bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNAs-Based Nano-Strategies as New Therapeutic Approach in Multiple Myeloma to Overcome Disease Progression and Drug Resistance
Authors: Desantis Vanessa , Saltarella Ilaria , Lamanuzzi Aurelia , Melaccio Assunta , Solimando Antonio Giovanni , Mariggiò Maria Addolorata , Racanelli Vito , Paradiso Angelo , Vacca Angelo , Frassanito Maria Antonia
Published: April 2020

MicroRNAs (miRNAs, or miRs) are single-strand short non-coding RNAs with a pivotal role in the regulation of physiological- or disease-associated cellular processes. They bind to target miRs modulating gene expression at post-transcriptional levels. Here, we present an overview of miRs deregulation in the pathogenesis of multiple myeloma (MM), and discuss the potential use of miRs/nanocarriers association in clinic. Since miRs can act as oncogenes or tumor suppressors, strategies based on their inhibition and/or replacement represent the new opportunities in cancer therapy. The miRs delivery systems include liposomes, polymers, and exosomes that increase their physical stability and prevent nuclease degradation. Phase I/II clinical trials support the importance of miRs as an innovative therapeutic approach in nanomedicine to prevent cancer progression and drug resistance. Results in clinical practice are promising.
Gene-Wise Burden of Coding Variants Correlates to Noncoding Pharmacogenetic Risk Variants
Authors: Park Jihye , Lee Soo Youn , Baik Su Youn , Park Chan Hee , Yoon Jun Hee , Ryu Brian Y. , Kim Ju Han
Published: April 2020

Genetic variability can modulate individual drug responses. A significant portion of pharmacogenetic variants reside in the noncoding genome yet it is unclear if the noncoding variants directly influence protein function and expression or are present on a haplotype including a functionally relevant genetic variation (synthetic association). Gene-wise variant burden (GVB) is a gene-level measure of deleteriousness, reflecting the cumulative effects of deleterious coding variants, predicted in silico. To test potential associations between noncoding and coding pharmacogenetic variants, we computed a drug-level GVB for 5099 drugs from DrugBank for 2504 genomes of the 1000 Genomes Project and evaluated the correlation between the long-known noncoding variant-drug associations in PharmGKB, with functionally relevant rare and common coding variants aggregated into GVBs. We obtained the area under the receiver operating characteristics curve (AUC) by comparing the drug-level GVB ranks against the corresponding pharmacogenetic variants-drug associations in PharmGKB. We obtained high overall AUCs (0.710 ± 0.022–0.734 ± 0.018) for six different methods (i.e., SIFT, MutationTaster, Polyphen-2 HVAR, Polyphen-2 HDIV, phyloP, and GERP++), and further improved the ethnicity-specific validations (0.759 ± 0.066–0.791 ± 0.078). These results suggest that a significant portion of the long-known noncoding variant-drug associations can be explained as synthetic associations with rare and common coding variants burden of the corresponding pharmacogenes.
Structural and Evolutionary Analysis Indicate That the SARS-CoV-2 Mpro Is a Challenging Target for Small-Molecule Inhibitor Design
Authors: Bzówka Maria , Mitusińska Karolina , Raczyńska Agata , Samol Aleksandra , Tuszyński Jack A. , Góra Artur
Published: April 2020

The novel coronavirus whose outbreak took place in December 2019 continues to spread at a rapid rate worldwide. In the absence of an effective vaccine, inhibitor repurposing or de novo drug design may offer a longer-term strategy to combat this and future infections due to similar viruses. Here, we report on detailed classical and mixed-solvent molecular dynamics simulations of the main protease (Mpro) enriched by evolutionary and stability analysis of the protein. The results were compared with those for a highly similar severe acute respiratory syndrome (SARS) Mpro protein. In spite of a high level of sequence similarity, the active sites in both proteins showed major differences in both shape and size, indicating that repurposing SARS drugs for COVID-19 may be futile. Furthermore, analysis of the binding site’s conformational changes during the simulation time indicated its flexibility and plasticity, which dashes hopes for rapid and reliable drug design. Conversely, structural stability of the protein with respect to flexible loop mutations indicated that the virus’ mutability will pose a further challenge to the rational design of small-molecule inhibitors. However, few residues contribute significantly to the protein stability and thus can be considered as key anchoring residues for Mpro inhibitor design.
Redox Homeostasis and Metabolism in Cancer: A Complex Mechanism and Potential Targeted Therapeutics
Authors: Ghoneum Alia , Abdulfattah Ammar Yasser , Warren Bailey Olivia , Shu Junjun , Said Neveen
Published: April 2020

Reactive Oxygen Species or “ROS” encompass several molecules derived from oxygen that can oxidize other molecules and subsequently transition rapidly between species. The key roles of ROS in biological processes are cell signaling, biosynthetic processes, and host defense. In cancer cells, increased ROS production and oxidative stress are instigated by carcinogens, oncogenic mutations, and importantly, metabolic reprograming of the rapidly proliferating cancer cells. Increased ROS production activates myriad downstream survival pathways that further cancer progression and metastasis. In this review, we highlight the relation between ROS, the metabolic programing of cancer, and stromal and immune cells with emphasis on and the transcription machinery involved in redox homeostasis, metabolic programing and malignant phenotype. We also shed light on the therapeutic targeting of metabolic pathways generating ROS as we investigate: Orlistat, Biguandes, AICAR, 2 Deoxyglucose, CPI-613, and Etomoxir.
Sensor Histidine Kinase NarQ Activates via Helical Rotation, Diagonal Scissoring, and Eventually Piston-Like Shifts
Authors: Gushchin Ivan , Orekhov Philipp , Melnikov Igor , Polovinkin Vitaly , Yuzhakova Anastasia , Gordeliy Valentin
Published: April 2020

Membrane-embedded sensor histidine kinases (HKs) and chemoreceptors are used ubiquitously by bacteria and archaea to percept the environment, and are often crucial for their survival and pathogenicity. The proteins can transmit the signal from the sensor domain to the catalytic kinase domain reliably over the span of several hundreds of angstroms, and regulate the activity of the cognate response regulator proteins, with which they form two-component signaling systems (TCSs). Several mechanisms of transmembrane signal transduction in TCS receptors have been proposed, dubbed (swinging) piston, helical rotation, and diagonal scissoring. Yet, despite decades of studies, there is no consensus on whether these mechanisms are common for all TCS receptors. Here, we extend our previous work on Escherichia coli nitrate/nitrite sensor kinase NarQ. We determined a crystallographic structure of the sensor-TM-HAMP fragment of the R50S mutant, which, unexpectedly, was found in a ligand-bound-like conformation, despite an inability to bind nitrate. Subsequently, we reanalyzed the structures of the ligand-free and ligand-bound NarQ and NarX sensor domains, and conducted extensive molecular dynamics simulations of ligand-free and ligand-bound wild type and mutated NarQ. Based on the data, we show that binding of nitrate to NarQ causes, first and foremost, helical rotation and diagonal scissoring of the α-helices at the core of the sensor domain. These conformational changes are accompanied by a subtle piston-like motion, which is amplified by a switch in the secondary structure of the linker between the sensor and TM domains. We conclude that helical rotation, diagonal scissoring, and piston are simply different degrees of freedom in coiled-coil proteins and are not mutually exclusive in NarQ, and likely in other nitrate sensors and TCS proteins as well.
Binder-Free α-MnO2 Nanowires on Carbon Cloth as Cathode Material for Zinc-Ion Batteries
Authors: Corpuz Ryan Dula , De Juan-Corpuz Lyn Marie , Nguyen Mai Thanh , Yonezawa Tetsu , Wu Heng-Liang , Somwangthanaroj Anongnat , Kheawhom Soorathep
Published: April 2020

Recently, rechargeable zinc-ion batteries (ZIBs) have gained a considerable amount of attention due to their high safety, low toxicity, abundance, and low cost. Traditionally, a composite manganese oxide (MnO2) and a conductive carbon having a polymeric binder are used as a positive electrode. In general, a binder is employed to bond all materials together and to prevent detachment and dissolution of the active materials. Herein, the synthesis of α-MnO2 nanowires on carbon cloth via a simple one-step hydrothermal process and its electrochemical performance, as a binder-free cathode in aqueous and nonaqueous-based ZIBs, is duly reported. Morphological and elemental analyses reveal a single crystal α-MnO2 having homogeneous nanowire morphology with preferential growth along {001}. It is significant that analysis of the electrochemical performance of the α-MnO2 nanowires demonstrates more stable capacity and superior cyclability in a dimethyl sulfoxide (DMSO) electrolyte ZIB than in an aqueous electrolyte system. This is because DMSO can prevent irreversible proton insertion as well as unfavorable dendritic zinc deposition. The application of the binder-free α-MnO2 nanowires cathode in DMSO can promote follow-up research on the high cyclability of ZIBs.
Effect of Antimony Buffer Layer on the Electric and Magnetic Properties of 200 and 600 nm Thick Bismuth Films on Mica Substrate
Authors: Makarova Elena S. , Tukmakova Anastasiia S. , Novotelnova Anna V. , Komarov Vladimir A. , Gerega Vasilisa A. , Kablukova Natallya S. , Khodzitsky Mikhail K.
Published: April 2020

We report on the production of 200 and 600 nm thick Bi films on mica substrate with 10 nm thick Sb sublayer between Bi and mica. Two types of films have been studied: block and single crystal. Films were obtained using the thermal evaporation technique using continuous and discrete spraying. Discrete spraying allows smaller film blocks size: 2–6 μ m compared to 10–30 μ m, obtained by the continuous spraying. Single crystal films were made by the zone recrystallization method. Microscopic examination of Bi films with and without Sb sublayer did not reveal an essential distinction in crystal structure. A galvanomagnetic study shows that Sb sublayer results in the change of Bi films properties. Sb sublayer results in the increase of specific resistivity of block films and has no significant impact on single crystal films. For single-crystal films with Sb sublayer with a thickness of 200 nm the Hall coefficient has value 1.5 times higher than for the 600 nm thickness films at 77 K. The change of the Hall coefficient points to change of the contribution of carriers in the conductivity. This fact indicates a change in the energy band structure of the thin Bi film. The most significant impact of the Sb sublayer is on the magnetoresistance of single-crystal films at low temperatures. The increase of magnetoresistance points to the increase of mobility of the charge carriers. In case of detecting and sensing applications the increased carriers mobility can result in a faster device response time.
Corrosion Behavior of Surface-Treated Metallic Implant Materials
Authors: Bormann Therese , Mai Phuong Thao , Gibmeier Jens , Sonntag Robert , Müller Ulrike , Kretzer J. Philippe
Published: April 2020

Corrosion of taper connections in total hip arthroplasty remains of concern, as particles and ions generated by corrosive processes can cause clinical problems such as periprosthetic osteolysis or adverse reaction to metallic debris. Mechanical surface treatments that introduce compressive residual stresses (RSs) in metallic materials can lead to a better performance in terms of fretting and fatigue and may lower the susceptibility to corrosion. The study investigates the impact of mechanical surface treatments on the corrosion behavior of metallic biomaterials. Compressive RSs were introduced by deep rolling and microblasting in Ti6Al4V and CoCrMo samples. Polished samples served as reference. Corrosion behavior was characterized by repeated anodic polarization. Residual stresses of up to about −900 MPa were introduced by deep rolling with a reach in depth of approximately 500 µm. Microblasting led to compressive RSs up to approximately −800 and −600 MPa for Ti6Al4V and CoCrMo, respectively, in the immediate vicinity of the surface. For Ti6Al4V, microblasting resulted in decreased corrosion resistance with lower breakdown potentials and/or increased passive current densities in comparison to the polished and deep-rolled samples. The corrosion behavior of CoCrMo on the other hand was not affected by the mechanical surface treatments.
Effect of Annealing Time and Temperature Parameters on the Microstructure, Hardness, and Strain-Hardening Coefficients of 42CrMo4 Steel
Authors: Szala Mirosław , Winiarski Grzegorz , Wójcik Łukasz , Bulzak Tomasz
Published: April 2020

The study presents the effect of annealing process parameters on the microstructure, hardness, and strain-hardening coefficients, that is, the strength coefficient c and the strain-hardening exponent n, of 42CrMo4 steel. Seven selected annealing time–temperature schemes are examined for superior steel formability in cold metal forming conditions. The c and n coefficients are first determined in experimental upsetting of annealed samples and then used in FEM (finite element method) simulations of the upsetting process. The results demonstrate that the strain-hardening coefficients (c and n) depend on the employed annealing scheme. Compared with the as-received sample, the annealing process reduces the true stress and effectively decrease the hardness of 42CrMo4 steel; improves microstructural spheroidization; and, consequently, facilitates deformability of this material. The annealing schemes, relying on heating the material to 750 °C and its subsequent slow cooling, lead to the highest decrease in hardness ranging from 162 to 168 HV. The results obtained with the SEM-EDS (scanning electron microscopy-energy dispersive spectrometer), LOM (light optical microscopy), and XRD (X-ray diffraction) methods lead to the conclusion that the employed heat treatment schemes cause the initial ferritic-pearlitic microstructure to develop granular and semi-lamellar precipitation of cementite enriched with Mo and Cr in the ferrite matrix. In addition, the annealing process affects the growth of α-Fe grains. The highest cold hardening rate, and thus formability, is obtained for the annealing scheme producing the lowest hardness. The results of FEM simulations are positively validated by experimental results. The obtained results are crucial for further numerical simulations and experimental research connected with developing new cold metal forming methods for producing parts made of 42CrMo4 steel.
Alumina-based Coating for Coke Reduction in Steam Crackers
Authors: A. Sarris Stamatis , H. Symoens Steffen , Olahova Natalia , Reyniers Marie-Françoise , B. Marin Guy , M. Van Geem Kevin
Published: April 2020

Alumina-based coatings have been claimed as being an advantageous modification in industrial ethylene furnaces. In this work, on-line experimentally measured coking rates of a commercial coating (CoatAlloy™) have pointed out its superiority compared to an uncoated reference material in an electrobalance set-up. Additionally, the effects of presulfiding with 500 ppmw DMDS per H2O, continuous addition of 41 ppmw S per HC of DMDS, and a combination thereof were evaluated during ethane steam cracking under industrially relevant conditions (Tgasphase = 1173 K, Ptot = 0.1 MPa, XC2H6 = 70%, dilution δ = 0.33 kgH2O/kgHC). The examined samples were further evaluated using online thermogravimetry, scanning electron microscopy and energy diffractive X-ray for surface and cross-section analysis together with X-ray photoelectron spectroscopy and wavelength-dispersive X-ray spectroscopy for surface analysis. The passivating coating illustrated a better performance than the reference Ni-Cr Fe-base alloy after application of an improved pretreatment, followed by piddling changes on the product distribution. Presulfiding of the coating affected negatively the observed coking rates in comparison with the reference alloy, so alternative presulfiding and sulfur addition strategies are recommended when using this barrier coating.
High Quality Graphene Thin Films Synthesized by Glow Discharge Method in A Chemical Vapor Deposition System Using Solid Carbon Source
Authors: Wang Le , Sun Jie , Guo Weiling , Dong Yibo , Xie Yiyang , Xiong Fangzhu , Du Zaifa , Li Longfei , Deng Jun , Xu Chen
Published: April 2020

Arc discharge is traditionally used to synthesize randomly arranged graphene flakes. In this paper, we substantially modify it into a glow discharge method so that the discharge current is much more reduced. The H2 and/or Ar plasma etching of the graphitic electrode (used to ignite the plasma) is hence much gentler, rendering it possible to grow graphene in thin film format. During the growth at a few mbar, there is no external carbon gas precursor introduced. The carbon atoms and/or carbon containing particles as a result of the plasma etching are emitted in the chamber, some of which undergo gas phase scattering and deposit onto the metallic catalyst substrates (Cu-Ni alloy thin films or Cu foils) as graphene sheets. It is found that high quality monolayer graphene can be synthesized on Cu foil at 900 °C. On Cu-Ni, under the same growth condition, somewhat more bilayer regions are observed. It is observed that the material quality is almost indifferent to the gas ratios, which makes the optimization of the deposition process relatively easy. Detailed study on the deposition procedure and the material characterization have been carried out. This work reveals the possibility of producing thin film graphene by a gas discharge based process, not only from fundamental point of view, but it also provides an alternative technique other than standard chemical vapor deposition to synthesize graphene that is compatible with the semiconductor planar process. As the process uses solid graphite as a source material that is rich in the crust, it is a facile and relatively cheap method to obtain high quality graphene thin films in this respect.
Intrinsic and Dopant-Related Luminescence of Undoped and Tb Plus Tm Double-Doped Lithium Magnesium Phosphate (LiMgPO4, LMP) Crystals
Authors: Gieszczyk Wojciech , Bilski Paweł , Mrozik Anna , Kłosowski Mariusz , Marczewska Barbara , Sas-Bieniarz Anna , Perzanowski Marcin , Zorenko Tetiana , Zorenko Yuriy
Published: April 2020

In this work, the luminescence properties of undoped, Tm3+ doped, and Tb3+ plus Tm3+ double-doped crystals of the lithium magnesium phosphate (LiMgPO4, LMP) compound were investigated. The crystals under study were grown from melt using the micro-pulling-down method. The intrinsic and dopant-related luminescence of these crystals were studied using cathodo-, radio-, photo-, and thermoluminescence methods. Double doping with Tb3+ and Tm3+ ions was analyzed as these dopants are expected to exhibit an opposite trapping nature, namely to create the hole and electron-trapping sites, respectively. The spectra measured for the undoped samples revealed three prominent broad emission bands with maxima at around 3.50, 2.48, and 1.95 eV, which were associated with intrinsic structural defects within the studied compound. These were expected due to the anion vacancies forming F+-like centers while trapping the electrons. The spectra measured for Tb and Tm double-doped crystals showed characteristic peaks corresponding to the 4f–4f transitions of these dopants. A simplified model of a recombination mechanism was proposed to explain the temperature dependence of the measured thermally stimulated luminescence spectra. It seems that at low temperatures (below 300 °C), the charge carriers were released from 5D3-related Tb3+ trapping sites and recombination took place at Tm-related sites, giving rise to the characteristic emission of Tm3+ ions. At higher temperatures, above 300 °C, the electrons occupying the Tm3+-related trapping sites started to be released, and recombination took place at 5D4-related Tb3+ recombination centers, giving rise to the characteristic emission of Tb3+ ions. The model explains the temperature dependence observed for the luminescence emission from double-doped LiMgPO4 crystals and may be fully applicable for the consideration of emissions of other double-doped compounds.
Effect of Different Shear Rates on Particle Microstructure of Cementitious Materials in a Wide Gap Vane-in-cup Rheometer
Authors: Eslami Pirharati Mahmoud , Krauss Hans-W. , Schilde Carsten , Lowke Dirk
Published: April 2020

Rheological properties of cementitious suspensions are affected not only by their mixture composition but also by process-related factors such as shear history. To enable a model-based description, investigations were carried out on the effect of shear history (shear rate variation over time) on the cement paste agglomeration state. Therefore, a Focused Beam Reflectance Measurement (FBRM) system and a wide gap rheometer were coupled to study the relation between shear history and in-situ chord length distribution simultaneously, indicating particle agglomeration. Hence, the effect of average shear rates (resulting from the applied shear profile), as well as shear rate distribution within the gap (local shear rates) on the particle agglomeration state have been investigated. The rheological properties of cement paste were evaluated with the Reiner–Riwlin approach. Furthermore, the agglomeration state of the particles was compared for different average shear rates and local shear rates at various positions of the FBRM probe. The results show that the median chord length increases in all positions when the average shear rate is decreased, indicating increasing particle agglomeration. Moreover, due to variable local shear rates at different FBRM probe positions, different agglomeration states are observed, resulting from two factors, shear rate dependent particle agglomeration and shear-induced particle migration.
Thermal Performance of Mortars Based on Different Binders and Containing a Novel Sustainable Phase Change Material (PCM)
Authors: Sarcinella Antonella , De Aguiar José Luìs Barroso , Lettieri Mariateresa , Cunha Sandra , Frigione Mariaenrica
Published: April 2020

Increasing concerns about climate change and global warming bring about technical steps for the development of several energy-efficient technologies. Since the building sector is one of the largest energy users for cooling and heating necessities, the incorporation of a proper energy-efficient material into the building envelopes could be an interesting solution for saving energy. Phase change material (PCM)-based thermal energy storage (TES) seems suitable to provide efficient energy redistribution. This is possible because the PCM is able to store and release its latent heat during the phase change processes that occurs according to the environmental temperature. The purpose of this paper was the characterization of the thermal properties of a composite PCM (i.e., Lecce stone/poly-ethylene glycol, previously developed) incorporated into mortar compositions based on different binders (i.e., hydraulic lime and cement). The study was carried out using an experimental set up through which it was possible to simulate the different seasons of the years. It was observed that the addition of PCM in mortars leads to a decrease of the maximum temperatures and increase of the minimum temperatures. Furthermore, the results shown a reduction of the heating and cooling needs, thus confirming the capability of this material to save energy.
Natural Products from Marine Fungi
Authors: Shin Hee Jae
Published: April 2020

Marine fungi have been studied since the first record of the species Sphaeria posidoniae (Halotthia posidoniae) on the rhizome of the sea grass Posidonia oceanica by Durieu and Montagne in 1846 [...]
Detailed Structural Characterization of the Lipooligosaccharide from the Extracellular Membrane Vesicles of Shewanella vesiculosa HM13
Authors: Di Guida Rossella , Casillo Angela , Yokoyama Fumiaki , Kawamoto Jun , Kurihara Tatsuo , Corsaro Maria Michela
Published: April 2020

Bacterial extracellular membrane vesicles (EMVs) are membrane-bound particles released during cell growth by a variety of microorganisms, among which are cold-adapted bacteria. Shewanella vesiculosa HM13, a cold-adapted Gram-negative bacterium isolated from the intestine of a horse mackerel, is able to produce a large amount of EMVs. S. vesiculosa HM13 has been found to include a cargo protein, P49, in the EMVs, but the entire mechanism in which P49 is preferentially included in the vesicles has still not been completely deciphered. Given these premises, and since the structural study of the components of the EMVs is crucial for deciphering the P49 transport mechanism, in this study the complete characterization of the lipooligosaccharide (LOS) isolated from the cells and from the EMVs of S. vesiculosa HM13 grown at 18 °C is reported. Both lipid A and core oligosaccharide have been characterized by chemical and spectroscopic methods.
Open-Healing Socket Preservation with a Novel Dense Polytetrafluoroethylene (dPTFE) Membrane: A Retrospective Clinical Study
Authors: Zafiropoulos Gregor-Georg , Kačarević Zeljka , Qasim Syed , Trajkovski Branko
Published: April 2020

Background and objectives: Non-resorbable dense polytetrafluoroethylene (dPTFE) membranes are widely used for regeneration procedures, alone or in combination with particulate materials. The aim of this work was to examine the efficacy of a newly developed dPTFE membrane in the management of extraction socket healing. Materials and Methods: The extraction premolar sockets of 44 patients (20 men and 24 women) were preserved. One group received prosthetic rehabilitation with a fixed partial denture (FPD) (PROS group, N = 19) and a second group received immediate implant placement (IMPL group, N = 25). The PROS group sockets were augmented with a bovine derived xenograft and covered with a newly developed dPTFE membrane prior to FPD rehabilitation. Results: In the IMPL group, socket preservation was combined with immediate implant placement. Before (T0) and 6 months after surgery (T1), horizontal and vertical dimensions were measured with customized stents. No significant differences in alveolar bone loss from T0 to T1 were observed between the PROS and IMPL groups in the horizontal dimension for any tooth type. There was a significant difference in alveolar bone loss from T0 to T1 between the two groups for only single-rooted maxillary premolars in the vertical dimension. Conclusions: The use of the examined new dPTFE membrane consistently led to the preservation of hard tissue in the extraction sites.
Uncharted Source of Medicinal Products: The Case of the Hedychium Genus
Authors: Tavares Wilson R. , Barreto Maria do Carmo , Seca Ana M. L.
Published: April 2020

A current research topic of great interest is the study of the therapeutic properties of plants and of their bioactive secondary metabolites. Plants have been used to treat all types of health problems from allergies to cancer, in addition to their use in the perfumery industry and as food. Hedychium species are among those plants used in folk medicine in several countries and several works have been reported to verify if and how effectively these plants exert the effects reported in folk medicine, studying their essential oils, extracts and pure secondary metabolites. Hedychium coronarium and Hedychium spicatum are the most studied species. Interesting compounds have been identified like coronarin D, which possesses antibacterial, antifungal and antitumor activities, as well as isocoronarin D, linalool and villosin that exhibit better cytotoxicity towards tumor cell lines than the reference compounds used, with villosin not affecting the non-tumor cell line. Linalool and α-pinene are the most active compounds found in Hedychium essential oils, while β-pinene is identified as the most widespread compound, being reported in 12 different Hedychium species. Since only some Hedychium species have been investigated, this review hopes to shed some light on the uncharted territory that is the Hedychium genus.
Vitamin B Supplementation and Nutritional Intake of Methyl Donors in Patients with Chronic Kidney Disease: A Critical Review of the Impact on Epigenetic Machinery
Authors: Cappuccilli Maria , Bergamini Camilla , Giacomelli Floriana A. , Cianciolo Giuseppe , Donati Gabriele , Conte Diletta , Natali Teresa , La Manna Gaetano , Capelli Irene
Published: April 2020

Cardiovascular morbidity and mortality are several-fold higher in patients with advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) than in the general population. Hyperhomocysteinemia has undoubtedly a central role in such a prominent cardiovascular burden. The levels of homocysteine are regulated by methyl donors (folate, methionine, choline, betaine), and cofactors (vitamin B6, vitamin B12,). Uremia-induced hyperhomocysteinemia has as its main targets DNA methyltransferases, and this leads to an altered epigenetic control of genes regulated through methylation. In renal patients, the epigenetic landscape is strictly correlated with the uremic phenotype and dependent on dietary intake of micronutrients, inflammation, gut microbiome, inflammatory status, oxidative stress, and lifestyle habits. All these factors are key contributors in methylome maintenance and in the modulation of gene transcription through DNA hypo- or hypermethylation in CKD. This is an overview of the epigenetic changes related to DNA methylation in patients with advanced CKD and ESRD. We explored the currently available data on the molecular dysregulations resulting from altered gene expression in uremia. Special attention was paid to the efficacy of B-vitamins supplementation and dietary intake of methyl donors on homocysteine lowering and cardiovascular protection.
Potato Protein Isolate Stimulates Muscle Protein Synthesis at Rest and with Resistance Exercise in Young Women
Authors: Oikawa Sara Y. , Bahniwal Ravninder , Holloway Tanya M. , Lim Changhyun , McLeod Jonathan C. , McGlory Chris , Baker Steven K. , Phillips Stuart M.
Published: April 2020

Skeletal muscle myofibrillar protein synthesis (MPS) increases in response to protein feeding and to resistance exercise (RE), where each stimuli acts synergistically when combined. The efficacy of plant proteins such as potato protein (PP) isolate to stimulate MPS is unknown. We aimed to determine the effects of PP ingestion on daily MPS with and without RE in healthy women. In a single blind, parallel-group design, 24 young women (21 ± 3 years, n = 12/group) consumed a weight-maintaining baseline diet containing 0.8 g/kg/d of protein before being randomized to consume either 25 g of PP twice daily (1.6 g/kg/d total protein) or a control diet (CON) (0.8 g/kg/d total protein) for 2 wks. Unilateral RE (~30% of maximal strength to failure) was performed thrice weekly with the opposite limb serving as a non-exercised control (Rest). MPS was measured by deuterated water ingestion at baseline, following supplementation (Rest), and following supplementation + RE (Exercise). Ingestion of PP stimulated MPS by 0.14 ± 0.09 %/d at Rest, and by 0.32 ± 0.14 %/d in the Exercise limb. MPS was significantly elevated by 0.20 ± 0.11 %/d in the Exercise limb in CON (p = 0.008). Consuming PP to increase protein intake to levels twice the recommended dietary allowance for protein augmented rates of MPS. Performance of RE stimulated MPS regardless of protein intake. PP is a high-quality, plant-based protein supplement that augments MPS at rest and following RE in healthy young women.
Preoperative Exclusive Total Parental Nutrition is Associated with Clinical and Laboratory Remission in Severe Active Crohn’s Disease—A Pilot Study
Authors: Zittan Eran , Gralnek Ian M. , Hatoum Ossama A. , Sakran Nasser , Kolonimos Nitzan
Published: April 2020

Background: The effect of 1–3 months of preoperative exclusive total parental nutrition (TPN) in active Crohn’s disease (CD) patients is not well established. We investigated the efficacy of exclusive TPN in active CD patients. Methods: In a retrospective multi-visit study with data according to our standard care therapy, we assessed clinical and laboratory remission to refractory CD with exclusive preoperative TPN. Inclusion required exclusive preoperative home TPN without additional oral intake for 1–3 months prior to planning surgery. Results: Twenty preoperative CD patients (65% male; 35% female) were on exclusive TPN. The mean age of the cohort was 30.8 ± 11.6 years. Mean duration of preoperative TPN treatment was 73 days (range: 24–142 days). Most patients had terminal ileal (35%) or ileocolonic CD (30%), and with stricturing (B2) phenotype. All 20 patients had significant clinical improvement in all disease activity indices at the end of preoperative TPN (baseline vs. post TPN): HBI 14.5 vs. 4.0 (p = 0.001); BMI 19.2 vs. 19.7 kg/m2 (p = 0.017); CRP 57.2 vs. 10.3 mg/L (p = 0.001); Fecal calprotectin (FC) 672 vs. 200 (μg/g); albumin 2.7 vs. 3.6 g/dL (p = 0.001). Two patients (10%) no longer required surgery after completion of exclusive TPN. Conclusion: Exclusive preoperative TPN was found to provide significant improvement in nutritional status, and clinical and laboratory remission in severe active Crohn’s patients.
Circulating Ionized Magnesium as a Measure of Supplement Bioavailability: Results from a Pilot Study for Randomized Clinical Trial
Authors: Zhan Jiada , Wallace Taylor C. , Butts Sarah J. , Cao Sisi , Ansu Velarie , Spence Lisa A. , Weaver Connie M. , Gletsu-Miller Nana
Published: April 2020

Oral supplementation may improve the dietary intake of magnesium, which has been identified as a shortfall nutrient. We conducted a pilot study to evaluate appropriate methods for assessing responses to the ingestion of oral magnesium supplements, including ionized magnesium in whole blood (iMg2+) concentration, serum total magnesium concentration, and total urinary magnesium content. In a single-blinded crossover study, 17 healthy adults were randomly assigned to consume 300 mg of magnesium from MgCl2 (ReMag®, a picosized magnesium formulation) or placebo, while having a low-magnesium breakfast. Blood and urine samples were obtained for the measurement of iMg2+, serum total magnesium, and total urine magnesium, during 24 h following the magnesium supplement or placebo dosing. Bioavailability was assessed using area-under-the-curve (AUC) as well as maximum (Cmax) and time-to-maximum (Tmax) concentration. Depending on normality, data were expressed as the mean ± standard deviation or median (range), and differences between responses to MgCl2 or placebo were measured using the paired t-test or Wilcoxon signed-rank test. Following MgCl2 administration versus placebo administration, we observed significantly greater increases in iMg2+ concentrations (AUC = 1.51 ± 0.96 vs. 0.84 ± 0.82 mg/dL•24h; Cmax = 1.38 ± 0.13 vs. 1.32 ± 0.07 mg/dL, respectively; both p < 0.05) but not in serum total magnesium (AUC = 27.00 [0, 172.93] vs. 14.55 [0, 91.18] mg/dL•24h; Cmax = 2.38 [1.97, 4.01] vs. 2.24 [1.98, 4.31] mg/dL) or in urinary magnesium (AUC = 201.74 ± 161.63 vs. 139.30 ± 92.84 mg•24h; Cmax = 26.12 [12.91, 88.63] vs. 24.38 [13.51, 81.51] mg/dL; p > 0.05). Whole blood iMg2+ may be a more sensitive measure of acute oral intake of magnesium compared to serum and urinary magnesium and may be preferred for assessing supplement bioavailability.
Large Variability of Iodine Content in Retail Cow’s Milk in the U.S.
Authors: Roseland Janet M. , Phillips Katherine M. , Patterson Kristine Y. , Pehrsson Pamela R. , Bahadur Rahul , Ershow Abby G. , Somanchi Meena
Published: April 2020

Iodine intake is of contemporary public health interest. The recommended daily iodine intake is 150 µg for most adults, and milk is an important source of iodine in the U.S. diet. Iodine concentration in cow’s milk is affected by diet and iodine supplementation levels, milking sanitation practices, and other factors. Current analytical iodine data in U.S. retail milk are crucial for evaluating population-wide health outcomes related to diet. Samples of whole (3.25% fat), 2%, 1%, and skim (0–0.5% fat) milk were procured from 24 supermarkets across the U.S. using a census-based statistical plan. Iodine was analyzed by inductively coupled plasma mass spectrometry, including certified reference materials and control samples to validate results. No difference in iodine content was found between milkfat levels (F3,69 1.033, p = 0.4). Overall mean (SEM) was 85(5.5) µg/serving (240 mL). However, the 95% prediction interval of 39–185 µg/serving for individual samples indicated high variability among individual samples. Given the recommended 150 µg iodine per day for most adults along with the study mean, one milk serving can provide approximately 57% of daily intake. Researchers, health care professionals, and consumers should be aware of iodine variability in milk, while additional research is needed to investigate the impact of iodine variability factors.
Preventive Effects of Schisandrin A, A Bioactive Component of Schisandra chinensis, on Dexamethasone-Induced Muscle Atrophy
Authors: Yeon MyeongHoon , Choi Hojung , Jun Hee-Sook
Published: April 2020

Muscle wasting is caused by various factors, such as aging, cancer, diabetes, and chronic kidney disease, and significantly decreases the quality of life. However, therapeutic interventions for muscle atrophy have not yet been well-developed. In this study, we investigated the effects of schisandrin A (SNA), a component extracted from the fruits of Schisandra chinensis, on dexamethasone (DEX)-induced muscle atrophy in mice and studied the underlying mechanisms. DEX+SNA-treated mice had significantly increased grip strength, muscle weight, and muscle fiber size compared with DEX+vehicle-treated mice. In addition, SNA treatment significantly reduced the expression of muscle degradation factors such as myostatin, MAFbx (atrogin1), and muscle RING-finger protein-1 (MuRF1) and enhanced the expression of myosin heavy chain (MyHC) compared to the vehicle. In vitro studies using differentiated C2C12 myotubes also showed that SNA treatment decreased the expression of muscle degradation factors induced by dexamethasone and increased protein synthesis and expression of MyHCs by regulation of Akt/FoxO and Akt/70S6K pathways, respectively. These results suggest that SNA reduces protein degradation and increases protein synthesis in the muscle, contributing to the amelioration of dexamethasone-induced muscle atrophy and may be a potential candidate for the prevention and treatment of muscle atrophy.
Paradoxical Anticonvulsant Effect of Cefepime in the Pentylenetetrazole Model of Seizures in Rats
Authors: Amakhin Dmitry V. , Smolensky Ilya V. , Soboleva Elena B. , Zaitsev Aleksey V.
Published: April 2020

Many β-lactam antibiotics, including cephalosporins, may cause neurotoxic and proconvulsant effects. The main molecular mechanism of such effects is considered to be γ-aminobutyric acid type a (GABAa) receptor blockade, leading to the suppression of GABAergic inhibition and subsequent overexcitation. We found that cefepime (CFP), a cephalosporin, has a pronounced antiepileptic effect in the pentylenetetrazole (PTZ)-induced seizure model by decreasing the duration and severity of the seizure and animal mortality. This effect was specific to the PTZ model. In line with findings of previous studies, CFP exhibited a proconvulsant effect in other models, including the maximal electroshock model and 4-aminopyridine model of epileptiform activity, in vitro. To determine the antiepileptic mechanism of CFP in the PTZ model, we used whole-cell patch-clamp recordings. We demonstrated that CFP or PTZ decreased the amplitude of GABAa receptor-mediated postsynaptic currents. PTZ also decreased the current decay time constant and temporal summation of synaptic responses. In contrast, CFP slightly increased the decay time constant and did not affect summation. When applied together, CFP prevented alterations to the summation of responses by PTZ, strongly reducing the effects of PTZ on repetitive inhibitory synaptic transmission. The latter may explain the antiepileptic effect of CFP in the PTZ model.
Experimental Evaluation of Anticancer Efficiency and Acute Toxicity of Anthrafuran for Oral Administration
Authors: Shchekotikhin Andrey E. , Treshalina Helen M. , Treshchalin Michael I. , Pereverzeva Eleonora R. , Isakova Helen B. , Tikhomirov Alexander S.
Published: April 2020

The new antitumor agent anthrafuran has demonstrated a consistent effect in murine tumor models when administered parenterally due to the simultaneous inhibition of multiple cellular targets such as topoisomerases I/II and protein kinases. In this study, we assessed the anticancer efficiency and acute toxicity of anthrafuran administered orally. The action of anthrafuran was studied on transplanted tumor models which included P388 leukemia, Ca755 mammary adenocarcinoma, LLC lung carcinoma, and T47D human breast cancer xenografts on Balb/c nude mice. A significant antitumor efficacy of oral anthrafuran was revealed for all tested tumor models as follows: T/Cmax = 219% for P388, TGImax = 91% for Ca755, TGImax = 84% with CRmax = 54% for LLC, and T/C = 38% for T47D. The optimal treatment schedule of orally administered anthrafuran was 70–100 mg/kg given daily for five days. The LD50 value of orally administered anthrafuran (306.7 mg/kg) in mice was six times higher than that for i.p. administration (52.5 mg/kg). The rates of antitumor efficacy and acute toxicity indicate the high potential for further research on anthrafuran as a new original oral anticancer multitarget agent with an expected satisfactory tolerability and bioavailability.
Quantum Electrochemical Equilibrium: Quantum Version of the Goldman–Hodgkin–Katz Equation
Authors: Qaswal Abdallah Barjas
Published: April 2020

The resting membrane voltage of excitable cells such as neurons and muscle cells is determined by the electrochemical equilibrium of potassium and sodium ions. This voltage is calculated by using the Goldman–Hodgkin–Katz equation. However, from the quantum perspective, ions with significant quantum tunneling through closed channels can interfere with the electrochemical equilibrium and affect the value of the membrane voltage. Hence, in this case the equilibrium becomes quantum electrochemical. Therefore, the model of quantum tunneling of ions is used in this study to modify the Goldman–Hodgkin–Katz equation in such a way to calculate the resting membrane voltage at the point of equilibrium. According to the present calculations, it is found that lithium—with its lower mass—shows a significant depolarizing shift in membrane voltage. In addition to this, when the free gating energy of the closed channels decreases, even sodium and potassium ions depolarize the resting membrane voltage via quantum tunneling. This study proposes the concept of quantum electrochemical equilibrium, at which the electrical potential gradient, the concentration gradient and the quantum gradient (due to quantum tunneling) are balanced. Additionally, this concept may be used to solve many issues and problems in which the quantum behavior becomes more influential.
Sacred Places and Planetary Stresses: Sanctuaries as Laboratories of Religious and Ecological Change
Authors: Jenkins Willis
Published: April 2020

How are global relations and planetary flows experienced, interpreted, and managed from places set aside from everyday use, as “sacred” in that sense? Sanctuary Lab, a transdisciplinary initiative at UVA, investigates how religious processes interact with planetary stresses. Provisionally adopting a keyword in religious studies, the sacred, opens a post-disciplinary angle of inquiry into Anthropocene processes of cultural and environmental change. Focusing on dynamics of change in places regarded as sanctuaries affords unique perspective on how rapid planetary changes interact with particular inherited streams of normativity and imagination. This essay integrates field note illustrations from Yellowstone and Bhutan with critical reflection on the lab’s approach in order to share initial hypotheses, collaborative research practices, and potential significance. It suggests that sacralization is part of the process through which cultures make sense of rapid changes; that nonhumans participate in sacralization; that sanctuaries offer unique laboratories of coupled change; and that arts-based exercises can help drive critical reflection on experience and method.
Review of Satellite Interferometry for Landslide Detection in Italy
Authors: Solari Lorenzo , Del Soldato Matteo , Raspini Federico , Barra Anna , Bianchini Silvia , Confuorto Pierluigi , Casagli Nicola , Crosetto Michele
Published: April 2020

Landslides recurrently impact the Italian territory, producing huge economic losses and casualties. Because of this, there is a large demand for monitoring tools to support landslide management strategies. Among the variety of remote sensing techniques, Interferometric Synthetic Aperture Radar (InSAR) has become one of the most widely applied for landslide studies. This work reviews a variety of InSAR-related applications for landslide studies in Italy. More than 250 papers were analyzed in this review. The first application dates back to 1999. The average production of InSAR-related papers for landslide studies is around 12 per year, with a peak of 37 papers in 2015. Almost 70% of the papers are written by authors in academia. InSAR is used (i) for landslide back analysis (3% of the papers); (ii) for landslide characterization (40% of the papers); (iii) as input for landslide models (7% of the papers); (iv) to update landslide inventories (15% of the papers); (v) for landslide mapping (32% of the papers), and (vi) for monitoring (3% of the papers). Sixty-eight percent of the authors validated the satellite results with ground information or other remote sensing data. Although well-known limitations exist, this bibliographic overview confirms that InSAR is a consolidated tool for many landslide-related applications.