bluuebunny/crossref_metadata_2025 huggingface dataset:
Some Unsolved Problems in Stability and Optimal Control Theory of Stochastic Systems
Authors: Shaikhet Leonid
Published: February 2022

In spite of the fact that the theory of stability and optimal control for different types of stochastic systems is well developed and very popular in research, there are some simply and clearly formulated problems, solutions of which have not been found so far. To the readers’ attention six open stability problems for stochastic differential equations with delay, for stochastic difference equations with discrete and continuous time and one open optimal control problem for stochastic hyperbolic equation with two-parameter white noise are offered.
Analytical Solutions of Viscoelastic Nonlocal Timoshenko Beams
Authors: Pinnola Francesco Paolo , Barretta Raffaele , Marotti de Sciarra Francesco , Pirrotta Antonina
Published: February 2022

A consistent nonlocal viscoelastic beam model is proposed in this paper. Specifically, a Timoshenko bending problem, where size- and time-dependent effects cannot be neglected, is investigated. In order to inspect scale phenomena, a stress-driven nonlocal formulation is used, whereas to simulate time-dependent effects, fractional linear viscoelasticity is considered. These two approaches are adopted to develop a new Timoshenko bending model. Analytical solutions and application samples of the proposed formulation are presented. Moreover, in order to show influences of viscoelastic and size effects on mechanical response, parametric analyses are provided. The contributed results can be useful for the design and optimization of small-scale devices exhibiting flexural behaviour.
Kinetic and Stoichiometric Modeling-Based Analysis of Docosahexaenoic Acid (DHA) Production Potential by Crypthecodinium cohnii from Glycerol, Glucose and Ethanol
Authors: Berzins Kristaps , Muiznieks Reinis , Baumanis Matiss R. , Strazdina Inese , Shvirksts Karlis , Prikule Santa , Galvanauskas Vytautas , Pleissner Daniel , Pentjuss Agris , Grube Mara , Kalnenieks Uldis , Stalidzans Egils
Published: February 2022

Docosahexaenoic acid (DHA) is one of the most important long-chain polyunsaturated fatty acids (LC-PUFAs), with numerous health benefits. Crypthecodinium cohnii, a marine heterotrophic dinoflagellate, is successfully used for the industrial production of DHA because it can accumulate DHA at high concentrations within the cells. Glycerol is an interesting renewable substrate for DHA production since it is a by-product of biodiesel production and other industries, and is globally generated in large quantities. The DHA production potential from glycerol, ethanol and glucose is compared by combining fermentation experiments with the pathway-scale kinetic modeling and constraint-based stoichiometric modeling of C. cohnii metabolism. Glycerol has the slowest biomass growth rate among the tested substrates. This is partially compensated by the highest PUFAs fraction, where DHA is dominant. Mathematical modeling reveals that glycerol has the best experimentally observed carbon transformation rate into biomass, reaching the closest values to the theoretical upper limit. In addition to our observations, the published experimental evidence indicates that crude glycerol is readily consumed by C. cohnii, making glycerol an attractive substrate for DHA production.
Sulfated Polysaccharides from Seaweed Strandings as Renewable Source for Potential Antivirals against Herpes simplex Virus 1
Authors: Pliego-Cortés Hugo , Hardouin Kévin , Bedoux Gilles , Marty Christel , Cérantola Stéphane , Freile-Pelegrín Yolanda , Robledo Daniel , Bourgougnon Nathalie
Published: February 2022

Herpes simplex virus 1 (HSV-1) remains a prominent health concern widespread all over the world. The increasing genital infections by HSV-1 that might facilitate acquisition and transmission of HIV-1, the cumulative evidence that HSV-1 promotes neurodegenerative disorders, and the emergence of drug resistance signify the need for new antiviral agents. In this study, the in vitro anti-herpetic activity of sulfated polysaccharides (SPs) extracted by enzyme or hot water from seaweeds collected in France and Mexico from stranding events, were evaluated. The anti-herpetic activity evaluation of the semi-refined-polysaccharides (sr-SPs) and different ion exchange purified fractions showed a wide range of antiviral activity. Among them, the sr-SPs from the Rhodophyta Halymenia floresii showed stronger activity EC50 0.68 μg/mL with SI 1470, without cytotoxicity. Further, the antiviral activity of the sr-SPs evaluated at different treatment schemes showed a high EC50 of 0.38 μg/mL during the viral adsorption assays when the polysaccharide and the virus were added simultaneously, whilst the protection on Vero cell during the post-infection assay was effective up to 1 h. The chemical composition, FTIR and 1H NMR spectroscopic, and molecular weights of the sr-SPs from H. floresii were determined and discussed based on the anti-herpetic activity. The potential utilization of seaweed stranding as a source of antiviral compounds is addressed.
The Safety and Efficacy of Nusinersen in the Treatment of Spinal Muscular Atrophy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Abbas Kirellos Said , Eltaras Mennatullah Mohamed , El-Shahat Nahla Ahmed , Abdelazeem Basel , Shaqfeh Mahmoud , Brašić James Robert
Published: February 2022

Background and objectives: Spinal muscular atrophy (SMA) is a neurodegenerative disease that leads to progressive proximal muscle weakness and muscle atrophy. To assess the beneficial and adverse effects of nusinersen, a promising intervention for SMA, we conducted a systematic search and meta-analysis of the published randomized control trials (RCTs) of nusinersen for SMA. Materials and methods: Utilizing the Preferred Reporting for Systematic Review and Meta-Analysis (PRISMA), we searched PubMed, Scopus, Web of Science, Cochrane Central, and Clinicaltrials.gov from inception to 22 July 2021. Results: Three RCTs satisfying the inclusion and exclusion criteria covered 274 patients: 178 patients in the nusinersen group. Our results show a significant risk difference (RD) in the motor milestone response (RD: 0.51; 95% CI: 0.39, 0.62; p < 0.00001) and improvement in the HINE-2 score (RD: 0.26; 95% CI: 0.12, 0.40; p < 0.0003) in the nusinersen group compared to the control group. Moreover, a significant decrease in the risk ratio (RR) for severe adverse events (RR: 0.72; 95% CI: 0.57, 0.92; p = 0.007) and any adverse event leading to treatment discontinuation (RR: 0.40; 95% CI: 0.22, 0.74; p = 0.004) was observed. An insignificant result was found for any adverse effects (RR: 0.93; 95% CI: 0.97, 1.01; p = 0.14) and for serious adverse effects (RR: 0.81; 95% CI: 0.60, 1.07; p = 0.14). Conclusions: This review provides evidence that nusinersen treatment was effective in treatment for infants with SMA and was associated with fewer severe adverse events; however, more RCTs are needed to establish evidence.
Peritoneal Dialysis for Potential Kidney Transplant Recipients: Pride or Prejudice?
Authors: Nardelli Luca , Scalamogna Antonio , Messa Piergiorgio , Gallieni Maurizio , Cacciola Roberto , Tripodi Federica , Castellano Giuseppe , Favi Evaldo
Published: February 2022

Kidney transplantation (KT) is recognized as the gold-standard of treatment for patients with end-stage renal disease. Additionally, it has been demonstrated that receiving a pre-emptive KT ensures the best recipient and graft survivals. However, due to an overwhelming discrepancy between the organs available and the patients on the transplant waiting list, the vast majority of transplant candidates require prolonged periods of dialysis before being transplanted. For many years, peritoneal dialysis (PD) and hemodialysis (HD) have been considered competitive renal replacement therapies (RRT). This dualistic vision has recently been questioned by evidence suggesting that an individualized and flexible approach may be more appropriate. In fact, tailored and cleverly planned changes between different RRT modalities, according to the patient’s needs and characteristics, are often needed in order to achieve the best results. While home HD is still under scrutiny in this particular setting, current data seems to favor the use of PD over in-center HD in patients awaiting a KT. In this specific population, the demonstrated advantages of PD are superior quality of life, longer preservation of residual renal function, lower incidence of delayed graft function, better recipient survival, and reduced cost.
Serum Cystatin C as a Biomarker for Early Diabetic Kidney Disease and Dyslipidemia in Young Type 1 Diabetes Patients
Authors: Stankute Ingrida , Radzeviciene Lina , Monstaviciene Ausra , Dobrovolskiene Rimante , Danyte Evalda , Verkauskiene Rasa
Published: February 2022

Background and objectives: This study aimed to assess the clinical significance of serum cystatin C in the early diagnosis of renal injury and its association with dyslipidemia in young T1D patients. Materials and Methods: A total of 779 subjects were evaluated for kidney function by estimating glomerular filtration rate (eGFR) based on serum creatinine (eGFRcreat) and cystatin C (eGFRcys). Results: The median age of study subjects was 16.2 years (2.1;26.4), diabetes duration—5.3 years (0.51;24.0). The median of HbA1c was 8% (5.2;19.9) (64 mmol/mol (33.3;194)); 24.2% of participants had HbA1c < 7% (53 mmol/mol). Elevated albumin excretion rate was found in 13.5% of subjects. The median of cystatin C was 0.8 mg/L (0.33;1.71), the median of creatinine—63 µmol/L (6;126). The median of eGFRcys was lower than eGFRcreat (92 mL/min/1.73 m2 vs. 101 mL/min/1.73 m2, p < 0.001). A total of 30.2% of all patients were classified as having worse kidney function when using cystatin C vs. creatinine for eGFR calculation. Linear correlations were found between cystatin C and HbA1c, r = −0.088, p < 0.05, as well as cystatin C and HDL, r = −0.097, p < 0.01. Conclusions: This study showed that cystatin C might be used as an additional biomarker of early kidney injury in young patients with T1D.
Renal Cell Carcinoma or Oncocytoma? The Contribution of Diffusion-Weighted Magnetic Resonance Imaging to the Differential Diagnosis of Renal Masses
Authors: Metin Melike , Aydın Hasan , Karaoğlanoğlu Mustafa
Published: February 2022

Background and Objectives: Renal Cell Carcinoma (RCC) accounts for 85% and oncocytomas constitute 3–7% of solid renal masses. Oncocytomas can be confused, especially with hypovascular RCC. The purpose of this research was to evaluate the contribution of diffusion-weighted imaging (DWI) and contrast-enhanced MRI sequences in the differential diagnosis of RCC and oncocytoma Materials and Methods: 465 patients with the diagnosis of RCC and 45 patients diagnosed with oncocytoma were retrospectively reviewed between 2009 to 2020. All MRI acquisitions were handled by a 1.5 T device (Achieva, Philips Healthcare, Best, The Netherlands) and all images were evaluated by the consensus of two radiologists with 10–15 years’ experience. The SPSS package program version 15.0 software was used for statistical analysis of the study. Chi-square test, Mann–Whitney U test or the Kruskal–Wallis tests were used in the statistical analysis. A receiver operating characteristic (ROC) curve was used to calculate the cut-off values Results: The results were evaluated with a 95% confidence interval and a significance threshold of p < 0.05. ADC values (p < 0.001) and enhancement index (p < 0.01) were significantly lower in the RCC group than the oncocytoma group. Conclusion: DWI might become an alternative technique to the contrast-enhanced MRI in patients with contrast agent nephropathy or with a high risk of nephrogenic systemic fibrosis, calculation of CI of the oncocytoma and RCCs in the contrast-enhanced acquisitions would contribute to the differential diagnosis.
Evaluation of Er Doped CeO2-δ as Oxygen Transport Membrane
Authors: Balaguer María , Solís Cecilia , Escolástico Sonia , Garcia-Fayos Julio , Serra Jose
Published: February 2022

Ceria based materials are robust candidates for a range of applications involving redox reactions and high oxygen activity. The substitution of erbium in the ceria lattice introduces extrinsic oxygen vacancies. Further addition of Co introduces electronic carriers. We have studied the structural and redox behavior of Ce1−xErxO2-δ (x = 0.1 and 0.2) and the influence of adding 2 mol% of Co in the electrochemical properties. A limitation in the solubility of Er cation is found. Diffusion and surface exchange coefficients have been obtained by electrical conductivity relaxation and the DC-conductivity and O2 permeation measurements show the importance of the electronic component in the transport properties, obtaining an oxygen permeation flux of 0.07 mL·min−1·cm−2 at 1000 °C, for a 769 μm thick membrane.
A Critical Review of Renewable Hydrogen Production Methods: Factors Affecting Their Scale-Up and Its Role in Future Energy Generation
Authors: Agyekum Ephraim Bonah , Nutakor Christabel , Agwa Ahmed M. , Kamel Salah
Published: February 2022

An increase in human activities and population growth have significantly increased the world’s energy demands. The major source of energy for the world today is from fossil fuels, which are polluting and degrading the environment due to the emission of greenhouse gases. Hydrogen is an identified efficient energy carrier and can be obtained through renewable and non-renewable sources. An overview of renewable sources of hydrogen production which focuses on water splitting (electrolysis, thermolysis, and photolysis) and biomass (biological and thermochemical) mechanisms is presented in this study. The limitations associated with these mechanisms are discussed. The study also looks at some critical factors that hinders the scaling up of the hydrogen economy globally. Key among these factors are issues relating to the absence of a value chain for clean hydrogen, storage and transportation of hydrogen, high cost of production, lack of international standards, and risks in investment. The study ends with some future research recommendations for researchers to help enhance the technical efficiencies of some production mechanisms, and policy direction to governments to reduce investment risks in the sector to scale the hydrogen economy up.
Comparison Study on Welding Temperature and Joint Characteristics of AZ31 Magnesium Alloy by Ultrasonic and Heat Pipe Assisted FSW
Authors: Wei Cheng-Gang , Lu Sheng , Chen Liang-Yu , Xu Mao-You
Published: February 2022

As an important factor in friction stir welding (FSW) process, temperature directly affects the microstructures and mechanical properties of welded joints. The present work aims to investigate the welding temperature and joint characteristics of AZ31 magnesium alloy under three FSW conditions: conventional friction stir welding (FSW), ultrasonic assisted friction stir welding (UaFSW), and ultrasonic and heat pipe assisted friction stir welding (UHaFSW), respectively. The results show that the welding temperature distributions and the characteristic of “non-uniformity” are presented in the FSW and UaFSW joints along the welding and horizontal directions. Compared with conventional FSW, UaFSW can effectively balance and improve the non-uniform temperature distribution in the joints, resulting in the significant decreases in the peak temperatures and durations of high temperature. Hence, the grains are refined in the microstructure of the nugget zone in the UHaFSW joints, which enhances their microhardness and tensile properties. Based on these results, it can be concluded that UHaFSW could be an effective method to improve the mechanical properties of AZ31 magnesium alloy welded joints.
Effects of Thermomechanical Processing on Hydrogen Embrittlement Properties of UltraHigh-Strength TRIP-Aided Bainitic Ferrite Steels
Authors: Hojo Tomohiko , Zhou Yutao , Kobayashi Junya , Sugimoto Koh-ichi , Takemoto Yoshito , Nagasaka Akihiko , Koyama Motomichi , Ajito Saya , Akiyama Eiji
Published: February 2022

The effects of thermomechanical processing on the microstructure and hydrogen embrittlement properties of ultrahigh-strength, low-alloy, transformation-induced plasticity (TRIP)-aided bainitic ferrite (TBF) steels were investigated to apply to automobile forging parts such as engine and drivetrain parts. The hydrogen embrittlement properties were evaluated by conducting conventional tensile tests after hydrogen charging and constant load four-point bending tests with hydrogen charging. The 0.4 mass%C-TBF steel achieved refinement of the microstructure, improved retained austenite characteristics, and strengthening, owing to thermomechanical processing. This might be attributed to dynamic and static recrystallizations during thermomechanical processing in TBF steels. Moreover, the hydrogen embrittlement resistances were improved by the thermomechanical processing in TBF steels. This might be caused by the refinement of the microstructure, an increase in the stability of the retained austenite, and low hydrogen absorption of the thermomechanically processed TBF steels.
Correlation between Flotation and Rheology of Fine Particle Suspensions
Authors: Sajjad Mohsin , Otsuki Akira
Published: February 2022

This paper summarizes and discusses previous investigations into the correlation between the rheology and flotation process of fine particle suspensions. This summary provides a better understanding of the challenges and current status of this subject and useful feedback based on the revision of relevant theories and practical implications for fine particle characterization and processing. Such processes include the sustainable beneficiation of complex ores and wastes for valuable material extraction and the segregation of toxic substances. For example, there has been increasing demand for the beneficiation of complex ores often carrying the values (e.g., critical raw materials) in fine grains, due to the noticeable decrease in the accessibility of high-grade and easily extractable ores. To maintain the sustainable use of limited resources, the effective beneficiation of complex ores is urgently required. It can be successfully achieved only with selective particle/mineral dispersion/liberation and the assistance of mineralogical and fine particle characterization including a proper understanding of the rheological behavior of complex ores in the context of fine particle separation/processing. In correlating flotation with suspension rheology, previous works were summarized and we found that the modeling of their correlations as well as comprehensive contributions of pulp and froth rheology on flotation performance have been studied very limitedly, and comprehensive developments in these aspects are thus strongly suggested.
The Role of the Metabolome and Non-Coding RNA on Pheochromocytomas and Paragangliomas: An Update
Authors: Bouça Bruno , Bogalho Paula , Rizzo Manfredi , Silva-Nunes José
Published: February 2022

Pheochromocytoma and paragangliomas (PPGL) are rare neuroendocrine tumors. In some patients they exhibit malignant behavior characterized by the presence of metastases, limiting treatment options and survival rates. Therapeutic options are limited to surgery, localized radiotherapy, and a few systemic therapies. However, in several recent studies, non-coding RNA molecules are gaining increasing attention as markers of malignancy for PPGL. The understanding of PPGL development molecular mechanisms has improved in the last years, with some of the epigenetic regulatory mechanisms such as DNA and histones methylation, being better understood than RNA-based mechanisms. Metabolome deregulation in PPGL, with increased synthesis of molecules that facilitated tumor growth, results from the activation of hypoxia signaling pathways, affecting tumorigenesis. In addition, the assessment of these metabolites can be useful for the management of these tumors. This review summarizes recent discoveries linking metabolome and non-coding RNA to PPGL and their relevance for diagnosis and therapeutics.
Glycosphingolipid Levels in Urine Extracellular Vesicles Enhance Prediction of Therapeutic Response in Lupus Nephritis
Authors: Troyer Brian , Rodgers Jessalyn , Wolf Bethany J. , Oates James C. , Drake Richard R. , Nowling Tamara K.
Published: February 2022

The development of nephritis increases the risk of morbidity and mortality in systemic lupus erythematosus (SLE) patients. While standard induction therapies, such as mycophenolate mofetil (MMF) induce clinical remission (i.e., complete response) in approximately 50% of SLE patients with nephritis, many patients fail to respond. Therapeutic response is often not assessed until 6–12 months after beginning treatment. Those patients that fail to respond to treatment continue to accumulate organ damage, thus, there is a critical need to predict which patients will fail therapy before beginning treatment, allowing physicians to optimize therapy. Our previous studies demonstrated elevated urine, but not serum, glycosphingolipids (GSLs) in SLE patients with nephritis compared to SLE patients without nephritis, suggesting the urine GSLs were derived from the kidney. In this study, we measured the GSLs hexosylceramide and lactosylceramide in extracellular vesicles isolated from longitudinal urine samples of LN patients that were treated with MMF for 12 months. GSL levels were significantly elevated in the baseline samples (prior to treatment) of non-responders compared to complete responders. While a few other proteins measured in the whole urine were higher in non-responders at baseline, only GSLs demonstrated a significant ability to discriminate treatment response in lupus nephritis patients.
Comparative Evaluation of Plasma Metabolomic Data from Multiple Laboratories
Authors: Nishiumi Shin , Izumi Yoshihiro , Hirayama Akiyoshi , Takahashi Masatomo , Nakao Motonao , Hata Kosuke , Saigusa Daisuke , Hishinuma Eiji , Matsukawa Naomi , Tokuoka Suzumi M. , Kita Yoshihiro , Hamano Fumie , Okahashi Nobuyuki , Ikeda Kazutaka , Nakanishi Hiroki , Saito Kosuke , Hirai Masami Yokota , Yoshida Masaru , Oda Yoshiya , Matsuda Fumio , Bamba Takeshi
Published: February 2022

In mass spectrometry-based metabolomics, the differences in the analytical results from different laboratories/machines are an issue to be considered because various types of machines are used in each laboratory. Moreover, the analytical methods are unique to each laboratory. It is important to understand the reality of inter-laboratory differences in metabolomics. Therefore, we have evaluated whether the differences in analytical methods, with the exception sample pretreatment and including metabolite extraction, are involved in the inter-laboratory differences or not. In this study, nine facilities are evaluated for inter-laboratory comparisons of metabolomic analysis. Identical dried samples prepared from human and mouse plasma are distributed to each laboratory, and the metabolites are measured without the pretreatment that is unique to each laboratory. In these measurements, hydrophilic and hydrophobic metabolites are analyzed using 11 and 7 analytical methods, respectively. The metabolomic data acquired at each laboratory are integrated, and the differences in the metabolomic data from the laboratories are evaluated. No substantial difference in the relative quantitative data (human/mouse) for a little less than 50% of the detected metabolites is observed, and the hydrophilic metabolites have fewer differences between the laboratories compared with hydrophobic metabolites. From evaluating selected quantitatively guaranteed metabolites, the proportion of metabolites without the inter-laboratory differences is observed to be slightly high. It is difficult to resolve the inter-laboratory differences in metabolomics because all laboratories cannot prepare the same analytical environments. However, the results from this study indicate that the inter-laboratory differences in metabolomic data are due to measurement and data analysis rather than sample preparation, which will facilitate the understanding of the problems in metabolomics studies involving multiple laboratories.
Assessment of Hydrocarbon Degradation Potential in Microbial Communities in Arctic Sea Ice
Authors: Peeb Angela , Dang Nga Phuong , Truu Marika , Nõlvak Hiie , Petrich Chris , Truu Jaak
Published: February 2022

The anthropogenic release of oil hydrocarbons into the cold marine environment is an increasing concern due to the elevated usage of sea routes and the exploration of new oil drilling sites in Arctic areas. The aim of this study was to evaluate prokaryotic community structures and the genetic potential of hydrocarbon degradation in the metagenomes of seawater, sea ice, and crude oil encapsulating the sea ice of the Norwegian fjord, Ofotfjorden. Although the results indicated substantial differences between the structure of prokaryotic communities in seawater and sea ice, the crude oil encapsulating sea ice (SIO) showed increased abundances of many genera-containing hydrocarbon-degrading organisms, including Bermanella, Colwellia, and Glaciecola. Although the metagenome of seawater was rich in a variety of hydrocarbon degradation-related functional genes (HDGs) associated with the metabolism of n-alkanes, and mono- and polyaromatic hydrocarbons, most of the normalized gene counts were highest in the clean sea ice metagenome, whereas in SIO, these counts were the lowest. The long-chain alkane degradation gene almA was detected from all the studied metagenomes and its counts exceeded ladA and alkB counts in both sea ice metagenomes. In addition, almA was related to the most diverse group of prokaryotic genera. Almost all 18 good- and high-quality metagenome-assembled genomes (MAGs) had diverse HDGs profiles. The MAGs recovered from the SIO metagenome belonged to the abundant taxa, such as Glaciecola, Bermanella, and Rhodobacteracea, in this environment. The genera associated with HDGs were often previously known as hydrocarbon-degrading genera. However, a substantial number of new associations, either between already known hydrocarbon-degrading genera and new HDGs or between genera not known to contain hydrocarbon degraders and multiple HDGs, were found. The superimposition of the results of comparing HDG associations with taxonomy, the HDG profiles of MAGs, and the full genomes of organisms in the KEGG database suggest that the found relationships need further investigation and verification.
Depletion of the Microbiota Has a Modest but Important Impact on the Fungal Burden of the Heart and Lungs during Early Systemic Candida auris Infection in Neutropenic Mice
Authors: Pichowicz Amber M. , Torres Steven R. , Torres-Velez Fernando J. , Longyear Adina D. , Singh Navjot , Lasek-Nesselquist Erica , De Jesus Magdia
Published: February 2022

The progression and systemic pathobiology of C. auris in the absence of a microbiota have not been described. Here, we describe the influence of the microbiota during the first 5 days of C. auris infection in germ-free or antibiotic-depleted mice. Depletion of the bacterial microbiota in both germ-free and antibiotic-depleted models results in a modest but important increase in the early stages of C. auris infection. Particularly the heart and lungs, followed by the cecum, uterus, and stomach, of intravenously (i.v.) infected neutropenic mice showed significant fungal organ burden. Understanding disease progression and pathobiology of C. auris in individuals with a depleted microbiota could potentially help in the development of care protocols that incorporate supplementation or restoration of the microbiota before invasive procedures, such as transplantation surgeries.
High-Resolution Melting PCR as Rapid Genotyping Tool for Brucella Species
Authors: Girault Guillaume , Perrot Ludivine , Mick Virginie , Ponsart Claire
Published: February 2022

Brucella sp. are the causative agents of brucellosis. One of the main characteristics of the Brucella genus concerns its very high genetic homogeneity. To date, classical bacteriology typing is still considered as the gold standard assay for direct diagnosis of Brucella. Molecular approaches are routinely used for the identification of Brucella at the genus level. However, genotyping is more complex, and to date, no method exists to quickly assign a strain into species and biovar levels, and new approaches are required. Next generation sequencing (NGS) opened a new era into the diagnosis of bacterial diseases. In this study, we designed a high-resolution melting (HRM) method for the rapid screening of DNA and direct assignment into one of the 12 species of the Brucella genus. This method is based on 17 relevant single nucleotide polymorphisms (SNPs), identified and selected from a whole genome SNP (wgSNP) analysis based on 988 genomes (complete and drafts). These markers were tested against the collection of the European Reference Laboratory (EU-RL) for brucellosis (1440 DNAs extracted from Brucella strains). The results confirmed the reliability of the panel of 17 SNP markers, allowing the differentiation of each species of Brucella together with biovars 1, 2, and 3 of B. suis and vaccine strain Rev1 (B. melitensis) within 3 h, which is a considerable gain of time for brucellosis diagnosis. Therefore, this genotyping tool provides a new and quick alternative for Brucella identification based on SNPs with the HRM-PCR assay.
Paraprobiotics in Non-Surgical Periodontal Therapy: Clinical and Microbiological Aspects in a 6-Month Follow-Up Domiciliary Protocol for Oral Hygiene
Authors: Butera Andrea , Gallo Simone , Pascadopoli Maurizio , Maiorani Carolina , Milone Antonella , Alovisi Mario , Scribante Andrea
Published: February 2022

Periodontal disease represents a progressive destruction of tooth-supporting tissues. Recently, paraprobiotics are regarded as an adjunctive therapy to the non-surgical Scaling-and-Root-Planing (SRP). The aim of this study is to evaluate the efficacy of two new formulations of paraprobiotics, a toothpaste and a mouthwash, respectively, for the domiciliary hygiene. A total of 40 patients were randomly assigned to the following domiciliary treatments: Group 1 (SRP + Curasept Intensive Treatment 0.2% chlorhexidine) (control) and Group 2 (SRP + Biorepair Peribioma toothpaste + Biorepair Peribioma Mousse mouthwash) (trial). At baseline (T0) and after 3 and 6 months (T1–T2), periodontal clinical (Bleeding on Probing, Probing Pocket Depth, Clinical Attachment Loss, Bleeding Score, Sulcus Bleeding Index, Plaque Index, Approximal Plaque Index, Adherent Gingiva, Gingival Recession, and Pathological Sites) and microbiological parameters (Pathological Bacteria, Saprophytic Bacteria, Enlarged Red Complex, Red Complex, Orange Complex, and counts of Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythensys, Treponema denticola, Prevotella intermedia, and Fusobacterium nucleatum). The use of the experimental products resulted in a significant reduction of most of the clinical indices assessed, which occurred at a major degree with respect to the conventional chlorhexidine considered as control. Additionally, after 6 months of use, the abovementioned products significantly decreased the percentage of pathological bacteria and the counts of those bacteria constituting the “Red Complex”, more related to the periodontal disease. Accordingly, the paraprobiotics-based products tested in this study seem to represent a valid support to SRP with a benefit on both clinical indices and on specific periodontopathogens.
Diatom Biogeography, Temporal Dynamics, and Links to Bacterioplankton across Seven Oceanographic Time-Series Sites Spanning the Australian Continent
Authors: Le Reun Nine , Bramucci Anna , O’Brien James , Ostrowski Martin , Brown Mark V. , Van de Kamp Jodie , Bodrossy Levente , Raina Jean-Baptiste , Ajani Penelope , Seymour Justin
Published: February 2022

Diatom communities significantly influence ocean primary productivity and carbon cycling, but their spatial and temporal dynamics are highly heterogeneous and are governed by a complex diverse suite of abiotic and biotic factors. We examined the seasonal and biogeographical dynamics of diatom communities in Australian coastal waters using amplicon sequencing data (18S-16S rRNA gene) derived from a network of oceanographic time-series spanning the Australian continent. We demonstrate that diatom community composition in this region displays significant biogeography, with each site harbouring distinct community structures. Temperature and nutrients were identified as the key environmental contributors to differences in diatom communities at all sites, collectively explaining 21% of the variability observed in diatoms assemblages. However, specific groups of bacteria previously implicated in mutualistic ecological interactions with diatoms (Rhodobacteraceae, Flavobacteriaceae and Alteromonadaceae) also explained a further 4% of the spatial dynamics observed in diatom community structure. We also demonstrate that the two most temperate sites (Port Hacking and Maria Island) exhibited strong seasonality in diatom community and that at these sites, winter diatom communities co-occurred with higher proportion of Alteromonadaceae. In addition, we identified significant co-occurrence between specific diatom and bacterial amplicon sequence variants (ASVs), with members of the Roseobacter and Flavobacteria clades strongly correlated with some of the most abundant diatom genera (Skeletonema, Thalassiosira, and Cylindrotheca). We propose that some of these co-occurrences might be indicative of ecologically important interactions between diatoms and bacteria. Our analyses reveal that in addition to physico-chemical conditions (i.e., temperature, nutrients), the relative abundance of specific groups of bacteria appear to play an important role in shaping the spatial and temporal dynamics of marine diatom communities.
Endophytic Fungal Terpenoids: Natural Role and Bioactivities
Authors: Galindo-Solís Juan M. , Fernández Francisco J.
Published: February 2022

Endophytic fungi are a highly diverse group of fungi that intermittently colonize all plants without causing symptoms of the disease. They sense and respond to physiological and environmental changes of their host plant and microbiome. The inter-organism interactions are largely driven by chemical networks mediated by specialized metabolites. The balance of these complex interactions leads to healthy and strong host plants. Endophytic strains have particular machinery to produce a plethora of secondary metabolites with a variety of bioactivities and unknown functions in an ecological niche. Terpenoids play a key role in endophytism and represent an important source of bioactive molecules for human health and agriculture. In this review, we describe the role of endophytic fungi in plant health, fungal terpenoids in multiple interactions, and bioactive fungal terpenoids recently reported from endophytes, mainly from plants used in traditional medicine, as well as from algae and mangroves. Additionally, we highlight endophytic fungi as producers of important chemotherapeutic terpenoids, initially discovered in plants. Despite advances in understanding endophytism, we still have much to learn in this field. The study of the role, the evolution of interactions of endophytic fungi and their terpenoids provide an opportunity for better applications in human health and agriculture.
Development and Validation of a New TaqMan Real-Time PCR for the Detection of Ornithobacterium rhinotracheale
Authors: Hashish Amro , Sinha Avanti , Sato Yuko , Macedo Nubia , El-Gazzar Mohamed
Published: February 2022

Ornithobacterium rhinotracheale (ORT) has been associated with poultry respiratory disease worldwide. The organism is fastidious and isolation is challenging. One TaqMan real-time PCR (qPCR) assay has been developed for the detection of ORT. However, during validating the ORT qPCR, the assay performance was suboptimal. During the in silico evaluation, deviations from the basic parameters for primers and probes designs (e.g., presence of stable undesirable primer-dimers) were observed. The suboptimal design led to low efficiency and low sensitivity of the assay. Initially, modification on the probe was carried out to improve the performance of the assay. However, the assay’s performance (efficiency and sensitivity) was still suboptimal. In this manuscript, we describe the development of a new qPCR assay and the comparison of its performance with the currently available assay. A highly efficient, sensitive, and specific qPCR assay was developed with approximately 1000-folds reduction in the limit of detection (from 3 × 106 plasmid DNA copies/mL to 1 × 103 plasmid DNA copies/mL). Additionally, the efficiency of the new assay (E = 98.70%) was significantly better than the current assay (E = 73.18%). The newly developed assay is an improved diagnostic tool for the sensitive and efficient diagnosis of ORT from clinical samples.
The nsp15 Nuclease as a Good Target to Combat SARS-CoV-2: Mechanism of Action and Its Inactivation with FDA-Approved Drugs
Authors: Saramago Margarida , Costa Vanessa , Souza Caio , Bárria Cátia , Domingues Susana , Viegas Sandra , Lousa Diana , Soares Cláudio , Arraiano Cecília , Matos Rute
Published: February 2022

The pandemic caused by SARS-CoV-2 is not over yet, despite all the efforts from the scientific community. Vaccination is a crucial weapon to fight this virus; however, we still urge the development of antivirals to reduce the severity and progression of the COVID-19 disease. For that, a deep understanding of the mechanisms involved in viral replication is necessary. nsp15 is an endoribonuclease critical for the degradation of viral polyuridine sequences that activate host immune sensors. This enzyme is known as one of the major interferon antagonists from SARS-CoV-2. In this work, a biochemical characterization of SARS-CoV-2 nsp15 was performed. We saw that nsp15 is active as a hexamer, and zinc can block its activity. The role of conserved residues from SARS-CoV-2 nsp15 was investigated, and N164 was found to be important for protein hexamerization and to contribute to the specificity to degrade uridines. Several chemical groups that impact the activity of this ribonuclease were also identified. Additionally, FDA-approved drugs with the capacity to inhibit the in vitro activity of nsp15 are reported in this work. This study is of utmost importance by adding highly valuable information that can be used for the development and rational design of therapeutic strategies.
Dereplication and Quantification of Major Compounds of Convolvulus arvensis L. Extracts and Assessment of Their Effect on LPS-Activated J774 Macrophages
Authors: Abdul Khaliq Hafiz , Ortiz Sergio , Alhouayek Mireille , Muccioli Giulio G. , Quetin-Leclercq Joëlle
Published: February 2022

Convolvulus arvensis is used in Pakistani traditional medicine to treat inflammation-related disorders. Its anti-inflammatory potential was evaluated on hexane, dichloromethane, ethyl acetate, methanol, and aqueous extracts of whole plant on pro-inflammatory mediators in LPS-activated murine macrophage J774 cells at the non-cytotoxic concentration of 50 µg/mL. Ethyl acetate (ARE) and methanol (ARM) extracts significantly decreased mRNA levels of IL-6, TNF-α, MCP-1, COX-2, and iNOS. Furthermore, both extracts dose dependently decreased IL-6, TNF-α, and MCP-1 secretion. Forty-five compounds were putatively identified in ARE and ARM by dereplication (using HPLC-UV-HRMSn analysis and molecular networking), most of them are reported for the first time in C. arvensis, as for example, nineteen phenolic derivatives. Rutin, kaempferol-3-O-rutinoside, chlorogenic acid, 3,5-di-O-caffeoylquinic acid, N-trans-p-coumaroyl-tyramine, and N-trans-feruloyl-tyramine were main constituents identified and quantified by HPLC-PDA in ARE and ARM. Furthermore, chlorogenic acid, tyramine derivatives, and the mixture of the six identified major compounds significantly decreased IL-6 secretion by LPS-activated J774 cells. The activity of N-trans-p-coumaroyl-tyramine is shown here for the first time. Our results indicate that ARE, ARM and major constituents significantly inhibited the expression of pro-inflammatory mediators, which supports the use of this plant to treat inflammatory diseases.
Synthesis, Characterization, Thermal Analysis, DFT, and Cytotoxicity of Palladium Complexes with Nitrogen-Donor Ligands
Authors: Majeed Sattar R. , Amin Mina A. , Attaby Fawzy A. , Alberto Marta E. , Soliman Ahmed A.
Published: February 2022

Three new palladium complexes ([Pd(DABA)Cl2], [Pd(CPDA)Cl2], and [Pd(HZPY)Cl2]) bearing dinitrogen ligands (DABA: 3,4-diaminobenzoic acid; CPDA: 4-chloro–o-phenylenediamine; HZPY: 2-hydraziniopyridine) were synthesized, characterized, and tested against breast cancer (MCF-7), prostate carcinoma cell line (PC3) and liver carcinoma cell line (HEPG2). [Pd(DABA)Cl2] complex exhibited the highest inhibition percentage, lying between 68–71%. The hydrolysis mechanism of each palladium complex, the key step preceding the binding to the biological target, as well as their photophysical properties were explored by means of DFT and TDDFT computations. Results indicate a faster hydrolysis process for the Pd(DABA)Cl2 complex. The computed activation energies for the first and second hydrolysis processes suggest that all the compounds could reach DNA in their monohydrated form.
The Effect of α-Tocopherol on the Reduction of Inflammatory Processes and the Negative Effect of Acrylamide
Authors: Kopańska Marta , Batoryna Marta , Banaś-Ząbczyk Agnieszka , Błajda Joanna , Lis Marcin W.
Published: February 2022

Our research aimed to show acrylamide’s influence on inflammatory processes, the oxidative stress it causes in the cholinergic system, and the possibility of reducing inflammation via supplementation with α-tocopherol. For this purpose, an in ovo model was used where the embryos were exposed to acrylamide, α-tocopherol and a cocktail of these substances. After 48 h of exposure, we collected brain samples and performed biochemical assays to examine the effect of the chosen substances on oxidative stress (malondialdehyde-MDA and reduced glutathione-GSH) and acetylcholinesterase activity (AChE). The results showed that acrylamide decreased AChE activity in the examined brain samples by about 25% in comparison to the control group, and this effect was decreased by administering α-tocopherol. The concentration of malondialdehyde significantly increased in the group given acrylamide, while, in the group with α-tocopherol, the observed concentration was lower in comparison to the control group. Moreover, a decrease in glutathione concentration was observed after the administration of acrylamide; however, the protective effect of α-tocopherol was only slightly visible in this case. In conclusion, α-tocopherol minimizes the harmful effects of acrylamide on AchE, and it can minimize the concentration of MDA.
A Simple LC-MS/MS Method for the Quantification of PDA-66 in Human Plasma
Authors: Schwarz Rico , Seiler Elisabeth R. D. , Sender Sina , Pews-Davtyan Anahit , Murua Escobar Hugo , Zechner Dietmar , Beller Matthias , Junghanß Christian , Hinz Burkhard
Published: February 2022

The treatment of cancer is one of the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue of the inhibitor of serine–threonine kinase glycogen synthase kinase 3β SB216763, has shown preclinical antitumour effects in various cell lines, with the key pathways of its anticancer activity being cell cycle modulation, DNA replication and p53 signalling. For the monitoring of anticancer drug treatment in the context of therapeutic drug monitoring, the determination of plasma concentrations is essential, for which an LC-MS/MS method is particularly suitable. In the present study, a sensitive LC-MS/MS method for the quantification of the potential anticancer drug PDA-66 in human plasma with a lower limit of quantification of 2.5 nM is presented. The method was successfully validated and tested for the determination of PDA-66 in mouse plasma and sera.
Martini 3 Model of Cellulose Microfibrils: On the Route to Capture Large Conformational Changes of Polysaccharides
Authors: Moreira Rodrigo A. , Weber Stefan A. L. , Poma Adolfo B.
Published: February 2022

High resolution data from all-atom molecular simulations is used to parameterize a Martini 3 coarse-grained (CG) model of cellulose I allomorphs and cellulose type-II fibrils. In this case, elementary molecules are represented by four effective beads centred in the positions of O2, O3, C6, and O6 atoms in the D-glucose cellulose subunit. Non-bonded interactions between CG beads are tuned according to a low statistical criterion of structural deviation using the Martini 3 type of interactions and are capable of being indistinguishable for all studied cases. To maintain the crystalline structure of each single cellulose chain in the microfibrils, elastic potentials are employed to retain the ribbon-like structure in each chain. We find that our model is capable of describing different fibril-twist angles associated with each type of cellulose fibril in close agreement with atomistic simulation. Furthermore, our CG model poses a very small deviation from the native-like structure, making it appropriate to capture large conformational changes such as those that occur during the self-assembly process. We expect to provide a computational model suitable for several new applications such as cellulose self-assembly in different aqueous solutions and the thermal treatment of fibrils of great importance in bioindustrial applications.
An Overview of Modified Chitosan Adsorbents for the Removal of Precious Metals Species from Aqueous Media
Authors: Kong Dexu , Foley Stephen R. , Wilson Lee D.
Published: February 2022

This mini-review provides coverage of chitosan-based adsorbents and their modified forms as sustainable solid-phase extraction (SPE) materials for precious metal ions, such as gold species, and their complexes in aqueous media. Modified forms of chitosan-based adsorbents range from surface-functionalized systems to biomaterial composites that contain inorganic or other nanomaterial components. An overview of the SPE conditions such as pH, temperature, contact time, and adsorbent dosage was carried out to outline how these factors affect the efficiency of the sorption process, with an emphasis on gold species. This review provides insight into the structure-property relationships for chitinaceous adsorbents and their metal-ion removal mechanism in aqueous media. Cross-linked chitosan sorbents showed a maximum for Au(III) uptake capacity (600 mg/g), while S-containing cross-linked chitosan display favourable selectivity and uptake capacity with Au(III) species. Compared to industrial adsorbents such as activated carbon, modified chitosan sorbents display favourable uptake of Au(III) species, especially in aqueous media at low pH. In turn, this contribution is intended to catalyze further research directed at the rational design of tailored SPE materials that employ biopolymer scaffolds to yield improved uptake properties of precious metal species in aqueous systems. The controlled removal of gold and precious metal species from aqueous media is highly relevant to sustainable industrial processes and environmental remediation.