bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum γ-Glutamyltransferase Concentration Predicts Endothelial Dysfunction in Naïve Hypertensive Patients
Authors: Perticone Maria , Maio Raffaele , Caroleo Benedetto , Sciacqua Angela , Suraci Edoardo , Gigliotti Simona , Martino Francesco , Andreozzi Francesco , Sesti Giorgio , Perticone Francesco
Published: July 2020

Background: Serum gamma-glutamyltransferase (γ-GT) is recognized as a risk factor for cardiovascular diseases (CV). Traditional cardiovascular risk factors mediate endothelial dysfunction. Aim: to evaluate a possible correlation between serum γ-GT and endothelium-dependent vasodilation in naïve hypertensives. Methods: We enrolled 500 hypertensives. Endothelial function was studied by strain-gauge plethysmography. Receiver operating characteristic (ROC) analysis was used to assess the predictive value of γ-GT and to identify the optimal cut-off value of the same variable for endothelial dysfunction. Results: At univariate linear analysis peak percent increase in acetylcholine (ACh)-stimulated vasodilation was inversely related to γ-GT (r = −0.587), alanine aminotransferase (ALT) (r = −0.559), aspartate aminotransferase (AST) (r = −0.464), age (r = −0.171), body mass index (BMI) (r = −0.152), and fasting glucose (r = −101). In the stepwise multivariate regression model, endothelium-dependent vasodilation was significantly related to γ-GT (β = −0.362), ALT (β = −0.297), AST (β = −0.217), estimated glomerular filtration rate (e-GFR) (β = 0.199), gender (β = 0.166), and smoking (β = −0.061). The ROC analysis demonstrated that the accuracy of γ-GT for identifying patients with endothelial dysfunction was 82.1%; the optimal γ-GT cut-off value for discriminating patients with this alteration was 27 UI/L. Conclusions: Serum γ-GT values, within the normal range, are significantly associated with endothelial dysfunction in hypertensives, and may be considered a biomarker of early vascular damage.
Association of Exercise with Inhibitory Control and Prefrontal Brain Activity Under Acute Psychosocial Stress
Authors: Mücke Manuel , Ludyga Sebastian , Colledge Flora , Pühse Uwe , Gerber Markus
Published: July 2020

Psychosocial stress has negative effects on cognition in adolescents. The aim of this study was to investigate whether physical exercise can buffer such effects on inhibitory control and associated cortical brain areas. Forty-two male high school students aged 16–20 years and with either low or high exercise levels performed a Stroop task under stress-free conditions and after the Trier Social Stress Test (TSST). Oxygenation of the dorsolateral prefrontal cortex (DLPFC) was measured with functional near-infrared spectroscopy. For inhibitory control, there was no significant primary effect of condition (F(1,40) = 1.09, p = 303., ηp² = 0.027) and no significant condition × group interaction (F(1,40) = 2.40, p = 0.129, ηp² = 0.057). For DLPFC oxygenation, a significant primary effect of condition was observed (F (1,38) = 6.10, p = 0.018, ηp² = 0.138). However, the condition × group interaction (F (1,38) = 0.05, p = 0.823, ηp² = 0.001) remained not significant. Adolescents’ exercise level was not associated with inhibitory control before and after stress. An impact of stress on a neurocognitive level was observed.
Sustained Isometric Wrist Flexion and Extension Maximal Voluntary Contractions on Corticospinal Excitability to Forearm Muscles during Low-Intensity Hand-Gripping
Authors: Forman Davis A. , Forman Garrick N. , Murphy Bernadette A. , Holmes Michael W. R.
Published: July 2020

The wrist extensors demonstrate an earlier fatigue onset than the wrist flexors. However, it is currently unclear whether fatigue induces unique changes in muscle activity or corticospinal excitability between these muscle groups. The purpose of this study was to examine how sustained isometric wrist extension/flexion maximal voluntary contractions (MVCs) influence muscle activity and corticospinal excitability of the forearm. Corticospinal excitability to three wrist flexors and three wrist extensors were measured using motor evoked potentials (MEPs) elicited via transcranial magnetic stimulation. Responses were elicited while participants exerted 10% of their maximal handgrip force, before and after a sustained wrist flexion or extension MVC (performed on separate sessions). Post-fatigue measures were collected up to 10-min post-fatigue. Immediately post-fatigue, extensor muscle activity was significantly greater following the wrist flexion fatigue session, although corticospinal excitability (normalized to muscle activity) was greater on the wrist extension day. Responses were largely unchanged in the wrist flexors. However, for the flexor carpi ulnaris, normalized MEP amplitudes were significantly larger following wrist extension fatigue. These findings demonstrate that sustained isometric flexion/extension MVCs result in a complex reorganization of forearm muscle recruitment strategies during hand-gripping. Based on these findings, previously observed corticospinal behaviour following fatigue may not apply when the fatiguing task and measurement task are different.
Sex-Specific Effects of Early Life Stress on Brain Mitochondrial Function, Monoamine Levels and Neuroinflammation
Authors: González-Pardo Héctor , Arias Jorge L. , Gómez-Lázaro Eneritz , López Taboada Isabel , Conejo Nélida M.
Published: July 2020

Sex differences have been reported in the susceptibility to early life stress and its neurobiological correlates in humans and experimental animals. However, most of the current research with animal models of early stress has been performed mainly in males. In the present study, prolonged maternal separation (MS) paradigm was applied as an animal model to resemble the effects of adverse early experiences in male and female rats. Regional brain mitochondrial function, monoaminergic activity, and neuroinflammation were evaluated as adults. Mitochondrial energy metabolism was greatly decreased in MS females as compared with MS males in the prefrontal cortex, dorsal hippocampus, and the nucleus accumbens shell. In addition, MS males had lower serotonin levels and increased serotonin turnover in the prefrontal cortex and the hippocampus. However, MS females showed increased dopamine turnover in the prefrontal cortex and increased norepinephrine turnover in the striatum, but decreased dopamine turnover in the hippocampus. Sex differences were also found for pro-inflammatory cytokine levels, with increased levels of TNF-α and IL-6 in the prefrontal cortex and hippocampus of MS males, and increased IL-6 levels in the striatum of MS females. These results evidence the complex sex- and brain region-specific long-term consequences of early life stress.
Circulating Tumour DNA Is an Independent Prognostic Biomarker for Survival in Metastatic BRAF or NRAS-Mutated Melanoma Patients
Authors: Herbreteau Guillaume , Vallée Audrey , Knol Anne-Chantal , Théoleyre Sandrine , Quéreux Gaelle , Frénard Cécile , Varey Emilie , Hofman Paul , Khammari Amir , Dréno Brigitte , Denis Marc G.
Published: July 2020

Circulating tumour DNA (ctDNA) can be used to identify gene alterations. The purpose of this study was to determine whether the detection of ctDNA, based on the identification of BRAF and NRAS mutations before systemic treatment initiation, was associated with the prognosis of metastatic melanoma. In total, 68 BRAF or NRAS-mutated stage IV or unresectable stage III metastatic cutaneous melanoma patients were included and tested for the presence of BRAF and NRAS mutations in circulating DNA before treatment initiation, using the Cobas BRAF/NRAS Mutation Test (Roche). The expected mutation was detected in the plasma of 34/68 patients (50% sensitivity). ctDNA detection was associated with AJCC stage, along with the number and nature of metastases. ctDNA was less frequently detected in NRAS-mutated than in BRAF-mutated melanoma (36% and 66%, respectively). At initiation of first-line treatment, ctDNA detection was associated with poor prognosis in Progression Free Survival (PFS) and Overall Survival (OS) in univariate analysis (log-rank: p = 0.002 and p < 0.0001, respectively). In multivariate analysis, ctDNA detection was an independent factor of poor prognosis in OS, after adjustment for AJCC stage, number and nature of metastases and gender (HR = 4.384; 95% CI: (1.308; 14.699); p = 0.017).
Molecular Mechanisms and Potential Therapeutic Reversal of Pancreatic Cancer-Induced Immune Evasion
Authors: Gan Li-Lian , Hii Ling-Wei , Wong Shew-Fung , Leong Chee-Onn , Mai Chun-Wai
Published: July 2020

Pancreatic cancer ranks high among the causes of cancer-related mortality. The prognosis of this grim condition has not improved significantly over the past 50 years, despite advancement in imaging techniques, cancer genetics and treatment modalities. Due to the relative difficulty in the early detection of pancreatic tumors, as low as 20% of patients are eligible for potentially curative surgery; moreover, chemotherapy and radiotherapy (RT) do not confer a great benefit in the overall survival of the patients. Currently, emerging developments in immunotherapy have yet to bring a significant clinical advantage among pancreatic cancer patients. In fact, pancreatic tumor-driven immune evasion possesses one of the greatest challenges leading to immunotherapeutic resistance. Most of the immune escape pathways are innate, while poor priming of hosts’ immune response and immunoediting constitute the adaptive immunosuppressive machinery. In this review, we extensively discuss the pathway perturbations undermining the anti-tumor immunity specific to pancreatic cancer. We also explore feasible up-and-coming therapeutic strategies that may restore immunity and address therapeutic resistance, bringing hope to eliminate the status quo in pancreatic cancer prognosis.
A Retrospective Analysis of the Efficacy of Immunotherapy in Metastatic Soft-Tissue Sarcomas
Authors: Monga Varun , Skubitz Keith M. , Maliske Seth , Mott Sarah L. , Dietz Hilary , Hirbe Angela C. , Van Tine Brian A. , Oppelt Peter , Okuno Scott , Robinson Steven , O’Connor Madeline , Seetharam Mahesh , Attia Steven , Charlson John , Agulnik Mark , Milhem Mohammed
Published: July 2020

Although checkpoint inhibitors have been approved in multiple cancers, they are still under investigation in soft tissue sarcoma (STS). We conducted a retrospective review to report the safety, efficacy, and prognostic factors related to checkpoint inhibitors in STS. A sequential cohort of metastatic STS patients from four institutions treated with checkpoint inhibitors was assembled. Logistic and Cox regression models were applied to determine the effect of patient characteristics, prior treatment, and baseline factors on achieving the best overall response of complete response (CR), partial response (PR), or stable disease (SD) as determined by the treating physician. Eighty-eight patients with two median prior therapies received checkpoint inhibitors. Treatments included pembrolizumab in 47, nivolumab in 6, ipilimumab in 1, combination ipilimumab/nivolumab in 27, and other combination immunotherapies in 7 patients. Immunotherapy was discontinued in 54 patients—72.2% for progression, 16.7% for toxicity, and 11.1% for other reasons. Median progression-free survival (PFS) was 4.1 months and median overall survival was 19.1 months. One patient with undifferentiated pleomorphic sarcoma (UPS) achieved a CR, while 20 patients had a PR, including 7 UPS, 9 leiomyosarcoma (LMS), and 1 each with alveolar soft part sarcoma, fibroblastic sarcoma, sclerosing epithelioid fibrosarcoma, and myxofibrosarcoma. Forty-five percent (9 of 20) of LMS patients achieved a PR. Twenty-eight patients had SD. Our results confirm the activity and safety of anti-PD-1 therapy in metastatic STS. A notable response rate was observed in UPS and LMS subtypes. This study expands the knowledge base beyond what is currently available from clinical trials involving checkpoint inhibitors in metastatic STS.
Combinatorial Immunotherapies for Metastatic Colorectal Cancer
Authors: Janssen Eline , Subtil Beatriz , de la Jara Ortiz Fàtima , Verheul Henk M. W. , Tauriello Daniele V. F.
Published: July 2020

Colorectal cancer (CRC) is one of the most frequent and deadly forms of cancer. About half of patients are affected by metastasis, with the cancer spreading to e.g., liver, lungs or the peritoneum. The majority of these patients cannot be cured despite steady advances in treatment options. Immunotherapies are currently not widely applicable for this disease, yet show potential in preclinical models and clinical translation. The tumour microenvironment (TME) has emerged as a key factor in CRC metastasis, including by means of immune evasion—forming a major barrier to effective immuno-oncology. Several approaches are in development that aim to overcome the immunosuppressive environment and boost anti-tumour immunity. Among them are vaccination strategies, cellular transplantation therapies, and targeted treatments. Given the complexity of the system, we argue for rational design of combinatorial therapies and consider the implications of precision medicine in this context.
Aspartic Aminopeptidase Is a Novel Biomarker of Aggressive Chronic Lymphocytic Leukemia
Authors: Kakodkar Pramath , More Sanket , András Kinga , Papakonstantinou Nikos , Kelly Sharon , Makrooni Mohammad Adib , Ortutay Csaba , Szegezdi Eva
Published: July 2020

Treatment of chronic lymphocytic leukemia has advanced substantially as our understanding of the kinase signal transduction pathways driven by the B cell receptor (BcR) has developed. Particularly, understanding the role of Bruton tyrosine kinase and phosphatidyl inositol 3 kinase delta in driving prosurvival signal transduction in chronic lymphocytic leukemia (CLL) cells and their targeting with pharmacological inhibitors (ibrutinib and idelalisib, respectively) has improved patient outcomes significantly. The kinase signaling pathway induced by the BcR is highly complex and has multiple interconnecting branches mediated by tyrosine and serine/threonine kinases activated downstream of the BcR. There is a high level of redundancy in the biological responses, with several BcR-signaling kinases driving nuclear factor kappa B activation or inducing antiapoptotic Bcl-2 genes. Accordingly, common gene targets of BcR-signaling kinases may serve as biomarkers indicating enhanced BCR-signaling and aggressive disease progression. This study used a gene expression correlation analysis of malignant B cell lines and primary CLL cells to identify genes whose expression correlated with BCR-signaling kinases overexpressed and/or overactivated in CLL, namely: AKT1, AKT2, BTK, MAPK1, MAPK3, PI3KCD and ZAP70. The analysis identified a 32-gene signature with a strong prognostic potential and DNPEP, the gene coding for aspartic aminopeptidase, as a predictor of aggressive CLL. DNPEP gene expression correlated with MAPK3, PI3KCD, and ZAP70 expression and, in the primary CLL test dataset, showed a strong prognostic potential. The inhibition of DNPEP with a pharmacological inhibitor enhanced the cytotoxic potential of idelalisib and ibrutinib, indicating a biological functionality of DNPEP in CLL. DNPEP, as an aminopeptidase, contributes to the maintenance of the free amino acid pool in CLL cells found to be an essential process for the survival of many cancer cell types, and thus, these results warrant further research into the exploitation of aminopeptidase inhibitors in the treatment of drug-resistant CLL.
Loss of Function SETD2 Mutations in Poorly Differentiated Metastases from Two Hürthle Cell Carcinomas of the Thyroid
Authors: Pecce Valeria , Verrienti Antonella , Abballe Luana , Carletti Raffaella , Grani Giorgio , Falcone Rosa , Ramundo Valeria , Durante Cosimo , Di Gioia Cira , Russo Diego , Filetti Sebastiano , Sponziello Marialuisa
Published: July 2020

Hürthle cell carcinomas (HCC) are rare differentiated thyroid cancers that display low avidity for radioactive iodine and respond poorly to kinase inhibitors. Here, using next-generation sequencing, we analyzed the mutational status of primary tissue and poorly differentiated metastatic tissue from two HCC patients. In both cases, metastatic tissues harbored a mutation of SETD2, each resulting in loss of the SRI and WW domains of SETD2, a methyltransferase that trimethylates H3K36 (H3K36me3) and also interacts with p53 to promote its stability. Functional studies of the novel p.D1890fs6* mutation (case 1) revealed significantly reduced H3K36me3 levels in SETD2-mutated tissue and primary cell cultures and decreased levels of the active form of p53. Restoration of SETD2-wildtype expression in the SETD2-mutant cells significantly reduced the expression of four well-known stemness markers (OCT-4, SOX2, IPF1, Goosecoid). These findings suggest potential roles for SETD2 loss-of-function mutations in HCC progression, possibly involving p53 destabilization and promotion of stemness. Their prevalence and potential treatment implications in thyroid cancer, especially HCC, require further study.
The Ubiquitin Proteasome System in Hematological Malignancies: New Insight into Its Functional Role and Therapeutic Options
Authors: Di Costanzo Antonella , Del Gaudio Nunzio , Conte Lidio , Altucci Lucia
Published: July 2020

The ubiquitin proteasome system (UPS) is the main cellular degradation machinery designed for controlling turnover of critical proteins involved in cancer pathogenesis, including hematological malignancies. UPS plays a functional role in regulating turnover of key proteins involved in cell cycle arrest, apoptosis and terminal differentiation. When deregulated, it leads to several disorders, including cancer. Several studies indicate that, in some subtypes of human hematological neoplasms such as multiple myeloma and Burkitt’s lymphoma, abnormalities in the UPS made it an attractive therapeutic target due to pro-cancer activity. In this review, we discuss the aberrant role of UPS evaluating its impact in hematological malignancies. Finally, we also review the most promising therapeutic approaches to target UPS as powerful strategies to improve treatment of blood cancers.
Formation of Aberrant Myotubes by Myoblasts Lacking Myosin VI Is Associated with Alterations in the Cytoskeleton Organization, Myoblast Adhesion and Fusion
Authors: Lehka Lilya , Topolewska Małgorzata , Wojton Dominika , Karatsai Olena , Alvarez-Suarez Paloma , Pomorski Paweł , Rędowicz Maria Jolanta
Published: July 2020

We have previously postulated that unconventional myosin VI (MVI) could be involved in myoblast differentiation. Here, we addressed the mechanism(s) of its involvement using primary myoblast culture derived from the hindlimb muscles of Snell’s waltzer mice, the natural MVI knockouts (MVI-KO). We observed that MVI-KO myotubes were formed faster than control heterozygous myoblasts (MVI-WT), with a three-fold increase in the number of myosac-like myotubes with centrally positioned nuclei. There were also changes in the levels of the myogenic transcription factors Pax7, MyoD and myogenin. This was accompanied by changes in the actin cytoskeleton and adhesive structure organization. We observed significant decreases in the levels of proteins involved in focal contact formation, such as talin and focal adhesion kinase (FAK). Interestingly, the levels of proteins involved in intercellular communication, M-cadherin and drebrin, were also affected. Furthermore, time-dependent alterations in the levels of the key proteins for myoblast membrane fusion, myomaker and myomerger, without effect on their cellular localization, were observed. Our data indicate that in the absence of MVI, the mechanisms controlling cytoskeleton organization, as well as myoblast adhesion and fusion, are dysregulated, leading to the formation of aberrant myotubes.
Maternal Immune Activation Sensitizes Male Offspring Rats to Lipopolysaccharide-Induced Microglial Deficits Involving the Dysfunction of CD200–CD200R and CX3CL1–CX3CR1 Systems
Authors: Chamera Katarzyna , Szuster-Głuszczak Magdalena , Trojan Ewa , Basta-Kaim Agnieszka
Published: July 2020

Early life challenges resulting from maternal immune activation (MIA) may exert persistent effects on the offspring, including the development of psychiatric disorders, such as schizophrenia. Recent evidence has suggested that the adverse effects of MIA may be mediated by neuron–microglia crosstalk, particularly CX3CL1–CX3CR1 and CD200–CD200R dyads. Therefore, the present study assessed the behavioural parameters resembling schizophrenia-like symptoms in the adult male offspring of Sprague-Dawley rats that were exposed to MIA and to an additional acute lipopolysaccharide (LPS) challenge in adulthood, according to the “two-hit” hypothesis of schizophrenia. Simultaneously, we aimed to clarify the role of the CX3CL1–CX3CR1 and CD200–CD200R axes and microglial reactivity in the brains of adult offspring subjected to MIA and the “second hit” wit LPS. In the present study, MIA generated a range of behavioural changes in the adult male offspring, including increased exploratory activity and anxiety-like behaviours. The most intriguing finding was observed in the prepulse inhibition (PPI) test, where the deficit in the sensorimotor gating was age-dependent and present only in part of the rats. We were able to distinguish the occurrence of two groups: responsive and non-responsive (without the deficit). Concurrently, based on the results of the biochemical studies, MIA disrupted mainly the CD200–CD200R system, while the changes of the CX3CL1–CX3CR1 axis were less evident in the frontal cortex of adult non-responsive offspring. MIA markedly affected the immune regulators of the CD200–CD200R pathway as we observed an increase in cortical IL-6 release in the responsive group and IL-4 in the non-responsive offspring. Importantly, the “second hit” generated disturbances at the behavioural and biochemical levels mostly in the non-responsive adult animals. Those offspring were characterized both by disturbed PPI and “priming” microglia. Altogether, the exposure to MIA altered the immunomodulatory mechanisms, including the CD200–CD200R axis, in the brain and sensitized animals to subsequent immunological challenges, leading to the manifestation of schizophrenia-like alterations.
Addition of High Molecular Weight Hyaluronic Acid to Fibroblast-Like Stromal Cells Modulates Endogenous Hyaluronic Acid Metabolism and Enhances Proteolytic Processing and Secretion of Versican
Authors: Xue Jiapeng , Chen Jinnan , Shen Quan , Chan Deva , Li Jun , Tanguay Adam P. , Schmidt Tannin A. , Niazi Faizan , Plaas Anna
Published: July 2020

We have examined the effect of exogenous linear chain high molecular weight hyaluronic acid (HMW HA) on endogenously synthesized hyaluronic acid (HA) and associated binding proteins in primary cultures of fibroblast-like stromal cells that were obtained by collagenase digestion of the murine peripatellar fat pad. The cultures were expanded in DMEM that was supplemented with fetal bovine serum and basic fibroblast growth factor (bFGF) then exposed to macrophage-colony-stimulating factor (MCSF) to induce macrophage properties, before activation of inflammatory pathways using E. coli lipopolysaccharide (LPS). Under all culture conditions, a significant amount of endogenously synthesized HA localized in LAMP1-positive lysosomal vesicles. However, this intracellular pool was depleted after the addition of exogenous HMW HA and was accompanied by enhanced proteolytic processing and secretion of de novo synthesized versican, much of which was associated with endosomal compartments. No changes were detected in synthesis, secretion, or proteolytic processing of aggrecan or lubricin (PRG4). The addition of HMW HA also modulated a range of LPS-affected genes in the TLR signaling and phagocytosis pathways, as well as endogenous HA metabolism genes, such as Has1, Hyal1, Hyal2, and Tmem2. However, there was no evidence for association of endogenous or exogenous HMW HA with cell surface CD44, TLR2 or TLR4 protein, suggesting that its physiochemical effects on pericelluar pH and/or ionic strength might be the primary modulators of signal transduction and vesicular trafficking by this cell type. We discuss the implications of these findings in terms of a potential in vivo effect of therapeutically applied HMW HA on the modification of osteoarthritis-related joint pathologies, such as pro-inflammatory and degradative responses of multipotent mesenchymal cells residing in the synovial membrane, the underlying adipose tissue, and the articular cartilage surface.
Sphingosine-1-Phosphate Metabolism in the Regulation of Obesity/Type 2 Diabetes
Authors: Guitton Jeanne , Bandet Cécile L. , Mariko Mohamed L. , Tan-Chen Sophie , Bourron Olivier , Benomar Yacir , Hajduch Eric , Le Stunff Hervé
Published: July 2020

Obesity is a pathophysiological condition where excess free fatty acids (FFA) target and promote the dysfunctioning of insulin sensitive tissues and of pancreatic β cells. This leads to the dysregulation of glucose homeostasis, which culminates in the onset of type 2 diabetes (T2D). FFA, which accumulate in these tissues, are metabolized as lipid derivatives such as ceramide, and the ectopic accumulation of the latter has been shown to lead to lipotoxicity. Ceramide is an active lipid that inhibits the insulin signaling pathway as well as inducing pancreatic β cell death. In mammals, ceramide is a key lipid intermediate for sphingolipid metabolism as is sphingosine-1-phosphate (S1P). S1P levels have also been associated with the development of obesity and T2D. In this review, the current knowledge on S1P metabolism in regulating insulin signaling in pancreatic β cell fate and in the regulation of feeding by the hypothalamus in the context of obesity and T2D is summarized. It demonstrates that S1P can display opposite effects on insulin sensitive tissues and pancreatic β cells, which depends on its origin or its degradation pathway.
Human and Rodent Skeletal Muscles Express Angiotensin II Type 1 Receptors
Authors: Deminice Rafael , Hyatt Hayden , Yoshihara Toshinori , Ozdemir Mustafa , Nguyen Branden , Levine Sanford , Powers Scott
Published: July 2020

Abundant evidence reveals that activation of the renin-angiotensin system promotes skeletal muscle atrophy in several conditions including congestive heart failure, chronic kidney disease, and prolonged mechanical ventilation. However, controversy exists about whether circulating angiotensin II (AngII) promotes skeletal muscle atrophy by direct or indirect effects; the centerpiece of this debate is the issue of whether skeletal muscle fibers express AngII type 1 receptors (AT1Rs). While some investigators assert that skeletal muscle expresses AT1Rs, others argue that skeletal muscle fibers do not contain AT1Rs. These discordant findings in the literature are likely the result of study design flaws and additional research using a rigorous experimental approach is required to resolve this issue. We tested the hypothesis that AT1Rs are expressed in both human and rat skeletal muscle fibers. Our premise was tested using a rigorous, multi-technique experimental design. First, we established both the location and abundance of AT1Rs on human and rat skeletal muscle fibers by means of an AngII ligand-binding assay. Second, using a new and highly selective AT1R antibody, we carried out Western blotting and determined the abundance of AT1R protein within isolated single muscle fibers from humans and rats. Finally, we confirmed the presence of AT1R mRNA in isolated single muscle fibers from rats. Our results support the hypothesis that AT1Rs are present in both human and rat skeletal muscle fibers. Moreover, our experiments provide the first evidence that AT1Rs are more abundant in fast, type II muscle fibers as compared with slow, type I fibers. Together, these discoveries provide the foundation for an improved understanding of the mechanism(s) responsible for AngII-induced skeletal muscle atrophy.
The Micro-Scaled Characterization of Natural Terrestrial Ferromanganese Coatings and Their Semiconducting Properties
Authors: Xu Xiaoming , Ding Hongrui , Li Yan , Wang Haoran , Lu Anhuai
Published: July 2020

Different types of ferromanganese coatings were collected from the Chinese mainland to study their mineralogical characteristics and semiconducting properties. Measurements, including by optical microscope, scanning electron microscope, energy dispersive X-ray spectroscopy, micro-Raman spectrometer and transmission electron microscope, were employed to study their morphology, mineral assemblage, element abundance and distribution patterns. Soil Fe coatings are mainly composed of Al-rich hematite and clays. Soil Fe/Mn coatings can be divided into an outer belt rich in birnessite and an inner belt rich in hematite, goethite, ilmenite and magnetite. Goethite is the only component of rock Fe coatings. Rock Fe/Mn coatings mainly consist of birnessite and hematite, and alternating Fe/Mn-rich layers and Fe/Mn-poor layers can be observed. Powders were scraped off from the topmost part of ferromanganese coatings to conduct laboratory photochemical experiments. The photocurrent–time behavior indicates that natural coating electrodes exhibit an immediate increase in photocurrent intensity when exposed to light irradiation. Natural coatings can photo-catalytically degrade 14.3%–58.4% of methyl orange in 10 h. Under light irradiation, the photocurrent enhancement and organic degradation efficiency of the rock Fe/Mn coating, which has a close intergrowth structure of Fe and Mn components, is most significant. This phenomenon is attributed to the formation of semiconductor heterojunctions, which can promote the separation of electrons and holes. Terrestrial ferromanganese coatings are common in natural settings and rich in semiconducting Fe/Mn oxide minerals. Under solar light irradiation, these coatings can catalyze important photochemical processes and will thus have an impact on the surrounding environment.
Bechmann’s Number for Harmonic Overtones of Thickness-Shear Vibrations of Rotated Y-Cut Quartz Crystal Plates
Authors: Zhang Han , Chen Yumei , Wang Ji
Published: July 2020

A procedure based on approximate solutions of three-dimensional equations of wave propagation is utilized for calculating Bechmann’s number for the harmonic overtones of thickness-shear modes in the rotated Y-cut quartz crystal plates. Bechmann’s number is used for the optimization and improvement of electrodes to yield superior performance in the design of quartz crystal resonators. Originally, Bechmann’s number is found through practical experiences, and analytical results were provided afterward to enable optimal design of novel resonator structures. The outcomes in this study are from a simplified theoretical prediction and they are consistent with known empirical results, making it is possible to design optimal quartz crystal resonators for cases without adequate experimental data for a higher frequency and smaller size.
Synthesis of Resorcinol Derivatives and their Effects on Melanin Production
Authors: Tokudome Yoshihiro , Hoshi Tsuyoshi , Mori Sayaka , Hijikuro Ichiro
Published: July 2020

Several resorcinol derivatives were synthesized and their effects on the survival rate of B16 murine melanoma cells, melanin production, and tyrosinase activity were investigated with an aim to evaluate their skin whitening effect. Twelve resorcinol derivatives were synthesized by esterification with three functional groups (L-ascorb-6-yl, ethyl, and glyceryl) linked via four alkyl chains of varying lengths (n = 2–5) at the 4-position. The structures of the 12 resorcinol derivatives were confirmed by Nuclear Magnetic Resonance (NMR). The derivatives were added to B16 murine melanoma cells and the melanin contents in the cells and culture medium were measured. To measure the tyrosinase activity, the substrate L-DOPA was added to a mushroom-derived tyrosinase solution, and the inhibition of the tyrosinase activity was determined. At 10 µM, the resorcinol derivatives did not affect the survival of the B16 murine melanoma cells, but the melanin content was reduced. At 1 µM, the derivatives significantly inhibited the tyrosinase activity in the mushroom-derived tyrosinase solution. A plot of the inhibitory effect on melanin production against the cLogP value for each resorcinol derivative indicated that the highest inhibition occurred at a cLogP value of approximately 2. Therefore, these resorcinol derivatives are expected to serve as effective skin whitening agents.
How to Use the Normalized Hydrophilic-Lipophilic Deviation (HLDN) Concept for the Formulation of Equilibrated and Emulsified Surfactant-Oil-Water Systems for Cosmetics and Pharmaceutical Products
Authors: Salager Jean-Louis , Antón Raquel , Bullón Johnny , Forgiarini Ana , Marquez Ronald
Published: July 2020

The effects of surfactant molecules involved in macro-, mini-, nano-, and microemulsions used in cosmetics and pharmaceuticals are related to their amphiphilic interactions with oil and water phases. Basic ideas on their behavior when they are put together in a system have resulted in the energy balance concept labeled the hydrophilic-lipophilic deviation (HLD) from optimum formulation. This semiempirical equation integrates in a simple linear relationship the effects of six to eight variables including surfactant head and tail, sometimes a cosurfactant, oil-phase nature, aqueous-phase salinity, temperature, and pressure. This is undoubtedly much more efficient than the hydrophilic-lipophilic balance (HLB) which has been used since 1950. The new HLD is quite important because it allows researchers to model and somehow predict the phase behavior, the interfacial tension between oil and water phases, their solubilization in single-phase microemulsion, as well as the corresponding properties for various kinds of macroemulsions. However, the HLD correlation, which has been developed and used in petroleum applications, is sometimes difficult to apply accurately in real cases involving ionic–nonionic surfactant mixtures and natural polar oils, as it is the case in cosmetics and pharmaceuticals. This review shows the confusion resulting from the multiple definitions of HLD and of the surfactant parameter, and proposes a “normalized” Hydrophilic-Lipophilic Deviation (HLDN) equation with a surfactant contribution parameter (SCP), to handle more exactly the effects of formulation variables on the phase behavior and the micro/macroemulsion properties.
An Arabic Dataset for Disease Named Entity Recognition with Multi-Annotation Schemes
Authors: Alshammari Nasser , Alanazi Saad
Published: July 2020

This article outlines a novel data descriptor that provides the Arabic natural language processing community with a dataset dedicated to named entity recognition tasks for diseases. The dataset comprises more than 60 thousand words, which were annotated manually by two independent annotators using the inside–outside (IO) annotation scheme. To ensure the reliability of the annotation process, the inter-annotator agreements rate was calculated, and it scored 95.14%. Due to the lack of research efforts in the literature dedicated to studying Arabic multi-annotation schemes, a distinguishing and a novel aspect of this dataset is the inclusion of six more annotation schemes that will bridge the gap by allowing researchers to explore and compare the effects of these schemes on the performance of the Arabic named entity recognizers. These annotation schemes are IOE, IOB, BIES, IOBES, IE, and BI. Additionally, five linguistic features, including part-of-speech tags, stopwords, gazetteers, lexical markers, and the presence of the definite article, are provided for each record in the dataset.
On the Self-Calibration of Aerodynamic Coefficients in Vehicle Dynamic Model-Based Navigation
Authors: Laupré Gabriel , Skaloud Jan
Published: July 2020

The performance of vehicle dynamic model (VDM)-based navigation largely depends on the accurate determination of aerodynamic coefficients that are unknown a priori. Among different techniques, such as model simulations or experimental analysis in a wind tunnel, the method of self-calibration via state-space augmentation benefiting Global Navigation Satellite System (GNSS) positioning represents an interesting and economical alternative. We study this technique under simulation with the goal of determining the impact of aircraft maneuvers on the precision and (de)-correlation of the aerodynamic coefficients among themselves and with respect to other error-states. A combination of different maneuvers indicates to be essential for obtaining satisfactory aerodynamic coefficients estimation and reduce their uncertainty.
Quantifying Land Cover Changes in a Mediterranean Environment Using Landsat TM and Support Vector Machines
Authors: Fragou Sotiria , Kalogeropoulos Kleomenis , Stathopoulos Nikolaos , Louka Panagiota , Srivastava Prashant K. , Karpouzas Sotiris , P. Kalivas Dionissios , P. Petropoulos George
Published: July 2020

The rapid advent in geoinformation technologies, such as Earth Observation (EO) and Geographical Information Systems (GIS), has made it possible to observe and monitor the Earth’s environment on variable geographical scales and analyze those changes in both time and space. This study explores the synergistic use of Landsat EO imagery and Support Vector Machines (SVMs) in obtaining Land Use/Land Cover (LULC) mapping and quantifying its spatio-temporal changes for the municipality of Mandra–Idyllia, Attica Region, Greece. The study area is representative of typical Mediterranean landscape in terms of physical structure and coverage of species composition. Landsat TM (Thematic Mapper) images from 1993, 2001 and 2010 were acquired, pre-processed and classified using the SVMs classifier. A total of nine basic classes were established. Eight spectral band ratios were created in order to incorporate them in the initial variables of the image. For validating the classification, in-situ data were collected for each LULC type during several field surveys that were conducted in the area. The overall classification accuracy for 1993, 2001 and 2010 Landsat images was reported as 89.85%, 91.01% and 90.24%, respectively, and with a statistical factor (K) of 0.96, 0.89 and 0.99, respectively. The classification results showed that the total extent of forests within the studied period represents the predominant LULC, despite the intense human presence and its impacts. A marginal change happened in the forest cover from 1993 to 2010, although mixed forest decreased significantly during the studied period. This information is very important for future management of the natural resources in the studied area and for understanding the pressures of the anthropogenic activities on the natural environment. All in all, the present study demonstrated the considerable promise towards the support of geoinformation technologies in sustainable environmental development and prudent resource management.
Challenges and Solutions for Non-Timber Forest Product Businesses in Finland–An Application of the SODA Analysis
Authors: Tikkanen Jukka , Takala Tuomo , Järvelä Marja-Liisa , Kurttila Mikko , Vanhanen Henri
Published: July 2020

This study aims to present a holistic image of the strategic development needs and potential solutions within the Finnish non-timber forest product (NTFP) business sector and demonstrate a new hybrid methodology for collaborative strategy formulation. The perceived challenges and solutions were collected with the 635 group-working method in a nationwide series of NTFP actor workshops. The analysis applied the Strategic Option Development and Analysis (SODA) approach and the formal network analysis. Business actors emphasised two complex and interrelated aims of development at the core of the business activity: (1) to improve the profitability of the NTFP business and (2) to facilitate the growth of the sector. The present bottleneck is perceived in the raw material acquisition and productising, and many wider development themes, such as business logic and sustainability, received little attention.
Collaborative Facilitation and Collaborative Inhibition in Virtual Environments
Authors: Guazzini Andrea , Guidi Elisa , Cecchini Cristina , Yoneki Eiko
Published: July 2020

Worldwide, organizations and small and medium-sized enterprises have already disruptively changed in many ways their physiological inner mechanisms, because of information and communication technologies (ICT) revolution. Nevertheless, the still ongoing COVID-19 worldwide emergency definitely promoted a wide adoption of teleworking modalities for many people around the world, making it more relevant than before to understand the real impact of virtual environments (VEs) on teamwork dynamics. From a psychological point of view, a critical question about teleworking modalities is how the social and cognitive dynamics of collaborative facilitation and collaborative inhibition would affect teamwork within VEs. This study analyzed the impact of a virtual environment (VE) on the recall of individuals and members of nominal and collaborative groups. The research assessed costs and benefits for collaborative retrieval by testing the effect of experimental conditions, stimulus materials, group size, experimental conditions order, anxiety state, personality traits, gender group composition and social interactions. A total of 144 participants were engaged in a virtual Deese-Roediger-McDermott (DRM) classical paradigm, which involved remembering word lists across two successive sessions, in one of four protocols: I-individual/nominal, I I -nominal/individual, I I I -nominal/collaborative, I V -collaborative/nominal. Results suggested, in general, a reduced collaborative inhibition effect in the collaborative condition than the nominal and individual condition. A combined effect between experimental condition and difficulty of the task appears to explain the presence of collaborative inhibition or facilitation. Nominal groups appeared to enhance the collaborative groups’ performance when virtual nominal groups come before collaborative groups. Variables such as personality traits, gender and social interactions may have a contribution to collaborative retrieval. In conclusion, this study indicated how VEs could maintain those peculiar social dynamics characterizing the participants’ engagement in a task, both working together and individually, and could affect their intrinsic motivation as well as performances. These results could be exploited in order to design brand new and evidenced-based practices, to improve teleworking procedures and workers well-being, as well as teleworking teamwork effectiveness.
Validation of a CFD-Based Numerical Wave Tank Model of the 1/20th Scale Wavestar Wave Energy Converter
Authors: Windt Christian , Faedo Nicolás , García-Violini Demián , Peña-Sanchez Yerai , Davidson Josh , Ferri Francesco , Ringwood John V.
Published: July 2020

Numerical wave tanks (NWTs) provide efficient test beds for the numerical analysis at various stages during the development of wave energy converters (WECs). To ensure the acquisition of accurate, high-fidelity data sets, validation of NWTs is a crucial step. However, using experimental data as reference during model validation, exact knowledge of all system parameters is required, which may not always be available, thus making an incremental validation inevitable. The present paper documents the numerical model validation of a 1/20 scale Wavestar WEC. The validation is performed considering different test case of increasing complexity: wave-only, wave excitation force, free decay, forced oscillation, and wave-induced motion cases. The results show acceptable agreement between the numerical and experimental data so that, under the well-known modelling constraints for mechanical friction and uncertainties in the physical model properties, the developed numerical model can be declared as validated.
Non-Destructive Technologies for Detecting Insect Infestation in Fruits and Vegetables under Postharvest Conditions: A Critical Review
Authors: Adedeji Akinbode A. , Ekramirad Nader , Rady Ahmed , Hamidisepehr Ali , Donohue Kevin D. , Villanueva Raul T. , Parrish Chadwick A. , Li Mengxing
Published: July 2020

In the last two decades, food scientists have attempted to develop new technologies that can improve the detection of insect infestation in fruits and vegetables under postharvest conditions using a multitude of non-destructive technologies. While consumers’ expectations for higher nutritive and sensorial value of fresh produce has increased over time, they have also become more critical on using insecticides or synthetic chemicals to preserve food quality from insects’ attacks or enhance the quality attributes of minimally processed fresh produce. In addition, the increasingly stringent quarantine measures by regulatory agencies for commercial import–export of fresh produce needs more reliable technologies for quickly detecting insect infestation in fruits and vegetables before their commercialization. For these reasons, the food industry investigates alternative and non-destructive means to improve food quality. Several studies have been conducted on the development of rapid, accurate, and reliable insect infestation monitoring systems to replace invasive and subjective methods that are often inefficient. There are still major limitations to the effective in-field, as well as postharvest on-line, monitoring applications. This review presents a general overview of current non-destructive techniques for the detection of insect damage in fruits and vegetables and discusses basic principles and applications. The paper also elaborates on the specific post-harvest fruit infestation detection methods, which include principles, protocols, specific application examples, merits, and limitations. The methods reviewed include those based on spectroscopy, imaging, acoustic sensing, and chemical interactions, with greater emphasis on the noninvasive methods. This review also discusses the current research gaps as well as the future research directions for non-destructive methods’ application in the detection and classification of insect infestation in fruits and vegetables.
Indication of Premelanosome Protein (PMEL) Expression Outside of Pigmented Bovine Skin Suggests Functions Beyond Eumelanogenesis
Authors: Knaust Jacqueline , Weikard Rosemarie , Albrecht Elke , Brunner Ronald M. , Günther Juliane , Kühn Christa
Published: July 2020

The premelanosome protein (PMEL) is important for fibril formation within melanosomes during vertebrate melanogenesis. Fibrils form a matrix for pigment deposition within pigmented tissues such as skin and hair. PMEL mutations are known to modulate eumelanic pigmentation in vertebrates. However, in bovines, PMEL mutations were also found to alter pheomelanic pigmentation resulting in coat color dilution. Furthermore, epistatic effects of a mutated PMEL allele were detected in the phenotypic expression of the bovine hair defect “rat-tail syndrome” (RTS) characterized by charcoal coat color and hair deformation. Reports about PMEL gene expression in non-pigmented tissues raised the hypothesis that there may be unknown functions of the PMEL protein beyond eumelanin deposition to PMEL fibrils. In our study, we analysed the PMEL protein expression in pigmented skin and non-pigmented bovine tissues (non-pigmented skin, thyroid gland, rumen, liver, kidney, and adrenal gland cortex). We found that a processed form of the bovine PMEL protein is expressed in pigmented as well as in non-pigmented tissues, which is in line with gene expression data from targeted RT-PCR and whole transcriptome RNAseq analysis. The PMEL protein is located in membranes and within the cytosol of epithelial cells. Based on our data from bovine tissues, we concluded that at least in cattle PMEL potentially has additional, yet unexplored functions, which might contribute to effects of PMEL mutations on pheomelanin coat color dilution and charcoal coat color in RTS animals. However, indication of PMEL protein in unpigmented cells and tissues will require further confirmation in the future, because there have been no confirmed reports before, which had detected bovine PMEL protein with specific antibodies either in pigmented or unpigmented tissue.