bluuebunny/crossref_metadata_2025 huggingface dataset:
Monoterpene Chemical Speciation with High Time Resolution Using a FastGC/PTR-MS: Results from the COV3ER Experiment on Quercus ilex
Authors: Bsaibes Sandy , Piel Felix , Gros Valérie , Truong François , Lafouge Florence , Ciuraru Raluca , Buysse Pauline , Kammer Julien , Loubet Benjamin , Staudt Michael
Published: June 2020

Monoterpenes (MTs) represent an important family of biogenic volatile organic compounds (BVOCs) in terms of amount and chemical diversity. This family has been extensively studied using gas chromatography (GC) and proton transfer reaction-mass spectrometry (PTR-MS). Upon recent advances with Fast Gas Chromatography (FastGC), it was also commercialized with proton transfer reaction-time of flight-mass spectrometry (PTR-ToF-MS) instruments. The combination of both techniques showed promising results in the near real-time separation of isomers, with the need of further improvements. In this study, a FastGC prototype was coupled to a conventional PTR-MS (PTR-QuadMS). Extensive laboratory experiments were performed, in order to test the system’s performance and to optimize its operational parameters for MT separation. The detection limit was determined to be around 0.8–1.7 ppbv, depending on the MT. The system was afterwards deployed during a three-week field campaign in a mixed holm oak (Quercus ilex) forest known for its important MT emissions. MTs were measured in the incoming and the outgoing air of dynamic enclosures installed on the branches of four different trees. Three chemotypes of holm oak trees could be distinguished showing consistently different proportions of the emitted MTs throughout the measurement campaign: pinene-type, myrcene-type and limonene-type. Measurements showed a systematic diel variation in emissions typical of light and temperature-dependent, de novo-synthesized VOCs. The results demonstrated the feasibility of the FastGC/PTR-MS system for continuous measurements from dynamic chambers in the field, whereas further improvements would be necessary to lower the detection limit for ambient air measurements.
Historical Radial Growth of Chinese Torreya Trees and Adaptation to Climate Change
Authors: Chen Xiongwen
Published: June 2020

Chinese Torreya is a vital crop tree with an average life span of a thousand years in subtropical China. Plantations of this tree are broadly under construction, to benefit the local economy. Information on the growth and adaptation to climate change for this species is limited, but tree rings might show responses to historical climate dynamics. In this study, six stem sections from Chinese Torreya trees between 60 and 90 years old were acquired and analyzed with local climate data. The results indicated that the accumulated radial growth increased linearly with time, even at the age of 90 years, and the average radial increment of each tree ranged from 1.9 to 5.1 mm/year. The variances of basal area increment (BAI) increased with time, and correlated with the variances of precipitation in the growing seasons. Taylor’s power law was present in the radial growth, with the scaling exponents concentrated within 1.9–2.1. A “Triangle”-shaped relationship was found between the precipitation in the growing seasons and annual radial increments. Similar patterns also appeared for the standard precipitation index, maximum monthly air temperature and minimum monthly air temperature. The annual increases were highly correlated with the local climate. Slow growth, resilience to drought and multiple stems in one tree might help the tree species adapt to different climate conditions, with the implications for plantation management discussed in this paper.
Damaging Convective and Non-Convective Winds in Southwestern Iberia during Windstorm Xola
Authors: Pinto Paulo , Belo-Pereira Margarida
Published: June 2020

On 23/12/2009, windstorm Xola struck mainland Portugal, causing serious damage in a small area north of Lisbon (Oeste region) and in the south region, inflicting economic losses of over EUR 100 million. In both areas, several power towers, designed to withstand up to 46 m s−1 winds, were destroyed. The causes of these two distinct damaging wind events were investigated. Xola was revealed to have a prominent cloud head and a split cold front structure. In the southern region, the damages were due to downburst winds, associated with a mesovortex, observed in a bow echo line triggered by an upper cold front. The cloud head presented several dry air intrusion signatures, co-located with tops progressively lowering towards the hooked tip. This tip revealed features consistent with the presence of slantwise convection, the descending branches of which may have been strengthened by evaporating cooling. At the reflectivity cloud head tip, a jet streak pattern was identified on weather radar, with Doppler velocities exceeding 55 m s−1, just 400 m above ground. This signature is coherent with the presence of a Sting jet, and this phenomenon was associated with the strongest wind gusts (over 40 m s−1) and the largest damages in the Oeste region.
How Unusual Were June 2019 Temperatures in the Context of European Climatology?
Authors: Sulikowska Agnieszka , Wypych Agnieszka
Published: June 2020

The aims of the study were to assess the severity of temperature conditions in Europe, in June 2019, using a newly developed extremes index, as well as to evaluate circulation conditions that favored the occurrence of extremely hot days in June 2019, as seen over the long term. The main focus of this work was on two European regions particularly affected by high temperatures in June 2019, namely Central Europe and Iberia. To comprehensively characterize heat events in terms of their spatial extent and intensity, we proposed the extremity index (EI) and used it to compare hot days occurring in areas of different sizes and with different climatic conditions. The role of atmospheric circulation in the occurrence of hot days was evaluated using the Grosswetterlagen (GWL) circulation types catalog, as well as composite maps created with the bootstrap resampling technique. Our results reveal that June 2019 was unusually hot, and in terms of the magnitude of the anomaly, it has no analogue in the 70-year-long temperature record for Europe. However, the properties of heat events in the two considered regions were substantially different. The occurrence of hot days in June 2019, in Europe, was mainly associated with the GWL types forcing advection from the southern sector and co-occurrence of high-pressure systems which was significantly proven by the results of bootstrap resampling. In terms of the applicability of the new approach, the EI proved to be a useful tool for the analysis and evaluation of the severity of hot days based on their intensity and spatial range.
Markers of Regenerative Processes in Patients with Bipolar Disorder: A Case-control Study
Authors: Reginia Artur , Samochowiec Jerzy , Jabłoński Marcin , Ferensztajn-Rochowiak Ewa , Rybakowski Janusz K. , Telesiński Arkadiusz , Tarnowski Maciej , Misiak Błażej , Ratajczak Mariusz Z. , Kucharska-Mazur Jolanta
Published: June 2020

Progress in medical science has allowed the discovery of many factors affecting the pathogenesis of bipolar disorder, and among the most recent research directions are found regenerative and inflammatory processes. The role of regenerative processes remains particularly poorly explored, but available data encourage further research, which may explain the pathogenesis of bipolar disorder (BD). The aim of this study was to evaluate the mobilization of stem cells into peripheral blood, in patients with bipolar disorder during stable phase, not treated with lithium salts. The study included 30 unrelated individuals with the diagnosis of bipolar disorder, with disease duration of at least 10 years, not treated with lithium salts for at least five years prior to the study. The control group consisted of 30 healthy subjects, matched for age, sex, body mass index (BMI), origin, socio-demographic factors and nicotine use. Blood samples underwent cytometric analyses to assess concentrations of: Very Small Embryonic Like (VSEL) CD34+, VSEL AC133+, HSC CD34+, HSC AC133+. There were no significant differences in stem cell levels between patients with BD and healthy controls. However, the level of VSEL cells AC133 + was significantly higher in type I BD patients compared to healthy controls. Our results indicate a disturbance in regenerative processes in patients with bipolar disorder.
Mixed Type Histology as a Predictive Factor for Esophagojejunostomy Leak in Advanced Gastric Cancer
Authors: Rawicz-Pruszyński Karol , Sędłak Katarzyna , Mlak Radosław , Mielko Jerzy , Polkowski Wojciech P.
Published: June 2020

Since esophagojejunostomy leak (EJL) after gastrectomy is a potentially fatal complication and may impact the survival of patients with advanced gastric cancer (GC), it is important to establish risk factors for the EJL and to prevent this surgical complication. The aim of this study was analysis of predictors for the postoperative clinically apparent EJL. All patients operated for advanced GC between October 2016 and December 2019 were analyzed from a prospectively maintained database. The evaluation of the EJL and postoperative complications according to the demographic and clinical (categorized) variables was performed with odds ratio test (multivariate analysis was performed with the use of logistic regression method). Among the 114 patients included in the study, 71.1% received neoadjuvant chemotherapy and 19.3% underwent gastrectomy followed by the hyperthermic intraperitoneal chemotherapy (HIPEC). Postoperative EJL was found in 4.6% patients. The risk of EJL was significantly higher for mixed-type GC (OR = 12.45, 95% CI: 1.03–150.10; p = 0.0472). The risk of other postoperative complications was significantly higher in patients undergoing HIPEC (OR = 3.88, 95% CI: 1.40–10.80, p = 0.0094). The number of lymph nodes removed (>38) was characterized by 80% sensitivity and 79.6% specificity in predicting EJL (AUC = 0.80, 95% CI: 0.72–0.87; p < 0.0001). Mixed histological type of GC is a tumor-related risk factor for the EJL. HIPEC was confirmed to be a risk factor for postoperative complications after gastrectomy.
Multi-Habitat Radiomics Unravels Distinct Phenotypic Subtypes of Glioblastoma with Clinical and Genomic Significance
Authors: Choi Seung Won , Cho Hwan-Ho , Koo Harim , Cho Kyung Rae , Nenning Karl-Heinz , Langs Georg , Furtner Julia , Baumann Bernhard , Woehrer Adelheid , Cho Hee Jin , Sa Jason K. , Kong Doo-Sik , Seol Ho Jun , Lee Jung-Il , Nam Do-Hyun , Park Hyunjin
Published: June 2020

We aimed to evaluate the potential of radiomics as an imaging biomarker for glioblastoma (GBM) patients and explore the molecular rationale behind radiomics using a radio-genomics approach. A total of 144 primary GBM patients were included in this study (training cohort). Using multi-parametric MR images, radiomics features were extracted from multi-habitats of the tumor. We applied Cox-LASSO algorithm to build a survival prediction model, which we validated using an independent validation cohort. GBM patients were consensus clustered to reveal inherent phenotypic subtypes. GBM patients were successfully stratified by the radiomics risk score, a weighted sum of radiomics features, corroborating the potential of radiomics as a prognostic biomarker. Using consensus clustering, we identified three distinct subtypes which significantly differed in the prognosis (“heterogenous enhancing”, “rim-enhancing necrotic”, and “cystic” subtypes). Transcriptomic traits enriched in individual subtypes were in accordance with imaging phenotypes summarized by radiomics. For example, rim-enhancing necrotic subtype was well described by radiomics profiling (T2 autocorrelation and flat shape) and highlighted by the inflammatory genomic signatures, which well correlated to its phenotypic peculiarity (necrosis). This study showed that imaging subtypes derived from radiomics successfully recapitulated the genomic underpinnings of GBMs and thereby confirmed the feasibility of radiomics as an imaging biomarker for GBM patients with comprehensible biologic annotation.
Protein Conformational Changes in Breast Cancer Sera Using Infrared Spectroscopic Analysis
Authors: Ghimire Hemendra , Garlapati Chakravarthy , Janssen Emiel A. M. , Krishnamurti Uma , Qin Gengsheng , Aneja Ritu , Perera A. G. Unil
Published: June 2020

Protein structural alterations, including misfolding and aggregation, are a hallmark of several diseases, including cancer. However, the possible clinical application of protein conformational analysis using infrared spectroscopy to detect cancer-associated structural changes in proteins has not been established yet. The present study investigates the applicability of Fourier transform infrared spectroscopy in distinguishing the sera of healthy individuals and breast cancer patients. The cancer-associated alterations in the protein structure were analyzed by fitting the amide I (1600–1700 cm−1) band of experimental curves, as well as by comparing the ratio of the absorbance values at the amide II and amide III bands, assigning those as the infrared spectral signatures. The snapshot of the breast cancer-associated alteration in circulating DNA and RNA was also evaluated by extending the spectral fitting protocol to the complex region of carbohydrates and nucleic acids, 1140–1000 cm−1. The sensitivity and specificity of these signatures, representing the ratio of the α-helix and β-pleated sheet in proteins, were both 90%. Likewise, the ratio of amides II and amide III (I1556/I1295) had a sensitivity and specificity of 100% and 80%, respectively. Thus, infrared spectroscopy can serve as a powerful tool to understand the protein structural alterations besides distinguishing breast cancer and healthy serum samples.
Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy
Authors: Buigues Cristina , Navarro-Martínez Rut , Sánchez-Martínez Vanessa , Serrano-Carrascosa María , Rubio-Briones José , Cauli Omar
Published: June 2020

Frailty syndrome is a functional state that includes a loss of ability to react to stressors, and is associated with poor outcomes, morbidity and premature mortality. The first line treatment in many men with prostate cancer (PCa) consists of an androgen-deprivation therapy (ADT) which can promote or favor frailty syndrome and ADT may therefore favor the progression of frailty over time. Among the pathophysiological bases of frailty, the presence of chronic low-grade inflammation has been associated with its adverse outcomes, but longitudinal studies are needed to validate these biomarkers. In this study, we prospectively evaluate frailty syndrome and blood inflammatory markers (IL1-beta, IL-6, IL-8, TNF alpha, C reactive protein) and leukocytes were measured at baseline and an average of 1 year later in PCa under ADT. Frailty was defined as having three or more of the following components: low lean mass, weakness, self-reported exhaustion, low activity level, and slow walking speed; prefrailty was defined as having one or two of those components. Multinomial regression analysis showed that among the inflammatory biomarkers, those significantly and repeatedly (baseline and follow-up time points) (p < 0.05) associated with frailty syndrome were high IL-6 levels and low lymphocyte counts in blood. Other biomarkers such as IL-8, monocyte counts and C reactive protein were significantly associated with frailty syndrome (p < 0.05) in cross-sectional analyses, but they do not predict frailty progression at 1 year-follow-up. Receiver operating characteristic curve analysis showed that both lymphocyte counts and IL-6 concentration significantly (p < 0.05) (although moderately) discriminate PCa patients that progressed in the severity of frailty syndrome. IL-6 and lymphocytes count are possible biomarkers, useful for identifying frail patients and predicting the progression of frailty in PCa under ADT. Our study suggests the use of these biomarkers to guide clinical decisions on prostate cancer treatment based on a multidisciplinary approach.
The Expression of Carbonic Anhydrases II, IX and XII in Brain Tumors
Authors: Haapasalo Joonas , Nordfors Kristiina , Haapasalo Hannu , Parkkila Seppo
Published: June 2020

Carbonic anhydrases (CAs) are zinc-containing metalloenzymes that participate in the regulation of pH homeostasis in addition to many other important physiological functions. Importantly, CAs have been associated with neoplastic processes and cancer. Brain tumors represent a heterogeneous group of diseases with a frequently dismal prognosis, and new treatment options are urgently needed. In this review article, we summarize the previously published literature about CAs in brain tumors, especially on CA II and hypoxia-inducible CA IX and CA XII. We review here their role in tumorigenesis and potential value in predicting prognosis of brain tumors, including astrocytomas, oligodendrogliomas, ependymomas, medulloblastomas, meningiomas, and craniopharyngiomas. We also introduce both already completed and ongoing studies focusing on CA inhibition as a potential anti-cancer strategy.
Erratum: Castellví, M. et al. Pharmacological Modulation of SAMHD1 Activity by CDK4/6 Inhibitors Improves Anticancer Therapy. Cancers 2020, 12, 713
Authors: Castellví Marc , Felip Eudald , Ezeonwumelu Ifeanyi Jude , Badia Roger , Garcia-Vidal Edurne , Pujantell Maria , Gutiérrez-Chamorro Lucía , Teruel Iris , Martínez-Cardús Anna , Clotet Bonaventura , Riveira-Muñoz Eva , Margelí Mireia , Esté José A. , Ballana Ester
Published: June 2020

The authors wish you make the following corrections to this paper [...]
Single Nucleotide Polymorphisms in MiRNA Binding Sites of Nucleotide Excision Repair-Related Genes Predict Clinical Benefit of Oxaliplatin in FOLFOXIRI Plus Bevacizumab: Analysis of the TRIBE Trial
Authors: Suenaga Mitsukuni , Schirripa Marta , Cao Shu , Zhang Wu , Yang Dongyun , Cremolini Chiara , Murgioni Sabina , Lonardi Sara , Ning Yan , Okazaki Satoshi , Berger Martin D. , Miyamoto Yuji , Barzi Afsaneh , Loupakis Fotios , Falcone Alfredo , Lenz Heinz-Josef
Published: June 2020

Background: The nucleotide excision repair (NER) pathway participates in platinum-induced DNA damage repair. Single nucleotide polymorphisms (SNPs) in miRNA-binding sites in the NER genes RPA2 and GTF2H1 are associated with the risk of colorectal cancer (CRC). Here, we analyzed whether RPA2 and GTF2H1 SNPs predict the efficacy of oxaliplatin in metastatic CRC (mCRC) patients. Patients and methods: Genomic DNA was extracted from blood samples from 457 patients with mCRC enrolled in the TRIBE trial, which compared first-line FOLFOXIRI plus bevacizumab (BEV) (n = 230, discovery cohort) and first-line FOLFIRI plus BEV (n = 227, control cohort). SNPs were analyzed by PCR-based direct sequencing. Results: In the FOLFOXIRI + BEV-treated cohort expressing wild-type KRAS, progression-free survival (PFS) was shorter for the RPA2 rs7356 C/C variant subgroup than the any T allele subgroup in univariate analysis (9.1 versus 13.3 months respectively, hazard ratio (HR) 2.32, 95% confidence interval (CI): 1.07–5.03, p = 0.020) and this remained significant in multivariable analysis (HR 2.97, 95%CI: 1.27–6.94, p = 0.012). A similar trend was observed for overall survival. In contrast, patients expressing mutant RAS and RPA2 rs7356 C/C variant had longer PFS with FOLFOXIRI + BEV than with FOLFIRI + BEV (12.1 versus 7.6 months, HR 0.23, 95%CI: 0.09–0.62, p = 0.002) but no superiority of FOLFOXIRI + BEV was observed for the RAS mutant, RPA2 rs7356 any T variant subgroup (11.7 versus 9.6 months, HR 0.77, 95%CI: 0.56–1.07, p = 0.12) or the RAS wild-type, RPA2 rs7356 C/C variant subgroup. Conclusion: RPA2 SNPs may serve as predictive and prognostic markers of oxaliplatin responsiveness in a RAS status-dependent manner in mCRC patients receiving FOLFOXIRI + BEV.
The Potential of MLN3651 in Combination with Selumetinib as a Treatment for Merlin-Deficient Meningioma
Authors: Lyons Rimmer Jade , Ercolano Emanuela , Baiz Daniele , Makhija Mahindra , Berger Allison , Sells Todd , Stroud Steve , Hilton David , Adams Claire L. , Hanemann C Oliver
Published: June 2020

Meningioma is the most common primary intracranial tumour, and surgical resection is the main therapeutic option. Merlin is a tumour suppressor protein that is frequently mutated in meningioma. The activity of the E3 ubiquitin ligase complex, CRL4-DCAF1, and the Raf/MEK/ERK scaffold protein Kinase suppressor of Ras 1 (KSR1) are upregulated in Merlin-deficient tumours, which drives tumour growth. Identifying small molecules that inhibit these key pathways may provide an effective treatment option for patients with meningioma. We used meningioma tissue and primary cells derived from meningioma tumours to investigate the expression of DDB1 and Cullin 4-associated factor 1 (DCAF1) and KSR1, and confirmed these proteins were overexpressed. We then used primary cells to assess the therapeutic potential of MLN3651, a neddylation inhibitor which impacts the activity of the CRL family of E3 ubiquitin ligases and the MAPK/ERK kinase (MEK1/2) inhibitor selumetinib. MLN3651 treatment reduced proliferation and activated apoptosis, whilst increasing Raf/MEK/ERK pathway activation. The combination of MLN3651 and the MEK1/2 inhibitor selumetinib prevented the increase in Raf/MEK/ERK activity, and had an additive effect compared with either treatment alone. Therefore, the combined targeting of CRL4-DCAF1 and Raf/MEK/ERK activity represents an attractive novel strategy in the treatment of Merlin-deficient meningioma.
Cathelicidin-Related Antimicrobial Peptide Regulates CD73 Expression in Mouse Th17 Cells via p38
Authors: Lee Jeonghyun , Shin Kyong-Oh , Kim Yesol , Cho Jaewon , Lim Hyung W. , Yoon Sung-Il , Lee Geun-Shik , Ko Hyun-Jeong , Kim Pyeung-Hyeun , Uchida Yoshikazu , Park Kyungho , Kang Seung Goo
Published: June 2020

The effector function of tumor-infiltrated CD4+ T cells is readily suppressed by many types of immune regulators in the tumor microenvironment, which is one of the major mechanisms of immune tolerance against cancer. Cathelicidin-related antimicrobial peptide (CRAMP), the mouse analog of LL-37 peptide in humans, is a cationic antimicrobial peptide belonging to the cathelicidin family; however, its secretion by cancer cells and role in the tumor microenvironment (TME) remain unclear. In this study, we explored the possibility of an interaction between effector CD4+ T cells and CRAMP using in vitro-generated mouse Th17 cells. We found that CRAMP stimulates Th17 cells to express the ectonucleotidase CD73, while simultaneously inducing cell death. This finding suggested that CD73-expressing Th17 cells may function as immune suppressor cells instead of effector cells. In addition, treatment of pharmacological inhibitors of the transforming growth factor-beta (TGF-β) signaling pathway showed that induction of CD73 expression is mediated by the p38 signaling pathway. Overall, our findings suggest that tumor-derived LL-37 likely functions as an immune suppressor that induces immune tolerance against tumors through shaping effector Th17 cells into suppressor Th17 cells, suggesting a new intervention target to improve cancer immunotherapy.
mTORC2 Is Involved in the Induction of RSK Phosphorylation by Serum or Nutrient Starvation
Authors: Chou Po-Chien , Rajput Swati , Zhao Xiaoyun , Patel Chadni , Albaciete Danielle , Oh Won Jun , Daguplo Heineken Queen , Patel Nikhil , Su Bing , Werlen Guy , Jacinto Estela
Published: June 2020

Cells adjust to nutrient fluctuations to restore metabolic homeostasis. The mechanistic target of rapamycin (mTOR) complex 2 responds to nutrient levels and growth signals to phosphorylate protein kinases belonging to the AGC (Protein Kinases A,G,C) family such as Akt and PKC. Phosphorylation of these AGC kinases at their conserved hydrophobic motif (HM) site by mTORC2 enhances their activation and mediates the functions of mTORC2 in cell growth and metabolism. Another AGC kinase family member that is known to undergo increased phosphorylation at the homologous HM site (Ser380) is the p90 ribosomal S6 kinase (RSK). Phosphorylation at Ser380 is facilitated by the activation of the mitogen-activated protein kinase/extracellular signal regulated kinase (MAPK/ERK) in response to growth factor stimulation. Here, we demonstrate that optimal phosphorylation of RSK at this site requires an intact mTORC2. We also found that RSK is robustly phosphorylated at Ser380 upon nutrient withdrawal or inhibition of glycolysis, conditions that increase mTORC2 activation. However, pharmacological inhibition of mTOR did not abolish RSK phosphorylation at Ser380, indicating that mTOR catalytic activity is not required for this phosphorylation. Since RSK and SIN1β colocalize at the membrane during serum restimulation and acute glutamine withdrawal, mTORC2 could act as a scaffold to enhance RSK HM site phosphorylation. Among the known RSK substrates, the CCTβ subunit of the chaperonin containing TCP-1 (CCT) complex had defective phosphorylation in the absence of mTORC2. Our findings indicate that the mTORC2-mediated phosphorylation of the RSK HM site could confer RSK substrate specificity and reveal that RSK responds to nutrient fluctuations.
Boosting the Intra-Articular Efficacy of Low Dose Corticosteroid through a Biopolymeric Matrix: An In Vivo Model of Osteoarthritis
Authors: Tschon Matilde , Salamanna Francesca , Martini Lucia , Giavaresi Gianluca , Lorenzini Luca , Calzà Laura , Fini Milena
Published: June 2020

The purpose of this study was to verify the efficacy of a single intra-articular (i.a.) injection of a hyaluronic acid-chitlac (HY-CTL) enriched with two low dosages of triamcinolone acetonide (TA, 2.0 mg/mL and 4.5 mg/mL), in comparison with HY-CTL alone, with a clinical control (TA 40 mg/mL) and with saline solution (NaCl) in an in vivo osteoarthritis (OA) model. Seven days after chemical induction of OA, 80 Sprague Dawley male rats were grouped into five arms (n = 16) and received a single i.a. injection of: 40 mg/mL TA, HY-CTL alone, HY-CTL with 2.0 mg/mL TA (RV2), HY-CTL with 4.5 mg/mL TA (RV4.5) and 0.9% NaCl. Pain sensitivity and Catwalk were performed at baseline and at 7, 14 and 21 days after the i.a. treatments. The histopathology of the joint, meniscus and synovial reaction, type II collagen expression and aggrecan expression were assessed 21 days after treatments. RV4.5 improved the local pain sensitivity in comparison with TA and NaCl. RV4.5 and TA exerted similar beneficial effects in all gait parameters. Histopathological analyses, measured by Osteoarthritis Research Society International (OARSI) and Kumar scores and by immunohistochemistry, evidenced that RV4.5 and TA reduced OA features in the same manner and showed a stronger type II collagen and aggrecan expression; both treatments reduced synovitis, as measured by Krenn score and, at the meniscus level, RV4.5 improved degenerative signs as evaluated by Pauli score. TA or RV4.5 treatments limited the local articular cartilage deterioration in knee OA with an improvement of the physical structure of articular cartilage, gait parameters, the sensitivity to local pain and a reduction of the synovial inflammation.
Notch-Inflammation Networks in Regulation of Breast Cancer Progression
Authors: Liubomirski Yulia , Ben-Baruch Adit
Published: June 2020

Members of the Notch family and chronic inflammation were each separately demonstrated to have prominent malignancy-supporting roles in breast cancer. Recent investigations indicate that bi-directional interactions that exist between these two pathways promote the malignancy phenotype of breast tumor cells and of their tumor microenvironment. In this review article, we demonstrate the importance of Notch-inflammation interplays in malignancy by describing three key networks that act in breast cancer and their impacts on functions that contribute to disease progression: (1) Cross-talks of the Notch pathway with myeloid cells that are important players in cancer-related inflammation, focusing mainly on macrophages; (2) Cross-talks of the Notch pathway with pro-inflammatory factors, exemplified mainly by Notch interactions with interleukin 6 and its downstream pathways (STAT3); (3) Cross-talks of the Notch pathway with typical inflammatory transcription factors, primarily NF-κB. These three networks enhance tumor-promoting functions in different breast tumor subtypes and act in reciprocal manners, whereby Notch family members activate inflammatory elements and vice versa. These characteristics illustrate the fundamental roles played by Notch-inflammation interactions in elevating breast cancer progression and propose that joint targeting of both pathways together may provide more effective and less toxic treatment approaches in this disease.
K+ and Ca2+ Channels Regulate Ca2+ Signaling in Chondrocytes: An Illustrated Review
Authors: Suzuki Yoshiaki , Yamamura Hisao , Imaizumi Yuji , Clark Robert B. , Giles Wayne R.
Published: June 2020

An improved understanding of fundamental physiological principles and progressive pathophysiological processes in human articular joints (e.g., shoulders, knees, elbows) requires detailed investigations of two principal cell types: synovial fibroblasts and chondrocytes. Our studies, done in the past 8–10 years, have used electrophysiological, Ca2+ imaging, single molecule monitoring, immunocytochemical, and molecular methods to investigate regulation of the resting membrane potential (ER) and intracellular Ca2+ levels in human chondrocytes maintained in 2-D culture. Insights from these published papers are as follows: (1) Chondrocyte preparations express a number of different ion channels that can regulate their ER. (2) Understanding the basis for ER requires knowledge of (a) the presence or absence of ligand (ATP/histamine) stimulation and (b) the extraordinary ionic composition and ionic strength of synovial fluid. (3) In our chondrocyte preparations, at least two types of Ca2+-activated K+ channels are expressed and can significantly hyperpolarize ER. (4) Accounting for changes in ER can provide insights into the functional roles of the ligand-dependent Ca2+ influx through store-operated Ca2+ channels. Some of the findings are illustrated in this review. Our summary diagram suggests that, in chondrocytes, the K+ and Ca2+ channels are linked in a positive feedback loop that can augment Ca2+ influx and therefore regulate lubricant and cytokine secretion and gene transcription.
Glypican-1 Level Is Elevated in Extracellular Vesicles Released from MC38 Colon Adenocarcinoma Cells Overexpressing Snail
Authors: Papiewska-Pająk Izabela , Krzyżanowski Damian , Katela Maria , Rivet Romain , Michlewska Sylwia , Przygodzka Patrycja , Kowalska M. Anna , Brézillon Stéphane
Published: June 2020

The transcription factor Snail triggers epithelial-to-mesenchymal transition (EMT), endowing cancer cells with invasive properties during tumor progression. Extracellular vesicles (EVs) released from cancer cells at various stages of cancer progression are known to influence the tumor pre-metastatic niche and metastatic potential. The aim of this study was to analyze the effect of Snail on murine colon adenocarcinoma cells (MC38 line) and on the characteristics of their EVs. Stable clones of Snail-overexpressing MC38 cells were investigated in vitro versus Mock cells. Increased expression of matrix metalloproteinase MMP-14 and augmented activity of MMP-9 and -14 were observed in Snail-MC38 cells. There was no change in the transcriptomic profile of proteoglycans in Snail-MC38 cells; however, the protein level of Glypican-1 (GPC1) was enhanced in EVs released from those cells. Our finding that GPC1 protein level was enhanced in EVs released from MC38 cells that overexpressed Snail and were in an early EMT stage might explain the specificity of the GPC1 biomarker in colon cancer diagnosis. Further, our data suggest that Snail, by changing the level of GPC1 on EVs released by colon cancer cells, may affect the generation of a distant premetastatic niche and metastatic organotropism in colon adenocarcinoma.
Role of FOXO Transcription Factors in Cancer Metabolism and Angiogenesis
Authors: Farhan Mohd , Silva Marta , Xingan Xing , Huang Yu , Zheng Wenhua
Published: June 2020

Forkhead box O transcription factors (FOXOs) regulate several signaling pathways and play crucial roles in health and disease. FOXOs are key regulators of the expression of genes involved in multiple cellular processes and their deregulation has been implicated in cancer. FOXOs are generally considered tumor suppressors and evidence also suggests that they may have a role in the regulation of cancer metabolism and angiogenesis. In order to continue growing and proliferating, tumor cells have to reprogram their metabolism and induce angiogenesis. Angiogenesis refers to the process of new blood capillary formation from pre-existing vessels, which is an essential driving force in cancer progression and metastasis through supplying tumor cells with oxygen and nutrients. This review summarizes the roles of FOXOs in the regulation of cancer metabolism and angiogenesis. A deeper knowledge of the involvement of FOXOs in these two key processes involved in cancer dissemination may help to develop novel therapeutic approaches for cancer treatment.
Manufacturing of Continuous Carbon Fiber Reinforced Aluminum by Spark Plasma Sintering
Authors: Jiménez Miguel , Ott Felix , Kern Frank , Gadow Rainer
Published: June 2020

In the field of metal matrix composites (MMC), spark plasma sintering (SPS) technique has been used so far for the manufacture of particle, whisker and short-fiber reinforced alloys. In this work, SPS technique is employed for the first time to produce continuous fiber reinforced light metals. For this purpose, metal matrix composite prepregs with aluminum as a surface coating on carbon fiber textiles are manufactured by twin arc wire spraying and subsequently consolidated by SPS in the semi-solid temperature range of the alloy. Shear thinning rheological behavior of the metal alloy at temperatures between solidus and liquidus enables the infiltration of fiber rovings under reduced forming loads. SPS offered a better controlled and more efficient heat transfer in the green body and faster consolidation cycles in comparison with alternative densification methods. Fully densified samples with no porosity proved the suitability of SPS for densification of MMC with a remarkable stiffness increase in comparison with samples densified by thixoforging, an alternative consolidation method. However, the pulse activated sintering process leads to a quite strong fiber/matrix adhesion with evidence of aluminum carbide formation.
Material Allowable Generation and AM Process Parameters Effect on Porosity
Authors: Abdi Frank , Yavari Parviz , Harik Vasyl , Godines Cody
Published: June 2020

Additive manufacturing (AM) process methods such as powder bed fusion (LPBF) of metal powder layers can produce layered material systems with designed microstructures, which may exhibit scatter in mechanical properties (e.g., lower yield and lower failure strain), corrosion due to porosity and print anomalies. This study shows the development of AM process simulation to predict As-built material characteristic and their scatter comparing with experimental test data. ICME (Integrated Computational Materials Engineering) was used to simulate yield, ultimate, strain, and reduction of the area of sample AM. The method was extended to predict oxidation and damage of as-built parts. The samples were fabricated horizontally and vertically in multiple and scatter directions to find the effect on the mechanical properties such as ultimate tensile strength (UTS) and yield strength (YS). The probabilistic sensitivities show that in order for the next-generation technology to improve the strength of 3D printed materials, they must control the void volume fraction (trapped gas) and orientation of voids. The studied 3D print modality processes: (a) LPBF of AlSi10Mg, and (b) Electron Beam (EBM) of Ti-6Al-4V materials are shown to be over 99.99% reliable. The statistics of 3D printed Ti-6Al-4V have been observed for room and high temperature (RT/HT). The ICME Material Characterization and Qualification (MCQ) software material model prediction capabilities were used to predict (a) Material Allowable, a variation in Stress Strain Curves Characteristic Points and Residual Stress due to air particle (void/defect) shape and size and orientation. The probabilistic simulation computes Cumulative Distribution Function (CDF) and probabilistic sensitivities for YS, UTS, and %Elongation as well as A and B basis allowable of the As-Built 3D printed material and; and (b) Fracture Control Plan fracture toughness determination, and fatigue crack growth vs. stress intensity.
Introduction to Plasma Electrolytic Oxidation—An Overview of the Process and Applications
Authors: Simchen Frank , Sieber Maximilian , Kopp Alexander , Lampke Thomas
Published: June 2020

Plasma electrolytic oxidation (PEO), also called micro-arc oxidation (MAO), is an innovative method in producing oxide-ceramic coatings on metals, such as aluminum, titanium, magnesium, zirconium, etc. The process is characterized by discharges, which develop in a strong electric field, in a system consisting of the substrate, the oxide layer, a gas envelope, and the electrolyte. The electric breakdown in this system establishes a plasma state, in which, under anodic polarization, the substrate material is locally converted to a compound consisting of the substrate material itself (including alloying elements) and oxygen in addition to the electrolyte components. The review presents the process kinetics according to the existing models of the discharge phenomena, as well as the influence of the process parameters on the process, and thus, on the resulting coating properties, e.g., morphology and composition.
Cross-Linking of Thermally Hydrolyzed Specified Risk Materials with Epoxidized Poly (Vinyl Alcohol) for Tackifier Applications
Authors: Shui Tao , Chae Michael , Bressler David C.
Published: June 2020

Prions have been identified as the infection source for bovine spongiform encephalopathy or ‘mad cow disease’. Safety concerns relating to this disease have led to strict feed regulations for specified risk materials (SRMs) in North America, which are characterized as the tissues in cattle where prions are likely to concentrate. As one of the approved SRM disposal methods, thermal hydrolysis converts proteinaceous materials, including prions into non-infective peptides, which have been examined for incorporation into a variety of value-added applications. Here, we describe the bio-conversion of SRM-derived peptides into tackifiers for hydro-mulch applications. Tackifiers are employed in erosion control strategies and help to bind seed and mulch to eroded areas to promote the restoration of vegetation. In this study, epoxidized poly (vinyl alcohol) (PVA) was synthesized and employed for cross-linking of SRM-derived peptides. The reaction conditions and the molar ratio of the reagents applied for the cross-linking reaction were shown to have significant effects on cross-linking behaviour. Furthermore, SRM-derived peptides that were modified with epoxidized PVA displayed viscosity, binding, and moisture maintaining capacity that were comparable to commercially available tackifiers. Hence, this research further strengthens the argument for using SRM-derived peptides as feedstock for sustainable tackifiers development.
Research on Tribological Characteristics of Hard Metal WC-Co Tools with TiAlN and CrN PVD Coatings for Processing Solid Oak Wood
Authors: Kazlauskas Deividas , Jankauskas Vytenis , Tučkutė Simona
Published: June 2020

The article presents research results that demonstrate the impacts of mechanical and tribological characteristics on the efficiency of cutting tools made from hard metal WC-Co. Uncoated tools and tools coated with physical vapor deposition (PVD) coatings (CrN and TiAlN) were tested. The thickness of coatings was determined, and tests of roughness, microhardness, and adhesion were performed. The coefficient of friction (COF) was established by different methods, and the wear of the tested cutters which occurs during the milling of solid oak wood, and the impact of this on surface roughness, were determined. The results revealed that uncoated WC-Co cutters are the least resistant to wear, while cutters coated with chromium nitride (CrN) are the most resistant. Both PVD coatings were damaged in the 9050 m in area of the cutting edge.
Study on the Wear and Seawater Corrosion Resistance of Ni–Co–P Alloy Coatings with Jet Electrodeposition in Different Jet Voltages and Temperatures of Plating Solution
Authors: Zhang Yin , Kang Min , Yao Liang , Mbugua Nyambura Samuel , Jin Meifu , Zhu Jiping
Published: June 2020

In order to improve the wear and seawater corrosion resistance of metals, Ni–Co–P alloy coatings were fabricated on 45 steel substrates with jet electrodeposition in different jet voltages and temperatures of plating solution. The cross-section morphology, chemical composition, crystalline structure, microhardness, wear, and seawater corrosion resistance of the samples were analyzed and characterized using scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), X-ray diffraction (XRD), microhardness tester, friction wear tester, and electrochemical workstation, respectively. The results showed that the contents of Co in Ni–Co–P alloy coatings changed with the variation of jet voltages and temperature of plating solution. The content of Co in Ni–Co–P alloy coatings reached a maximum value of 47.46 wt·% when the jet voltage was 12 V and the temperature of the plating solution was 60 °C. The XRD patterns of Ni–Co–P alloy coatings showed that there was an obvious preferred orientation in the (111) plane. With an increase in the jet voltages and temperature of the plating solution, the microhardness of Ni–Co–P alloy coatings first increased and then decreased, with the maximum value obtained being 634.9 HV0.1. When the jet voltage was 12 V and the temperature of the plating solution was 60 °C, the wear scar width of the Ni–Co–P alloy coatings reached a minimum value of 463.4 µm. In addition, the polarization curves in the electrochemical test indicated that the samples deposited at 60 °C and 12 V exhibited the lowest corrosion current density (Icorr) of 1.72 µA/cm2 and highest polarization resistance (Rp) of 19.61 kΩ·cm−2, which indicated that the coatings had better seawater corrosion resistance.
Green Corrosion Inhibition of Mild Steel by Hydrazone Derivatives in 1.0 M HCl
Authors: Chaouiki Abdelkarim , Chafiq Maryam , Lgaz Hassane , Al-Hadeethi Mustafa R. , Ali Ismat H. , Masroor Sheerin , Chung Ill-Min
Published: June 2020

In the present study, the inhibition performance of two synthesized hydrazone derivatives (HDZs), namely, (E)-N′-(2,4-dimethoxybenzylidene)-2-(6-methoxynaphthalen-2-yl) propanehydrazide (HYD-1) and N′-cyclohexylidene-2-(6-methoxynaphthalen-2-yl) propanehydrazide (HYD-2) on mild steel (MS) in 1.0 M HCl was investigated using weight loss measurements, electrochemical techniques, and scanning electron microscope (SEM) coupled with energy-dispersive X-ray spectroscopy (EDX). The experimental data suggested that the hydrazone derivatives exhibited a high inhibition performance, which increases with increasing their concentrations. HYD-1 and HYD-2 presented maximum inhibition efficiencies of 96% and 84%, respectively, at an optimal concentration of 5 × 10–3 M. The principal observations that resulted from electrochemical studies are that HYDs affected both anodic and cathodic reactions (mixed inhibitors). Their adsorption, which is a combination of chemisorption and physisorption, obeyed the Langmuir isotherm model. Furthermore, the temperature effect was carried out at various temperatures ranging from 303 to 333 K to verify the corrosion inhibition performance of HYD-1 at higher temperatures. Moreover, SEM-EDX analysis confirmed that HYDs can ensure remarkable prevention against corrosion through the adsorption onto the metal surface.
X-ray Based in Situ Investigation of Silicon Growth Mechanism Dynamics—Application to Grain and Defect Formation
Authors: Ouaddah Hadjer , Becker Maike , Riberi-Béridot Thècle , Tsoutsouva Maria , Stamelou Vasiliki , Regula Gabrielle , Reinhart Guillaume , Périchaud Isabelle , Guittonneau Fabrice , Barrallier Laurent , Valade Jean-Paul , Rack Alexander , Boller Elodie , Baruchel José , Mangelinck-Noël Nathalie
Published: June 2020

To control the final grain structure and the density of structural crystalline defects in silicon (Si) ingots is still a main issue for Si used in photovoltaic solar cells. It concerns both innovative and conventional fabrication processes. Due to the dynamic essence of the phenomena and to the coupling of mechanisms at different scales, the post-mortem study of the solidified ingots gives limited results. In the past years, we developed an original system named GaTSBI for Growth at high Temperature observed by Synchrotron Beam Imaging, to investigate in situ the mechanisms involved during solidification. X-ray radiography and X-ray Bragg diffraction imaging (topography) are combined and implemented together with the running of a high temperature (up to 2073 K) solidification furnace. The experiments are conducted at the European Synchrotron Radiation Facility (ESRF). Both imaging techniques provide in situ and real time information during growth on the morphology and kinetics of the solid/liquid (S/L) interface, as well as on the deformation of the crystal structure and on the dynamics of structural defects including dislocations. Essential features of twinning, grain nucleation, competition, strain building, and dislocations during Si solidification are characterized and allow a deeper understanding of the fundamental mechanisms of its growth.
The Biodiversity of Demodecid Mites (Acariformes: Prostigmata), Specific Parasites of Mammals with a Global Checklist and a New Finding for Demodex sciurinus
Authors: Izdebska Joanna N. , Rolbiecki Leszek
Published: June 2020

Demodecidae are the most specialized parasitic mites of mammals; they typically inhabit the skin, but they have been found in other tissues and organs. They can cause demodecosis (a disease which is hazardous and difficult to cure) in humans, domestic animals and livestock. They are parasites with high host and topical specificity. They have been found for most orders of mammals, and they are common in the populations of numerous host species. Therefore, they not only constitute an important subject of veterinary and medical study, but also comprise an excellent model for faunistic and parasitological analyses concerning different aspects of functioning and evolution of the host–parasite relationship. The current level or knowledge of demodecid mites is irregular and fragmentary, and numerous questions require elaboration and ordering, from the taxonomic diversity to geographic distribution and relations with hosts. Such data may be of use i.a. for the development of more efficient and reliable diagnostic methods, as well as understanding the etiology and pathogenesis mechanisms of demodecosis, currently a contentious issue. The present paper lists all formally-described valid species of demodecid mites, together with other functioning specific names, verified and with comments on their status. This is significant for correct species identification and demodecosis diagnostics. The list has been drawn up on the basis of data acquired in the period 1842−2020. It contains 122 valid species of parasite, including their hosts and geographic distribution, data on parasitism, as well as only the second record of Demodex sciurinus in Eurasian red squirrel Sciurus vulgaris in over 100 years since its initial discovery.