bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Pulse Wave Velocity and Parameters Reflecting Android Type Fat Distribution on Left Ventricular Diastolic Dysfunction in Patients with Chronic Coronary Syndromes
Authors: Paniczko Marlena , Chlabicz Małgorzata , Jamiołkowski Jacek , Sowa Paweł , Szpakowicz Małgorzata , Łapińska Magda , Kondraciuk Marcin , Ptaszyńska-Kopczyńska Katarzyna , Raczkowski Andrzej , Szpakowicz Anna , Kamiński Karol Adam
Published: December 2020

Background: Left ventricular diastolic dysfunction (LVDD) is caused by a decreased left ventricle relaxation and is associated with an increased risk of symptomatic heart failure (HF) and excessive mortality. Aim: To evaluate the frequency and factors related to LVDD in the population with chronic coronary syndromes (CCS). Methods: 200 patients (mean age 63.18 ± 8.12 years, 75.5% male) with CCS were included. LVDD was diagnosed based on the recent echocardiography guidelines. Results: LVDD was diagnosed in 38.5% of CCS population. From the studied factors, after adjustment for age, sex, and N-terminal pro-brain natriuretic peptide (NT-proBNP), LVDD associated positively with android/gynoid (A/G) fat mass ratio, left ventricular mass index (LVMI), and negatively with Z-score and left ventricular ejection fraction (LVEF). In stepwise backward logistic regression analysis, the strongest factors associated with LVDD were pulse wave velocity value, handgrip strength and waist to hip ratio (WHR). Conclusions: LVDD is common among CCS patients and it is associated with parameters reflecting android type fat distribution regardless of NT-proBNP and high-sensitivity troponin T concentrations. Deterioration in diastolic dysfunction is linked with increased aortic stiffness independently of age and sex. Further studies evaluating the effects of increasing physical fitness and lowering abdominal fat accumulations on LVDD in CCS patients should be considered.
Presence of Cutaneous Complement Deposition Distinguishes between Immunological and Histological Features of Bullous Pemphigoid—Insights from a Retrospective Cohort Study
Authors: Ständer Sascha , Holtsche Maike M. , Schmidt Enno , Hammers Christoph M. , Zillikens Detlef , Ludwig Ralf J. , Kridin Khalaf
Published: December 2020

The practical implications of complement deposition in direct immunofluorescence (DIF) microscopy and its influence on the disease phenotype are poorly understood. We aimed to investigate whether the presence of complement deposition in DIF microscopy gives rise to differences in the morphological, immunological, and histological characteristics of patients with BP (bullous pemphigoid). We performed a retrospective study encompassing patients with BP in a specialized tertiary referral center. Logistic regression model was utilized to identify variables independently associated with complement deposition. The study included 233 patients with BP, of whom 196 (84.1%) demonstrated linear C3 deposition along the dermal-epidermal junction (DEJ) in DIF analysis. BP patients with C3 deposition had higher mean (SD) levels (645.2 (1418.5) vs. 172.5 (243.9) U/mL; p < 0.001) and seropositivity rate (86.3% vs.64.9%; p = 0.002) of anti-BP180 NC16A and less prevalent neutrophilic infiltrate in lesional skin specimens (29.8% vs. 52.4%; p = 0.041). C3 deposition was found positively associated with the detection of anti-BP180 NC16A autoantibodies (OR, 4.25; 95% CI, 1.38–13.05) and inversely associated with the presence of neutrophils in lesional skin (OR, 3.03; 95% CI, 1.09–8.33). To conclude, complement deposition influences the immunological and histological features of BP. These findings are in line with experimental data describing the pathogenic role of complement in BP.
Experimental and Numerical Investigation on the Steel Reinforced Grout (SRG) Composite-to-Concrete Bond
Authors: Ombres Luciano , Verre Salvatore
Published: December 2020

In the paper, the bond between a composite strengthening system consisting of steel textiles embedded into an inorganic matrix (steel reinforced grout, SRG) and the concrete substrate, is investigated. An experimental investigation was carried out on medium density SRG specimens; direct shear tests were conducted on 20 specimens to analyze the effect of the bond length, and the age of the composite strip on the SRG-to-concrete bond behavior. In particular, the tests were conducted considering five bond length (100, 200, 250, 330, and 450 mm), and the composite strip’s age 14th, 21st, and 28th day after the bonding. Test results in the form of peak load, failure modes and, bond-slip diagrams were presented and discussed. A finite element model developed through commercial software to replicate the behavior of SRG strips, is also proposed. The effectiveness of the proposed numerical model was validated by the comparison between its predictions and experimental results.
Rye Snow Mold-Associated Microdochium nivale Strains Inhabiting a Common Area: Variability in Genetics, Morphotype, Extracellular Enzymatic Activities, and Virulence
Authors: Gorshkov Vladimir , Osipova Elena , Ponomareva Mira , Ponomarev Sergey , Gogoleva Natalia , Petrova Olga , Gogoleva Olga , Meshcherov Azat , Balkin Alexander , Vetchinkina Elena , Potapov Kim , Gogolev Yuri , Korzun Viktor
Published: December 2020

Snow mold is a severe plant disease caused by psychrophilic or psychrotolerant fungi, of which Microdochium species are the most harmful. A clear understanding of Microdochium biology has many gaps; the pathocomplex and its dynamic are poorly characterized, virulence factors are unknown, genome sequences are not available, and the criteria of plant snow mold resistance are not elucidated. Our study aimed to identify comprehensive characteristics of a local community of snow mold-causing Microdochium species colonizing a particular crop culture. By using the next-generation sequencing (NGS) technique, we characterized fungal and bacterial communities of pink snow mold-affected winter rye (Secale cereale) plants within a given geographical location shortly after snowmelt. Twenty-one strains of M. nivale were isolated, classified on the basis of internal transcribed spacer 2 (ITS2) region, and characterized by morphology, synthesis of extracellular enzymes, and virulence. Several types of extracellular enzymatic activities, the level of which had no correlations with the degree of virulence, were revealed for Microdochium species for the first time. Our study shows that genetically and phenotypically diverse M. nivale strains simultaneously colonize winter rye plants within a common area, and each strain is likely to utilize its own, unique strategy to cause the disease using “a personal” pattern of extracellular enzymes.
Bank Characteristics Effect on Capital Structure: Evidence from PMG and CS-ARDL
Authors: Erülgen Ahmet , Rjoub Husam , Adalıer Ahmet
Published: December 2020

The main aim of this paper was to investigate the impact of bank characteristics on capital structure empirically. The study employed a panel data analysis, Pooled Mean Group (PMG) and Cross-Sectionally Augmented Autoregressive Distributed Lag (CS-ARDL) estimators were utilized, for the period spans between the years 2008 and 2018. Both the borrowing (leverage) ratio and equity ratio used in the analysis cover short-term deposits and long-term deposits as a fundamental determinant variable on the capital structure. The main findings confirm that the deposit ratio has a positive relationship with the size of the bank. In other words, big banks use more foreign sources than small banks to use the tax shield advantage. At the same time, a percentage increase in bank size and liquidity ratio enhance the bank deposit rate by 0.0068% and 0.479%, respectively, in the long-run, while a percentage change in interest income coverage will reduce the bank deposit rate by 0.004% in the long-run. Meanwhile, the significant causal relationship of growth rate with the bank deposit rate could not be established. In addition, the short-run coefficients of the variables reveal that size, interest coverage, and liquidity have a positive and significant causal relationship with bank deposit rate in the short-run. The findings of the study are in line with the results of capital structure theories, especially the hierarchy theory and balancing theory.
Inactivation of Three RG(S/T)GR Pentapeptide-Containing Negative Regulators of HetR Results in Lethal Differentiation of Anabaena PCC 7120
Authors: Khudyakov Ivan , Gladkov Grigory , Elhai Jeff
Published: December 2020

The filamentous cyanobacterium Anabaena sp. PCC 7120 produces, during the differentiation of heterocysts, a short peptide PatS and a protein HetN, both containing an RGSGR pentapeptide essential for activity. Both act on the master regulator HetR to guide heterocyst pattern formation by controlling the binding of HetR to DNA and its turnover. A third small protein, PatX, with an RG(S/T)GR motif is present in all HetR-containing cyanobacteria. In a nitrogen-depleted medium, inactivation of patX does not produce a discernible change in phenotype, but its overexpression blocks heterocyst formation. Mutational analysis revealed that PatX is not required for normal intercellular signaling, but it nonetheless is required when PatS is absent to prevent rapid ectopic differentiation. Deprivation of all three negative regulators—PatS, PatX, and HetN—resulted in synchronous differentiation. However, in a nitrogen-containing medium, such deprivation leads to extensive fragmentation, cell lysis, and aberrant differentiation, while either PatX or PatS as the sole HetR regulator can establish and maintain a semiregular heterocyst pattern. These results suggest that tight control over HetR by PatS and PatX is needed to sustain vegetative growth and regulated development. The mutational analysis has been interpreted in light of the opposing roles of negative regulators of HetR and the positive regulator HetL.
On the Quest for In Vitro Platelet Production by Re-Tailoring the Concepts of Megakaryocyte Differentiation
Authors: Martínez-Botía Patricia , Acebes-Huerta Andrea , Seghatchian Jerard , Gutiérrez Laura
Published: December 2020

The demand of platelet transfusions is steadily growing worldwide, inter-donor variation, donor dependency, or storability/viability being the main contributing factors to the current global, donor-dependent platelet concentrate shortage concern. In vitro platelet production has been proposed as a plausible alternative to cover, at least partially, the increasing demand. However, in practice, such a logical production strategy does not lack complexity, and hence, efforts are focused internationally on developing large scale industrial methods and technologies to provide efficient, viable, and functional platelet production. This would allow obtaining not only sufficient numbers of platelets but also functional ones fit for all clinical purposes and civil scenarios. In this review, we cover the evolution around the in vitro culture and differentiation of megakaryocytes into platelets, the progress made thus far to bring the culture concept from basic research towards good manufacturing practices certified production, and subsequent clinical trial studies. However, little is known about how these in vitro products should be stored or whether any safety measure should be implemented (e.g., pathogen reduction technology), as well as their quality assessment (how to isolate platelets from the rest of the culture cells, debris, microvesicles, or what their molecular and functional profile is). Importantly, we highlight how the scientific community has overcome the old dogmas and how the new perspectives influence the future of platelet-based therapy for transfusion purposes.
Encapsulation of Risperidone by Methylated β-Cyclodextrins: Physicochemical and Molecular Modeling Studies
Authors: Sbârcea Laura , Tănase Ionuț-Mihai , Ledeți Adriana , Cîrcioban Denisa , Vlase Gabriela , Barvinschi Paul , Miclău Marinela , Văruţ Renata-Maria , Trandafirescu Cristina , Ledeți Ionuț
Published: December 2020

Risperidone (RSP) is an atypical antipsychotic drug which acts as a potent antagonist of serotonin-2 (5TH2) and dopamine-2 (D2) receptors in the brain; it is used to treat schizophrenia, behavioral and psychological symptoms of dementia and irritability associated with autism. It is a poorly water soluble benzoxazole derivative with high lipophilicity. Supramolecular adducts between drug substance and two methylated β-cyclodextrins, namely heptakis(2,6-di-O-methyl)-β-cyclodextrin (DM-β-CD) and heptakis(2,3,6-tri-O-methyl)-β-cyclodextrin (TM-β-CD) were obtained in order to enhance RSP solubility and improve its biopharmaceutical profile. The inclusion complexes were evaluated by means of thermoanalytical methods (TG—thermogravimetry/DTG—derivative thermogravimetry/HF—heat flow), powder X-ray diffractometry (PXRD), universal-attenuated total reflectance Fourier transform infrared (UATR-FTIR), UV spectroscopy and saturation solubility studies. Job’s method was employed for the determination of the stoichiometry of the inclusion complexes, which was found to be 2:1 for both guest–host systems. Molecular modeling studies were carried out for an in-depth characterization of the interaction between drug substance and cyclodextrins (CDs). The physicochemical properties of the supramolecular systems differ from those of RSP, demonstrating the inclusion complex formation between drug and CDs. The RSP solubility was enhanced as a result of drug encapsulation in the CDs cavity, the higher increase being obtained with DM-β-CD as host; the guest–host system RSP/DM-β-CD can thus be a starting point for further research in developing new formulations containing RSP, with enhanced bioavailability.
Quantum Chemical Investigation of Polychlorinated Dibenzodioxins, Dibenzofurans and Biphenyls: Relative Stability and Planarity Analysis
Authors: Datta Sopanant , Limpanuparb Taweetham
Published: December 2020

All the possible polychlorinated aromatic compounds in the classes of dibenzodioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) were studied by the quantum chemical methods of HF/6-311++G(d,p), B3LYP/6-311++G(d,p), and MP2/cc-pVTZ. The calculated stabilities and structures of these compounds were compared with the available data on their abundance and toxicity. Prediction models for trends in energy and planarity among these congeners were proposed. The results discussed here can help contribute to the understanding of the role of dioxin-like compounds (DLCs) in the environment.
Oligomerization Profile of Human Transthyretin Variants with Distinct Amyloidogenicity
Authors: Frangolho Ana , Correia Bruno E. , Vaz Daniela C. , Almeida Zaida L. , Brito Rui M. M.
Published: December 2020

One of the molecular hallmarks of amyloidoses is ordered protein aggregation involving the initial formation of soluble protein oligomers that eventually grow into insoluble fibrils. The identification and characterization of molecular species critical for amyloid fibril formation and disease development have been the focus of intense analysis in the literature. Here, using photo-induced cross-linking of unmodified proteins (PICUP), we studied the early stages of oligomerization of human transthyretin (TTR), a plasma protein involved in amyloid diseases (ATTR amyloidosis) with multiple clinical manifestations. Upon comparison, the oligomerization processes of wild-type TTR (TTRwt) and several TTR variants (TTRV30M, TTRL55P, and TTRT119M) clearly show distinct oligomerization kinetics for the amyloidogenic variants but a similar oligomerization mechanism. The oligomerization kinetics of the TTR amyloidogenic variants under analysis showed a good correlation with their amyloidogenic potential, with the most amyloidogenic variants aggregating faster (TTRL55P > TTRV30M > TTRwt). Moreover, the early stage oligomerization mechanism for these variants involves stepwise addition of monomeric units to the growing oligomer. A completely different behavior was observed for the nonamyloidogenic TTRT119M variant, which does not form oligomers in the same acidic conditions and even for longer incubation times. Thorough characterization of the initial steps of TTR oligomerization is critical for better understanding the origin of ATTR cytotoxicity and developing novel therapeutic strategies for the treatment of ATTR amyloidosis.
Synthesis of [18F]F-γ-T-3, a Redox-Silent γ-Tocotrienol (γ-T-3) Vitamin E Analogue for Image-Based In Vivo Studies of Vitamin E Biodistribution and Dynamics
Authors: Roselt Peter , Cullinane Carleen , Noonan Wayne , Elsaidi Hassan , Eu Peter , Wiebe Leonard I.
Published: December 2020

Vitamin E, a natural antioxidant, is of interest to scientists, health care pundits and faddists; its nutritional and biomedical attributes may be validated, anecdotal or fantasy. Vitamin E is a mixture of tocopherols (TPs) and tocotrienols (T-3s), each class having four substitutional isomers (α-, β-, γ-, δ-). Vitamin E analogues attain only low concentrations in most tissues, necessitating exacting invasive techniques for analytical research. Quantitative positron emission tomography (PET) with an F-18-labeled molecular probe would expedite access to Vitamin E’s biodistributions and pharmacokinetics via non-invasive temporal imaging. (R)-6-(3-[18F]Fluoropropoxy)-2,7,8-trimethyl-2-(4,8,12-trimethyltrideca-3,7,11-trien-1-yl)-chromane ([18F]F-γ-T-3) was prepared for this purpose. [18F]F-γ-T-3 was synthesized from γ-T-3 in two steps: (i) 1,3-di-O-tosylpropane was introduced at C6-O to form TsO-γ-T-3, and (ii) reaction of this tosylate with [18F]fluoride in DMF/K222. Non-radioactive F-γ-T-3 was synthesized by reaction of γ-T-3 with 3-fluoropropyl methanesulfonate. [18F]F-γ-T-3 biodistribution in a murine tumor model was imaged using a small-animal PET scanner. F-γ-T-3 was prepared in 61% chemical yield. [18F]F-γ-T-3 was synthesized in acceptable radiochemical yield (RCY 12%) with high radiochemical purity (>99% RCP) in 45 min. Preliminary F-18 PET images in mice showed upper abdominal accumulation with evidence of renal clearance, only low concentrations in the thorax (lung/heart) and head, and rapid clearance from blood. [18F]F-γ-T-3 shows promise as an F-18 PET tracer for detailed in vivo studies of Vitamin E. The labeling procedure provides acceptable RCY, high RCP and pertinence to all eight Vitamin E analogues.
From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems
Authors: Pasquer Quentin T. L. , Tsakoumagkos Ioannis A. , Hoogendoorn Sascha
Published: December 2020

Biologically active small molecules have a central role in drug development, and as chemical probes and tool compounds to perturb and elucidate biological processes. Small molecules can be rationally designed for a given target, or a library of molecules can be screened against a target or phenotype of interest. Especially in the case of phenotypic screening approaches, a major challenge is to translate the compound-induced phenotype into a well-defined cellular target and mode of action of the hit compound. There is no “one size fits all” approach, and recent years have seen an increase in available target deconvolution strategies, rooted in organic chemistry, proteomics, and genetics. This review provides an overview of advances in target identification and mechanism of action studies, describes the strengths and weaknesses of the different approaches, and illustrates the need for chemical biologists to integrate and expand the existing tools to increase the probability of evolving screen hits to robust chemical probes.
Miniaturized Salting-Out Assisted Liquid-Liquid Extraction Combined with Disposable Pipette Extraction for Fast Sample Preparation of Neonicotinoid Pesticides in Bee Pollen
Authors: Tu Xijuan , Chen Wenbin
Published: December 2020

As the main source of nutrients for the important pollinator honeybee, bee pollen is crucial for the health of the honeybee and the agro-ecosystem. In the present study, a new sample preparation procedure has been developed for the determination of neonicotinoid pesticides in bee pollen. The neonicotinoid pesticides were extracted using miniaturized salting-out assisted liquid-liquid extraction (mini-SALLE), followed by disposable pipette extraction (DPX) for the clean-up of analytes. Effects of DPX parameters on the clean-up performance were systematically investigated, including sorbent types (PSA, C18, and silica gel), mass of sorbent, loading modes, and elution conditions. In addition, the clean-up effect of classical dispersive solid-phase extraction (d-SPE) was compared with that of the DPX method. Results indicated that PSA-based DPX showed excellent clean-up ability for the high performance liquid chromatography (HPLC) analysis of neonicotinoid pesticides in bee pollen. The proposed DPX method was fully validated and demonstrated to provide the advantage of simple and rapid clean-up with low consumption of solvent. This is the first report of DPX method applied in bee pollen matrix, and would be valuable for the development of a fast sample preparation method for this challenging and important matrix.
Aromatypicity of Austrian Pinot Blanc Wines
Authors: Philipp Christian , Eder Phillip , Sari Sezer , Hussain Nizakat , Patzl-Fischerleitner Elsa , Eder Reinhard
Published: December 2020

Pinot blanc is a grape variety found in all wine-growing regions of Austria. However, there are only few scientific studies which deal with the aroma of wines of this variety. In the course of this project, the relationship between aroma profile and the typicity of Austrian Pinot blanc wines was studied. The aim was to describe the typicity and to find significant differences in aroma profiles and aroma descriptors of typical and atypical Pinot blanc wines. Since the typicity of a jointly anchored prototype is embedded in the memory, typical attributes for Austrian Pinot blanc wines were first identified by consumers and experts or producers. According to this, 131 flawless commercial Austrian wines of the variety Pinot blanc of the vintages 2015 to 2017 were analysed for more than 100 volatile substances. The wines of the vintages 2015 to 2017 were judged by a panel of producers and experts for their typicity; furthermore, the wines of the vintage 2017 were also evaluated by a consumer panel and a trained descriptive panel. Subsequently, typical and atypical wines were described by the trained descriptive panel. It was found that Pinot blanc wines typical of Austria showed significantly higher concentrations of the ester compounds ethyl hexanoate, ethyl butanoate, ethyl octanoate, ethyl decanoate, methyl hexanoate, hexyl acetate and isoamyl acetate, while atypical wines had higher concentrations of free monoterpenes such as linalool, trans-linalool oxide, nerol oxide, nerol and alpha-terpineol. The sensory description of typical Pinot blanc wines was significantly more pronounced for the attribute “yellow pome fruit”, and tended to be more pronounced for the attributes “green pome fruit”, “pear”, “walnut”, “pineapple”, “banana” and “vanilla”, while the atypical Pinot blanc wines were described more by the attribute “citrus”. These findings could help to ensure that, through targeted measures, Austrian Pinot blanc wines become even more typical and distinguish themselves from other origins such as Germany or South Tyrol through a clear concept of typicity.
Methods for Studying Endocytotic Pathways of Herpesvirus Encoded G Protein-Coupled Receptors
Authors: Mavri Maša , Spiess Katja , Rosenkilde Mette Marie , Rutland Catrin Sian , Vrecl Milka , Kubale Valentina
Published: December 2020

Endocytosis is a fundamental process involved in trafficking of various extracellular and transmembrane molecules from the cell surface to its interior. This enables cells to communicate and respond to external environments, maintain cellular homeostasis, and transduce signals. G protein-coupled receptors (GPCRs) constitute a family of receptors with seven transmembrane alpha-helical domains (7TM receptors) expressed at the cell surface, where they regulate physiological and pathological cellular processes. Several herpesviruses encode receptors (vGPCRs) which benefits the virus by avoiding host immune surveillance, supporting viral dissemination, and thereby establishing widespread and lifelong infection, processes where receptor signaling and/or endocytosis seem central. vGPCRs are rising as potential drug targets as exemplified by the cytomegalovirus-encoded receptor US28, where its constitutive internalization has been exploited for selective drug delivery in virus infected cells. Therefore, studying GPCR trafficking is of great importance. This review provides an overview of the current knowledge of endocytic and cell localization properties of vGPCRs and methodological approaches used for studying receptor internalization. Using such novel approaches, we show constitutive internalization of the BILF1 receptor from human and porcine γ-1 herpesviruses and present motifs from the eukaryotic linear motif (ELM) resources with importance for vGPCR endocytosis.
Comparison of Electropolishing of Aluminum in a Deep Eutectic Medium and Acidic Electrolyte
Authors: Abdel-Fattah Tarek M. , Loftis J. Derek
Published: December 2020

Research advances in electropolishing, with respect to the field of metalworking, have afforded significant improvements in the surface roughness and conductivity properties of aluminum polished surfaces in ways that machine polishing and simple chemical polishing cannot. The effects of a deep eutectic medium as an acid-free electrolyte were tested to determine the potential energy thresholds during electropolishing treatments based upon temperature, experiment duration, current, and voltage. Using voltammetry and chronoamperometry tests during electropolishing to supplement representative recordings via atomic force microscopy (AFM), surface morphology comparisons were performed regarding the electropolishing efficiency of phosphoric acid and acid-free ionic liquid treatments for aluminum. This eco-friendly solution produced polished surfaces superior to those surfaces treated with industry standard acid electrochemistry treatments of 1 M phosphoric acid. The roughness average of the as-received sample became 6.11 times smoother, improving from 159 nm to 26 nm when electropolished with the deep eutectic solvent. This result was accompanied by a mass loss of 0.039 g and a 7.2 µm change in step height along the edge of the electropolishing interface, whereas the acid treatment resulted in a slight improvement in surface roughness, becoming 1.63 times smoother with an average post-electropolishing roughness of 97.7 nm, yielding a mass loss of 0.0458 g and a step height of 8.1 µm.
DNA Damaged Induced Cell Death in Oocytes
Authors: Gebel Jakob , Tuppi Marcel , Sänger Nicole , Schumacher Björn , Dötsch Volker
Published: December 2020

The production of haploid gametes through meiosis is central to the principle of sexual reproduction. The genetic diversity is further enhanced by exchange of genetic material between homologous chromosomes by the crossover mechanism. This mechanism not only requires correct pairing of homologous chromosomes but also efficient repair of the induced DNA double-strand breaks. Oocytes have evolved a unique quality control system that eliminates cells if chromosomes do not correctly align or if DNA repair is not possible. Central to this monitoring system that is conserved from nematodes and fruit fly to humans is the p53 protein family, and in vertebrates in particular p63. In mammals, oocytes are stored for a long time in the prophase of meiosis I which, in humans, can last more than 50 years. During the entire time of this arrest phase, the DNA damage checkpoint remains active. The treatment of female cancer patients with DNA damaging irradiation or chemotherapeutics activates this checkpoint and results in elimination of the oocyte pool causing premature menopause and infertility. Here, we review the molecular mechanisms of this quality control system and discuss potential therapeutic intervention for the preservation of the oocyte pool during chemotherapy.
An Insight into the Mechanism of Holamine- and Funtumine-Induced Cell Death in Cancer Cells
Authors: Badmus Jelili A. , Ekpo Okobi E. , Sharma Jyoti R. , Sibuyi Nicole Remaliah S. , Meyer Mervin , Hussein Ahmed A. , Hiss Donavon C.
Published: December 2020

Holamine and funtumine, steroidal alkaloids with strong and diverse pharmacological activities are commonly found in the Apocynaceae family of Holarrhena. The selective anti-proliferative and cell cycle arrest effects of holamine and funtumine on cancer cells have been previously reported. The present study evaluated the anti-proliferative mechanism of action of these two steroidal alkaloids on cancer cell lines (HT-29, MCF-7 and HeLa) by exploring the mitochondrial depolarization effects, reactive oxygen species (ROS) induction, apoptosis, F-actin perturbation, and inhibition of topoisomerase-I. The apoptosis-inducing effects of the compounds were studied by flow cytometry using the APOPercentageTM dye and Caspase-3/7 Glo assay kit. The two compounds showed a significantly greater cytotoxicity in cancer cells compared to non-cancer (normal) fibroblasts. The observed antiproliferative effects of the two alkaloids presumably are facilitated through the stimulation of apoptosis. The apoptotic effect was elicited through the modulation of mitochondrial function, elevated ROS production, and caspase-3/7 activation. Both compounds also induced F-actin disorganization and inhibited topoisomerase-I activity. Although holamine and funtumine appear to have translational potential for the development of novel anticancer agents, further mechanistic and molecular studies are recommended to fully understand their anticancer effects.
Antioxidative, Antiapoptotic, and Anti-Inflammatory Effects of Apamin in a Murine Model of Lipopolysaccharide-Induced Acute Kidney Injury
Authors: Kim Jung-Yeon , Leem Jaechan , Park Kwan-Kyu
Published: December 2020

Sepsis is the major cause of acute kidney injury (AKI) in severely ill patients, but only limited therapeutic options are available. During sepsis, lipopolysaccharide (LPS), an endotoxin derived from bacteria, activates signaling cascades involved in inflammatory responses and tissue injury. Apamin is a component of bee venom and has been shown to exert antioxidative, antiapoptotic, and anti-inflammatory activities. However, the effect of apamin on LPS-induced AKI has not been elucidated. Here, we show that apamin treatment significantly ameliorated renal dysfunction and histological injury, especially tubular injury, in LPS-injected mice. Apamin also suppressed LPS-induced oxidative stress through modulating the expression of nicotinamide adenine dinucleotide phosphate oxidase 4 and heme oxygenase-1. Moreover, tubular cell apoptosis with caspase-3 activation in LPS-injected mice was significantly attenuated by apamin. Apamin also inhibited cytokine production and immune cell accumulation, suppressed toll-like receptor 4 pathway, and downregulated vascular adhesion molecules. Taken together, these results suggest that apamin ameliorates LPS-induced renal injury through inhibiting oxidative stress, apoptosis of tubular epithelial cells, and inflammation. Apamin might be a potential therapeutic option for septic AKI.
Rcs Phosphorelay Responses to Truncated Lipopolysaccharide-Induced Cell Envelope Stress in Yersinia enterocolitica
Authors: Meng Jiao , Xu Junhong , Huang Can , Chen Jingyu
Published: December 2020

Lipopolysaccharide (LPS) is the major component of the outer membrane of Gram-negative bacteria, and its integrity is monitored by various stress response systems. Although the Rcs system is involved in the envelope stress response and regulates genes controlling numerous bacterial cell functions of Yersinia enterocolitica, whether it can sense the truncated LPS in Y. enterocolitica remains unclear. In this study, the deletion of the Y. enterocolitica waaF gene truncated the structure of LPS and produced a deep rough LPS. The truncated LPS increased the cell surface hydrophobicity and outer membrane permeability, generating cell envelope stress. The truncated LPS also directly exposed the smooth outer membrane to the external environment and attenuated the resistance to adverse conditions, such as impaired survival under polymyxin B and sodium dodecyl sulfate (SDS) exposure. Further phenotypic experiment and gene expression analysis indicated that the truncated LPS was correlated with the activation of the Rcs phosphorelay, thereby repressing cell motility and biofilm formation. Our findings highlight the importance of LPS integrity in maintaining membrane function and broaden the understanding of Rcs phosphorelay signaling in response to cell envelope stress, thus opening new avenues to develop effective antimicrobial agents for combating Y. enterocolitica infections.
ab-Initio Study of Hydrogen Bond Networks in 1,2,3-Triazole Phases
Authors: Peschel Christopher , Dreßler Christian , Sebastiani Daniel
Published: December 2020

The research in storage and conversion of energy is an everlasting process. The use of fuel cells is very tempting but up to now there are still several conceptual challenges to overcome. Especially, the requirement of liquid water causes difficulties due to the temperature limit. Therefore, imidazoles and triazoles are increasingly investigated in a manifold of experimental and theoretical publications as they are both very promising in overcoming this problem. Recently, triazoles were found to be superior to imidazoles in proton conduction. An ab-initio molecular dynamics simulation of pure triazole phases for investigating the behavior of both tautomer species of the triazole molecule has never been done. In this work, we investigate the structural and dynamical properties of two different solid phases and the liquid phase at two different temperatures. We are able to show how the distinct tautomers contribute to the mechanism of proton conduction, to compute dynamical properties of the four systems and to suggest a mechanism of reorientation in solid phase.
The Cost of Production in Elicitation Studies and the Legacy Bias-Consensus Trade off
Authors: Williams Adam S. , Garcia Jason , De Zayas Fernando , Hernandez Fidel , Sharp Julia , Ortega Francisco R.
Published: December 2020

Gesture elicitation studies are a popular means of gaining valuable insights into how users interact with novel input devices. One of the problems elicitation faces is that of legacy bias, when elicited interactions are biased by prior technologies use. In response, methodologies have been introduced to reduce legacy bias. This is the first study that formally examines the production method of reducing legacy bias (i.e., repeated proposals for a single referent). This is done through a between-subject study that had 27 participants per group (control and production) with 17 referents placed in a virtual environment using a head-mounted display. This study found that over a range of referents, legacy bias was not significantly reduced over production trials. Instead, production reduced participant consensus on proposals. However, in the set of referents that elicited the most legacy biased proposals, production was an effective means of reducing legacy bias, with an overall reduction of 11.93% for the chance of eliciting a legacy bias proposal.
Synthesis of Microporous Mo2C-W2C Binary Carbides by Thermal Decomposition of Molybdenum-Tungsten Blues
Authors: Gavrilova Natalia , Myachina Maria , Dyakonov Victor , Nazarov Victor , Skudin Valery
Published: December 2020

Molybdenum and tungsten carbides are perspective catalytic systems. Their activity in many reactions is comparable to the activity of platinum group metals. The development of the synthesis method for of highly dispersed binary molybdenum and tungsten carbides is an important task. Dispersions of molybdenum-tungsten blue were used as a precursor for synthesis of binary molybdenum and tungsten carbides. The synthesis of carbides was carried out by thermal decomposition of molybdenum-tungsten blue xerogels in an inert atmosphere. The binary carbides were characterized by XRD, TGA, SEM and nitrogen adsorption. The influence of the molar ratio reducing agent/Me [R]/[ΣMe], molar ratio molybdenum/tungsten [Mo]/[W] on phase composition, and morphology and porous structure of binary carbides was investigated. Samples of binary molybdenum and tungsten carbides with a highly developed porous structure and a specific surface area were synthesized.
Fabrication of Anisotropic Cu Ferrite-Polymer Core-Shell Nanoparticles for Photodynamic Ablation of Cervical Cancer Cells
Authors: Kuo Shuo-Hsiu , Wu Po-Ting , Huang Jing-Yin , Chiu Chin-Pao , Yu Jiashing , Liao Mei-Yi
Published: December 2020

In this work we developed methylene blue-immobilized copper-iron nanoparticles (MB-CuFe NPs) through a facile one-step hydrothermal reaction to achieve a better phototherapeutic effect. The Fe/Cu ratio of the CuFe NPs was controllable by merely changing the loading amount of iron precursor concentration. The CuFe NPs could serve as a Fenton catalyst to convert hydrogen peroxide (H2O2) into reactive oxygen species (ROS), while the superparamagnetic properties also suggest magnetic resonance imaging (MRI) potential. Furthermore, the Food and Drug Administration (FDA)-approved MB photosensitizer could strongly adsorb onto the surface of CuFe NPs to facilitate the drug delivery into cells and improve the photodynamic therapy at 660 nm via significant generation of singlet oxygen species, leading to enhanced cancer cell-damaging efficacy. An MTT (thiazolyl blue tetrazolium bromide) assay proved the low cytotoxicity of the CuFe NPs to cervical cancer cells (HeLa cells), namely above 80% at 25 ppm of the sample dose. A slight dissolution of Cu and Fe ions from the CuFe NPs in an acidic environment was obtained, providing direct evidence for CuFe NPs being degradable without the risk of long-term retention in the body. Moreover, the tremendous photo-to-thermal conversion of CuFe NPs was examined, which might be combined with photodynamic therapy (PDT) for promising development in the depletion of cancer cells after a single pulse of deep-red light irradiation at high laser power.
Plasticity of the Root System Architecture and Leaf Gas Exchange Parameters Are Important for Maintaining Bottle Gourd Responses under Water Deficit
Authors: Zacarias Rafael Dinoclaudio , Arriagada Osvin , Toro Guillermo , Mashilo Jacob , Mora-Poblete Freddy , Contreras-Soto Rodrigo Iván
Published: December 2020

The evaluation of root system architecture (RSA) development and the physiological responses of crop plants grown under water-limited conditions are of great importance. The purpose of this study was to examine the short-term variation of the morphological and physiological plasticity of Lagenaria siceraria genotypes under water deficit, evaluating the changes in the relationship between the root system architecture and leaf physiological responses. Bottle gourd genotypes were grown in rhizoboxes under well-watered and water deficit conditions. Significant genotype-water regime interactions were observed for several RSA traits and physiological parameters. Biplot analyses confirmed that the drought-tolerant genotypes (BG-48 and GC) showed a high net CO2 assimilation rate, stomatal conductance, transpiration rates with a smaller length, and a reduced root length density of second-order lateral roots, whereas the genotypes BG-67 and Osorno were identified as drought-sensitive and showed greater values for average root length and the density of second-order lateral roots. Consequently, a reduced length and density of lateral roots in bottle gourd should constitute a response to water deficit. The root traits studied here can be used to evaluate bottle gourd performance under novel water management strategies and as criteria for breeding selection.
The Versatile Roles of Sulfur-Containing Biomolecules in Plant Defense—A Road to Disease Resistance
Authors: Künstler András , Gullner Gábor , Ádám Attila L. , Kolozsváriné Nagy Judit Kolozsváriné , Király Lóránt
Published: December 2020

Sulfur (S) is an essential plant macronutrient and the pivotal role of sulfur compounds in plant disease resistance has become obvious in recent decades. This review attempts to recapitulate results on the various functions of sulfur-containing defense compounds (SDCs) in plant defense responses to pathogens. These compounds include sulfur containing amino acids such as cysteine and methionine, the tripeptide glutathione, thionins and defensins, glucosinolates and phytoalexins and, last but not least, reactive sulfur species and hydrogen sulfide. SDCs play versatile roles both in pathogen perception and initiating signal transduction pathways that are interconnected with various defense processes regulated by plant hormones (salicylic acid, jasmonic acid and ethylene) and reactive oxygen species (ROS). Importantly, ROS-mediated reversible oxidation of cysteine residues on plant proteins have profound effects on protein functions like signal transduction of plant defense responses during pathogen infections. Indeed, the multifaceted plant defense responses initiated by SDCs should provide novel tools for plant breeding to endow crops with efficient defense responses to invading pathogens.
Review of Novel and Emerging Proximal Soil Moisture Sensors for Use in Agriculture
Authors: Hardie Marcus
Published: December 2020

The measurement of soil moisture in agriculture is currently dominated by a small number of sensors, the use of which is greatly limited by their small sampling volume, high cost, need for close soil–sensor contact, and poor performance in saline, vertic and stony soils. This review was undertaken to explore the plethora of novel and emerging soil moisture sensors, and evaluate their potential use in agriculture. The review found that improvements to existing techniques over the last two decades are limited, and largely restricted to frequency domain reflectometry approaches. However, a broad range of new, novel and emerging means of measuring soil moisture were identified including, actively heated fiber optics (AHFO), high capacity tensiometers, paired acoustic / radio / seismic transceiver approaches, microwave-based approaches, radio frequency identification (RFID), hydrogels and seismoelectric approaches. Excitement over this range of potential new technologies is however tempered by the observation that most of these technologies are at early stages of development, and that few of these techniques have been adequately evaluated in situ agricultural soils.
Smart Economy and Startup Enterprises in the Visegrád Countries—A Comparative Analysis Based on the Crunchbase Database
Authors: Kézai Petra Kinga , Fischer Szabolcs , Lados Mihály
Published: December 2020

The present study seeks to explore the concept of “smart economy” through the definition of the smart city. It also presents smart city subsystems and the smart city model. It focuses on smart and creative startups within the smart city model. The research examines medium-sized cities in the Visegrád countries (Czech Republic, Slovakia, Poland, Hungary) with a population ranging from 100,000 to 1 million inhabitants for startups. The research question is: Where are the medium-sized cities in the Visegrád countries that are both startup centers and smart cities? In the course of the research, the term “smart cities” was based on the definition set by the European Commission and the definition of startup centers was made using data analysis of the American Crunchbase database. As a result of the two studies, it can be concluded that there are no cities in the Visegrád countries with an above average level of both startup presence and smart cities.
Pteris vittata Arsenic Accumulation Only Partially Explains Soil Arsenic Depletion during Field-Scale Phytoextraction
Authors: Matzen Sarick , Fakra Sirine , Nico Peter , Pallud Céline
Published: December 2020

Soil arsenic heterogeneity complicates our understanding of phytoextraction rates during arsenic phytoextraction with Pteris vittata, including in response to rate stimulation with nutrient treatments. In a 58-week arsenic phytoextraction field study, we determined the effects of soil arsenic concentrations, fertilizer application, and mycorrhizal fungi inoculation on P. vittata arsenic uptake rates, soil arsenic depletion, and arsenic soil–plant mass balances. Initial soil arsenic concentrations were positively correlated with arsenic uptake rates. Soil inoculation with mycorrhizal fungus Funneliformis mosseae led to 1.5–2 times higher fern aboveground biomass. Across all treatments, ferns accumulated a mean of 3.6% of the initial soil arsenic, and mean soil arsenic concentrations decreased by up to 44%. At depths of 0–10 cm, arsenic accumulation in P. vittata matched soil arsenic depletion. However, at depths of 0–20 cm, fern arsenic accumulation could not account for 61.5% of the soil arsenic depletion, suggesting that the missing arsenic could have been lost to leaching. A higher fraction of arsenic (III) (12.8–71.5%) in the rhizosphere compared to bulk soils suggests that the rhizosphere is a distinct geochemical environment featuring processes that could solubilize arsenic. To our knowledge, this is the first mass balance relating arsenic accumulation in P. vittata to significant decreases in soil arsenic concentrations under field conditions.
Neuromuscular exercise for chronic musculoskeletal pain in older people: a randomised controlled trial in primary care in Hong Kong
Authors: Sit Regina Wing Shan , Choi Shirley Yue Kwan , Wang Bo , Chan Dicken Cheong Chun , Zhang Dexing , Yip Benjamin Hon Kei , Wong Samuel Yeung Shan
Published: December 2020

Background

Exercise therapy is commonly prescribed by primary care physicians (PCPs) in the management of chronic musculoskeletal (MSK) pain.

Aim

To evaluate the clinical effectiveness of a supervised neuromuscular (NM) exercise programme in older people with chronic MSK pain.

Design and setting

This was a 12-week, two-arm, randomised controlled trial comparing 6 weeks of supervised NM exercise versus waiting list controls. The authors enrolled 72 participants with chronic MSK pain at seven public primary care clinics.

Method

Participants were randomly allocated in block sizes of 12 to the NM (n = 36) and control groups (n = 36) in a 1:1 ratio. Data were collected at baseline, 6, and 12 weeks. The primary outcome was the Brief Pain Inventory (BPI) pain severity score at 6 weeks post-intervention. Secondary outcomes included the BPI interference score; Pain Self-Efficacy Questionnaire (PSEQ), Short Form Health Survey (SF-12), 7-item Generalised Anxiety Disorder (GAD-7), and 9-item Patient Health Questionnaire (PHQ-9) scores; and functional measurements using the Timed-Up- and-Go test and handgrip strength.

Results

At 6 weeks, the NM group demonstrated a significantly greater improvement in the BPI pain severity score (between-group difference = −1.27; 95% confidence interval [CI] = −2.08 to −0.45; P<0.01), PSEQ (between-group difference = 6.5; 95% CI = 2.22 to 10.77; P<0.01), and SF-12 physical scores (between-group difference = 3.4; 95% CI = 0.05 to 6.75; P<0.05) compared with the control group. Statistically significant overall trends of improvement were also observed for the BPI interference and PHQ-9 scores.

Conclusion

NM exercise has the potential to reduce pain and improve self-efficacy and physical function in older people with chronic MSK pain. It can be an option for PCPs in exercise prescriptions.
Правове виховання в управлінській діяльності
Authors: Хаварівська Г. С.
Published: December 2020

Розглянуто поняття, зміст, суб’єкти та об’єкт правового виховання. Охарактеризовано його мету та забезпечення правовиховного впливу в управлінській діяльності державних службовців. Визначено кризові умови, які безпосередньо впливають на процес правового виховання та розглянуто завдання і напрями оптимізації правового виховання в сучасних умовах.