Miracle-dz/UniFAR-FTUs huggingface dataset:
Virulence during Newcastle Disease Viruses Cross Species Adaptation

The hypothesis that host adaptation in virulent Newcastle disease viruses (NDV) has been accompanied by virulence modulation is reviewed here. Historical records, experimental data, and phylogenetic analyses from available GenBank sequences suggest that currently circulating NDVs emerged in the 1920–1940′s from low virulence viruses by mutation at the fusion protein cleavage site. These viruses later gave rise to multiple virulent genotypes by modulating virulence in opposite directions. Phylogenetic and pathotyping studies demonstrate that older virulent NDVs further evolved into chicken-adapted genotypes by increasing virulence (velogenic-viscerotropic pathotypes with intracerebral pathogenicity indexes [ICPIs] of 1.6 to 2), or into cormorant-adapted NDVs by moderating virulence (velogenic–neurotropic pathotypes with ICPIs of 1.4 to 1.6), or into pigeon-adapted viruses by further attenuating virulence (mesogenic pathotypes with ICPIs of 0.9 to 1.4). Pathogenesis and transmission experiments on adult chickens demonstrate that chicken-adapted velogenic-viscerotropic viruses are more capable of causing disease than older velogenic-neurotropic viruses. Currently circulating velogenic–viscerotropic viruses are also more capable of replicating and of being transmitted in naïve chickens than viruses from cormorants and pigeons. These evolutionary virulence changes are consistent with theories that predict that virulence may evolve in many directions in order to achieve maximum fitness, as determined by genetic and ecologic constraints.
A Global Review on Short Peptides: Frontiers and Perspectives

Peptides are fragments of proteins that carry out biological functions. They act as signaling entities via all domains of life and interfere with protein-protein interactions, which are indispensable in bio-processes. Short peptides include fundamental molecular information for a prelude to the symphony of life. They have aroused considerable interest due to their unique features and great promise in innovative bio-therapies. This work focusing on the current state-of-the-art short peptide-based therapeutical developments is the first global review written by researchers from all continents, as a celebration of 100 years of peptide therapeutics since the commencement of insulin therapy in the 1920s. Peptide “drugs” initially played only the role of hormone analogs to balance disorders. Nowadays, they achieve numerous biomedical tasks, can cross membranes, or reach intracellular targets. The role of peptides in bio-processes can hardly be mimicked by other chemical substances. The article is divided into independent sections, which are related to either the progress in short peptide-based theranostics or the problems posing challenge to bio-medicine. In particular, the SWOT analysis of short peptides, their relevance in therapies of diverse diseases, improvements in (bio)synthesis platforms, advanced nano-supramolecular technologies, aptamers, altered peptide ligands and in silico methodologies to overcome peptide limitations, modern smart bio-functional materials, vaccines, and drug/gene-targeted delivery systems are discussed.
Study of Piezoresistive Behavior of Smart Cement Filled with Graphene Oxide

A cement-based piezoelectric composite, modified by graphene oxide (GO), was prepared to study piezoresistive capacity. The testing confirms that GO is more effective than other carbon nanomaterials at improving piezoresistive sensitivity of cement-based composites, because the content of GO in cement paste was much lower than other carbon nanomaterials used in previously published research. Further investigation indicates that the addition of GO significantly improved the stability and repeatability for piezoresistive capacity of cement paste under cycle loads. Based on experiment results, the piezoresistive sensitivity of this composite depended on GO content, water-to-cement weight ratio (w/c) and water-loss rate, since the highest piezoresistive gauge factor value (GF = 35) was obtained when GO content was 0.05 wt. %, w/c was 0.35 and water-loss rate was 3%. Finally, microstructure analysis confirmed that conductivity and piezoresistivity were achieved through a tunneling effect and by contacting conduction that caused deformation of GO networks in the cement matrix.
Towards elucidating the structure, function, and druggability of coronavirus cis-acting RNA motifs/ Zglebiajac zawilosci struktur, funkcji i lekowalnosci cis motywów RNA u koronawirusów

Coronaviruses are the causative agents of mild to severe respiratory and intestinal infections in humans. They are the largest RNA viruses, which genomes and encoded RNAs are known to fold into the highly-order structures that play essential roles in the viral replication and infectivity cycle. The recent outbreaks of new pathogenic coronaviruses steered researchers' attention into the possibility of targeting their RNAs directly with novel RNA-specific drugs and therapeutic strategies. In this manuscript, we highlight the recent biochemical and biophysical methodological advancements that yielded more in-depth insight into the structural and functional composition of coronaviruses cis-acting RNA motifs. We discuss the complexity of these RNA regulatory elements, their intermolecular interactions, post-transcriptional regulation, and their potential as druggable targets. We also indicate the location and function of unstructured and highly-conserved regions in coronaviruses RNA genomes representing viable aims for antisense oligonucleotide or CRISPR-based antiviral strategies.
From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones

This work reviews the contributions of the corresponding author (M.M.M.P.) and her research group to Medicinal Chemistry concerning the isolation from plant and marine sources of xanthone derivatives as well as their synthesis, biological/pharmacological activities, formulation and analytical applications. Although her group activity has been spread over several chemical families with relevance in Medicinal Chemistry, the main focus of the investigation and research has been in the xanthone family. Xanthone derivatives have a variety of activities with great potential for therapeutic applications due to their versatile framework. The group has contributed with several libraries of xanthones derivatives, with a variety of activities such as antitumor, anticoagulant, antiplatelet, anti-inflammatory, antimalarial, antimicrobial, hepatoprotective, antioxidant, and multidrug resistance reversal effects. Besides therapeutic applications, our group has also developed xanthone derivatives with analytical applications as chiral selectors for liquid chromatography and for maritime application as antifouling agents for marine paints. Chemically, it has been challenging to afford green chemistry methods and achieve enantiomeric purity of chiral derivatives. In this review, the structures of the most significant compounds will be presented.
Towards the Preparation of Ordered Mesoporous Carbon/Carbon Composite Membranes for Gas Separation

Carbon/carbon composite membranes (CCMs) were made using the blend of polyimide with ordered mesoporous carbon (OMC) as precursor at a pyrolysis temperature of 650°C. The thermal stability of precursors, the structure evolution, and the morphology and gas separation performance of CCMs were investigated. The results have shown that the CCMs are one of the most attractive membrane materials for gas separation. The thermal stability of the precursor is improved by the addition of OMC. OMC can tightly embed in the membrane matrix due to the carbonaceous homology of matrix. As a result of the addition of OMC into carbon membranes, the gas permeability of O2 increases ten times, together with the O2/N2 selectivity significantly boosting from 10.3 to 12.9.
Selection and Validation of Reference Genes for Quantitative RT-PCR Analysis in Corylus heterophylla Fisch. × Corylus avellana L.

(1) Background: the species of Corylus have sporophytic type of self-incompatibility. Several genes related to recognition reaction between pollen and stigma have been identified in hazelnuts. To better understand the self-incompatibility (SI) response, we screened the suitable reference genes by using quantitative real-time reverse transcription PCR (qRT-PCR) analysis in hazelnut for the first time. (2) Methods: the major cultivar “Dawei” was used as material. A total of 12 candidate genes were identified and their expression profiles were compared among different tissues and in response to various treatments (different times after self- and cross-pollination) by RT-qPCR. The expression stability of these 12 candidate reference genes was evaluated using geNorm, NormFinder, BestKeeper, Delta Ct, and RefFinder programs. (3) Results: the comprehensive ranking of RefFinder indicated that ChaActin, VvActin, ChaUBQ14, and ChaEF1-α were the most suitable reference genes. According to the stability analysis of 12 candidate reference genes for each sample group based on four software packages, ChaActin and ChaEF1-α were most stable in different times after self-pollination and 4 h after self- and cross-pollination, respectively. To further validate the suitability of the reference genes identified in this study, CavPrx, which the expression profiles in Corylus have been reported, was quantified by using ChaActin and ChaEF1-α as reference genes. (4) Conclusions: our study of reference genes selection in hazelnut shows that the two reference genes, ChaActin and ChaEF1-α, are suitable for the evaluation of gene expression, and can be used for the analysis of pollen-pistil interaction in Corylus. The results supply a reliable foundation for accurate gene quantifications in Corylus species, which will facilitate the studies related to the reproductive biology in Corylus.
A Dual Role of Heme Oxygenase-1 in Angiotensin II-Induced Abdominal Aortic Aneurysm in the Normolipidemic Mice

Abdominal aortic aneurysm (AAA) bears a high risk of rupture and sudden death of the patient. The pathogenic mechanisms of AAA remain elusive, and surgical intervention represents the only treatment option. Heme oxygenase-1 (HO-1), a heme degrading enzyme, is induced in AAA, both in mice and humans. HO-1 was reported to mitigate AAA development in an angiotensin II (AngII)-induced model of AAA in hyperlipidemic ApoE-/- mice. Since the role of hyperlipidaemia in the pathogenesis of AAA remains controversial, we aimed to evaluate the significance of HO-1 in the development and progression of AAA in normolipidemic animals. The experiments were performed in HO-1-deficient mice and their wild-type counterparts. We demonstrated in non-hypercholesterolemic mice that the high-dose of AngII leads to the efficient formation of AAA, which is attenuated by HO-1 deficiency. Yet, if formed, they are significantly more prone to rupture upon HO-1 shortage. Differential susceptibility to AAA formation does not rely on enhanced inflammatory response or oxidative stress. AAA-resistant mice are characterized by an increase in regulators of aortic remodeling and angiotensin receptor-2 expression, significant medial thickening, and delayed blood pressure elevation in response to AngII. To conclude, we unveil a dual role of HO-1 deficiency in AAA in normolipidemic mice, where it protects against AAA development, but exacerbates the state of formed AAA.
Effect of Polyhexamethylene Biguanide in Combination with Undecylenamidopropyl Betaine or PslG on Biofilm Clearance

Hospital-acquired infection is a great challenge for clinical treatment due to pathogens’ biofilm formation and their antibiotic resistance. Here, we investigate the effect of antiseptic agent polyhexamethylene biguanide (PHMB) and undecylenamidopropyl betaine (UB) against biofilms of four pathogens that are often found in hospitals, including Gram-negative bacteria Pseudomonas aeruginosa and Escherichia coli, Gram-positive bacteria Staphylococcus aureus, and pathogenic fungus, Candida albicans. We show that 0.02% PHMB, which is 10-fold lower than the concentration of commercial products, has a strong inhibitory effect on the growth, initial attachment, and biofilm formation of all tested pathogens. PHMB can also disrupt the preformed biofilms of these pathogens. In contrast, 0.1% UB exhibits a mild inhibitory effect on biofilm formation of the four pathogens. This concentration inhibits the growth of S. aureus and C. albicans yet has no growth effect on P. aeruginosa or E. coli. UB only slightly enhances the anti-biofilm efficacy of PHMB on P. aeruginosa biofilms. However, pretreatment with PslG, a glycosyl hydrolase that can efficiently inhibit and disrupt P. aeruginosa biofilm, highly enhances the clearance effect of PHMB on P. aeruginosa biofilms. Meanwhile, PslG can also disassemble the preformed biofilms of the other three pathogens within 30 min to a similar extent as UB treatment for 24 h.
Effects of Fruit and Vegetable-Based Nutraceutical on Cognitive Function in a Healthy Population: Placebo-Controlled, Double-Blind, and Randomized Clinical Trial

There is scientific evidence of the positive effect of polyphenols from plant foods on cognition, but not enough is known about the synergistic effect when multiple polyphenols are consumed and even less in a healthy non-elderly population. The aim of the present study is to investigate the possible effects of improvements in cognitive function in healthy people as a preparation based on micronized fruit and vegetables consumed. One hundred and eight subjects were selected, stratified by sex in the control intervention group (n = 53) and placebo (n = 55). Volunteers completed the study after two 16-week periods of consumption with a 4-week wash period between each phase. At the beginning and the end of each phase, volunteers performed the Stroop, TESEN, and RIST tests for the measurement of different cognitive function patterns. The results revealed statistically significant differences in all the variables of the tests carried out, especially compared with the placebo. Specially, the results obtained in the Stroop and TESEN test, in addition to the processing speed even with semantic interferences, were markedly better after the treatment with the product under study. Moreover, the consumption of the product under study clearly improves short-term memory, verbal and non-verbal, according to the results obtained in the RIST test. The results showed an improvement in executive function in terms of short-term memory, working memory, selective and sustained attention, and speed of processing.
The short third intracellular loop and cytoplasmic tail of bitter taste receptors provide functionally relevant GRK phosphorylation sites in TAS2R14

For most G protein–coupled receptors, the third intracellular loop (IL3) and carboxy-terminal tail (CT) are sites for G protein–coupled receptor kinase (GRK)–mediated phosphorylation, leading to β-arrestin binding and agonist-specific desensitization. These regions of bitter taste receptors (TAS2Rs) are extremely short compared with the superfamily, and their function in desensitization is unknown. TAS2R14 expressed on human airway smooth muscle cells relax the cell, suggesting a novel target for bronchodilators. To assess IL3 and CT in agonist-promoted TAS2R14 desensitization (tachyphylaxis), we generated fusion proteins of both the WT sequence and Ala substituted for Ser/Thr in the IL3 and CT sequences. In vitro, activated GRK2 phosphorylated WT IL3 and WT CT proteins but not Ala-substituted forms. TAS2R14s with mutations in IL3 (IL-5A), CT (CT-5A), and in both regions (IL/CT-10A) were expressed in human embryonic kidney 293T cells. IL/CT-10A and CT-5A failed to undergo desensitization of the intracellular calcium response compared with WT, indicating that functional desensitization by GRK phosphorylation is at residues in the CT. Desensitization of TAS2R14 was blocked by GRK2 knockdown in human airway smooth muscle cells. Receptor:β-arrestin binding was absent in IL/CT-10A and CT-5A and reduced in IL-5A, indicating a role for IL3 phosphorylation in the β-arrestin interaction for this function. Agonist-promoted internalization of IL-5A and CT-5A receptors was impaired, and they failed to colocalize with early endosomes. Thus, agonist-promoted functional desensitization of TAS2R14 occurs by GRK phosphorylation of CT residues and β-arrestin binding. However, β-arrestin function in the internalization and trafficking of the receptor also requires GRK phosphorylation of IL3 residues.
Assessing the Toxicity of Individual Aromatic Compounds and Mixtures to American Lobster (Homarus americanus) Larvae Using a Passive Dosing System

Aquatic exposures to aromatic compounds (ACs) may be important contributors to biological effects of oil spills. The present study examined the acute toxicity of 11 ACs and 3 binary AC mixtures on stage 1 American lobster larvae using a passive dosing test design. The ACs investigated covered a range of classes and log octanol–water partition coefficient values (KOW; 2.5–5.5). Silicone O‐rings were used to partition ACs into seawater and maintain stable exposures. Exposed lobster larvae were assessed for mobility and survival at 3, 6, 12, 24, 36, and 48 h. Fluorometry and gas chromatography‐mass spectrometry measurements confirmed well‐defined substance exposures. Expressing lethality in terms of chemical activities yielded values between 0.01 and 0.1, consistent with a baseline mode of action. Analysis of time‐dependent median lethal/effect concentration (L/EC50) values were used to determine incipient values. An expected linear relationship between the incipient log L/EC50 and log KOW was fit to the empirical toxicity data to derive critical target lipid body burdens for immobilization and lethality endpoints. These values indicate that American lobster larvae fall on the sensitive end of the acute species sensitivity distribution. We used AC toxicity data to successfully predict toxicity of binary mixtures assuming additive toxicity. The observed time‐dependent toxicity was inversely related to log KOW and occurred more quickly than reported previously. The results contribute to improving models for predicting oil spill impacts on American lobster larvae populations. Environ Toxicol Chem 2021;40:1379–1388. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Application of an Adaptive, Digital, Game-Based Approach for Cognitive Assessment in Multiple Sclerosis: Observational Study

Background Cognitive impairment is one of the most debilitating manifestations of multiple sclerosis. Currently, the assessment of cognition relies on a time-consuming and extensive neuropsychological examination, which is only available in some centers. Objective To enable simpler, more accessible cognitive screening, we sought to determine the feasibility and potential assessment sensitivity of an unsupervised, adaptive, video game–based digital therapeutic to assess cognition in multiple sclerosis. Methods A total of 100 people with multiple sclerosis (33 with cognitive impairment and 67 without cognitive impairment) and 24 adults without multiple sclerosis were tested with the tablet game (EVO Monitor) and standard measures, including the Brief International Cognitive Assessment for Multiple Sclerosis (which included the Symbol Digit Modalities Test [SDMT]) and Multiple Sclerosis Functional Composite 4 (which included the Timed 25-Foot Walk test). Patients with multiple sclerosis also underwent neurological evaluations and contributed recent structural magnetic resonance imaging scans. Group differences in EVO Monitor performance and the association between EVO Monitor performance and standard measures were investigated. Results Participants with multiple sclerosis and cognitive impairment showed worse performance in EVO Monitor compared with participants without multiple sclerosis (P=.01) and participants with multiple sclerosis without cognitive impairment (all P<.002). Regression analyses indicated that participants with a lower SDMT score showed lower performance in EVO Monitor (r=0.52, P<.001). Further exploratory analyses revealed associations between performance in EVO Monitor and walking speed (r=–0.45, P<.001) as well as brain volumetric data (left thalamic volume: r=0.47, P<.001; right thalamic volume: r=0.39, P=.002; left rostral middle frontal volume: r=0.28, P=.03; right rostral middle frontal volume: r=0.27, P=.03). Conclusions These findings suggest that EVO Monitor, an unsupervised, video game–based digital program integrated with adaptive mechanics, is a clinically valuable approach to measuring cognitive performance in patients with multiple sclerosis. Trial Registration ClinicalTrials.gov NCT03569618; https://clinicaltrials.gov/ct2/show/NCT03569618
Managing Precarity: Understanding Latinas’ Sexual and Reproductive Care-Seeking in a Midwest Emergent Latino Community

In this qualitative interview study, we took a two-pronged approach to understand the complexities of sexual and reproductive health (SRH) care access for Latinas in an emerging Latino community (ELC). Phase 1 assessed the SRH resources available for uninsured Latinas through provider interviews. In Phase 2, we interviewed 15 Latina-identified women about their considerations for SRH care-seeking. The scant options for SRH care are focused largely on contraception and pregnancy. Providers viewed themselves as prevention-oriented and perceived Latinas did not prioritize preventive care. Women described compounding challenges and precarious conditions. Annual checkups, accessing contraception, and treating vaginal infections were identified as needs. Barriers to SRH care were enhanced in an ELC. Participants described too much paperwork and limited time as organizational barriers which aggravated others, such as language limitations and feeling embarrassed to ask questions. Further research on SRH care using a reproductive justice approach is needed in ELCs.
Estimating Functional Threshold Power in Endurance Running from Shorter Time Trials Using a 6-Axis Inertial Measurement Sensor

Wearable technology has allowed for the real-time assessment of mechanical work employed in several sporting activities. Through novel power metrics, Functional Threshold Power have shown a reliable indicator of training intensities. This study aims to determine the relationship between mean power output (MPO) values obtained during three submaximal running time trials (i.e., 10 min, 20 min, and 30 min) and the functional threshold power (FTP). Twenty-two recreationally trained male endurance runners completed four submaximal running time trials of 10, 20, 30, and 60 min, trying to cover the longest possible distance on a motorized treadmill. Absolute MPO (W), normalized MPO (W/kg) and standard deviation (SD) were calculated for each time trial with a power meter device attached to the shoelaces. All simplified FTP trials analyzed (i.e., FTP10, FTP20, and FTP30) showed a significant association with the calculated FTP (p < 0.001) for both MPO and normalized MPO, whereas stronger correlations were found with longer time trials. Individual correction factors (ICF% = FTP60/FTPn) of ~90% for FTP10, ~94% for FTP20, and ~96% for FTP30 were obtained. The present study procures important practical applications for coaches and athletes as it provides a more accurate estimation of FTP in endurance running through less fatiguing, reproducible tests.