bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy Efficiency Policies to Face Buildings’ Climate Change Effects in Paraguay
Authors: Silvero Fabiana , Rodrigues Fernanda , Montelpare Sergio
Published: June 2020

Nowadays, the importance of implementing energy efficiency (EE) measures is growing significantly worldwide, based on its potential to reduce energy demands and mitigate climate change effects. Paraguay is a developing country with the highest per capita hydroelectric energy generation in the world, but only 18% of local consumption is hydroelectric and 41% of its energy matrix corresponds to oil products. This paper aims to analyse the importance the Country places on EE as a strategy towards sustainable development and to highlight as EE is an effective pathway to mitigate the climate changes and contrast their effects. The authors initially provide an insight into the climate scenarios for Paraguay and underline the effects of the climate changes on the buildings’ comfort. Subsequently, the authors provide, by resourcing a bibliographic review, a description of the Paraguayan sectors of greater energy consumption, its policies and targets set for increasing EE. Besides, the main EE projects developed by other neighbouring South American countries are analysed to show the level of development of each one in the scope of EE and to offer a reference basis of potential virtuous solutions to be adopted in Paraguay. A focus on the building sector is also made to provide a foundation for policy analyses to enhance EE in this sector. As a result of this review, evidence that EE is beginning to take part in Paraguay’s public policies was found, with the leaders becoming aware of its importance. Nevertheless, many concrete results could not be achieved as of yet and overcoming these barriers still involve a great challenge. Regarding the building sector, few advances have been noticed regarding the regulations of buildings’ thermal performance, a reason for which the National objectives set need to be more specific to achieve greater collective awareness to enforce them. Finally, key actions are recommended for Paraguay aiming to improve EE levels to face the climate change phenomenon.
Carbonation Process of Reinforced Concrete Beams under the Combined Effects of Fatigue Damage and Environmental Factors
Authors: Song Li , Liu Jin-liang , Cui Chen-xing , Yu Zhi-wu , Fan Zhi-wei , Hou Jian
Published: June 2020

The carbonation process of reinforced concrete (RC) beams considering the combined effect of fatigue load and environmental factors was investigated experimentally in an environmental simulation chamber based on meteorological environmental data. Fourteen beams were constructed and tested, and a carbonation numerical model (CNM) considering medium transport and fatigue damage characteristics was proposed to simulate the carbonation process of RC beams. Based on the experimental results, CNM is extended to reveal the effects of ambient temperature, relative humidity, carbon dioxide concentration, and fatigue damage on the carbonation process of RC beams. The results showed that the change in the pore structure of concrete can directly and accurately characterize the effect of fatigue damage on the transport characteristics of concrete. The porosity of concrete substantially increased with increasing levels of fatigue damage. Although fatigue damage did not have a significant effect on the most probable pore radius of the concrete, the total pore volume of the most probable pore notably increased. The results showed that both the carbonation depth and fatigue damage exhibit a three-stage development law. The depth and rate of carbonation are related to concrete pores and macroscopic cracks. In the carbonation analysis of fatigue-damaged RC beams, the changes in both the pore structure and fatigue cracks caused by repeated fatigue loading on carbonation should be considered.
Photodynamic Properties of CdSe/CdS Quantum Dots in Intracellular Media
Authors: Nguyen Thanh Binh , Vu Thi Bich , Nguyen Dinh Cong , Do Thi Thao , Pham Hong Minh , Cadatal-Raduban Marilou
Published: June 2020

CdSe/CdS quantum dots (QDs) were seeded into Jurkat cells using polyethylene glycol (PEG-1500) at different treatment times. Fluorescence microscopy images show that some QDs stick to the surface of the cells, while others appeared to be inside the cells. As it is difficult to ascertain whether the QDs are indeed inside the cells or just behind the cells, additional spectroscopic studies were performed. Photoluminescence spectra show that the fluorescence intensities of the CdSe/CdS QDs are different between samples at different treatment times. Interestingly, the fluorescence lifetimes are also different. This confirms the interaction between the CdSe/CdS QDs and the intracellular media and that the QDs were successfully seeded into the cells.
How IoT Can Integrate Biotechnological Approaches for City Applications—Review of Recent Advancements, Issues, and Perspectives
Authors: Gotovtsev Pavel
Published: June 2020

There are a number of significant changes taking place in modern city development and most of them are based on the number of recent technological progress. This paper provides a review and analysis of recent approaches of biotechnology that can find a place in today’s cities and discusses how those technologies can be integrated into a city’s Internet of Things (IoT). Firstly, several biotechnologies that focus on rain gardens, urban vertical farming systems, and city photobioreactors are discussed in the context of their integration in a city’s IoT. The next possible application of biofuel cells to the sensor network’s energy supply is discussed. It is shown that such devices can influence the low-power sensor network structure as an additional energy source for transmitters. This paper shows the possibility of bioelectrochemical biosensor applications, discusses self-powered biosensors, and shows that such a system can be widely applied to rainwater monitoring in rain gardens and green streets. Significant attention is paid to recent approaches in synthetic biology. Both cell-based biosensors and bioactuators with synthetic genetic circuits are discussed. The development of cell-based biosensors can significantly enhance the sensing possibilities of a city’s IoT. We show the possible ways to develop cyber-physical systems (CPSs) with the systems mentioned above. Aspects of data handling for the discussed biotechnologies and the methods of intelligent systems, including those that are machine learning-based, applied to the IoT in a city are presented.
Machining Accuracy Enhancement of a Machine Tool by a Cooling Channel Design for a Built-in Spindle
Authors: Li Kun-Ying , Luo Win-Jet , Wei Shih-Jie
Published: June 2020

This study presents a multiphysics simulation analysis that was performed for the cooling channel of a built-in spindle. The design of experiments (DOE) method was employed to optimize the dimension of the cooling channel, and a practical machining experiment was performed to validate the effect of the design. In terms of the temperature, pressure drop, thermal deformation, manufacturing cost, and initial cost considerations, the paralleling type cooling channel of the front bearing and the helical type cooling channel of the motor were adopted in the study. After the optimal design of the cooling channel was applied, the bearing temperature was reduced by a maximum decrease of 6.7 °C, the spindle deformation decreased from 53.8 μm to 30.9 μm, and the required operational time for attaining the steady state of the machine tool was shortened from 185.3 min to 132.6 min. For the machining validation, the spindle with the optimal cooling channel design was employed for vehicle part machining, the flatness of the finished workpiece was increased by 61.3%, and the surface roughness (Ra) was increased by 52%. According to the findings for the optimal cooling channel, when the spindle cooling efficiency is increased by the optimal cooling channel design, the thermal deformation and warm-up period can be reduced effectively, and the machining precision can be enhanced. This method is an efficient way to increase the accuracy of a machine tool.
Investigation of Zero Moment Point in a Partially Filled Liquid Vessel Subjected to Roll Motion
Authors: Usman Muhammad , Sajid Muhammad , Uddin Emad , Ayaz Yasar
Published: June 2020

Liquid-handling robots are designed to dispense sub-microliter quantities of fluids for applications including laboratory tests. When larger amounts of liquids are involved, sloshing must be considered as a parameter affecting stability, which is of significance for autonomous vehicles. The measurement and quantification of slosh in enclosed volumes poses a challenge to researchers who have traditionally resorted to tracking the air–liquid interface for two-phase flow analysis. There is a need for a simpler method to predict rollover in these applications. In this work, a novel solution to address this problem is proposed in the form of the Zero Moment Point (ZMP) of a dynamic liquid region. Computational experiments of a partially filled, two-dimensional liquid vessel were carried out using the Volume of Fluid (VOF) method in a finite volume based open-source computational fluid dynamics solver. The movement of the air–liquid interface was tracked, while the Center of Mass and the resulting Zero Moment Point were determined from the numerical simulations at each time step. The computational model was validated by comparing the wall pressure and movement of the liquid-free surface to experimentally obtained values. It was concluded that for a dynamic liquid domain, the Zero Moment Point can be instrumental in determining the stability of partially filled containers subjected to sloshing.
Towards Sustainable Neighborhoods in Europe: Mitigating 12 Environmental Impacts by Successively Applying 8 Scenarios
Authors: Kameni Nematchoua Modeste , Sevin Matthieu , Reiter Sigrid
Published: June 2020

The purpose of this research is to determine the most impactful and important source of environmental change at the neighborhood level. The study of multiple scenarios allows us to determine the influence of several parameters on the results of the life cycle analysis of the neighborhood. We are looking at quantifying the impact of orientation, storm water management, density, mobility and the use of renewable energies on the environmental balance sheet of a neighborhood, based on eleven environmental indicators. An eco-neighborhood, located in Belgium, has been selected as the modeling site. The results show that the management of mobility is the parameter that can reduce the impact the most, in terms of greenhouse effect, odor, damage to biodiversity and health. With the adaptation of photovoltaic panels on the site, the production exceeds the consumption all through the year, except for the months of December and January, when the installation covers 45% and 75% of the consumption, respectively. Increasing the built density of the neighborhood by roof stacking allows the different environmental impacts, calculated per inhabitant, to be homogeneously minimized.
Energy Efficiency, Thermal Comfort, and Heritage Conservation in Residential Historic Buildings as Dynamic and Systemic Socio-Cultural Practices
Authors: Fouseki Kalliopi , Newton David , Murillo Camacho Krisangella Sofia , Nandi Sohini , Koukou Theodora
Published: June 2020

With buildings being responsible for nearly a quarter of global greenhouse gas emissions, intensive building decarbonization programs are in place worldwide, with unintended consequences for historic buildings. To this end, national and international guidance on energy efficiency for historic buildings advocate for the adoption of a ‘whole house approach’ that integrates heritage values in energy efficiency plans. Most guidance, though, relies on non-evidence based, pre-assumptions of residents’ heritage values. And yet, unless we understand how and why residents negotiate their decisions between energy efficiency, thermal comfort, and heritage conservation, such guidance will not be applicable. Despite the urgency to decarbonize the building stock, research on how inhabitants of old buildings make such decisions is extremely limited. It is also case-study specific, often lacking the required depth. To address this gap, this paper offers the first international, in-depth study on the topic. It does so through a rigorous double-coded, thematic analysis of 59 in-depth semi-structured interviews (totaling 206,771 words) carried out in Greece, Mexico, and the UK. The thematic analysis is combined with system dynamic analysis, essential for unveiling what parameters affect inhabitants’ decisions over time. Drawing on theories on the dynamics of social practices, we conclude that the process of decision-making on energy efficiency, thermal comfort improvement, and heritage conservation is a socio-cultural, dynamic practice, the change and continuation of which depends on how the following elements are connected or disconnected: materials (e.g., original features), competencies (e.g., restoration skills), resources (e.g., costs), values, space/environment (e.g., natural light), senses (e.g., thermal comfort), and time (e.g., years living in the house). The connection or disconnection of those elements will depend on (a) the nature of the context (e.g., rural, urban, conservation area); (b) the listing status; (c) age and construction materials of building; (d) local climate; and (e) ownership status.
Effectivity and Cost Efficiency of a Tax on Nitrogen Fertilizer to Reduce GHG Emissions from Agriculture
Authors: Meyer-Aurich Andreas , Karatay Yusuf Nadi , Nausediene Ausra , Kirschke Dieter
Published: June 2020

The use of nitrogen (N) fertilizer substantially contributes to greenhouse gas (GHG) emissions due to N2O emissions from agricultural soils and energy-intensive fertilizer manufacturing. Thus, a reduction of mineral N fertilizer use can contribute to reduced GHG emissions. Fertilizer tax is a potential instrument to provide incentives to apply less fertilizer and contribute to the mitigation of GHG emissions. This study provides model results based on a production function analysis from field experiments in Brandenburg and Schleswig-Holstein, with respect to risk aversion by calculating certainty equivalents for different levels of risk aversion. The model results were used to identify effective and cost-efficient options considering farmers’ risk aversion to reduce N fertilizer, and to compare the potential and cost of GHG mitigation with different N fertilizer tax schemes. The results show that moderate N tax levels are effective in reducing N fertilizer levels, and thus, in curbing GHG emissions at costs below 100 €/t CO2eq for rye, barley and canola. However, in wheat production, N tax has limited effects on economically optimal N use due to the effects of N fertilizer on crop quality, which affect the sale prices of wheat. The findings indicate that the level of risk aversion does not have a consistent impact on the reduction of N fertilizer with a tax, even though the level of N fertilizer use is generally lower for risk-averse agents. The differences in N fertilizer response might have an impact on the relative advantage of different crops, which should be taken into account for an effective implementation of a tax on N fertilizer.
Assessment of Total Climate Change Impacts on the Agricultural Sector of Cyprus
Authors: Papadaskalopoulou Christina , Moriondo Marco , Lemesios Ioannis , Karali Anna , Konsta Angeliki , Dibari Camilla , Brilli Lorenzo , Varotsos Konstantinos V. , Stylianou Andreas , Loizidou Maria , Markou Marinos , Giannakopoulos Christos
Published: June 2020

In this paper, the results of a climate change impact and vulnerability assessment conducted for the agricultural sector of Cyprus are presented. The assessment is based on the outputs of specialized climatic and crop models, while it incorporates quantified socio-economic vulnerability indicators of the Cypriot agriculture. The results are aggregated at municipal level in order to support regional and local adaptation planning. The assessment was performed for two representative concentration pathways (RCP4.5, RCP8.5), as well as for extreme climatic scenarios. Following, an economic assessment was made on the expected change in revenues of the agricultural sector. The results of climatic simulations indicated that future increases in temperature will be characterized by a strong seasonal trend, with the highest increases occurring in summer. Precipitation is expected to decrease throughout the island, where the highest decreases (50%) are expected during summer (RCP8.5). This trend will affect mainly tomato, grapevine, and olive tree, whose growing cycle takes place during summer. By contrast, crops covering autumn-winter season, such as potato, barley, and wheat, are expected to partially avoid harsh summer conditions. The results of the economic assessment show that the changes in total revenues are insignificant, because, under all scenarios, a loss in one crop is compensated by a gain in another crop. However, the farmers as well as the government should take action to increase the resilience of the agricultural sector, with a special focus on those crops and areas that are expected to be adversely affected by climate change impacts.
Moisture Source Tagging Confirming the Polar Amplification Effect in Amplifying the Temperature-δ18O Temporal Slope Since the LGM
Authors: Guan Jian , Liu Zhengyu , Chen Guangshan
Published: June 2020

Stable water isotopologues in paleoclimate archives ( δ 18 O ) have been widely used as an indicator to derive past climate variations. The modern observed spatial δ 18 O -temperature relation in the middle and high latitudes has been used to infer the paleotemperatures changes from ice core data. However, various studies have shown that the spatial slope is larger than the temporal slope at the drill site by a factor of 2. Physically, the different spatial and temporal slope has been suggested to result from the amplified local surface air temperature cooling in the polar region at Last Glacial Maximum (LGM), according to the slope ratio equation derived in our previous study. To explicitly confirm the “polar amplification” effect in understanding the differences between temporal and spatial isotope–temperature relations, here we use the same isotope-enabled atmospheric general circulation model with a moisture-tracing module embedded to quantitatively estimate the contributions of different sources to the precipitated heavy oxygen isotopes in the middle and high latitudes. Our results show that the major sources of δ 18 O in precipitation over middle and high latitudes are from oceans where the sea surface temperature cooling at Last Glacial Maximum (LGM) is less than −2   ° C , while the local moisture sources with a higher cooling can be also relevant for polar regions, such as north Greenland. Additionally, the neglect of the strengthened local inversion layer strength at LGM could be the main cause for the overestimated source temperature cooling by the slope ratio equation, especially for the polar regions in the Northern Hemisphere.
Generalized Nabla Differentiability and Integrability for Fuzzy Functions on Time Scales
Authors: Leelavathi R. , Suresh Kumar G. , Agarwal Ravi P. , Wang Chao , Murty M.S.N.
Published: June 2020

This paper mainly deals with introducing and studying the properties of generalized nabla differentiability for fuzzy functions on time scales via Hukuhara difference. Further, we obtain embedding results on E n for generalized nabla differentiable fuzzy functions. Finally, we prove a fundamental theorem of a nabla integral calculus for fuzzy functions on time scales under generalized nabla differentiability. The obtained results are illustrated with suitable examples.
The “Social” Side of Big Data: Teaching BD Analytics to Political Science Students
Authors: Giacomello Giampiero , Preka Oltion
Published: June 2020

In an increasingly technology-dependent world, it is not surprising that STEM (Science, Technology, Engineering, and Mathematics) graduates are in high demand. This state of affairs, however, has made the public overlook the case that not only computing and artificial intelligence are naturally interdisciplinary, but that a huge portion of generated data comes from human–computer interactions, thus they are social in character and nature. Hence, social science practitioners should be in demand too, but this does not seem the case. One of the reasons for such a situation is that political and social science departments worldwide tend to remain in their “comfort zone” and see their disciplines quite traditionally, but by doing so they cut themselves off from many positions today. The authors believed that these conditions should and could be changed and thus in a few years created a specifically tailored course for students in Political Science. This paper examines the experience of the last year of such a program, which, after several tweaks and adjustments, is now fully operational. The results and students’ appreciation are quite remarkable. Hence the authors considered the experience was worth sharing, so that colleagues in social and political science departments may feel encouraged to follow and replicate such an example.
Regional Phenotypic Differences of the Opener Muscle in Procambarus clarkii: Sarcomere Length, Fiber Diameter, and Force Development
Authors: Holsinger Rachel C. , Cooper Robin L.
Published: June 2020

The opener muscle in the walking legs of the crayfish (Procambarus clarkii) has three distinct phenotypic regions although innervated by only one excitatory motor neuron. These regions (distal, central, and proximal) have varied biochemistry and physiology, including synaptic structure, troponin-T levels, fiber diameter, input resistance, sarcomere length, and force generation. The force generated by the central fibers when the excitatory neuron was stimulated at 40 Hz was more than the force generated by the other regions. This increase in force was correlated with the central fibers having longer sarcomeres when measured in a relaxed claw. These data support the idea that the central fibers are tonic-like and that the proximal fibers are phasic-like. The addition of serotonin directly on the fibers was hypothesized to increase the force generated by the central fibers more than in the other regions, but this did not occur at 40-Hz stimulation. We hypothesized that the central distal fibers would generate the most force due to the arrangement on the apodeme. This study demonstrates how malleable the motor unit is with modulation and frequency of stimulation.
An Acromegaly Disease Zebrafish Model Reveals Decline in Body Stem Cell Number along with Signs of Premature Aging
Authors: Elbialy Abdalla , Igarashi Yoji , Asakawa Shuichi , Watabe Shugo , Kinoshita Shigeharu
Published: June 2020

In our previous publication, it was shown that growth hormone (GH) excess in acromegaly affects the cell integrity of somatic cells through increased DNA damage throughout the body and impaired DNA repair pathways. Acromegaly is a hormone disorder pathological condition that develops as a result of growth hormone over-secretion from the pituitary gland. We produced a zebrafish acromegaly model to gain a better understanding of the excess GH effects at the cellular level. Here we show that the acromegaly zebrafish model progressively reduced the number of stem cells in different organs and increased oxidative stress in stem cells. Importantly, the decline in the stem cells was even more apparent than in aged fish. The controversy and debate over the use of GH as an anti-aging therapy have been going on for several years. In this study, excess GH induced aging signs such as increased senescence-associated (SA)-β-galactosidase staining of abdominal skin and similarity of the pattern of gene expression between aged and acromegaly zebrafish. Thus, this study highlights the role of excess GH in acromegaly stem cells.
Comparative Genomics Determines Strain-Dependent Secondary Metabolite Production in Streptomyces venezuelae Strains
Authors: Kim Woori , Lee Namil , Hwang Soonkyu , Lee Yongjae , Kim Jihun , Cho Suhyung , Palsson Bernhard , Cho Byung-Kwan
Published: June 2020

Streptomyces venezuelae is well known to produce various secondary metabolites, including chloramphenicol, jadomycin, and pikromycin. Although many strains have been classified as S. venezuelae species, only a limited number of strains have been explored extensively for their genomic contents. Moreover, genomic differences and diversity in secondary metabolite production between the strains have never been compared. Here, we report complete genome sequences of three S. venezuelae strains (ATCC 10712, ATCC 10595, and ATCC 21113) harboring chloramphenicol and jadomycin biosynthetic gene clusters (BGC). With these high-quality genome sequences, we revealed that the three strains share more than 85% of total genes and most of the secondary metabolite biosynthetic gene clusters (smBGC). Despite such conservation, the strains produced different amounts of chloramphenicol and jadomycin, indicating differential regulation of secondary metabolite production at the strain level. Interestingly, antagonistic production of chloramphenicol and jadomycin was observed in these strains. Through comparison of the chloramphenicol and jadomycin BGCs among the three strains, we found sequence variations in many genes, the non-coding RNA coding regions, and binding sites of regulators, which affect the production of the secondary metabolites. We anticipate that these genome sequences of closely related strains would serve as useful resources for understanding the complex secondary metabolism and for designing an optimal production process using Streptomyces strains.
IL-22 Promotes IFN-γ-Mediated Immunity against Histoplasma capsulatum Infection
Authors: Prado Morgana K.B. , Fontanari Caroline , Souza Camila O.S. , Gardinassi Luiz G. , Zoccal Karina F. , de Paula-Silva Francisco W.G. , Peti Ana P.F. , Sorgi Carlos A. , Meirelles Alyne F.G. , Ramos Simone G. , Alves-Filho José C. , Faccioli Lúcia H.
Published: June 2020

Histoplasma capsulatum is the agent of histoplasmosis, one of the most frequent mycoses in the world. The infection initiates with fungal spore inhalation, transformation into yeasts in the lungs and establishment of a granulomatous disease, which is characterized by a Th1 response. The production of Th1 signature cytokines, such as IFN-γ, is crucial for yeast clearance from the lungs, and to prevent dissemination. Recently, it was demonstrated that IL-17, a Th17 signature cytokine, is also important for fungal control, particularly in the absence of Th1 response. IL-22 is another cytokine with multiple functions on host response and disease progression. However, little is known about the role of IL-22 during histoplasmosis. In this study, we demonstrated that absence of IL-22 affected the clearance of yeasts from the lungs and increased the spreading to the spleen. In addition, IL-22 deficient mice (Il22−/−) succumbed to infection, which correlated with reductions in the numbers of CD4+ IFN-γ+ T cells, reduced IFN-γ levels, and diminished nitric oxide synthase type 2 (NOS2) expression in the lungs. Importantly, treatment with rIFN-γ mitigated the susceptibility of Il22−/− mice to H. capsulatum infection. These data indicate that IL-22 is crucial for IFN-γ/NO production and resistance to experimental histoplasmosis.
Chemical Diversity and Biological Activities of Essential Oils from Licaria, Nectrandra and Ocotea Species (Lauraceae) with Occurrence in Brazilian Biomes
Authors: Xavier Júlia Karla A. M. , Alves Nayara Sabrina F. , Setzer William N. , da Silva Joyce Kelly R.
Published: June 2020

Lauraceae species are known as excellent essential oil (EO) producers, and their taxa are distributed throughout the territory of Brazil. This study presents a systematic review of chemical composition, seasonal studies, occurrence of chemical profiles, and biological activities to EOs of species of Licaria, Nectandra, and Ocotea genera collected in different Brazilian biomes. Based on our survey, 39 species were studied, with a total of 86 oils extracted from seeds, leaves, stem barks, and twigs. The most representative geographic area in specimens was the Atlantic Forest (14 spp., 30 samples) followed by the Amazon (13 spp., 30 samples), Cerrado (6 spp., 14 samples), Pampa (4 spp., 10 samples), and Caatinga (2 spp., 2 samples) forests. The majority of compound classes identified in the oils were sesquiterpene hydrocarbons and oxygenated sesquiterpenoids. Among them, β-caryophyllene, germacrene D, bicyclogermacrene, caryophyllene oxide, α-bisabolol, and bicyclogermacrenal were the main constituents. Additionally, large amounts of phenylpropanoids and monoterpenes such as safrole, 6-methoxyelemicin, apiole, limonene, α-pinene, β-pinene, 1,8-cineole, and camphor were reported. Nectandra megatopomica showed considerable variation with the occurrence of fourteen chemical profiles according to seasonality and collection site. Several biological activities have been attributed to these oils, especially cytotoxic, antibacterial, antioxidant and antifungal potential, among other pharmacological applications.
Secondary Metabolites from Plants Possessing Inhibitory Properties against Beta-Amyloid Aggregation as Revealed by Thioflavin-T Assay and Correlations with Investigations on Transgenic Mouse Models of Alzheimer’s Disease
Authors: Stefanescu Raluca , Stanciu Gabriela Dumitriṭa , Luca Andrei , Paduraru Luminita , Tamba Bogdan-Ionel
Published: June 2020

Alzheimer’s disease is a neurodegenerative disorder for which there is a continuous search of drugs able to reduce or stop the cognitive decline. Beta-amyloid peptides are composed of 40 and 42 amino acids and are considered a major cause of neuronal toxicity. They are prone to aggregation, yielding oligomers and fibrils through the inter-molecular binding between the amino acid sequences (17–42) of multiple amyloid-beta molecules. Additionally, amyloid deposition causes cerebral amyloid angiopathy. The present study aims to identify, in the existing literature, natural plant derived products possessing inhibitory properties against aggregation. The studies searched proved the anti-aggregating effects by the thioflavin T assay and through behavioral, biochemical, and histological analysis carried out upon administration of natural chemical compounds to transgenic mouse models of Alzheimer’s disease. According to our present study results, fifteen secondary metabolites from plants were identified which presented both evidence coming from the thioflavin T assay and transgenic mouse models developing Alzheimer’s disease and six additional metabolites were mentioned due to their inhibitory effects against fibrillogenesis. Among them, epigallocatechin-3-gallate, luteolin, myricetin, and silibinin were proven to lower the aggregation to less than 40%.
Human Telomerase RNA: Telomerase Component or More?
Authors: Rubtsova Maria , Dontsova Olga
Published: June 2020

Telomerase is a ribonucleoprotein complex that maintains the lengths of telomeres. Most studies of telomerase function have focused on the involvement of telomerase activation in the immortalization of cancer cells and cellular rejuvenation. However, some studies demonstrated that the results do not meet expectations for telomerase action in telomere maintenance. Recent results give reason to think that major telomerase components—the reverse transcriptase protein subunit and telomerase RNA—may participate in many cellular processes, including the regulation of apoptosis and autophagy, cell survival, pro-proliferative effects, regulation of gene expression, and protection against oxidative stress. However, the difficulties faced by scientist when researching telomerase component functions often reduce confidence in the minor effects observed in experiments. In this review, we focus on the analysis of the functions of telomerase components (paying more attention to the telomerase RNA component), both as a complex and as independent components, providing effects that are not associated with telomerase activity and telomere length maintenance. Despite the fact that the data on alternative roles of telomerase components look illusory, it would be wrong to completely reject the possibility of their involvement in other biological processes excluded from research/discussion. Investigations to improve the understanding of every aspect of the functioning of telomerase components will provide the basis for a more precise development of approaches to regulate cellular homeostasis, which is important for carcinogenesis and aging.
Advances and Prospects of Phenolic Acids Production, Biorefinery and Analysis
Authors: Valanciene Egle , Jonuskiene Ilona , Syrpas Michail , Augustiniene Ernesta , Matulis Paulius , Simonavicius Andrius , Malys Naglis
Published: June 2020

Biotechnological production of phenolic acids is attracting increased interest due to their superior antioxidant activity, as well as other antimicrobial, dietary, and health benefits. As secondary metabolites, primarily found in plants and fungi, they are effective free radical scavengers due to the phenolic group available in their structure. Therefore, phenolic acids are widely utilised by pharmaceutical, food, cosmetic, and chemical industries. A demand for phenolic acids is mostly satisfied by utilising chemically synthesised compounds, with only a low quantity obtained from natural sources. As an alternative to chemical synthesis, environmentally friendly bio-based technologies are necessary for development in large-scale production. One of the most promising sustainable technologies is the utilisation of microbial cell factories for biosynthesis of phenolic acids. In this paper, we perform a systematic comparison of the best known natural sources of phenolic acids. The advances and prospects in the development of microbial cell factories for biosynthesis of these bioactive compounds are discussed in more detail. A special consideration is given to the modern production methods and analytics of phenolic acids.
PSIONplusm Server for Accurate Multi-Label Prediction of Ion Channels and Their Types
Authors: Gao Jianzhao , Wei Hong , Cano Alberto , Kurgan Lukasz
Published: June 2020

Computational prediction of ion channels facilitates the identification of putative ion channels from protein sequences. Several predictors of ion channels and their types were developed in the last quindecennial. While they offer reasonably accurate predictions, they also suffer a few shortcomings including lack of availability, parallel prediction mode, single-label prediction (inability to predict multiple channel subtypes), and incomplete scope (inability to predict subtypes of the voltage-gated channels). We developed a first-of-its-kind PSIONplusm method that performs sequential multi-label prediction of ion channels and their subtypes for both voltage-gated and ligand-gated channels. PSIONplusm sequentially combines the outputs produced by three support vector machine-based models from the PSIONplus predictor and is available as a webserver. Empirical tests show that PSIONplusm outperforms current methods for the multi-label prediction of the ion channel subtypes. This includes the existing single-label methods that are available to the users, a naïve multi-label predictor that combines results produced by multiple single-label methods, and methods that make predictions based on sequence alignment and domain annotations. We also found that the current methods (including PSIONplusm) fail to accurately predict a few of the least frequently occurring ion channel subtypes. Thus, new predictors should be developed when a larger quantity of annotated ion channels will be available to train predictive models.
Fibrinogen Glycation and Presence of Glucose Impair Fibrin Polymerization—An In Vitro Study of Isolated Fibrinogen and Plasma from Patients with Diabetes Mellitus
Authors: Luzak Boguslawa , Boncler Magdalena , Kosmalski Marcin , Mnich Ewelina , Stanczyk Lidia , Przygodzki Tomasz , Watala Cezary
Published: June 2020

Background: Fibrin formation and structure may be affected by a plethora of factors, including both genetic and posttranslational modifications, such as glycation, nitration or acetylation. Methods: The present study examines the effect of fibrinogen glycation on fibrin polymerization, measured in fibrinogen concentration-standardized plasma of subjects with type 2 diabetes mellitus (T2DM) and in a solution of human fibrinogen exposed to 30 mM glucose for four days. Results: The fibrin polymerization velocity (Vmax) observed in the T2DM plasma (median 0.0056; IQR 0.0049‒0.0061 AU/s) was significantly lower than in non-diabetic plasma (median 0.0063; IQR 0.0058‒0.0071 AU/s) (p < 0.05). Furthermore, significantly lower Vmax was observed for glucose-treated fibrinogen (Vmax 0.046; IQR 0.022‒0.085 AU/s) compared to control protein incubated with a pure vehicle (Vmax 0.053; IQR 0.034‒0.097 AU/s) (p < 0.05). The same tendency was observed in the fibrinogen samples supplemented with 6 mM glucose just before measurements. It is assumed that glucose may affect the ability of fibrinogen to form a stable clot in T2DM subjects, and that this impairment is likely to influence the outcomes of some diagnostic assays. As the example, the impaired clotting ability of glycated fibrinogen may considerably influence the results of the standard Clauss method, routinely used to determine fibrinogen concentration in plasma. The stoichiometric analysis demonstrated that spontaneous glycation at both the sites with high and low glycation potential clearly dominated in T2DM individuals in all fibrinogen chains.
Premna odorata: Seasonal Metabolic Variation in the Essential Oil Composition of Its Leaf and Verification of Its Anti-Ageing Potential via In Vitro Assays and Molecular Modelling
Authors: Altyar Ahmed E. , Ashour Mohamed L. , Youssef Fadia S.
Published: June 2020

The metabolic variation in the essential oil composition of Premna odorata leaves obtained from different seasons was quantitatively and qualitatively determined employing GC/MS (Gas Chromatography coupled with Mass Spectrometry) and GC/FID (Gas chromatography equipped with flame ionization detector) techniques. It displayed the existence of 97 constituents accounting for 94.19%, 92.27%, 91.95% and 92.63% for POS (spring), POM (summer), POA (autumn) and POW (winter) whole essential oils. β-Caryophyllene constituting the main metabolite in the oil in the different seasons. To better visualize the differences between them, GC data were exposed to chemometric analysis. A PCA (principal component analysis) score plot revealed the closeness of POS and POW. Molecular modelling on collagenase, elastase and hyaluronidase enzymes active centres shows that different compounds existing in the essential oil of Premna odorata leaves shows binding to the active sites with variable degrees that suggested its anti-ageing potential. Palmitic acid displayed the highest fitting for both the collagenase and elastase active centres in both pH-based and rule-based ionization methods with ∆G equals −78.27 and −44.77 kcal/mol, respectively; meanwhile, heptacosane showed the highest fitting score in the hyaluronidase centre with ∆G = −43.78 kcal/mol. In vitro assays consolidates the obtained modelling studies in which essential oil shows considerable anti-elastase and anti-hyaluronidase potential as evidenced by their IC50 values being 49.3 and 37.7 μg/mL, respectively; meanwhile, the essential oil of Premna odorata leaves displayed mild anti-collagenase potential. Thus, it can be concluded that Premna odorata could serve as a promising anti-ageing naturally occurring drug that could be effectively incorporated by pharmaceutical industries in cosmetics combating ageing and skin wrinkling.
Fibrillization of 40-residue β-Amyloid Peptides in Membrane-Like Environments Leads to Different Fibril Structures and Reduced Molecular Polymorphisms
Authors: Cheng Qinghui , Hu Zhi-Wen , Tobin-Miyaji Yuto , Perkins Amy E. , Deak Terrence , Qiang Wei
Published: June 2020

The molecular-level polymorphism in β-Amyloid (Aβ) fibrils have recently been considered as a pathologically relevant factor in Alzheimer’s disease (AD). Studies showed that the structural deviations in human-brain-seeded Aβ fibrils potentially correlated with the clinical histories of AD patients. For the 40-residue Aβ (Aβ40) fibrils derived from human brain tissues, a predominant molecular structure was proposed based on solid-state nuclear magnetic resonance (ssNMR) spectroscopy. However, previous studies have shown that the molecular structures of Aβ40 fibrils were sensitive to their growth conditions in aqueous environments. We show in this work that biological membranes and their phospholipid bilayer mimics serve as environmental factors to reduce the structural heterogeneity in Aβ40 fibrils. Fibrillization in the presence of membranes leads to fibril structures that are significantly different to the Aβ40 fibrils grown in aqueous solutions. Fibrils grown from multiple types of membranes, including the biological membranes extracted from the rats’ synaptosomes, shared similar ssNMR spectral features. Our studies emphasize the biological relevance of membranes in Aβ40 fibril structures and fibrillization processes.
Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging
Authors: Dahiya Rashmi , Mohammad Taj , Alajmi Mohamed F. , Rehman Md. Tabish , Hasan Gulam Mustafa , Hussain Afzal , Hassan Md. Imtaiyaz
Published: June 2020

Aging represents a significant biological process having strong associations with cancer, diabetes, and neurodegenerative and cardiovascular disorders, which leads to progressive loss of cellular functions and viability. Astonishingly, age-related disorders share several genetic and molecular mechanisms with the normal aging process. Over the last three decades, budding yeast Saccharomyces cerevisiae has emerged as a powerful yet simple model organism for aging research. Genetic approaches using yeast RLS have led to the identification of hundreds of genes impacting lifespan in higher eukaryotes. Numerous interventions to extend yeast lifespan showed an analogous outcome in multi-cellular eukaryotes like fruit flies, nematodes, rodents, and humans. We collected and analyzed a multitude of observations from published literature and provide the contribution of yeast in the understanding of aging hallmarks most applicable to humans. Here, we discuss key pathways and molecular mechanisms that underpin the evolutionarily conserved aging process and summarize the current understanding and clinical applicability of its trajectories. Gathering critical information on aging biology would pave the way for future investigation targeted at the discovery of aging interventions.
The Mutant p53-Driven Secretome Has Oncogenic Functions in Pancreatic Ductal Adenocarcinoma Cells
Authors: Butera Giovanna , Brandi Jessica , Cavallini Chiara , Scarpa Aldo , Lawlor Rita T. , Scupoli Maria Teresa , Marengo Emílio , Cecconi Daniela , Manfredi Marcello , Donadelli Massimo
Published: June 2020

The cancer secretome is a rich repository of useful information for both cancer biology and clinical oncology. A better understanding of cancer secretome is particularly relevant for pancreatic ductal adenocarcinoma (PDAC), whose extremely high mortality rate is mainly due to early metastasis, resistance to conventional treatments, lack of recognizable symptoms, and assays for early detection. TP53 gene is a master transcriptional regulator controlling several key cellular pathways and it is mutated in ~75% of PDACs. We report the functional effect of the hot-spot p53 mutant isoforms R175H and R273H on cancer cell secretome, showing their influence on proliferation, chemoresistance, apoptosis, and autophagy, as well as cell migration and epithelial-mesenchymal transition. We compared the secretome of p53-null AsPC-1 PDAC cells after ectopic over-expression of R175H-mutp53 or R273H-mutp53 to identify the differentially secreted proteins by mutant p53. By using high-resolution SWATH-MS technology, we found a great number of differentially secreted proteins by the two p53 mutants, 15 of which are common to both mutants. Most of these secreted proteins are reported to promote cancer progression and epithelial-mesenchymal transition and might constitute a biomarker secreted signature that is driven by the hot-spot p53 mutants in PDAC.
Possible Correlation between Cholinergic System Alterations and Neuro/Inflammation in Multiple Sclerosis
Authors: Gatta Valentina , Mengod Guadalupe , Reale Marcella , Tata Ada Maria
Published: June 2020

Multiple sclerosis (MS) is an autoimmune and demyelinating disease of the central nervous system. Although the etiology of MS is still unknown, both genetic and environmental factors contribute to the pathogenesis of the disease. Acetylcholine participates in the modulation of central and peripheral inflammation. The cells of the immune system, as well as microglia, astrocytes and oligodendrocytes express cholinergic markers and receptors of muscarinic and nicotinic type. The role played by acetylcholine in MS has been recently investigated. In the present review, we summarize the evidence indicating the cholinergic dysfunction in serum and cerebrospinal fluid of relapsing–remitting (RR)-MS patients and in the brains of the MS animal model experimental autoimmune encephalomyelitis (EAE). The correlation between the increased activity of the cholinergic hydrolyzing enzymes acetylcholinesterase and butyrylcholinesterase, the reduced levels of acetylcholine and the increase of pro-inflammatory cytokines production were recently described in immune cells of MS patients. Moreover, the genetic polymorphisms for both hydrolyzing enzymes and the possible correlation with the altered levels of their enzymatic activity have been also reported. Finally, the changes in cholinergic markers expression in the central nervous system of EAE mice in peak and chronic phases suggest the involvement of the acetylcholine also in neuro-inflammatory processes.
Metal Oxide Nanoparticles as Biomedical Materials
Authors: Nikolova Maria P. , Chavali Murthy S.
Published: June 2020

The development of new nanomaterials with high biomedical performance and low toxicity is essential to obtain more efficient therapy and precise diagnostic tools and devices. Recently, scientists often face issues of balancing between positive therapeutic effects of metal oxide nanoparticles and their toxic side effects. In this review, considering metal oxide nanoparticles as important technological and biomedical materials, the authors provide a comprehensive review of researches on metal oxide nanoparticles, their nanoscale physicochemical properties, defining specific applications in the various fields of nanomedicine. Authors discuss the recent development of metal oxide nanoparticles that were employed as biomedical materials in tissue therapy, immunotherapy, diagnosis, dentistry, regenerative medicine, wound healing and biosensing platforms. Besides, their antimicrobial, antifungal, antiviral properties along with biotoxicology were debated in detail. The significant breakthroughs in the field of nanobiomedicine have emerged in areas and numbers predicting tremendous application potential and enormous market value for metal oxide nanoparticles.