Miracle-dz/UniFAR-FTUs huggingface dataset:
Host Suitability for Crapemyrtle Bark Scale (Acanthococcus lagerstroemiae) Differed Significantly among Crapemyrtle Species

Simple Summary An exotic insect, crapemyrtle bark scale (CMBS, Acanthococcus lagerstroemiae), has spread across 14 states of the U.S. The infestation of CMBS has negatively impacted the growth, flowering, and even fruiting of some Lythraceae plants to various extent, including cultivars of Lagerstroemia indica, L. fauriei, and Punica granatum. This raises concerns that CMBS would threaten other crapemyrtle species and native Lythraceae plants. Understanding the host range and the host suitability for CMBS would help evaluate the potential risks to landscapes and other ecosystems. Information on the host suitability provides beneficial information for breeding resistant cultivars. In this study, we conducted a host range test on six Lagerstroemia species (L. caudata, L. fauriei ‘Kiowa’, L. indica ‘Dynamite’, L. limii, L. speciosa, and L. subcostata) and a native Lythraceae plant in California (California loosestrife, Lythrum californicum) over 25 weeks. The infestation of CMBS was observed on all the tested Lythraceae plants. The suitability for CMBS differed significantly among the Lagerstroemia species. Lagerstroemia limii was the most suitable, whereas L. speciosa was the least suitable. This study expands the current knowledge on the host range for CMBS. Our results suggest that L. speciosa could be utilized in developing new cultivars with low CMBS suitability. Abstract Crapemyrtle bark scale (CMBS, Acanthococcus lagerstroemiae), an invasive polyphagous sap-sucking hemipteran, has spread across 14 states of the United States since 2004. The infestation of CMBS has negatively impacted the flowering of ornamental plants and even the fruiting of some crops. Host identification is critical for determining potential risks in ecosystems and industries and helps develop strategic management. A host confirmation test was performed over 25 weeks using six Lagerstroemia species (L. caudata, L. fauriei ‘Kiowa’, L. indica ‘Dynamite’, L. limii, L. speciosa, and L. subcostata) and California loosestrife (Lythrum californicum). The 25-week observations confirmed all tested plants as the hosts. The repeated measures of analysis of variance (ANOVA; Tukey’s HSD, α = 0.05) indicated that the average number of CMBS females differed significantly between L. limii and L. speciosa. The highest number of the females observed on L. limii was 576 ± 25 (mean ± SE) at 17 weeks after inoculation (WAI), while the highest number was 57 ± 15 on L. speciosa at 19 WAI. In addition, L. subcostata and L. speciosa had significantly high and low numbers of males, respectively, among the Lagerstroemia species. Our results suggest that L. speciosa could be incorporated in developing new cultivars with low CMBS suitability.
Visual System Impairment in a Mouse Model of Krabbe Disease: The Twitcher Mouse

Krabbe disease (KD, or globoid cell leukodystrophy; OMIM #245200) is an inherited neurodegenerative condition belonging to the class of the lysosomal storage disorders. It is caused by genetic alterations in the gene encoding for the enzyme galactosylceramidase, which is responsible for cleaving the glycosydic linkage of galatosylsphingosine (psychosine or PSY), a highly cytotoxic molecule. Here, we describe morphological and functional alterations in the visual system of the Twitcher (TWI) mouse, the most used animal model of Krabbe disease. We report in vivo electrophysiological recordings showing defective basic functional properties of the TWI primary visual cortex. In particular, we demonstrate a reduced visual acuity and contrast sensitivity, and a delayed visual response. Specific neuropathological alterations are present in the TWI visual cortex, with reduced myelination, increased astrogliosis and microglia activation, and around the whole brain. Finally, we quantify PSY content in the brain and optic nerves by high-pressure liquid chromatography-mass spectrometry methods. An increasing PSY accumulation with time, the characteristic hallmark of KD, is found in both districts. These results represent the first complete characterization of the TWI visual system. Our data set a baseline for an easy testing of potential therapies for this district, which is also dramatically affected in KD patients.
Structural Variability, Expression Profile, and Pharmacogenetic Properties of TMPRSS2 Gene as a Potential Target for COVID-19 Therapy

The human serine protease serine 2 TMPRSS2 is involved in the priming of proteins of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and represents a possible target for COVID-19 therapy. The TMPRSS2 gene may be co-expressed with SARS-CoV-2 cell receptor genes angiotensin-converting enzyme 2 (ACE2) and Basigin (BSG), but only TMPRSS2 demonstrates tissue-specific expression in alveolar cells according to single-cell RNA sequencing data. Our analysis of the structural variability of the TMPRSS2 gene based on genome-wide data from 76 human populations demonstrates that a functionally significant missense mutation in exon 6/7 in the TMPRSS2 gene is found in many human populations at relatively high frequencies, with region-specific distribution patterns. The frequency of the missense mutation encoded by rs12329760, which has previously been found to be associated with prostate cancer, ranged between 10% and 63% and was significantly higher in populations of Asian origin compared with European populations. In addition to single-nucleotide polymorphisms, two copy number variants were detected in the TMPRSS2 gene. A number of microRNAs have been predicted to regulate TMPRSS2 and BSG expression levels, but none of them is enriched in lung or respiratory tract cells. Several well-studied drugs can downregulate the expression of TMPRSS2 in human cells, including acetaminophen (paracetamol) and curcumin. Thus, the interactions of TMPRSS2 with SARS-CoV-2, together with its structural variability, gene–gene interactions, expression regulation profiles, and pharmacogenomic properties, characterize this gene as a potential target for COVID-19 therapy.
Quadriceps Strength Symmetry Does Not Modify Gait Mechanics After Anterior Cruciate Ligament Reconstruction, Rehabilitation, and Return-to-Sport Training

Background: After anterior cruciate ligament (ACL) reconstruction (ACLR), biomechanical asymmetries during gait are highly prevalent, persistent, and linked to posttraumatic knee osteoarthritis. Quadriceps strength is an important clinical measure associated with preoperative gait asymmetries and postoperative function and is a primary criterion for return-to-sport clearance. Evidence relating symmetry in quadriceps strength with gait biomechanics is limited to preoperative and early rehabilitation time points before return-to-sport training. Purpose/Hypothesis: The purpose was to determine the relationship between symmetry in isometric quadriceps strength and gait biomechanics after return-to-sport training in athletes after ACLR. We hypothesized that as quadriceps strength symmetry increases, athletes will demonstrate more symmetric knee joint biomechanics, including tibiofemoral joint loading during gait. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Of 79 athletes enrolled in the ACL-SPORTS Trial, 76 were participants in this study after completing postoperative rehabilitation and 10 return-to-sport training sessions (mean ± SD, 7.1 ± 2.0 months after ACLR). All participants completed biomechanical walking gait analysis and isometric quadriceps strength assessment using an electromechanical dynamometer. Quadriceps strength was calculated using a limb symmetry index (involved limb value / uninvolved limb value × 100). The biomechanical variables of interest included peak knee flexion angle, peak knee internal extension moment, sagittal plane knee excursion at weight acceptance and midstance, quadriceps muscle force at peak knee flexion angle, and peak medial compartment contact force. Spearman rank correlation (ρ) coefficients were used to determine the relationship between limb symmetry indexes in quadriceps strength and each biomechanical variable; alpha was set to . 05. Results: Of the 76 participants, 27 (35%) demonstrated asymmetries in quadriceps strength, defined by quadriceps strength symmetry <90% (n = 23) or >110% (n = 4) (range, 56.9%-131.7%). For the biomechanical variables of interest, 67% demonstrated asymmetry in peak knee flexion angle; 68% and 83% in knee excursion during weight acceptance and midstance, respectively; 74% in internal peak knee extension moment; 57% in medial compartment contact force; and 74% in quadriceps muscle force. There were no significant correlations between quadriceps strength index and limb symmetry indexes for any biomechanical variable after return-to-sport training (P > .129). Conclusion: Among those who completed return-to-sport training after ACLR, subsequent quadriceps strength symmetry was not correlated with the persistent asymmetries in gait biomechanics. After a threshold of quadriceps strength is reached, restoring strength alone may not ameliorate gait asymmetries, and current clinical interventions and return-to-sport training may not adequately target gait.
MYC DNA Methylation in Prostate Tumor Tissue is Associated with Gleason Score

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3′ UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: −14.74 to −0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10−4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.
Coping Mechanisms: Exploring Strategies Utilized by Japanese Healthcare Workers to Reduce Stress and Improve Mental Health during the COVID-19 Pandemic

The COVID-19 pandemic is a major problem affecting the mental health of millions of people, including healthcare workers. In this study, we analyzed risk factors and coping mechanisms that could reduce the risk of poor mental health among healthcare workers during the COVID-19 pandemic in Japan. A cross-sectional survey was conducted for 7 days from 30 April 2020 using a web-based questionnaire. The survey assessed various outcome measures, including the General Health Questionnaire-12 (GHQ-12), health status, satisfaction with daily life activities, work, leisure, and new activities, and anxiety over COVID-19. Data from 661 participants were analyzed, and 440 participants (66.6%) showed poor mental health (GHQ-12 ≥ 4). Also, our result showed that female gender, lower levels of communication with friends, and high anxiety were associated with poorer mental health. In contrast, good health status, high work satisfaction, and high satisfaction from new activities were associated with buffering mental health problem. Most participants chose an escape-avoidance coping strategy, and participants with worse mental health were more likely to adopt seeking social support as a coping strategy. These results may support healthcare workers to cope with mental health problems associated with the COVID-19 pandemic.
Structure and mechanism of Staphylococcus aureus oleate hydratase (OhyA)

Flavin adenine dinucleotide (FAD)-dependent bacterial oleate hydratases (OhyAs) catalyze the addition of water to isolated fatty acid carbon–carbon double bonds. Staphylococcus aureus uses OhyA to counteract the host innate immune response by inactivating antimicrobial unsaturated fatty acids. Mechanistic information explaining how OhyAs catalyze regiospecific and stereospecific hydration is required to understand their biological functions and the potential for engineering new products. In this study, we deduced the catalytic mechanism of OhyA from multiple structures of S. aureus OhyA in binary and ternary complexes with combinations of ligands along with biochemical analyses of relevant mutants. The substrate-free state shows Arg81 is the gatekeeper that controls fatty acid entrance to the active site. FAD binding engages the catalytic loop to simultaneously rotate Glu82 into its active conformation and Arg81 out of the hydrophobic substrate tunnel, allowing the fatty acid to rotate into the active site. FAD binding also dehydrates the active site, leaving a single water molecule connected to Glu82. This active site water is a hydronium ion based on the analysis of its hydrogen bond network in the OhyA•PEG400•FAD complex. We conclude that OhyA accelerates acid-catalyzed alkene hydration by positioning the fatty acid double bond to attack the active site hydronium ion, followed by the addition of water to the transient carbocation intermediate. Structural transitions within S. aureus OhyA channel oleate to the active site, curl oleate around the substrate water, and stabilize the hydroxylated product to inactivate antimicrobial fatty acids.
Repurposing the McoTI-II Rigid Molecular Scaffold in to Inhibitor of ‘Papain Superfamily’ Cysteine Proteases

Clan C1A or ‘papain superfamily’ cysteine proteases are key players in many important physiological processes and diseases in most living systems. Novel approaches towards the development of their inhibitors can open new avenues in translational medicine. Here, we report a novel design of a re-engineered chimera inhibitor Mco-cysteine protease inhibitor (CPI) to inhibit the activity of C1A cysteine proteases. This was accomplished by grafting the cystatin first hairpin loop conserved motif (QVVAG) onto loop 1 of the ultrastable cyclic peptide scaffold McoTI-II. The recombinantly expressed Mco-CPI protein was able to bind with micromolar affinity to papain and showed remarkable thermostability owing to the formation of multi-disulphide bonds. Using an in silico approach based on homology modelling, protein–protein docking, the calculation of the free-energy of binding, the mechanism of inhibition of Mco-CPI against representative C1A cysteine proteases (papain and cathepsin L) was validated. Furthermore, molecular dynamics simulation of the Mco-CPI–papain complex validated the interaction as stable. To conclude, in this McoTI-II analogue, the specificity had been successfully redirected towards C1A cysteine proteases while retaining the moderate affinity. The outcomes of this study pave the way for further modifications of the Mco-CPI design for realizing its full potential in therapeutics. This study also demonstrates the relevance of ultrastable peptide-based scaffolds for the development of novel inhibitors via grafting.
Label-Free Amperometric Immunosensor Based on Versatile Carbon Nanofibers Network Coupled with Au Nanoparticles for Aflatoxin B1 Detection

Facile detection methods for mycotoxins with high sensitivity are of great significance to prevent potential harm to humans. Herein, a label-free amperometric immunosensor based on a 3-D interconnected carbon nanofibers (CNFs) network coupled with well-dispersed Au nanoparticles (AuNPs) is proposed for the quantitative determination of aflatoxin B1 (AFB1) in wheat samples. In comparison to common carbon nanotubes (CNTs), the CNFs network derived from bacterial cellulose biomass possesses a unique hierarchically porous structure for fast electrolyte diffusion and a larger electrochemical active area, which increases the peak current of differential pulse voltammetry curves for an immunosensor. Combined with AuNPs that are incorporated into CNFs by using linear polyethyleneimine (PEI) as a soft template, the developed Au@PEI@CNFs-based immunosensor showed a good linear response to AFB1 concentrations in a wide range from 0.05 to 25 ng mL−1. The limit of detection was 0.027 ng mL−1 (S/N = 3), more than three-fold lower than that of an Au@PEI@CNTs-based sensor. The reproducibility, storage stability and selectivity of the immunosensor were proved to be satisfactory. The developed immunosensor with appropriate sensitivity and reliable accuracy can be used for the analysis of wheat samples.
Identification of a blaVIM-1-Carrying IncA/C2 Multiresistance Plasmid in an Escherichia coli Isolate Recovered from the German Food Chain

Within the German national monitoring of zoonotic agents, antimicrobial resistance determination also targets carbapenemase-producing (CP) Escherichia coli by selective isolation from food and livestock. In this monitoring in 2019, the CP E. coli 19-AB01133 was recovered from pork shoulder. The isolate was assigned to the phylogenetic group B1 and exhibited the multi-locus sequence-type ST5869. Molecular investigations, including whole genome sequencing, of 19-AB01133 revealed that the isolate carried the resistance genes blaVIM-1, blaSHV-5 and blaCMY-13 on a self-transmissible IncA/C2 plasmid. The plasmid was closely related to the previously described VIM-1-encoding plasmid S15FP06257_p from E. coli of pork origin in Belgium. Our results indicate an occasional spread of the blaVIM-1 gene in Enterobacteriaceae of the European pig population. Moreover, the blaVIM-1 located on an IncA/C2 plasmid supports the presumption of a new, probably human source of carbapenemase-producing Enterobacteriaceae (CPE) entering the livestock and food chain sector.
Potential Effects of Human Papillomavirus Type Substitution, Superinfection Exclusion and Latency on the Efficacy of the Current L1 Prophylactic Vaccines

There are >200 different types of human papilloma virus (HPV) of which >51 infect genital epithelium, with ~14 of these classed as high-risk being more commonly associated with cervical cancer. During development of the disease, high-risk types have an increased tendency to develop a truncated non-replicative life cycle, whereas low-risk, non-cancer-associated HPV types are either asymptomatic or cause benign lesions completing their full replicative life cycle. HPVs can also be present as non-replicative so-called “latent” infections and they can also show superinfection exclusion, where cells with pre-existing infections with one type cannot be infected with a different HPV type. Thus, the HPV repertoire and replication status present in an individual can form a complex dynamic meta-community which changes with respect to both time and exposure to different HPV types. In light of these considerations, it is not clear how current prophylactic HPV vaccines will affect this system and the potential for iatrogenic outcomes is discussed in light of recent outcome data.
Investigation of non‐covalent ligand binding to the intact streptavidin tetramer by electrospray ionization mass spectrometry

The relative non-covalent binding behavior of two small molecule ligands to the tetrameric protein streptavidin was investigated by electrospray ionization mass spectrometry (ESI-MS). An extended m/z range quadrupole mass spectrometer was employed to observe the intact multimeric form of the protein and to probe the relative stabilities of the tetrameric protein- ligand complexes in the gas phase. Various protein:ligand molar ratio concentrations and incubation times were studied for the ligands biotin (Kd ≈ 10−15 M) and iminobiotin (Kd ≈ 10−7 M), in combination with the adjustment of variables in the ESI atmosphere-vacuum interface region. Positive-ion ESI-MS of a 1:7 molar ratio streptvidin–biotin sample produced peaks corresponding to the intact tetrameric complex (16+ to 14+ charge states) with four ligands binding to the active from of the protein. Only the expected specific non-covalent complexes of four ligand molecules binding to the protein tetramer were detected, consistent with known solution behavior and without the appearance of any random aggregation. However, under identical interface conditions, complete iminobiotin binding to the protein was not observed, even when higher ligand concentrations, longer complexation times and gentler interface conditions were employed. The thermally induced dissociation (TID) of the non-covalent complexes was studied by applying more severe conditions in the ESI interface region. In addition, observation of an intact streptavidin–biotinylated oligonucleotide non-covalent complex (17– to 14– tetrameric charge states) by negative-ion ESI-MS at m/z 4500–5000 is presented. The results show that the complexes observed in the mass spectrometer are representative of those that exist in solution, under the ESI conditions employed, and that the ability to observe such complexes is at least qualitatively related to stability in solution.
Do Canine Behavioural Assessments and Characteristics Predict the Human-Dog Interaction When Walking on a Leash in a Shelter Setting?

Simple Summary We explored 370 human-dog interactions in an animal shelter when volunteers walked shelter dogs on a leash, considering the effects of canine demographics and the results of the shelter’s canine behavioural assessments. Results showed that dogs that were more relaxed during the shelter assessment (i.e., when socialising with humans or being left alone in a new environment) were less reactive on the leash, with lower tension and pulling frequency. Moreover, socialised and relaxed dogs displayed more positive body language, such as tail in a high position, gazing at the handler, and exploring the environment. When walking with these dogs, volunteers utilised fewer verbal guidance cues and body language during the walk. In addition to the canine behaviour assessment, there were correlations between canine demographics (i.e., age, skull shape, body size, and previous ownership history) and the behavioural interaction and humans’ perception. Finally, volunteers perceived the walk as less satisfactory when they needed to pull the leash harder during the walk. This research suggests that the RSPCA behavioural assessment may be useful in predicting the behaviour of shelter dogs when walked by volunteers. Abstract Inappropriate leash reactivity is one of the most common problems in shelter dogs, which negatively affects the health of dogs and reduces their adoptability. We explored 370 human-dog interactions, involving 74 volunteers and 111 dogs, in an animal shelter when volunteers walked shelter dogs on a leash, considering the effects of canine demographics and the results of the shelter’s canine behavioural assessments. The interaction was video recorded and coded using ethograms, and a leash tension meter was used to measure the pull strength of dogs and handlers. Results showed that dogs that were more relaxed during the shelter assessment (i.e., when socialising with humans or being left alone in a new environment) were less reactive on the leash, with lower tension and pulling frequency. Moreover, socialised and relaxed dogs displayed more positive body language, such as tail in a high position, gazing at the handler, and exploring the environment. When walking with these dogs, volunteers utilised fewer verbal cues and body language during the walk. In addition to the canine behaviour assessment, there were correlations between canine demographics and the behavioural interaction and humans’ perception. Finally, volunteers perceived the walk as less satisfactory when they needed to pull the leash harder during the walk. This research suggests that the RSPCA behavioural assessment may be useful in predicting the behaviour of shelter dogs when walked by volunteers.