Stages Of Development Research Articles

Adaptive immunity in Mus musculus influences the acquisition and abundance of Borrelia burgdorferi in Ixodes scapularis ticks.

The Lyme disease spirochete Borrelia burgdorferi cycles between immature black-legged ticks (Ixodes scapularis) and vertebrate reservoir hosts, such as rodents. Larval ticks acquire spirochetes from infected hosts, and the resultant nymphs transmit the spirochetes to naïve hosts. This study investigated the impact of immunocompetence and host tissue spirochete load on host-to-tick transmission (HTT) of B. burgdorferi and the spirochete load inside immature I. scapularis ticks. Wild-type (WT) C57BL/6J mice and mice with severe combined immunodeficiency (SCID) were experimentally infected with B. burgdorferi. To measure HTT, WT and SCID mice were repeatedly infested with I. scapularis larvae, and ticks were sacrificed at three different developmental stages: engorged larvae, 1-month-old, and 12-month-old nymphs. The spirochete loads in immature ticks and mouse tissues were estimated using qPCR. In WT mice, HTT decreased from 90% to 65% over the course of the infection, whereas in the SCID mice, HTT was always 100%. Larvae that fed on SCID mice acquired a much larger dose of spirochetes compared to larvae that fed on WT mice. This difference in spirochete load persisted over tick development where nymphs that fed as larvae on SCID mice had significantly higher spirochete loads compared to their WT counterparts. HTT and the tick spirochete loads were strongly correlated with the mouse tissue spirochete loads. Our study shows that the host immune system (e.g., the presence of antibodies) influences HTT of B. burgdorferi and the spirochete load in immature I. scapularis ticks.IMPORTANCEThe tick-borne spirochete Borrelia burgdorferi causes Lyme disease in humans. This pathogen is maintained in nature by cycles involving black-legged ticks and wildlife hosts. The present study investigated the host factors that influence the transmission of B. burgdorferi from infected hosts to feeding ticks. We infected immunocompetent mice and immunocompromised mice (that cannot develop antibodies) with B. burgdorferi and repeatedly infested these mice with ticks. We determined the percentage of infected ticks and their spirochete loads. This percentage was 100% for immunocompromised mice but decreased from 90% to 65% over time (8 weeks) for immunocompetent mice. The tick spirochete load was much higher in ticks fed on immunocompromised mice compared to ticks fed on immunocompetent mice. In summary, the host immune system influences the transmission of B. burgdorferi from infected hosts to ticks and the spirochete loads in those ticks, which, in turn, determines the risk of Lyme disease for people.

The Law of Data-driven on Employee Growth in Enterprise Human Resource Management in the Era of Digital Transformation

In the era of digital transformation, the popularity of artificial intelligence technology has driven the development of the field of Human Resource Management (HRM) in enterprises, and data-driven HRM has become the key to the development and success of enterprises. Due to the late start, data-driven HRM is still in the development stage in China. To address the problem that traditional HRM lacks accuracy and real-time, this study proposes a Growth Potential Prediction (GPP) model based on the combination of all class features and a Random Forest (RF) classifier. The results of the study showed that the prediction accuracy of interpersonal background, work ability, educational status and organisational environment characteristics under the screening index based on [Formula: see text]1 value were 85.01%, 66.34%, 66.41%, 44.19% and 64.27%, respectively. The accuracy of ROS under the RF classifier and the macro [Formula: see text]1 value were 87.31% and 87.24%. After adding the network features, the accuracy and macro [Formula: see text]1 values of the feature ensemble could reach 90%, and the accuracy and macro [Formula: see text]1 values of all class feature combinations were 89.01% and 89.10%, respectively. In summary, the GPP model based on the combination of all class features and the RF classifier proposed in the study can accurately predict the growth potential of employees and provide some guarantee for mining the growth pattern of employees.

Prenatal Maternal Stress Suppresses Embryonic Neurogenesis via Elevated Glucocorticoid Levels.

Although it is known that prenatal maternal stress (PNMS) has negative influence on nervous system development in offspring, there has been no solid evidence showing the effect of PNMS on early neurogenesis during development. In this study, we established a chick embryo model to investigate how PNMS affects early neurogenesis by mimicking an intrauterine environment with high dexamethasone (Dex) levels. The results showed that Dex-mimicked PNMS significantly suppressed the development of gastrula embryos and increased the risks of neural tube defects and cranial deformity. Using immunofluorescence staining and Western blots to determine the expression levels of pHIS3, PCNA/Sox2, we found that PNMS significantly inhibited the proliferation of neural progenitor cells, and the downregulation of TGFβ signaling pathway might be responsible for the inhibition. Furthermore, immunofluorescence staining and Western blots manifested that PNMS could suppress the differentiation of neural progenitor cells to neuronal lineages, but promote them to transform into neuroglial cells, which might be due to the restriction of expressions of key genes (BMP4, SHH, Wnt3a, Slug, and Msx1) related to neural differentiation. In summary, our data reveal that PNMS dramatically impacts the earliest stages of neural development, thereby greatly increasing the risk of physical and mental health problems in childhood or adulthood.

Pengembangan Media Video Animasi Pembelajaran Berbasis Pendekatan Inkuiri pada Mata Pelajaran Bahasa Inggris Kelas VIII SMP

The development of learning video media is carried out as an effort to solve student learning problems. This Learning Media can be used as an alternative to reduce problems in learning. This study aims to produce products in English class VIII subjects and determine the quality of validity and practicality of the products developed so that they are feasible to use. This study is a type of Research and Development (R&D) development or by using a 4-D development model (four-D model). This Model consists of 4 stages of development include Define, Design, Develop, Disseminate. The product validity test was conducted by 3 validators, namely 2 media validators and 1 material validator. Practicalities test was conducted on 31 students of Class VIII SMP Negeri 1 Junjung Sirih. The results of this study explain that the average percentage of media validators I and II respectively is 97.5% and 96.25% with the category of "Very Valid". From the assessment of material experts, an average percentage of 94.54% was obtained with the category of "Very Valid". For the assessment of practicality from students, a percentage of 93.22% was obtained with the product category "Very Practical" Based on these calculations, it can be concluded that the learning animation video media based on the inquiry approach in English subjects developed "Very Feasible" is used in learning

Pengembangan Media Puzzle Interaktif untuk Pengenalan Huruf pada Anak Usia 5-6 Tahun di Taman Kanak-Kanak

This research aims to develop interactive puzzle-based learning media that is specifically designed to introduce letters to early childhood in Kindergarten Negeri Madani. Conventional learning media are considered less interactive in the letter recognition process, while visual- and play-based approaches have proven to be more effective for children. This research is a type of Research and Development (R&D) research with a 4-D development model (four-D model). This model consists of 4 stages of development including Define, Design, Develop, Disseminate. This media was developed systematically and tested for validity and practicality using a questionnaire. The results of the validity test reached 87.17% for the material aspect and 86.11% for the media aspect, while the practicality test achieved an average score of 81.25%. This interactive puzzle media is proven to be able to increase children's interest in learning letters with a fun approach and support their motor and cognitive development

Gradual chromosomal lagging drive programmed genome elimination in hemiclonal fishes from the genus Hypseleotris.

Most eukaryotes maintain the stability of their cellular genome sizes to ensure genome transmission to offspring through sexual reproduction. However, some alter their genome size by selectively eliminating parts or increasing ploidy at specific developmental stages. This phenomenon of genome elimination or whole genome duplication occurs in animal hybrids reproducing asexually. Such genome alterations occur during gonocyte development ensuring successful reproduction of these hybrids. Although multiple examples of genome alterations are known, the underlying molecular and cellular processes involved in selective genome elimination and duplication remain largely unknown. Here, we uncovered the process of selective genome elimination and genome endoreplication in hemiclonal fish hybrids from the genus Hypseleotris. Specifically, we examined parental sexual species H. bucephala and hybrid H. bucephala × H. gymnocephala (HB × HX). We observed micronuclei in the cytoplasm of gonial cells in the gonads of hybrids, but not in the parental sexual species. We also observed misaligned chromosomes during mitosis which were unable to attach to the spindle. Moreover, we found that misaligned chromosomes lag during anaphase and subsequently enclose in the micronuclei. Using whole mount immunofluorescent staining, we showed that chromatid segregation has failed in lagging chromosomes. We also performed three-dimensional comparative genomic hybridization (3D-CGH) using species-specific probes to determine the role of micronuclei in selective genome elimination. We repeatedly observed that misaligned chromosomes of the H. bucephala genome were preferentially enclosed in micronuclei of hybrids. In addition, we detected mitotic cells without a mitotic spindle as a potential cause of genome duplication. We conclude that selective genome elimination in the gonads of hybrids occurs through gradual elimination of individual chromosomes of one parental genome. Such chromosomes, unable to attach to the spindle, lag and become enclosed in micronuclei.

Educational quality policies and student satisfaction in public and private universities in Peru

Educational quality policies are a basic principle that every Peruvian university educational institution pursues in accordance with Law No. 30220, with the objective of training highly competent professionals who contribute to the development of the country. This study to analyzes educational quality policies with the student’s satisfaction of public and private universities in Peru, according to social variables. The study was descriptive-comparative, quantitative, non-experimental, and cross-sectional. One thousand (1000) students from two Peruvian universities, one public (n = 500) and one private (n = 500), were purposively selected by quota using the SERVQUALing instrument. The findings indicate a moderate level of satisfaction reported by 49.2% of participants, with a notable tendency towards high satisfaction observed in 40.9% of respondents. These results suggest that most students perceive that the actual state of service quality policies are in a developmental stage. The results, therefore, indicate that regulatory measures, including university laws, licensing, and accreditation, significantly influence outcomes. These measures are essential for the effective functioning of universities. In addition, the analysis revealed that female and male students at private universities showed higher levels of satisfaction with the educational services offered. It is concluded that educational quality policies in Peru are still being executed, because the implementation of the University Law is in process, according to the satisfaction of the student, this must be improved in central aspects such as optimizing human resources, infrastructure, equipment, curricular plans that differ from the public to the private university, In addition, this should lead to improving and redefining current policies on educational quality and the economic policies that finance the educational service.

A different approach to identifying thermal parameters for invasive species.

The brown marmorated stinkbug, Halyomorpha halys Stål (Hemiptera: Pentatomidae), is a polyphagous invasive insect found in the eastern United States in 1998 but became a major agricultural pest in 2010. Environmental temperatures regulate the location of invasive species establishment in new locations. To determine those areas where an invasive species might establish it is essential to understand the metabolic response of all life stages to temperature. Differential scanning calorimetry is a useful tool to monitor living organisms' metabolism at different temperatures, providing vital information related to the ability of the species to survive in new environments. The information obtained from isothermal and scanning calorimetric experiments on all the life stages of H. halys indicates that the third instar is the most thermoresponsive stage and eggs and fifth instar are the least thermoresponsive, whereas the third instars exhibit a broad range of thermoresponsiveness as compared to all other developmental stages. The recorded values for lower, optimal, and upper developmental temperatures in this study were similar to those reported by other researchers using laboratory and field data to develop degree-day models. This method can help in the rapid development of degree day models to improve and synchronize control efforts for newly invasive species.

Enhanced Efficiency of Latent Heat Energy Storage by Inclination

Latent heat storage (LHS) has emerged as a promising solution for addressing the challenges of large-scale and long-term energy storage, offering a clean and reusable system. Being in the developmental stage, and with only limited theoretical predictions being available, there is a need to enhance the efficiency of LHS systems. In this study, we use numerical simulations to study the melting process of a phase-change material (PCM) in a rectangular domain. A significant enhancement in the melt rate of the PCM is found by a simple inclination of the domain, with a 60% increase in melt rate compared to a standard square unit without inclination through enhanced heat transfer. We establish a theoretical relation for the optimal PCM melt rate, based on the inclination angle and the domain aspect ratio, outlining the optimal conditions for the PCM melt rate, which is solely dependent on the domain geometry. We further propose a heat-transfer model that predicts the optimal aspect ratio for achieving the maximum melt rate as a function of the Rayleigh and Prandtl numbers. Published by the American Physical Society 2024

Efficacy of the construction industry legislative framework in developing countries – an Eswatini case

PurposeThe regulation of the construction industry remains a significant obstacle to economic progress in developing nations. Therefore, this study aimed to assess the efficacy of the legislative framework in the construction industry, focusing on Eswatini. The construction industry plays a critical role in the upliftment of the economy and an effective and efficient legislative framework is essential to ensure that as a developing country, Eswatini derives maximum benefits from the sector.Design/methodology/approachA phenomenological research design was used to explore stakeholders’ perceptions about the purpose of the legislative framework in the Eswatini construction industry and to establish the effectiveness of the current legislative framework in fulfilling its mandate. The data were collected using semi-structured interviews with open-ended questions. A total of 45 participants occupying different positions within the construction industry were selected using purposive sampling. The data were analysed thematically.FindingsThe results reiterate that the legislative framework’s purpose is to regulate, control and guide sectoral operations, including enforcing compliance with statutes and payment of construction levies. However, the legislative framework does not effectively fulfil its purpose of addressing stakeholder needs. Overall, the findings indicate shortcomings and inefficiencies within the framework aimed at regulating the construction industry of Eswatini. The inefficiencies have a great potential of defeating the purpose of the entire framework.Research limitations/implicationsRegarding implications for future research, the current study has set a new pathway for legislative framework analysis and evaluation. Therefore, future research on the topic can build on the current study and compare the legislative frameworks across developing countries. The purpose would be to establish the similarities and differences, and to identify strengths and weaknesses, possibly leading to established principles of what works in a given context. Other studies on the topic could focus on benchmarking against developed countries on how they measure the efficacy of the legislative framework within their constriction industry.Practical implicationsBased on the preceding, these findings may apply to similar developing countries at a similar stage of construction industry development. However, the findings should be considered within the limitations of the study. The focus was on developing countries, particularly the Eswatini context. Each country presents a unique context and challenges, so the findings should be cautiously generalized.Originality/valueWhile other studies in different contexts focus on developing legislative frameworks, the current study evaluated an existing legislative framework using defined criteria. The current study made a unique contribution by streamlining the features of effective and ineffective legislative frameworks. Hitherto, such information was scattered in literature but has been consolidated and applied empirically. Thus, the study has set benchmarks for analysing and evaluating legislative frameworks in developing countries.

Surface instability driven by wetting-drying cycles hinders the colonization by biocrusts in Tabernas Desert

AbstractCatchment asymmetry in the Tabernas Desert suggests a relatively greater instability in the sunnier hillslope in a very early stage of catchment development due to abiotic factors, which would hinder the biocrust colonization. In the absence of erosion, such a difference in stability between opposite hillslopes could be due to differences in wetting-drying cycles. To verify this, as biocrust types assumed as successional stages are associated with different microhabitats, the surface movements of three types of physical crusts (Structural, Depositional and Island) and four biocrust types, representative of different stages of succession (Incipient, Cyanobacteria, Squamarina and Lepraria), were analyzed based on the distances calculated between markers placed on a grid on the soil surface. Two sample groups were analyzed: in situ samples, with four plots per crust type, and ex situ, with four unaltered samples per crust type extracted from the field site to control the effect of slope angle, orientation, trampling by animals, etc. Physical crusts showed greater surface instability compared to biocrusts, and this instability was influenced by the amount and frequency of precipitation. Biocrusts were more stable and elastic to surface movements, often recovering their initial position, and this stability increased throughout succession. Furthermore, the results showed that reducing instability (when sediment deposition ceases) favors colonization. Our results support the hypothesis that, in absence of erosive events, larger surface instability due to wetting-drying cycles hinders biocrust colonization on the relatively sunnier hillslopes with physical crusts; however, it is unknown where (or when) biocrust can develop.

MODERNIZATION OF STATE POLICY IN THE FIELD OF STATE CONTROL (SUPERVISION) OVER ECONOMIC ACTIVITY

The article analyzes the essence of modernization of the State policy in the field of control (supervision) over economic activity with due regard for the changing political and economic situation in the country. The author examines the main conceptual approaches to the definition of basic terms, and also identifies the features and purpose of state control (supervision) in the economic sphere. It is found that the state of the system of control (supervision) over economic activity does not always correspond to the realities of today. Hence, the author concludes that the control system is not always relevant and effective. The author identifies the main problems on the way to modernization of legislation in the field of control (supervision) over economic activity. The author proposes to use adequate means of regulating and controlling economic activity during a special period caused, for example, by a pandemic, military operations on the territory of Ukraine, etc. The author examines the key areas of state policy in the field of legal regulation of control (supervision) over economic activity. The author defines the system of regulatory and legal support of the state policy in the field of control over economic activity at different stages of economic development of the country. The author analyzes the legal acts adopted under the legal regime of martial law aimed at stabilizing the situation in the economic system of our country.

Adolescent microsurgical varicocelectomy and changes in sperm parameters: A matched cohort analysis.

Varicocele, a common vascular abnormality surrounding the testis, is known to be associated with impaired semen parameters and male infertility in adults. However, its impact on the adolescent and young adult (AYA) population is less well known. The study aimed to assess the improvement in sperm parameters following varicocelectomy in the AYA population, comparing them to matched adult counterparts, and investigating potential advantages of early intervention. A retrospective analysis was conducted using a comprehensive database at the University of Miami spanning from 2012 to 2023. We included AYA (under 25 years of age) men who underwent varicocelectomy. To ensure comparability, they were matched with adult patients (over 30 years of age) based on preoperative follicle-stimulating hormone (FSH) values and varicocele grade in a 1:2 ratio. Semen parameters were evaluated before and after surgery, including sperm count, motility, morphology, and overall semen quality. We included 45 patients in the Adolescents and Young Adults (AYA) category, and matched them with 116 adults based on FSH and varicocele grade, all of whom underwent microsurgical varicocelectomy. The AYA group exhibited greater improvements post-varicocelectomy compared to the matched cohort. Furthermore, postoperative sperm concentration in the AYA men demonstrated a remarkable increase, with a 1.7-fold increase in mean concentration compared to the adult group (p<0.001). Additionally, motility also displayed significant enhancement among the AYA men, with a final mean total motile sperm count (TMSC) improvement of 2.25-fold compared to the adult cohort (p=0.002). This study highlights the potential benefits of varicocelectomy as a viable treatment option for adolescents and young adults with varicocele, particularly those with impaired semen parameters. By intervening at an earlier stage of development, patients in this age group can achieve significant improvements in semen quality, as compared to their adult counterparts. These findings underscore the importance of considering varicocelectomy as a valuable therapeutic approach for the younger demographic, potentially alleviating future fertility concerns.

The bone Gla protein osteocalcin is expressed in cranial neural crest cells.

Osteocalcin is a small protein abundant in the bone extracellular-matrix, that serves as a marker for mature osteoblasts. To become activated, osteocalcin undergoes a specific post-translational carboxylation. Osteocalcin is expressed at advanced stages of embryogenesis and after birth, when bone formation takes place. Neural crest cells (NCCs) are a unique cell population that evolves during early stages of development. While initially NCCs populate the dorsal neural-tube, later they undergo epithelial-to-mesenchymal-transition and migrate throughout the embryo in highly-regulated manner. NCCs give rise to multiple cell types including neurons and glia of the peripheral nervous system, chromaffin cells and skin melanocytes. Remarkably, in the head region, NCCs give rise to cartilage and bone. Here we report that osteocalcin is detected in cranial NCCs. Analysis of chick embryos at stages of cranial NCC migration revealed that osteocalcin mRNA and protein is expressed in pre-migratory and migratory NCCs in-vivo and ex-vivo. Addition of warfarin, an inhibitor of osteocalcin carboxylation, onto neural-tube explants, reduced the amount of NCC migration. These results provide the first evidence of osteocalcin presence in cranial NCCs, much before they give rise to craniofacial skeleton, and propose its possible involvement in the regulation of NCC migration.

Cultural adaptation of an internet-based self-help app for grieving Syrian refugees in Switzerland.

Loss and grief pose significant challenges for victims of armed conflicts, such as Syrian refugees. Internet-based interventions (IBIs) present a promising solution to address this treatment gap and provide adequate support. However, research on grief, grief support, and IBIs remain largely limited to Western cultural contexts, and culturally adapted IBIs for grief are needed. Following the Reporting Cultural Adaptation in Psychological Trials (RECAPT) framework, this study aimed to develop and further adapt a culturally sensitive IBI for bereaved Syrian refugees in Switzerland. The study employed qualitative methods. Initially, formative research was conducted to create a first version of the intervention, including semi-structured interviews with 10 experts to identify necessary cultural adaptations. The preliminary version of the intervention was then presented to six potential users and three experts to gather feedback on additional cultural adaptations through two iterative feedback rounds. The first round involved semi-structured interviews using a "paper version" of the intervention, followed by a second round with a walk-through think-aloud protocol with a beta version. Data were analyzed using framework analysis. The input from various key informants at different stages of development provided valuable feedback on surface and deep structure adaptation, which may enhance treatment adherence, acceptance, and motivation. These findings provide important insights and recommendations for the cultural adaptation of interventions and may help address the treatment gap for bereaved Syrian refugees.

Nuclear transfer leads to aberrant cell cycle regulation and translation, as determined by gene expression, and selection of mitochondrial DNA in porcine blastocysts

Abstract Nuclear transfer technologies, such as metaphase II spindle transfer (MII-ST), are being developed to overcome poor oocyte quality and prevent children from acquiring severe mitochondrial DNA (mtDNA) disease. However, it is unclear whether these technologies perturb gene expression; and mtDNA carryover can be reduced to minimal levels. Using our pig model, we isolated individual karyoplasts with limited mtDNA carryover (306 ± 49 copies) from mature oocytes. Firstly, we reintroduced the spindle into its original cytoplast (autologous), fertilised, and cultured the resultant embryos to the hatching blastocyst stage of development. Following RNA-seq, 64 genes were differentially expressed at FDR &amp;lt; 0.05; and 1327 genes at P &amp;lt; 0.05. Pathways associated with cell cycle and epigenetic regulation and genes associated with nuclear-mitochondrial interactions were upregulated whilst protein translation pathways were downregulated. We then transferred karyoplasts to third party cytoplasts (heterologous) and undertook mtDNA next generation sequencing of 2-cell to hatching blastocyst stage preimplantation embryos. Nine of 20 embryos possessed two mitochondrial genomes. Our outcomes show that autologous nuclear transfer alone significantly changes hatching blastocyst gene expression; very low levels of mtDNA carryover can be preferentially replicated during early development; and nuclear and mitochondrial synchrony has not been reestablished.

Neuroscientific Approaches to Understanding Adolescent Susceptibility to Substance Abuse

Adolescence is a pivotal developmental stage characterised by significant neurobiological changes that heighten susceptibility to substance abuse. This period is marked by the maturation of the brain regions responsible for decision-making and impulse control, alongside an increased sensitivity to rewards driven by dopaminergic pathways. This review aimed to understand adolescent susceptibility to substance abuse using a neuroscientific approach. In line with best practices, data were collected from a variety reliable source to ensure a comprehensive view of the topic. Research studies on adolescent neurodevelopment have contributed to a broader understanding of the physiological and psychological factors at play during adolescence, while grey literature, including expert interviews and focused group discussions, has offered practical insights from frontline professionals, such as psychologists, social workers, and healthcare providers, who deal directly with adolescent substance use. These results demonstrate that the relationship between genetic factors and environmental conditions, such as stress and trauma, intensifies this vulnerability, thereby heightening the likelihood of individuals participating in risky behaviours. This review examines the neuroscientific foundations of substance use during adolescence, highlighting the critical role of timely interventions that utilize neuroplasticity to enhance resilience and reduce risk. By integrating cognitive training and behavioural therapies into public health initiatives, adolescents' cognitive control mechanisms and their propensity for substance abuse can be reduced.

Risk Perception and Knowledge Following a Social Game-Based Tobacco Prevention Program for Adolescents: Pilot Randomized Comparative Trial.

Adolescence is a critical developmental stage that is particularly vulnerable to the initiation of tobacco use. Despite the well-documented health risks associated with tobacco use, it remains prevalent among adolescents. Games for health are a promising strategy for tobacco prevention, using experiential and social learning theories to enhance engagement and improve behavior change. This pilot study aims to (1) compare the social game-based program Storm-Heroes to a nonsocial program regarding adolescents' personal and social experiences and (2) examine how these experiences predict higher tobacco knowledge and perceived risks of vaping and conventional tobacco use. In a cluster-randomized comparative design, 4 after-school sites (N=79 adolescents) were recruited in person and randomized in a single-blinded format to 1 of 2 interventions: the social game Storm-Heroes (44/79, 56%) or the nonsocial program A Smoking Prevention Interactive Experience (ASPIRE; 35/79, 44%). A study team member supervised both interventions. Data were collected at baseline, immediate follow-up, and a 1.5-month follow-up (45/74, 61% retained). Repeated measures mixed effects models were conducted. A total of 45 participants continued until the 1.5-month follow-up. Participants in the Strom-Heroes group were more likely to increase their perceived risk of vaping (B=0.40; P<.001), perceived risk of conventional tobacco use (B=0.35; P=.046), and tobacco knowledge (B=1.63; P<.001) than those in the control condition. The usability level of the program was related to a higher perceived risk of vaping (B=0.16; P=.003) and conventional tobacco use (B=0.16; P=.02) by follow-up. Attention to the program was also related to higher perceived risk of vaping (B=0.12; P=.002) and conventional tobacco use (B=0.14; P<.001). Distraction was not related to either perceived risk of vaping (P=.15) or perceived risk of conventional tobacco use (P=.71). In contrast, both more attention (B=0.60; P<.001) and less distraction (B=-0.37; P<.001) were related to higher tobacco knowledge. The increased perceived risk of vaping and conventional tobacco among Storm-Heroes participants aligns with the program's goals of improving participants' awareness of the risks associated with tobacco use and their tobacco knowledge. However, distraction weakened the effect of the program on tobacco knowledge, indicating that emphasis needs to be placed on minimizing distraction for better outcomes. With the results of this study, researchers can work to advance the current version of Storm-Heroes and amplify engagement in the program to improve its potential for preventing adolescents' initiation of tobacco use. ClinicalTrials.gov NCT02703597; https://clinicaltrials.gov/study/NCT02703597.

The Spatial-Temporal Alternative Splicing Profile Reveals the Functional Diversity of FXR1 Isoforms in Myogenesis.

Alternative splicing (AS) is a fundamental mechanism contributing to proteome diversity, yet its comprehensive landscape and regulatory dynamics during skeletal muscle development remain largely unexplored. Here, the temporal AS profiles are investigated during myogenesis in five vertebrates, conducting comprehensive profiling across 27 developmental stages in skeletal muscle and encompassing ten tissues in adult pigs. The analysis reveals a pervasive and evolutionarily conserved pattern of alternative exon usage throughout myogenic differentiation, with hundreds of skipped exons (SEs) showing developmental regulation, particularly within skeletal muscle. Notably, this study identifies a muscle-specific SE (exon 15) within the Fxr1 gene, whose AS generates two dynamically expressed isoforms with distinct functions: the isoform without exon 15 (Fxr1E15 -) regulates myoblasts proliferation, while the isoform incorporating exon 15 (Fxr1E15+) promotes myogenic differentiation and fusion. Transcriptome analysis suggests that specifically knocking-down Fxr1E15+ isoform in myoblasts modulates differentiation by influencing gene expression and splicing of specific targets. The increased inclusion of exon 15 during differentiation is mediated by the binding of Rbm24 to the intron. Furthermore, in vivo experiments indicate that the Fxr1E15+ isoform facilitates muscle regeneration. Collectively, these findings provide a comprehensive resource for AS studies in skeletal muscle development, underscoring the diverse functions and regulatory mechanisms governing distinct Fxr1 isoforms in myogenesis.

Modeling of Skeletal Development and Diseases Using Human Pluripotent Stem Cells.

Human skeletal elements are formed from distinct origins at distinct positions of the embryo. For example, the neural crest produces the facial bones, the paraxial mesoderm produces the axial skeleton, and the lateral plate mesoderm produces the appendicular skeleton. During skeletal development, different combinations of signaling pathways are coordinated from distinct origins during the sequential developmental stages. Models for human skeletal development have been established using human pluripotent stem cells (hPSCs) and by exploiting our understanding of skeletal development. Stepwise protocols for generating skeletal cells from different origins have been designed to mimic developmental trails. Recently, organoid methods have allowed the multicellular organization of skeletal cell types to recapitulate complicated skeletal development and metabolism. Similarly, several genetic diseases of the skeleton have been modeled using patient-derived induced pluripotent stem cells and genome-editing technologies. Model-based drug screening is a powerful tool for identifying drug candidates. This review briefly summarizes our current understanding of the embryonic development of skeletal tissues and introduces the current state-of-the-art hPSC methods for recapitulating skeletal development, metabolism, and diseases. We also discuss the current limitations and future perspectives for applications of the hPSC-based modeling system in precision medicine in this research field.