bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptive Clustering through Multi-Agent Technology: Development and Perspectives
Authors: Grachev Sergey , Skobelev Petr , Mayorov Igor , Simonova Elena
Published: September 2020

The paper is devoted to an overview of multi-agent principles, methods, and technologies intended to adaptive real-time data clustering. The proposed methods provide new principles of self-organization of records and clusters, represented by software agents, making it possible to increase the adaptability of different clustering processes significantly. The paper also presents a comparative review of the methods and results recently developed in this area and their industrial applications. An ability of self-organization of items and clusters suggests a new perspective to form groups in a bottom-up online fashion together with continuous adaption previously obtained decisions. Multi-agent technology allows implementing this methodology in a parallel and asynchronous multi-thread manner, providing highly flexible, scalable, and reliable solutions. Industrial applications of the intended for solving too complex engineering problems are discussed together with several practical examples of data clustering in manufacturing applications, such as the pre-analysis of customer datasets in the sales process, pattern discovery, and ongoing forecasting and consolidation of orders and resources in logistics, clustering semantic networks in insurance document processing. Future research is outlined in the areas such as capturing the semantics of problem domains and guided self-organization on the virtual market.
Initial Boundary Value Problems of Semi-Linear Sub-Diffusion with Gradient Terms
Authors: Gao Yabing , Li Yongxiang
Published: September 2020

We consider the existence and uniqueness of the saturated classical solutions and the positive classical solutions to initial boundary value problems of semi-linear sub-diffusion with gradient terms. Applying this to the fractional power of the sectorial operator theory and the imbedding theory in the interpolation spaces, where the nonlinear term satisfies more general conditions, we obtain the existence and uniqueness of the saturated classical solutions. The results obtained generalize the recent conclusions on this topic. Finally, an example is given to illustrate the feasibility of our main results.
Feynman Integral and a Change of Scale Formula about the First Variation and a Fourier–Stieltjes Transform
Authors: Kim Young Sik
Published: September 2020

We prove that the Wiener integral, the analytic Wiener integral and the analytic Feynman integral of the first variation of F(x)=exp{∫0Tθ(t,x(t))dt} successfully exist under the certain condition, where θ(t,u)=∫Rexp{iuv}dσt(v) is a Fourier–Stieltjes transform of a complex Borel measure σt∈M(R) and M(R) is a set of complex Borel measures defined on R. We will find this condition. Moreover, we prove that the change of scale formula for Wiener integrals about the first variation of F(x) sucessfully holds on the Wiener space.
New Bounds for the α-Indices of Graphs
Authors: Lenes Eber , Mallea-Zepeda Exequiel , Rodríguez Jonnathan
Published: September 2020

Let G be a graph, for any real 0≤α≤1, Nikiforov defines the matrix Aα(G) as Aα(G)=αD(G)+(1−α)A(G), where A(G) and D(G) are the adjacency matrix and diagonal matrix of degrees of the vertices of G. This paper presents some extremal results about the spectral radius ρα(G) of the matrix Aα(G). In particular, we give a lower bound on the spectral radius ρα(G) in terms of order and independence number. In addition, we obtain an upper bound for the spectral radius ρα(G) in terms of order and minimal degree. Furthermore, for n>l>0 and 1≤p≤⌊n−l2⌋, let Gp≅Kl∨(Kp∪Kn−p−l) be the graph obtained from the graphs Kl and Kp∪Kn−p−l and edges connecting each vertex of Kl with every vertex of Kp∪Kn−p−l. We prove that ρα(Gp+1)<ρα(Gp) for 1≤p≤⌊n−l2⌋−1.
Explicit Characterization of Feedback Nash Equilibria for Indefinite, Linear-Quadratic, Mean-Field-Type Stochastic Zero-Sum Differential Games with Jump-Diffusion Models
Authors: Moon Jun , Kim Wonhee
Published: September 2020

We consider the indefinite, linear-quadratic, mean-field-type stochastic zero-sum differential game for jump-diffusion models (I-LQ-MF-SZSDG-JD). Specifically, there are two players in the I-LQ-MF-SZSDG-JD, where Player 1 minimizes the objective functional, while Player 2 maximizes the same objective functional. In the I-LQ-MF-SZSDG-JD, the jump-diffusion-type state dynamics controlled by the two players and the objective functional include the mean-field variables, i.e., the expected values of state and control variables, and the parameters of the objective functional do not need to be (positive) definite matrices. These general settings of the I-LQ-MF-SZSDG-JD make the problem challenging, compared with the existing literature. By considering the interaction between two players and using the completion of the squares approach, we obtain the explicit feedback Nash equilibrium, which is linear in state and its expected value, and expressed as the coupled integro-Riccati differential equations (CIRDEs). Note that the interaction between the players is analyzed via a class of nonanticipative strategies and the “ordered interchangeability” property of multiple Nash equilibria in zero-sum games. We obtain explicit conditions to obtain the Nash equilibrium in terms of the CIRDEs. We also discuss the different solvability conditions of the CIRDEs, which lead to characterization of the Nash equilibrium for the I-LQ-MF-SZSDG-JD. Finally, our results are applied to the mean-field-type stochastic mean-variance differential game, for which the explicit Nash equilibrium is obtained and the simulation results are provided.
Chaos Control and Anti-Control of the Heterogeneous Cournot Oligopoly Model
Authors: Lampart Marek , Lampartová Alžběta
Published: September 2020

The main aim of this paper focuses on chaos suppression (control) and stimulation (anti-control) of a heterogeneous Cournot oligopoly model. This goal is reached by applying the theory of dynamical systems, namely impulsive control. The main aim was to demonstrate, through massive numerical simulations and estimation of the maximal Lyapunov exponent, the 0-1test for chaos, and bifurcation analysis, that it is possible to control the dynamical behavior of the investigated model by finding injection values under which the desired phenomena are attained. Moreover, it was shown that there are injection values for which the injected system admits a self-excited cycle or chaotic trajectory.
Mathematical Attack of RSA by Extending the Sum of Squares of Primes to Factorize a Semi-Prime
Authors: Overmars Anthony , Venkatraman Sitalakshmi
Published: September 2020

The security of RSA relies on the computationally challenging factorization of RSA modulus N=p1 p2 with N being a large semi-prime consisting of two primes p1and p2, for the generation of RSA keys in commonly adopted cryptosystems. The property of p1 and p2, both congruent to 1 mod 4, is used in Euler’s factorization method to theoretically factorize them. While this caters to only a quarter of the possible combinations of primes, the rest of the combinations congruent to 3 mod 4 can be found by extending the method using Gaussian primes. However, based on Pythagorean primes that are applied in RSA, the semi-prime has only two sums of two squares in the range of possible squares N−1, N/2 . As N becomes large, the probability of finding the two sums of two squares becomes computationally intractable in the practical world. In this paper, we apply Pythagorean primes to explore how the number of sums of two squares in the search field can be increased thereby increasing the likelihood that a sum of two squares can be found. Once two such sums of squares are found, even though many may exist, we show that it is sufficient to only find two solutions to factorize the original semi-prime. We present the algorithm showing the simplicity of steps that use rudimentary arithmetic operations requiring minimal memory, with search cycle time being a factor for very large semi-primes, which can be contained. We demonstrate the correctness of our approach with practical illustrations for breaking RSA keys. Our enhanced factorization method is an improvement on our previous work with results compared to other factorization algorithms and continues to be an ongoing area of our research.
Assessment of Postural Balance in Women Treated for Breast Cancer
Authors: Głowacka-Mrotek Iwona , Tarkowska Magdalena , Nowikiewicz Tomasz , Hagner-Derengowska Magdalena , Goch Aleksander
Published: September 2020

Background and objectives: Surgery is the primary and most effective treatment of breast cancer. Unilateral mastectomy disrupts the distribution of muscle tension between the right and the left sides of the body. The aim of the study was to evaluate postural balance in patients treated for breast cancer by mastectomy. Materials and methods: A controlled clinical study was conducted on 90 patients who have undergone surgical treatment for breast cancer (mastectomy) 5–6 years prior (Breast Group—BG). The control group (CG) consisted of 74 healthy female volunteers. Analysis of balance was performed using the Alfa stabilography platform. A static test (Romberg’s test) with open and closed eyes was used to assess balance. The following balance parameters were analyzed: path length, statokinesigram area, parameters of deflection and velocity of the foot pressure center. Results: The study demonstrated that patients from BG (5–6 years after surgery) obtained worse results in both tests with open (maximum back deviation, maximum forward deviation, average Y deviation, average Y velocity, path length and path surface area) (p < 0.05) as well as with closed eyes (maximum backward deviation, maximum forward deviation, mean Y deviation and path length) (p < 0.05). Conclusions: Our study demonstrated that women 5–6 years after surgery for breast cancer have impaired balance compared to healthy women, despite physiotherapy.
Psychogenic Non-Epileptic Status as Refractory, Generalized Hypertonic Posturing: Report of Two Adolescents
Authors: Coppola Giangennaro , Pastorino Grazia Maria Giovanna , Morcaldi Lucia , D’Onofrio Floriana , Operto Francesca Felicia
Published: September 2020

Psychogenic non-epileptic seizures (PNES) or dissociative seizures are found under the umbrella headings of functional/dissociative neurological disorders (FND) in psychiatric classifications (DSM-5; ICD-11). PNES are not characterized by any specific ictal or postictal EEG abnormalities. Patients with PNES can present with motor or non-motor symptoms, frequently associated with a change in the level of consciousness. PNES duration is variable, often longer than that of epileptic seizures. Prolonged PNES, sometimes termed PNES status, involve continuous or repetitive events that exceed 30 min. Prolonged PNES are often misdiagnosed as an epileptic event and are often inappropriately treated with high doses of antiseizure drugs. In this report, we describe two adolescent patients who presented with prolonged PNES characterized by generalized hypertonic posturing and low levels of consciousness. Despite multiple presentation to the Emergency department, and multiple normal video-EEG, the patients were misdiagnosed with epilepsy and were inappropriately treated with antiseizure medications. Both patients presented psychiatric comorbidity, consisting of a major depressive disorder, obsessive-compulsive symptoms, social withdrawal, difficulty of social interaction, and anxious-perfectionist personality traits. The episodes of prolonged PNES gradually declined within 18 months in both patients.
Treatment of Swine Closed Head Injury with Perfluorocarbon NVX-428
Authors: Arnaud Francoise , Haque Ashraful , Morris MAJ Erin , Moon-Massat Paula , Auker Charles , Biswajit Saha , Hazzard Brittany , Tran Ho Lam Thuy Vi , McCarron Richard , Scultetus Anke
Published: September 2020

Pre-hospital treatment of traumatic brain injury (TBI) with co-existing polytrauma is complicated by requirements for intravenous fluid volume vs. hypotensive resuscitation. A low volume, small particle-size-oxygen-carrier perfluorocarbon emulsion NVX-428 (dodecafluoropentane emulsion; 2% w/v) could improve brain tissue with minimal additional fluid volume. This study examined whether the oxygen-carrier NVX-428 shows safety and efficacy for pre-hospital treatment of TBI. Anesthetized swine underwent fluid percussion injury TBI and received 1 mL/kg IV NVX-428 (TBI-NVX) at 15 min (T15) or normal saline (no-treatment) (TBI-NON). Similarly, uninjured swine received NVX-428 (SHAM-NVX) or normal saline (SHAM-NON). Animals were monitored and measurements were taken for physiological and neurological parameters before euthanasia at the six-hour mark (T360). Histopathological analysis was performed on paraffin embedded tissues. Physiological, biochemical and blood gas parameters were not different, with the exception of a significant but transient increase in mean pulmonary artery pressure observed in the TBI-experimental group immediately after drug administration. There were no initial differences in brain oxygenation at baseline, but over time oxygen decreased ~50% in both TBI groups. Histological brain injury scores were similar between TBI-NVX and TBI-NON, although a number of subcategories (spongiosis-ischemic/dead neurons-hemorrhage-edema) in TBI-NVX had a tendency for lower scores. The cerebellum showed significantly lower spongiosis and ischemic/dead neuron injury scores and a lower number of Fluoro-Jade-B-positive cerebellar-Purkinje-cells after NVX-428 treatment compared to controls. NVX-428 may assist in mitigating secondary cellular brain damage.
Identification and Reproducibility of Plasma Metabolomic Biomarkers of Habitual Food Intake in a US Diet Validation Study
Authors: Wang Ying , Hodge Rebecca A. , Stevens Victoria L. , Hartman Terryl J. , McCullough Marjorie L.
Published: September 2020

Previous metabolomic studies have identified putative blood biomarkers of dietary intake. These biomarkers need to be replicated in other populations and tested for reproducibility over time for the potential use in future epidemiological studies. We conducted a metabolomics analysis among 671 racially/ethnically diverse men and women included in a diet validation study to examine the correlation between >100 food groups/items (101 by a food frequency questionnaire (FFQ), 105 by 24-h diet recalls (24HRs)) with 1141 metabolites measured in fasting plasma sample replicates, six months apart. Diet–metabolite associations were examined by Pearson’s partial correlation analysis. Biomarker reproducibility was assessed using intraclass correlation coefficients (ICCs). A total of 677 diet–metabolite associations were identified after Bonferroni adjustment for multiple comparisons and restricting absolute correlation coefficients to greater than 0.2 (601 associations using the FFQ and 395 using 24HRs). The median ICCs of the 238 putative biomarkers was 0.56 (interquartile range 0.46–0.68). In this study, with repeated FFQs, 24HRs and plasma metabolic profiles, we identified several potentially novel food biomarkers and replicated others found in our previous study. Our findings contribute to the growing literature on food-based biomarkers and provide important information on biomarker reproducibility which could facilitate their utilization in future nutritional epidemiological studies.
Maternal or Paternal Diabetes and Its Crucial Role in Offspring Birth Weight and MODY Diagnosis
Authors: Calcaterra Valeria , Zanfardino Angela , Zuccotti Gian Vincenzo , Iafusco Dario
Published: September 2020

Maturity-onset diabetes of the young (MODY) represents a heterogenous group of monogenic autosomal dominant diseases, which accounts for 1–2% of all diabetes cases. Pregnancy represents a crucial time to diagnose MODY forms due to the 50% risk of inheritance in offspring of affected subjects and the potential implications on adequate fetal weight. Not only a history of maternal diabetes may affect the birth weight of offspring, paternal diabetes should also be taken into consideration for a correct pathogenetic diagnosis. The crucial role of maternal and paternal diabetes inheritance patterns and the impact of this inherited mutation on birthweight and the MODY diagnosis was discussed.
The Stable Fly (Stomoxys calcitrans) as a Possible Vector Transmitting Pathogens in Austrian Pig Farms
Authors: Schwarz Lukas , Strauss Andreas , Loncaric Igor , Spergser Joachim , Auer Angelika , Rümenapf Till , Ladinig Andrea
Published: September 2020

This pilot study aimed to investigate stable flies from Austrian pig farms for the presence of defined swine pathogens, such as porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus 2 (PCV2), hemotrophic mycoplasmas in ingested blood and/or body parts and bacteria on the surface of the flies. Furthermore, the use of stable flies as a diagnostic matrix for the detection of pathogens in the ingested pig blood should be investigated. In total, 69 different microorganisms could be found on the surface of tested S. calcitrans from 20 different pig farms. Escherichia coli was the most common bacterium and could be found on flies from seven farms. In seven farms, hemotrophic mycoplasmas were detected in stable flies. PRRSV could not be found in any of the samples of these 20 farms but PCV2 was detected in six farms. Whether the stable fly can be used as a matrix to monitor the health status cannot be accurately determined through this study, especially in regard to PRRSV. Nevertheless, it might be possible to use the stable fly as diagnostic material for defined pathogens like Mycoplasma suis and PCV2.
Protection of Citrus Fruits from Postharvest Infection with Penicillium digitatum and Degradation of Patulin by Biocontrol Yeast Clavispora lusitaniae 146
Authors: Díaz Mariana Andrea , Pereyra Martina María , Santander Fabricio Fabián Soliz , Perez María Florencia , Córdoba Josefina María , Alhussein Mohammad , Karlovsky Petr , Dib Julián Rafael
Published: September 2020

Fungal rots are one of the main causes of large economic losses and deterioration in the quality and nutrient composition of fruits during the postharvest stage. The yeast Clavispora lusitaniae 146 has previously been shown to efficiently protect lemons from green mold caused by Penicillium digitatum. In this work, the effect of yeast concentration and exposure time on biocontrol efficiency was assessed; the protection of various citrus fruits against P. digitatum by C. lusitaniae 146 was evaluated; the ability of strain 146 to degrade mycotoxin patulin was tested; and the effect of the treatment on the sensory properties of fruits was determined. An efficient protection of lemons was achieved after minimum exposure to a relatively low yeast cell concentration. Apart from lemons, the yeast prevented green mold in grapefruits, mandarins, oranges, and tangerines, implying that it can be used as a broad-range biocontrol agent in citrus. The ability to degrade patulin indicated that strain 146 may be suitable for the control of further Penicillium species. Yeast treatment did not alter the sensory perception of the aroma of fruits. These results corroborate the potential of C. lusitaniae 146 for the control of postharvest diseases of citrus fruits and indicate its suitability for industrial-scale fruit processing.
Canine Bone Marrow Mesenchymal Stem Cell Conditioned Media Affect Bacterial Growth, Biofilm-Associated Staphylococcus aureus and AHL-Dependent Quorum Sensing
Authors: Bujňáková Dobroslava , Čuvalová Anna , Čížek Milan , Humenik Filip , Salzet Michel , Čížková Daša
Published: September 2020

The present study investigated the in vitro antibacterial, antibiofilm and anti-Quorum Sensing (anti-QS) activities of canine bone marrow mesenchymal stem cell-conditioned media (cBM MSC CM) containing all secreted factors <30 K, using a disc diffusion test (DDT), spectrophotometric Crystal Violet Assay (SCVA) and Bioluminescence Assay (BA) with QS-reporter Escherichia coli JM109 pSB1142. The results show a sample-specific bacterial growth inhibition (zones varied between 7–30 mm), statistically significant modulation of biofilm-associated Staphylococcus aureus and Escherichia coli bioluminescence (0.391 ± 0.062 in the positive control to the lowest 0.150 ± 0.096 in the experimental group, cf. 11,714 ± 1362 to 7753 ± 700, given as average values of absorbance A550 ± SD versus average values of relative light units to growth RLU/A550 ± SD). The proteomic analysis performed in our previous experiment revealed the presence of several substances with documented antibacterial, antibiofilm and immunomodulatory properties (namely, apolipoprotein B and D; amyloid-β peptide; cathepsin B; protein S100-A4, galectin 3, CLEC3A, granulin, transferrin). This study highlights that cBM MSC CM may represent an important new approach to managing biofilm-associated and QS signal molecule-dependent bacterial infections. To the best of our knowledge, there is no previous documentation of canine BM MSC CM associated with in vitro antibiofilm and anti-QS activity.
Host Specificity and Differential Pathogenicity of Pectobacterium Strains from Dicot and Monocot Hosts
Authors: Khadka Nirmal , Joshi Janak Raj , Reznik Noam , Chriker Nofar , Nudel Adi , Zelinger Einat , Kerem Zohar , Yedidia Iris
Published: September 2020

Recent phylogenetic studies have transferred certain isolates from monocot plants previously included in the heterogeneous group of Pectobacteriumcarotovorum (Pc) to a species level termed Pectobacterium aroidearum. The specificity of Pectobacterium associated infections had received less attention, and may be of high scientific and economic importance. Here, we have characterized differential responses of Pectobacterium isolates from potato (WPP14) and calla lily (PC16) on two typical hosts: Brassica oleracea var. capitata (cabbage) a dicot host; and Zantedeschia aethiopica (calla lily) a monocot host. The results revealed clear host specific responses following infection with the two bacterial strains. This was demonstrated by differential production of volatile organic compounds (VOCs) and the expression of plant defense-related genes (pal, PR-1, lox2, ast). A related pattern was observed in bacterial responses to each of the host’s extract, with differential expression of virulence-related determinants and genes associated with quorum-sensing and plant cell wall-degrading enzymes. The differences were associated with each strain’s competence on its respective host.
Optimization of a Method for the Concentration of Genetic Material in Bacterial and Fungal Communities on Fresh Apple Peel Surfaces
Authors: Hamilton Alexis , Harper Scott J. , Critzer Faith
Published: September 2020

Apples are the most consumed fruit in the United States and have recently been shown to exhibit some vulnerability to contamination across the supply chain. It is unclear what role a fruit microbiome analysis may serve in future food safety programs interested in understanding changes in the product and the processing environment. Ultimately, sample integrity is key if any of these approaches are to be employed; low microbial loads on apple surfaces, the inability to sample the entire surface, and inefficiency of removal may act as barriers to achieving high-quality DNA. As such, the objective of this study was to identify a reproducible method to concentrate and quantify bacterial and fungal DNA from fresh apple surfaces. Five methods were evaluated: two variations of wash solutions for bath sonication, wash filtration, epidermis excision, and surface swabbing. Epidermis excision returned the highest mean DNA quantities, followed by the sonicated washes and wash filtration. Surface swabbing was consistently below the limit of detection. Based on the quantity of host DNA contamination in surface excision, the sonicated wash solution containing a surfactant presents the greatest opportunity for consistent, high-yielding DNA recovery from the entire apple surface.
Seasonal Variations in Soil Microbiota Profile of Termite (Syntermes wheeleri) Mounds in the Brazilian Tropical Savanna
Authors: Guimaraes Helena Ipe Pinheiro , Santana Renata Henrique , Silveira Rafaella , Pinto Otavio Henrique Bezerra , Quirino Betania Ferraz , Barreto Cristine Chaves , Bustamante Mercedes Maria da Cunha , Krüger Ricardo Henrique
Published: September 2020

Eusocial animals, such as the termites, often build a nest-like structure called a mound that provides shelter with stable internal conditions and protection against predators. Termites are important components of the Brazilian Cerrado biota. This study aimed to investigate the bacterial community composition and diversity of the Syntermes wheeleri termite-mound soil using culture-independent approaches. We considered the vertical profile by comparing two different mound depths (mound surface and 60 cm) and seasonality with samplings during the rainy and dry seasons. We compared the mound soil microbiota to the adjacent soil without the influence of the mound to test the hypothesis that the Cerrado soil bacterial community was more diverse and more susceptible to seasonality than the mound soil microbiota. The results support the hypothesis that the Cerrado soil bacterial community is more diverse than the mound soil and also has a higher variability among seasons. The number of observed OTUs (Operational Taxonomic Units) was used to express bacterial richness, and it indicates that soil moisture has an effect on the community distribution and richness of the Cerrado samples in comparison to mound samples, which remain stable across seasons. This could be a consequence of the protective role of the mound for the termite colony. The overall community taxonomic profile was similar between soil samples, especially when compared to the taxonomic composition of the Syntermes wheeleri termite’s gut, which might be explained by the different characteristics and functionality between the soil and the gut microbial community.
Characterization of a Novel Quorum-Quenching Bacterial Strain, Burkholderia anthina HN-8, and Its Biocontrol Potential against Black Rot Disease Caused by Xanthomonas campestris pv. campestris
Authors: Ye Tian , Zhang Wenping , Feng Zhixuan , Fan Xinghui , Xu Xudan , Mishra Sandhya , Zhang Lianhui , Chen Shaohua
Published: September 2020

Diffusible signal factor (DSF) is a type of cis unsaturated fatty acid, with a chemical structure of 11-methyl-2-dodecylene acid. DSF is widely conserved in a variety of Gram-negative bacterial pathogens and is involved in the regulation of pathogenic virulence. Quorum quenching (QQ) is a promising strategy for preventing and controlling quorum sensing (QS)-mediated bacterial infections by interfering with the QS system of pathogens. In this study, a novel DSF-degrading bacterium, Burkholderia anthina strain HN-8, was isolated and characterized for its degradation ability and potential biocontrol of black rot disease caused by Xanthomonas campestris pv. campestris (Xcc). The HN-8 strain exhibited superb DSF degradation activity and completely degraded 2 mM DSF within 48 h. In addition, we present the first evidence of bacterium having a metabolic pathway for the complete degradation and metabolism of DSF. Analysis of DSF metabolic products by gas chromatography–mass spectrometry led to the identification of dodecanal as the main intermediate product, revealing that DSF could be degraded via oxidation–reduction. Furthermore, application of strain HN-8 as a potent biocontrol agent was able to significantly reduce the severity of black rot disease in radishes and Chinese cabbage. Taken together, these results shed light on the QQ mechanisms of DSF, and they provide useful information showing the potential for the biocontrol of infectious diseases caused by DSF-dependent bacterial pathogens.
Fecal Microbiota Transplant in Two Ulcerative Colitis Pediatric Cases: Gut Microbiota and Clinical Course Correlations
Authors: Quagliariello Andrea , Del Chierico Federica , Reddel Sofia , Russo Alessandra , Onetti Muda Andrea , D’Argenio Patrizia , Angelino Giulia , Romeo Erminia , Dall’Oglio Luigi , De Angelis Paola , Putignani Lorenza ,   all the other FMT OPBG Committee Collaborators
Published: September 2020

Fecal microbiota transplantation (FMT) is a promising strategy in the management of inflammatory bowel disease (IBD). The clinical effects of this practice are still largely unknown and unpredictable. In this study, two children affected by mild and moderate ulcerative colitis (UC), were pre- and post-FMT monitored for clinical conditions and gut bacterial ecology. Microbiota profiling relied on receipts’ time-point profiles, donors and control cohorts’ baseline descriptions. After FMT, the improvement of clinical conditions was recorded for both patients. After 12 months, the mild UC patient was in clinical remission, while the moderate UC patient, after 12 weeks, had a clinical worsening. Ecological analyses highlighted an increase in microbiota richness and phylogenetic distance after FMT. This increase was mainly due to Collinsella aerofaciens and Eubacterium biforme, inherited by respective donors. Moreover, a decrease of Proteus and Blautia producta, and the increment of Parabacteroides, Mogibacteriaceae, Bacteroides eggerthi, Bacteroides plebeius, Ruminococcus bromii, and BBacteroidesovatus were associated with remission of the patient’s condition. FMT results in a long-term response in mild UC, while in the moderate form there is probably need for multiple FMT administrations. FMT leads to a decrease in potential pathogens and an increase in microorganisms correlated to remission status.
Antimicrobial Effect of Zophobas morio Hemolymph against Bovine Mastitis Pathogens
Authors: Du Mengze , Liu Xiaodan , Xu Jiajia , Li Shuxian , Wang Shenghua , Zhu Yaohong , Wang Jiufeng
Published: September 2020

Coliforms and Staphylococcus spp. infections are the leading causes of bovine mastitis. Despite extensive research and development in antibiotics, they have remained inadequately effective in treating bovine mastitis induced by multiple pathogen infection. In the present study, we showed the protective effect of Zophobas morio (Z. morio) hemolymph on bovine mammary epithelial cells against bacterial infection. Z. morio hemolymph directly kills both Gram-positive and Gram-negative bacteria through membrane permeation and prevents the adhesion of E. coli or the clinically isolated S. simulans strain to bovine mammary epithelial (MAC-T) cells. In addition, Z. morio hemolymph downregulates the expression of nucleotide-binding oligomerization domain (NOD)-like receptor family member pyrin domain-containing protein 3 (NLRP3), caspase-1, and NLRP6, as well as inhibits the secretion of interleukin-1β (IL-1β) and IL-18, which attenuates E. coli or S. simulans-induced pyroptosis. Overall, our results suggest the potential role of Z. morio hemolymph as a novel therapeutic candidate for bovine mastitis.
Elimination of Extracellular Adenosine Triphosphate for the Rapid Prediction of Quantitative Plate Counts in 24 h Time-Kill Studies against Carbapenem-Resistant Gram-Negative Bacteria
Authors: Cai Yiying , Ng Jonathan J. , Leck Hui , Teo Jocelyn Q. , Goh Jia-Xuan , Lee Winnie , Koh Tse-Hsien , Tan Thuan-Tong , Lim Tze-Peng , Kwa Andrea L.
Published: September 2020

Traditional in vitro time-kill studies (TKSs) require viable plating, which is tedious and time-consuming. We used ATP bioluminescence, with the removal of extracellular ATP (EC-ATP), as a surrogate for viable plating in TKSs against carbapenem-resistant Gram-negative bacteria (CR-GNB). Twenty-four-hour TKSs were conducted using eight clinical CR-GNB (two Escherichia coli, two Klebsiella spp., two Acinetobacter baumannii, two Pseudomonas aeruginosa) with multiple single and two-antibiotic combinations. ATP bioluminescence and viable counts were determined at each timepoint (0, 2, 4, 8, 24 h), with and without apyrase treatment. Correlation between ATP bioluminescence and viable counts was determined for apyrase-treated and non-apyrase-treated samples. Receiver operator characteristic curves were plotted to determine the optimal luminescence threshold to discriminate between inhibitory/non-inhibitory and bactericidal/non-bactericidal combinations, compared to viable counts. After treatment of bacteria with 2 U/mL apyrase for 15 min at 37 °C, correlation to viable counts was significantly higher compared to untreated samples (p < 0.01). Predictive accuracies of ATP bioluminescence were also significantly higher for apyrase-treated samples in distinguishing inhibitory (p < 0.01) and bactericidal (p = 0.03) combinations against CR-GNB compared to untreated samples, when all species were collectively analyzed. We found that ATP bioluminescence can potentially replace viable plating in TKS. Our assay also has applications in in vitro and in vivo infection models.
AR12286 Alleviates TGF-β-Related Myofibroblast Transdifferentiation and Reduces Fibrosis after Glaucoma Filtration Surgery
Authors: Cheng Wen-Sheng , Chen Ching-Long , Chen Jiann-Torng , Lin Le-Tien , Pao Shu-I , Chen Yi-Hao , Lu Da-Wen
Published: September 2020

Scar formation can cause the failure of glaucoma filtration surgery. We investigated the effect of AR12286, a selective Rho-associated kinase inhibitor, on myofibroblast transdifferentiation and intraocular pressure assessment in rabbit glaucoma filtration surgery models. Cell migration and collagen contraction were used to demonstrate the functionality of AR12286-modulated human conjunctival fibroblasts (HConFs). Polymerase chain reaction quantitative analysis was used to determine the effect of AR12286 on the production of collagen Type 1A1 and fibronectin 1. Cell migration and collagen contraction in HConFs were activated by TGF-β1. However, compared with the control group, rabbit models treated with AR12286 exhibited higher reduction in intraocular pressure after filtration surgery, and decreased collagen levels at the wound site in vivo. Therefore, increased α-SMA expression in HConFs induced by TGF-β1 could be inhibited by AR12286, and the production of Type 1A1 collagen and fibronectin 1 in TGF-β1-treated HConFs was inhibited by AR12286. Overall, the stimulation of HConFs by TGF-β1 was alleviated by AR12286, and this effect was mediated by the downregulation of TGF-β receptor-related SMAD signaling pathways. In vivo results indicated that AR12286 thus improves the outcome of filtration surgery as a result of its antifibrotic action in the bleb tissue because AR12286 inhibited the TGF-β receptor-related signaling pathway, suppressing several downstream reactions in myofibroblast transdifferentiation.
Structure-Function Analyses of Human Bitter Taste Receptors—Where Do We Stand?
Authors: Behrens Maik , Ziegler Florian
Published: September 2020

The finding that bitter taste receptors are expressed in numerous tissues outside the oral cavity and fulfill important roles in metabolic regulation, innate immunity and respiratory control, have made these receptors important targets for drug discovery. Efficient drug discovery depends heavily on detailed knowledge on structure-function-relationships of the target receptors. Unfortunately, experimental structures of bitter taste receptors are still lacking, and hence, the field relies mostly on structures obtained by molecular modeling combined with functional experiments and point mutageneses. The present article summarizes the current knowledge on the structure–function relationships of human bitter taste receptors. Although these receptors are difficult to express in heterologous systems and their homology with other G protein-coupled receptors is very low, detailed information are available at least for some of these receptors.
Anti-Influenza Virus Activity and Chemical Components from the Parasitic Plant Cuscuta japonica Choisy on Dimocarpus longans Lour.
Authors: Cheng Ju-Chien , Liaw Chia-Ching , Lin Ming-Kuem , Chen Chao-Jung , Chao Chien-Liang , Chao Chih-Hua , Kuo Yueh-Hsiung , Chiu Yen-Po , Peng Yu-Shin , Huang Hui-Chi
Published: September 2020

Dodder (Cuscuta spp.) is a parasitic weed damaging many plants and agricultural production. The native obligate parasite Cuscuta japonica Choisy (Japanese dodder) parasitizes Dimocarpus longans Lour., Ficus septica Burm. F., Ficus microcarpa L.f., Mikania micrantha H.B.K. and Melia azedarach Linn, respectively. Five Japanese dodders growing on different plants exhibit slightly different metabolites and amounts which present different pharmacological effects. Among these plants, a significant antiviral activity against influenza A virus (IAV) was found in Japanese dodder parasitizing on D. longans Lour. (CL). To further explore methanol extract components in Japanese dodder (CL), four undescribed aromatic glycosides, cuscutasides A–D (compounds 1–4) were isolated, together with twenty-six known compounds 5–30. The chemical structures of 1–4 were elucidated using a combination of spectroscopic techniques. The eighteen isolated compounds were evaluated for antiviral activity against IAV activity. Among them, 1-monopalmitin (29) displayed potent activity against influenza A virus (A/WSN/1933(H1N1)) with EC50 2.28 ± 0.04 μM and without noteworthy cytotoxicity in MDCK cells. The interrupt step of 29 on the IAV life cycle was determined. These data provide invaluable information for new applications for this otherwise harmful weed.
Attraction of Adults of Cyclocephala lunulata and Cyclocephala barrerai (Coleoptera: Scarabaeoidea: Melolonthidae) towards Bacteria Volatiles Isolated from Their Genital Chambers
Authors: Sanchez-Cruz Abraham , Robledo Norma , Rosete-Enríquez María , Romero-López Angel A.
Published: September 2020

In the study of the chemical communication of adults of the Melolonthidae family, bacteria have been observed in the epithelium of the genital chamber; possibly, bacteria are involved in the production of sex attractants in their hosts. Therefore, it is important to identify the volatile organic compounds from bacteria (VOCsB) released by these microorganisms and study the biological activity stimulated by VOBCs in adults of Melolonthidae. In this study, bacteria were isolated from the genital chamber of Cyclocephala lunulata and Cyclocephala barrerai, from which VOCsB were extracted using static headspace solid-phase microextraction (SHS-SPME) and dynamic headspace Super Q solid-phase extraction (DHS-SPE) and analyzed using gas chromatography-mass spectrometry. The effect of VOCsB on the hosts and conspecifics was evaluated utilizing an olfactometer and electroantennography (EAG). Two species of Enterobacteria were isolated from the genital chamber of each female species, and VOCsB derived from sulfur-containing compounds, alcohols, esters, and fatty acids were identified. An attraction response was observed in olfactometry studies, and antennal responses to VOCsB were confirmed in EAG bioassays. With these results, new perspectives on the relationship between these beetles and their bacteria emerge, in addition to establishing a basis for management programs in the future.
A Colorimetric Assay for the Detection of Glucose and H2O2 Based on Cu-Ag/g-C3N4/ZIF Hybrids with Superior Peroxidase Mimetic Activity
Authors: Pan Quan , Kong Yuelin , Chen Kuan , Mao Mi , Wan Xiaohui , She Xiaoyan , Gao Qingsong , He Yu , Song Gongwu
Published: September 2020

In this work, we report the synthesis of Cu-Ag bimetallic nanopartiles and g-C3N4 nanosheets decorated on zeolitic imidazolate framework-8 (ZIF-8) to form a Cu-Ag/g-C3N4/ZIF hybrid. The hybrid was synthesized and characterized by Transmission electron microscopy (TEM), Fourier transformed infrared (FTIR), the X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS). The Cu-Ag/g-C3N4/ZIF hybrid has intrinsic peroxidaselike catalytic activity towards the oxidation of TMB in the presence of H2O2. The situ synthesis of Cu-Ag bimetallic nanopartiles on 2D support such as g-C3N4 nanosheets would significantly enhance the peroxidaselike catalytic properties of individual Cu-Ag bimetallic nanopartiles and the g-C3N4 nanosheets. After loading of Cu-Ag bimetallic nanopartiles and g-C3N4 nanosheets on the ZIF-8, the hybrids exhibited superior peroxidaselike catalytic activity and good recyclability. Then, this method was applied for detecting glucose in human serum, owing the significant potential for detection of metabolites with H2O2-generation reactions.
3,7-Dihydroxytropolones Inhibit Initiation of Hepatitis B Virus Minus-Strand DNA Synthesis
Authors: Bak Ellen , Miller Jennifer T. , Noronha Andrea , Tavis John , Gallicchio Emilio , Murelli Ryan P. , Le Grice Stuart F. J.
Published: September 2020

Initiation of protein-primed (-) strand DNA synthesis in hepatitis B virus (HBV) requires interaction of the viral reverse transcriptase with epsilon (ε), a cis-acting regulatory signal located at the 5’ terminus of pre-genomic RNA (pgRNA), and several host-encoded chaperone proteins. Binding of the viral polymerase (P protein) to ε is necessary for pgRNA encapsidation and synthesis of a short primer covalently attached to its terminal domain. Although we identified small molecules that recognize HBV ε RNA, these failed to inhibit protein-primed DNA synthesis. However, since initiation of HBV (-) strand DNA synthesis occurs within a complex of viral and host components (e.g., Hsp90, DDX3 and APOBEC3G), we considered an alternative therapeutic strategy of allosteric inhibition by disrupting the initiation complex or modifying its topology. To this end, we show here that 3,7-dihydroxytropolones (3,7-dHTs) can inhibit HBV protein-primed DNA synthesis. Since DNA polymerase activity of a ribonuclease (RNase H)-deficient HBV reverse transcriptase that otherwise retains DNA polymerase function is also abrogated, this eliminates direct involvement of RNase (ribonuclease) H activity of HBV reverse transcriptase and supports the notion that the HBV initiation complex might be therapeutically targeted. Modeling studies also provide a rationale for preferential activity of 3,7-dHTs over structurally related α-hydroxytropolones (α-HTs).
The Potential Role and Regulatory Mechanisms of MUC5AC in Chronic Obstructive Pulmonary Disease
Authors: Li Jingyuan , Ye Zuguang
Published: September 2020

Chronic obstructive pulmonary disease (COPD) is associated with high morbidity and mortality globally. Studies show that airway mucus hypersecretion strongly compromises lung function, leading to frequent hospitalization and mortality, highlighting an urgent need for effective COPD treatments. MUC5AC is known to contribute to severe muco-obstructive lung diseases, worsening COPD pathogenesis. Various pathways are implicated in the aberrant MUC5AC production and secretion MUC5AC. These include signaling pathways associated with mucus-secreting cell differentiation [nuclear factor-κB (NF-κB)and IL-13-STAT6- SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF), as well as epithelial sodium channel (ENaC) and cystic fibrosis transmembrane conductance regulator (CFTR)], and signaling pathways related to mucus transport and excretion-ciliary beat frequency (CBF). Various inhibitors of mucus hypersecretion are in clinical use but have had limited benefits against COPD. Thus, novel therapies targeting airway mucus hypersecretion should be developed for effective management of muco-obstructive lung disease. Here, we systematically review the mechanisms and pathogenesis of airway mucus hypersecretion, with emphasis on multi-target and multi-link intervention strategies for the elucidation of novel inhibitors of airway mucus hypersecretion.
A Total of Eight Novel Steroidal Glycosides Based on Spirostan, Furostan, Pseudofurostan, and Cholestane from the Leaves of Cestrum newellii
Authors: Iguchi Tomoki , Takahashi Naoki , Mimaki Yoshihiro
Published: September 2020

Previously, various steroidal glycosides were reported from plants of Cestrum species. However, phytochemical investigation has not been conducted on Cestrum newellii. A systematic phytochemical investigation of the leaves of C. newellii resulted in the isolation of eight novel steroidal glycosides (1–8), which were classified into three spirostanol glycosides (1–3), two furostanol glycosides (4 and 5), two pseudofurostanol glycosides (6 and 7), and one cholestane glycoside (8). In addition, three known cholestane glycosides (9–11) were isolated and identified. The structures of the new compounds were determined based on spectroscopic data and chemical transformations. Compounds 1 and 2 are spirostanol glycosides having hydroxy groups at C-2, C-3, C-12, and C-24 of the aglycone moiety. Although C. newellii is known to be a poisonous plant, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide assay exhibited that none of the isolated compounds were cytotoxic to HL-60 human promyelocytic leukemia cells.
The Emerging Promise of Touchscreen Devices for Individuals with Intellectual Disabilities
Authors: Skogly Kversøy Kjartan , Kellems Ryan O. , Kuyini Alhassan Abdul-Razak , Bussey Heidi C. , Daae Kversøy Sofie
Published: September 2020

This article explores the emerging promise touchscreen devices hold for individuals with intellectual disabilities (ID). Many individuals with ID that struggle to read, write or use voice assisted strategies can use touchscreen devices in many aspects of their lives. Research has shown that touchscreen technology is available, easy to use and can open an array of empowering possibilities for individuals with ID. In this article we will be sharing research and a vision for possible uses of touchscreen devices in the future for individuals with ID. Our perspectives are shaped by our experiences with using touchscreen technology in collaboration with people who have ID. A special aspect of our research methodology is the fact that one of our co-researchers has ID.
Red Propolis and Its Dyslipidemic Regulator Formononetin: Evaluation of Antioxidant Activity and Gastroprotective Effects in Rat Model of Gastric Ulcer
Authors: Mendonça Marcio A. A. de , Ribeiro Ana R. S. , Lima Adriana K. de , Bezerra Gislaine B. , Pinheiro Malone S. , Albuquerque-Júnior Ricardo L. C. de , Gomes Margarete Z. , Padilha Francine F. , Thomazzi Sara M. , Novellino Ettore , Santini Antonello , Severino Patricia , B. Souto Eliana , Cardoso Juliana C.
Published: September 2020

Propolis has various pharmacological properties of clinical interest, and is also considered a functional food. In particular, hydroalcoholic extracts of red propolis (HERP), together with its isoflavonoid formononetin, have recognized antioxidant and anti-inflammatory properties, with known added value against dyslipidemia. In this study, we report the gastroprotective effects of HERP (50–500 mg/kg, p.o.) and formononetin (10 mg/kg, p.o.) in ethanol and non-steroidal anti-inflammatory drug-induced models of rat ulcer. The volume, pH, and total acidity were the evaluated gastric secretion parameters using the pylorus ligature model, together with the assessment of gastric mucus contents. The anti-Helicobacter pylori activities of HERP were evaluated using the agar-well diffusion method. In our experiments, HERP (250 and 500 mg/kg) and formononetin (10 mg/kg) reduced (p < 0.001) total lesion areas in the ethanol-induced rat ulcer model, and reduced (p < 0.05) ulcer indices in the indomethacin-induced rat ulcer model. Administration of HERP and formononetin to pylorus ligature models significantly decreased (p < 0.01) gastric secretion volumes and increased (p < 0.05) mucus production. We have also shown the antioxidant and anti-Helicobacter pylori activities of HERP. The obtained results indicate that HERP and formononetin are gastroprotective in acute ulcer models, suggesting a prominent role of formononetin in the effects of HERP.