bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeting Peripherally Restricted Cannabinoid Receptor 1, Cannabinoid Receptor 2, and Endocannabinoid-Degrading Enzymes for the Treatment of Neuropathic Pain Including Neuropathic Orofacial Pain
Authors: Hossain Mohammad Zakir , Ando Hiroshi , Unno Shumpei , Kitagawa Junichi
Published: February 2020

Neuropathic pain conditions including neuropathic orofacial pain (NOP) are difficult to treat. Contemporary therapeutic agents for neuropathic pain are often ineffective in relieving pain and are associated with various adverse effects. Finding new options for treating neuropathic pain is a major priority in pain-related research. Cannabinoid-based therapeutic strategies have emerged as promising new options. Cannabinoids mainly act on cannabinoid 1 (CB1) and 2 (CB2) receptors, and the former is widely distributed in the brain. The therapeutic significance of cannabinoids is masked by their adverse effects including sedation, motor impairment, addiction and cognitive impairment, which are thought to be mediated by CB1 receptors in the brain. Alternative approaches have been developed to overcome this problem by selectively targeting CB2 receptors, peripherally restricted CB1 receptors and endocannabinoids that may be locally synthesized on demand at sites where their actions are pertinent. Many preclinical studies have reported that these strategies are effective for treating neuropathic pain and produce no or minimal side effects. Recently, we observed that inhibition of degradation of a major endocannabinoid, 2-arachydonoylglycerol, can attenuate NOP following trigeminal nerve injury in mice. This review will discuss the above-mentioned alternative approaches that show potential for treating neuropathic pain including NOP.
Transcriptome Analysis and Identification of Genes Associated with Starch Metabolism in Castanea henryi Seed (Fagaceae)
Authors: Liu Bin , Lin Ruqiang , Jiang Yuting , Jiang Shuzhen , Xiong Yuanfang , Lian Hui , Zeng Qinmeng , Liu Xuedie , Liu Zhong-Jian , Chen Shipin
Published: February 2020

Starch is the most important form of carbohydrate storage and is the major energy reserve in some seeds, especially Castanea henryi. Seed germination is the beginning of the plant’s life cycle, and starch metabolism is important for seed germination. As a complex metabolic pathway, the regulation of starch metabolism in C. henryi is still poorly understood. To explore the mechanism of starch metabolism during the germination of C. henryi, we conducted a comparative gene expression analysis at the transcriptional level using RNA-seq across four different germination stages, and analyzed the changes in the starch and soluble sugar contents. The results showed that the starch content increased in 0–10 days and decreased in 10–35 days, while the soluble sugar content continuously decreased in 0–30 days and increased in 30–35 days. We identified 49 candidate genes that may be associated with starch and sucrose metabolism. Three ADP-glucose pyrophosphorylase (AGPase) genes, two nucleotide pyrophosphatase/phosphodiesterases (NPPS) genes and three starch synthases (SS) genes may be related to starch accumulation. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the expression levels of these genes. Our study combined transcriptome data with physiological and biochemical data, revealing potential candidate genes that affect starch metabolism during seed germination, and provides important data about starch metabolism and seed germination in seed plants.
Metabolomic Analysis of Morus Cultivar Root Extracts and Their Ameliorative Effect on Testosterone-Induced Prostate Enlargement in Sprague-Dawley Rats
Authors: Choi Young-Jin , Lee Jae In , Fan Meiqi , Tang Yujiao , Yoon Eun-Jung , Ryu Young Bae , Kim Eun-Kyung
Published: February 2020

We investigated the metabolite changes of Morus roots (MRs) according to different cultivar families (Simheung, Daesim, Cheong-il, Sangchon, Daeseong, Suhong, Suwon, and Igsu) using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–QTOF-MS) to understand the relationship between different cultivars and metabolite changes. Data were analyzed by partial least squares discriminant analysis (PLS-DA), and samples were successfully separated in PLS-DA scores. Eight metabolites in the electrospray ionization (ESI)-positive mode and 16 metabolites in the ESI-negative mode contributed to the separation in PLS-DA. Our data suggest that comparative analysis of MR metabolites according to different cultivars is useful to better understand the relationship between the different cultivars and metabolite changes. Furthermore, we analyzed the MRs for their ability to improve benign prostatic hyperplasia (BPH). LNCaP cells were used to evaluate the prostate-specific antigen (PSA) inhibitory activity of MRs, and, amongst them, the extract with the highest activity was selected. Igsu demonstrated the highest inhibition effect of prostate-specific antigen (PSA) expression among the MR cultivars. Igsu was also evaluated by administration in a testosterone-induced benign prostatic hyperplasia model in Sprague-Dawley rats. Igsu was shown to ameliorate BPH as evidenced by the prostate index, expression of androgen receptor (AR) signaling-related protein, growth factors, cell proliferation-related proteins, apoptosis-related proteins, mitogen-activated protein kinase (MAPK) signaling proteins, and histological analysis. Hence, this study strongly suggests that Igsu may have a beneficial effect of on BPH.
Thyrotropin-Releasing Hormone (TRH) and Somatostatin (SST), but not Growth Hormone-Releasing Hormone (GHRH) nor Ghrelin (GHRL), Regulate Expression and Release of Immune Growth Hormone (GH) from Chicken Bursal B-Lymphocyte Cultures
Authors: Pech-Pool Santiago , Berumen Laura C. , Martínez-Moreno Carlos G. , García-Alcocer Guadalupe , Carranza Martha , Luna Maricela , Arámburo Carlos
Published: February 2020

It is known that growth hormone (GH) is expressed in immune cells, where it exerts immunomodulatory effects. However, the mechanisms of expression and release of GH in the immune system remain unclear. We analyzed the effect of growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), ghrelin (GHRL), and somatostatin (SST) upon GH mRNA expression, intracellular and released GH, Ser133-phosphorylation of CREB (pCREBS133), intracellular Ca2+ levels, as well as B-cell activating factor (BAFF) mRNA expression in bursal B-lymphocytes (BBLs) cell cultures since several GH secretagogues, as well as their corresponding receptors (-R), are expressed in B-lymphocytes of several species. The expression of TRH/TRH-R, ghrelin/GHS-R1a, and SST/SST-Rs (Subtypes 1 to 5) was observed in BBLs by RT-PCR and immunocytochemistry (ICC), whereas GHRH/GHRH-R were absent in these cells. We found that TRH treatment significantly increased local GH mRNA expression and CREB phosphorylation. Conversely, SST decreased GH mRNA expression. Additionally, when added together, SST prevented TRH-induced GH mRNA expression, but no changes were observed in pCREBS133 levels. Furthermore, TRH stimulated GH release to the culture media, while SST increased the intracellular content of this hormone. Interestingly, SST inhibited TRH-induced GH release in a dose-dependent manner. The coaddition of TRH and SST decreased the intracellular content of GH. After 10 min. of incubation with either TRH or SST, the intracellular calcium levels significantly decreased, but they were increased at 60 min. However, the combined treatment with both peptides maintained the Ca2+ levels reduced up to 60-min. of incubation. On the other hand, BAFF cytokine mRNA expression was significantly increased by TRH administration. Altogether, our results suggest that TRH and SST are implicated in the regulation of GH expression and release in BBL cultures, which also involve changes in pCREBS133 and intracellular Ca2+ concentration. It is likely that TRH, SST, and GH exert autocrine/paracrine immunomodulatory actions and participate in the maturation of chicken BBLs.
Characterization of Convergent Suppression by UCL-2077 (3-(Triphenylmethylaminomethyl)pyridine), Known to Inhibit Slow Afterhyperpolarization, of erg-Mediated Potassium Currents and Intermediate-Conductance Calcium-Activated Potassium Channels
Authors: Hsu Hung-Te , Lo Yi-Ching , Wu Sheng-Nan
Published: February 2020

UCL-2077 (triphenylmethylaminomethyl)pyridine) was previously reported to suppress slow afterhyperpolarization in neurons. However, the information with respect to the effects of UCL-2077 on ionic currents is quite scarce. The addition of UCL-2077 decreased the amplitude of erg-mediated K+ current (IK(erg)) together with an increased deactivation rate of the current in pituitary GH3 cells. The IC50 and KD values of UCL-2077-induced inhibition of IK(erg) were 4.7 and 5.1 μM, respectively. UCL-2077 (10 μM) distinctly shifted the midpoint in the activation curve of IK(erg) to less hyperpolarizing potentials by 17 mV. Its presence decreased the degree of voltage hysteresis for IK(erg) elicitation by long-lasting triangular ramp pulse. It also diminished the probability of the opening of intermediate-conductance Ca2+-activated K+ channels. In cell-attached current recordings, UCL-2077 raised the frequency of action currents. When KCNH2 mRNA was knocked down, a UCL-2077-mediated increase in AC firing was attenuated. Collectively, the actions elaborated herein conceivably contribute to the perturbating effects of this compound on electrical behaviors of excitable cells.
(+)-Limonene 1,2-Epoxide-Loaded SLNs: Evaluation of Drug Release, Antioxidant Activity, and Cytotoxicity in an HaCaT Cell Line
Authors: Souto Eliana B. , Zielinska Aleksandra , Souto Selma B. , Durazzo Alessandra , Lucarini Massimo , Santini Antonello , Silva Amélia M. , Atanasov Atanas G. , Marques Conrado , Andrade Luciana N. , Severino Patricia
Published: February 2020

In this work, we developed a solid lipid nanoparticle (SLN) formulation with (+)-limonene 1,2-epoxide and glycerol monostearate (Lim-SLNs), stabilized with Poloxamer® 188 in aqueous dispersion to modify the release profile of the loaded monoterpene derivative. We also evaluated the role of SLNs in lipid peroxidation and cytotoxicity in a spontaneously transformed aneuploid immortal keratinocyte cell line from adult human skin (the HaCaT cell line). For the cell viability assay, the colorimetric 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used. Lim-SLNs with a loading capacity and encapsulation efficiency of 0.39% and 63%, respectively, were produced by high pressure homogenization. A mean particle size of 194 ± 3.4 nm and polydispersity index of 0.244 were recorded for the loaded Lim-SLNs, as compared to 203 ± 1.5 nm (PI 0.213) for the non-loaded (blank) SLNs. The loading of the monoterpene derivative into glycerol monostearate SLNs fitted into the zero-order kinetics, and ameliorated both lipid peroxidation and cytotoxicity in a keratinocyte cell line. A promising formulation for antioxidant and anti-tumoral activities is here proposed.
The Surprising Effect of Phenformin on Cutaneous Darkening and Characterization of Its Underlying Mechanism by a Forward Chemical Genetics Approach
Authors: Takano Kei , Hachiya Akira , Murase Daiki , Kawasaki Akiko , Uda Hirokazu , Kasamatsu Shinya , Sugai Yoshiya , Takahashi Yoshito , Hase Tadashi , Ohuchi Atsushi , Suzuki Tamio
Published: February 2020

Melanin in the epidermis is known to ultimately regulate human skin pigmentation. Recently, we exploited a phenotypic-based screening system composed of ex vivo human skin cultures to search for effective materials to regulate skin pigmentation. Since a previous study reported the potent inhibitory effect of metformin on melanogenesis, we evaluated several biguanide compounds. The unexpected effect of phenformin, once used as an oral anti-diabetic drug, on cutaneous darkening motivated us to investigate its underlying mechanism utilizing a chemical genetics approach, and especially to identify alternatives to phenformin because of its risk of severe lactic acidosis. Chemical pull-down assays with phenformin-immobilized beads were performed on lysates of human epidermal keratinocytes, and subsequent mass spectrometry identified 7-dehydrocholesterol reductase (DHCR7). Consistent with this, AY9944, an inhibitor of DHCR7, was found to decrease autophagic melanosome degradation in keratinocytes and to intensely darken skin in ex vivo cultures, suggesting the involvement of cholesterol biosynthesis in the metabolism of melanosomes. Thus, our results validated the combined utilization of the phenotypic screening system and chemical genetics as a new approach to develop promising materials for brightening/lightening and/or tanning technologies.
Analysis of Non-Structural Carbohydrates and Xylem Anatomy of Leaf Petioles Offers New Insights in the Drought Response of Two Grapevine Cultivars
Authors: Falchi Rachele , Petrussa Elisa , Braidot Enrico , Sivilotti Paolo , Boscutti Francesco , Vuerich Marco , Calligaro Carla , Filippi Antonio , Herrera José Carlos , Sabbatini Paolo , Zancani Marco , Nardini Andrea , Peterlunger Enrico , Casolo Valentino
Published: February 2020

In grapevine, the anatomy of xylem conduits and the non-structural carbohydrates (NSCs) content of the associated living parenchyma are expected to influence water transport under water limitation. In fact, both NSC and xylem features play a role in plant recovery from drought stress. We evaluated these traits in petioles of Cabernet Sauvignon (CS) and Syrah (SY) cultivars during water stress (WS) and recovery. In CS, the stress response was associated to NSC consumption, supporting the hypothesis that starch mobilization is related to an increased supply of maltose and sucrose, putatively involved in drought stress responses at the xylem level. In contrast, in SY, the WS-induced increase in the latter soluble NSCs was maintained even 2 days after re-watering, suggesting a different pattern of utilization of NSC resources. Interestingly, the anatomical analysis revealed that conduits are constitutively wider in SY in well-watered (WW) plants, and that water stress led to the production of narrower conduits only in this cultivar.
PTEN Expression as a Complementary Biomarker for Mismatch Repair Testing in Breast Cancer
Authors: Lopez Gianluca , Noale Marianna , Corti Chiara , Gaudioso Gabriella , Sajjadi Elham , Venetis Konstantinos , Gambini Donatella , Runza Letterio , Costanza Jole , Pesenti Chiara , Grossi Francesco , Maggi Stefania , Ferrero Stefano , Bosari Silvano , Fusco Nicola
Published: February 2020

Mismatch repair (MMR) analysis in breast cancer may help to inform immunotherapy decisions but it lacks breast-specific guidelines. Unlike in other neoplasms, MMR protein loss shows intra-tumor heterogeneity and it is not mirrored by microsatellite instability in the breast. Additional biomarkers can improve MMR clinical testing. Phosphatase and tensin homolog (PTEN) inactivation is an early oncogenic event that is associated with MMR deficiency (dMMR) in several tumors. Here, we sought to characterize the diagnostic utility of PTEN expression analysis for MMR status assessment in breast cancer. A total of 608 breast cancers were profiled for their MMR and PTEN status. Proteins expression and distribution were analyzed by immunohistochemistry (IHC) on tissue microarrays and confirmed on full sections; PTEN copy number alterations were detected using a real-time PCR assay. Overall, 78 (12.8%) cases were MMR-heterogeneous (hMMR), while all patterns of PTEN expression showed no intra-tumor heterogeneity. Wild-type PTEN expression was observed in 15 (18.5%) dMMR tumors (p < 0.0001). Survival analyses revealed significant correlations between MMR-proficient (pMMR), PTEN expression, and a better outcome. The positive predictive value of PTEN-retained status for pMMR ranged from 94.6% in estrogen receptor (ER)+/HER2- tumors to 100% in HER2-amplified and ER-/HER2- cases. We propose a novel diagnostic algorithm where PTEN expression analysis can be employed to identify pMMR breast cancers.
Development of a Modified Three-Day T-maze Protocol for Evaluating Learning and Memory Capacity of Adult Zebrafish
Authors: Ngoc Hieu Bui Thi , Ngoc Anh Nguyen Thi , Audira Gilbert , Juniardi Stevhen , Liman Rhenz Alfred D. , Villaflores Oliver B. , Lai Yu-Heng , Chen Jung-Ren , Liang Sung-Tzu , Huang Jong-Chin , Hsiao Chung-Der
Published: February 2020

A T-maze test is an experimental approach that is used in congenital research. However, the food reward-based protocol for the T-maze test in fish has low efficiency and a long training period. The aim of this study is to facilitate the T-maze conditions by using a combination of the principles of passive avoidance and a spatial memory test. In our modified T-maze settings, electric shock punishment (1–2 V, 0.3–0.5 mA) is given at the left arm, with a green cue at the right arm. Also, the depth of both arms of the T-maze was increased. The parameters measured in our T-maze design were latency, freezing time, and time spent in different areas of the T-maze. We validated the utility of our modified T-maze protocol by showing the consistent finding of memory impairment in ZnCl2−treated fish, which has been previously detected with the passive avoidance test. In addition, we also tested the spatial memory performance of leptin a (lepa) mutants which displayed an obesity phenotype. The results showed that although the learning and memory performance for lepa KO fish were similar to control fish, they displayed a higher freezing behavior during the training phase. In conclusion, we have established a modified T-maze protocol that can be used to evaluate the anxiety, learning, and memory capacity of adult zebrafish within three days, for the first time.
Bone Marrow Stromal Cells Drive Key Hallmarks of B Cell Malignancies
Authors: Mangolini Maurizio , Ringshausen Ingo
Published: February 2020

All B cell leukaemias and a substantial fraction of lymphomas display a natural niche residency in the bone marrow. While the bone marrow compartment may only be one of several sites of disease manifestations, the strong clinical significance of minimal residual disease (MRD) in the bone marrow strongly suggests that privileged niches exist in this anatomical site favouring central elements of malignant transformation. Here, the co-existence of two hierarchical systems, originating from haematopoietic and mesenchymal stem cells, has extensively been characterised with regard to regulation of the former (blood production) by the latter. How these two systems cooperate under pathological conditions is far less understood and is the focus of many current investigations. More recent single-cell sequencing techniques have now identified an unappreciated cellular heterogeneity of the bone marrow microenvironment. How each of these cell subtypes interact with each other and regulate normal and malignant haematopoiesis remains to be investigated. Here we review the evidences of how bone marrow stroma cells and malignant B cells reciprocally interact. Evidently from published data, these cell–cell interactions induce profound changes in signalling, gene expression and metabolic adaptations. While the past research has largely focussed on understanding changes imposed by stroma- on tumour cells, it is now clear that tumour-cell contact also has fundamental ramifications for the biology of stroma cells. Their careful characterisations are not only interesting from a scientific biological viewpoint but also relevant to clinical practice: Since tumour cells heavily depend on stroma cells for cell survival, proliferation and dissemination, interference with bone marrow stroma–tumour interactions bear therapeutic potential. The molecular characterisation of tumour–stroma interactions can identify new vulnerabilities, which could be therapeutically exploited.
CG200745, a Novel HDAC Inhibitor, Attenuates Kidney Fibrosis in a Murine Model of Alport Syndrome
Authors: Suh Sang Heon , Choi Hong Sang , Kim Chang Seong , Kim In Jin , Cha Hyunju , Cho Joong Myung , Ma Seong Kwon , Kim Soo Wan , Bae Eun Hui
Published: February 2020

Histone deacetylases have been a target of therapy for organ fibrosis. Here, we report the protective effect of CG200745 (CG), a novel histone deacetylase inhibitor, on tubulointerstitial fibrosis in Col4a3−/− mice, a murine model of Alport syndrome. Morphological analyses revealed CG treatment markedly alleviated kidney fibrosis in Col4a3−/− mice at the age of 7 weeks. CG prevented the activation of transforming growth factor β (TGFβ) and its downstream SMAD signaling in the kidney of Col4a3−/− mice. As critical upstream regulators of TGFβ signaling, immunoblotting of whole kidney lysate of Col4a3−/− mice reveled that intra-renal renin–angiotensin system (RAS) was activated with concurrent upregulation of inflammation and apoptosis, which were effectively suppressed by CG treatment. CG suppressed both activation of RAS and up-regulation of TGFβ signals in angiotensin II-stimulated HK-2 cells, a human kidney proximal tubular epithelial cell line. CG inhibited activation of TGFβ-driven signals and fibrosis in NRK-49F cells, a rat kidney fibroblast cell line, under angiotensin II-rich conditions. Collectively, CG was found to be effective both in proximal tubular epithelial cells by inhibiting local RAS and TGFβ signaling activation, as well as in fibroblasts by blocking their transition to myofibroblasts, attenuating renal fibrosis in a murine model of Alport syndrome.
New Perspectives in Food Allergy
Authors: De Martinis Massimo , Sirufo Maria Maddalena , Suppa Mariano , Ginaldi Lia
Published: February 2020

The improvement of the knowledge of the pathophysiological mechanisms underlying the tolerance and sensitization to food antigens has recently led to a radical change in the clinical approach to food allergies. Epidemiological studies show a global increase in the prevalence of food allergy all over the world and manifestations of food allergy appear increasingly frequent also in elderly subjects. Environmental and nutritional changes have partly changed the epidemiology of allergic reactions to foods and new food allergic syndromes have emerged in recent years. The deepening of the study of the intestinal microbiota has highlighted important mechanisms of immunological adaptation of the mucosal immune system to food antigens, leading to a revolution in the concept of immunological tolerance. As a consequence, new prevention models and innovative therapeutic strategies aimed at a personalized approach to the patient affected by food allergy are emerging. This review focuses on these new perspectives and their practical implications in the management of food allergy, providing an updated view of this complex pathology.
Alterations in the Nervous System and Gut Microbiota after β-Hemolytic Streptococcus Group A Infection—Characteristics and Diagnostic Criteria of PANDAS Recognition
Authors: Baj Jacek , Sitarz Elżbieta , Forma Alicja , Wróblewska Katarzyna , Karakuła-Juchnowicz Hanna
Published: February 2020

The objective of this paper is to review and summarize conclusions from the available literature regarding Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS). The authors have independently reviewed articles from 1977 onwards, primarily focusing on the etiopathology, symptoms, differentiation between similar psychiatric conditions, immunological reactions, alterations in the nervous system and gut microbiota, genetics, and the available treatment for PANDAS. Recent research indicates that PANDAS patients show noticeable alterations within the structures of the central nervous system, including caudate, putamen, globus pallidus, and striatum, as well as bilateral and lentiform nuclei. Likewise, the presence of autoantibodies that interact with basal ganglia was observed in PANDAS patients. Several studies also suggest a relationship between the presence of obsessive-compulsive disorders like PANDAS and alterations to the gut microbiota. Further, genetic predispositions—including variations in the MBL gene and TNF-α—seem to be relevant regarding PANDAS syndrome. Even though the literature is still scarce, the authors have attempted to provide a thorough insight into the PANDAS syndrome, bearing in mind the diagnostic difficulties of this condition.
FOXL2 is a Progesterone Target Gene in the Endometrium of Ruminants
Authors: Eozenou Caroline , Lesage-Padilla Audrey , Mauffré Vincent , Healey Gareth D. , Camous Sylvaine , Bolifraud Philippe , Giraud-Delville Corinne , Vaiman Daniel , Shimizu Takashi , Miyamoto Akio , Sheldon Iain Martin , Constant Fabienne , Pannetier Maëlle , Sandra Olivier
Published: February 2020

Forkhead Box L2 (FOXL2) is a member of the FOXL class of transcription factors, which are essential for ovarian differentiation and function. In the endometrium, FOXL2 is also thought to be important in cattle; however, it is not clear how its expression is regulated. The maternal recognition of pregnancy signal in cattle, interferon-Tau, does not regulate FOXL2 expression. Therefore, in the present study, we examined whether the ovarian steroid hormones that orchestrate implantation regulate FOXL2 gene expression in ruminants. In sheep, we confirmed that FOXL2 mRNA and protein was expressed in the endometrium across the oestrous cycle (day 4 to day 15 post-oestrus). Similar to the bovine endometrium, ovine FOXL2 endometrial expression was low during the luteal phase of the oestrous cycle (4 to 12 days post-oestrus) and at implantation (15 days post-oestrus) while mRNA and protein expression significantly increased during the luteolytic phase (day 15 post-oestrus in cycle). In pregnant ewes, inhibition of progesterone production by trilostane during the day 5 to 16 period prevented the rise in progesterone concentrations and led to a significant increase of FOXL2 expression in caruncles compared with the control group (1.4-fold, p < 0.05). Ovariectomized ewes or cows that were supplemented with exogenous progesterone for 12 days or 6 days, respectively, had lower endometrial FOXL2 expression compared with control ovariectomized females (sheep, mRNA, 1.8-fold; protein, 2.4-fold; cattle; mRNA, 2.2-fold; p < 0.05). Exogenous oestradiol treatments for 12 days in sheep or 2 days in cattle did not affect FOXL2 endometrial expression compared with control ovariectomized females, except at the protein level in both endometrial areas in the sheep. Moreover, treating bovine endometrial explants with exogenous progesterone for 48h reduced FOXL2 expression. Using in vitro assays with COS7 cells we also demonstrated that progesterone regulates the FOXL2 promoter activity through the progesterone receptor. Collectively, our findings imply that endometrial FOXL2 is, as a direct target of progesterone, involved in early pregnancy and implantation.
Insight into the Role of Epigenetic Processes in Abiotic and Biotic Stress Response in Wheat and Barley
Authors: Kong Lingyao , Liu Yanna , Wang Xiaoyu , Chang Cheng
Published: February 2020

Environmental stresses such as salinity, drought, heat, freezing, heavy metal and even pathogen infections seriously threaten the growth and yield of important cereal crops including wheat and barley. There is growing evidence indicating that plants employ sophisticated epigenetic mechanisms to fine-tune their responses to environmental stresses. Here, we provide an overview of recent developments in understanding the epigenetic processes and elements—such as DNA methylation, histone modification, chromatin remodeling, and non-coding RNAs—involved in plant responses to abiotic and biotic stresses in wheat and barley. Potentials of exploiting epigenetic variation for the improvement of wheat and barley are discussed.
The Impact of Situational Complexity and Familiarity on Takeover Quality in Uncritical Highly Automated Driving Scenarios
Authors: Scharfe Marlene Susanne Lisa , Zeeb Kathrin , Russwinkel Nele
Published: February 2020

In the development of highly automated driving systems (L3 and 4), much research has been done on the subject of driver takeover. Strong focus has been placed on the takeover quality. Previous research has shown that one of the main influencing factors is the complexity of a traffic situation that has not been sufficiently addressed so far, as different approaches towards complexity exist. This paper differentiates between the objective complexity and the subjectively perceived complexity. In addition, the familiarity with a takeover situation is examined. Gold et al. show that repetition of takeover scenarios strongly influences the take-over performance. Yet, both complexity and familiarity have not been considered at the same time. Therefore, the aim of the present study is to examine the impact of objective complexity and familiarity on the subjectively perceived complexity and the resulting takeover quality. In a driving simulator study, participants are requested to take over vehicle control in an uncritical situation. Familiarity and objective complexity are varied by the number of surrounding vehicles and scenario repetitions. Subjective complexity is measured using the NASA-TLX; the takeover quality is gathered using the take-over controllability rating (TOC-Rating). The statistical evaluation results show that the parameters significantly influence the takeover quality. This is an important finding for the design of cognitive assistance systems for future highly automated and intelligent vehicles.
Preserving Digital Privacy in e-Participation Environments: Towards GDPR Compliance
Authors: Diamantopoulou Vasiliki , Androutsopoulou Aggeliki , Gritzalis Stefanos , Charalabidis Yannis
Published: February 2020

The application of the General Data Protection Regulation (GDPR) 2016/679/EC, the Regulation for the protection of personal data, is a challenge and must be seen as an opportunity for the redesign of the systems that are being used for the processing of personal data. An unexplored area where systems are being used to collect and process personal data are the e-Participation environment. The latest generations of such environments refer to sociotechnical systems based on the exploitation of the increasing use of Social Media, by using them as valuable tools, able to provide answers and decision support in public policy formulation. This work explores the privacy requirements that GDPR imposes in such environments, contributing to the identification of challenges that e-Participation approaches have to deal with, with regard to privacy protection.
High-Efficiency Switched-Capacitor DC-DC Converter with Three Decades of Load Current Range Using Adaptively-Biased PFM
Authors: Veerabathini Anurag , Furth Paul M.
Published: February 2020

A fully-integrated switched-capacitor (SC) DC-DC converter that steps down 2.0 V to 0.9 V with a peak efficiency of 80% is implemented in a 0.18 μ m CMOS process. An ultra-low-power voltage-controlled oscillator that generates a wide range of switching frequencies is proposed to extend battery runtime. An efficiency >70% for load currents in the range of 12 μ A to 17.8 mA is achieved by implementing a novel adaptively-biased pulse frequency modulation (ABPFM) technique in the controller. A symmetric charge-discharge topology with two-phase time interleaving is used as a power stage to reduce the output voltage ripple to <72 mV over the entire load current range.
PlanetScope and Landsat 8 Imageries for Bathymetry Mapping
Authors: Gabr Bassam , Ahmed Mostafa , Marmoush Yehia
Published: February 2020

Bathymetry has a great importance in coastal projects. Obtaining proper bathymetric information is necessary for navigation, numerical modeling, and coastal zone management studies. Over the past three decades, a number of measuring protocols have been validated for bathymetry mapping, either by means of echosounding or LIght Detection and Ranging (LIDAR). Although these traditional methods hold a high vertical accuracy, they may have limitations in accessibility for some areas. Remote sensing (RS) techniques can be alternatively utilized for bathymetry extraction and update for such cases. The satellite derived bathymetry (SDB) can be analytically or empirically obtained based on various RS datasets with different spatiotemporal resolution. The current study proposes a methodology to spatially enhance the Landsat-derived bathymetry. Two different satellite images, i.e., Landsat and PlantScope with a spatial resolution of 30 and 3 m respectively have been assessed in bathymetry mapping. The Landsat image resolution has been spatially enhanced to match the Planetscope resolution. The panchromatic band of the Landsat image has been downscaled and used for pan-sharpening the multispectral bands. The bathymetry was empirically estimated from the blue and green spectral bands using the linear model by Lyzenga. The SDB model was calibrated using field measurements of water depths observed by a single beam echosounder. The Bathymetry detection methodology has been applied in an area of the Northern coast of Egypt. The SDB from the PlanetScope, Landsat 8 OLI, and Enhanced Landsat 8 OLI were assessed using error analysis. It was found that the Enhanced Landsat has a comparable result with the PlanetScope. The root mean square error is 0.38 and 0.43 m for PlanetScope and Enhanced Landsat, respectively. The current methodology was also tested by the ratio transform model for SDB and the results revealed the same conclusion as the linear model. Thus, the developed algorithm provides SDB using free Landsat images that is of comparable accuracy to the relatively expensive PlanetScope SDB.
HER2 Heterogeneity in Personalized Therapy of Gastro-Oesophageal Malignancies: An Overview by Different Methodologies
Authors: Ieni Antonio , Cardia Roberta , Pizzimenti Cristina , Zeppa Pio , Tuccari Giovanni
Published: February 2020

Human epidermal growth factor receptor-2 (HER2)-expression gastro-oesophageal adenocarcinomas (GEA) gained interest as an important target for therapy with trastuzumab. In the current review, we focused the current knowledge on HER2 status in dysplastic and neoplastic gastric conditions, analyzing the methodological procedures to identify HER2 expression/amplification, as well as the proposed scoring recommendations. One of the most relevant questions to evaluate the useful impact of HER2 status on therapeutic choice in GEAs is represented by the significant heterogeneity of HER2 protein and gene expression that may affect the targeted treatment selection. Future development of biotechnology will continue to evolve in order to offer more powerful detection systems for the assessment of HER2 status. Finally, liquid biopsy as well as mutation/amplification of several additional genes may furnish an early detection of secondary HER2 resistance mechanisms in GEAs with a better monitoring of the treatment response.
High-Efficiency Removal of Cr(VI) from Wastewater by Mg-Loaded Biochars: Adsorption Process and Removal Mechanism
Authors: Li Anyu , Deng Hua , Jiang Yanhong , Ye Chenghui
Published: February 2020

Biochars were produced with magnesium chloride as an additive for the sorption of hexavalent chromium dissolved in water using five types of straw (from taro, corn, cassava, Chinese fir, and banana) and one type of shell (Camellia oleifera) as the raw materials. The removal of hexavalent chromium by the six biochars mainly occurred within 60 min and then gradually stabilized. The kinetics of the adsorption process were second order, the Langmuir model was followed, and the adsorption of Cr(VI) by the six biochars was characterized by Langmuir monolayer chemisorption on a heterogeneous surface. Banana straw biochar (BSB) had the best performance, which perhaps benefitted from its special structure and best adsorption effect on Cr(VI), and the theoretical adsorption capacity was calculated as 125.00 mg/g. For the mechanism analysis, Mg-loaded biochars were characterized before and after adsorption by Fourier transform infrared spectroscopy (FTIR), X-ray diffractometry (XRD), and scanning electron microscopy/energy dispersive spectroscopy (SEM-EDS). The adsorption mechanism differed from the adsorption process of conventional magnetic biochar, and biochar interactions with Cr(VI) were controlled mainly by electrostatic attraction, complexation, and functional group bonding. In summary, the six Mg-loaded biochars exhibit great potential advantages in removing Cr(VI) from wastewater and have promising potential for practical use, especially BSB, which shows super-high adsorption performance.
Dimension Effects on the Acoustic Behavior of TRC Plates
Authors: Ospitia Nicolas , Aggelis Dimitrios G. , Tsangouri Eleni
Published: February 2020

Acoustic emission (AE) is a monitoring technique that has proven its suitability in and outside of the laboratory in characterizing the structural condition of materials. In composites for construction and repair, several breakthroughs have been recently noted involving mainly fracture mode evaluation based on the AE waveform characteristics. However, the acquired signals, apart from the cracking source strongly depend on the size and shape of the plate specimens. While the effect of wave propagation distance has been studied, the effect of the lateral dimension of the plate has not been given proper attention, being a broken link in translating the results from small coupons to real size plates. This paper examines wave propagation from artificial sources as well as actual AE signals in textile-reinforced cement (TRC) plates indicating the strong differences in the results that are attributed just to the shape and size of the specimens and showing that interpretation toward the actual sources is firmly connected to geometric factors.
Investigation of Peritectic Solidification Morphologies by Using the Binary Organic Model System TRIS-NPG
Authors: Mogeritsch Johann P. , Abdi Mehran , Ludwig Andreas
Published: February 2020

Under pure diffusive growth conditions, layered peritectic solidification is possible. In reality, the competitive growth of the primary α-phase and the peritectic β-phase revealed some complex peritectic solidification morphologies due to thermo-solutal convection. The binary organic components Tris-(hydroxylmenthyl) aminomethane-(Neopentylglycol) were used as a model system for metal-like solidification. The transparency of the high-temperature non-faceted phases allows for the studying of the dynamic of the solid/liquid interface that lead to peritectic solidification morphologies. Investigations were carried out by using the Bridgman technic for process conditions where one or both phases solidify in a non-planar manner. Different growth conditions were observed, leeding to competitive peritectic growth morphologies. Additionally, the competitive growth was solved numerically to interpret the observed transparent solidification patterns.
Bond-Slip Behavior between Stainless Steel Rebars and Concrete
Authors: Pauletta Margherita , Rovere Nicola , Randl Norbert , Russo Gaetano
Published: February 2020

Maintenance of reinforced concrete structures is a prevailing topic, especially with regard to lifeline structures and bridges, many of which are now designed with a service life beyond 100 years. Reinforcement made of ordinary (carbon) steel may corrode in aggressive environments. Stainless steel, being much more resistant to corrosion, is a valid solution to facilitate the protection of the works, increasing the service life and reducing the need for repair and maintenance. Despite the potential for stainless steel to reduce maintenance costs, studies investigating the influence of stainless steel on the behavior of reinforced concrete structures are limited. This study investigated the bond behavior of stainless steel rebars by means of experimental tests on reinforced concrete specimens with different concrete cover thicknesses, concrete strengths, and bar diameters. In each case, identical specimens with carbon steel reinforcement were tested for comparison. The failure modes of the specimens were examined, and a bond stress–slip relationship for stainless steel bars was established. This research shows that the bond behavior of stainless steel rebars is comparable to that of carbon steel bars.
Identification of Quorum Sensing Activators and Inhibitors in The Marine Sponge Sarcotragus spinosulus
Authors: Saurav Kumar , Borbone Nicola , Burgsdorf Ilia , Teta Roberta , Caso Alessia , Bar-Shalom Rinat , Esposito Germana , Britstein Maya , Steindler Laura , Costantino Valeria
Published: February 2020

Marine sponges, a well-documented prolific source of natural products, harbor highly diverse microbial communities. Their extracts were previously shown to contain quorum sensing (QS) signal molecules of the N-acyl homoserine lactone (AHL) type, known to orchestrate bacterial gene regulation. Some bacteria and eukaryotic organisms are known to produce molecules that can interfere with QS signaling, thus affecting microbial genetic regulation and function. In the present study, we established the production of both QS signal molecules as well as QS inhibitory (QSI) molecules in the sponge species Sarcotragus spinosulus. A total of eighteen saturated acyl chain AHLs were identified along with six unsaturated acyl chain AHLs. Bioassay-guided purification led to the isolation of two brominated metabolites with QSI activity. The structures of these compounds were elucidated by comparative spectral analysis of 1HNMR and HR-MS data and were identified as 3-bromo-4-methoxyphenethylamine (1) and 5,6-dibromo-N,N-dimethyltryptamine (2). The QSI activity of compounds 1 and 2 was evaluated using reporter gene assays for long- and short-chain AHL signals (Escherichia coli pSB1075 and E. coli pSB401, respectively). QSI activity was further confirmed by measuring dose-dependent inhibition of proteolytic activity and pyocyanin production in Pseudomonas aeruginosa PAO1. The obtained results show the coexistence of QS and QSI in S. spinosulus, a complex signal network that may mediate the orchestrated function of the microbiome within the sponge holobiont.
Visible-Light Active Photocatalytic Dual Layer Hollow Fiber (DLHF) Membrane and Its Potential in Mitigating the Detrimental Effects of Bisphenol A in Water
Authors: Kamaludin Roziana , Rasdi Zatilfarihiah , Othman Mohd Hafiz Dzarfan , Abdul Kadir Siti Hamimah Sheikh , Mohd Nor Noor Shafina , Khan Jesmine , Wan Mohamad Zain Wan Nor I’zzah , Ismail Ahmad Fauzi , A Rahman Mukhlis , Jaafar Juhana
Published: February 2020

The presence of bisphenol A (BPA) in various water sources has potentially led to numerous adverse effects in human such as increased in blood pressure and derangement in liver function. Thus, a reliable treatment for the removing BPA is highly required. This present work aimed to study the efficiency of visible light driven photocatalytic dual-layer hollow fiber (DLHF) membrane for the removal of BPA from water and further investigated its detrimental effects by using an in-vivo model. The prepared membranes were characterized for their morphology, particles distribution, surface roughness, crystallinity and light absorption spectra. The removal of 81.6% and 86.7% in BPA concentration was achieved for N-doped TiO2 DLHF after 360 min of visible and UV light irradiation, respectively. No significant changes for all three groups were observed in liver function test meanwhile the rats-exposed to untreated BPA water shows significance blood pressure increment contrary to rats-exposed to treated BPA water. Similarly, the normal morphology in both jejunum and ileum were altered in rats-exposed to untreated BPA water group. Altogether, the presence of N-doped TiO2 in DLHF are shown to significantly enhance the photocatalytic degradation activity under visible irradiation, which effectively mitigates the effect of BPA in an in-vivo model.
CMT-Based Wire Arc Additive Manufacturing Using 316L Stainless Steel: Effect of Heat Accumulation on the Multi-Layer Deposits
Authors: Lee Seung Hwan
Published: February 2020

CMT welding sources are garnering attention as alternative heat sources for wire arc additive manufacturing because of their low-heat input. A comprehensive experimental and numerical study on the multi-layer deposition of STS316L was performed to investigate effect of heat accumulation during the deposition. The numerical model which is appropriate for WAMM was developed considering the characteristics of the CMT heat source for the first time. Using a high-speed camera, the transient behavior of the CMT arc was investigated, and applied to the heat source of the numerical model. The model was then used to analyze 10-layered deposits of STS316L, fabricated using CMT-based WAAM. During deposition, the temperature is measured using a pyrometer to analyze the microstructure, after which the cooling rate of each layer is estimated. The measured and simulated SDAS were compared. Based on the comparison, a guideline for the equation regarding the SDAS size and cooling rate was suggested.
Multi-Objective Optimization of Intermediate Roll Profile for a 6-High Cold Rolling Mill
Authors: Jin Xin , Li Chang-sheng , Wang Yu , Li Xiao-gang , Gu Tian , Xiang Yong-guang
Published: February 2020

The multi-objective optimization of the SmartCrown intermediate roll profile for a cold rolling mill was proposed in this paper in order to improve the strip flatness quality. A coupling model of roll profile and strip flatness was established, and the roll gap profile, roll gap crown adjustment range, rolls contact pressure, and strip flatness under different intermediate roll profile parameters were calculated based on the coupling model. The results showed that the roll gap crown adjustment range and rolls contact pressure difference increased with increasing roll profile parameters. The roll profile parameters were multi-optimized based on the non-dominated sorting genetic algorithm II (NSGA-II). The minimum rolls contact pressure difference and maximum roll gap crown adjustment range were taken as the objective function of multi-objective optimization. The optimal roll profile parameters were applied to a six-high five stand tandem cold rolling mills, which improved the flatness quality of the DP780 steel strip.
Third Worldwide Occurrence of Juangodoyite, Na2Cu(CO3)2, and Other Secondary Na, Cu, Mg, and Ca Minerals in the Fore-Sudetic Monocline (Lower Silesia, SW Poland)
Authors: Kruszewski Łukasz , Świerk Mateusz , Siuda Rafał , Szełęg Eligiusz , Marciniak-Maliszewska Beata
Published: February 2020

Na-Cu carbonates are relatively rare secondary minerals in weathering zones of ore deposits. Hereby we describe mineral composition and crystal chemistry of the most important secondary (Na)Cu minerals and their Na- and Mg-bearing associates forming rich paragenesis in Rudna IX mine. A non-bulky Ca-rich dripstone-like paragenesis from Lubin Główny mine is also characterized, using Powder X-Ray Diffraction, Rietveld, and Electron Microprobe methods. Light blue juangodoyite (3rd occurrence worldwide) and darker chalconatronite are the most important members of the Rudna IX paragenesis, being associated with malachite, aragonite (intergrown with hydromagnesite and northupite), and probably cornwallite. Most of the minerals are chemically close to their ideal composition, with minor Mg substitution in malachite. Cu chlorides are mainly represented by clinoatacamite and probably herbertsmithite. Additional, minor phases include trace Cu minerals langite, wroewolfeite, and a lavendulan-group mineral, and monohydrocalcite. Separate halite-rich encrustations are shown to be filled with eriochalcite, ktenasite, and kröhnkite. The most likely to be confirmed coexisting species include paratacamite, wooldridgeite/nesquehonite, johillerite, melanothallite, and kipushite. The Lubin paragenesis mainly comprises aragonite, gypsum, rapidcreekite, and monohydrocalcite, with trace vaterite. Blue colouration is mainly provided by a yet unspecified Ni-, Co-, Mg-, and Mn-bearing Cu-Zn-Ca arsenate mineral close to parnauite.