bluuebunny/crossref_metadata_2025 huggingface dataset:
The Ubiquity and Development-Related Abundance Dynamics of Ophiocordyceps Fungi in Soft Scale Insects
Authors: Deng Jun , Yu Yuhua , Wang Xu , Liu Qian , Huang Xiaolei
Published: February 2021

Mutual relationships with symbionts play a crucial role in the evolution and ecology of plant-feeding hemipteran insects. However, there was no specific dominant bacterium observed in soft scales (Coccidae) in the previous studies, it is still unclear whether soft scales have specific primary symbionts. In this study, a nuclear ribosomal internal transcribed spacer (ITS)gene fragment was used to analyze the diversity of fungal communities in 28 Coccidae species based on next-generation sequencing (NGS). Furthermore, samples from different developmental stages of Ceroplastes japonicus were sequenced to illustrate the dynamics of fungal community. Our results showed that Coccidae-associated Ophiocordyceps fungi (COF) were prevalent in all 28 tested species with high relative abundance. Meanwhile, the first and second instars of C. japonicus, two important stages for growth and development, had high relative abundance of COF, while the relative abundances in other stages were low, ranging from 0.68% to 2.07%. The result of fluorescent in situ hybridization showed that the COF were widely present in hemolymph and vertically transmitted from mother to offspring. Our study confirms that the COF have intimate associations with the growth and development of soft scales, and provides new evidence to support that COF are primary fungal symbionts for Coccidae.
Identification of Trypanosoma cruzi Growth Inhibitors with Activity In Vivo within a Collection of Licensed Drugs
Authors: Martinez-Peinado Nieves , Cortes-Serra Nuria , Sherman Julian , Rodriguez Ana , Bustamante Juan M. , Gascon Joaquim , Pinazo Maria-Jesus , Alonso-Padilla Julio
Published: February 2021

Chagas disease, caused by the parasite Trypanosoma cruzi (T. cruzi), affects more than six million people worldwide, with its greatest burden in Latin America. Available treatments present frequent toxicity and variable efficacy at the chronic phase of the infection, when the disease is usually diagnosed. Hence, development of new therapeutic strategies is urgent. Repositioning of licensed drugs stands as an attractive fast-track low-cost approach for the identification of safer and more effective chemotherapies. With this purpose we screened 32 licensed drugs for different indications against T. cruzi. We used a primary in vitro assay of Vero cells infection by T. cruzi. Five drugs showed potent activity rates against it (IC50 < 4 µmol L−1), which were also specific (selectivity index >15) with respect to host cells. T. cruzi inhibitory activity of four of them was confirmed by a secondary anti-parasitic assay based on NIH-3T3 cells. Then, we assessed toxicity to human HepG2 cells and anti-amastigote specific activity of those drugs progressed. Ultimately, atovaquone-proguanil, miltefosine, and verapamil were tested in a mouse model of acute T. cruzi infection. Miltefosine performance in vitro and in vivo encourages further investigating its use against T. cruzi.
Effects of Durum Wheat Cultivars with Different Degrees of FHB Susceptibility Grown under Different Meteorological Conditions on the Contamination of Regulated, Modified and Emerging Mycotoxins
Authors: Scarpino Valentina , Blandino Massimo
Published: February 2021

The enhancement of Fusarium head blight (FHB) resistance is one of the best options to reduce mycotoxin contamination in wheat. This study has aimed to verify that the genotypes with high tolerance to deoxynivalenol could guarantee an overall minimization of the sanitary risk, by evaluating the contamination of regulated, modified and emerging mycotoxins on durum wheat cvs with different degrees of FHB susceptibility, grown under different meteorological conditions, in 8 growing seasons in North-West Italy. The years which were characterized by frequent and heavy rainfall in spring were also those with the highest contamination of deoxynivalenol, zearalenone, moniliformin, and enniatins. The most FHB resistant genotypes resulted in the lowest contamination of all the mycotoxins but showed the highest deoxynivalenol-3-glucoside/deoxynivalenol ratio and moniliformin/deoxynivalenol ratio. An inverse relationship between the amount of deoxynivalenol and the deoxynivalenol-3-glucoside/deoxynivalenol ratio was recorded for all the cvs and all the years. Conversely, the enniatins/deoxynivalenol ratio had a less intense relationship with cv tolerance to FHB. In conclusion, even though the more tolerant cvs, showed higher relative relationships between modified/emerging mycotoxins and native/target mycotoxins than the susceptible ones, they showed lower absolute levels of contamination of both emerging and modified mycotoxins.
Requirement of the LtsA Protein for Formation of the Mycolic Acid-Containing Layer on the Cell Surface of Corynebacterium glutamicum
Authors: Kumagai Yutaro , Hirasawa Takashi , Wachi Masaaki
Published: February 2021

The ltsA gene of Corynebacterium glutamicum encodes a purF-type glutamine-dependent amidotransferase, and mutations in this gene result in increased susceptibility to lysozyme. Recently, it was shown that the LtsA protein catalyzes the amidation of diaminopimelate residues in the lipid intermediates of peptidoglycan biosynthesis. In this study, intracellular localization of wild-type and mutant LtsA proteins fused with green fluorescent protein (GFP) was investigated. The GFP-fused wild-type LtsA protein showed a peripheral localization pattern characteristic of membrane-associated proteins. The GFP-fusions with a mutation in the N-terminal domain of LtsA, which is necessary for the glutamine amido transfer reaction, exhibited a similar localization to the wild type, whereas those with a mutation or a truncation in the C-terminal domain, which is not conserved among the purF-type glutamine-dependent amidotransferases, did not. These results suggest that the C-terminal domain is required for peripheral localization. Differential staining of cell wall structures with fluorescent dyes revealed that formation of the mycolic acid-containing layer at the cell division planes was affected in the ltsA mutant cells. This was also confirmed by observation that bulge formation was induced at the cell division planes in the ltsA mutant cells upon lysozyme treatment. These results suggest that the LtsA protein function is required for the formation of a mycolic acid-containing layer at the cell division planes and that this impairment results in increased susceptibility to lysozyme.
Measurement on Diffusion Coefficients and Isotope Fractionation Factors by a Through-Diffusion Experiment
Authors: Hasegawa Takuma , Nakata Kotaro , Gwynne Rhys
Published: February 2021

For radioactive waste disposal, it is important that local groundwater flow is slow as groundwater flow is the main transport medium for radioactive nuclides in geological formations. When the groundwater flow is very slow, diffusion is the dominant transport mechanism (diffusion-dominant domain). Key pieces of evidence indicating a diffusion-dominant domain are the separation of components and the fractionation of isotopes by diffusion. To prove this, it is necessary to investigate the different diffusion coefficients for each component and the related stable isotope fractionation factors. Thus, in this study, through-diffusion and effective-porosity experiments were conducted on selected artificial materials and natural rocks. We also undertook measurements relating to the isotope fractionation factors of Cl and Br isotopes for natural samples. For natural rock samples, the diffusion coefficients of water isotopes (HDO and H218O) were three to four times higher than those of monovalent anions (Cl−, Br- and NO3−), and the isotope fractionation factor of 37Cl (1.0017–1.0021) was slightly higher than that of free water. It was experimentally confirmed that the isotope fractionation factor of 81Br was approximately 1.0007–1.0010, which is equivalent to that of free water. The enrichment factor of 81Br was almost half that of 37Cl. The effective porosity ratios of HDO and Cl were slightly different, but the difference was not significant compared to the ratio of their diffusion coefficients. As a result, component separation was dominated by diffusion. For artificial samples, the diffusion coefficients and effective porosities of HDO and Cl were almost the same; it was thus difficult to assess the component separation by diffusion. However, isotope fractionation of Cl and Br was confirmed using a through-diffusion experiment. The results show that HDO and Cl separation and isotope fractionation of Cl and Br can be expected in diffusion-dominant domains in geological formations.
Genetic Link between Podiform Chromitites in the Mantle and Stratiform Chromitites in the Crust: A Hypothesis
Authors: Arai Shoji
Published: February 2021

No genetic link between the two main types of chromitite, stratiform and podiform chromitites, has ever been discussed. These two types of chromitite have very different geological contexts; the stratiform one is a member of layered intrusions, representing fossil magma chambers, in the crust, and the podiform one forms pod-like bodies, representing fossil magma conduits, in the upper mantle. Chromite grains contain peculiar polymineralic inclusions derived from Na-bearing hydrous melts, whose features are so similar between the two types that they may form in a similar fashion. The origin of the chromite-hosted inclusions in chromitites has been controversial but left unclear. The chromite-hosted inclusions also characterize the products of the peridotite–melt reaction or melt-assisted partial melting, such as dunites, troctolites and even mantle harzburgites. I propose a common origin for the inclusion-bearing chromites, i.e., a reaction between the mantle peridotite and magma. Some of the chromite grains in the stratiform chromitite originally formed in the mantle through the peridotite–magma reaction, possibly as loose-packed young podiform chromitites, and were subsequently disintegrated and transported to a crustal magma chamber as suspended grains. It is noted, however, that the podiform chromitites left in the mantle beneath the layered intrusions are different from most of the podiform chromitites now exposed in the ophiolites.
Stability and Photoisomerization of Stilbenes Isolated from the Bark of Norway Spruce Roots
Authors: Latva-Mäenpää Harri , Wufu Riziwanguli , Mulat Daniel , Sarjala Tytti , Saranpää Pekka , Wähälä Kristiina
Published: February 2021

Stilbenes or stilbenoids, major polyphenolic compounds of the bark of Norway spruce (Picea abies L. Karst), have potential future applications as drugs, preservatives and other functional ingredients due to their antioxidative, antibacterial and antifungal properties. Stilbenes are photosensitive and UV and fluorescent light induce trans to cis isomerisation via intramolecular cyclization. So far, the characterizations of possible new compounds derived from trans-stilbenes under UV light exposure have been mainly tentative based only on UV or MS spectra without utilizing more detailed structural spectroscopy techniques such as NMR. The objective of this work was to study the stability of biologically interesting and readily available stilbenes such as astringin and isorhapontin and their aglucones piceatannol and isorhapontigenin, which have not been studied previously. The effects of fluorescent and UV light and storage on the stability of trans stilbenes were assessed and the identification and characterisation of new compounds formed during our experiments were carried out by chromatographic (HPLC, GC) and spectroscopic techniques (UV, MS, NMR). The stilbenes undergo a trans to cis isomerisation under extended UV irradiation by intramolecular cyclisation (by the formation of a new C-C bond and the loss of two hydrogens) to phenanthrene structures. The characterised compounds are novel and not described previously.
Anti-Inflammatory, Antidiabetic Properties and In Silico Modeling of Cucurbitane-Type Triterpene Glycosides from Fruits of an Indian Cultivar of Momordica charantia L.
Authors: Perera Wilmer H. , Shivanagoudra Siddanagouda R. , Pérez Jose L. , Kim Da Mi , Sun Yuxiang , K. Jayaprakasha Guddadarangavvanahally , S. Patil Bhimanagouda
Published: February 2021

Diabetes mellitus is a chronic disease and one of the fastest-growing health challenges of the last decades. Studies have shown that chronic low-grade inflammation and activation of the innate immune system are intimately involved in type 2 diabetes pathogenesis. Momordica charantia L. fruits are used in traditional medicine to manage diabetes. Herein, we report the purification of a new 23-O-β-d-allopyranosyl-5β,19-epoxycucurbitane-6,24-diene triterpene (charantoside XV, 6) along with 25ξ-isopropenylchole-5(6)-ene-3-O-β-d-glucopyranoside (1), karaviloside VI (2), karaviloside VIII (3), momordicoside L (4), momordicoside A (5) and kuguaglycoside C (7) from an Indian cultivar of Momordica charantia. At 50 µM compounds, 2–6 differentially affected the expression of pro-inflammatory markers IL-6, TNF-α, and iNOS, and mitochondrial marker COX-2. Compounds tested for the inhibition of α-amylase and α-glucosidase enzymes at 0.87 mM and 1.33 mM, respectively. Compounds showed similar α-amylase inhibitory activity than acarbose (0.13 mM) of control (68.0–76.6%). Karaviloside VIII (56.5%) was the most active compound in the α-glucosidase assay, followed by karaviloside VI (40.3%), while momordicoside L (23.7%), A (33.5%), and charantoside XV (23.9%) were the least active compounds. To better understand the mode of binding of cucurbitane-triterpenes to these enzymes, in silico docking of the isolated compounds was evaluated with α-amylase and α-glucosidase.
Ice-Templated Cellulose Nanofiber Filaments as a Reinforcement Material in Epoxy Composites
Authors: Nissilä Tuukka , Wei Jiayuan , Geng Shiyu , Teleman Anita , Oksman Kristiina
Published: February 2021

Finding renewable alternatives to the commonly used reinforcement materials in composites is attracting a significant amount of research interest. Nanocellulose is a promising candidate owing to its wide availability and favorable properties such as high Young’s modulus. This study addressed the major problems inherent to cellulose nanocomposites, namely, controlling the fiber structure and obtaining a sufficient interfacial adhesion between nanocellulose and a non-hydrophilic matrix. Unidirectionally aligned cellulose nanofiber filament mats were obtained via ice-templating, and chemical vapor deposition was used to cover the filament surfaces with an aminosilane before impregnating the mats with a bio-epoxy resin. The process resulted in cellulose nanocomposites with an oriented structure and a strong fiber–matrix interface. Diffuse reflectance infrared Fourier transform and X-ray photoelectron spectroscopy studies revealed the presence of silane on the filaments. The improved interface, resulting from the surface treatment, was observable in electron microscopy images and was further confirmed by the significant increase in the tan delta peak temperature. The storage modulus of the matrix could be improved up to 2.5-fold with 18 wt% filament content and was significantly higher in the filament direction. Wide-angle X-ray scattering was used to study the orientation of cellulose nanofibers in the filament mats and the composites, and the corresponding orientation indices were 0.6 and 0.53, respectively, indicating a significant level of alignment.
Interface Trap-Induced Temperature Dependent Hysteresis and Mobility in β-Ga2O3 Field-Effect Transistors
Authors: Park Youngseo , Ma Jiyeon , Yoo Geonwook , Heo Junseok
Published: February 2021

Interface traps between a gate insulator and beta-gallium oxide (β-Ga2O3) channel are extensively studied because of the interface trap charge-induced instability and hysteresis. In this work, their effects on mobility degradation at low temperature and hysteresis at high temperature are investigated by characterizing electrical properties of the device in a temperature range of 20–300 K. As acceptor-like traps at the interface are frozen below 230 K, the hysteresis becomes negligible but simultaneously the channel mobility significantly degrades because the inactive neutral traps allow additional collisions of electrons at the interface. This is confirmed by the fact that a gate bias adversely affects the channel mobility. An activation energy of such traps is estimated as 170 meV. The activated trap charges’ trapping and de-trapping processes in response to the gate pulse bias reveal that the time constants for the slow and fast processes decrease due to additionally activated traps as the temperature increases.
Coarse-Grained Quantum Theory of Organic Photovoltaic Devices
Authors: Sánchez Fernando , Sánchez Vicenta , Wang Chumin
Published: February 2021

Understanding the exciton dissociation process in organic solar cells is a fundamental issue for the design of high-performance photovoltaic devices. In this article, a parameterized quantum theory based on a coarse-grained tight-binding model plus non-local electron-hole interactions is presented, while the diffusion and recombination of excitons are studied in a square lattice of excitonic states, where a real-space renormalization method on effective chains has been used. The Hamiltonian parameters are determined by fitting the measured quantum efficiency spectra and the theoretical short-circuit currents without adjustable parameters show a good agreement with the experimental ones obtained from several polymer:fullerene and polymer:polymer heterojunctions. Moreover, the present study reveals the degree of polymerization and the true driving force at donor-acceptor interface in each analyzed organic photovoltaic device.
Chemically-Gated and Sustained Molecular Transport through Nanoporous Gold Thin Films in Biofouling Conditions
Authors: Palanisamy Barath , Goshi Noah , Seker Erkin
Published: February 2021

Sustained release and replenishment of the drug depot are essential for the long-term functionality of implantable drug-delivery devices. This study demonstrates the use nanoporous gold (np-Au) thin films for in-plane transport of fluorescein (a small-molecule drug surrogate) over large (mm-scale) distances from a distal reservoir to the site of delivery, thereby establishing a constant flux of molecular release. In the absence of halides, the fluorescein transport is negligible due to a strong non-specific interaction of fluorescein with the pore walls. However, in the presence of physiologically relevant concentration of ions, halides preferentially adsorb onto the gold surface, minimizing the fluorescein–gold interactions and thus enabling in-plane fluorescein transport. In addition, the nanoporous film serves as an intrinsic size-exclusion matrix and allows for sustained release in biofouling conditions (dilute serum). The molecular release is reproducibly controlled by gating it in response to the presence of halides at the reservoir (source) and the release site (sink) without external triggers (e.g., electrical and mechanical).
A Review on the Role of Food-Derived Bioactive Molecules and the Microbiota–Gut–Brain Axis in Satiety Regulation
Authors: Pizarroso Nuria , Fuciños Pablo , Gonçalves Catarina , Pastrana Lorenzo , Amado Isabel
Published: February 2021

Obesity is a chronic disease resulting from an imbalance between energy intake and expenditure. The growing relevance of this metabolic disease lies in its association with other comorbidities. Obesity is a multifaceted disease where intestinal hormones such as cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and peptide YY (PYY), produced by enteroendocrine cells (EECs), have a pivotal role as signaling systems. Receptors for these hormones have been identified in the gut and different brain regions, highlighting the interconnection between gut and brain in satiation mechanisms. The intestinal microbiota (IM), directly interacting with EECs, can be modulated by the diet by providing specific nutrients that induce environmental changes in the gut ecosystem. Therefore, macronutrients may trigger the microbiota–gut–brain axis (MGBA) through mechanisms including specific nutrient-sensing receptors in EECs, inducing the secretion of specific hormones that lead to decreased appetite or increased energy expenditure. Designing drugs/functional foods based in bioactive compounds exploiting these nutrient-sensing mechanisms may offer an alternative treatment for obesity and/or associated metabolic diseases. Organ-on-a-chip technology represents a suitable approach to model multi-organ communication that can provide a robust platform for studying the potential of these compounds as modulators of the MGBA.
Sex-Dependent Effects of 7,8-Dihydroxyflavone on Metabolic Health Are Associated with Alterations in the Host Gut Microbiome
Authors: Sharma Priyanka , Wu Guojun , Kumaraswamy Deeptha , Burchat Natalie , Ye Hong , Gong Yongjia , Zhao Liping , Lam Yan Y. , Sampath Harini
Published: February 2021

7,8-Dihydroxyflavone (DHF) is a naturally occurring flavonoid that has been reported to protect against a variety of pathologies. Chronic administration of DHF prevents high-fat diet (HFD)-induced obesity in female, but not male, mice. However, the mechanisms underlying this sexual dimorphism have not been elucidated. We have discovered that oral DHF supplementation significantly attenuates fat mass, hepatic lipid accumulation, and adipose tissue inflammation in female mice. In contrast, male mice were not protected from adiposity, and had a paradoxical worsening of hepatic lipid accumulation and adipose tissue inflammation upon DHF supplementation. Consistent with these sexually dimorphic effects on body weight and metabolic health, 7,8-DHF induced early and stable remodeling of the female intestinal microbiome. DHF supplementation significantly increased gut microbial diversity, and suppressed potentially detrimental bacteria, particularly Desulfovibrionaceae, which are pro-inflammatory and positively associated with obesity and inflammation. Changes in the female gut microbiome preceded alterations in body weights, and in silico analyses indicated that these early microbial changes were highly predictive of subsequent weight gain in female mice. While some alterations in the intestinal microbiome were also observed in male DHF-supplemented mice, these changes were distinct from those in females and, importantly, were not predictive of subsequent body weight changes in male animals. The temporality of microbial changes preceding alterations in body weight in female mice suggests a role for the gut microbiome in mediating the sexually dimorphic effects of DHF on body weight. Given the significant clinical interest in this flavonoid across a wide range of pathologies, further elucidation of these sexually dimorphic effects will aid the development of effective clinical therapies.
Component-Resolved Diagnosis of Hazelnut Allergy in Children
Authors: Caffarelli Carlo , Mastrorilli Carla , Santoro Angelica , Criscione Massimo , Procaccianti Michela
Published: February 2021

Hazelnuts commonly elicit allergic reactions starting from childhood and adolescence, with a rare resolution over time. The definite diagnosis of a hazelnut allergy relies on an oral food challenge. The role of component resolved diagnostics in reducing the need for oral food challenges in the diagnosis of hazelnut allergies is still debated. Therefore, three electronic databases were systematically searched for studies on the diagnostic accuracy of specific-IgE (sIgE) on hazelnut proteins for identifying children with a hazelnut allergy. Studies regarding IgE testing on at least one hazelnut allergen component in children whose final diagnosis was determined by oral food challenges or a suggestive history of serious symptoms due to a hazelnut allergy were included. Study quality was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Eight studies enrolling 757 children, were identified. Overall, sensitivity, specificity, area under the curve and diagnostic odd ratio of Cor a 1 sIgE were lower than those of Cor a 9 and Cor a 14 sIge. When the test results were positive, the post-test probability of a hazelnut allergy was 34% for Cor a 1 sIgE, 60% for Cor a9 sIgE and 73% for Cor a 14 sIgE. When the test results were negative, the post-test probability of a hazelnut allergy was 55% for Cor a 1 sIgE, 16% for Cor a9 sIgE and 14% for Cor a 14 sIgE. Measurement of IgE levels to Cor a 9 and Cor a 14 might have the potential to improve specificity in detecting clinically tolerant children among hazelnut-sensitized ones, reducing the need to perform oral food challenges.
Application of β-Phosphorylated Nitroethenes in [3+2] Cycloaddition Reactions Involving Benzonitrile N-Oxide in the Light of a DFT Computational Study
Authors: Zawadzińska Karolina , Kula Karolina
Published: February 2021

The regiochemistry of [3+2] cycloaddition (32CA) processes between benzonitrile N-oxide 1 and β-phosphorylated analogues of nitroethenes 2a–c has been studied using the Density Functional Theory (DFT) at the M062X/6-31+G(d) theory level. The obtained results of reactivity indices show that benzonitrile N-oxide 1 can be classified both as a moderate electrophile and moderate nucleophile, while β-phosphorylated analogues of nitroethenes 2a–c can be classified as strong electrophiles and marginal nucleophiles. Moreover, the analysis of CDFT shows that for [3+2] cycloadditions with the participation of β-phosphorylatednitroethene 2a and β-phosphorylated α-cyanonitroethene 2b, the more favored reaction path forms 4-nitro-substituted Δ2-isoxazolines 3a–b, while for a reaction with β-phosphorylated β-cyanonitroethene 2c, the more favored path forms 5-nitro-substituted Δ2-isoxazoline 4c. This is due to the presence of a cyano group in the alkene. The CDFT study correlates well with the analysis of the kinetic description of the considered reaction channels. Moreover, DFT calculations have proven the clearly polar nature of all analyzed [3+2] cycloaddition reactions according to the polar one-step mechanism.
Antifungal Activity of Cyclic Tetrapeptide from Bacillus velezensis CE 100 against Plant Pathogen Colletotrichum gloeosporioides
Authors: Choub Vantha , Maung Chaw Ei Htwe , Won Sang-Jae , Moon Jae-Hyun , Kim Kil Yong , Han Yeon Soo , Cho Jeong-Yong , Ahn Young Sang
Published: February 2021

The aim of this study was to investigate the antifungal activity of a cyclic tetrapeptide from Bacillus velezensis CE 100 against anthracnose-causing fungal pathogen Colletotrichum gloeosporioides. Antifungal compound produced by B. velezensis CE 100 was isolated and purified from ethyl acetate extract of B. velezensis CE 100 culture broth using octadecylsilane column chromatography. The purified compound was identified as cyclo-(prolyl-valyl-alanyl-isoleucyl) based on mass spectrometer and nuclear magnetic resonance analyses. This is the first report of the isolation of a cyclic tetrapeptide from B. velezensis CE 100 culture filtrate. Cyclic tetrapeptide displayed strong antifungal activity at concentration of 1000 µg/mL against C. gloeosporioides mycelial growth and spore germination. Our results demonstrate that the antifungal cyclic tetrapeptide from B. velezensis CE 100 has potential in bioprotection against anthracnose disease of plants caused by C. gloeosporioides.
Assessing Trypanosoma cruzi Parasite Diversity through Comparative Genomics: Implications for Disease Epidemiology and Diagnostics
Authors: Majeau Alicia , Murphy Laura , Herrera Claudia , Dumonteil Eric
Published: February 2021

Chagas disease is an important vector-borne neglected tropical disease that causes great health and economic losses. The etiological agent, Trypanosoma cruzi, is a protozoan parasite endemic to the Americas, comprised by important diversity, which has been suggested to contribute to poor serological diagnostic performance. Current nomenclature describes seven discrete typing units (DTUs), or lineages. We performed the first large scale analysis of T. cruzi diversity among 52 previously published genomes from strains covering multiple countries and parasite DTUs and assessed how different markers summarize this genetic diversity. We also examined how seven antigens currently used in commercial serologic tests are conserved across this diversity of strains. DTU structuration was confirmed at the whole-genome level, with evidence of sub-DTU diversity, associated in part to geographic structuring. We observed very comparable phylogenetic tree topographies for most of the 32 markers investigated, with clear clustering of sequences by DTU, and a few of these markers suggested some degree of intra-lineage diversity. At least three of the currently used antigens represent poorly conserved sequences, with sequences used in tests quite divergent from sequences in many strains. Most markers are well suited for estimating parasite diversity to DTU level, and a few are particularly well-suited to assess intra-DTU diversity. Analysis of antigen sequences across all strains indicates that antigenic diversity is a likely explanation for limited diagnostic performance in Central and North America.
Impact of the Peptide WMR-K on Dual-Species Biofilm Candida albicans/Klebsiella pneumoniae and on the Untargeted Metabolomic Profile
Authors: Galdiero Emilia , Salvatore Maria Michela , Maione Angela , Carraturo Federica , Galdiero Stefania , Falanga Annarita , Andolfi Anna , Salvatore Francesco , Guida Marco
Published: February 2021

In recent years, the scientific community has focused on the development of new antibiotics to address the difficulties linked to biofilm-forming microorganisms and drug-resistant infections. In this respect, synthetic antimicrobial peptides (AMPs) are particularly regarded for their therapeutic potential against a broad spectrum of pathogens. In this work, the antimicrobial and antibiofilm activities of the peptide WMR-K towards single and dual species cultures of Candida albicans and Klebsiella pneumoniae were investigated. We found minimum inhibitory concentration (MIC) values for WMR-K of 10 µM for K. pneumoniae and of 200 µM for C. albicans. Furthermore, sub-MIC concentrations of peptide showed an in vitro inhibition of biofilm formation of mono and polymicrobial systems and also a good biofilm eradication even if higher concentrations of it are needed. In order to provide additional evidence for the effect of the examined peptide, a study of changes in extracellular metabolites excreted and/or uptaken from the culture medium (metabolomic footprinting) in the poly-microbial association of C. albicans and K. pneumoniae in presence and absence of WMR-K was performed. Comparing to the untreated dual species biofilm culture, the metabolomic profile of the WMR-K treated culture appears significantly altered. The differentially expressed compounds are mainly related to the primary metabolic pathways, including amino acids, trehalose, pyruvic acid, glycerol and vitamin B6.
Tumor Type Agnostic Therapy Carrying BRAF Mutation: Case Reports and Review of Literature
Authors: Bernocchi Ottavia , Sirico Marianna , Corona Silvia Paola , Strina Carla , Milani Manuela , Cappelletti Maria Rosa , Ferrero Giuseppina , Ziglioli Nicoletta , Cervoni Valeria , Macchiavelli Andrea , Roviello Giandomenico , Generali Daniele
Published: February 2021

Background: Precision medicine is based on molecular and genotypic patient characterization to define specific target treatment. BRAF mutation is an oncogenic driver, and the Cancer Genome Atlas has identified BRAF mutations in different cancer types. Tumor type agnostic therapy is based on targeting genomic alterations, regardless of tumor origin. In this context, novel therapeutic agents including BRAF and MEK inhibitors based on the molecular landscape in solid tumors have been investigated. Case presentation, Case 1: The first case is chemotherapy-refractory, BRAF V600E mutated intrahepaticcholangiocarcinoma treated with vemurafenib and cobimetinib as third line therapy. In this setting the dual BRAF and MEK inhibition resulted in improved progression-free survival and quality of life; Case 2: The second case shows aBRAF G466A mutated Bellini duct carcinoma (BDC), treated with dabrafenib and trametinib in second line therapy. The disease remained under control for 11 months after the first relapse. Discussion: In the literature there is strong evidence that melanoma, colorectal cancer, non small cell lung cancer and anaplastic thyroid cancer with BRAF mutations are good targets for BRAF/MEK pathway inhibitors. The VE-BASKET and ROAR basket trials explored the efficacy of vemurafenib and the combination of dabrafenib/trametinib, respectively, in BRAF V600 mutation-positive cancers other than melanoma, papillary thyroid cancer, colorectal cancer and non small cell lung cancer. Within the concept of tumor type agnostic therapy, we decided to treat our BRAF-mutated tumors with the association of BRAF and MEK inhibitors. Conclusions: Our results confirm the emerging importance of molecular tumor profiling for the successful management of cancer, and the potential of BRAF-targeted therapy in the treatment of rare solid tumors with poor prognosis and no clinical benefit from systemic therapies with.
Drug–Drug Interactions in Elderly Patients with Potentially Inappropriate Medications in Primary Care, Nursing Home and Hospital Settings: A Systematic Review and a Preliminary Study
Authors: Bories Mathilde , Bouzillé Guillaume , Cuggia Marc , Le Corre Pascal
Published: February 2021

Drug–drug interactions (DDI) occurring with potentially inappropriate medications (PIM) are additional risk factors that may increase the inappropriate character of PIM. The aim of this study was (1) to describe the prevalence and severity of DDI in patients with PIM and (2) to evaluate the DDI specifically regarding PIM. This systematic review is based on a search carried out on PubMed and Web-of-Science from inception to June 30, 2020. We extracted data of original studies that assessed the prevalence of both DDI and PIM in elderly patients in primary care, nursing home and hospital settings. Four hundred and forty unique studies were identified: 91 were included in the qualitative analysis and 66 were included in the quantitative analysis. The prevalence of PIM in primary care, nursing home and hospital were 19.1% (95% confidence intervals (CI): 15.1–23.0%), 29.7% (95% CI: 27.8–31.6%) and 44.6% (95% CI: 28.3–60.9%), respectively. Clinically significant severe risk-rated DDI averaged 28.9% (95% CI: 17.2–40.6), in a hospital setting; and were approximately 7-to-9 lower in primary care and nursing home, respectively. Surprisingly, only four of these studies investigated DDI involving specifically PIM. Hence, given the high prevalence of severe DDI in patients with PIM, further investigations should be carried out on DDI involving specifically PIM which may increase their inappropriate character, and the risk of adverse drug reactions.
Transmucosal Solid Lipid Nanoparticles to Improve Genistein Absorption via Intestinal Lymphatic Transport
Authors: Obinu Antonella , Burrai Giovanni Pietro , Cavalli Roberta , Galleri Grazia , Migheli Rossana , Antuofermo Elisabetta , Rassu Giovanna , Gavini Elisabetta , Giunchedi Paolo
Published: February 2021

Genistein (GEN) is a soy-derived isoflavone that exhibits several biological effects, such as neuroprotective activity and the prevention of several types of cancer and cardiovascular disease. However, due to its poor water solubility and the extensive first-pass metabolism, the oral bioavailability of GEN is limited. In this work, solid lipid nanoparticles (SLN) were developed to preferentially reach the intestinal lymphatic vessels, avoiding the first-pass metabolism of GEN. GEN-loaded SLN were obtained by a hot homogenization process, and the formulation parameters were chosen based on already formulated studies. The nanoparticles were characterized, and the preliminary in vitro chylomicron formation was evaluated. The cell uptake of selected nanocarriers was studied on the Caco-2 cell line and intestinal mucosa. The SLN, characterized by a spherical shape, showed an average diameter (about 280 nm) suitable for an intestinal lymphatic uptake, good stability during the testing time, and high drug loading capacity. Furthermore, the intestinal mucosa and Caco-2 cells were found to uptake SLN. The approximately two-fold increase in particle size suggested a possible interaction between SLN and the lipid components of chylomicrons like phospholipid; therefore, the results may support the potential for these SLN to improve oral GEN bioavailability via intestinal lymphatic absorption.
Analytical Strategies to Analyze the Oxidation Products of Phytosterols, and Formulation-Based Approaches to Reduce Their Generation
Authors: Gachumi George , Poudel Asmita , Wasan Kishor M. , El-Aneed Anas
Published: February 2021

Phytosterols are a class of lipid molecules present in plants that are structurally similar to cholesterol and have been widely utilized as cholesterol-lowering agents. However, the susceptibility of phytosterols to oxidation has led to concerns regarding their safety and tolerability. Phytosterol oxidation products (POPs) present in a variety of enriched and non-enriched foods can show pro-atherogenic and pro-inflammatory properties. Therefore, it is crucial to screen and analyze various phytosterol-containing products for the presence of POPs and ultimately design or modify phytosterols in such a way that prevents the generation of POPs and yet maintains their pharmacological activity. The main approaches for the analysis of POPs include the use of mass spectrometry (MS) linked to a suitable separation technique, notably gas chromatography (GC). However, liquid chromatography (LC)-MS has the potential to simplify the analysis due to the elimination of any derivatization step, usually required for GC-MS. To reduce the transformation of phytosterols to their oxidized counterparts, formulation strategies can theoretically be adopted, including the use of microemulsions, microcapsules, micelles, nanoparticles, and liposomes. In addition, co-formulation with antioxidants, such as tocopherols, may prove useful in substantially preventing POP generation. The main objectives of this review article are to evaluate the various analytical strategies that have been adopted for analyzing them. In addition, formulation approaches that can prevent the generation of these oxidation products are proposed.
Application of Zwitterions in Forward Osmosis: A Short Review
Authors: Chiao Yu-Hsuan , Sengupta Arijit , Ang Micah Belle Marie Yap , Chen Shu-Ting , Haan Teow Yeit , Almodovar Jorge , Hung Wei-Song , Wickramasinghe S. Ranil
Published: February 2021

Forward osmosis (FO) is an important desalination method to produce potable water. It was also used to treat different wastewater streams, including industrial as well as municipal wastewater. Though FO is environmentally benign, energy intensive, and highly efficient; it still suffers from four types of fouling namely: organic fouling, inorganic scaling, biofouling and colloidal fouling or a combination of these types of fouling. Membrane fouling may require simple shear force and physical cleaning for sufficient recovery of membrane performance. Severe fouling may need chemical cleaning, especially when a slimy biofilm or severe microbial colony is formed. Modification of FO membrane through introducing zwitterionic moieties on the membrane surface has been proven to enhance antifouling property. In addition, it could also significantly improve the separation efficiency and longevity of the membrane. Zwitterion moieties can also incorporate in draw solution as electrolytes in FO process. It could be in a form of a monomer or a polymer. Hence, this review comprehensively discussed several methods of inclusion of zwitterionic moieties in FO membrane. These methods include atom transfer radical polymerization (ATRP); second interfacial polymerization (SIP); coating and in situ formation. Furthermore, an attempt was made to understand the mechanism of improvement in FO performance by zwitterionic moieties. Finally, the future prospective of the application of zwitterions in FO has been discussed.
Biodegradation of Poly(Lactic Acid) Biocomposites under Controlled Composting Conditions and Freshwater Biotope
Authors: Brdlík Pavel , Borůvka Martin , Běhálek Luboš , Lenfeld Petr
Published: February 2021

The influence of additives such as natural-based plasticiser acetyl tributyl citrate (ATBC), CaCO3 and lignin-coated cellulose nanocrystals (L-CNC) on the biodegradation of polylactic acid (PLA) biocomposites was studied by monitoring microbial metabolic activity through respirometry. Ternary biocomposites and control samples were processed by a twin-screw extruder equipped with a flat film die. Commonly available compost was used for the determination of the ultimate aerobic biodegradability of PLA biocomposites under controlled composting conditions (ISO 14855-1). In addition, the hydro-degradability of prepared films in a freshwater biotope was analysed. To determine the efficiency of hydro-degradation, qualitative analyses (SEM, DSC, TGA and FTIR) were conducted. The results showed obvious differences in the degradation rate of PLA biocomposites. The application of ATBC at 10 wt.% loading increased the biodegradation rate of PLA. The addition of 10 wt.% of CaCO3 into the plasticised PLA matrix ensured an even higher degradation rate at aerobic thermophilic composting conditions. In such samples (PLA/ATBC/CaCO3), 94% biodegradation in 60 days was observed. In contrast, neat PLA exposed to the same conditions achieved only 16% biodegradation. Slightly inhibited microorganism activity was also observed for ternary PLA biocomposites containing L-CNC (1 wt.% loading). The results of qualitative analyses of degradation in a freshwater biotope confirmed increased biodegradation potential of ternary biocomposites containing both CaCO3 and ATBC. Significant differences in the chemical and structural compositions of PLA biocomposites were found in the evaluated period of three months.
Designing and Manufacturing of Automatic Robotic Lawn Mower
Authors: Liao Juinne-Ching , Chen Shun-Hsing , Zhuang Zi-Yi , Wu Bo-Wei , Chen Yu-Jen
Published: February 2021

This study is about the manufacturing of a personified automatic robotic lawn mower with image recognition. The system structure is that the platform above the crawler tracks is combined with the lawn mower, steering motor, slide rail, and webcam to achieve the purpose of personification. Crawler tracks with a strong grip and good ability to adapt to terrain are selected as a moving vehicle to simulate human feet. In addition, a lawn mower mechanism is designed to simulate the left and right swing of human mowing to promote efficiency and innovation, and then human eyes are replaced by Webcam to identify obstacles. A human-machine interface is added so that through the mobile phone remote operation, users can choose a slow mode, inching mode, and obstacle avoidance mode on the human-machine interface. When the length of both sides of the rectangular area is input to the program, the automatic robotic lawn mower will complete the instruction according to the specified path. The chip of a Digital Signal Processor (DSP) TMS320F2808 is used as the core controller, and Raspberry Pi is used as image recognition and human-machine interface design. This robot can reduce labor costs and improve the efficiency of mowing by remote control. In addition to the use as an automatic mower on farms, this study concept can also be used in the lawn maintenance of golf courses and school playgrounds.
Biodegradable Polyester Synthesis in Renewed Aqueous Polycondensation Media: The Core of the New Greener Polymer-5B Technology
Authors: Pfluck Ana C. D. , de Barros Dragana P.C. , Fonseca Luis P.
Published: February 2021

An innovative enzymatic polycondensation of dicarboxylic acids and dialcohols in aqueous polymerization media using free and immobilized lipases was developed. Various parameters (type of lipases, temperature, pH, stirring type and rate, and monomer carbon chain length) of the polycondensation in an oil-in-water (o/w) miniemulsion (>80% in water) were evaluated. The best results for polycondensation were achieved with an equimolar monomer concentration (0.5 M) of octanedioic acid and 1,8-octanediol in the miniemulsion and water, both at initial pH 5.0 with immobilized Pseudozyma antarctica lipase B (PBLI). The synthesized poly(octamethylene suberate) (POS) in the miniemulsion is characterized by a molecular weight of 7800 g mol−1 and a conversion of 98% at 45 °C after 48 h of polycondensation in batch operation mode. A comparative study of polycondensation using different operation modes (batch and fed-batch), stirring type, and biocatalyst reutilization in the miniemulsion, water, and an organic solvent (cyclohexane:tetrahydrofuran 5:1 v/v) was performed. Regarding the polymer molecular weight and conversion (%), batch operation mode was more appropriate for the synthesis of POS in the miniemulsion and water, and fed-batch operation mode showed better results for polycondensation in the organic solvent. The miniemulsion and water used as polymerization media showed promising potential for enzymatic polycondensation since they presented no enzyme inhibition for high monomer concentrations and excellent POS synthesis reproducibility. The PBLI biocatalyst presented high reutilization capability over seven cycles (conversion > 90%) and high stability equivalent to 72 h at 60 °C on polycondensation in the miniemulsion and water. The benefits of polycondensation in aqueous media using an o/w miniemulsion or water are the origin of the new concept strategy of the green process with a green product that constitutes the core of the new greener polymer-5B technology.
Trust in Public Relations in the Age of Mistrusted Media: A European Perspective
Authors: Moreno Ángeles , Tench Ralph , Verhoeven Piet
Published: February 2021

One of the core problems of misinformation and post-trust societies is, indeed, trust in communications. The undermining of the credibility of media as the backbone of democratic societies is becoming a serious problem that affects democracy, business and all kinds of public institutions and organizations in society(ies). This paper explores perceptions of trust in key stakeholders involved in communication on behalf of organizations. Findings are considered at the professional (macro), departmental (meso) and individual (micro) level as well as considering the trusted role of non-specialist communicators for organizations including internal and external spokespeople. Data were collected from an online survey of 2883 respondents from 46 countries across Europe. Key findings were at the macro level that: antagonism between management communication professionals and journalists remains. The lowest trust in the profession is felt to be by the general public. At the meso level, top executives are perceived to trust the department the most followed by journalists in second place. External experts such as professors and consultants are perceived to be the most trusted by the general public. Finally, at the micro level individuals are more trusted than organizations or departments and the communication profession more widely.