Excellent Model Research Articles

Abstract P433: Impaired Renin Activity in a Bicistronic Ren1 c -T2A-tdTomato Reporter Mouse

The study of renin cell identity and function often requires the isolation of this rare cell type –0.01% of the kidney cells. Multicistronic constructs are commonly used to express reporter genes in mice. They consist of two or more genes linked by 2A peptide sequences, which produce separate proteins through a ribosomal skipping mechanism. Here, we report on the generation of a mouse model to label renin-expressing cells with a bright fluorescent reporter for the tracking and isolation of renin cells. Ren1 ctdTomato mice were generated by inserting a bicistronic T2A-tdTomato knock-in cassette upstream of the TGA stop codon of the Ren1 c gene. Kidneys from adult heterozygous (het) Ren1 ctdTomat o mice showed tdTomato signal confined to the JG area under basal conditions, and extending along the afferent arterioles and in the intraglomerular mesangium upon treatment with captopril + low-salt diet to induce the endocrine transformation of renin cells. Unexpectedly, homozygous (homo) mice exhibited increased tdTomato signal that extended in the afferent arterioles and the mesangium even under normal physiological conditions, and progressive thickening of the kidney arterioles with age. Despite reduced Renin immunostaining in the renal cortex, homo mice exhibited significantly higher kidney Ren1 mRNA (7.9 ± 1.2 vs 1.2 ± 0.6, p< 0.0001) and circulating Renin levels (121.7 ± 44.0 vs 66.7 ± 29.4 ng/ml, p< 0.003) when compared to het controls. Moreover, homo mice showed significantly lower blood pressure measured under anesthesia (62.3 ± 5.9 vs 90.0 ± 5.7 mmHg, p< 0.0001), and Ang I plasma levels (159.3 ± 34.8 vs 500.0 ± 184.1 pmol/L, p< 0.05), indicating compromised Renin activity. The concentric arteriolar hypertrophy phenotype observed in these mice is identical to that described when RAS is genetically or pharmacologically inhibited, including the presence of mutations in the renin gene. Unlike mice with global deletion of renin, these animals did not require neonatal saline injections to survive and did not develop other kidney abnormalities, indicating that the bicistronic approach rendered a renin hypomorphic mouse. Ren1 ctdTomato mice constitute an excellent model for the labeling of renin-expressing cells and for the study of the mechanisms involved in the development of concentric vascular hypertrophy under RAS inhibition. In addition, this model may provide a better understanding of factors controlling renin protein folding, stability, packaging, and release.

Preclinical characterization of [18F]D2-LW223: an improved metabolically stable PET tracer for imaging the translocator protein 18 kDa (TSPO) in neuroinflammatory rodent models and non-human primates.

Positron emission tomography (PET) targeting translocator protein 18 kDa (TSPO) can be used for the noninvasive detection of neuroinflammation. Improved in vivo stability of a TSPO tracer is beneficial for minimizing the potential confounding effects of radiometabolites. Deuteration represents an important strategy for improving the pharmacokinetics and stability of existing drug molecules in the plasma. This study developed a novel tracer via the deuteration of [18F]LW223 and evaluated its in vivo stability and specific binding in neuroinflammatory rodent models and nonhuman primate (NHP) brains. Compared with LW223, D2-LW223 exhibited improved binding affinity to TSPO. Compared with [18F]LW223, [18F]D2-LW223 has superior physicochemical properties and favorable brain kinetics, with enhanced metabolic stability and reduced defluorination. Preclinical investigations in rodent models of LPS-induced neuroinflammation and cerebral ischemia revealed specific [18F]D2-LW223 binding to TSPO in regions affected by neuroinflammation. Two-tissue compartment model analyses provided excellent model fits and allowed the quantitative mapping of TSPO across the NHP brain. These results indicate that [18F]D2-LW223 holds significant promise for the precise quantification of TSPO expression in neuroinflammatory pathologies of the brain.

Optogenetic techniques for understanding the gut peristalsis during chicken embryonic development.

Gut peristaltic movements transport ingested materials along the gut axis, which is critical for food digestion and nutrient absorption. While a large amount of studies have been devoted to analyzing the physiological functions of peristalsis in adults, little is known about how the peristaltic system is established during embryogenesis. In recent years, the chicken developing gut has emerged as an excellent model, in which specific sites along the gut axis can be genetically labeled enabling live imaging and optogenetic analyses. This review provides an overview of recent progress in optogenetic studies of gut peristalsis. Analyses with an improved channelrhodopsin-2 variant demonstrated that the peristalsis can artificially be generated in the developing gut. These studies unveiled novel functional coordination between different regions along the gut axis. In addition, imaging with GCaMP6s, a genetically encoded calcium indicator, enabled a fine mapping of developmental changes in the peristaltic patterns as Ca2+ signals. These advanced techniques will broaden our knowledge of how embryonic peristalsis is established at the cellular and molecular level, leading to the understanding of physiological and pathological processes in adult peristalsis.

An immunoinformatics approach for a potential NY-ESO-1 and WT1 based multi-epitope vaccine designing against triple-negative breast cancer

Breast cancer emerges as one of the most prevalent malignancies in women, its incidence showing a concerning upward trend. Among the diverse array of breast cancer subtypes, triple-negative breast cancer (TNBC) assumes notable significance, due to lack of estrogen, progesterone, and HER-2 receptors. More focus has to be placed on creating effective therapy due to the high prevalence and rising incidence of TNBC. Currently, conventional passive treatments have several drawbacks that have not yet been resolved. On the other hand, as innovative immunotherapy approaches, cancer vaccines have offered promising prospects in combatting advanced stages of TNBC. Therefore, the main objective of this study was to utilize WT1 and NY-ESO-1 antigenic proteins in designing a multiepitope vaccine against TNBC. Initially, to generate robust immune responses, we identified antigenic epitopes of both proteins and assessed their immunogenicity. In order to reduce junctional immunogenicity, promiscuous epitopes were joined using the suitable adjuvant (50S ribosomal L7/L12 protein) and incorporated appropriate linkers (GPGPG, AAY, and EAAAK). The best predicted 3D model was refined and validated to achieve an excellent 3D model. Molecular docking analysis and dynamic simulation were conducted to demonstrate the structural stability and integrity of the vaccine/TLR-4 complex. Finally, the vaccine was cloned into the vector pET28 (+). Thus, analysis of the constructed vaccine through immunoinformatics indicates its capability to elicit robust humoral and cellular immune responses in the targeted organism. As such, it holds promise as a therapeutic weapon against TNBC and may open doors for further research in the field.

Research on 3D Geological and Numerical Unified Model of in Mining Slope Based on Multi-Source Data

As mining engineering progresses into the deep excavation phase, the intensification of high pressure, high temperature, strong disturbances, and complex geological conditions becomes increasingly prominent. Researchers perform stability analysis on the excavation area to reduce potential safety hazards during the extraction process. Developing a detailed numerical calculation model that accurately reflects the true geological structure is essential for numerical simulation analysis in mining engineering. Based on the excellent 3D geological modeling capabilities of 3D Mine software, this paper introduces a new 3D geological and numerical unified modeling method (3DMine-Rhino-HyperMesh) involving multi-software coupling and details the specific steps and concepts of this modeling approach. Subsequently, using a certain open-pit mine in Panzhihua as a backdrop, a detailed geological and numerical unified model is established, reflecting the true geological structure of the mining area, and the potential failure mechanisms of the mine slope are analyzed. The results indicate that the modeling method aligns well with the actual geological conditions, enhancing the grid quality of the numerical model and offering a new modeling approach for simulating and analyzing large complex geological entities in mining operations.

Genes to specialized metabolites: accumulation of scopoletin, umbelliferone and their glycosides in natural populations of Arabidopsis thaliana

BackgroundScopoletin and umbelliferone belong to coumarins, which are plant specialized metabolites with potent and wide biological activities, the accumulation of which is induced by various environmental stresses. Coumarins have been detected in various plant species, including medicinal plants and the model organism Arabidopsis thaliana. In recent years, key role of coumarins in maintaining iron (Fe) homeostasis in plants has been demonstrated, as well as their significant impact on the rhizosphere microbiome through exudates secreted into the soil environment. Several mechanisms underlying these processes require clarification. Previously, we demonstrated that Arabidopsis is an excellent model for studying genetic variation and molecular basis of coumarin accumulation in plants.ResultsHere, through targeted metabolic profiling and gene expression analysis, the gene-metabolite network of scopoletin and umbelliferone accumulation was examined in more detail in selected Arabidopsis accessions (Col-0, Est-1, Tsu-1) undergoing different culture conditions and characterized by variation in coumarin content. The highest accumulation of coumarins was detected in roots grown in vitro liquid culture. The expression of 10 phenylpropanoid genes (4CL1, 4CL2, 4CL3, CCoAOMT1, C3’H, HCT, F6’H1, F6’H2,CCR1 and CCR2) was assessed by qPCR in three genetic backgrounds, cultured in vitro and in soil, and in two types of tissues (leaves and roots). We not only detected the expected variability in gene expression and coumarin accumulation among Arabidopsis accessions, but also found interesting polymorphisms in the coding sequences of the selected genes through in silico analysis and resequencing.ConclusionsTo the best of our knowledge, this is the first study comparing accumulation of simple coumarins and expression of phenylpropanoid-related genes in Arabidopsis accessions grown in soil and in liquid cultures. The large variations we detected in the content of coumarins and gene expression are genetically determined, but also tissue and culture dependent. It is particularly important considering that growing plants in liquid media is a widely used technology that provides a large amount of root tissue suitable for metabolomics. Research on differential accumulation of coumarins and related gene expression will be useful in future studies aimed at better understanding the physiological role of coumarins in roots and the surrounding environments.

Relationship between Playing Musical Instruments and Subjective Well-Being: Enjoyment of Playing Instruments Scale.

While the positive effects of listening to music on mental health and well-being have been extensively studied, the effects of enjoying playing musical instruments have rarely been examined. Many tools have been developed to measure music listening; however, tools to measure the enjoyment of playing instruments have not yet been developed. This study aimed to develop and validate a tool to measure such enjoyment and to examine its relationship with subjective well-being and happiness. Primary information about the aforementioned enjoyment were collected from fourteen Chinese laypersons, five music graduates, and five music teachers using open-ended questions. Item and exploratory factor analyses were conducted using data from 361 Chinese adults, and the reliability and validity of the scale and the relationships between the variables were analyzed using data from 277 Chinese adults. The results revealed that the three-factor model for the enjoyment of playing instruments demonstrated excellent model fit, and satisfactory internal consistency, test-retest reliability, and criterion-related validity were demonstrated for the learning/social bonds, achievement/pride, and cognitive refreshment/stimulation subscales. All subscales of enjoyment were positively correlated with subjective well-being and happiness. This study highlights the usefulness of the Enjoyment of Playing Instruments Scale (EPIS) as a measure for research, educational, and clinical use, providing a rationale for using instrument playing as a therapeutic approach to promote subjective well-being.

The mRNA and microRNA Landscape of the Blastema Niche in Regenerating Newt Limbs.

Newts are excellent vertebrate models for investigating tissue regeneration due to their remarkable regenerative capabilities. To investigate the mRNA and microRNAs (miRNAs) profiles within the blastema niche of regenerating newt limbs, we amputated the limbs of Chinese fire belly newts (Cynops orientalis) and conducted comprehensive analyses of the transcriptome and microRNA profiles at five distinct time points post-amputation (0 hours, 1 day, 5 days 10 days and 20 days). We identified 24 significantly differentially expressed (DE) genes and 20 significantly DE miRNAs. Utilizing weighted gene co-expression network analysis (WGCNA) and gene ontology (GO) enrichment analysis, we identified four genes likely to playing crucial roles in the early stages of limb regeneration: Cemip, Rhou, Gpd2 and Pcna. Moreover, mRNA-miRNA integration analysis uncovered seven human miRNAs (miR-19b-1, miR-19b-2, miR-21-5p, miR-127-5p, miR-150-5p, miR-194-5p, and miR-210-5p) may regulate the expression of these four key genes. The temporal expression patterns of these key genes and miRNAs further validated the robustness of the identified mRNA-miRNA landscape. Our study successfully identified candidate key genes and elucidated a portion of the genetic regulatory mechanisms involved in newt limb regeneration. These findings offer valuable insights for further exploration of the intricate processes of tissue regeneration.

Massive fabrication of functional hepatic cancer spheroids by micropatterned GelMA hydrogel chip for drug screening

Since hepatic cancer incidence and mortality continue to grow worldwide, it is necessary to develop the biomimetic tumor models for drug development and tumor therapeutics. Cellular spheroids as an excellent simple 3D model can bridge the gap between 2D cell culture and live tissue. In this study, we proposed a biological methacrylated gelatin (GelMA) hydrogel-based microplatform for the massive generation of hepatocellular spheroids and downstream investigation of drug resistance. Micropatterned GelMA hydrogel microwell chip (GHM-chip) with tunable array was easily achieved in standard 24-culture well plates through the micro-molding fabrication strategy. The fabricated GHM-chip induced multicellular self-assembly behavior within the defined topography and further formed spheroidal structure. By regulating cell seeding density and designing microwell size, uniform hepatic cancer spheroids with tunable diameters were obtained in a simplicity, stability and controllable manner. In addition, the screening chemotherapy study of anti-cancer drug was completed through non-destructive recovery of spheroids from the GHM-chip. Beyond that, the recovered functional spheroids have potential application value in various biomedical fields such as tumor biology, pharmacology, and tissue microengineering. Finally, the proposed GHM-chip incorporated into standard cell culture plates with easy to manufacture and operate properties, may be an efficient culture microplatform for cancer research applications.

Canine RNF170 Single Base Deletion in a Naturally Occurring Model for Human Neuroaxonal Dystrophy.

Neuroaxonal dystrophy (NAD) is a group of inherited neurodegenerative disorders characterized primarily by the presence of spheroids (swollen axons) throughout the central nervous system. In humans, NAD is heterogeneous, both clinically and genetically. NAD has also been described to naturally occur in large animal models, such as dogs. A newly recognized disorder in Miniature American Shepherd dogs (MAS), consisting of a slowly progressive neurodegenerative syndrome, was diagnosed as NAD via histopathology. To describe the clinical and pathological phenotype together with the identification of the underlying genetic cause. Clinical and postmortem evaluations, together with a genome-wide association study and autozygosity mapping approach, followed by whole-genome sequencing. Affected dogs were typically young adults and displayed an abnormal gait characterized by pelvic limb weakness and ataxia. The underlying genetic cause was identified as a 1-bp (base pair) deletion in RNF170 encoding ring finger protein 170, which perfectly segregates in an autosomal recessive pattern. This deletion is predicted to create a frameshift (XM_038559916.1:c.367delG) and early truncation of the RNF170 protein (XP_038415844.1:(p.Ala123Glnfs*11)). The age of this canine RNF170 variant was estimated at ~30 years, before the reproductive isolation of the MAS breed. RNF170 variants were previously identified in human patients with autosomal recessive spastic paraplegia-85 (SPG85); this clinical phenotype shows similarities to the dogs described herein. We therefore propose that this novel MAS NAD could serve as an excellent large animal model for equivalent human diseases, particularly since affected dogs demonstrate a relatively long lifespan, which represents an opportunity for therapeutic trials. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Contribution of dual-tasking to social participation in persons with multiple sclerosis: A structural equation modeling approach

IntroductionThis study aimed to explore the patterns of association between dual-tasking, cognition, ambulation disability, fatigue, and self-efficacy and their pathways in predicting social participation in persons with multiple sclerosis (MS). MethodsAdults with MS (n = 1162) completed an online survey. Social participation was assessed by the Quality of Life in Neurological Disorders. The Dual-task Impact on Daily-Living Activities Questionnaire, Multiple Sclerosis Walking Scale-12v2, and Modified Fatigue Impact Scale measured dual-tasking, ambulation, and fatigue, respectively. Fall Efficacy Scale-International and Self-Efficacy for Community Mobility were assessed and modeled as a latent variable for efficacy. ResultsThe correlation matrix showed significant associations of social participation with dual-tasking, cognition, ambulation, efficacy, and fatigue (all p < 0.001) and interrelationships among the independent variables (p < 0.05). The final model showed excellent global model fit (CFI = 0.99, TLI = 0.96), with all variables significantly predicting social participation either directly or indirectly. Efficacy significantly mediated the effects of dual-tasking (β=-0.32, p < 0.001) and ambulation disability (β=-0.42, p < 0.001) on social participation. ConclusionThis study indicated that dual-tasking, ambulation disability, fatigue, and efficacy play important roles in social participation in persons with MS. The findings can help provide insight into factors that may underpin social participation and offer targets for interventions in persons with MS.

Modifications of Mitochondrial Network Morphology Affect the MAVS-Dependent Immune Response in L929 Murine Fibroblasts during Ectromelia Virus Infection.

Since smallpox vaccination was discontinued in 1980, there has been a resurgence of poxvirus infections, particularly the monkeypox virus. Without a global recommendation to use the smallpox vaccine, the population is not immune, posing a severe threat to public health. Given these circumstances, it is crucial to understand the relationship between poxviruses and their hosts. Therefore, this study focuses on the ectromelia virus, the causative agent of mousepox, which serves as an excellent model for studying poxvirus pathogenesis. Additionally, we investigated the role of mitochondria in innate antiviral immunity during ECTV infection, focusing specifically on mitochondrial antiviral signaling protein. The study used a Moscow strain of ECTV and L929 mouse fibroblasts. Cells were treated with ECTV and chemical modulators of mitochondrial network: Mdivi-1 and CCCP. Our investigation revealed that an elongated mitochondrial network attenuates the suppression of MAVS-dependent immunity by ECTV and reduces ECTV replication in L929 fibroblasts compared to cells with an unaltered mitochondrial network. Conversely, a fragmented mitochondrial network reduces the number of progeny virions while increasing the inhibition of the virus-induced immune response during infection. In conclusion, our study showed that modifications of mitochondrial network morphology alter MAVS-dependent immunity in ECTV-infected mouse L929 fibroblasts.

Using Analytical Hierarchy Process (AHP) for Developing a Performance Evaluation Model for A Human Resources Department in Private Sector in Saudi Arabia

Evaluating human resource departments discovers weak areas and supports performance measurements and continuous quality improvement. However, most research concentrates on the development of models that primarily assess the performance of individual human resources rather than focusing on the evaluation of the entire department. This study aims to formulate a model for evaluating the performance of human resource departments in Saudi Arabia&amp;#39;s private sector. The proposed model studies HR standards using five well-known quality awards excellence models. Exploratory Factor Analysis (EFA) was then used to discover the factor structure of this model and examine its internal reliability to identify the underlying relationships between the assessment model criteria (factors). A questionnaire was designed and distributed to middle and high management levels, such as section head positions and above, in different organizations in the private sector in Jeddah. The analytic hierarchy process (AHP) was used to quantify the weights of the assessment factors and subfactors. Human resource experts estimated the relative magnitudes of the factors and sub-factors through pairwise comparisons. The results identified six main factors and seventy-eight subfactors for evaluating human resources department performance in any private sector. The findings indicated that the most substantial weight, constituting nearly 50 of the entire modules, was assigned to Factor 2, denoting &amp;quot;Justice and Human Development&amp;quot; (44.746%). This was followed by Factor 5, related to &amp;quot;Job Performance Management&amp;quot; (18.945%), and Factor 6, about &amp;quot;Occupational Safety&amp;quot; (12.554%). The factor with the lowest weight was Factor 1, representing &amp;quot;Career Guidance and Counseling&amp;quot; (7.601%).

Marker-free genomic editing in Saccharomyces cerevisiae using universal donor templates and multiplexing CRISPR-CAS9.

The budding yeast Saccharomyces cerevisiae is an excellent model organism for studying a variety of critical cellular processes. Traditional methods to knock in or -out at specific yeast loci utilize polymerase chain reaction-based techniques, in which marker cassettes with gene-specific homologies are integrated into the genome via homologous recombination. While simple and cost-effective, these methods are limited by marker availability when multiple edits are desired. More recently, CRISPR-Cas9 technology has introduced methods to edit the yeast genome without the need for selectable markers. Although efficient, this method is hindered by additional reagents and lengthy protocols to design and test unique guide RNAs and donor templates for each desired edit. In this study, we have combined these two approaches and have developed a highly efficient economical method to edit the yeast genome marker-free. We have designed two universal donor templates that efficiently repair commonly used selectable markers when targeted by a novel guideRNA-Cas9 designed to promoter regions in Ashbya gossypii found in most integration modules. Furthermore, we find our newly designed guideRNA-Cas9 successfully multiplexes when multiple markers are present. Using these new tools, we have significantly improved the cost and efficiency to generate single or multiple marker-free genetic modifications. In this study, we demonstrate the effectiveness of these new tools by marker-free ablating PRC1, PEP4, and PRB1 vacuolar proteases typically inactivated before many biochemical and membrane-trafficking studies using budding yeast.

Liana attachment to supports leads to profound changes in xylem anatomy and transcriptional profile of cambium and differentiating xylem.

Wood serves crucial functions in plants, yet our understanding of the mechanisms governing the composition, arrangement, and dimensions of its cells remains limited. The abrupt transition from nonlianescent to lianescent xylem in lianas represents an excellent model to address the underlying mechanisms, although consistent triggering factors for this process remain uncertain. In this study we examined how physical support attachment impacts the development of lianescent xylem in Bignonia magnifica (Bignoniaceae), employing a comprehensive approach integrating detailed anatomical analysis with gene expression profiling of cambium and differentiating xylem. Our findings demonstrate that attachment to physical supports triggers the formation of lianescent xylem, leading to increased vessel size, broader vessel distribution, reduced fibre content, and higher potential specific water conductivity than nonlianescent xylem. These shifts in wood anatomy coincide with the downregulation of genes associated with cell division and cell wall biosynthesis, and the upregulation of transcription factors, defense/cell death, and hormone-responsive genes in the lianescent xylem. Our findings provide insights into the regulation of xylem differentiation, driven by response to environmental stimuli. Additionally, they shed light on the mechanisms underlying the adaptation of lianas to climbing.

Machine learning-based process design of a novel sustainable cooling system

An exponential rise in cooling requirements occurred in the last few years because of rising global surface temperatures, population growth, faster urbanization, and income growth. Developing countries are facing major issues because of the larger impact of these cooling drivers. Conventional vapor compression systems are energy-demanding and involve dangerous chemicals. The current paper proposed an innovative indirect evaporative cooling system with high energy performance, less emissions, and chemical-free operation. To map the full-scale performance, a prototype was developed,and tested in a variety of outside air conditions. Then artificial neural network (ANN)-based machine learning model was developed incorporating important input parameters including outdoor air temperature, air flow rate ratio, working air temperature, and working air wet bulb temperature to predict the supply air temperature. The ANN model having nine neurons in the hidden layer exhibits excellent modeling performance with a coefficient of determination (R2) value of ∼ 1 and root mean square error of 0.046 °C, 0.06 °C, and 0.06 °C in the training, testing, and validation phases respectively. The variable significance analysis carried out by one factor at a time (OFAT) technique reveals that working air inlet temperature is the most important parameter to predict supply temperature with a significance factor of 33 %. According to the combined experimental and ML model, the proposed system generated 130 W of cooling capacity and dropped the temperature by more than 20 °C at 48 °C of outdoor air. The corresponding coefficient of performance achieved (just for cooling) was 32. It is also shown that the enhanced IEC operates steadily in ambient temperatures ranging from 30 to 48 °C and maintains supply air temperatures within the comfort zone of ASHRAE-55 and ISO7730.

Nanotopography Influences Host-Pathogen Quorum Sensing and Facilitates Selection of Bioactive Metabolites in Mesenchymal Stromal Cells and Pseudomonas aeruginosa Co-Cultures.

Orthopedic implant-related bacterial infections and resultant antibiotic-resistant biofilms hinder implant-tissue integration and failure. Biofilm quorum sensing (QS) communication determines the pathogen colonization success. However, it remains unclear how implant modifications and host cells are influenced by, or influence, QS. High aspect ratio nanotopographies have shown to reduce biofilm formation of Pseudomonas aeruginosa, a sepsis causing pathogen with well-defined QS molecules. Producing such nanotopographies in relevant orthopedic materials (i.e., titanium) allows for probing QS using mass spectrometry-based metabolomics. However, nanotopographies can reduce host cell adhesion and regeneration. Therefore, we developed a polymer (poly(ethyl acrylate), PEA) coating that organizes extracellular matrix proteins, promoting bioactivity to host cells such as human mesenchymal stromal cells (hMSCs), maintaining biofilm reduction. This allowed us to investigate how hMSCs, after winning the race for the surface against pathogenic cells, interact with the biofilm. Our approach revealed that nanotopographies reduced major virulence pathways, such as LasR. The enhanced hMSCs support provided by the coated nanotopographies was shown to suppress virulence pathways and biofilm formation. Finally, we selected bioactive metabolites and demonstrated that these could be used as adjuncts to the nanostructured surfaces to reduce biofilm formation and enhance hMSC activity. These surfaces make excellent models to study hMSC-pathogen interactions and could be envisaged for use in novel orthopedic implants.

The Development and Validation of a Disordered Eating Screening Tool for Current and Former Athletes: The Athletic Disordered Eating (ADE) Screening Tool.

Current and former athletes are one of the most at-risk population groups for disordered eating (DE), impacting their dietary practices, body composition, performance and health during and following their athletic careers. Few comprehensive DE screening tools exist for this group. To help address this, the current study utilised a mixed-methods approach of Classic Test Theory (CTT) and Item Response Theory (IRT) to develop and validate a DE screening tool suitable for current and former athletes. Novel scale development methodologies were used to develop and assess the validity (content, face, cross-cultural, construct), test-retest reliability, internal consistency reliability, factor analysis and Rasch analysis of a new DE scale. A new validated Athletic Disordered Eating (ADE) screening tool was created, with 17 items and four subscales (food control, bingeing, body control, body discontent), with an internal consistency reliability of 0.91, excellent content and construct validity, an Intraclass Correlation Coefficient of 0.97 and excellent Rasch model fit. The ADE screening tool has been dually developed for research purposes and as a clinically applicable screening tool to detect DE in current and former athletes and is suitable for a global use across sporting categories, diverse genders and levels of competition.

Dimensionality of instructional quality in physical education. Obtaining students' perceptions using bifactor exploratory structural equation modeling and multilevel confirmatory factor analysis.

In research on instructional quality, the generic model of the three basic dimensions is an established framework, which postulates that the three dimensions of classroom management, student support and cognitive activation represent quality characteristics of instruction that can be generalized across subjects. However, there are hardly any studies that examine if the three basic dimensions model could represent a suitable approach to measure instructional quality in physical education. Based on an extended model of the basic dimensions, a measurement model of instructional quality for physical education is presented, which integrates different theoretical approaches from the fields of educational and psychological research as well as different subfields of sports science in order to test the factorial structure of the corresponding measurement model. 1,047 students from 72 seventh to ninth grade classes from different German-speaking Swiss cantons participated in the study. The conceptualization of the instrument is based on a hybrid approach that integrates generic and subject-specific characteristics. The simultaneous analysis at the individual and class level using MCFA was supplemented by more complex methodological techniques within the relatively new B-ESEM framework at the individual level. The postulated five-factor structure was initially tested using ICM-CFA and showed a good model fit (e.g., χ2/df = 2.32, RMSEA = 0.03, CFI = 0.97, TLI = 0.97, SRMR = 0.04). MCFA revealed a differential factorial structure at both levels of analysis with five factors at the individual level and four factors at the class level (e.g., χ2/df = 2.23, RMSEA = 0.03, CFI = 0.96, TLI = 0.96, SRMR within = 0.04, SRMR between = 0.10). ESEM and B-ESEM outperformed the ICM-CFA and showed an excellent model fit (B-ESEM: χ2/df = 1.19, RMSEA = 0.01, CFI = 1.00, TLI = 1.00, SRMR = 0.01). Inter-factor correlations and factor loadings are largely in line with expectations, indicating arguments for construct validity. The study represents a substantial contribution in linking physical education and the generic research on instructional quality. Overall, strong arguments for the factorial structure of the measurement model were demonstrated. The study can be interpreted as a first step in a multi-step procedure in terms of further validity arguments.

Dynamic tank-in-series modelling and simulation of gas-liquid interaction in trickle bed reactor designed for gas fermentation

Trickle bed reactors (TBR), historically utilized in petroleum processing and wastewater treatment, now extend their applicability in biological gas conversions, including syngas biomethanation for renewable methane production. Despite operational benefits, optimizing TBR design and scale-up demands a good understanding of the reactor's hydraulic behavior and mass transfer phenomena. This study's novelty is TBR's hydraulic characterization in respect to liquid and gas flowrates and simulation of the gas-liquid interaction by a dynamic gas-liquid transfer model. Residence time distribution (RTD) experiments in 220 mL lab- and 5000 mL pilot-scale TBRs with co-current flow of gas and liquid were conducted to determine the liquid and gas working volume and the number of tanks for a dynamic tank-in-series (TIS) model. RTD experiments revealed 2–6 tanks for varying liquid flowrate (constant gas flowrate) and 5–8 tanks for varying gas flowrate (constant liquid flowrate). A dimensionless equation, fitted to RTD experimental data, predicted the liquid working volume of a TBR at various liquid flowrates and reactor configurations. TBR simulation by TIS model considering 8 well mixed gas and liquid phase tanks connected in series, resulted in an excellent model validation with an R2 at 0.99. Finally, the model simulated the mass transfer kinetics of H2, CO, and CO2 in water under varying gas and liquid flowrates for lab- and pilot-scale TBRs. Simulation results showed increased dissolved gas concentration with higher gas flowrate (constant liquid flowrate) for both scales TBR. It was also noticeable that under constant gas flowrate, the dissolved gas concentration initially decreased (0.01 < ReL < 17), then increased (17 < ReL < 34), and again decreased (34 < ReL < 105). This behavior was the same for both scales TBR and revealed an optimum ReL value irrespective of TBR size.