bluuebunny/crossref_metadata_2025 huggingface dataset:
Description of a Remarkable New Skate Species of Leucoraja Malm, 1877 (Rajiformes, Rajidae) from the Southwestern Indian Ocean: Introducing 3D Modeling as an Innovative Tool for the Visualization of Clasper Characters
Authors: Weigmann Simon , Stehmann Matthias F. W. , Séret Bernard , Ishihara Hajime
Published: June 2024

A remarkable new deep-water skate, Leucoraja longirostris n. sp., is described based on eight specimens caught during different expeditions to the southern Madagascar Ridge in the southwestern Indian Ocean. The new species differs from all congeners by its remarkably long and acutely angled snout (horizontal preorbital length 17.2–22.6% TL vs. 8.5–11.9% TL and 4.2–6.1 vs. 1.7–3.5 times orbit length, snout angle 65–85° vs. 90–150°). Furthermore, it is apparently endemic to the Madagascar Ridge, distant from the known distribution areas of all congeners. In addition to L. fullonica and L. pristispina, L. longirostris n. sp. is also the only species with plain dorsal coloration. Furthermore, the new species is the only Leucoraja species with an external clasper component dike and, besides L. wallacei, the only one with four dorsal terminal (dt) cartilages. The shape of the accessory terminal 1 (at1) cartilage with four tips is also unique within the genus. A new approach for the visualization of the clasper characters is introduced based on 3D models of all skeletal and external features. This enables a much easier and much more precise interpretation of every single clasper component, of the entire structure, and, in particular, the relationship between external features and skeletal cartilages. A new English translation of the first diagnosis of Leucoraja is provided, along with a revised generic diagnosis and a key to the species of Leucoraja in the Indian Ocean.
Barking Up the Wrong Tree—Motor–Sensory Elements as Prodrome in Autism
Authors: Lotan Meir
Published: June 2024

Autism spectrum disorder (ASD) has been intensely investigated since the term was first used over 80 years ago. The prevalence of ASD is constantly rising, and, currently, 1:36 children are diagnosed with this disorder. Despite the intense interest in ASD, the origins of this disorder remain obscure. This article explores motor issues and proprioceptive interoception difficulties as the prodrome of ASD. The importance of early intervention in the prognosis of ASD is common knowledge. Yet, since the communicational and social behaviors typical of ASD are observable only after the age of 18 months, diagnosis and early intervention are delayed. Therefore, the quest into the involvement of sensory–motor difficulties as a source of ASD traits, or at least as a potential early indicator, is warranted, with the intention of enabling early diagnosis and early intervention. This article examines the justification for this new avenue of early diagnosis and intervention and may open up a completely different way of viewing ASD. This new point of view may suggest an original path of assessment and intervention in infancy with this group of clients, possibly leading to improved prognosis for children and their families.
Investigation on Seismic Performance of Reinforced Concrete Frame Retrofitted by Carbon Fiber-Reinforced Polymer
Authors: Zhou Yang , Liu Xiangyu , Zhang Xuetan , Guo Xiaoyun
Published: June 2024

In order to improve the seismic performance of reinforced concrete (RC) frames, carbon fiber-reinforced polymer (CFRP) was used to retrofit reinforced concrete frame structures. The comparison pseudo-static test results show that the peak load, initial stiffness and ductility of the CFRP retrofitted model were increased by 43.89%, 39.27% and 30.1%, respectively. Based on the parametric study of the finite element model, the contribution of CFRP to the seismic upgrading effect of RC columns was quantitatively revealed, and an optimized design of retrofitted CFRP was proposed. The results show that the peak load, ductility and energy dissipation capacity of the whole structure are improved by using CFRP full-wrap reinforcement and strip reinforcement models with different coverage areas. The damage degree of the column decreases, the damage degree of the beam increases, and the failure mode changes from “column hinge” to “beam hinge”. Simultaneously, different CFRP reinforcement areas and the distance between strip CFRP have different reinforcement effects on concrete structures. Based on the investigation results, the recommended ratio of CFRP strip to spacing is 1 to 1.25.
Flexural Behavior of Partially Encased Composite Beams with a Large Tensile Reinforcement Ratio
Authors: Jiang Yuchen , Hu Xiamin , Zheng Hao , Shuai Haoyang
Published: June 2024

Partially encased composite beams (PECBs) have advantages over conventional steel–concrete composite beams in load-carrying capacity, flexural stiffness and fire resistance. In order to determine whether the shearing force is sufficient to ensure the yield of the tensile reinforcement in the case of a large tensile reinforcement ratio, as well as the influence of encasing concrete strength and the addition of studs on the steel web, three PECB specimens were tested under bending. The results show that, in the case of a 5% tensile reinforcement ratio, natural bonding and friction forces ensure the yield of tensile reinforcement whether studs are added on the steel web or not. The encasing concrete strength and the addition of studs on the steel web have no obvious effect on both the elastic and plastic bending resistance of PECBs. The addition of studs on the steel web significantly slows down the stiffness deterioration of PECBs within the elastoplastic stage, while the flexural stiffness is not obviously affected by the strength of encasing concrete. The simplified plastic theory is proved to be applicable to predict the flexural capacity of PECBs with a large tensile reinforcement ratio. It is also indicated by calculation that, by increasing the tensile reinforcement ratio from 2% to 5%, the flexural capacity of PECBs has a significant increase, by about 32%.
Exploring the Determinants of Quality of Work Life in the Construction Industry: A Quantitative Approach
Authors: Soundarya Priya M. G. , Anandh K. S.
Published: June 2024

This research aims to identify and quantify the factors affecting quality of work life (QWL) among professionals in the Indian construction industry. The study employs a structured questionnaire, distributed to 900 construction professionals, yielding a response rate of 80.44%. The QWL construct was assessed through eight factors: career growth, management, job satisfaction, remuneration and fringe benefits, the work–family interface, emotional intelligence, work culture, and work commitment. Both descriptive and inferential analysis were carried out. The relative importance index method was used to rank these factors based on their relative importance. Work commitment (RII = 0.772) ranked as the most important factor, this was due to work commitment including significant items. The high ranking of this factor suggests that commitment to work is highly valued in the construction industry. The study also employed structural equation modelling to validate the association among these QWL factors. The findings reveal that job satisfaction (t = 0.765) and career growth (t = 0.751) play significant roles in QWL, suggesting that these factors should be prioritized to enhance QWL in the construction industry. The results of this study provide valuable insights for organizations, HR practitioners, and researchers in the construction industry, emphasizing the need to focus on job satisfaction and career growth to enhance QWL. This study contributes to the existing literature by providing a comprehensive analysis of QWL in the construction industry, offering valuable insights for organizations, HR practitioners, and researchers. Future research could adopt longitudinal study designs or qualitative methods to further explore the QWL among construction professionals.
Effectiveness of the Concrete Equivalent Mortar Method for the Prediction of Fresh and Hardened Properties of Concrete
Authors: Ibrahim Haruna , Wardeh George , Fares Hanaa , Ghorbel Elhem
Published: June 2024

Modern concrete mix design is a complex process involving superplasticisers, fine powders, and fibres, requiring time and energy due to the high number of trial tests needed to achieve rheological properties in the fresh state. Concrete batching involves the extensive use of materials, time, and the testing of chemical admixtures, with various methodologies proposed. Therefore, in some instances, the required design properties (physical and mechanical) are not achieved, leading to the loss of resources. The concrete equivalent mortar (CEM) method was introduced to anticipate concrete behaviour at fresh and hardened states. Moreover, the CEM method saves time and costs by replacing coarse aggregates with an equivalent sand mass, resulting in an equivalent specific surface area at the mortar scale. This study aims to evaluate the performance of fibre in CEM and concrete and determine the relationships between the CEM and the concrete in fresh and hardened states. Steel and polypropylene fibres were used to design three series of mixtures (CEM and concrete): normal-strength concrete (NSC), high-strength concrete (HSC), high-strength concrete with fly ash (HSCFA), and equivalent normal-strength mortar (NSM), high-strength mortar (HSM), and high-strength mortar with fly ash (HSMFA). This study used three-point bending tests and digital image correlation to evaluate load and crack mouth opening displacement (CMOD) curves. An analytical mode I crack propagation model was developed using a tri-linear stress–crack opening relationship. Post-cracking parameters were optimised using inverse analysis and compared to actual MC2010 characteristic values. The concrete slump is approximately half of the CEM flow; its compressive strength ranges between 78% and 82% of CEM strength, while its flexural strength is 60% of CEM strength. The post-cracking behaviour showed a significant difference attributed to the presence of aggregates in concrete. The fracture energy of concrete is 28.6% of the CEM fracture energy, while the critical crack opening of the concrete is 60% of that of the CEM.
Dynamic Response Analysis Method of a High-Strength RC Beam Subjected to Long-Duration Blast Loading
Authors: Zhao Haochuan , Zeng Fan , Feng Xiaowei , Wang Shouqian , Huang Chao , Liu Na , Zhang Jian
Published: June 2024

An analysis method of normalized pressure–impulse (P-I) diagrams related to the ductility ratio of structural components is proposed, to quickly estimate the dynamic response of high-strength reinforcement concrete (RC) beams subjected to long-duration blast loading. Firstly, the overall bending deformation mode of RC beams is uncovered via explosion tests in a closed chamber, where the durations of the near-planar blast loadings are varied within 80–105 ms. Then, a single-degree-of-freedom (SDOF) model is established based on the bending deformation mode. The resistance function for the uniform pressure loading is developed using a novel approach, consisting of (1) developing and benchmarking a three-dimensional (3D) improved steel–concrete separated finite-element (FE) model; (2) using the benchmarked FE model to conduct numerical simulations for uniform pressure loading; and (3) idealizing the resistance function for uniform pressure using a bilinear relationship. Finally, the SDOF model is used to conduct parametric analyses and develop a normalized P-I diagram that can be used to analyze or design RC beams for far-field blast effects. This P-I diagram is verified using results from blast load tests that are primarily in the dynamic region. A total of 188 additional 3D nonlinear FE analyses of RC beams are conducted to expand the database in the impulse and quasi-static regions. Considering the limitations of the proposed method in predicting the shear-dominated deformation and the fracture behavior of members, the P-I diagram is applicable to the dynamic response of the bending deformation of members under far-field explosion, which can provide an important reference for the blast-resistant design and analysis of high-strength RC beams.
Enhancing Architectural Education through Artificial Intelligence: A Case Study of an AI-Assisted Architectural Programming and Design Course
Authors: Jin Shitao , Tu Huijun , Li Jiangfeng , Fang Yuwei , Qu Zhang , Xu Fan , Liu Kun , Lin Yiquan
Published: June 2024

This study addresses the current lack of research on the effectiveness assessment of Artificial Intelligence (AI) technology in architectural education. Our aim is to evaluate the impact of AI-assisted architectural teaching on student learning. To achieve this, we developed an AI-embedded teaching model. A total of 24 students from different countries participated in this 9-week course, completing a comprehensive analysis of architectural programming and design using AI technologies. This study conducted questionnaire surveys with students at both midterm and final stages of the course, followed by structured interviews after the course completion, to explore the effectiveness and application status of the teaching model. The results indicate that the AI-embedded teaching model positively and effectively influenced student learning. The “innovative capability” and “work efficiency” of AI technologies were identified as key factors affecting the effectiveness of the teaching model. Furthermore, the study revealed a close integration of AI technologies with architectural programming but identified challenges in the uncontrollable expression of architectural design outcomes. Student utilization of AI technologies appeared fragmented, lacking a systematic approach. Lastly, the study provides targeted optimization suggestions based on the current application status of AI technologies among students. This research offers theoretical and practical support for the further integration of AI technologies in architectural education.
Sensitivity of a Lumped-Capacitance Building Thermal Modelling Approach for Energy-Market-Scale Flexibility Studies
Authors: Rasku Topi , Simson Raimo , Kiviluoma Juha
Published: June 2024

Despite all the literature on building energy management, building-stock-scale models depicting its impact for energy-market-scale optimisation models are lacking. To address this shortcoming, an open-source tool called ArchetypeBuildingModel.jl has been developed for aggregating building-stock-level data into simplified lumped-capacitance thermal models compatible with existing open-source energy-system modelling frameworks. This paper aims to demonstrate the feasibility of these simplified thermal models by comparing their performance against dedicated building simulation software, as well as examining their sensitivity to key modelling and parameter assumptions. Modelling and parameter assumptions comparable to the existing literature achieved an acceptable performance according to ASHRAE Guideline 14 across all tested buildings and nodal configurations. The most robust performance was achieved with a period of variations above 13 days and interior node depth between 0.1 and 0.2 for structural thermal mass calibrations, and with external shading coefficients between 0.6 and 1.0 and solar heat gain convective fractions between 0.4 and 0.6 for solar heat gain calibrations. Furthermore, three-plus-node lumped-capacitance thermal models are recommended when modelling buildings with structures varying in terms of thermal mass. Nevertheless, the ArchetypeBuildingModel.jl performance was found to be robust against uncertain key parameter assumptions, making it plausible for energy-market-scale applications.
Understanding the Future Competitive Advantages of the Construction Industry
Authors: Aigbe Fortune , Aigbavboa Clinton , Aliu John , Amusan Lekan
Published: June 2024

Technological changes (such as Construction 4.0) in an organization cause the workforce to exhibit resistance to change, job redundancy, etc. Geographical location will no longer provide a competitive advantage, but resources will be the source of competitive advantage in the future, and these resources will be intangible, valuable, and not be easily imitated. The aim of this study is to provide an understanding of the future competitive advantages of organizations in the construction industry that could help the construction workforce easily adapt to technological changes. This study is based on resource-based theory and the ADKAR change management model. This study developed an ADREKA sequence for organizations to achieve future competitive advantage during technological changes in the construction industry. Hence, building social, relational, and human capital is necessary during technological changes to achieve competitive advantage for an organization and foster workforce adaptability to change.
The Cyclic Performance and Macro-Simplified Analytical Model of Internal Joints in RC-Assembled Frame Structures Connected by Unbonded Prestressed Strands and Mortise-Tenon Based on Numerical Studies
Authors: Wang Junwei , Zhang Wenxue , Zhang Cheng
Published: June 2024

This paper introduces a novel type of connection that integrates unbonded prestressed strands (UPS) and mortise-tenon in an assembly frame structure (UPS-MTF). First, the damage process and failure modes of the joints under reciprocating horizontal loads were systematically analyzed using refined numerical models. The recommended values of the design parameters of the joints were derived from the parametric analysis results. Refined numerical modeling results reveal the diagonal compression strut mechanism within the core region of the joint. The diagonal compression struts model assists in establishing the theoretical calculation formula for the skeleton curve of shear stress–strain in the core region. Second, a genetic algorithm (GA) parameter was identified for the restoring force model of the core region to determine the parameters of the hysteresis rules. Finally, a macro-simplified analytical model of the joint was created based on the restoring force model of the core region, and parameter analysis was conducted to verify the applicability of this macro-simplified analytical model. The research results prove that the damaged form of the joint proposed in this paper originates from the shear and relative slip damage between the components in the core region. The axial compression ratio significantly affects the hysteretic performance of the joints, and the upper and lower limit values were identified for the axial compression ratio of the joints. The area and initial effective stress of the UPS exert a minimal effect on the hysteretic performance of the joint. Based on the method proposed in this paper for determining the restoring force model in the core region of the joints, the hysteresis curves obtained from the macro-simplified analytical model closely match the refined numerical analysis model results. This correspondence verifies the applicability of the macro-simplified analytical model.
Lateral Performance Analysis of Trapezoidal Orthogonal Stiffened Steel Plate Shear Walls
Authors: Zheng Hong , Cai Lele , Qin Jiawei , Mi Yuxi , Jiang Liqiang , Ma Xiaoming , Sun Zhiwei
Published: June 2024

This paper introduces a trapezoidal orthogonal stiffener steel plate shear wall (TSW). The finite element model of the TSW was developed following the validation of low-cycle repeated tests conducted on a single-span double-layer steel plate shear wall. The paper studies the effects of the flat steel plate thickness, stiffener thickness, stiffener height, and stiffener bottom width on the seismic performance of TSW. Building upon these findings, a theoretical formula for the ultimate shear capacity of TSW was developed. The results prove the following: (1) By changing the flat steel plate thickness, the stiffener thickness, and the stiffener height, the seismic behavior of TSW can be enhanced. It is suggested that the flat steel plate thickness is 4~6 mm, the stiffener thickness is 4~6 mm, and the stiffener height is not more than 60 mm, while the effect of the stiffener bottom width on the seismic behavior of TSW can be neglected. (2) The maximum error is 22.16%, compared to the theoretical value of TSW ultimate shear capacity with the finite element simulation value. However, as the finite element results surpass the test results, it indicates that the formula-derived results are unsafe, necessitating a recommendation for correction.
Structural Condition Assessment of Steel Anchorage Using Convolutional Neural Networks and Admittance Response
Authors: Ho Duc-Duy , Kim Jeong-Tae , Hoang Nhat-Duc , Tran Manh-Hung , Pradhan Ananta Man Singh , Truong Gia Toai , Huynh Thanh-Canh
Published: June 2024

Structural damage in the steel bridge anchorage, if not diagnosed early, could pose a severe risk of structural collapse. Previous studies have mainly focused on diagnosing prestress loss as a specific type of damage. This study is among the first for the automated identification of multiple types of anchorage damage, including strand damage and bearing plate damage, using deep learning combined with the EMA (electromechanical admittance) technique. The proposed approach employs the 1D CNN (one-dimensional convolutional neural network) algorithm to autonomously learn optimal features from the raw EMA data without complex transformations. The proposed approach is validated using the raw EMA response of a steel bridge anchorage specimen, which contains substantial nonlinearities in damage characteristics. A K-fold cross-validation approach is used to secure a rigorous performance evaluation and generalization across different scenarios. The method demonstrates superior performance compared to established 1D CNN models in assessing multiple damage types in the anchorage specimen, offering a potential alternative paradigm for data-driven damage identification in steel bridge anchorages.
Experimental Study on the Bonding Performance between Shaped Steel and High-Strength Concrete
Authors: Tao Qinglin , Pei Weiping , Zhang Hao , Hu Yi , Qian Yuandi , Wang Yingtong , Kong Zhengyi
Published: June 2024

The integration of steel fibers into high-strength concrete (HSC) offers a solution to address the brittleness and limited ductility typically associated with conventional HSC structures. To investigate the bonding properties between shaped steel and high-strength concrete with steel fiber (SFRC), thirteen tests of the shaped steel/SFRC specimens are conducted to explore the effects of various factors such as steel fiber volume ratio, concrete strength grade, reinforcement ratio, steel embedment depth, and cover thickness on bond–slip behavior. Three distinct failure modes, such as pushout failure, bond splitting, and yielding failure of steel, are identified during the pushout tests. Three different types of bond strength, such as the initial bond strength, the ultimate bond strength, and the residual bond strength, are observed from the load–slip curves between the shaped steel and concrete. By incorporating nonlinear spring elements, a numerical model for accurately simulating the bond performance between the shaped steel and SFRC specimens is developed. The bond strength between the shaped steel and concrete increase as the concrete strength, cover thickness, steel fiber volume ratio, and stirrup ratio increase, while it decreases as the steel embedment depth increases. A model for the bond strength between shaped steel and SFRC is developed, and it agrees well with the test data.
Enhanced Indoor Air Quality Dashboard Framework and Index for Higher Educational Institutions
Authors: Shoukry Farah , Goubran Sherif , Tarabieh Khaled
Published: June 2024

This research proposes a 10-step methodology for developing an enhanced IAQ dashboard and classroom index (CI) in higher educational facilities located in arid environments. The identified parameters of the enhanced IAQ dashboard–inspired by the pandemic experience, result from the literature review and the outcome of two electronic surveys of (52) respondents, including health professionals and facility management experts. On the other hand, the indicators included in the CI are based on (80) occupant survey responses, including parameters related to IAQ, Indoor Environmental Quality (IEQ), and thermal comfort, amongst other classroom operative considerations. The CI is further tested in four learning spaces at the American University in Cairo, Egypt. The main contribution of this research is to suggest a conceptual visualization of the dashboard and a practical classroom index that integrates a representative number of contextual indicators to recommend optimal IAQ scenarios for a given educational facility. This study concludes by highlighting several key findings: (1) both qualitative and quantitative metrics are necessary to capture indoor air quality-related parameters accurately; (2) tailoring the dashboard as well as the CI to specific contexts enhances its applicability across diverse locations; and finally, (3) the IAQ dashboard and CI offer flexibility for ad-hoc applications.
Production of Glass Foam in a Microwave Oven Using Agro-Industrial Waste as Raw Material
Authors: Fernandes Fernando Antonio da Silva , Fernandes Thamara Fernanda da Silva , Rossignolo João Adriano
Published: June 2024

Climate change is characterized by shifts in temperature and climate patterns. Constructing new high-rise environments using materials that incorporate agro-industrial waste can help mitigate this impact without compromising technological properties. This study produced vitreous foams intended to replace natural aggregates in lightweight concrete partially. These foams were sintered in a microwave oven at temperatures of 750 °C, 800 °C, and 850 °C, utilizing glass powder and sugarcane bagasse ash as raw materials. The homogenization and preparation of these materials were conducted through a mechanical pelletization process, employing a constant rotation engine at approximately 40 rpm. The efficacy of microwave sintering was assessed by comparing the outcomes with those from sintering in a conventional electric muffle furnace under identical conditions. The results indicated that the microwave-sintered vitreous foams exhibited the following values for apparent density (≤0.30 g/cm3), porosity (86% to 94%), and compressive strength (0.48 MPa to 0.58 MPa), which align with the global standards for commercial vitreous foams. The microwave sintering route proved to be economically feasible by reducing sintering time and, consequently, energy costs, without sacrificing technological properties. The materials produced in this study offer a promising solution to minimize the environmental impact associated with constructing new buildings, particularly tall structures. Additionally, they support the circular economy by converting waste into valuable by-products.
Modification of NiSe2 Nanoparticles by ZIF-8-Derived NC for Boosting H2O2 Production from Electrochemical Oxygen Reduction in Acidic Media
Authors: Cheng Qiaoting , Ding Hu , Chen Lang , Dong Jiatong , Yu Hao , Yan Shen , Wang Hua
Published: June 2024

The two-electron oxygen reduction reaction (2e− ORR) has emerged as an attractive alternative for H2O2 production. Developing efficient earth-abundant transition metal electrocatalysts and reaction mechanism exploration for H2O2 production are important but remain challenging. Herein, a nitrogen-doped carbon-coated NiSe2 (NiSe2@NC) electrocatalyst was prepared by successive annealing treatment. Benefiting from the synergistic effect between the NiSe2 nanoparticles and NC, the 2e− ORR activity, selectivity, and stability of NiSe2@NC in 0.1 M HClO4 was greatly enhanced, with the yield of H2O2 being 4.4 times that of the bare NiSe2 nanoparticles. The in situ Raman spectra and density functional theory (DFT) calculation revealed that the presence of NC was beneficial for regulating the electronic state of NiSe2 and optimizing the adsorption free energy of *OOH, which could enhance the adsorption of O2, stabilize the O-O bond, and boost the production of H2O2. This work provides an effective strategy to improve the performance of the transition metal chalcogenide for 2e− ORR to H2O2.
Transcription Factors Sox2 and Sox3 Directly Regulate the Expression of Genes Involved in the Onset of Oligodendrocyte Differentiation
Authors: Rupprecht Jesse , Reiprich Simone , Baroti Tina , Christoph Carmen , Sock Elisabeth , Fröb Franziska , Wegner Michael
Published: June 2024

Rapid information processing in the central nervous system requires the myelination of axons by oligodendrocytes. The transcription factor Sox2 and its close relative Sox3 redundantly regulate the development of myelin-forming oligodendrocytes, but little is known about the underlying molecular mechanisms. Here, we characterized the expression profile of cultured oligodendroglial cells during early differentiation and identified Bcas1, Enpp6, Zfp488 and Nkx2.2 as major downregulated genes upon Sox2 and Sox3 deletion. An analysis of mice with oligodendrocyte-specific deletion of Sox2 and Sox3 validated all four genes as downstream targets in vivo. Additional functional assays identified regulatory regions in the vicinity of each gene that are responsive to and bind both Sox proteins. Bcas1, Enpp6, Zfp488 and Nkx2.2 therefore likely represent direct target genes and major effectors of Sox2 and Sox3. Considering the preferential expression and role of these genes in premyelinating oligodendrocytes, our findings suggest that Sox2 and Sox3 impact oligodendroglial development at the premyelinating stage with Bcas1, Enpp6, Zfp488 and Nkx2.2 as their major effectors.
The Influence of N-Acetyl-selenomethionine on Two RONS-Generating Cancer Cell Lines Compared to N-Acetyl-methionine
Authors: Greilberger Joachim , Stiegler Philipp , Greilberger Michaela , Wintersteiger Reinhold
Published: June 2024

N-acetyl-selenomethionine (NASeLM), a representative of the selenium compounds, failed to convince in clinical studies and cell cultures that it neither inhibits cancer growth nor has a chemoprotective effect. This study aims to find out whether NASeLM shows a growth-inhibiting property compared to the carrier substance N-Acetyl-L-methionine (NALM) on two different cancer cells, namely Jurkat cells and MTC-SK cells. Methods: Jurkat and MTC-SK cells were cultured in the absence or presence of varying concentrations (0–500 µg/mL) of NASeLM and NALM solutions. After 0, 24, 48, and 72 h, mitochondrial activity, cancer cell membrane CP levels, cell growth, and caspase-3 activity were assessed in aliquots of Jurkat and MTC-SK cells. Results: Both substances, NASeLM and NALM, were similarly able to inhibit cell growth and mitochondrial activity of Jurkat cells in a concentration-dependent and time-dependent manner up to 70%. Only the determination of caspase activity showed that only NASeLM was able to increase this to almost 40% compared to the control as well as the same lack of NALM. However, the experiments on MTC-SK cells showed a clear difference in favor of NASeLM compared to NALM. While NASeLM was able to reduce cell growth to up to 55%, the same amount of NALM was only at around 15%, which turned out to be highly significant (p < 0.001). The same could also be measured for the reduction in MTC-SK mitochondrial activity. Time dependence could also be recognized: the longer both substances, NASeLM and NALM, were incubated, the higher the effect on cell growth and mitochondrial activity, in favour of NASeLM. Only NASeLM was able to increase caspase-3 activity in MTC-SK cells: at 250 µg/mL NASeLM, caspase-3 activity increased significantly to 28% after 24 and 48 h compared to the control (14%) or the same NALM concentration (14%). After 72 h, this could still increase to 37%. A further increase in the NASeLM concentration did not result in higher caspase-3 activity. Conclusion: NASeLM could clearly increase caspase-3 activity in both cell types, Jurkat or MTC-SK cells, and thus induce cell death. NALM and NASeLM showed a reduction in cell growth and mitochondrial activity in both cell lines: While NALM and NASeLM showed almost identical measurements on Jurkat cells, NASeLM was much more effective on MTC-SK than the non-selenium-containing carrier, indicating that it has additional anti-chemoprotective effects.
KR158 Spheres Harboring Slow-Cycling Cells Recapitulate High-Grade Glioma Features in an Immunocompetent System
Authors: Chakraborty Avirup , Yang Changlin , Kresak Jesse L. , Silver Aryeh J. , Feier Diana , Tian Guimei , Andrews Michael , Sobanjo Olusegun O. , Hodge Ethan D. , Engelbart Mia K. , Huang Jianping , Harrison Jeffrey K. , Sarkisian Matthew R. , Mitchell Duane A. , Deleyrolle Loic P.
Published: June 2024

Glioblastoma (GBM) poses a significant challenge in clinical oncology due to its aggressive nature, heterogeneity, and resistance to therapies. Cancer stem cells (CSCs) play a critical role in GBM, particularly in treatment resistance and tumor relapse, emphasizing the need to comprehend the mechanisms regulating these cells. Also, their multifaceted contributions to the tumor microenvironment (TME) underline their significance, driven by their unique properties. This study aimed to characterize glioblastoma stem cells (GSCs), specifically slow-cycling cells (SCCs), in an immunocompetent murine GBM model to explore their similarities with their human counterparts. Using the KR158 mouse model, we confirmed that SCCs isolated from this model exhibited key traits and functional properties akin to human SCCs. KR158 murine SCCs, expanded in the gliomasphere assay, demonstrated sphere forming ability, self-renewing capacity, positive tumorigenicity, enhanced stemness and resistance to chemotherapy. Together, our findings validate the KR158 murine model as a framework to investigate GSCs and SCCs in GBM pathology, and explore specifically the SCC–immune system communications, understand their role in disease progression, and evaluate the effect of therapeutic strategies targeting these specific connections.
Defining Human Regulatory T Cells beyond FOXP3: The Need to Combine Phenotype with Function
Authors: Gootjes Chelsea , Zwaginga Jaap Jan , Roep Bart O. , Nikolic Tatjana
Published: June 2024

Regulatory T cells (Tregs) are essential to maintain immune homeostasis by promoting self-tolerance. Reduced Treg numbers or functionality can lead to a loss of tolerance, increasing the risk of developing autoimmune diseases. An overwhelming variety of human Tregs has been described, based on either specific phenotype, tissue compartment, or pathological condition, yet the bulk of the literature only addresses CD25-positive and CD127-negative cells, coined by naturally occurring Tregs (nTregs), most of which express the transcription factor Forkhead box protein 3 (FOXP3). While the discovery of FOXP3 was seminal to understanding the origin and biology of nTregs, there is evidence in humans that not all T cells expressing FOXP3 are regulatory, and that not all Tregs express FOXP3. Namely, the activation of human T cells induces the transient expression of FOXP3, irrespective of whether they are regulatory or inflammatory effectors, while some induced T cells that may be broadly defined as Tregs (e.g., Tr1 cells) typically lack demethylation and do not express FOXP3. Furthermore, it is unknown whether and how many nTregs exist without FOXP3 expression. Several other candidate regulatory molecules, such as GITR, Lag-3, GARP, GPA33, Helios, and Neuropilin, have been identified but subsequently discarded as Treg-specific markers. Multiparametric analyses have uncovered a plethora of Treg phenotypes, and neither single markers nor combinations thereof can define all and only Tregs. To date, only the functional capacity to inhibit immune responses defines a Treg and distinguishes Tregs from inflammatory T cells (Teffs) in humans. This review revisits current knowledge of the Treg universe with respect to their heterogeneity in phenotype and function. We propose that it is unavoidable to characterize human Tregs by their phenotype in combination with their function, since phenotype alone does not unambiguously define Tregs. There is an unmet need to align the expression of specific markers or combinations thereof with a particular suppressive function to coin functional Treg entities and categorize Treg diversity.
Adipo-Epithelial Transdifferentiation in In Vitro Models of the Mammary Gland
Authors: Perugini Jessica , Smorlesi Arianna , Acciarini Samantha , Mondini Eleonora , Colleluori Georgia , Pirazzini Chiara , Kwiatkowska Katarzyna Malgorzata , Garagnani Paolo , Franceschi Claudio , Zingaretti Maria Cristina , Dani Christian , Giordano Antonio , Cinti Saverio
Published: June 2024

Subcutaneous adipocytes are crucial for mammary gland epithelial development during pregnancy. Our and others’ previous data have suggested that adipo-epithelial transdifferentiation could play a key role in the mammary gland alveolar development. In this study, we tested whether adipo-epithelial transdifferentiation occurs in vitro. Data show that, under appropriate co-culture conditions with mammary epithelial organoids (MEOs), mature adipocytes lose their phenotype and acquire an epithelial one. Interestingly, even in the absence of MEOs, extracellular matrix and diffusible growth factors are able to promote adipo-epithelial transdifferentiation. Gene and protein expression studies indicate that transdifferentiating adipocytes exhibit some characteristics of milk-secreting alveolar glands, including significantly higher expression of milk proteins such as whey acidic protein and β-casein. Similar data were also obtained in cultured human multipotent adipose-derived stem cell adipocytes. A miRNA sequencing experiment on the supernatant highlighted mir200c, which has a well-established role in the mesenchymal–epithelial transition, as a potential player in this phenomenon. Collectively, our data show that adipo-epithelial transdifferentiation can be reproduced in in vitro models where this phenomenon can be investigated at the molecular level.
High-Resolution Proteomics Unravel a Native Functional Complex of Cav1.3, SK3, and Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in Midbrain Dopaminergic Neurons
Authors: Belghazi Maya , Iborra Cécile , Toutendji Ophélie , Lasserre Manon , Debanne Dominique , Goaillard Jean-Marc , Marquèze-Pouey Béatrice
Published: June 2024

Pacemaking activity in substantia nigra dopaminergic neurons is generated by the coordinated activity of a variety of distinct somatodendritic voltage- and calcium-gated ion channels. We investigated whether these functional interactions could arise from a common localization in macromolecular complexes where physical proximity would allow for efficient interaction and co-regulations. For that purpose, we immunopurified six ion channel proteins involved in substantia nigra neuron autonomous firing to identify their molecular interactions. The ion channels chosen as bait were Cav1.2, Cav1.3, HCN2, HCN4, Kv4.3, and SK3 channel proteins, and the methods chosen to determine interactions were co-immunoprecipitation analyzed through immunoblot and mass spectrometry as well as proximity ligation assay. A macromolecular complex composed of Cav1.3, HCN, and SK3 channels was unraveled. In addition, novel potential interactions between SK3 channels and sclerosis tuberous complex (Tsc) proteins, inhibitors of mTOR, and between HCN4 channels and the pro-degenerative protein Sarm1 were uncovered. In order to demonstrate the presence of these molecular interactions in situ, we used proximity ligation assay (PLA) imaging on midbrain slices containing the substantia nigra, and we could ascertain the presence of these protein complexes specifically in substantia nigra dopaminergic neurons. Based on the complementary functional role of the ion channels in the macromolecular complex identified, these results suggest that such tight interactions could partly underly the robustness of pacemaking in dopaminergic neurons.
Velvet Family Protein FpVelB Affects Virulence in Association with Secondary Metabolism in Fusarium pseudograminearum
Authors: Wu Yuxing , Han Sen , Wang Yajiao , Li Qiusheng , Kong Lingxiao
Published: June 2024

Fusarium pseudograminearum causes destructive crown disease in wheat. The velvet protein family is a crucial regulator in development, virulence, and secondary metabolism of fungi. We conducted a functional analysis of FpVelB using a gene replacement strategy. The deletion of FpVelB decreased radial growth and enhanced conidial production compared to that of wild type. Furthermore, FpVelB modulates the fungal responses to abiotic stress through diverse mechanisms. Significantly, virulence decreased after the deletion of FpVelB in both the stem base and head of wheat. Genome-wide gene expression profiling revealed that the regulation of genes by FpVelB is associated with several processes related to the aforementioned phenotype, including “immune”, “membrane”, and “antioxidant activity”, particularly with regard to secondary metabolites. Most importantly, we demonstrated that FpVelB regulates pathogen virulence by influencing deoxynivalenol production and modulating the expression of the PKS11 gene. In conclusion, FpVelB is crucial for plant growth, asexual development, and abiotic stress response and is essential for full virulence via secondary metabolism in F. pseudograminearum.
Hyperspectral and Chlorophyll Fluorescence Analyses of Comparative Leaf Surfaces Reveal Cellular Influences on Leaf Optical Properties in Tradescantia Plants
Authors: Falcioni Renan , Antunes Werner Camargos , Berti de Oliveira Roney , Chicati Marcelo Luiz , Demattê José Alexandre M. , Nanni Marcos Rafael
Published: June 2024

The differential effects of cellular and ultrastructural characteristics on the optical properties of adaxial and abaxial leaf surfaces in the genus Tradescantia highlight the intricate relationships between cellular arrangement and pigment distribution in the plant cells. We examined hyperspectral and chlorophyll a fluorescence (ChlF) kinetics using spectroradiometers and optical and electron microscopy techniques. The leaves were analysed for their spectral properties and cellular makeup. The biochemical compounds were measured and correlated with the biophysical and ultrastructural features. The main findings showed that the top and bottom leaf surfaces had different amounts and patterns of pigments, especially anthocyanins, flavonoids, total phenolics, chlorophyll-carotenoids, and cell and organelle structures, as revealed by the hyperspectral vegetation index (HVI). These differences were further elucidated by the correlation coefficients, which influence the optical signatures of the leaves. Additionally, ChlF kinetics varied between leaf surfaces, correlating with VIS-NIR-SWIR bands through distinct cellular structures and pigment concentrations in the hypodermis cells. We confirmed that the unique optical properties of each leaf surface arise not only from pigmentation but also from complex cellular arrangements and structural adaptations. Some of the factors that affect how leaves reflect light are the arrangement of chloroplasts, thylakoid membranes, vacuoles, and the relative size of the cells themselves. These findings improve our knowledge of the biophysical and biochemical reasons for leaf optical diversity, and indicate possible implications for photosynthetic efficiency and stress adaptation under different environmental conditions in the mesophyll cells of Tradescantia plants.
Stable Dietary Ora-Curcumin Formulation Protects from Experimental Colitis and Colorectal Cancer
Authors: Valiveti Chaitanya K. , Kumar Balawant , Singh Anuj D. , Biradar Sham K. , Ahmad Rizwan , Singh Amar B. , Tummala Hemachand
Published: June 2024

Inflammatory bowel disease (IBD) is a chronic gut disorder that also elevates the risk of colorectal cancer (CRC). The global incidence and severity of IBD are rising, yet existing therapies often lead to severe side effects. Curcumin offers potent anti-inflammatory and chemotherapeutic properties. However, its clinical translation is hindered by rapid metabolism, as well as poor water solubility and stability, which limits its bioavailability. To address these challenges, we developed OC-S, a water-soluble and colon-targeted curcumin formulation that protects against colitis in mice. The current study advances OC-S as a dietary supplement by establishing its stability and compatibility with various commercial dietary products. Further, OC-S exhibited specific binding to inflamed colon tissue, potentially aiding in targeted drug retention at the inflammation site in colitis with diarrhea symptoms. We further investigated its efficacy in vivo and in vitro using a murine model of colitis and tumoroids from APCmin mice. OC-S significantly reduced colitis severity and pro-inflammatory cytokine expression compared with curcumin, even at very low doses (5 mg/kg/day). It also demonstrated higher anti-proliferative activity in CRC cells and colon cancer tumoroids vs. curcumin. Overall, this study demonstrated that OC-S effectively targets and retains water-soluble curcumin at the inflamed colon sites, while showing promise in addressing both colitis and colorectal cancer, which potentially paves the way for OC-S to advance into clinical development as a dietary product for both IBD and CRC.
Many Faces of Regulatory T Cells: Heterogeneity or Plasticity?
Authors: Blinova Varvara G. , Zhdanov Dmitry D.
Published: June 2024

Regulatory T cells (Tregs) are essential for maintaining the immune balance in normal and pathological conditions. In autoimmune diseases and transplantation, they restrain the loss of self-tolerance and promote engraftment, whereas in cancer, an increase in Treg numbers is mostly associated with tumor growth and poor prognosis. Numerous markers and their combinations have been used to identify Treg subsets, demonstrating the phenotypic diversity of Tregs. The complexity of Treg identification can be hampered by the unstable expression of some markers, the decrease in the expression of a specific marker over time or the emergence of a new marker. It remains unclear whether such phenotypic shifts are due to new conditions or whether the observed changes are due to initially different populations. In the first case, cellular plasticity is observed, whereas in the second, cellular heterogeneity is observed. The difference between these terms in relation to Tregs is rather blurred. Considering the promising perspectives of Tregs in regenerative cell-based therapy, the existing confusing data on Treg phenotypes require further investigation and analysis. In our review, we introduce criteria that allow us to distinguish between the heterogeneity and plasticity of Tregs normally and pathologically, taking a closer look at their diversity and drawing the line between two terms.
LeakPred: An Approach for Identifying Components with Resource Leaks in Android Mobile Applications
Authors: Lima Josias Gomes , Giusti Rafael , Dias-Neto Arilo Claudio
Published: June 2024

Context: Mobile devices contain some resources, for example, the camera, battery, and memory, that are allocated, used, and then deallocated by mobile applications. Whenever a resource is allocated and not correctly released, a defect called a resource leak occurs, which can cause crashes and slowdowns. Objective: In this study, we intended to demonstrate the usefulness of the LeakPred approach in terms of the number of components with resource leak problems identified in applications. Method: We compared the approach’s effectiveness with three state-of-the-art methods in identifying leaks in 15 Android applications. Result: LeakPred obtained the best median (85.37%) of components with identified leaks, the best coverage (96.15%) of the classes of leaks that could be identified in the applications, and an accuracy of 81.25%. The Android Lint method achieved the second best median (76.92%) and the highest accuracy (100%), but only covered 1.92% of the leak classes. Conclusions: LeakPred is effective in identifying leaky components in applications.