bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of Baikal Psychrophilic Actinobacteria for Synthesis of Biologically Active Natural Products from Sawdust Waste
Authors: Pereliaeva Ekaterina V. , Dmitrieva Maria E. , Morgunova Maria M. , Belyshenko Alexander Y. , Imidoeva Natalia A. , Ostyak Alexander S. , Axenov-Gribanov Denis V.
Published: May 2022

One of the relevant areas in microbiology and biotechnology is the study of microorganisms that induce the destruction of different materials, buildings, and machines and lead to negative effects. At the same time, the positive ecological effects of degradation can be explained by the detoxication of industrial and agricultural wastes, chemical substances, petroleum products, xenobiotics, pesticides, and other chemical pollutants. Many of these industrial wastes include hard-to-degrade components, such as lignocellulose or plastics. The biosynthesis of natural products based on the transformation of lignocellulosic wastes is of particular interest. One of the world’s unique ecosystems is presented by Lake Baikal. This ecosystem is characterized by the highest level of biodiversity, low temperatures, and a high purity of the water. Here, we studied the ability of several psychrophilic representatives of Baikal Actinobacteria to grow on sawdust wastes and transform them into bioactive natural products. Different strains of both widely spread genus of Actinobacteria and rare genera of Actinobacteria were tested. We used the LC-MS methods to show that Actinobacteria living in sawmill wastes can produce both known and novel natural products with antibiotic activity. We demonstrated that the type of sawmill wastes and their concentration influence the Actinobacteria biosynthetic potential. We have shown for the first time that the use of Baikal psychrophilic microorganisms as a factory for biodegradation is applicable for the transformation of lignocellulosic wastes. Thus, the development of techniques for screening novel natural products leads to an elaboration on the active ingredients for novel drugs.
New Results Involving Riemann Zeta Function Using Its Distributional Representation
Authors: Tassaddiq Asifa , Srivastava Rekha
Published: May 2022

The relation of special functions with fractional integral transforms has a great influence on modern science and research. For example, an old special function, namely, the Mittag–Leffler function, became the queen of fractional calculus because its image under the Laplace transform is known to a large audience only in this century. By taking motivation from these facts, we use distributional representation of the Riemann zeta function to compute its Laplace transform, which has played a fundamental role in applying the operators of generalized fractional calculus to this well-studied function. Hence, similar new images under various other popular fractional transforms can be obtained as special cases. A new fractional kinetic equation involving the Riemann zeta function is formulated and solved. Thereafter, a new relation involving the Laplace transform of the Riemann zeta function and the Fox–Wright function is explored, which proved to significantly simplify the results. Various new distributional properties are also derived.
(p(x),q(x))-Kirchhoff-Type Problems Involving Logarithmic Nonlinearity with Variable Exponent and Convection Term
Authors: Bu Weichun , An Tianqing , Qian Deliang , Li Yingjie
Published: May 2022

In the present article, we study a class of Kirchhoff-type equations driven by the (p(x),q(x))-Laplacian. Due to the lack of a variational structure, ellipticity, and monotonicity, the well-known variational methods are not applicable. With the help of the Galerkin method and Brezis theorem, we obtain the existence of finite-dimensional approximate solutions and weak solutions. One of the main difficulties and innovations of the present article is that we consider competing (p(x),q(x))-Laplacian, convective terms, and logarithmic nonlinearity with variable exponents, another one is the weaker assumptions on nonlocal term Mυ(x) and nonlinear term g.
Pilot Study of Polymerization Dynamics in nMAG Dose Gel
Authors: Merkis Mantvydas , Urbonavicius Benas Gabrielis , Adliene Diana , Laurikaitiene Jurgita , Puiso Judita
Published: May 2022

The essential component of modern radiation therapy is the application of steep dose gradients during patient treatment in order to maximize the radiation dose to the target volume and protect neighboring heathy tissues. However, volumetric dose distribution in an irradiated target is still a bottleneck of dose verification in modern radiotherapy. Dose gels are almost the only known dosimetry tool which allows for the evaluation of dose distribution in the irradiated volume due to gel’s polymerization upon irradiation. The accuracy of dose gel dosimetry has its own obstacle, which is related to the continuation of the gel’s polymerization after the radiation treatment procedure is finished. In this article, a method to monitor the polymerization dynamics of dose gels in real-time is proposed using a modified optical spectrometry system. Using the proposed method, the changes of the optical characteristics of irradiated nMAG dose gels in situ were assessed. The investigation revealed that the detectable polymerization in dose gel proceeds up to 6 h after irradiation. This time is significantly shorter compared with a commonly recommended 24 h waiting time allocated for polymer gel to settle. It was also found that dose rate significantly influences the temporal response of the nMAG dosimeter. By increasing the irradiation dose rate by a factor of 2, the time needed for the polymerization process to settle was increased by 22%. Identification of the gel’s post-irradiation polymerization time interval and its dependence on irradiation parameters will contribute to more accurate dose verification using dose gel dosimetry.
Temperature- and Salt-Resistant Micro-Crosslinked Polyampholyte Gel as Fluid-Loss Additive for Water-Based Drilling Fluids
Authors: Li Jian , Sun Jinsheng , Lv Kaihe , Ji Yuxi , Liu Jingping , Huang Xianbin , Bai Yingrui , Wang Jintang , Jin Jiafeng , Shi Shenglong
Published: May 2022

With increasing global energy consumption, oil/gas drilling has gradually expanded from conventional shallow reservoirs to deep and ultra-deep reservoirs. However, the harsh geological features including high temperature and high salinity in ultra-deep reservoirs have become a critical challenge faced by water-based drilling fluids (WDFs), which seriously deteriorate the rheology and fluid loss properties, causing drilling accidents, such as wellbore instability and formation collapse. In this study, a novel temperature- and salt-resistant micro-crosslinked polyampholyte gel was synthesized using N,N-dimethylacrylamide, diallyldimethyl ammonium chloride, 2-acrylamido-2-methylpropanesulfonic acid, maleic anhydride and chemical crosslinking agent triallylamine through free radical copolymerization. Due to the synergistic effect of covalent micro-crosslinking and the reverse polyelectrolyte effect of amphoteric polymers, the copolymer-based drilling fluids exhibit outstanding rheological and filtration properties even after aging at high temperatures (up to 200 °C) and high salinity (saturated salt) environments. In addition, the zeta potential and particle size distribution of copolymer-based drilling fluids further confirmed that the copolymer can greatly improve the stability of the base fluid suspension, which is important for reducing the fluid-loss volume of WDFs. Therefore, this work will point out a new direction for the development of temperature- and salt-resistant drilling fluid treatment agents.
Nutritional Assessment of Greek Liver Cirrhosis Patients: Mini Nutritional Assessment Predicts Mortality
Authors: Koulentaki Mairi , Drygiannakis Ioannis , Mantaka Aikaterini , Moschapidakis Evangelos , Chalkiadaki Anna , Augoustaki Aikaterini , Spyridaki Aspasia , Kouroumalis Elias , Markaki Anastasia
Published: May 2022

Malnutrition is highly prevalent in liver cirrhosis (LC). It increases as the severity of the disease progresses and it is related to poor survival. The objectives of the study were the nutritional assessment of Greek LC patients, using various nutritional assessment and screening tools, and the comparison of their predictive value for mortality. In total, 137 (77 male) consecutive LC patients (median age: 67 years) were assessed with subjective global assessment (SGA) and mini nutritional assessment (MNA) questionnaires, anthropometrics, handgrip strength (HGS) tests, and bioelectric impedance analysis (BIA), in comparison to a control group of 148 healthy people. Disease severity was assessed using the model for end-stage liver disease (MELD) scores. Patients were followed up for a median of 19 months. Survival curves were calculated using the Kaplan–Meier method. In total, 60% and 43% of patients were of adequate nutritional status by SGA and MNA, respectively, which was confirmed by most anthropometric measurements. MNA and SGA scores correlated significantly with anthropometrics and BIA-derived parameters. Besides the MELD score, mid-arm circumference (MAC), triceps skinfold (TSF), BIA’s phase angle (Pha), and MNA predicted mortality in cirrhotic patients. The nutritional assessment demonstrated an unexpectedly high prevalence of well-nourished LC patients. MNA was a strong predictor of mortality.
The Daily Basic Psychological Need Satisfaction and Work Engagement of Nurses: A ‘Shortitudinal’ Diary Study
Authors: Liebenberg Jo-Mari , Scholtz Salomé E. , De Beer Leon T.
Published: May 2022

Nurses’ satisfaction and work engagement have been linked to patient outcomes. Nightshift nurses provide healthcare to the population and experience unique challenges in performing their healthcare tasks. Therefore, the current study aimed to investigate the daily basic needs satisfaction and work engagement of nightshift nurses in accordance with the satisfaction of three basic psychological needs as indicated by the Self-Determination Theory. A quantitative, ‘shortitudinal’ design (diary study; over a few days) with a multi-level research approach using a daily diary survey method was completed by a convenience sample of nurses working the nightshift in a public hospital (n = 33). The results revealed that the daily need for autonomy and need for relatedness did not significantly predict variance in daily work engagement. However, need for competence did significantly predict variance in daily work engagement, and general emotional load explained significant variability in daily need satisfaction of competence. Lastly, general role clarity had a negative impact on the daily variability in work engagement. This study provides healthcare organisations with explanations for variance in nursing performance and suggests possible interventions to address nursing outcomes in accordance with the three basic needs of nightshift nurses in daily activity.
RhAGL24 Regulating Auxin-Related Gene RhARF18 Affects Stamen Petaloidy in Rose
Authors: Liu Lin , Guo Yanchao , Wu Zhicheng , Ren Haoran , Jiang Yunhe , Ma Nan , Gao Junping , Sun Xiaoming
Published: May 2022

AGAMOUS-LIKE 24 (AGL24) is a key gene regulating floral transition, but its involvement in flower organ identity remains largely unknown. In this study, we found that RhAGL24 is strongly related to petal and stamen development in rose. Its expression increases rapidly at the petal primordium development stage and maintains a high level until the complete differentiation stage. RhAGL24 silencing increases the number of malformed petals and decreases the number of stamens, indicating that this gene affects stamen petaloidy. RhAG (AGAMOUS), a class C gene associated with petal and stamen development, is downregulated in RhAGL24-silenced plants. Moreover, we found that RhAGL24 could directly bind to the promoter region of RhARF18 (AUXIN RESPONSE FACTORS 18), a regulator of RhAG. Our results suggested that RhAGL24-RhARF18 module regulates stamen petaloidy in rose and provide new insights into the function of AGL24 for plants.
Enzyme Activities in the Lignin Metabolism of Chinese Olive (Canarium album) with Different Flesh Characteristics
Authors: Wang Jie , Cai Jingrong , Zhao Junyue , Guo Zhixiong , Pan Tengfei , Yu Yuan , She Wenqin
Published: May 2022

Lignin is crucial to the formation of fruit texture quality. Here, we aimed to explore the relationship between lignin metabolism and fruit texture by investigating the lignin content, total phenols and their related enzyme activities among three Chinese olive (Canarium album (Lour.) Raeusch) genotypes. Our results showed that lignin deposition moved from the exocarp to the flesh in Chinese olive fruit. The lignin, total phenols and enzyme activities were all different between the three Chinese olive cultivars at each developmental stage. The lignin content was positively correlated with the PAL, 4CL and POD activities. These results demonstrated that lignin metabolism was regulated through the related enzyme activities. Therefore, our findings may provide insight to facilitate further improvement in fruit texture quality in Chinese olive.
Biostimulatory Action of a Plant-Derived Protein Hydrolysate on Morphological Traits, Photosynthetic Parameters, and Mineral Composition of Two Basil Cultivars Grown Hydroponically under Variable Electrical Conductivity
Authors: Ciriello Michele , Formisano Luigi , El-Nakhel Christophe , Corrado Giandomenico , Rouphael Youssef
Published: May 2022

Hydroponics is a viable alternative to open field cultivation for year-round vegetable production in urban areas. However, the total dependence on external chemical inputs (fertilizers) makes these systems often less environmentally sustainable. In this perspective, the use of biostimulants could represent a valuable and eco-friendly tool to limit the excessive use of fertilizers without a negative impact on the yield. To this end, our work aimed to evaluate the productive and physiological response of two cultivars of ‘Genovese’ basil (Eleonora and Italiano Classico) for the industrial production of “pesto” grown for 22 days in two nutrient solutions with different electrical conductivity (1 and 2 dS m−1) and the application of two doses of protein hydrolysates (0.15- and 0.30-mL L−1 of Trainer® in the nutrient solution). The mineral profile was evaluated by ion chromatography coupled with a conductivity detector, while pigments were evaluated by UV-Vis spectrophotometry. Generally, the nutrient solution concentration did not significantly affect the fresh yield of the two cultivars tested. On the contrary, the use of the maximum dose of biostimulant (BT2 = 0.30 mL L−1 of nutrient solution) increased fresh yield, leaf area, and ACO2 by 20.7, 27.5, and 17.6%, respectively, compared with the control. Using the lowest dose of biostimulant (BT1 = 0.15 mL L−1 of the nutrient solution) reduced nitrate by 6.6% compared with the control. The results obtained showed that basil cultivation in a floating raft system combined with biostimulant in the nutrient solution could be an excellent solution to improve productivity, reduce nitrate, and cut fertilizer costs.
Biological Control of the Cucumber Downy Mildew Pathogen Pseudoperonospora cubensis
Authors: Sun Zhanbin , Yu Shufan , Hu Yafeng , Wen Yanchen
Published: May 2022

Cucumber downy mildew (CDM) is a destructive plant disease caused by the air-borne oomycete pathogen Pseudoperonospora cubensis. CDM causes severe yield reduction of cucumber and significant economic losses. Biocontrol is a promising method to control CDM with the advantage of being beneficial to sustainable agricultural development. However, until now, no reviews of biocontrol of CDM have been reported. The objective of this review is to more comprehensively understand the biocontrol of CDM. In this review, the biological characteristics of P. cubensis are introduced, and strategies for screening biocontrol agents to suppress CDM are recommended. Then the current biocontrol agents, including fungi such as Trichoderma and biocontrol bacteria such as Bacillus, which possess the ability to control CDM, and their control characteristics and ability against CDM are also summarized. The potential mechanisms by which these biocontrol agents prevent CDM are discussed. Finally, several suggestions for future research on the biocontrol of CDM are provided.
Advances in Evaporation and Evaporative Demand
Authors: Malamos Nikolaos , Tegos Aristoteles
Published: May 2022

The importance of evapotranspiration is well-established in various disciplines such as hydrology, agronomy, climatology, and other geosciences [...]
Aerosolization Behaviour of Fungi and Its Potential Health Effects during the Composting of Animal Manure
Authors: Wang Ruonan , Yu Aoyuan , Qiu Tianlei , Guo Yajie , Gao Haoze , Sun Xingbin , Gao Min , Wang Xuming
Published: May 2022

Compost is an important source of airborne fungi that can adversely affect occupational health. However, the aerosol behavior of fungi and their underlying factors in composting facilities are poorly understood. We collected samples from compost piles and the surrounding air during the composting of animal manure and analyzed the aerosolization behavior of fungi and its potential health effects based on the fungal composition and abundance in two media using high-throughput sequencing and ddPCR. There were differences in fungal diversity and richness between the air and composting piles. Ascomycota and Basidiomycota were the two primary fungal phyla in both media. The dominant fungal genera in composting piles were Aspergillus, Thermomyces, and Alternaria, while the dominant airborne fungal genes were Alternaria, Cladosporium, and Sporobolomyces. Although the communities of total fungal genera and pathogenic/allergenic genera were different in the two media, fungal abundance in composting piles was significantly correlated with abundance in air. According to the analysis on fungal composition, a total of 69.10% of the fungal genera and 91.30% of pathogenic/allergenic genera might escape from composting pile into the air. A total of 77 (26.64%) of the fungal genera and six (20%) of pathogenic/allergenic genera were likely to aerosolize. The influence of physicochemical parameters and heavy metals on the aerosol behavior of fungal genera, including pathogenic/allergenic genera, varied among the fungal genera. These results increase our understanding of fungal escape during composting and highlight the importance of aerosolization behavior for predicting the airborne fungal composition and corresponding human health risks in compost facilities.
Occupational Mortality Matrix: A Tool for Epidemiological Assessment of Work-Related Risk Based on Current Data Sources
Authors: Massari Stefania , Malpassuti Vittoria Carolina , Binazzi Alessandra , Paris Lorena , Gariazzo Claudio , Marinaccio Alessandro
Published: May 2022

Mortality from occupational diseases significantly afflicts society, in terms of both economic costs and human suffering. The International Labour Organization (ILO) estimated that 2.4 million workers die from work-related diseases every year. In Europe, around 80,000 workers die from cancer attributed to occupational exposure to carcinogens. This study developed the Occupational Mortality Matrix (OMM) aimed to identify significant associations between causes of death and occupational sectors through an individual record linkage between mortality data and the administrative archive of occupational histories. The study population consisted of 6,433,492 deceased subjects in Italy (in the period 2005–2015), of which 2,723,152 records of work histories were retrieved (42%). The proportional mortality ratio (PMR) was estimated to investigate the excess of mortality for specific causes associated with occupational sectors. Higher PMRs were reported for traditionally risky occupations such as shipbuilding for mesothelioma cases (PMR: 8.15; 95% CI: 7.28–9.13) and leather production for sino-nasal cancer (PMR: 5.04; 95% CI: 3.54–7.19), as well as for unexpected risks such as male breast cancer in the pharmaceutical industry (PMR: 2.56; 95% CI: 1.33–4.93) and brain cancer in railways (PMR: 1.43; 95% CI: 1.24–1.66). The OMM proved to be a valid tool for research studies to generate hypotheses about the occupational etiology of diseases, and to monitor and support priority actions for risk reduction in workplaces.
Perspectives and Factors Affecting the Preventive Behavior Pertinent to COVID-19 among School Employees in Chiang Mai, Thailand: A Cross-Sectional Study
Authors: Assavanopakun Pheerasak , Promkutkao Tharntip , Promkutkeo Suchat , Sirikul Wachiranun
Published: May 2022

The school is one of the most challenging environments for management to prevent the spread of COVID-19 infection. School employees play important roles as the main practitioners of recommended preventive measures. Consistent application of preventive measures by school employees strengthens the school’s readiness to reopen for on-site education. The study objectives are (1) to assess school employee agreement and actions in accordance with the preventive measures and recommendations for COVID-19 prevention and control, (2) to assess the readiness of the school and employees for on-site education, and (3) to determine factors associated with consistent performance of these measures. A cross-sectional study was conducted via an online survey from 5 November 2021 to 25 January 2022. Self-reported online questionnaires were used to collect school employees’ data. The readiness of schools for on-site education was assessed using 44 indicators from the practical guidelines by the Thai Department of Health. Of the 402 study participants, the majority of participants had agreed to all measures and recommendations for COVID-19 prevention and control in school. High levels of concern and disagreement in school re-opening (aOR 3.78, 95%CI 1.04 to 13.70; p = 0.043) were associated with higher consistent performance of the measures and recommendations for COVID-19 prevention and control in schools. Male teachers (aOR 0.43, 95%CI 0.23 to 0.80; p = 0.008) and any disagreement with these measures and recommendations (aOR 0.03, 95%CI 0.01 to 0.23; p < 0.001) were associated with lower consistent performance. Our study findings can inform the stakeholders to decide on the re-opening and supportive strategies. School employees, especially in male employees, must be supported from the relevant sectors to decrease disagreement to the measures and enhance awareness of the pandemic situation before the school re-opening.
Impact of the COVID-19 Pandemic Era on Residential Property Features: Pilot Studies in Poland
Authors: Kocur-Bera Katarzyna
Published: May 2022

Flats/houses in the COVID-19 pandemic era became the central place for living, working, learning, studying and entertainment. According to Maslow’s pyramid, all the basic needs had to be satisfied within a single space, which caused a change in the importance of certain locational and physical features of the flat/house. This study aimed to investigate how the COVID-19 pandemic changed the perception of the environmental features and the physical features of flats/houses. The research material was obtained from a questionnaire study disseminated through different online channels. The study was conducted in Poland, and citizens’ preferences are linked to the prevailing spatial and socio-economic determinants. A group of respondents were presented with 23 features describing the location and 17 features describing the physical features of flats/houses. They were also asked questions about the level of satisfaction with the current location and housing features. The results were analysed, and the statistical significance of the difference in the perception of the location features and the physical features of the flat/house was verified using a Chi-squared test. The results demonstrated a change in the importance of certain attributes concerning both external and internal factors. The physical features of the flat/house appeared to be more important (from the respondents’ perspective) than the features related to the location, as most changes occurred in that group. The respondents indicated that access to medical care facilities had gained importance (+8%), while good access to public transport had declined (−9%). For the physical features of flats/houses, respondents from other countries also indicated the importance of other attributes, i.e., the floor area (+12%), number of rooms (+14%), additional rooms (+14%), and access to broadband Internet and digital platforms (+28%). The study showed that over 30% of respondents would change their flats/houses if their financial means permitted.
Characterisation of Salmonella Enteritidis ST11 and ST1925 Associated with Human Intestinal and Extra-Intestinal Infections in Singapore
Authors: Aung Kyaw Thu , Khor Wei Ching , Ong Kar Hui , Tan Wei Ling , Wong Zhi Ning , Oh Jia Quan , Wong Wai Kwan , Tan Brian Zi Yan , Maiwald Matthias , Tee Nancy Wen Sim , Barkham Timothy , Koh Tse Hsien , Dalsgaard Anders , Chen Swaine L. , Schlundt Joergen , Ng Lee Ching
Published: May 2022

Salmonella Enteritidis is a major foodborne pathogen worldwide. In this study, a total of 276 S. enteritidis isolates, collected between 2016 and 2017 from human, food and farm/slaughterhouse samples, were studied to enhance the understanding of the epidemiology of human salmonellosis in Singapore. Results showed all 276 isolates belonged either to ST1925 (70.3%) or ST11 (29.7%), with ST11 being significantly more frequent in extra-intestinal isolates and chicken isolates. Food isolates, most of which were from poultry, showed the highest prevalence of resistance (33–37%) against beta-lactams or beta-lactams/beta-lactamase inhibitor combination (ampicillin, piperacillin and ampicillin/sulbactam). The analysis showed the detection of genes associated with resistance to aminoglycoside genes (99.6%), tetracycline (55.1%), and beta-lactams (14.9%) of all isolates. Nine types of plasmids were found in 266 isolates; the most common incompatibility group profiles were IncFIB(S)-IncFII(S)-IncX1 (72.2%) and IncFIB(S)-IncFII(S) (15.8%). Most plasmid harbouring isolates from chicken (63.6%, 14/22) and from human (73.8%, 175/237) shared the same plasmid profile (IncFIB(S)-IncFII(S)-IncX1). SNP analysis showed clustering of several isolates from poultry food products and human isolates, suggesting phylogenetic relatedness among these isolates. Lastly, this study provides important epidemiological insights on the application of phenotypic and next-generation sequencing (NGS) tools for improved food safety and public health surveillance and outbreak investigation of S.enteritidis.
Engineering CRISPR/Cas9 for Multiplexed Recombinant Coagulation Factor Production
Authors: Feser Colby J. , Lees Christopher J. , Lammers Daniel T. , Riddle Megan J. , Bingham Jason R. , Eckert Matthew J. , Tolar Jakub , Osborn Mark J.
Published: May 2022

Current hemostatic agents are obtained from pooled plasma from multiple donors requiring costly pathogen screening and processing. Recombinant DNA-based production represents an engineering solution that could improve supply, uniformity, and safety. Current approaches are typically for single gene candidate peptides and often employ non-human cells. We devised an approach where multiple gene products could be produced from a single population of cells. We identified gene specific Synergistic Activation Mediators (SAM) from the CRISPR/Cas9 system for targeted overexpression of coagulation factors II, VII, IX, X, and fibrinogen. The components of the CRISPR-SAM system were expressed in Human Embryonic Kidney Cells (HEK293), and single (singleplex) or multi-gene (multiplex) upregulation was assessed by quantitative RT-PCR (qRT-PCR) and protein expression by ELISA analysis. Factor II, VII, IX, and X singleplex and multiplex activation resulted in 120–4700-fold and 60–680-fold increases in gene expression, respectively. Fibrinogen sub-unit gene activation resulted in a 1700–92,000-fold increases and 80–5500-fold increases in singleplex or multiplex approaches, respectively. ELISA analysis showed a concomitant upregulation of candidate gene products. Our findings demonstrate the capability of CRISPR/Cas9 SAMs for single or multi-agent production in human cells and represent an engineering advance that augments current recombinant peptide production techniques.
Molecular Dynamics of DHHC20 Acyltransferase Suggests Principles of Lipid and Protein Substrate Selectivity
Authors: Panina Irina , Krylov Nikolay , Gadalla Mohamed Rasheed , Aliper Elena , Kordyukova Larisa , Veit Michael , Chugunov Anton , Efremov Roman
Published: May 2022

Lipid modification of viral proteins with fatty acids of different lengths (S-acylation) is crucial for virus pathogenesis. The reaction is catalyzed by members of the DHHC family and proceeds in two steps: the autoacylation is followed by the acyl chain transfer onto protein substrates. The crystal structure of human DHHC20 (hDHHC20), an enzyme involved in the acylation of S-protein of SARS-CoV-2, revealed that the acyl chain may be inserted into a hydrophobic cavity formed by four transmembrane (TM) α-helices. To test this model, we used molecular dynamics of membrane-embedded hDHHC20 and its mutants either in the absence or presence of various acyl-CoAs. We found that among a range of acyl chain lengths probed only C16 adopts a conformation suitable for hDHHC20 autoacylation. This specificity is altered if the small or bulky residues at the cavity’s ceiling are exchanged, e.g., the V185G mutant obtains strong preferences for binding C18. Surprisingly, an unusual hydrophilic ridge was found in TM helix 4 of hDHHC20, and the responsive hydrophilic patch supposedly involved in association was found in the 3D model of the S-protein TM-domain trimer. Finally, the exchange of critical Thr and Ser residues in the spike led to a significant decrease in its S-acylation. Our data allow further development of peptide/lipid-based inhibitors of hDHHC20 that might impede replication of Corona- and other enveloped viruses.
Actin Stress Fibers Response and Adaptation under Stretch
Authors: Bernal Roberto , Van Hemelryck Milenka , Gurchenkov Basile , Cuvelier Damien
Published: May 2022

One of the many effects of soft tissues under mechanical solicitation in the cellular damage produced by highly localized strain. Here, we study the response of peripheral stress fibers (SFs) to external stretch in mammalian cells, plated onto deformable micropatterned substrates. A local fluorescence analysis reveals that an adaptation response is observed at the vicinity of the focal adhesion sites (FAs) due to its mechanosensor function. The response depends on the type of mechanical stress, from a Maxwell-type material in compression to a complex scenario in extension, where a mechanotransduction and a self-healing process takes place in order to prevent the induced severing of the SF. A model is proposed to take into account the effect of the applied stretch on the mechanics of the SF, from which relevant parameters of the healing process are obtained. In contrast, the repair of the actin bundle occurs at the weak point of the SF and depends on the amount of applied strain. As a result, the SFs display strain-softening features due to the incorporation of new actin material into the bundle. In contrast, the response under compression shows a reorganization with a constant actin material suggesting a gliding process of the SFs by the myosin II motors.
Relationship between Neuronal Damage/Death and Astrogliosis in the Cerebral Motor Cortex of Gerbil Models of Mild and Severe Ischemia and Reperfusion Injury
Authors: Lee Choong-Hyun , Lee Tae-Kyeong , Kim Dae Won , Lim Soon Sung , Kang Il Jun , Ahn Ji Hyeon , Park Joon Ha , Lee Jae-Chul , Kim Choong-Hyo , Park Yoonsoo , Won Moo-Ho , Choi Soo Young
Published: May 2022

Neuronal loss (death) occurs selectively in vulnerable brain regions after ischemic insults. Astrogliosis is accompanied by neuronal death. It can change the molecular expression and morphology of astrocytes following ischemic insults. However, little is known about cerebral ischemia and reperfusion injury that can variously lead to damage of astrocytes according to the degree of ischemic injury, which is related to neuronal damage/death. Thus, the purpose of this study was to examine the relationship between damage to cortical neurons and astrocytes using gerbil models of mild and severe transient forebrain ischemia induced by blocking the blood supply to the forebrain for five or 15 min. Significant ischemia tFI-induced neuronal death occurred in the deep layers (layers V and VI) of the motor cortex: neuronal death occurred earlier and more severely in gerbils with severe ischemia than in gerbils with mild ischemia. Distinct astrogliosis was detected in layers V and VI. It gradually increased with time after both ischemiae. The astrogliosis was significantly higher in severe ischemia than in mild ischemia. The ischemia-induced increase of glial fibrillary acidic protein (GFAP; a maker of astrocyte) expression in severe ischemia was significantly higher than that in mild ischemia. However, GFAP-immunoreactive astrocytes were apparently damaged two days after both ischemiae. At five days after ischemiae, astrocyte endfeet around capillary endothelial cells were severely ruptured. They were more severely ruptured by severe ischemia than by mild ischemia. However, the number of astrocytes stained with S100 was significantly higher in severe ischemia than in mild ischemia. These results indicate that the degree of astrogliosis, including the disruption (loss) of astrocyte endfeet following ischemia and reperfusion in the forebrain, might depend on the severity of ischemia and that the degree of ischemia-induced neuronal damage may be associated with the degree of astrogliosis.
Yeast as a Model to Find New Drugs and Drug Targets for VPS13-Dependent Neurodegenerative Diseases
Authors: Kaminska Joanna , Soczewka Piotr , Rzepnikowska Weronika , Zoladek Teresa
Published: May 2022

Mutations in human VPS13A-D genes result in rare neurological diseases, including chorea-acanthocytosis. The pathogenesis of these diseases is poorly understood, and no effective treatment is available. As VPS13 genes are evolutionarily conserved, the effects of the pathogenic mutations could be studied in model organisms, including yeast, where one VPS13 gene is present. In this review, we summarize advancements obtained using yeast. In recent studies, vps13Δ and vps13-I2749 yeast mutants, which are models of chorea-acanthocytosis, were used to screen for multicopy and chemical suppressors. Two of the suppressors, a fragment of the MYO3 and RCN2 genes, act by downregulating calcineurin activity. In addition, vps13Δ suppression was achieved by using calcineurin inhibitors. The other group of multicopy suppressors were genes: FET4, encoding iron transporter, and CTR1, CTR3 and CCC2, encoding copper transporters. Mechanisms of their suppression rely on causing an increase in the intracellular iron content. Moreover, among the identified chemical suppressors were copper ionophores, which require a functional iron uptake system for activity, and flavonoids, which bind iron. These findings point at areas for further investigation in a higher eukaryotic model of VPS13-related diseases and to new therapeutic targets: calcium signalling and copper and iron homeostasis. Furthermore, the identified drugs are interesting candidates for drug repurposing for these diseases.
Global Noncoding microRNA Profiling in Mice Infected with Partial Human Mouth Microbes (PAHMM) Using an Ecological Time-Sequential Polybacterial Periodontal Infection (ETSPPI) Model Reveals Sex-Specific Differential microRNA Expression
Authors: Aravindraja Chairmandurai , Kashef Matteen R. , Vekariya Krishna Mukesh , Ghanta Ravi K. , Karanth Shama , Chan Edward K. L. , Kesavalu Lakshmyya
Published: May 2022

Periodontitis (PD) is a polymicrobial dysbiotic immuno-inflammatory disease. It is more prevalent in males and has poorly understood pathogenic molecular mechanisms. Our primary objective was to characterize alterations in sex-specific microRNA (miRNA, miR) after periodontal bacterial infection. Using partial human mouth microbes (PAHMM) (Streptococcus gordonii, Fusobacterium nucleatum, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia) in an ecological time-sequential polybacterial periodontal infection (ETSPPI) mouse model, we evaluated differential mandibular miRNA profiles by using high-throughput Nanostring nCounter® miRNA expression panels. All PAHMM mice showed bacterial colonization (100%) in the gingival surface, an increase in alveolar bone resorption (p < 0.0001), and the induction of a specific immunoglobin G antibody immune response (p < 0.001). Sex-specific differences in distal organ bacterial dissemination were observed in the heart (82% male vs. 28% female) and lungs (2% male vs. 68% female). Moreover, sex-specific differential expression (DE) of miRNA was identified in PAHMM mice. Out of 378 differentially expressed miRNAs, we identified seven miRNAs (miR-9, miR-148a, miR-669a, miR-199a-3p, miR-1274a, miR-377, and miR-690) in both sexes that may be implicated in the pathogenesis of periodontitis. A strong relationship was found between male-specific miR-377 upregulation and bacterial dissemination to the heart. This study demonstrates sex-specific differences in bacterial dissemination and in miRNA differential expression. A novel PAHMM mouse and ETSPPI model that replicates human pathobiology can be used to identify miRNA biomarkers in periodontitis.
Select Per- and Polyfluoroalkyl Substances (PFAS) Induce Resistance to Carboplatin in Ovarian Cancer Cell Lines
Authors: Rickard Brittany P. , Tan Xianming , Fenton Suzanne E. , Rizvi Imran
Published: May 2022

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous environmental contaminants associated with adverse reproductive outcomes including reproductive cancers in women. PFAS can alter normal ovarian function, but the effects of PFAS on ovarian cancer progression and therapy response remain understudied. Ovarian cancer is the most lethal gynecologic malignancy, and a major barrier to effective treatment is resistance to platinum-based chemotherapy. Platinum resistance may arise from exposure to external stimuli such as environmental contaminants. This study evaluated PFAS and PFAS mixture exposures to two human ovarian cancer cell lines to evaluate the ability of PFAS exposure to affect survival fraction following treatment with carboplatin. This is the first study to demonstrate that, at sub-cytotoxic concentrations, select PFAS and PFAS mixtures increased survival fraction in ovarian cancer cells following carboplatin treatment, indicative of platinum resistance. A concomitant increase in mitochondrial membrane potential, measured by the JC-1 fluorescent probe, was observed in PFAS-exposed and PFAS + carboplatin-treated cells, suggesting a potential role for altered mitochondrial function that requires further investigation.
Collective Knowledge Used to Unveil Cardiovascular Injury Emerged during COVID-19
Authors: Tanaka Atsushi , Node Koichi
Published: May 2022

Two years have passed since the unprecedented breakout of the global pandemic of the coronavirus disease COVID-19, which began at the end of 2019 [...]
Non-Photochemical Quenching under Drought and Fluctuating Light
Authors: Nosalewicz Artur , Okoń Karolina , Skorupka Maria
Published: May 2022

Plants grow in a variable environment in regard to soil water and light driving photochemical reactions. Light energy exceeding plant capability to use it for photochemical reactions must be dissipated by processes of non-photochemical quenching (NPQ). The aim of the study was to evaluate the impact of various components of NPQ on the response of Arabidopsis thaliana to fluctuating light and water availability. A laboratory experiment with Arabidopsis thaliana wild type (WT) and mutants npq1 and npq4 grown under optimum or reduced water availability was conducted. Dark-adapted plants were illuminated with fluctuating light (FL) of two intensities (55 and 530 μmol m−2 s−1) with each of the phases lasting for 20 s. The impact of water availability on the role of zeaxanthin and PsbS protein in NPQ induced at FL was analysed. The water deficit affected the dynamics of NPQ induced by FL. The lack of zeaxanthin or PsbS reduced plant capability to cope with FL. The synergy of both of these components was enhanced in regard to the amplitude of NPQ in the drought conditions. PsbS was shown as a component of primary importance in suiting plant response to FL under optimum and reduced water availability.
SMTP-44D Exerts Antioxidant and Anti-Inflammatory Effects through Its Soluble Epoxide Hydrolase Inhibitory Action in Immortalized Mouse Schwann Cells upon High Glucose Treatment
Authors: Shinouchi Ryosuke , Shibata Keita , Jono Shiori , Hasumi Keiji , Nobe Koji
Published: May 2022

Diabetic neuropathy (DN) is a major complication of diabetes mellitus. We have previously reported the efficacy of Stachybotrys microspora triprenyl phenol-44D (SMTP-44D) for DN through its potential antioxidant and anti-inflammatory activities. However, the mechanisms underlying the antioxidant and anti-inflammatory activities of SMTP-44D remain unclear. The present study aimed to explore the mechanism of these effects of SMTP-44D in regard to its inhibition of soluble epoxide hydrolase (sEH) in immortalized mouse Schwann cells (IMS32) following high glucose treatment. IMS32 cells were incubated in a high glucose medium for 48 h and then treated with SMTP-44D for 48 h. After incubation, the ratio of epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acids (DHETs), oxidative stress markers, such as NADPH oxidase-1 and malondialdehyde, inflammatory factors, such as the ratio of nuclear to cytosolic levels of NF-κB and the levels of IL-6, MCP-1, MMP-9, the receptor for the advanced glycation end product (RAGE), and apoptosis, were evaluated. SMTP-44D treatment considerably increased the ratio of EETs to DHETs and mitigated oxidative stress, inflammation, RAGE induction, and apoptosis after high glucose treatment. In conclusion, SMTP-44D can suppress the induction of apoptosis by exerting antioxidant and anti-inflammatory effects, possibly through sEH inhibition. SMTP-44D can be a potential therapeutic agent against DN.
Dilated-Left Ventricular Non-Compaction Cardiomyopathy in a Pediatric Case with SPEG Compound Heterozygous Variants
Authors: Jaouadi Hager , El Louali Fedoua , Wanert Chloé , Cano Aline , Ovaert Caroline , Zaffran Stéphane
Published: May 2022

Left Ventricular Non-Compaction (LVNC) is defined by the triad prominent myocardial trabecular meshwork, thin compacted layer, and deep intertrabecular recesses. LVNC associated with dilation is characterized by the coexistence of left ventricular dilation and systolic dysfunction. Pediatric cases with dilated-LVNC have worse outcomes than those with isolated dilated cardiomyopathy and adult patients. Herein, we report a clinical and genetic investigation using trio-based whole-exome sequencing of a pediatric case with early-onset dilated-LVNC. Compound heterozygous mutations were identified in the Striated Muscle Enriched Protein Kinase (SPEG) gene, a key regulator of cardiac calcium homeostasis. A paternally inherited mutation: SPEG; p.(Arg2470Ser) and the second variant, SPEG; p.(Pro2687Thr), is common and occurred de novo. Subsequently, Sanger sequencing was performed for the family in order to segregate the variants. Thus, the index case, his father, and both sisters carried the SPEG: p.(Arg2470Ser) variant. Only the index patient carried both SPEG variants. Both sisters, as well as the patient’s father, showed LVNC without cardiac dysfunction. The unaffected mother did not harbor any of the variants. The in silico analysis of the identified variants (rare and common) showed a decrease in protein stability with alterations of the physical properties as well as high conservation scores for the mutated residues. Interestingly, using the Project HOPE tool, the SPEG; p.(Pro2687Thr) variant is predicted to disturb the second fibronectin type III domain of the protein and may abolish its function. To our knowledge, the present case is the first description of compound heterozygous SPEG mutations involving a de novo variant and causing dilated-LVNC without neuropathy or centronuclear myopathy.
Transcriptional Contribution of Transposable Elements in Relation to Salinity Conditions in Teleosts and Silencing Mechanisms Involved
Authors: Carotti Elisa , Carducci Federica , Greco Samuele , Gerdol Marco , Di Marino Daniele , Perta Nunzio , La Teana Anna , Canapa Adriana , Barucca Marco , Biscotti Maria Assunta
Published: May 2022

Fish are an interesting taxon comprising species adapted to a wide range of environments. In this work, we analyzed the transcriptional contribution of transposable elements (TEs) in the gill transcriptomes of three fish species exposed to different salinity conditions. We considered the giant marbled eel Anguilla marmorata and the chum salmon Oncorhynchus keta, both diadromous, and the marine medaka Oryzias melastigma, an euryhaline organism sensu stricto. Our analyses revealed an interesting activity of TEs in the case of juvenile eels, commonly adapted to salty water, when exposed to brackish and freshwater conditions. Moreover, the expression assessment of genes involved in TE silencing mechanisms (six in heterochromatin formation, fourteen known to be part of the nucleosome remodeling deacetylase (NuRD) complex, and four of the Argonaute subfamily) unveiled that they are active. Finally, our results evidenced for the first time a krüppel-associated box (KRAB)-like domain specific to actinopterygians that, together with TRIM33, might allow the functioning of NuRD complex also in fish species. The possible interaction between these two proteins was supported by structural prediction analyses.
A Deep Learning Approach for Repairing Missing Activity Labels in Event Logs for Process Mining
Authors: Lu Yang , Chen Qifan , Poon Simon K.
Published: May 2022

Process mining is a relatively new subject that builds a bridge between traditional process modeling and data mining. Process discovery is one of the most critical parts of process mining, which aims at discovering process models automatically from event logs. Like other data mining techniques, the performance of existing process discovery algorithms can be affected when there are missing activity labels in event logs. In this paper, we assume that the control-flow information in event logs could be useful in repairing missing activity labels. We propose an LSTM-based prediction model, which takes both the prefix and suffix sequences of the events with missing activity labels as input to predict missing activity labels. Additional attributes of event logs are also utilized to improve the performance. Our evaluation of several publicly available datasets shows that the proposed method performed consistently better than existing methods in terms of repairing missing activity labels in event logs.