bluuebunny/crossref_metadata_2025 huggingface dataset:
Intestinal Epithelial Cell-Derived Extracellular Vesicles Modulate Hepatic Injury via the Gut-Liver Axis During Acute Alcohol Injury
Authors: Lamas-Paz Arantza , Morán Laura , Peng Jin , Salinas Beatriz , López-Alcántara Nuria , Sydor Svenja , Vilchez-Vargas Ramiro , Asensio Iris , Hao Fengjie , Zheng Kang , Martín-Adrados Beatriz , Moreno Laura , Cogolludo Angel , Gómez del Moral Manuel , Bechmann Lars , Martínez-Naves Eduardo , Vaquero Javier , Bañares Rafael , Nevzorova Yulia A. , Cubero Francisco Javier
Published: December 2020

Binge drinking, i.e., heavy episodic drinking in a short time, has recently become an alarming societal problem with negative health impact. However, the harmful effects of acute alcohol injury in the gut-liver axis remain elusive. Hence, we focused on the physiological and pathological changes and the underlying mechanisms of experimental binge drinking in the context of the gut-liver axis. Eight-week-old mice with a C57BL/6 background received a single dose (p.o.) of ethanol (EtOH) [6 g/kg b.w.] as a preclinical model of acute alcohol injury. Controls received a single dose of PBS. Mice were sacrificed 8 h later. In parallel, HepaRGs and Caco-2 cells, human cell lines of differentiated hepatocytes and intestinal epithelial cells intestinal epithelial cells (IECs), respectively, were challenged in the presence or absence of EtOH [0–100 mM]. Extracellular vesicles (EVs) isolated by ultracentrifugation from culture media of IECs were added to hepatocyte cell cultures. Increased intestinal permeability, loss of zonula occludens-1 (ZO-1) and MUCIN-2 expression, and alterations in microbiota—increased Lactobacillus and decreased Lachnospiraceae species—were found in the large intestine of mice exposed to EtOH. Increased TUNEL-positive cells, infiltration of CD11b-positive immune cells, pro-inflammatory cytokines (e.g., tlr4, tnf, il1β), and markers of lipid accumulation (Oil Red O, srbep1) were evident in livers of mice exposed to EtOH, particularly in females. In vitro experiments indicated that EVs released by IECs in response to ethanol exerted a deleterious effect on hepatocyte viability and lipid accumulation. Overall, our data identified a novel mechanism responsible for driving hepatic injury in the gut-liver axis, opening novel avenues for therapy.
Perspective: One-Cell and Cleavage-Stage Mouse Embryos Thrive in Hyperosmotic Oviductal Fluid Through Expression of a Glycine Neurotransmitter Transporter and a Glycine-Gated Chloride Channel: Clinical and Transgenerational Implications
Authors: Van Winkle Lon J.
Published: December 2020

The osmolality of mouse oviductal fluid ranges from about 300 mOsmol/kg in the ampulla 0–3 h post coitus (h p.c.) to more than 350 mOsmol/kg in the isthmus 34–36 h p.c. Thus, it has been surprising to find that development of one-cell and cleavage-stage mouse embryos arrestsin vitroin media exceeding 300 mOsmol/kg, and they develop best in unphysiological, hypotonic media. The glycine concentration in oviductal fluid can, however, rescue development in hypertonic media, so physiological conditionsin vivoandin vitrolikely work together to foster embryo well-being. Glycine acts on one-cell and cleavage-stage mouse embryos through the glycine-gated chloride channel, GLRA4, and uptakeviathe glycine neurotransmitter transporter, GLYT1. Since these processes lead to further signaling in neurons, the presence and function of such signaling in preimplantation embryos also should be investigated. The more we know about the interactions of physiological processes and conditionsin vivo, the better we would be able to reproduce themin vitro. Such improvements in assisted reproductive technology (ART) could improve patient outcomes for IVF and potentially help prevent unwanted developmental abnormalities in early embryos, which might include undesirable epigenetic DNA and histone modifications. These epigenetic modifications may lead to transgenerational adult disorders such as metabolic syndrome and related conditions.
Minds, Brains, and Capacities: Situated Cognition and Neo-Aristotelianism
Authors: Glock Hans-Johann
Published: December 2020

This article compares situated cognition to contemporary Neo-Aristotelian approaches to the mind. The article distinguishes two components in this paradigm: an Aristotelian essentialism which is alien to situated cognition and a Wittgensteinian “capacity approach” to the mind which is not just congenial to it but provides important conceptual and argumentative resources in defending social cognition against orthodox cognitive (neuro-)science. It focuses on a central tenet of that orthodoxy. According to what I call “encephalocentrism,” cognition is primarily or even exclusively a computational process occurring inside the brain. Neo-Aristotelians accuse this claim of committing a “homuncular” (Kenny) or “mereological fallacy” (Bennett and Hacker). The article explains why the label “fallacy” is misleading, reconstructs the argument to the effect that encephalocentric applications of psychological predicates to the brain and its parts amount to a category mistake, and defends this argument against objections by Dennett, Searle, and Figdor. At the same time it criticizes the Neo-Aristotelian denial that the brain is the organ of cognition. It ends by suggesting ways in which the capacity approach and situated cognition might be combined to provide a realistic and ecologically sound picture of cognition as a suite of powers that flesh-and-blood animals exercise within their physical and social environments.
Social Embeddedness of Firefighters, Paramedics, Specialized Nurses, Police Officers, and Military Personnel: Systematic Review in Relation to the Risk of Traumatization
Authors: Geuzinge Renate , Visse Merel , Duyndam Joachim , Vermetten Eric
Published: December 2020

Background:Firefighters, paramedics, specialized nurses working in Intensive Care Units (ICUs), Operating Rooms (OR), and Emergency Rooms (ER), police officers and military personnel are more frequently exposed to potentially traumatic events than the general population; they are considered high-risk professionals. To reduce the risk of traumatization it is of great importance to be embedded in a social environment with supportive relationships.

Methods:We performed a systematic review (based on the PRISMA-Guidelines) looking for social connections within the environment in which high-risk professionals are embedded (work, home, community), to obtain evidence on the impact of these connections on the risk of traumatization. Additionally, we aim to identify relevant supportive relationships in the professionals' environments. We identified the relevant scientific literature by searching, without time, and language restriction, five electronic bibliographic databases: MEDLINE, PsycINFO, Sociological Abstracts, CINAHL, and Web of Science. These databases were last searched in January 2019.

Results:A qualitative analysis of the 89 eligible (out of 9,047 screened) studies shows that for firefighters, paramedics, and emergency nurses social connections in their work environment are predominantly supportive relationships and may protect them against traumatization. In other occupations (OR-nurses, ICU-nurses, police officers), however, social connections at work are not only a source of support but are also a source of stress. For military personnel study results are inconclusive as to whether their social connections at work or at home support them against traumatization. In so far as connections are supportive, their sources vary greatly from one occupational group to another; they differ between work vs. home as well as within work between peers vs. supervisor.

Conclusions:Being embedded in a social environment, i.e., having social connections, is important but not always sufficient to protect high-risk professionals against traumatization. For, while these connections may be the antecedents of supportive relationships, they can also be the antecedents of damaging relationships. Additionally, the sources of supportive relationships differ among groups. This suggests that knowledge of how the social structures of the occupational groups differ may increase our understanding of the impact of social connections and relationships, including socialization, on the risk of traumatization of high-risk professionals.
Mycorrhizal Interventions for Sustainable Potato Production in Africa
Authors: Chifetete Varaidzo W. , Dames Joanna F.
Published: December 2020

The potato (Solanum tuberosum L.) is an important tuber crop with high dietary value that could potentially help to alleviate malnutrition and hunger in Africa. However, production is expensive, with high fertilizer and pesticide demands that lead to environmental pollution, and tillage practices that negatively affect soil structure. Microorganisms of different types have increasingly been found to be useful as biofertilizers, and arbuscular mycorrhizal (AM) fungi are an important crop symbiont. AM fungi have been shown to increase tolerance of crop plants to drought, salinity and disease by facilitating water and nutrient acquisition and by improving overall soil structure. However, the establishment and maintenance of the symbioses are greatly affected by agricultural practices. Here, we review the benefits that AM fungi confer in potato production, discuss the role and importance of mycorrhiza helper bacteria, and focus on how AM fungal diversity and abundance can be affected by conventional agricultural practices, such as those used in potato production. We suggest approaches for maintaining AM fungal abundance in potato production by highlighting the potential of conservation tillage practices augmented with cover crops and crop rotations. An approach that balances weed control, nutrient provision, and AM fungal helper bacterial populations, whilst promoting functional AM fungal populations for varying potato genotypes, will stimulate efficient mycorrhizal interventions.
The Application of Geometric Morphometrics to Explore Potential Impacts of Anthropocentric Selection on Animals' Ability to Communicate via the Face: The Domestic Cat as a Case Study
Authors: Finka Lauren R. , Luna Stelio P. L. , Mills Daniel S. , Farnworth Mark J.
Published: December 2020

During their domestication via artificial selection, humans have substantially modified the morphology and thus visual appearance of non-human animals. While research highlights the negative impact of these modifications on physical functioning, little is known about their impact on behavior and signaling, either toward humans or conspecifics. Changes in the appearance of the face, such as those associated with, but not limited to, facial expressions, form an important part of non-verbal communication. In companion animals, the face is one of their most visually diverse features (due to human-driven selection), which may impact the visual clarity of expressions and other forms of signaling. Using the domestic cat as our model, we applied a new analytical technique in order to understand the impact of breed variation on relative positioning of facial landmarks, chosen specifically for their association with the production of various facial movements, and the expression of affect. We then assessed the extent to which facial appearances known to be associated with a specific underlying state (i.e., pain, assessed via a validated, facial pain score), could be reliably detected in a morphologically diverse population. Substantial baseline variation in landmarks was identified at both the cephalic (e.g., brachycephalic, dolichocephalic, mesocephalic) as well as breed levels. While differences in facial pain scores could successfully differentiate between “pain” and “no pain” in the facial appearance of domestic shorthaired cats (DSH), these differences were no longer detectable when assessed within a larger more morphologically diverse population, after corrections for multiple testing were applied. There was also considerable overlap between pain scores in the DSH “pain” population and the neutral faces of other breeds. Additionally, for several paedomorphic breeds, their neutral face shapes produced scores indicative of greater pain, compared to most other breeds, including the DSH cats actually in pain. Our findings highlight the degree to which anthropocentric selection might disrupt the communicative content of animals' faces, in this case the domestic cat. These results also suggest a potential human preference for features extending beyond the infantile, to include negatively-valenced facial forms such as pain.
Relevance of Biomarkers Currently in Use or Research for Practical Diagnosis Approach of Neonatal Early-Onset Sepsis
Authors: Hincu Maura-Adelina , Zonda Gabriela-Ildiko , Stanciu Gabriela Dumitrita , Nemescu Dragos , Paduraru Luminita
Published: December 2020

Neonatal early-onset sepsis (EOS) is defined as an invasive infection that occurs in the first 72 h of life. The incidence of EOS varies from 0.5–2% live births in developed countries, up to 9.8% live births in low resource settings, generating a high mortality rate, especially in extremely low birth weight neonates. Clinical signs are nonspecific, leading to a late diagnosis and high mortality. Currently, there are several markers used for sepsis evaluation, such as hematological indices, acute phase reactants, cytokines, which by themselves do not show acceptable sensitivity and specificity for the diagnosis of EOS in neonates. Newer and more selective markers have surfaced recently, such as presepsin and endocan, but they are currently only in the experimental research stages. This comprehensive review article is based on the role of biomarkers currently in use or in the research phase from a basic, translational, and clinical viewpoint that helps us to improve the quality of neonatal early-onset sepsis diagnosis and management.
Risk Perception of COVID-19 Infection and Adherence to Preventive Measures among Adolescents and Young Adults
Authors: Yang Xin Yu , Gong Rui Ning , Sassine Samuel , Morsa Maxime , Tchogna Alexandra Sonia , Drouin Olivier , Chadi Nicholas , Jantchou Prévost
Published: December 2020

To explore factors influencing adolescents and young adults’ (AYAs) risk perception of COVID-19 and adherence to public health measures, we conducted a cross-sectional online survey of AYAs (14–22 years old) from Quebec (Canada) recruited through school and community partners in April 2020 during the first wave of the COVID-19 pandemic. The study included 3037 participants (mean age = 17.7 years, 74.6% female). AYAs had higher mean (standard deviation (SD)) risk perception of COVID-19 for their relatives (8.2 (1.9)) than for themselves (5.6 (2.6)) (p < 0.001). Factors associated with higher risk perception included higher disease knowledge (adjusted odds ratio (aOR) 1.06, 95% CI 1.01–1.11), presence of chronic disease (aOR 2.31, 95%CI 1.82–2.93) and use of immunosuppressants (aOR 2.53, 95%CI 1.67–3.87). AYAs with a higher risk perception (aOR 1.06, 95%CI 1.02–1.10) those wishing to help flatten the disease curve (aOR 1.18, 95%CI 1.12–1.25) or to protect their family/friends (aOR 1.14, 95%CI 1.05–1.24) were more likely to engage in preventive behaviors. Self-perceived risk and desire to protect others were significantly associated with adherence to preventive measures among youth. These findings may help inform public health messaging to AYAs in the current and future pandemics.
Healing through Ancestral Knowledge and Letters to Our Children: Mothering Infants during a Global Pandemic
Authors: Valdovinos Miriam G. , Rodríguez-Coss Noralis , Parekh Rupal
Published: December 2020

The struggle for work–life balance amongst women in academia who are both mothers and scholars continues to be apparent during a global pandemic highlighting the systemic fissures and social inequalities ingrained in our society, including systems of higher learning. Women of color professors on the tenure track are vulnerable to the intersecting ways capitalism, sexism, and racism exacerbate the challenges faced by motherscholars, making it imperative to explore these nuances. While motherscholars may share advice about navigating family leave policies or strategizing scholarship goals, no one could have prepared us for our motherscholar roles during a pandemic. We were, in some ways, unprepared for giving birth with a heightened level of social isolation and feelings of loneliness, while racial unrest and loud exigencies to protect the lives of Black, Indigenous, and People of Color (BIPOC) persist. Through three testimonios, we explore how ancestral/indigenous knowledge provides us with ways to persist, transform, and heal during these moments. We share letters written to each of our babies to encapsulate our praxis with ancestral knowledge on mothering. We reflect on matriarchal elders, constricted movement in our daily routines, and ongoing worries and hopes. We theorize this knowledge to offer solidarity with a motherscholar epistemology.
Shift Work and Breast Cancer
Authors: Gehlert Sarah , Clanton Mark ,   on behalf of the Shift Work and Breast Cancer Strategic Advisory Group
Published: December 2020

The rates of shift work outside of daylight hours have increased in recent years, and nighttime shift work is now considered a potential carcinogenic occupational exposure. Light at night exposure, lower melatonin production, and the production of stress-related mediators disrupt normal sleep–wake cycles. Women who work lower-wage jobs and part-time workers whose shifts are determined entirely by their supervisors (rotating shifts) may be subject to stress related to efforts to align childcare and other needs with the unpredictable nature of rotating shift work. The causal link between breast cancer and the sleep cycle or circadian disruption are yet to be established; however, disruption of the circadian cycles by light at night exposure or chronic exposure to stress-related mediators have all been linked to the increased risk of breast cancer. We review the existing literature on shift work and breast cancer, identify knowledge gaps, and suggest future directions for research.
The Effectiveness of Mass Transfer in the MHD Upper-Convected Maxwell Fluid Flow on a Stretched Porous Sheet near Stagnation Point: A Numerical Investigation
Authors: Shahid Anwar
Published: December 2020

The present inquiry studies the influence of mass transfer in magnetohydrodynamics (MHD) upper-convected Maxwell (UCM) fluid flow on a stretchable, porous subsurface. The governing partial differential equations for the flow problem are reformed to ordinary differential equations through similarity transformations. The numerical outcomes for the arising non-linear boundary value problem are determined by implementing the successive linearization method (SLM) via Matlab software. The accuracy of the SLM is confirmed through known methods, and convergence analysis is also presented. The graphical behavior for all the parametric quantities in the governing equations across the velocity and concentration magnitudes, as well as the skin friction and Sherwood number, is presented and debated in detail. A comparability inquiry of the novel proposed technique, along with the preceding explored literature, is also provided. It is expected that the current achieved results will furnish fruitful knowledge in industrious utilities and correlate with the prevailing literature.
The Influence of Physical Load on Dynamic Postural Control—A Systematic Replication Study
Authors: Heil Jessica , Schulte Sarah , Büsch Dirk
Published: December 2020

Dynamic postural control is challenged during many actions in sport such as when landing or cutting. A decrease of dynamic postural control is one possible risk factor for non-contact injuries. Moreover, these injuries mainly occur under loading conditions. Hence, to assess an athlete’s injury risk properly, it is essential to know how dynamic postural control is influenced by physical load. Therefore, the study’s objective was to examine the influence of maximal anaerobic load on dynamic postural control. Sixty-four sport students (32 males and 32 females, age: 24.11 ± 2.42, height: 175.53 ± 8.17 cm, weight: 67.16 ± 10.08 kg) were tested with the Y-Balance Test before and after a Wingate Anaerobic Test on a bicycle ergometer. In both legs, reach distances (anterior) and composite scores were statistically significantly reduced immediately after the loading protocol. The values almost returned to pre-load levels in about 20 min post-load. Overall, findings indicate an acute negative effect of load on dynamic postural control and a higher potential injury risk during a period of about 20 min post-load. To assess an athlete’s sports-specific injury risk, we recommend testing dynamic postural control under loaded conditions.
Deep Learning and Handcrafted Features for Virus Image Classification
Authors: Nanni Loris , De Luca Eugenio , Facin Marco Ludovico , Maguolo Gianluca
Published: December 2020

In this work, we present an ensemble of descriptors for the classification of virus images acquired using transmission electron microscopy. We trained multiple support vector machines on different sets of features extracted from the data. We used both handcrafted algorithms and a pretrained deep neural network as feature extractors. The proposed fusion strongly boosts the performance obtained by each stand-alone approach, obtaining state of the art performance.
Reliability of Extreme Significant Wave Height Estimation from Satellite Altimetry and In Situ Measurements in the Coastal Zone
Authors: Timmermans Ben , Shaw Andrew , Gommenginger Christine
Published: December 2020

Measurements of significant wave height from satellite altimeter missions are finding increasing application in investigations of wave climate, sea state variability and trends, in particular as the means to mitigate the general sparsity of in situ measurements. However, many questions remain over the suitability of altimeter data for the representation of extreme sea states and applications in the coastal zone. In this paper, the limitations of altimeter data to estimate coastal Hs extremes (<10 km from shore) are investigated using the European Space Agency Sea State Climate Change Initiative L2P altimeter data v1.1 product recently released. This Sea State CCI product provides near complete global coverage and a continuous record of 28 years. It is used here together with in situ data from moored wave buoys at six sites around the coast of the United States. The limitations of estimating extreme values based on satellite data are quantified and linked to several factors including the impact of data corruption nearshore, the influence of coastline morphology and local wave climate dynamics, and the spatio-temporal sampling achieved by altimeters. The factors combine to lead to considerable underestimation of estimated Hs 10-yr return levels. Sensitivity to these factors is evaluated at specific sites, leading to recommendations about the use of satellite data to estimate extremes and their temporal evolution in coastal environments.
Assessing Commonality in Liquidity with Principal Component Analysis: The Case of the Warsaw Stock Exchange
Authors: Olbryś Joanna , Majewska Elżbieta
Published: December 2020

The studies concerning commonality in liquidity on emerging markets in Central and Eastern Europe are scarce and, in particular, they do not utilize the Principal Component Analysis (PCA) to identify latent factors in liquidity. Therefore, the main aim of this research is to assess commonality in liquidity on the Warsaw Stock Exchange (WSE) with the use of the PCA to extract common components of liquidity across a sample of stocks, and from a set of several liquidity proxies. The robustness tests within the whole sample and sub-periods are provided. The PCA results reveal that common latent factors in liquidity estimates exist on the Polish stock market, and three principal components are sufficient to substitute for the seven liquidity proxies utilized in this research. The regressions using these three principal components of liquidity proxies as latent factors in the market model of liquidity indicate no evidence of co-movements in liquidity on the WSE. The results are homogenous for all investigated periods so no reason has been found to reject the research hypothesis that commonality in liquidity does not exist on the Polish stock market. To the best of the authors’ knowledge, no similar research has been conducted for the WSE thus far.
Consumer Behaviour towards Organic Products: The Moderating Role of Environmental Concern
Authors: Cachero-Martínez Silvia
Published: December 2020

The pandemic caused by COVID-19 has changed the mindset of many consumers. They are increasingly aware of the risks of not caring for the planet. Before the pandemic, there was a perceived increase in collective environmental concern and sustainability, but COVID-19 has further accelerated this process and motivated more people to assume this responsibility. Thus, the health crisis could trigger the consumption of organic foods, which are foods produced through environmentally friendly agricultural methods and that have not been artificially altered. It is essential for retailers to know how these consumers of organic foods behave in order to try to modify their strategies. In this context, the objective of this research is to analyze the relationship between attitude, satisfaction, trust, purchase and word-of-mouth (WOM) intentions towards organic products. The results of a survey administered a survey to a sample of 195 consumers show that trust is influenced by satisfaction and attitude. In relation to the behavioural variables, satisfaction is the variable that has the greatest influence on purchase intentions and WOM intentions. In addition, a moderating effect of environmental concern is observed on the proposed relationships.
Numerical and Experimental Results on Charpy Tests for Blends Polypropylene + Polyamide + Ethylene Propylene Diene Monomer (PP + PA + EPDM)
Authors: Pîrvu Cătălin , Musteată Andreea , Ojoc George , Deleanu Lorena
Published: December 2020

This paper presents results from numerical and experimental investigation on Charpy tests in order to point out failure mechanisms and to evaluate new polymeric blends PP + PA6 + EPDM. Charpy tests were done for initial velocity of the impactor of 0.96 m/s and its mass of 3.219 kg and these data were also introduced in the finite element model. The proposed model takes into account the system of four balls, including support and the ring of fixing the three balls and it has a finer discretization of the impact area to highlight the mechanisms of failure and their development in time. The constitutive models for four materials (polypropylene with 1% Kritilen, two blends PP + PA6 + EPDM and a blend PA6 + EPDM) were derived from tensile tests. Running simulations for each constitutive model of material makes possible to differentiate the destruction mechanisms according to the material introduced in the simulation, including the initiation and the development of the crack(s), based on equivalent plastic strain at break (EPS) for each material. The validation of the model and the simulation results were done qualitatively, analyzing the shape of broken surfaces and comparing them to SEM images and quantitatively by comparing the impact duration, energy absorbed by the sample, the value of maximum force during impact. The duration of the destruction of the specimen is longer than the actual one, explainable by the fact that the material model does not take into account the influence of the material deformation speed in Charpy test, the model being designed with the help of tests done at 0.016 m/s (1000 mm/min) (maximum strain rate for the tensile tests). Experimental results are encouraging for recommending the blends 20% PP + 42% PA6 + 28% EPDM and 60% PA6 + 40% EPDM as materials for impact protection at low velocity (1 m/s). Simulation results are closer to the experimental ones for the more brittle tested materials (with less content of PA6 and EPDM) and more distanced for the more ductile materials (with higher content of PA6 and EPDM).
Regulations of T Cell Activation by Membrane and Cytoskeleton
Authors: Kaizuka Yoshihisa
Published: December 2020

Among various types of membrane proteins that are regulated by cytoskeleton, the T cell receptor (TCR) greatly benefits from these cellular machineries for its function. The T cell is activated by the ligation of TCR to its target agonist peptide. However, the binding affinity of the two is not very strong, while the T cell needs to discriminate agonist from many nonagonist peptides. Moreover, the strength and duration of the activation signaling need to be tuned for immunological functions. Many years of investigations revealed that dynamic acto-myosin cytoskeletons and plasma membranes in T cells facilitate such regulations by modulating the spatiotemporal distributions of proteins in plasma membranes and by applying mechanical loads on proteins. In these processes, protein dynamics in multiple scales are involved, ranging from collective molecular motions and macroscopic molecular organizations at the cell–cell interface to microscopic changes in distances between receptor and ligand molecules. In this review, details of how cytoskeletons and membranes regulate these processes are discussed, with the emphasis on how all these processes are coordinated to occur within a single cell system.
H89 Treatment Reduces Intestinal Inflammation and Candida albicans Overgrowth in Mice
Authors: Dumortier Corentin , Charlet Rogatien , Bettaieb Ali , Jawhara Samir
Published: December 2020

Deregulation of the dynamic crosstalk between the gut microbiota, intestinal epithelial cells, and immune cells is critically involved in the development of inflammatory bowel disease and the overgrowth of opportunistic pathogens, including the human opportunistic fungus Candida albicans. In the present study, we assessed the effect of N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H89), a protein kinase A inhibitor, on the migration of macrophages to C. albicans through dextran sulphate sodium (DSS)-challenged Caco-2 cells. We also investigated the impact of H89 on intestinal inflammation and C. albicans clearance from the gut, and determined the diversity of the gut microbiota in a murine model of DSS-induced colitis. H89 reduced the migration of macrophages to C. albicans through DSS-challenged Caco-2 cells. In addition, H89 decreased C. albicans viability and diminished the expression of pro-inflammatory cytokines and innate immune receptors in macrophages and colonic epithelial Caco-2 cells. In mice with DSS-induced colitis, H89 attenuated the clinical and histological scores of inflammation and promoted the elimination of C. albicans from the gut. H89 administration to mice decreased the overgrowth of Escherichia coli and Enterococcus faecalis populations while Lactobacillus johnsonii populations increased significantly. Overall, H89 reduced intestinal inflammation and promoted the elimination of C. albicans from the gut.
Comparative Gut Microbiome Differences between Ferric Citrate and Calcium Carbonate Phosphate Binders in Patients with End-Stage Kidney Disease
Authors: Wu Ping-Hsun , Liu Po-Yu , Chiu Yi-Wen , Hung Wei-Chun , Lin Yi-Ting , Lin Ting-Yun , Hung Szu-Chun , Delicano Rachel Ann , Kuo Mei-Chuan , Wu Chun-Ying
Published: December 2020

Gut dysbiosis in patients with chronic kidney disease (CKD) may induce chronic inflammation and increase morbidity. Phosphate-binding agents, generally used in patients with CKD, may potentially change the composition of the gut microbiota. This study aimed to compare the microbiota composition in hemodialysis patients treated with ferric citrate or calcium carbonate. The stool microbiota was investigated in hemodialysis patients treated with ferric citrate (n = 8) and calcium carbonate (n = 46) using 16S rRNA gene amplicon sequencing profiling using linear discriminant analysis of effect size. Further predictive functional profiling of microbial communities was obtained with Tax4Fun in R. Hemodialysis patients treated with calcium carbonate had a significantly reduced microbial species diversity (Shannon index and Simpson index) and an increased microbial alteration ratio compared with patients treated with ferric citrate. A distinct microbial community structure was found in patients treated with ferric citrate, with an increased abundance of the Bacteroidetes phylum and a decreased abundance of the phylum Firmicutes. Members of the order Lactobacillales were enriched in patients treated with calcium carbonate, whereas taxa of the genera Ruminococcaceae UCG-004, Flavonifractor, and Cronobacter were enriched in patients treated with ferric citrate phosphate binder. In conclusion, Ferric citrate therapy results in a more diverse microbiome community compared to calcium carbonate therapy in hemodialysis patients with phosphate binder treatment. The gut microbiome reflects the phosphate binder choice in hemodialysis patients, further affecting the physiological environment in the gastrointestinal tract.
Editorial for the Special Issue: Molecular Epidemiology, Diagnostics and Management of Respiratory Virus Infections
Authors: Kimura Hirokazu , Hayashi Yuriko , Sada Mitsuru , Ishii Haruyuki , Tsugawa Takeshi , Ryo Akihide
Published: December 2020

In Japan, there is a proverb that the common cold is associated with all diseases [...]
Time-Resolved Observation of the Destination of Microinjected Potato Spindle Tuber Viroid (PSTVd) in the Abaxial Leaf Epidermal Cells of Nicotiana benthamiana
Authors: Seo Hyesu , Wang Ying , Park Woong June
Published: December 2020

Viroids are single-stranded noncoding RNA molecules of 250–400 nucleotides that cause plant diseases. One of the two families of viroids is Pospiviroidae, the members of which replicate in the nuclei of host cells. To replicate in plants, viroids of Pospiviroidae must enter the nucleus. However, the nuclear import of viroids remains understudied. In this work, we documented the time-dependent characteristics of the changes in microinjected fluorescently labeled potato spindle tuber viroid (PSTVd). The cytoplasmic fluorescence disappeared gradually, with only nuclear fluorescence remaining as the PSTVd injected in the cytoplasm was imported into the nucleus. Through this work, we determined that the time for half-maximal nuclear accumulation of the viroid was about 23 min. Interestingly, we found some cells where the nuclear import did not occur, despite the high level of cytosolic viroid injected. In some cells, the injected viroids disappeared within 10–20 min. The nuclear import of PSTVd is not a simple concentration-dependent process but was probably under the regulation of diverse factors that may be missing from some cells used for our observation.
Agaricus bisporus Crude Extract: Characterization and Analytical Application
Authors: Morosanova Maria A. , Fedorova Tatyana V. , Polyakova Alexandra S. , Morosanova Elena I.
Published: December 2020

In the present work crude Agaricus bisporus extract (ABE) has been prepared and characterized by its tyrosinase activity, protein composition and substrate specificity. The presence of mushroom tyrosinase (PPO3) in ABE has been confirmed using two-dimensional electrophoresis, followed by MALDI TOF/TOF MS-based analysis. GH27 alpha-glucosidases, GH47 alpha-mannosidases, GH20 hexosaminidases, and alkaline phosphatases have been also detected in ABE. ABE substrate specificity has been studied using 19 phenolic compounds: polyphenols (catechol, gallic, caffeic, chlorogenic, and ferulic acids, quercetin, rutin, dihydroquercetin, l-dihydroxyphenylalanine, resorcinol, propyl gallate) and monophenols (l-tyrosine, phenol, p-nitrophenol, o-nitrophenol, guaiacol, o-cresol, m-cresol, p-cresol). The comparison of ABE substrate specificity and affinity to the corresponding parameters of purified A. bisporus tyrosinase has revealed no major differences. The conditions for spectrophotometric determination have been chosen and the analytical procedures for determination of 1.4 × 10−4–1.0 × 10−3 M l-tyrosine, 3.1 × 10−6–1.0 × 10−4 M phenol, 5.4 × 10−5–1.0 × 10−3 M catechol, 8.5 × 10−5–1.0 × 10−3 M caffeic acid, 1.5 × 10−4–7.5 × 10−4 M chlorogenic acid, 6.8 × 10−5–1.0 × 10−3 M l-DOPA have been proposed. The procedures have been applied for the determination of l-tyrosine in food supplements, l-DOPA in synthetic serum, and phenol in waste water from the food manufacturing plant. Thus, we have demonstrated the possibility of using ABE as a substitute for tyrosinase in such analytical applications, as food supplements, medical and environmental analysis.
Antimicrobial Constituents from Machaerium Pers.: Inhibitory Activities and Synergism of Machaeriols and Machaeridiols against Methicillin-Resistant Staphylococcus aureus, Vancomycin-Resistant Enterococcus faecium, and Permeabilized Gram-Negative Pathogens
Authors: Muhammad Ilias , Jacob Melissa R. , Ibrahim Mohamed A. , Raman Vijayasankar , Kumarihamy Mallika , Wang Mei , Al-Adhami Taha , Hind Charlotte , Clifford Melanie , Martin Bethany , Zhao Jianping , Sutton J. Mark , Rahman Khondaker Miraz
Published: December 2020

Two new epimeric bibenzylated monoterpenes machaerifurogerol (1a) and 5-epi-machaerifurogerol (1b), and four known isoflavonoids (+)-vestitol (2), 7-O-methylvestitol (3), (+)-medicarpin (4), and 3,8-dihydroxy-9-methoxypterocarpan (5) were isolated from Machaerium Pers. This plant was previously assigned as Machaerium multiflorum Spruce, from which machaeriols A-D (6–9) and machaeridiols A-C (10–12) were reported, and all were then re-isolated, except the minor compound 9, for a comprehensive antimicrobial activity evaluation. Structures of the isolated compounds were determined by full NMR and mass spectroscopic data. Among the isolated compounds, the mixture 10 + 11 was the most active with an MIC value of 1.25 μg/mL against methicillin-resistant Staphylococcus aureus (MRSA) strains BAA 1696, −1708, −1717, −33591, and vancomycin-resistant Enterococcus faecium (VRE 700221) and E. faecalis (VRE 51299) and vancomycin-sensitive E. faecalis (VSE 29212). Compounds 6–8 and 10–12 were found to be more potent against MRSA 1708, and 6, 11, and 12 against VRE 700221, than the drug control ciprofloxacin and vancomycin. A combination study using an in vitro Checkerboard method was carried out for machaeriols (7 or 8) and machaeridiols (11 or 12), which exhibited a strong synergistic activity of 12 + 8 (MIC 0.156 and 0.625 µg/mL), with >32- and >8-fold reduction of MIC’s, compared to 12, against MRSA 1708 and −1717, respectively. In the presence of sub-inhibitory concentrations on polymyxin B nonapeptide (PMBN), compounds 10 + 11, 11, 12, and 8 showed activity in the range of 0.5–8 µg/mL for two strains of Acinetobacter baumannii, 2–16 µg/mL against Pseudomonas aeruginosa PAO1, and 2 µg/mL against Escherichia coli NCTC 12923, but were inactive (MIC > 64 µg/mL) against the two isolates of Klebsiella pneumoniae.
Nutraceutical Approaches of Autophagy and Neuroinflammation in Alzheimer’s Disease: A Systematic Review
Authors: Gruendler Reinhard , Hippe Berit , Sendula Jengic Vesna , Peterlin Borut , Haslberger Alexander G.
Published: December 2020

Aging and the emergence of age-associated illnesses are one of the major challenges of our present society. Alzheimer’s disease (AD) is closely associated with aging and is defined by increasing memory loss and severe dementia. Currently, there are no therapy options available that halt AD progression. This work investigates three hallmarks of the disease (autophagy, neuroinflammation, and senescence) and systematically analyzes if there is a beneficial effect from three substances derived from food sources, the so called “nutraceuticals” epigallocatechin gallate, fisetin, and spermidine, on these hallmarks. The results imply a positive outlook for the reviewed substances to qualify as a novel treatment option for AD. A combination of nutraceutical substances and other preventive measures could have significant clinical impact in a multi-layered therapy approach to counter AD.
Maize Silage Pretreatment via Steam Refining and Subsequent Enzymatic Hydrolysis for the Production of Fermentable Carbohydrates
Authors: Krafft Malte Jörn , Frey Olga , Schwarz Katrin U. , Saake Bodo
Published: December 2020

Maize, also called corn, is one of the most available feedstocks worldwide for lignocellulosic biorefineries. However, a permanent biomass supply over the year is essential for industrial biorefinery application. In that context, ensiling is a well-known agricultural application to produce durable animal feed for the whole year. In this study, ensiled maize was used for steam refining experiments with subsequent enzymatic hydrolysis using the Cellic® CTec2 to test the application possibilities of an ensiled material for the biorefinery purpose of fermentable carbohydrate production. Steam refining was conducted from mild (log R0 = 1.59) to severe conditions (log R0 = 4.12). The yields were determined, and the resulting fractions were characterized. Hereafter, enzymatic hydrolysis of the solid fiber fraction was conducted, and the carbohydrate recovery was calculated. A conversion to monomers of around 50% was found for the mildest pretreatment (log R0 = 1.59). After pretreatment at the highest severity of 4.12, it was possible to achieve a conversion of 100% of the theoretical available carbohydrates. From these results, it is clear that a sufficient pretreatment is necessary to achieve sufficient recovery rates. Thus, it can be concluded that ensiled maize pretreated by steam refining is a suitable and highly available feedstock for lignocellulosic biorefineries. Ultimately, it can be assumed that ensiling is a promising storage method to pave the way for a full-year biomass supply for lignocellulosic biorefinery concepts.
Phenolic Constituents of Lamium album L. subsp. album Flowers: Anatomical, Histochemical, and Phytochemical Study
Authors: Sulborska Aneta , Konarska Agata , Matysik-Woźniak Anna , Dmitruk Marta , Weryszko-Chmielewska Elżbieta , Skalska-Kamińska Agnieszka , Rejdak Robert
Published: December 2020

Flos Lamii albi has a high biological activity and is widely used in herbal medicine. The aim of the study was to characterize the secretory structures present in Lamium album subsp. album corolla and the location of phenolic compounds. Additionally, we carried out qualitative phytochemical analyses of flavonoids and phenolic acids. Light, fluorescence, and scanning electron microscopy were used to analyze the structure of the floral organs. The main classes of phenolic compounds and their localization were determined histochemically. Phytochemical analyses were performed with high-performance thin-layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC). Six types of glandular trichomes were found which contained flavonoids, phenolic acids, and tannins. The phytochemical studies demonstrated the presence of caffeic, chlorogenic, ferulic, gallic, p-coumaric, protocatechuic, syringic, gentisic, and vanillic phenolic acids as well as rutoside, isoquercetin, and quercetin flavonoids. The corolla in L. album subsp. album has antioxidant properties due to the presence of various polyphenols, as shown by the histo- and phytochemical analyses. The distribution and morphology of trichomes and the content of phenolic compounds in the corolla have taxonomic, pharmacognostic, and practical importance, facilitating the identification of the raw material.
PARP Theranostic Auger Emitters Are Cytotoxic in BRCA Mutant Ovarian Cancer and Viable Tumors from Ovarian Cancer Patients Enable Ex-Vivo Screening of Tumor Response
Authors: Riad Aladdin , Gitto Sarah B. , Lee Hwan , Winters Harrison D. , Martorano Paul M. , Hsieh Chia-Ju , Xu Kuiying , Omran Dalia K. , Powell Daniel J. , Mach Robert H. , Makvandi Mehran
Published: December 2020

Theranostics are emerging as a pillar of cancer therapy that enable the use of single molecule constructs for diagnostic and therapeutic application. As poly adenosine diphosphate (ADP)-ribose polymerase 1 (PARP-1) is overexpressed in various cancer types, and is localized to the nucleus, PARP-1 can be safely targeted with Auger emitters to induce DNA damage in tumors. Here, we investigated a radioiodinated PARP inhibitor, [125I]KX1, and show drug target specific DNA damage and subsequent killing of BRCA1 and non-BRCA mutant ovarian cancer cells at sub-pharmacological concentrations several orders of magnitude lower than traditional PARP inhibitors. Furthermore, we demonstrated that viable tumor tissue from ovarian cancer patients can be used to screen tumor radiosensitivity ex-vivo, enabling the direct assessment of therapeutic efficacy. Finally, we showed tumors can be imaged by single-photon computed tomography (SPECT) with PARP theranostic, [123I]KX1, in a human ovarian cancer xenograft mouse model. These data support the utility of PARP-1 targeted radiopharmaceutical therapy as a theranostic option for PARP-1 overexpressing ovarian cancers.
Sample Preparation of Posaconazole Oral Suspensions for Identification of the Crystal Form of the Active Pharmaceutical Ingredient
Authors: Lykouras Michail , Fertaki Stefani , Orkoula Malvina , Kontoyannis Christos
Published: December 2020

Determination of the polymorphic form of an active pharmaceutical ingredient (API) in a suspension could be really challenging because of the water phase and the low concentration of the API in this formulation. Posaconazole is an antifungal drug available also as an oral suspension. The aim of this study was to develop a sample-preparation method for polymorphic identification of the dispersed API by increasing the concentration of the API but with no compromise of polymorph stability. For this purpose, filtration, drying and centrifugation were tested for separating the API from the suspending medium. Centrifugation was selected because it succeeded in separating Posaconazole API with no polymorph transformation during the process. During this study, it was found that Posaconazole in oral suspensions is Form-S. However, when slower scanning rates were used for acquiring an XRPD pattern with better signal/noise ratio, Posaconazole was converted to Form I due to water loss. In order to protect the sample from conversion, different approaches were tested to secure an airtight sample including a commercially available XRPD sample holder with a dome-like transparent cap, standard polymethylmethacrylate (PMMA) sample holders covered with Mylar film, transparent pressure-sensitive tape and a transparent food membrane. Only usage of the transparent food membrane was found to protect the API from conversion for a period of at least two weeks and resulted in a Posaconazole Form-S XRPD pattern with no artificial peaks.
Retrospective Study on the Occurrence of Antibodies against Coxiella burnetii in Dogs from Central Italy
Authors: Ebani Valentina Virginia
Published: December 2020

Coxiella burnetii, a cause of infection in humans and several animal species, is transmitted through inhalations and oral route but also tick bites. Its spreading in ruminants has been largely investigated, whereas data about the occurrence of this infection in canine population are scanty. In this retrospective study, blood serum samples of 516 dogs were tested by indirect immunofluorescence assay to detect antibodies against C. burnetii; 42 (8.13%) were positive with titers ranging from 1:64 to 1:512. The highest seroprevalences were detected in dogs aged > 5 years, employed in hunting activity and living in a peri-urban/rural environment. Diagnosis for C. burnetii infection should be always carried out in bitches with reproductive disorders. Moreover, in view of the zoonotic impact of this infection, asymptomatic dogs exposed to ticks’ bites and/or to contact with infected farm animals should be checked, too.