published: December 2020

The present review focuses on steroid-induced adrenal insufficiency (SIAI) in children and discusses the latest findings by surveying recent studies. SIAI is a condition involving adrenocorticotropic hormone (ACTH) and cortisol suppression due to high doses or prolonged administration of glucocorticoids. While its chronic symptoms, such as fatigue and loss of appetite, are nonspecific, exposure to physical stressors, such as infection and surgery, increases the risk of adrenal crisis development accompanied by hypoglycemia, hypotension, or shock. The low-dose ACTH stimulation test is generally used for diagnosis, and the early morning serum cortisol level has also been shown to be useful in screening for the condition. Medical management includes gradually reducing the amount of steroid treatment, continuing administration of hydrocortisone corresponding to the physiological range, and increasing the dosage when physical stressors are present.
Application of Fat-Tailed Sheep Tail and Backfat to Develop Novel Warthog Cabanossi with Distinct Sensory Attributes
Authors: Mahachi Leo Nyikadzino , Rudman Monlee , Arnaud Elodie , Muchenje Voster , Hoffman Louwrens Christiaan
Published: December 2020

This study compared the use of pork backfat (PF) and fat-tailed sheep tail and backfat (SF) on the physicochemical, fatty acids and sensory attributes of warthog cabanossi. There were no differences between weight loss during drying, moisture content, pH, water activity, salt content and lipid oxidation between the cabanossi types. However, protein and ash contents were higher in PF cabanossi whilst fat content was higher in SF cabanossi. The PF cabanossi had higher polyunsaturated fatty acids (especially n-6), lower monounsaturated fatty acids whilst the saturated fatty acid content was similar between the two cabanossi products. The n-3:n-6 ratio was more beneficial in the SF cabanossi. The descriptive sensory analysis showed two distinct products where PF cabanossi scored higher for most attributes. Although SF cabanossi scored less for these attributes, this cabanossi had unique and acceptable sensory attributes. This study concluded that fat-tailed sheep tail and backfat could be used to produce a unique cabanossi product of acceptable quality.
Identification of Arctic Food Fish Species for Anthropogenic Contaminant Testing Using Geography and Genetics
Authors: Walker Virginia K. , Das Pranab , Li Peiwen , Lougheed Stephen C. , Moniz Kristy , Schott Stephan , Qitsualik James , Koch Iris
Published: December 2020

The identification of food fish bearing anthropogenic contaminants is one of many priorities for Indigenous peoples living in the Arctic. Mercury (Hg), arsenic (As), and persistent organic pollutants including polychlorinated biphenyls (PCBs) are of concern, and these are reported, in some cases for the first time, for fish sampled in and around King William Island, located in Nunavut, Canada. More than 500 salmonids, comprising Arctic char, lake trout, lake whitefish, and ciscoes, were assayed for contaminants. The studied species are anadromous, migrating to the ocean to feed in the summers and returning to freshwater before sea ice formation in the autumn. Assessments of muscle Hg levels in salmonids from fishing sites on King William Island showed generally higher levels than from mainland sites, with mean concentrations generally below guidelines, except for lake trout. In contrast, mainland fish showed higher means for As, including non-toxic arsenobetaine, than island fish. Lake trout were highest in As and PCB levels, with salmonid PCB congener analysis showing signatures consistent with the legacy of cold-war distant early warning stations. After DNA-profiling, only 4–32 Arctic char single nucleotide polymorphisms were needed for successful population assignment. These results support our objective to demonstrate that genomic tools could facilitate efficient and cost-effective cluster assignment for contaminant analysis during ocean residency. We further suggest that routine pollutant testing during the current period of dramatic climate change would be helpful to safeguard the wellbeing of Inuit who depend on these fish as a staple input to their diet. Moreover, this strategy should be applicable elsewhere.