Miracle-dz/UniFAR-FTUs huggingface dataset:
Peroxidase evolution in white-rot fungi follows wood lignin evolution in plants

Significance We analyze the evolution of ligninolytic peroxidases from wood-rotting fungi using conifer and angiosperm lignin as representatives of 2 steps of lignin evolution. By enzyme resurrection, we show that during fungal evolution, these enzymes improved their activity and switched their degradative preferences with the rise of a surface tryptophan conferring on them the ability to oxidize nonphenolic lignin. We calibrated the peroxidase phylogeny and determined that this residue appeared coincident with angiosperm diversification, characterized by the synthesis of a more complex and less phenolic lignin due to the general incorporation of a new unit in its structure. This way, we show that fungal evolution followed that of lignin synthesis, pointing to a coevolution between fungal saprotrophs and their plant hosts. A comparison of sequenced Agaricomycotina genomes suggests that efficient degradation of wood lignin was associated with the appearance of secreted peroxidases with a solvent-exposed catalytic tryptophan. This hypothesis is experimentally demonstrated here by resurrecting ancestral fungal peroxidases, after sequence reconstruction from genomes of extant white-rot Polyporales, and evaluating their oxidative attack on the lignin polymer by state-of-the-art analytical techniques. Rapid stopped-flow estimation of the transient-state constants for the 2 successive one-electron transfers from lignin to the peroxide-activated enzyme (k2app and k3app) showed a progressive increase during peroxidase evolution (up to 50-fold higher values for the rate-limiting k3app). The above agreed with 2-dimensional NMR analyses during steady-state treatments of hardwood lignin, showing that its degradation (estimated from the normalized aromatic signals of lignin units compared with a control) and syringyl-to-guaiacyl ratio increased with the enzyme evolutionary distance from the first peroxidase ancestor. More interestingly, the stopped-flow estimations of electron transfer rates also showed how the most recent peroxidase ancestors that already incorporated the exposed tryptophan into their molecular structure (as well as the extant lignin peroxidase) were comparatively more efficient at oxidizing hardwood (angiosperm) lignin, while the most ancestral “tryptophanless” enzymes were more efficient at abstracting electrons from softwood (conifer) lignin. A time calibration of the ancestry of Polyporales peroxidases localized the appearance of the first peroxidase with a solvent-exposed catalytic tryptophan to 194 ± 70 Mya, coincident with the diversification of angiosperm plants characterized by the appearance of dimethoxylated syringyl lignin units.
Robustness of statistical methods when measure is affected by ceiling and/or floor effect

Goals and methods A simulation study investigated how ceiling and floor effect (CFE) affect the performance of Welch’s t-test, F-test, Mann-Whitney test, Kruskal-Wallis test, Scheirer-Ray-Hare-test, trimmed t-test, Bayesian t-test, and the “two one-sided tests” equivalence testing procedure. The effect of CFE on the estimate of group difference and on its confidence interval, and on Cohen’s d and on its confidence interval was also evaluated. In addition, the parametric methods were applied to data transformed with log or logit function and the performance was evaluated. The notion of essential maximum from abstract measurement theory is used to formally define CFE and the principle of maximum entropy was used to derive probability distributions with essential maximum/minimum. These distributions allow the manipulation of the magnitude of CFE through a parameter. Beta, Gamma, Beta prime and Beta-binomial distributions were obtained in this way with the CFE parameter corresponding to the logarithm of the geometric mean. Wald distribution and ordered logistic regression were also included in the study due to their measure-theoretic connection to CFE, even though these models lack essential minimum/maximum. Performance in two-group, three-group and 2 × 2 factor design scenarios was investigated by fixing the group differences in terms of CFE parameter and by adjusting the base level of CFE. Results and conclusions In general, bias and uncertainty increased with CFE. Most problematic were occasional instances of biased inference which became more certain and more biased as the magnitude of CFE increased. The bias affected the estimate of group difference, the estimate of Cohen’s d and the decisions of the equivalence testing methods. Statistical methods worked best with transformed data, albeit this depended on the match between the choice of transformation and the type of CFE. Log transform worked well with Gamma and Beta prime distribution while logit transform worked well with Beta distribution. Rank-based tests showed best performance with discrete data, but it was demonstrated that even there a model derived with measurement-theoretic principles may show superior performance. Trimmed t-test showed poor performance. In the factor design, CFE prevented the detection of main effects as well as the detection of interaction. Irrespective of CFE, F-test misidentified main effects and interactions on multiple occasions. Five different constellations of main effect and interactions were investigated for each probability distribution, and weaknesses of each statistical method were identified and reported. As part of the discussion, the use of generalized linear models based on abstract measurement theory is recommended to counter CFE. Furthermore, the necessity of measure validation/calibration studies to obtain the necessary knowledge of CFE to design and select an appropriate statistical tool, is stressed.
Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands

Abstract. Over- or under-expression of erythropoietin-production human hepatocellular receptors (Eph) and their ligands are associated with various diseases. Therefore, these molecular biomarkers can potentially be used as binding targets for the delivery of therapeutic and/or imaging agents to cells characterized by such irregular expressions. We have engineered nanoparticles derived from erythrocytes and doped with the near-infrared (NIR) FDA-approved dye, indocyanine green. We refer to these nanoparticles as NIR erythrocyte-derived transducers (NETs). We functionalized the NETs with the ligand-binding domain of a particular Eph receptor, EphB1, to target the genetically modified human dermal microvascular endothelial cells (hDMVECs) with coexpression of EphB1 receptor and its ligand ephrin-B2. This cell model mimics the pathological phenotypes of lesional endothelial cells (ECs) in port wine stains (PWSs). Our quantitative fluorescence imaging results demonstrate that such functionalized NETs bind to the ephrin-B2 ligands on these hDMVECs in a dose-dependent manner that varies sigmoidally with the number density of the particles. These nanoparticles may potentially serve as agents to target PWS lesional ECs and other diseases characterized with over-expression of Eph receptors or their associated ligands to mediate phototherapy.
VVBP-Tensor in the FBP Algorithm: Its Properties and Application in Low-Dose CT Reconstruction

For decades, commercial X-ray computed tomography (CT) scanners have been using the filtered backprojection (FBP) algorithm for image reconstruction. However, the desire for lower radiation doses has pushed the FBP algorithm to its limit. Previous studies have made significant efforts to improve the results of FBP through preprocessing the sinogram, modifying the ramp filter, or postprocessing the reconstructed images. In this paper, we focus on analyzing and processing the stacked view-by-view backprojections (named VVBP-Tensor) in the FBP algorithm. A key challenge for our analysis lies in the radial structures in each backprojection slice. To overcome this difficulty, a sorting operation was introduced to the VVBP-Tensor in its ${z}$ direction (the direction of the projection views). The results show that, after sorting, the tensor contains structures that are similar to those of the object, and structures in different slices of the tensor are correlated. We then analyzed the properties of the VVBP-Tensor, including structural self-similarity, tensor sparsity, and noise statistics. Considering these properties, we have developed an algorithm using the tensor singular value decomposition (named VVBP-tSVD) to denoise the VVBP-Tensor for low-mAs CT imaging. Experiments were conducted using a physical phantom and clinical patient data with different mAs levels. The results demonstrate that the VVBP-tSVD is superior to all competing methods under different reconstruction schemes, including sinogram preprocessing, image postprocessing, and iterative reconstruction. We conclude that the VVBP-Tensor is a suitable processing target for improving the quality of FBP reconstruction, and the proposed VVBP-tSVD is an effective algorithm for noise reduction in low-mAs CT imaging. This preliminary work might provide a heuristic perspective for reviewing and rethinking the FBP algorithm.
Accelerated Stimulated Raman Projection Tomography by Sparse Reconstruction From Sparse-View Data

Objective: Stimulated Raman projection tomography (SRPT), a recently developed label-free volumetric chemical imaging technology, has been reported to quantitatively reconstruct the distribution of chemicals in a three-dimensional (3D) complex system. The current image reconstruction scheme used in SRPT is based on a filtered back projection (FBP) algorithm that requires at least 180 angular-dependent projections to rebuild a reasonable SRPT image, resulting in a long total acquisition time. This is a big limitation for longitudinal studies on live systems. Methods: We present a sparse-view data-based sparse reconstruction scheme, in which sparsely sampled projections at 180 degrees were used to reconstruct the volumetric information. In the scheme, the simultaneous algebra reconstruction technique (SART), combined with total variation regularization, was used for iterative reconstruction. To better describe the projection process, a pixel vertex driven model (PVDM) was developed to act as projectors, whose performance was compared with those of the distance driven model (DDM). Results: We evaluated our scheme with numerical simulations and validated it for SRPT by mapping lipid contents in adipose cells. Simulation results showed that the PVDM performed better than the DDM in the case of using sparse-view data. Our scheme could maintain the quality of the reconstructed images even when the projection number was reduced to 15. The cell-based experimental results demonstrated that the proposed scheme can improve the imaging speed of the current FBP-based SRPT scheme by a factor of 9–12 without sacrificing discernible imaging details. Conclusion: Our proposed scheme significantly reduces the total acquisition time required for SRPT at a speed of one order of magnitude faster than the currently used scheme. This significant improvement in imaging speed would potentially promote the applicability of SRPT for imaging living organisms.
Exopolysaccharide Produced by Lactobacillus paracasei IJH-SONE68 Prevents and Improves the Picryl Chloride-Induced Contact Dermatitis

Allergic disease is one of the most important and common health problems worldwide. We have previously demonstrated that a fig leaf-derived lactic acid bacterium Lactobacillus (Lb.) paracasei IJH-SONE68 produces a novel exopolysaccharide (EPS). Furthermore, we have shown that the EPS inhibits the catalytic activity of hyaluronidase (EC 3.2.1.36) promoting inflammatory reactions. To evaluate the anti-allergy and anti-inflammatory effects of the EPS, in the present study, we employed the picryl-chloride-induced delayed-type (type IV) allergy model mice, which is used to evaluate the contact dermatitis. Oral administration of the EPS was observed to reduce the ear swelling in the model mice. We also observed that the overexpression of ear interleukin-4 (T helper (Th) 2 cytokine) mRNA and the increase in serum immunoglobulin E (IgE) are repressed. However, the expression of interferon-γ (Th1 cytokine) was not accelerated in all of the allergen-challenged model mice. The improvement may be responsible for the Th2 downregulation rather than the Th1 upregulation. In addition, the symptom of immediate-type (type I) allergy model mice was improved by oral administration of the IJH-SONE68 cell (data not shown). We can conclude that the IJH-SONE68-derived EPS is useful to improve the type I and IV allergies including atopic dermatitis.
Activation of Factor XII and Kallikrein-Kinin System Combined with Neutrophil Extracellular Trap Formation in Diabetic Retinopathy

Abstract Background In diabetic retinopathy (DR), neutrophil extracellular traps (NET) and kallikrein-kinin system are considered as contributing factors. However, the detail activation mechanisms has not been fully understood. Since the NET could provide negative-charged surface for factor XII activation and the activated factor XII (XIIa) can initiate kallikrein-kinin system, this study investigated whether patients with DR show activation of NET, factor XII and kallikrein-kinin system. Methods The markers related to NET (DNA-histone complex) and kallikrein-kinin system (high-molecular-weight kininogen, prekallikrein, bradykinin) and factor XIIa were measured in 253 patients with diabetes. To access ex vivo effect of glucose, DNA-histone complex and factor XIIa were measured in whole blood stimulated by glucose. Results The circulating level of DNA-histone complex and factor XIIa were significantly higher in patients with DR than those without DR. In logistic regression analysis, DNA-histone complex, factor XIIa, and high-molecular-weight kininogen were the risk factors of DR. In recursive partitioning analysis, among patients with diabetes duration less than 10 years, patients with high level of DNA-histone complex (>426 AU) showed high risk of DR. In ex vivo experiment, glucose significantly elevated both DNA-histone complex and factor XIIa. Conclusion Our findings suggest that activation of factor XII and kallikrein-kinin system combined with NET formation actively occur in patients with DR and circulating levels of DNA-histone complex, factor XIIa and HMWK can be potential biomarkers to estimate the risk of DR. Strategies against factor XII activation may be beneficial to inhibit DR.
Modification of Activity of the Thylakoid H+/K+ Antiporter KEA3 Disturbs ∆pH-Dependent Regulation of Photosynthesis1[OPEN]

Overexpression of two versions of KEA3 differentially affects the proton motive force and thereby the regulation of photosynthetic electron transport under stressful light conditions in Arabidopsis. The thylakoid K+ efflux antiporter 3 (KEA3) is required for regulating components of the proton motive force (pmf), proton concentration gradient (ΔpH), and membrane potential (Δψ). The Arabidopsis (Arabidopsis thaliana) disturbed proton gradient regulation mutant (dpgr) is a dominant allele of KEA3, conferring disturbed transport activity. Here, we show that overexpressing the DPGR-type KEA3 (DPGRox) retarded plant growth, whereas overexpressing the wild-type KEA3 (KEA3ox) did not. In KEA3ox lines, the contribution of Δψ to pmf was enhanced, but in DPGRox lines, the size of pmf was reduced. In DPGRox plants, proton conductivity of the thylakoid membrane (gH+) was elevated under high light, implying disturbed stoichiometry of H+/K+ antiport through DPGR-type KEA3 rather than simply enhanced activity. The ΔpH-dependent regulation consisting of thermal dissipation of excessively absorbed light energy and downregulation of cytochrome b6f complex activity was severely and mildly affected in DPGRox and KEA3ox plants, respectively. Consequently, photosystem I was sensitive to fluctuating light in both transgenic plants. Both photosystems were sensitive to constant high light and were slightly photodamaged even at standard growth light intensity in DPGRox plants. KEA3 regulates the components of pmf and optimizes the operation of ∆pH-dependent regulation of electron transport.
DFT Study of N2O Adsorption onto the Surface of M-Decorated Graphene Oxide (M = Mg, Cu or Ag)

In order to reduce the harm of nitrous oxide (N2O) on the environment, it is very important to find an effective way to capture and decompose this nitrous oxide. Based on the density functional theory (DFT), the adsorption mechanism of N2O on the surfaces of M-decorated (M = Mg, Cu or Ag) graphene oxide (GO) was studied in this paper. The results show that the effects of N2O adsorbed onto the surfaces of Mg–GO by O-end and Cu–GO by N-end are favorable among all of the adsorption types studied, whose adsorption energies are −1.40 eV and −1.47 eV, respectively. Both adsorption manners belong to chemisorption. For Ag–GO, however, both the adsorption strength and electron transfer with the N2O molecule are relatively weak, indicating it may not be promising for N2O removal. Moreover, when Gibbs free energy analyses were applied for the two adsorption types on Mg–GO by O-end and Cu–GO by N-end, it was found that the lowest temperatures required to undergo a chemisorption process are 209 °C and 338 °C, respectively. After being adsorbed onto the surface of Mg–GO by O-end, the N2O molecule will decompose into an N2 molecule and an active oxygen atom. Because of containing active oxygen atom, the structure O–Mg–GO has strong oxidizability, and can be reduced to Mg–GO. Therefore, Mg–GO can be used as a catalyst for N2O adsorption and decomposition. Cu–GO can be used as a candidate material for its strong adsorption to N2O.
Synergistic Meropenem-Tobramycin Combination Dosage Regimens against Clinical Hypermutable Pseudomonas aeruginosa at Simulated Epithelial Lining Fluid Concentrations in a Dynamic Biofilm Model

Exacerbations of chronic Pseudomonas aeruginosa infections are a major treatment challenge in cystic fibrosis due to biofilm formation and hypermutation. We aimed to evaluate different dosage regimens of meropenem and tobramycin as monotherapies and in combination against hypermutable carbapenem-resistant P. aeruginosa. A hypermutable P. aeruginosa isolate (meropenem and tobramycin MICs, 8 mg/liter) was investigated in the dynamic CDC biofilm reactor over 120 h. ABSTRACT Exacerbations of chronic Pseudomonas aeruginosa infections are a major treatment challenge in cystic fibrosis due to biofilm formation and hypermutation. We aimed to evaluate different dosage regimens of meropenem and tobramycin as monotherapies and in combination against hypermutable carbapenem-resistant P. aeruginosa. A hypermutable P. aeruginosa isolate (meropenem and tobramycin MICs, 8 mg/liter) was investigated in the dynamic CDC biofilm reactor over 120 h. Regimens were meropenem as the standard (2 g every 8 h, 30% epithelial lining fluid [ELF] penetration) and as a continuous infusion (CI; 6 g/day, 30% and 60% ELF penetration) and tobramycin at 10 mg/kg of body weight every 24 h (50% ELF penetration). The time courses of totally susceptible and less-susceptible bacteria and MICs were determined, and antibiotic concentrations were quantified by liquid chromatography-tandem mass spectrometry. All monotherapies failed, with the substantial regrowth of planktonic (>6 log10 CFU/ml) and biofilm (≥6 log10 CFU/cm2) bacteria occurring. Except for the meropenem CI (60% ELF penetration), all monotherapies amplified less-susceptible planktonic and biofilm bacteria by 120 h. The meropenem standard regimen with tobramycin caused initial killing followed by considerable regrowth with resistance (meropenem MIC, 64 mg/liter; tobramycin MIC, 32 mg/liter) for planktonic and biofilm bacteria. The combination containing the meropenem CI at both levels of ELF penetration synergistically suppressed the regrowth of total planktonic bacteria and the resistance of planktonic and biofilm bacteria. The combination with the meropenem CI at 60% ELF penetration, in addition, synergistically suppressed the regrowth of total biofilm bacteria. Standard regimens of meropenem and tobramycin were ineffective against planktonic and biofilm bacteria. The combination with meropenem CI exhibited enhanced bacterial killing and resistance suppression of carbapenem-resistant hypermutable P. aeruginosa.
Diet-Induced Metabolic Syndrome Reduced Heart Rate Variability and Increased Irregularity and Complexity of Short-Term RR Time Series in Rabbits

Simple Summary In recent years, obesity and metabolic syndrome (MetS) have become more prevalent, owing to increased unhealthy habits and sedentary lifestyles becoming public health problems. Both conditions are linked with a higher prevalence of sudden cardiac death (SCD), but the exact mechanisms are not known. An autonomic nervous system imbalance can produce atrial and ventricular arrhythmias, which cause SCD, and this can be quantified by analyzing heart rate variability (HRV). We investigated HRV using time-domain, frequency-domain and nonlinear analyses during the development of MetS in rabbits and found HRV modifications that could be associated with the higher prevalence of SCD in this pathological condition. Abstract Metabolic syndrome (MetS) has been linked to a higher prevalence of sudden cardiac death (SCD), but the mechanisms are not well understood. One possible underlying mechanism may be an abnormal modulation of autonomic activity, which can be quantified by analyzing heart rate variability (HRV). Our aim was to investigate the modifications of short-term HRV in an experimental rabbit model during the time-course of MetS development. NZW rabbits were randomly assigned to a control (n = 10) or a MetS group (n = 13), fed 28 weeks with control or high-fat, high-sucrose diets. After anesthesia, a 15-min ECG recording was acquired before diet administration and at weeks 14 and 28. We analyzed short RR time series using time-domain, frequency-domain and nonlinear analyses. A mixed-model factorial ANOVA was used for statistical analysis. Time-domain analysis showed a 52.4% decrease in the standard deviation of heart rate in animals from the MetS group at week 28, but no changes in the rest of parameters. In the frequency domain, we found a 9.7% decrease in the very low frequency and a 380.0% increase of the low frequency bands in MetS animals at week 28, whereas high frequency remained unchanged. Nonlinear analyses showed increased complexity and irregularity of the RR time series in MetS animals.
Acquired and Persistent Eldercare Demands: Impact on Worker Well-Being

Eldercare demands (ECD) may result in stress when finite resources needed to fulfill life roles (i.e., family, work) become scarce. ECD may be acquired, continue over time, or be relinquished. They thus may represent acute stress (immediate, severe) or chronic stress (persistent, milder). Workers at six U.S. manufacturing companies completed surveys (N = 520). ECD were operationalized as providing assistance to an adult aged 65+ years due to disability or illness. Workers were categorized into four ECD groups (persistent, relinquished, acquired, and none), and we examined the ECD groups’ association with person-centric and work-centric outcomes. Respondents with acquired ECD had worse mental health and greater depressive symptoms than those with none, and those with persistent ECD had greater work stress and family–work conflict than those with none. Findings suggesting that acute stress is more related to person-centric outcomes and chronic stress is more related to work-centric outcomes could inform development of tailored interventions.