bluuebunny/crossref_metadata_2025 huggingface dataset:
Suggestions for Standardized Identifiers for Fatty Acyl Compounds in Genome Scale Metabolic Models and Their Application to the WormJam Caenorhabditis elegans Model
Authors: Witting Michael
Published: April 2020

Genome scale metabolic models (GSMs) are a representation of the current knowledge on the metabolism of a given organism or superorganism. They group metabolites, genes, enzymes and reactions together to form a mathematical model and representation that can be used to analyze metabolic networks in silico or used for analysis of omics data. Beside correct mass and charge balance, correct structural annotation of metabolites represents an important factor for analysis of these metabolic networks. However, several metabolites in different GSMs have no or only partial structural information associated with them. Here, a new systematic nomenclature for acyl-based metabolites such as fatty acids, acyl-carnitines, acyl-coenzymes A or acyl-carrier proteins is presented. This nomenclature enables one to encode structural details in the metabolite identifiers and improves human readability of reactions. As proof of principle, it was applied to the fatty acid biosynthesis and degradation in the Caenorhabditis elegans consensus model WormJam.
Untargeted Metabolomics and Steroid Signatures in Urine of Male Pattern Baldness Patients after Finasteride Treatment for a Year
Authors: Lee Yu Ra , Im Eunju , Kim Haksoon , Lew Bark Lynn , Sim Woo-Young , Lee Jeongae , Oh Han Bin , Paeng Ki Jung , Hong Jongki , Chung Bong Chul
Published: April 2020

Male pattern baldness (MPB) has been associated with dihydrotestosterone (DHT) expression. Finasteride treats MPB by inhibiting 5-alpha reductase and blocking DHT production. In this study, we aimed to identify metabolic differences in urinary metabolomics profiles between MPB patients after a one-year treatment with finasteride and healthy controls. Untargeted and targeted metabolomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS). We hypothesized that there would be changes in overall metabolite concentrations, especially steroids, in the urine of hair loss patients treated with finasteride and normal subjects. Untargeted analysis indicated differences in steroid hormone biosynthesis. Therefore, we conducted targeted profiling for steroid hormone biosynthesis to identify potential biomarkers, especially androgens and estrogens. Our study confirmed the differences in the concentration of urinary androgens and estrogens between healthy controls and MPB patients. Moreover, the effect of finasteride was confirmed by the DHT/T ratio in urine samples of MPB patients. Our metabolomics approach provided insight into the physiological alterations in MPB patients who have been treated with finasteride for a year and provided evidence for the association of finasteride and estrogen levels. Through a targeted approach, our results suggest that urinary estrogens must be studied in relation to MPB and post-finasteride syndrome.
Enhancing Glycolysis Protects against Ischemia-Reperfusion Injury by Reducing ROS Production
Authors: Beltran Claudia , Pardo Rosario , Bou-Teen Diana , Ruiz-Meana Marisol , Villena Josep A. , Ferreira-González Ignacio , Barba Ignasi
Published: April 2020

After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. A better understanding of the mechanisms underlying the protection afforded by increased glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of reactive oxygen species (ROS) was involved in the protection afforded by increased glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of glucose or galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or ATP and PCr levels. However, galactose-grown cells consumed more oxygen and had an increased Krebs cycle turnover, while cells grown in glucose had increased aerobic glycolysis rate as demonstrated by higher lactate and alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during ischemia-reperfusion injury.
Proteobacteria Overgrowth and Butyrate-Producing Taxa Depletion in the Gut Microbiota of Glycogen Storage Disease Type 1 Patients
Authors: Ceccarani Camilla , Bassanini Giulia , Montanari Chiara , Casiraghi Maria Cristina , Ottaviano Emerenziana , Morace Giulia , Biasucci Giacomo , Paci Sabrina , Borghi Elisa , Verduci Elvira
Published: April 2020

A life-long dietary intervention can affect the substrates’ availability for gut fermentation in metabolic diseases such as the glycogen-storage diseases (GSD). Besides drug consumption, the main treatment of types GSD-Ia and Ib to prevent metabolic complications is a specific diet with definite nutrient intakes. In order to evaluate how deeply this dietary treatment affects gut bacteria, we compared the gut microbiota of nine GSD-I subjects and 12 healthy controls (HC) through 16S rRNA gene sequencing; we assessed their dietary intake and nutrients, their microbial short chain fatty acids (SCFAs) via gas chromatography and their hematic values. Both alpha-diversity and phylogenetic analysis revealed a significant biodiversity reduction in the GSD group compared to the HC group, and highlighted profound differences of their gut microbiota. GSD subjects were characterized by an increase in the relative abundance of Enterobacteriaceae and Veillonellaceae families, while the beneficial genera Faecalibacterium and Oscillospira were significantly reduced. SCFA quantification revealed a significant increase of fecal acetate and propionate in GSD subjects, but with a beneficial role probably reduced due to unbalanced bacterial interactions; nutritional values correlated to bacterial genera were significantly different between experimental groups, with nearly opposite cohort trends.
Structural Stability of Optofluidic Nanostructures in Flow-Through Operation
Authors: Bdour Yazan , Gomez-Cruz Juan , Escobedo Carlos
Published: April 2020

Optofluidic sensors based on periodic arrays of subwavelength apertures that support surface plasmon resonance can be employed as both optical sensors and nanofluidic structures. In flow-through operation, the nanoapertures experience pressure differences across the substrate in which they are fabricated, which imposes the risk for structural failure. This work presents an investigation of the deflection and structural stability of nanohole array-based optofluidic sensors operating in flow-through mode. The analysis was approached using experiments, simulations via finite element method, and established theoretical models. The results depict that certain areas of the sensor deflect under pressure, with some regions suffering high mechanical stress. The offset in the deflection values between theoretical models and actual experimental values is overturned when only the effective area of the substrate, of 450 µm, is considered. Experimental, theoretical, and simulation results suggest that the periodic nanostructures can safely operate under trans-membrane pressures of up to 20 psi, which induce deflections of up to ~20 μm.
Compact 20-W GaN Internally Matched Power Amplifier for 2.5 GHz to 6 GHz Jammer Systems
Authors: Lee Min-Pyo , Kim Seil , Hong Sung-June , Kim Dong-Wook
Published: April 2020

In this paper, we demonstrate a compact 20-W GaN internally matched power amplifier for 2.5 to 6 GHz jammer systems which uses a high dielectric constant substrate, single-layer capacitors, and shunt/series resistors for low-Q matching and low-frequency stabilization. A GaN high-electron-mobility transistor (HEMT) CGH60030D bare die from Wolfspeed was used as an active device, and input/output matching circuits were implemented on two different substrates using a thin-film process, relative dielectric constants of which were 9.8 and 40, respectively. A series resistor of 2.1 Ω was chosen to minimize the high-frequency loss and obtain a flat gain response. For the output matching circuit, double λ/4 shorted stubs were used to supply the drain current and reduce the output impedance variation of the transistor between the low-frequency and high-frequency regions, which also made wideband matching feasible. Single-layer capacitors effectively helped reduce the size of the matching circuit. The fabricated GaN internally matched power amplifier showed a linear gain of about 10.2 dB, and had an output power of 43.3–43.9 dBm (21.4–24.5 W), a power-added efficiency of 33.4–49.7% and a power gain of 6.2–8.3 dB at the continuous-wave output power condition, from 2.5 to 6 GHz.
An Optimized Metabarcoding Method for Mimiviridae
Authors: Prodinger Florian , Endo Hisashi , Gotoh Yasuhiro , Li Yanze , Morimoto Daichi , Omae Kimiho , Tominaga Kento , Blanc-Mathieu Romain , Takano Yoshihito , Hayashi Tetsuya , Nagasaki Keizo , Yoshida Takashi , Ogata Hiroyuki
Published: April 2020

Mimiviridae is a group of viruses with large genomes and virions. Ecological relevance of Mimiviridae in marine environments has been increasingly recognized through the discoveries of novel isolates and metagenomic studies. To facilitate ecological profiling of Mimiviridae, we previously proposed a meta-barcoding approach based on 82 degenerate primer pairs (i.e., MEGAPRIMER) targeting the DNA polymerase gene of Mimiviridae. The method detected a larger number of operational taxonomic units (OTUs) in environmental samples than previous methods. However, it required large quantities of DNA and was laborious due to the use of individual primer pairs. Here, we examined coastal seawater samples using varying PCR conditions and purification protocols to streamline the MEGAPRIMER method. Mixing primer pairs in “cocktails” reduced the required amount of environmental DNA by 90%, while reproducing the results obtained by the original protocol. We compared the results obtained by the meta-barcoding approach with quantifications using qPCR for selected OTUs. This revealed possible amplification biases among different OTUs, but the frequency profiles for individual OTUs across multiple samples were similar to those obtained by qPCR. We anticipate that the newly developed MEGAPRIMER protocols will be useful for ecological investigation of Mimiviridae in a larger set of environmental samples.
Microbial Resources as a Tool for Enhancing Sustainability in Winemaking
Authors: Nardi Tiziana
Published: April 2020

In agriculture, the wine sector is one of the industries most affected by the sustainability issue. It is responsible for about 0.3% of annual global greenhouse gas emissions from anthropogenic activities. Sustainability in vitiviniculture was firstly linked to vineyard management, where the use of fertilizers, pesticides and heavy metals is a major concern. More recently, the contribution of winemaking, from grape harvest to bottling, has also been considered. Several cellar processes could be improved for reducing the environmental impact of the whole chain, including microbe-driven transformations. This paper reviews the potential of microorganisms and interactions thereof as a natural, environmentally friendly tool to improve the sustainability aspects of winemaking, all along the production chain. The main phases identified as potentially interesting for exploiting microbial activities to lower inputs are: (i) pre-fermentative stages, (ii) alcoholic fermentation, (iii) stage between alcoholic and malolactic fermentation, (iv) malolactic fermentation, (v) stabilization and spoilage risk management, and (vi) by-products and wastewater treatment. The presence of proper yeast or bacterial strains, the management and timing of inoculation of starter cultures, and some appropriate technological modifications that favor selected microbial activities can lead to several positive effects, including (among other) energy savings, reduction of chemical additives such as sulfites, and reuse of certain residues.
Fractionation Trends and Variability of Rare Earth Elements and Selected Critical Metals in Pelagic Sediment from Abyssal Basin of NE Pacific (Clarion-Clipperton Fracture Zone)
Authors: Zawadzki Dominik , Maciąg Łukasz , Abramowski Tomasz , McCartney Kevin
Published: April 2020

The geochemical and mineralogical characteristics of pelagic sediments collected from the Interoceanmetal Joint Organization (IOM) claim area, located in the eastern part of the Clarion-Clipperton Fracture Zone (CCFZ; eastern tropical Pacific), are described in this paper. The concentrations of rare earth elements (REE), as well as other selected critical elements contained in 135 sediment samples of siliceous clayey silts, are presented. The vertical and spatial variabilities of elements, with particular emphasis on REE as well as metals of the highest economic interest such as Cu, Ni, and Co, are detailed. The applied methods include grain size analysis by laser diffraction, geochemistry examination using ICP-MS, XRF, AAS, and CNS spectrometry, and XRD analysis of mineral composition (Rietveld method). Additionally, statistical methods such as factor analysis (FA) and principal components analysis (PCA) were applied to the results. Finally, a series of maps was prepared by geostatistical methods (universal kriging). Grain size analysis showed poor sorting of the examined fine-grained silts. ICP-MS indicated that total REE contents varied from 200 to 577 ppm, with a mean of 285 ppm, which is generally low. The contents of critical metals such as Cu, Ni, and Co were also low to moderate, apart from some individual sampling stations where total contents were 0.15% or more. Metal composition in sediments was dominated by Cu, Ni, and Zn. A mineral composition analysis revealed the dominance of amorphous biogenic opaline silica (27–58%), which were mostly remnants of diatoms, radiolarians, and sponges associated with clay minerals (23% to 48%), mostly Fe-smectite and illite, with mixed-layered illite/smectite. The high abundance of diagenetic barite crystals found in SEM−EDX observations explains the high content of Ba (up to 2.4%). The sediments showed complex lateral and horizontal fractionation trends for REE and critical metals, caused mostly by clay components, early diagenetic processes, admixtures of allogenic detrital minerals, or scavenging by micronodules.
Applications of Carbon Nanotubes in Bone Regenerative Medicine
Authors: Tanaka Manabu , Aoki Kaoru , Haniu Hisao , Kamanaka Takayuki , Takizawa Takashi , Sobajima Atsushi , Yoshida Kazushige , Okamoto Masanori , Kato Hiroyuki , Saito Naoto
Published: April 2020

Scaffolds are essential for bone regeneration due to their ability to maintain a sustained release of growth factors and to provide a place where cells that form new bone can enter and proliferate. In recent years, scaffolds made of various materials have been developed and evaluated. Functionally effective scaffolds require excellent cell affinity, chemical properties, mechanical properties, and safety. Carbon nanotubes (CNTs) are fibrous nanoparticles with a nano-size diameter and have excellent strength and chemical stability. In the industrial field, they are used as fillers to improve the performance of materials. Because of their excellent physicochemical properties, CNTs are studied for their promising clinical applications as biomaterials. In this review article, we focused on the results of our research on CNT scaffolds for bone regeneration, introduced the promising properties of scaffolds for bone regeneration, and described the potential of CNT scaffolds.
In Situ Study of the Impact of Aberration-Corrected Electron-Beam Lithography on the Electronic Transport of Suspended Graphene Devices
Authors: Mizuno Naomi , Camino Fernando , Du Xu
Published: April 2020

The implementation of aberration-corrected electron beam lithography (AC-EBL) in a 200 keV scanning transmission electron microscope (STEM) is a novel technique that could be used for the fabrication of quantum devices based on 2D atomic crystals with single nanometer critical dimensions, allowing to observe more robust quantum effects. In this work we study electron beam sculpturing of nanostructures on suspended graphene field effect transistors using AC-EBL, focusing on the in situ characterization of the impact of electron beam exposure on device electronic transport quality. When AC-EBL is performed on a graphene channel (local exposure) or on the outside vicinity of a graphene channel (non-local exposure), the charge transport characteristics of graphene can be significantly affected due to charge doping and scattering. While the detrimental effect of non-local exposure can be largely removed by vigorous annealing, local-exposure induced damage is irreversible and cannot be fixed by annealing. We discuss the possible causes of the observed exposure effects. Our results provide guidance to the future development of high-energy electron beam lithography for nanomaterial device fabrication.
Childhood Eating and Feeding Disturbances
Authors: Hilbert Anja
Published: April 2020

Eating and feeding disturbances are prevalent yet understudied health conditions in youth. They are characterized by aberrant eating behaviors, cognitive and emotional dysfunctions, and dysregulated body weight. The Diagnostic and Statistical Manual of Mental Disorders Fifth Edition defines several feeding and eating disorders with a common onset in youth; however, data on their clinical validity at young ages are lacking. Further non-normative eating behaviors exist, but their clinical relevance needs elucidation. This Special Issue compiles state-of-the-art reviews and empirical research on the presentation, development, course, and maintenance of diverse eating and feeding disturbances as a prerequisite for delineating evidence-based interventions for treatment and prevention.
Low Levels of Serum Tryptophan Underlie Skeletal Muscle Atrophy
Authors: Ninomiya Soranobu , Nakamura Nobuhiko , Nakamura Hiroshi , Mizutani Taku , Kaneda Yuto , Yamaguchi Kimihiro , Matsumoto Takuro , Kitagawa Junichi , Kanemura Nobuhiro , Shiraki Makoto , Hara Takeshi , Shimizu Masahito , Tsurumi Hisashi
Published: April 2020

Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies.
Purchasing Drivers of Fresh Citrus Fruits in Urban Italy: Is It All about Taste?
Authors: Di Vita Giuseppe , Borrello Massimiliano , Vecchio Riccardo , Gulisano Giovanni , D’Amico Mario
Published: April 2020

While the medical community supports the growth of citrus consumption as part of a healthy diet, there is limited knowledge about consumer preferences for these fruits. The current study analyzed the purchasing patterns and drivers of fresh citrus fruits from a convenience sample of 346 Italian food shoppers. Results revealed that clementines were the citrus fruit purchased most, followed by oranges and tangerines. Sweetness and smell were important product attributes for respondents. Different drivers affect the purchasing frequencies of various citrus fruits. Taste motivation, with a specific preference for acidity, impacts orange purchasing. Similarly, clementines are purchased primarily for taste motivation, however, the core sensory attribute for respondents in this case was sweetness. Meanwhile, for tangerines, the taste motivation is less important than the energy motivation, and the size together with the color are the core purchasing drivers. These outcomes provide food scientists, agronomists and market practitioners with new insights into Italian consumers’ preferences for citrus fruits, thus contributing to a potential expansion of this market.
It is Time for a Universal Nutrition Policy in Very Preterm Neonates during the Neonatal Period? Comment on: “Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm Infants” Nutrients 2019, 11, 2772
Authors: Gounaris Antonios , Sokou Rozeta , Panagiotounakou Polytimi , Grivea Ioanna N.
Published: April 2020

We have read the article entitled “Applying Methods for Postnatal Growth Assessment in the Clinical Setting: Evaluation in a Longitudinal Cohort of Very Preterm infants” by Montserrat Izquierdo Renau et al [...]
Age-related Smell and Taste Impairments and Vitamin D Associations in the U.S. Adults National Health and Nutrition Examination Survey
Authors: Bigman Galya
Published: April 2020

Smell and taste decline with aging, and markedly deteriorate when nutritional deficiencies occur. This study aims to examine the associations between Vitamin D (VD) deficiency and smell and taste impairments among adults. This paper details a cross-sectional study utilizing data from the US National Health and Nutrition Examination Survey (NHANES, 2013–2014.). Smell impairment was assessed by the Pocket Smell Test and defined as failing to correctly identify six or more of the eight odors. Taste impairment was defined as failing to correctly identify quinine or sodium chloride. VD was measured as serum 25-hydroxyvitamin. Multivariable weighted logistic regressions were utilized. Adjusted odds ratio (OR) and 95% confidence interval (CI) were presented. Overall, 2216 (smell sample) and 2636 (taste sample) participants were included, aged between 40 and 80 years old. Of those, 18.3% had taste impairment, 12.2% had smell impairment, and 20% had VD deficiency (<20 ng/mL). Compared to participants with sufficient VD (>30 ng/mL), those with VD deficiency were more likely by 39% to report a higher prevalence of smell impairment (OR = 1.39, 95%CI: 1.02–1.89); and only participants aged 70–80 years with VD inadequacy (20–30 ng/mL) were more likely by 96% to report a higher prevalence of taste impairment (OR = 1.96, 95%CI: 1.35–1.85). VD may have a significant role in age-related smell impairment in adults aged 40 years or older, and in age-related taste impairment in the elderly aged 70–80 years.
The Effects of Different Degrees of Carbohydrate Restriction and Carbohydrate Replacement on Cardiometabolic Risk Markers in Humans—A Systematic Review and Meta-Analysis
Authors: Fechner Eva , Smeets Ellen , Schrauwen Patrick , Mensink Ronald
Published: April 2020

Low-carbohydrate diets (LCDs) often differ in their diet composition, which may lead to conflicting results between randomized controlled trials. Therefore, we aimed to compare the effects of different degrees of carbohydrate (CHO) restriction on cardiometabolic risk markers in humans. The experimental LCDs of 37 human trials were classified as (1) moderate-low CHO diets (<45–40 E%, n = 13), (2) low CHO diets (<40–30 E%, n = 16), and (3) very-low CHO diets (<30–3 E%; n = 8). Summary estimates of weighted mean differences (WMDs) in selected risk markers were calculated using random-effect meta-analyses. Differences between the LCD groups were assessed with univariate meta-regression analyses. Overall, the LCDs resulted in significant weight loss, reduced diastolic blood pressure BP, and increased total cholesterol and high-density lipoprotein cholesterol (HDL-C), without significant differences between the three LCD groups. Higher low-density lipoprotein cholesterol (LDL-C) concentrations were found with the very-low CHO diets compared to the moderate-low CHO diets. Decreases in triacylglycerol (TAG) concentrations were more pronounced with the low and very-low CHO diets, compared to the moderate-low CHO diets. Substitution of CHO by mainly saturated fatty acids (SFAs) increased total cholesterol, LDL-C, and HDL-C concentrations. Except for LDL-C and TAGs, effects were not related to the degree of CHO restriction. Potential effects of nutrient exchanges should be considered when following LCDs.
Astrophysics in the Laboratory—The CBM Experiment at FAIR
Authors: Senger Peter
Published: April 2020

The future “Facility for Antiproton and Ion Research” (FAIR) is an accelerator-based international center for fundamental and applied research, which presently is under construction in Darmstadt, Germany. An important part of the program is devoted to questions related to astrophysics, including the origin of elements in the universe and the properties of strongly interacting matter under extreme conditions, which are relevant for our understanding of the structure of neutron stars and the dynamics of supernova explosions and neutron star mergers. The Compressed Baryonic Matter (CBM) experiment at FAIR is designed to measure promising observables in high-energy heavy-ion collisions, which are expected to be sensitive to the high-density equation-of-state (EOS) of nuclear matter and to new phases of Quantum Chromo Dynamics (QCD) matter at high densities. The CBM physics program, the relevant observables and the experimental setup will be discussed.
A Host-Specific Blocking Primer Combined with Optimal DNA Extraction Improves the Detection Capability of a Metabarcoding Protocol for Canine Vector-Borne Bacteria
Authors: Huggins Lucas G. , Koehler Anson V. , Schunack Bettina , Inpankaew Tawin , Traub Rebecca J.
Published: April 2020

Bacterial canine vector-borne diseases are responsible for some of the most life-threatening conditions of dogs in the tropics and are typically poorly researched with some presenting a zoonotic risk to cohabiting people. Next-generation sequencing based methodologies have been demonstrated to accurately characterise a diverse range of vector-borne bacteria in dogs, whilst also proving to be more sensitive than conventional PCR techniques. We report two improvements to a previously developed metabarcoding tool that increased the sensitivity and diversity of vector-borne bacteria detected from canine blood. Firstly, we developed and tested a canine-specific blocking primer that prevents cross-reactivity of bacterial primer amplification on abundant canine mitochondrial sequences. Use of our blocking primer increased the number of canine vector-borne infections detected (five more Ehrlichia canis and three more Anaplasma platys infections) and increased the diversity of bacterial sequences found. Secondly, the DNA extraction kit employed can have a significant effect on the bacterial community characterised. Therefore, we compared four different DNA extraction kits finding the Qiagen DNeasy Blood and Tissue Kit to be superior for detection of blood-borne bacteria, identifying nine more A. platys, two more E. canis, one more Mycoplasma haemocanis infection and more putative bacterial pathogens than the lowest performing kit.
Polymeric Nanocarriers of Drug Delivery Systems in Cancer Therapy
Authors: Avramović Nataša , Mandić Boris , Savić-Radojević Ana , Simić Tatjana
Published: April 2020

Conventional chemotherapy is the most common therapeutic method for treating cancer by the application of small toxic molecules thatinteract with DNA and causecell death. Unfortunately, these chemotherapeutic agents are non-selective and can damage both cancer and healthy tissues, producing diverse side effects, andthey can have a short circulation half-life and limited targeting. Many synthetic polymers have found application as nanocarriers of intelligent drug delivery systems (DDSs). Their unique physicochemical properties allow them to carry drugs with high efficiency, specificallytarget cancer tissue and control drug release. In recent years, considerable efforts have been made to design smart nanoplatforms, including amphiphilic block copolymers, polymer-drug conjugates and in particular pH- and redox-stimuli-responsive nanoparticles (NPs). This review is focused on a new generation of polymer-based DDSs with specific chemical functionalities that improve their hydrophilicity, drug loading and cellular interactions.Recentlydesigned multifunctional DDSs used in cancer therapy are highlighted in this review.
The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG)
Authors: Duralliu Arnold , Matejtschuk Paul , Stickings Paul , Hassall Laura , Tierney Robert , Williams Daryl R.
Published: April 2020

High protein concentration products for targeted therapeutic use are often freeze-dried to enhance stability. The long-term storage stability of freeze-dried (FD) plasma-derived Immunoglobulin G (IgG) from moderate to high concentrations (10–200 mg/mL) was assessed. Monomer content, binding activity and reconstitution times were evaluated over a 12-month period under accelerated and real-term storage conditions. In the first case study it was shown that FD IgG from 10 to 200 mg/mL had minimal monomer/activity losses at up to ambient temperature after 12 months of storage. However, at 45 °C the sucrose-to-protein ratio played a significant impact on IgG stability above 50 mg/mL. All IgG concentrations witnessed moisture ingress over a 12-month period. The impact of moisture ingress from environmental exposure (between 0.1% and 5% w/w moisture) for IgG 50 mg/mL was assessed, being generated by exposing low moisture batches to an atmospheric environment for fixed time periods. Results showed that at −20 °C and 20 °C there was no significant difference in terms of monomer or antigen-binding activity losses over 6 months. However, at 45 °C, there were losses in monomer content, seemingly worse for higher moisture content samples although model binding activity indicated no losses. Finally, the difference between a low moisture product (0.1–1% w/w) and a moderately high moisture (3% w/w) product generated by alternative freeze-drying cycles, both stoppered under low oxygen headspace conditions, was evaluated. Results showed that at −20 °C and 20 °C there was no difference in terms of binding activity or monomer content. However, at 45 °C, the low moisture samples had greater monomer and binding activity losses than samples from the highest moisture cycle batch, indicating that over-drying can be an issue.
Dendritic Cells Pre-Pulsed with Wilms’ Tumor 1 in Optimized Culture for Cancer Vaccination
Authors: Koya Terutsugu , Date Ippei , Kawaguchi Haruhiko , Watanabe Asuka , Sakamoto Takuya , Togi Misa , Kato Tomohisa , Yoshida Kenichi , Kojima Shunsuke , Yanagisawa Ryu , Koido Shigeo , Sugiyama Haruo , Shimodaira Shigetaka
Published: April 2020

With recent advances in cancer vaccination therapy targeting tumor-associated antigens (TAAs), dendritic cells (DCs) are considered to play a central role as a cell-based drug delivery system in the bioactive immune environment. Ex vivo generation of monocyte-derived DCs has been conventionally applied in adherent manufacturing systems with separate loading of TAAs before clinical use. We developed DCs pre-pulsed with Wilms’ tumor (WT1) peptides in low-adhesion culture maturation (WT1-DCs). Quality tests (viability, phenotype, and functions) of WT1-DCs were performed for process validation, and findings were compared with those for conventional DCs (cDCs). In comparative analyses, WT1-DCs showed an increase in viability and recovery of the DC/monocyte ratio, displaying lower levels of IL-10 (an immune suppressive cytokine) and a similar antigen-presenting ability in an in vitro cytotoxic T lymphocytes (CTLs) assay with cytomegalovirus, despite lower levels of CD80 and PD-L2. A clinical study revealed that WT1-specific CTLs (WT1-CTLs) were detected upon using the WT1-DCs vaccine in patients with cancer. A DC vaccine containing TAAs produced under an optimized manufacturing protocol is a potentially promising cell-based drug delivery system to induce acquired immunity.
Fluconazole and Lipopeptide Surfactin Interplay During Candida albicans Plasma Membrane and Cell Wall Remodeling Increases Fungal Immune System Exposure
Authors: Suchodolski Jakub , Derkacz Daria , Muraszko Jakub , Panek Jarosław J. , Jezierska Aneta , Łukaszewicz Marcin , Krasowska Anna
Published: April 2020

Recognizing the β-glucan component of the Candida albicans cell wall is a necessary step involved in host immune system recognition. Compounds that result in exposed β-glucan recognizable to the immune system could be valuable antifungal drugs. Antifungal development is especially important because fungi are becoming increasingly drug resistant. This study demonstrates that lipopeptide, surfactin, unmasks β-glucan when the C. albicans cells lack ergosterol. This observation also holds when ergosterol is depleted by fluconazole. Surfactin does not enhance the effects of local chitin accumulation in the presence of fluconazole. Expression of the CHS3 gene, encoding a gene product resulting in 80% of cellular chitin, is downregulated. C. albicans exposure to fluconazole changes the composition and structure of the fungal plasma membrane. At the same time, the fungal cell wall is altered and remodeled in a way that makes the fungi susceptible to surfactin. In silico studies show that surfactin can form a complex with β-glucan. Surfactin forms a less stable complex with chitin, which in combination with lowering chitin synthesis, could be a second anti-fungal mechanism of action of this lipopeptide.
Semisolid Dosage
Authors: Lunter Dominique Jasmin , Daniels Rolf
Published: April 2020

Already in ancient times, semisolid preparations for cutaneous application, popularly known as ointments, played an important role in human society [...]
Availability of Authorizations from EMA and FDA for Age-Appropriate Medicines Contained in the WHO Essential Medicines List for Children 2019
Authors: delMoral-Sanchez Jose-Manuel , Gonzalez-Alvarez Isabel , Gonzalez-Alvarez Marta , Navarro-Ruiz Andres , Bermejo Marival
Published: April 2020

Lack of age-appropriate commercially drug products availability is a common problem in pediatric therapeutics; this population needs improved and safer drug delivery. In addition, biopharmaceutic aspects, dosage requirements, and swallowing abilities demand pediatric forms different to adult formulations. The objective of this study was to evaluate the authorization availability from United States Food and Drug Administration (FDA) and European Medicines Agency (EMA) of oral essential medicines for children and analyze its age-appropriateness for oral administration in children. All oral drugs from 7th List of Essential Medicines for Children by World Health Organization (WHO) were selected. Availability of commercial drug products was collected from OrangeBook, Spanish drug product catalogue, British electronic Medicines Compendium, and the International Vademecum. Tablets, effervescent tablets, and capsules were considered as not age-appropriate forms. Liquid forms, powder for oral suspension, mini tablets, granules, and soluble films were considered as age-appropriate forms due to their flexibility. More than 80% of the studied drugs possess a commercial authorization in oral forms in both EMA and FDA. Nevertheless, around 50% of these formulations are not age-appropriate for most pediatric groups. This study shows the lack of age-appropriate medicines for children. More efforts are needed to improve development and approval of pediatric medicines.
Stay in Touch—The Cortical ER of Moss Protonemata in Osmotic Stress Situations
Authors: Harant Dominik , Lang Ingeborg
Published: April 2020

Plasmolysis is usually introduced to cell biology students as a tool to illustrate the plasma membrane: hypertonic solutions cause the living protoplast to shrink by osmotic water loss; hence, it detaches from the surrounding cell wall. What happens, however, with the subcellular structures in the cell cortex during this process of turgor loss? Here, we investigated the cortical endoplasmic reticulum (ER) in moss protonema cells of Physcomitrella patens in a cell line carrying a transgenic ER marker (GFP-HDEL). The plasma membrane was labelled simultaneously with the fluorescent dye FM4-64 to achieve structural separation. By placing the protonemata in a hypertonic mannitol solution (0.8 M), we were able to follow the behaviour of the cortical ER and the protoplast during plasmolysis by confocal laser scanning microscopy (CLSM). The protoplast shape and structural changes of the ER were further examined after depolymerisation of actin microfilaments with latrunculin B (1 µM). In its natural state, the cortical ER is a dynamic network of fine tubes and cisternae underneath the plasma membrane. Under acute and long-term plasmolysis (up to 45 min), changes in the protoplast form and the cortical ER, as well as the formation of Hechtian strands and Hechtian reticula, were observed. The processing of the high-resolution z-scans allowed the creation of 3D models and gave detailed insight into the ER of living protonema cells before, during and after plasmolysis.
Role and Regulation of Cytokinins in Plant Response to Drought Stress
Authors: Hai Nguyen Ngoc , Chuong Nguyen Nguyen , Tu Nguyen Huu Cam , Kisiala Anna , Hoang Xuan Lan Thi , Thao Nguyen Phuong
Published: April 2020

Cytokinins (CKs) are key phytohormones that not only regulate plant growth and development but also mediate plant tolerance to drought stress. Recent advances in genome-wide association studies coupled with in planta characterization have opened new avenues to investigate the drought-responsive expression of CK metabolic and signaling genes, as well as their functions in plant adaptation to drought. Under water deficit, CK signaling has evolved as an inter-cellular communication network which is essential to crosstalk with other types of phytohormones and their regulating pathways in mediating plant stress response. In this review, we revise the current understanding of CK involvement in drought stress tolerance. Particularly, a genetic framework for CK signaling and CK crosstalk with abscisic acid (ABA) in the precise monitoring of drought responses is proposed. In addition, the potential of endogenous CK alteration in crops towards developing drought-tolerant crops is also discussed.
Patterns of Genetic Diversity in Highly Invasive Species: Cogongrass (Imperata cylindrica) Expansion in the Invaded Range of the Southern United States (US)
Authors: Lucardi Rima D. , Wallace Lisa E. , Ervin Gary N.
Published: April 2020

The spatial expansions of invasive organisms in the novel range are generally expected to follow an isolation-by-distance relationship (IBD) if the invasion is biologically driven; however, many invasions are facilitated anthropogenically. This research focused on the extant expansion patterns of cogongrass (Imperata cylindrica). Cogongrass is a widespread invasive species throughout the southern United States (US). Patterns of infestation vary among US states. Cogongrass is pyrogenic, and its invasion threatens softwood (Pinus spp.) plantations, a substantial economic market for this US region. Over 600 individuals were sampled from seven invaded US states, using amplified fragment length polymorphisms (AFLPs) to assess genetic diversity and population structure. We suspected that differences in historical management efforts among US states influenced differences in genetic diversity and structure. We detected two genetic lineages at the highest level of analysis. One genetic lineage was locally restricted, whereas the other was found throughout the study region. Admixed individuals were found in all US states and consistently co-occurred with the dominant lineage, suggesting that secondary contact and hybridization may have facilitated expansion. The widespread prevalence of only one of the two detected genetic lineages suggests a primary genetic lineage responsible for on-going population expansion in the US.
Colchicine-Induced Polyploidy in Rhododendron fortunei Lindl
Authors: Mo Lan , Chen Junhao , Lou Xiongzhen , Xu Qiangwei , Dong Renhui , Tong Zaikang , Huang Huahong , Lin Erpei
Published: April 2020

Polyploidy in Rhododendron fortunei has great potential to improve its horticultural and commercial value, and to also meet market demands. In this study, a feasible method for polyploid induction in R. fortunei via colchicine treatment was established, and the obtained polyploid plants were identified and characterized. As a result, the stem bases of tissue-cultured plantlets treated with 0.1% colchicine for 24 h showed the highest polyploid induction with a rate of 36.67%. By flow cytometric analysis, 69 tetraploids and 29 octoploids were identified in the regenerated plants that were examined. Phenotypic analysis indicated that the leaves of tetraploid and octoploid plants were smaller, rounder and thicker with more abundant and longer epidermal hairs than those of diploids. Furthermore, the stomata of polyploids were larger and sparser than those of diploids. An increase in chlorophyll content was also detected in polyploids, which resulted in darker green leaves. In conclusion, our study established an effective method to induce polyploidy in R. fortunei, which could be used to develop new genetic resources for breeding R. fortunei and other Rhododendron species in the future.
Citrus Polyamines: Structure, Biosynthesis, and Physiological Functions
Authors: Killiny Nabil , Nehela Yasser
Published: April 2020

Polyamines (PAs) are ubiquitous biogenic amines found in all living organisms from bacteria to Archaea, and Eukaryotes including plants and animals. Since the first description of putrescine conjugate, feruloyl-putrescine (originally called subaphylline), from grapefruit leaves and juice, many research studies have highlighted the importance of PAs in growth, development, and other physiological processes in citrus plants. PAs appear to be involved in a wide range of physiological processes in citrus plants; however, their exact roles are not fully understood. Accordingly, in the present review, we discuss the biosynthesis of PAs in citrus plants, with an emphasis on the recent advances in identifying and characterizing PAs-biosynthetic genes and other upstream regulatory genes involved in transcriptional regulation of PAs metabolism. In addition, we will discuss the recent metabolic, genetic, and molecular evidence illustrating the roles of PAs metabolism in citrus physiology including somatic embryogenesis; root system formation, morphology, and architecture; plant growth and shoot system architecture; inflorescence, flowering, and flowering-associated events; fruit set, development, and quality; stomatal closure and gas-exchange; and chlorophyll fluorescence and photosynthesis. We believe that the molecular and biochemical understanding of PAs metabolism and their physiological roles in citrus plants will help citrus breeding programs to enhance tolerance to biotic and abiotic stresses and provide bases for further research into potential applications.
Efficiency, Profitability and Carbon Footprint of Different Management Programs under No-Till to Control Herbicide Resistant Papaver rhoeas
Authors: Recasens Jordi , Royo-Esnal Aritz , Valencia-Gredilla Francisco , Torra Joel
Published: April 2020

The present work examines the effects of different integrated weed management (IWM) programs on multiple herbicide-resistant Papaver rhoeas populations in terms of effectiveness, profitability and carbon footprint. With this aim a trial was established in a winter cereal field under no-till in North-Eastern Spain during three consecutive seasons. Four IWM programs with different intensification levels, from less (crop rotation, mechanical control, and no herbicides) to more intense (wheat monoculture with high chemical inputs), were established. The different strategies integrated in the four programs were efficient in managing the weed after three years, with increased effectiveness after management program intensification. Whereas low input program (which includes fallow season) represented less economic cost than the other programs, on average, no differences were observed on carbon foot print, considered as kg CO2eq kg−1 product, between the different programs, except in the crop rotation program due to the low pea yield obtained. The results from this study show that in the search for a balance between crop profitability and reduction of the carbon footprint while controlling an herbicide resistant population is challenging, and particularly under no-till. In this scenario the short term priority should be to reduce the presence of multiple herbicide resistant biotypes integrating the different available chemical, cultural, and physical strategies.
In Vitro Antifungal Activity of Peltophorum dubium (Spreng.) Taub. extracts against Aspergillus flavus
Authors: Di Ciaccio Lucía S. , Catalano Alejandra V. , López Paula G. , Rojas Dante , Cristos Diego , Fortunato Renée H. , Salvat Adriana E.
Published: April 2020

Aspergillus flavus is a filamentous, saprophytic fungus, whose colonization occurs mainly in cereal grains and oilseeds once harvested. Under certain conditions, it could produce mycotoxins called aflatoxins, known as powerful human liver carcinogens. The aim of the present study was to describe the antifungal activity of extracts of Peltophorum dubium, a species from northern Argentina (Oriental Chaco), against A. flavus. The antifungal activities of different collection sites are reported. The extracts exhibited a minimum inhibitory concentration of 125 µg/mL, and the differences between the treatments and the inoculum control were 11 mm of P. dubium A and 10 mm of P. dubium F in colony growth. Moreover, hyphae treated with the extracts stained blue with Evans blue showed alterations in the membrane and/or cell wall, allowing the dye income. Bio-guided fractionation, High Performance Liquid Chromatography diode array ultraviolet/visible (HPLC UV/VIS DAD), and Ultra-High Performance Liquid Chromatography Electrospray Ionization Mass Spectrometry (UPLC ESI-MS) analyses were conducted to characterize the extracts and their active fractions. The HPLC UV/VIS DAD analysis allowed the determination of the presence of flavonoids (flavonols and flavones), coumarins, terpenes, and steroids. UPLC ESI/MS analysis of active fractions revealed the presence of Kaempferol, Apigenin, Naringenin, Chrysin and Daidzein.