bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of Escitalopram on Central Serotonergic and Dopaminergic Systems in Patients with Cervical Dystonia, and Its Relationship with Clinical Treatment Effects: A Double-Blind Placebo-Controlled Trial
Authors: Zoons Evelien , Tijssen Marina A.J. , Dreissen Yasmine E.M. , Smit Marenka , Booij Jan
Published: June 2020

Purpose: The pathophysiology of cervical dystonia (CD) is thought to be related to changes in dopamine and serotonin levels in the brain. We performed a double-blind trial with escitalopram (selective serotonin reuptake inhibitor; SSRI) in patients with CD. Here, we report on changes in dopamine D2/3 receptor (D2/3R), dopamine transporter (DAT) and serotonin transporter (SERT) binding potential (BPND) after a six-week treatment course with escitalopram or placebo. Methods: CD patients had [123I]FP-CIT SPECT (I-123 fluoropropyl carbomethoxy-3 beta-(4-iodophenyltropane) single-photon emission computed tomography) scans, to quantify extrastriatal SERT and striatal DAT, and [123I]IBZM SPECT (I-123 iodobenzamide SPECT) scans to quantify striatal D2/3R BPND before and after six weeks of treatment with either escitalopram or placebo. Treatment effect was evaluated with the Clinical Global Impression scale for dystonia, jerks and psychiatric symptoms, both by physicians and patients. Results: In both patients treated with escitalopram and placebo there were no significant differences after treatment in SERT, DAT or D2/3R BPND. Comparing scans after treatment with escitalopram (n = 8) to placebo (n = 8) showed a trend (p = 0.13) towards lower extrastriatal SERT BPND in the SSRI group (median SERT occupancy of 64.6%). After treatment with escitalopram, patients who reported a positive effect on dystonia or psychiatric symptoms had significantly higher SERT occupancy compared to patients who did not experience an effect. Conclusion: Higher extrastriatal SERT occupancy after treatment with escitalopram is associated with a trend towards a positive subjective effect on dystonia and psychiatric symptoms in CD patients.
Marine-Derived Surface Active Agents: Health-Promoting Properties and Blue Biotechnology-Based Applications
Authors: Anestopoulos Ioannis , Kiousi Despina-Evgenia , Klavaris Ariel , Maijo Monica , Serpico Annabel , Suarez Alba , Sanchez Guiomar , Salek Karina , Chasapi Stylliani A. , Zompra Aikaterini A. , Galanis Alex , Spyroulias Georgios A. , Gombau Lourdes , Euston Stephen R. , Pappa Aglaia , Panayiotidis Mihalis I.
Published: June 2020

Surface active agents are characterized for their capacity to adsorb to fluid and solid-water interfaces. They can be classified as surfactants and emulsifiers based on their molecular weight (MW) and properties. Over the years, the chemical surfactant industry has been rapidly increasing to meet consumer demands. Consequently, such a boost has led to the search for more sustainable and biodegradable alternatives, as chemical surfactants are non-biodegradable, thus causing an adverse effect on the environment. To these ends, many microbial and/or marine-derived molecules have been shown to possess various biological properties that could allow manufacturers to make additional health-promoting claims for their products. Our aim, in this review article, is to provide up to date information of critical health-promoting properties of these molecules and their use in blue-based biotechnology (i.e., biotechnology using aquatic organisms) with a focus on food, cosmetic and pharmaceutical/biomedical applications.
Leptin and Notch Signaling Cooperate in Sustaining Glioblastoma Multiforme Progression
Authors: Panza Salvatore , Russo Umberto , Giordano Francesca , Leggio Antonella , Barone Ines , Bonofiglio Daniela , Gelsomino Luca , Malivindi Rocco , Conforti Francesca Luisa , Naimo Giuseppina Daniela , Giordano Cinzia , Catalano Stefania , Andò Sebastiano
Published: June 2020

Glioblastoma multiforme (GBM) is the most malignant form of glioma, which represents one of the commonly occurring tumors of the central nervous system. Despite the continuous development of new clinical therapies against this malignancy, it still remains a deadly disease with very poor prognosis. Here, we demonstrated the existence of a biologically active interaction between leptin and Notch signaling pathways that sustains GBM development and progression. We found that the expression of leptin and its receptors was significantly higher in human glioblastoma cells, U-87 MG and T98G, than in a normal human glial cell line, SVG p12, and that activation of leptin signaling induced growth and motility in GBM cells. Interestingly, flow cytometry and real-time RT-PCR assays revealed that GBM cells, grown as neurospheres, displayed stem cell-like properties (CD133+) along with an enhanced expression of leptin receptors. Leptin treatment significantly increased the neurosphere forming efficiency, self-renewal capacity, and mRNA expression levels of the stemness markers CD133, Nestin, SOX2, and GFAP. Mechanistically, we evidenced a leptin-mediated upregulation of Notch 1 receptor and the activation of its downstream effectors and target molecules. Leptin-induced effects on U-87 MG and T98G cells were abrogated by the selective leptin antagonist, the peptide LDFI (Leu-Asp-Phe-Ile), as well as by the specific Notch signaling inhibitor, GSI (Gamma Secretase Inhibitor) and in the presence of a dominant-negative of mastermind-like-1. Overall, these findings demonstrate, for the first time, a functional interaction between leptin and Notch signaling in GBM, highlighting leptin/Notch crosstalk as a potential novel therapeutic target for GBM treatment.
Free Fatty Acid Receptors 2 and 3 as Microbial Metabolite Sensors to Shape Host Health: Pharmacophysiological View
Authors: Mishra Sidharth P. , Karunakar Prashantha , Taraphder Subhash , Yadav Hariom
Published: June 2020

The role of the gut microbiome in human health is becoming apparent. The major functional impact of the gut microbiome is transmitted through the microbial metabolites that are produced in the gut and interact with host cells either in the local gut environment or are absorbed into circulation to impact distant cells/organs. Short-chain fatty acids (SCFAs) are the major microbial metabolites that are produced in the gut through the fermentation of non-digestible fibers. SCFAs are known to function through various mechanisms, however, their signaling through free fatty acid receptors 2 and 3 (FFAR2/3; type of G-coupled protein receptors) is a new therapeutic approach. FFAR2/3 are widely expressed in diverse cell types in human and mice, and function as sensors of SCFAs to change several physiological and cellular functions. FFAR2/3 modulate neurological signaling, energy metabolism, intestinal cellular homeostasis, immune response, and hormone synthesis. FFAR2/3 function through Gi and/or Gq signaling, that is mediated through specific structural features of SCFAs-FFAR2/3 bindings and modulating specific signaling pathway. In this review, we discuss the wide-spread expression and structural homologies between human and mice FFAR2/3, and their role in different human health conditions. This information can unlock opportunities to weigh the potential of FFAR2/3 as a drug target to prevent human diseases.
From Correlational Signs to Markers. Current Trends in Neuroelectric Research on Visual Attentional Processing
Authors: Zani Alberto
Published: June 2020

Traditionally, electroencephalographic (EEG) and event-related brain potentials (ERPs) research on visual attentional processing attempted to account for mental processes in conceptual terms without reference to the way in which they were physically realized by the anatomical structures and physiological processes of the human brain. The brain science level of analysis, in contrast, attempted to explain the brain as an information processing system and to explain mental events in terms of brain processes. Somehow overcoming the separation between the two abovementioned levels of analysis, the cognitive neuroscience level considered how information was represented and processed in the brain. Neurofunctional processing takes place in a fraction of a second. Hence, the very high time resolution and the reliable sensitivity of EEG and ERPs in detecting fast functional changes in brain activity provided advantages over hemodynamic imaging techniques such as positron emission tomography (PET) or functional magnetic resonance imaging (fMRI), as well as over behavioral measures. However, volume conduction and lack of three-dimensionality limited applications of EEG and ERPs per se more than hemodynamic techniques for revealing locations in which brain processing occurs. These limits could only be overcome by subtraction methods for isolating attentional effects that might endure over time in EEG and may be riding even over several different ERP components, and by intracerebral single and distributed electric source analyses as well as the combining of these signals with high-spatial resolution hemodynamic signals (fMRI), both in healthy individuals and clinical patients. In my view, the articles of the Special Issue concerned with “ERP and EEG Markers of Brain Visual Attentional Processing” of the present journal Brain Sciences provide very good examples of all these levels of analysis.
Stress-Induced Increase in Cortisol Negatively Affects the Consolidation of Contextual Elements of Episodic Memories
Authors: Sabia Matthew , Hupbach Almut
Published: June 2020

Stress can modulate episodic memory in various ways. The present study asks how post-encoding stress affects visual context memory. Participants encoded object images centrally positioned on background scenes. After encoding, they were either exposed to cold pressure stress (CPS) or a warm water control procedure. Forty-right hours later, participants were cued with object images, and for each image, they were asked to select the background scene with which it was paired during study among three highly similar options. Only male but not female participants reacted with a significant increase in salivary cortisol to CPS, and the stress and control group did not differ in recognition performance. Comparing recognition performance between stress responders and non-responders, however, revealed a significant impairment in context memory in responders. Additionally, proportional increase in cortisol was negatively correlated with the number of correctly recognized scenes in responders. Due to the small number of responders, these findings need to be interpreted with caution but provide preliminary evidence that stress-induced cortisol increase negatively affects the consolidation of contextual elements of episodic memories.
T1 Glottic Cancer: Does Anterior Commissure Involvement Worsen Prognosis?
Authors: Mannelli Giuditta , Comini Lara Valentina , Santoro Roberto , Bettiol Alessandra , Vannacci Alfredo , Desideri Isacco , Bonomo Pierluigi , Piazza Cesare
Published: June 2020

Radiotherapy (RT) and transoral laser microsurgery (TLM) represent the main treatment modalities for early glottic carcinoma. Local failure is notoriously more frequent in T1b glottic cancer in comparison to T1a and T2 tumors. In this scenario, the role of anterior commissure (AC) involvement is still controversial. The aim of the present study was therefore to determine its potential prognostic power in worsening patients’ survival and outcomes. We categorized different tumor glottic fold locations with respect to the involvement of one (T1a) or both vocal cords, with or without AC involvement. We analyzed a retrospective cohort of 74 patients affected by Stage I glottic cancer, treated between 2011 and 2018 by TLM or RT at a single academic institution. There were 22 T1a (30%) and 52 T1b (70%) cases. The median follow-up period was 30 months (mean, 32.09 ± 18.738 months; range, 12–79). Three-year overall survival (OS), disease-specific survival (DSS), recurrence-free survival (RFS), and laryngectomy-free survival (LFS) were compared according to tumor location, extension, and cT category. According to both uni- and multivariate analyses, an increased risk for recurrence in T1b with AC involvement and T1a tumors was 7.31 and 9.45 times, respectively (p-values of 0.054 and 0.030, respectively). Among the 17 recurrences, T1b with AC involvement experienced 15 tumor relapses (88.2%), thus significantly affecting both the RFS and LFS in comparison to the other two tumor subcategories (T1a, p = 0.028 and T1b without AC involvement, p = 0.043). The deteriorating prognosis in the presence of AC involvement likely reflects the need to power the hazard consistency and discrimination of the T1b category when associated with such a risk factor, thus deserving an independent T category.
Diffusion-Weighted Imaging in Oncology: An Update
Authors: Messina Carmelo , Bignone Rodolfo , Bruno Alberto , Bruno Antonio , Bruno Federico , Calandri Marco , Caruso Damiano , Coppolino Pietro , De Robertis Riccardo , Gentili Francesco , Grazzini Irene , Natella Raffaele , Scalise Paola , Barile Antonio , Grassi Roberto , Albano Domenico ,   on behalf of the Young SIRM Working Group
Published: June 2020

To date, diffusion weighted imaging (DWI) is included in routine magnetic resonance imaging (MRI) protocols for several cancers. The real additive role of DWI lies in the “functional” information obtained by probing the free diffusivity of water molecules into intra and inter-cellular spaces that in tumors mainly depend on cellularity. Although DWI has not gained much space in some oncologic scenarios, this non-invasive tool is routinely used in clinical practice and still remains a hot research topic: it has been tested in almost all cancers to differentiate malignant from benign lesions, to distinguish different malignant histotypes or tumor grades, to predict and/or assess treatment responses, and to identify residual or recurrent tumors in follow-up examinations. In this review, we provide an up-to-date overview on the application of DWI in oncology.
Diagnosis and Treatment of Primary Cutaneous B-Cell Lymphomas: State of the Art and Perspectives
Authors: Dumont Maëlle , Battistella Maxime , Ram-Wolff Caroline , Bagot Martine , de Masson Adèle
Published: June 2020

Primary cutaneous B-cell lymphomas are rare entities that develop primarily in the skin. They constitute a heterogeneous group that represents around a quarter of primary cutaneous lymphomas. The 2018 update of the World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) classification differentiates primary cutaneous marginal zone lymphoma and primary cutaneous follicle center lymphoma with an indolent course from primary cutaneous diffuse large B-cell lymphoma, leg type with an aggressive behavior. The broad spectrum of clinical presentations and the disease course marked by frequent relapses are diagnostic and therapeutic challenges. The classification of these diseases has been refined in recent years, which allows to better define their immunopathogenesis and specific management. In the present article, we review the main clinico-biological characteristics and the current therapeutic options of these three main subsets. Based on the recent therapeutic advances in nodal B-cell lymphomas, we focus on the development of novel treatment options applicable to primary cutaneous B-cell lymphomas, including targeted therapies, combination treatments and immunotherapeutic approaches, and cover basic, translational and clinical aspects aiming to improve the treatment of cutaneous B-cell lymphomas.
Association of Genetic Variants in ANGPT/TEK and VEGF/VEGFR with Progression and Survival in Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy or Radiochemotherapy
Authors: Butkiewicz Dorota , Gdowicz-Kłosok Agnieszka , Krześniak Małgorzata , Rutkowski Tomasz , Krzywon Aleksandra , Cortez Alexander Jorge , Domińczyk Iwona , Składowski Krzysztof
Published: June 2020

Angiogenesis is essential for growth, progression, and metastasis of solid tumors. Vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) and angiopoietin (ANGPT)/ tyrosine kinase endothelial (TEK) signaling plays an important role in regulating angiogenesis. Very little is known about the effects of single-nucleotide polymorphisms (SNPs) in angiogenesis-related genes on treatment outcome in head and neck squamous cell carcinoma (HNSCC). Therefore, we evaluated the association between SNPs in ANGPT1, ANGPT2, TEK, VEGF, VEGFR1, and VEGFR2 genes and five clinical endpoints in 422 HNSCC patients receiving radiotherapy alone or combined with chemotherapy. Multivariate analysis showed an association of ANGPT2 rs3739391, rs3020221 and TEK rs639225 with overall survival, and VEGF rs2010963 with overall and metastasis-free survival. VEGFR2 rs1870377 and VEGF rs699947 affected local recurrence-free survival in all patients. In the combination treatment subgroup, rs699947 predicted local, nodal, and loco-regional recurrence-free survival, whereas VEGFR2 rs2071559 showed an association with nodal recurrence-free survival. However, these associations were not statistically significant after multiple testing correction. Moreover, a strong cumulative effect of SNPs was observed that survived this adjustment. These SNPs and their combinations were independent risk factors for specific endpoints. Our data suggest that certain germline variants in ANGPT2/TEK and VEGF/VEGFR2 axes may have predictive and prognostic potential in HNSCC treated with radiation or chemoradiation.
Tandem Catalysis: Synthesis of Nitrogen-Containing Heterocycles
Authors: Campos Joana F. , Berteina-Raboin Sabine
Published: June 2020

In this Review, we consider all the publications since the beginning of the century that describe tandem reactions resulting in the formation of five-membered aromatic nitrogen heterocycles (thiazole, imidazole, indole, tetrazole, triazole, and isoxazole). The contents of this review are organized by taxonomy and type of tandem catalysis. It covers orthogonal, auto-, and assisted tandem catalysis, providing an overview of tandem reactions applied tonitrogen heterocycles reported in the literature up to March 2020. We believe that this compilation of data will provide a necessary starting reference to developthe applications of tandem catalysis in medicinal chemistry.
Boron-Doped TiO2-CNT Nanocomposites with Improved Photocatalytic Efficiency toward Photodegradation of Toluene Gas and Photo-Inactivation of Escherichia coli
Authors: Koli Valmiki B. , Ke Shyue-Chu , Dodamani Ananta G. , Deshmukh Shamkumar P. , Kim Jung-Sik
Published: June 2020

An in-situ sol-gel method was used for the synthesis of boron-doped TiO2-CNT nanocomposites with varied boron concentrations from 1 to 4 mol%. The synthesized nanocomposites were characterized by various techniques, namely XRD, UV-DRS, TEM, PL, and XPS; all results show that 3 mol% B-TiO2-CNT nanocomposites have superior properties to pure TiO2, 3B-TiO2 nanoparticles, and other nanocomposites. TEM images clearly show the B-TiO2 nanoparticles decorated on the CNT surface. Photo-luminescence studies confirm that boron doping of up to 3 mol% in TiO2-CNT nanocomposites reduces the electron-hole pair recombination rate. The photocatalytic performance of the B-TiO2-CNT nanocomposites was tested against the photodegradation of toluene gas and the photocatalytic inactivation of E. coli in the presence of UV and visible light respectively. B-TiO2-CNT (3 mol%) nanocomposites show the highest photocatalytic activity.
Palladium-Catalyzed Benzodiazepines Synthesis
Authors: Christodoulou Michael S. , Beccalli Egle M. , Giofrè Sabrina
Published: June 2020

This review is focused on palladium-catalyzed reactions as efficient strategies aimed at the synthesis of different classes of benzodiazepines. Several reaction typologies are reported including hydroamination, amination, C–H arylation, N-arylation, and the Buchwald–Hartwig reaction, depending on the different substrates identified as halogenated starting materials (activated substrates) or unactivated unsaturated systems, which then exploit Pd(0)- or Pd(II)-catalytic species. In particular, the use of the domino reactions, as intra- or intermolecular processes, are reported as an efficient and eco-compatible tool to obtain differently functionalized benzodiazepines. Different domino reaction typologies are the carboamination, aminoarylation, aminoacethoxylation, aminohalogenation, and aminoazidation.
FeCeOx Supported Ni, Sn Catalysts for the High-Temperature Water–Gas Shift Reaction
Authors: Damma Devaiah , Smirniotis Panagiotis G.
Published: June 2020

In this work, the effect of monometallic Ni or Sn and bimetallic NiSn deposition on the activity of FeCeOx catalysts in high-temperature water–gas (HT-WGS) reactions was investigated. It was found that the HT-WGS performance of FeCeOx has significantly improved after the deposition of Sn together with Ni on it. Furthermore, the bimetallic NiSn/FeCeOx catalyst showed higher activity compared to the monometallic Ni/FeCeOx and Sn/FeCeOx catalysts within the tested temperature range (450–600 °C). Although the Ni/FeCeOx catalyst showed methanation activity at a temperature below 550 °C, the NiSn/FeCeOx catalyst suppressed the methane formation to zero in the WGS. Besides, the NiSn/FeCeOx catalyst exhibited an excellent time-on-stream stability without methanation reaction, even at a steam-to-CO ratio as low as 0.8. The combination of Ni and Sn supported on FeCeOx led to a large lattice strain, the formation of NiSn alloy, and a strong synergistic effect between the bimetallic NiSn and FeCeOx mixed oxide support interface. All these features are very important in achieving the best activity and stability of NiSn/FeCeOx in the HT-WGS reaction.
Ionic Liquid Catalyzed Per-O-Acetylation and Benzylidene Ring-Opening Reaction
Authors: Thul Mayur , Wu Yao-Peng , Lin Yi-Jyun , Du Shu-Lin , Wu Hsin-Ru , Ho Wen-Yueh , Luo Shun-Yuan
Published: June 2020

Tunable aryl imidazolium ionic liquids acting as Brønsted acid ionic liquids were found to be efficient catalysts for per-O-acetylation and reductive ring opening of benzylidene acetals. This method requires a truly catalytic amount of the least expensive available ionic liquids that are water-stable and reusable and also stable at room temperature. The reactions were obtained in one hour with good to excellent yields. These reactions can form C−O and C−H bonds with a high atom economy. Furthermore, the ionic liquid is an anomeric selective catalyst in per-O-acetylation and reductive ring opening of benzylidene acetals of sugar moieties.
Enhanced CO2 Methanation Reaction in C1 Chemistry over a Highly Dispersed Nickel Nanocatalyst Prepared Using the One-Step Melt-Infiltration Method
Authors: Cho Eui Hyun , Kim Woohyun , Ko Chang Hyun , Yoon Wang Lai
Published: June 2020

The Paris Agreement requires the world to put the best efforts to reduce CO2 emissions, due to the global warming problems. As a promising technology corresponding to this greenhouse gas treatment, the CO2 methanation process a.k.a power to gas (PtoG), which catalytically converts CO2 into methane, has been in the limelight. To develop an efficient catalytic process, it is necessary to design a low-cost and high-efficiency catalyst for high CO2 conversion and CH4 selectivity. In this study, we have developed Ni/γ-Al2O3 catalysts by the one-step melt-infiltration method, where both aging and calcination are done in one pot. For enhancement of the catalytic activity and selectivity, sufficient Ni content (>25 wt %) and a high dispersion (<10 nm) are simultaneously required. Thus, the aging conditions of the melt-infiltration methods, e.g., time and temperature, were optimized for the high dispersion with sufficient Ni content (15–50 wt %). The catalytic performance tests were carried out under atmospheric pressure, 275 to 400 °C and gas hourly velocity (GHSV) = 25,000 h−1. And the various characteristic analyses (Brunauer–Emmett–Teller (BET), X-ray diffraction (XRD), H2-chemisorption, temperature programmed reduction (TPR), etc.) were performed to confirm the effects on the catalytic performance. As a result, based on the experiments and the characterization data, the 30 wt %-Ni catalyst (Ni particles size = 11 nm) showed the best CO2 conversion at 300 °C and the 20 wt % one having the highest Ni dispersion (Ni particles size = 8.8 nm), which showed the best intrinsic reaction rate and CH4 selectivity in the entire temperature range.
Cell Type-Specific In Vitro Gene Expression Profiling of Stem Cell-Derived Neural Models
Authors: Gregory James A. , Hoelzli Emily , Abdelaal Rawan , Braine Catherine , Cuevas Miguel , Halpern Madeline , Barretto Natalie , Schrode Nadine , Akbalik Güney , Kang Kristy , Cheng Esther , Bowles Kathryn , Lotz Steven , Goderie Susan , Karch Celeste M. , Temple Sally , Goate Alison , Brennand Kristen J. , Phatnani Hemali
Published: June 2020

Genetic and genomic studies of brain disease increasingly demonstrate disease-associated interactions between the cell types of the brain. Increasingly complex and more physiologically relevant human-induced pluripotent stem cell (hiPSC)-based models better explore the molecular mechanisms underlying disease but also challenge our ability to resolve cell type-specific perturbations. Here, we report an extension of the RiboTag system, first developed to achieve cell type-restricted expression of epitope-tagged ribosomal protein (RPL22) in mouse tissue, to a variety of in vitro applications, including immortalized cell lines, primary mouse astrocytes, and hiPSC-derived neurons. RiboTag expression enables depletion of up to 87 percent of off-target RNA in mixed species co-cultures. Nonetheless, depletion efficiency varies across independent experimental replicates, particularly for hiPSC-derived motor neurons. The challenges and potential of implementing RiboTags in complex in vitro cultures are discussed.
Knockout of the Mitochondrial Calcium Uniporter Strongly Suppresses Stimulus-Metabolism Coupling in Pancreatic Acinar Cells but Does Not Reduce Severity of Experimental Acute Pancreatitis
Authors: Chvanov Michael , Voronina Svetlana , Zhang Xiaoying , Telnova Svetlana , Chard Robert , Ouyang Yulin , Armstrong Jane , Tanton Helen , Awais Muhammad , Latawiec Diane , Sutton Robert , Criddle David N. , Tepikin Alexei V.
Published: June 2020

Acute pancreatitis is a frequent disease that lacks specific drug treatment. Unravelling the molecular mechanisms of acute pancreatitis is essential for the development of new therapeutics. Several inducers of acute pancreatitis trigger sustained Ca2+ increases in the cytosol and mitochondria of pancreatic acinar cells. The mitochondrial calcium uniporter (MCU) mediates mitochondrial Ca2+ uptake that regulates bioenergetics and plays an important role in cell survival, damage and death. Aberrant Ca2+ signaling and mitochondrial damage in pancreatic acinar cells have been implicated in the initiation of acute pancreatitis. The primary aim of this study was to assess the involvement of the MCU in experimental acute pancreatitis. We found that pancreatic acinar cells from MCU−/− mice display dramatically reduced mitochondrial Ca2+ uptake. This is consistent with the drastic changes of stimulus-metabolism coupling, manifested by the reduction of mitochondrial NADH/FAD+ responses to cholecystokinin and in the decrease of cholecystokinin-stimulated oxygen consumption. However, in three experimental models of acute pancreatitis (induced by caerulein, taurolithocholic acid 3-sulfate or palmitoleic acid plus ethanol), MCU knockout failed to reduce the biochemical and histological changes characterizing the severity of local and systemic damage. A possible explanation of this surprising finding is the redundancy of damaging mechanisms activated by the inducers of acute pancreatitis.
Symmetry Breaking and Epithelial Cell Extrusion
Authors: Nanavati Bageshri Naimish , Yap Alpha S. , Teo Jessica L.
Published: June 2020

Cell extrusion is a striking morphological event found in epithelia and endothelia. It is distinguished by two symmetry-breaking events: a loss of planar symmetry, as cells are extruded in either apical or basal directions; and loss of mechanochemical homogeneity within monolayers, as cells that are fated to be extruded become biochemically and mechanically distinct from their neighbors. Cell extrusion is elicited by many diverse events, from apoptosis to the expression of transforming oncogenes. Does the morphological outcome of extrusion reflect cellular processes that are common to these diverse biological phenomena? To address this question, in this review we compare the progress that has been made in understanding how extrusion is elicited by epithelial apoptosis and cell transformation.
Glycogen Synthase Kinase-3β Facilitates Cytokine Production in 12-O-Tetradecanoylphorbol-13-Acetate/Ionomycin-Activated Human CD4+ T Lymphocytes
Authors: Tsai Cheng-Chieh , Tsai Chin-Kun , Tseng Po-Chun , Lin Chiou-Feng , Chen Chia-Ling
Published: June 2020

Cytokines are the major immune regulators secreted from activated CD4+ T lymphocytes that activate adaptive immunity to eradicate nonself cells, including pathogens, tumors, and allografts. The regulation of glycogen synthase kinase (GSK)-3β, a serine/threonine kinase, controls cytokine production by regulating transcription factors. The artificial in vitro activation of CD4+ T lymphocytes by a combination of 12-O-tetradecanoylphorbol-13-acetate and ionomycin, the so-called T/I model, led to an inducible production of cytokines, such as interferon-γ, tumor necrosis factor-α, and interleukin-2. As demonstrated by the approaches of pharmacological targeting and genetic knockdown of GSK-3β, T/I treatment effectively caused GSK-3β activation followed by GSK-3β-regulated cytokine production. In contrast, pharmacological inhibition of the proline-rich tyrosine kinase 2 and calcineurin signaling pathways blocked cytokine production, probably by deactivating GSK-3β. The blockade of GSK-3β led to the inhibition of the nuclear translocation of T-bet, a vital transcription factor of T lymphocyte cytokines. In a mouse model, treatment with the GSK-3β inhibitor 6-bromoindirubin-3’-oxime significantly inhibited T/I-induced mortality and serum cytokine levels. In summary, targeting GSK-3β effectively inhibits CD4+ T lymphocyte activation and cytokine production.
The Role of GSK-3 in Cancer Immunotherapy: GSK-3 Inhibitors as a New Frontier in Cancer Treatment
Authors: Augello Giuseppa , Emma Maria R. , Cusimano Antonella , Azzolina Antonina , Montalto Giuseppe , McCubrey James A. , Cervello Melchiorre
Published: June 2020

The serine/threonine kinase glycogen synthase kinase-3 (GSK-3) was initially identified because of its key role in the regulation of glycogen synthesis. However, it is now well-established that GSK-3 performs critical functions in many cellular processes, such as apoptosis, tumor growth, cell invasion, and metastasis. Aberrant GSK-3 activity has been associated with many human diseases, including cancer, highlighting its potential therapeutic relevance as a target for anticancer therapy. Recently, newly emerging data have demonstrated the pivotal role of GSK-3 in the anticancer immune response. In the last few years, many GSK-3 inhibitors have been developed, and some are currently being tested in clinical trials. This review will discuss preclinical and initial clinical results with GSK-3β inhibitors, highlighting the potential importance of this target in cancer immunotherapy. As described in this review, GSK-3 inhibitors have been shown to have antitumor activity in a wide range of human cancer cells, and they may also contribute to promoting a more efficacious immune response against tumor target cells, thus showing a double therapeutic advantage.
A Novel Approach of Harvesting Viable Single Cells from Donor Corneal Endothelium for Cell-Injection Therapy
Authors: Ong Hon Shing , Peh Gary , Neo Dawn Jin Hui , Ang Heng-Pei , Adnan Khadijah , Nyein Chan Lwin , Morales-Wong Fernando , Bhogal Maninder , Kocaba Viridiana , Mehta Jodhbir S.
Published: June 2020

Donor corneas with low endothelial cell densities (ECD) are deemed unsuitable for corneal endothelial transplantation. This study evaluated a two-step incubation and dissociation harvesting approach to isolate single corneal endothelial cells (CECs) from donor corneas for corneal endothelial cell-injection (CE-CI) therapy. To isolate CECs directly from donor corneas, optimization studies were performed where donor Descemet’s membrane/corneal endothelium (DM/CE) were peeled and incubated in either M4-F99 or M5-Endo media before enzymatic digestion. Morphometric analyses were performed on the isolated single cells. The functional capacities of these cells, isolated using the optimized simple non-cultured endothelial cells (SNEC) harvesting technique, for CE-CI therapy were investigated using a rabbit bullous keratopathy model. The two control groups were the positive controls, where rabbits received cultured CECs, and the negative controls, where rabbits received no CECs. Whilst it took longer for CECs to dislodge as single cells following donor DM/CE incubation in M5-Endo medium, CECs harvested were morphologically more homogenous and smaller compared to CECs obtained from DM/CE incubated in M4-F99 medium (p < 0.05). M5-Endo medium was hence selected as the DM/CE incubation medium prior to enzymatic digestion to harvest CECs for the in vivo cell-injection studies. Following SNEC injection, mean central corneal thickness (CCT) of rabbits increased to 802.9 ± 147.8 μm on day 1, gradually thinned, and remained clear with a CCT of 385.5 ± 38.6 μm at week 3. Recovery of corneas was comparable to rabbits receiving cultured CE-CI (p = 0.40, p = 0.17, and p = 0.08 at weeks 1, 2, and 3, respectively). Corneas that did not receive any cells remained significantly thicker compared to both SNEC injection and cultured CE-CI groups (p < 0.05). This study concluded that direct harvesting of single CECs from donor corneas for SNEC injection allows the utilization of donor corneas unsuitable for conventional endothelial transplantation.
Superstrate Structured FTO/TiO2/In2S3/Cu2ZnSnS4 Solar Cells Fabricated by a Spray Method with Aqueous Solutions
Authors: Lee Dongho , Yang JungYup
Published: June 2020

Copper Zinc Tin Sulfide (C2ZTS4) solar cells have become a fascinating research topic due to several advantages of the C2ZTS4 absorber layer, such as having non-toxic and abundantly available components. Superstrate structured C2ZTS4 solar cells were fabricated on the top of a fluorine-doped tin oxide (FTO) substrate with a spray pyrolysis method from the window layer to the absorber layer. Titanium dioxide (TiO2) and indium sulfide (In2S3) were used as the window and buffer layer, respectively. The source materials for the C2ZTS4 and buffer layers were all aqueous-based solutions. The metallic component ratio, Cu/(Zn + Sn), and the sulfur concentration in the solutions were systematically investigated. The optimum ratio of Cu/(Zn + Sn) in the film is about 0.785, while 0.18 M thiourea in the solution is the best condition for high performance. The C2ZTS4 layers deposited at lower temperatures (<360 °C) yielded a low quality resulting in low current density (JSC). On the other hand, the C2ZTS4 layers deposited at high temperature (~400 °C) showed a low fill factor (FF) without degradation of the open-circuit voltage (VOC) and JSC due to the junction degradation and high contact resistance between the absorber layer and metal contact. The best cell efficiency, VOC, JSC, and fill factor achieved were 3.34%, 383 mV, 24.6 mA/cm2, and 37.7%, respectively.
Atomistic Simulations and Experimental Investigations of the Diffusion Behavior of Steel/ZCuPb20Sn5 Bimetals
Authors: Wang Mingjie , Zhang Guowei , Xu Hong , Zhang Yufei
Published: June 2020

A hybrid verification method consisting of experiments and molecular dynamics simulations was implemented to investigate the diffusion behaviour of steel/ZCuPb20Sn5 bimetals. The effects of different carbon steels (Q235 steel, 45 steel, and T8 steel), pouring temperatures, and holding times on their microstructures and mechanical properties were studied to obtain the optimum process parameters. The experimental results indicated that the pouring temperature and holding time played an imperative role in improving the shear strength of the steel/copper bimetallic composite. The highest bonding strength of all the steel/copper bimetallic composites was obtained at 1523 K and the holding time of 40 min. Moreover, the carbon steel of 45 steel with a ZCuPb20Sn5 interface exhibited the highest bonding strength because of the appropriate pearlite content along with the preferable structure and micro-hardness for the considered diffusion width and bonding strength. Meanwhile, the diffusion distance of copper atoms in the carbon steel matrix was smaller than that of iron atoms in the ZCuPb20Sn5 matrix. In the simulation results, the diffusion coefficient of Cu atoms was smaller than that of Fe atoms, but the diffusion distance of Fe atoms in the Cu bulk was larger than that of Cu atoms in the Fe bulk; this showed a significant agreement with the experimental result.
Effect of Temperature on Morphology, Phase Transformations and Thermal Expansions of Coal Fly Ash Cenospheres
Authors: Choo Thye Foo , Mohd Salleh Mohamad Amran , Kok Kuan Ying , Matori Khamirul Amin , Abdul Rashid Suraya
Published: June 2020

Cenospheres are small, hard-shelled hollow spheres with high silica and alumina content. These micron-sized aluminosilicate hollow spheres constitute only a small percentage of the coal fly ash (CFA) obtained from the coal combustion processes. In this study, cenospheres were separated from CFA obtained from a coal-fired power plant located in Kapar, Malaysia. The cenospheres were heated at 1000, 1200 and 1400 °C to study the changes in morphologies, compositions, phase formation and thermal expansion. The sintering temperatures were selected based on the differential scanning calorimetry (DSC) curve results. X-ray diffractometry (XRD), field emission electron microscopy (FESEM), energy dispersive spectroscopy (EDS) as well as thermogravimetry and differential scanning calorimetry analysis (TG–DSC) were used for the characterization study. The study found that the cenospheres have excellent weight stability but are thermally unstable as a result of crystallization and melting. The phase ordering process and devitrification of the amorphous aluminosilicate glass phase at high temperatures lead to the increment and enrichment of the mullite phase in cenospheres. It is suggested that a preheating treatment at 1100 °C could be used to enhance the mechanical properties and thermally stabilize the cenospheres, which make it more suitable for use as a pore-forming agent in ceramics.
Inhibition of the Alkali-Carbonate Reaction Using Fly Ash and the Underlying Mechanism
Authors: Ren Xin , Li Wei , Mao Zhongyang , Deng Min
Published: June 2020

In this paper, fly ash is used to inhibit the alkali-carbonate reaction (ACR). The experimental results suggest that when the alkali equivalent (equivalent Na2Oeq) of the cement is 1.0%, the adding of 30% fly ash can significantly inhibit the expansion in low-reactivity aggregates. For moderately reactive aggregates, the expansion rate can also be reduced by adding 30% of fly ash. According to a polarizing microscope analysis, the cracks are expansion cracks mainly due to the ACR. The main mechanisms of fly ash inhibiting the ACR are that it refines the pore structure of the cement paste, and that the alkali migration rate in the curing solution to the interior of the concrete microbars is reduced. As the content of fly ash increases, the concentrations of K+ and Na+ and the pH value in the pore solution gradually decrease. This makes the ACR in the rocks slower, such that the cracks are reduced, and the expansion due to the ACR is inhibited.
Coordination Compounds Featuring Non-Toxic Chiral 1,4-Dicarboxylic Acids and Copper(II)
Authors: Kremer Marius , van Leusen Jan , Englert Ulli
Published: June 2020

Six new coordination compounds of copper cations and 1,4-dicarboxylic acids have been synthesized and structurally investigated. Aspartic acid (H2asp), enantiopure, racemic and meso tartaric acid (H2tart), di-para-toluyltartaric acid (H2dptta) and dibenzoyltartaric acid (H2dbta) represent environmentally benign water-soluble proligands which may be deprotonated for oxygen coordination. Chelating ligands such as tetramethylethylenediamine (TMEDA) and 2-aminomethylpyridine (AMPY) efficiently reduce the dimensionality of the target compounds, and additional aqua ligands complete the coordination environments. In this line of argument, the discrete mononuclear complexes [Cu(AMPY)(asp)(H2O)] and [Cu(Hdbta)2(H2O)4] were obtained; for the latter, only a preliminary structure model can be presented which, however, agrees with the powder diffraction pattern of the bulk. From enantiopure and racemic tartaric acid and TMEDA the closely related chain polymers [CuII(H2tart)(TMEDA)(H2O)2)]n were obtained; the racemic compound consists of individual homochiral strands of opposite chirality. The high steric demand of di-para-toluyltartaric acid leads to one-dimensional [Cu(dptta)(EtOH)(H2O)2]n with coordinated ethanol (EtOH) in the distant Jahn–Teller site of the coordination sphere. Cu(II), meso-tartaric acid and TMEDA aggregate to a trinuclear coordination compound [CuII2CuI(H2tart)(Htart)(TMEDA)2]. Its peripheral cations show the expected Jahn–Teller geometry of Cu(II), but the unambiguous assignment of the oxidation state +I for central cation required susceptibility measurements: their results prove the presence of only two and only very weakly interacting divalent cations, separated by a diamagnetic center.
Impacts of Egg White Assisted Combustion and Ceramic Methods on Structural, Morphological and Magnetic Properties of Nickel Manganite System
Authors: Deraz Nasrallah , Abd-Elkader Omar Hamed , Yassin Mohamed
Published: June 2020

This study focuses on two different techniques for preparation of nickel manganite (NiMn2O4) system. One approach is conventional ceramic method, and the second is based on replacing the ceramic route with green synthesis mediated by egg white. The goal of this strategy is produce a single nanomagnetic phase of NiMn2O4 using a mostly simple one-step method with specific characteristics as seen in the second route compared to the ceramic method. The as synthesized system was characterized by using various techniques such as X-ray diffraction (XRD), scanning electron micrographs (SEM), and Energy dispersive X-ray spectrometry (EDS). XRD, EDS and SEM analyses confirm a successful synthesis of NiMn2O4 single phase with cubic spinel and sponge crystal structures. The particles are polycrystalline in their nature and average crystallite size ranged between 76 and 90 nm. Egg white assisted combustion method imparted amelioration in the system crystallization, size of grain, distribution of cation and magnetic properties of the as prepared materials. The magnetic mensuration suggested that the obtained nickel manganite shows ferromagnetism at room temperature with an optimum value (3.56 emu/g) of saturation magnetization.
Diversification of African Rainforest Restricted Clades: Piptostigmateae and Annickieae (Annonaceae)
Authors: Brée Baptiste , Helmstetter Andrew J. , Bethune Kévin , Ghogue Jean-Paul , Sonké Bonaventure , Couvreur Thomas L. P.
Published: June 2020

African rainforests (ARFs) are species rich and occur in two main rainforest blocks: West/Central and East Africa. This diversity is suggested to be the result of recent diversification, high extinction rates and multiple vicariance events between west/central and East African forests. We reconstructed the diversification history of two subtribes (Annickieae and Piptostigmateae) from the ecologically dominant and diverse tropical rainforest plant family Annonaceae. Both tribes contain endemic taxa in the rainforests of West/Central and East Africa. Using a dated molecular phylogeny based on 32 nuclear markers, we estimated the timing of the origin of East African species. We then undertook several diversification analyses focusing on Piptostigmateae to infer variation in speciation and extinction rates, and test the impact of extinction events. Speciation in both tribes dated to the Pliocene and Pleistocene. In particular, Piptostigma (13 species) diversified mainly during the Pleistocene, representing one of the few examples of Pleistocene speciation in an African tree genus. Our results also provide evidence of an ARF fragmentation at the mid-Miocene linked to climatic changes across the region. Overall, our results suggest that continental-wide forest fragmentation during the Neogene (23.03–2.58 Myr), and potentially during the Pliocene, led to one or possibly two vicariance events within the ARF clade Piptostigmateae, in line with other studies. Among those tested, the best fitting diversification model was the one with an exponential speciation rate and no extinction. We did not detect any evidence of mass extinction events. This study gives weight to the idea that the ARF might not have been so negatively impacted by extinction during the Neogene, and that speciation mainly took place during the Pliocene and Pleistocene.
Lepidoptera are Relevant Bioindicators of Passive Regeneration in Tropical Dry Forests
Authors: Legal Luc , Valet Marine , Dorado Oscar , Jesus-Almonte Jose Maria de , López Karime , Céréghino Régis
Published: June 2020

Most evaluations of passive regeneration/natural succession or restoration have dealt with tropical rain forest or temperate ecosystems. Very few studies have examined the regeneration of tropical dry forests (TDF), one of the most damaged ecosystem types in the world. Owing to their species diversity and abundance, insects have been widely used as bioindicators of restoration. Butterflies were among the most abundant and useful groups. We sampled four sites with different levels of anthropogenic disturbance in a Mexican TDF (Morelos State) and compared butterfly communities. A first goal was to examine whether adult butterflies were significant bioindicators owing to their specificity to restricted habitats. A second aim was to determine if differences exist in butterfly communities between some fields abandoned from 4–8, 8–15 and 15–30 years and a reference zone considered as primary forest. We found 40% to 50% of the species of butterflies were specifically related to a habitat and/or a level of anthropogenic disturbance. The time it takes for passive regeneration and recovery of the Mexican tropical dry forest is much higher than 25 years (our older zone), considering that almost none of the butterflies found in our conserved reference zone were present in our 25 year aged study zone.
An Interdisciplinary Review of Camera Image Collection and Analysis Techniques, with Considerations for Environmental Conservation Social Science
Authors: Little Coleman L. , Perry Elizabeth E. , Fefer Jessica P. , Brownlee Matthew T. J. , Sharp Ryan L.
Published: June 2020

Camera-based data collection and image analysis are integral methods in many research disciplines. However, few studies are specifically dedicated to trends in these methods or opportunities for interdisciplinary learning. In this systematic literature review, we analyze published sources (n = 391) to synthesize camera use patterns and image collection and analysis techniques across research disciplines. We frame this inquiry with interdisciplinary learning theory to identify cross-disciplinary approaches and guiding principles. Within this, we explicitly focus on trends within and applicability to environmental conservation social science (ECSS). We suggest six guiding principles for standardized, collaborative approaches to camera usage and image analysis in research. Our analysis suggests that ECSS may offer inspiration for novel combinations of data collection, standardization tactics, and detailed presentations of findings and limitations. ECSS can correspondingly incorporate more image analysis tactics from other disciplines, especially in regard to automated image coding of pertinent attributes.