Different Stages Of Development Research Articles

Alternative Splicing in the Heart: The Therapeutic Potential of Regulating the Regulators

Alternative splicing allows a single gene to produce a variety of protein isoforms. Changes in splicing isoform usage characterize virtually every stage of the differentiation process and define the physiological differences between cardiomyocytes with different function, at different stages of development, and pathological function. Recent identification of cardiac splicing factors provided insights into the mechanisms underlying alternative splicing and revealed how these splicing factors impact functional properties of the heart. Alterations of the splicing of sarcomeric genes, cell signaling proteins, and ion channels have been associated with the development of pathological conditions such as cardiomyopathy and arrhythmia. RBM20, RBM24, PTBP1, RBFOX, and QKI play key roles in cardiac development and pathology. A better understanding of their regulation will yield insights into healthy cardiac development and inform the development of molecular therapeutics.

DNA Imprinting and Differentially Expressed Genes in Longissimus thoracis Muscle of Bos indicus Submitted to Early Weaning Management

Background/Objectives: Early weaning management followed by energy supplementation can lead to metabolic alterations in the calf that exert long-term effects on the animal’s health and performance. It is believed that the main molecular basis underlying these metabolic adaptations are epigenetic mechanisms that regulate, activate, or silence genes at different stages of development and/or in response to different environmental stimuli. However, little is known about postnatal metabolic programming in Bos indicus. Therefore, this study aimed to compare the DNA methylation profile of Nellore animals submitted to conventional and early weaning and to correlate the findings with genes differentially expressed in the Longissimus thoracis skeletal muscle of Bos indicus cattle. Methods: For this, we used Reduced Representation Bisulfite Sequencing (RRBS) and RNA-Sequencing techniques to prospect differentially methylated genes (DMGs). Results: A total of 481 differentially methylated regions were identified, with 52% (250) being hypermethylated and 48% (231) hypomethylated. Functional enrichment analysis of 53 differentially methylated and differentially expressed genes was performed. The main enriched terms and pathways were associated with 3′-5′-cyclic adenosine monophosphate (cAMP) signaling, which presents the upregulated adenylate cyclase 3 (ADCY3) gene and significatively hypomethylated in the promoter region. Alterations in cAMP signaling are involved in numerous processes, many of them related to lipid metabolism. The relative differential expression of key genes of this pathway demonstrates the relationship between cAMP signaling and de novo lipogenesis. Conclusions: These findings suggest an important role of postnatal metabolic programming through DNA methylation mechanisms in determining fat deposition in beef.

Integrated Transcriptomic and Metabolomic Analysis Reveals Possible Molecular Mechanisms of Leaf Growth and Development in Disanthus cercidifolius var. longipes

Background: Disanthus cercidifolius var. longipes is an ancient relic plant unique to China. However, the typical shade-loving plant is largely exposed to the sun, which poses a major challenge to its conservation. Methods: This study explored dynamic changes in primary and secondary metabolites in D. cercidifolius leaves at different stages of development, combining metabolomics and transcriptome analysis to discuss the differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs). Results: The DAMs and DEGs were enriched in pathways related to photosynthesis, carbon (C) metabolism, anthocyanin synthesis, plant hormone signal transduction, and flavonoid synthesis. At the initial stage of leaf development, many primary metabolites were synthesized in the leaves. Before leaf maturity, many primary metabolites were converted into secondary metabolites. Combined transcriptome and metabolome analysis showed that the metabolites and genes related to anthocyanin synthesis and flavonoid metabolism were upregulated. In contrast, the genes related to C metabolism and C fixation were downregulated. After leaf maturity, photosynthetic capacity increased, total flavonoid content peaked (implying the strongest photoprotection capacity), and the transformation of anthocyanins and flavonoids was weakened. Conclusions: Light intensity indirectly affects the accumulation of the primary and secondary metabolism of D. cercidifolius. With the enhancement of photoprotection, the photosynthetic energy capacity decreases. It is, therefore, inferable that D. cercidifolius has shading properties and achieves a stable nutrient supply during growth and development through these strategies. Thus, D. cercidifolius protection requires a shaded environment.

Heteroblasty in Conchocarpus heterophyllus (A.St.-Hil.) Kallunki & Pirani (Rutaceae): An approach of leaf development from the unifoliolate leaves

Heteroblasty is a phenomenon marked by abrupt changes in the development of organs of certain species. In our research on Conchocarpus heterophyllus, a shrub with palmately arranged leaflets ranging from 3(4) to 5(–7), we observed significant variations in leaf patterns between seedlings, young plants, and plants in the reproductive phase, indicating transition events during plant development. The focus of this study is to thoroughly investigate these events of heteroblasty and heterophylly in C. heterophyllus, with new evidence of the unifoliolate condition in Rutaceae. Morphological and anatomical observations were conducted from mature leaves of individuals at different stages of development. The results show that the heteroblasty in C. heterophyllus is marked by changes in leaf patterns across three stages. In stage 1, seedlings exclusively produce unifoliolate leaves from the first foliage leaf. After the eighth to tenth node from the cotyledons, heterophylly becomes evident with the emergence of leaves containing 2–3 leaflets, in addition to unifoliolate leaves, characterizing the second stage. The third stage is defined by the onset of the reproductive phase, marked by the presence of inflorescences. In this stage, the leaf complexity varies, with the number of leaflets ranging from 2 to 5, and unifoliolate leaves are lacking. Furthermore, our study identified the occurrence of vascular traces of leaflets in the swollen region located at the apex of the petiole of all unifoliolate leaves, occurring in stages 1 and 2. These vascular traces are interpreted as remnants of the lost lateral leaflets in unifoliolate leaves and represent novel evidence of this special condition in compound leaves. Heteroblasty in C. heterophyllus is a genetically controlled phenomenon, and consequently, prospective investigations involving microRNAs, particularly microRNAs 156 and 172, have the potential to provide valuable insights into the genetic mechanisms underlying the transition between different phases.

Exploring Barriers to Innovation in Public Administration

This study deepens our knowledge on innovation barriers within Public Sector Innovation (PSI) processes in local governments. It analyzes the barriers to PSI from a mixed method approach using an original survey directed to innovation managers in the largest Spanish city councils and semi-structured interviews within a case study. This study shows the most relevant barriers to innovation in different stages of development, the strategies used to overcome these barriers and the relationships among them. This research contributes to PSI literature by shedding light on the barriers' dynamics and how they operate in local governments within contexts of high levels of digitalization. Results suggest a significant prevalence of institutional barriers, more common in countries with a Napoleonic administrative tradition, and uncover the relevance of politics and human resource management foster innovation at the local level.

How to grow a self: development of self-representation in the Bayesian brain.

The last two decades saw multiple attempts to explain how the self is represented in the brain within the framework of the Bayesian brain. However, these attempts largely focused on describing a developed, adult self-representation. The current paper argues that looking at the developmental trajectory is crucial for understanding the structure of self-representation. It argues that emergence of self-representations should be understood as an instance of the process of acquisition of new internal models of hidden causes of sensory input. The paper proposes how such models emerge and develop over the course of life by looking at different stages of development of bodily and extra-bodily self-representations. It argues that the self arises gradually in a series of discrete steps: from first-person multisensory representations of one’s body to third-person multisensory body representation, and from basic forms of the extended and social selves to progressively more complex forms of abstract self-representation. It discusses how each of them might emerge based on domain-general learning mechanisms, while also taking into account the potential role of innate representations. Finally, it discusses how predictions of the proposed model might be experimentally tested.

Ensiling Characteristics, Bacterial Community Structure, Co-Occurrence Networks, and Their Predicted Functionality in Alfalfa Haylage Silage with or Without Foliar Selenium Application

Selenium (Se) is an essential trace element in living systems. In this study, we applied a spray of 50 mg/kg sodium selenite to alfalfa (Medicago sativa L.) at different stages of development (bud, initial bloom, and full bloom stages). After 0, 1, 3, 7, and 45 days of ensiling, we assessed the fermentation quality, chemical composition, and bacterial community of the alfalfa. Our findings indicated that the addition of Se led to an increase in the Se content and a decrease in the pH, acid detergent fiber (ADF), and neutral detergent fiber (NDF) contents. As ensiling fermentation progressed, the Se treatments increased the relative abundance of Lactobacillus, which was significantly greater than that in the control group (42.44% vs. 3.76%). In conclusion, the addition of sodium selenate to silage additive ensures the quality of the silage and reduces bacterial community diversity. This study provides valuable insights for the investigation of Se enrichment in alfalfa haylage silage.

The Complex of Steroid Hormones in Invertebrate Hydrobionts

The presence of a complex of biologically active steroid compounds (BASC) – hydrocortisone, corticosterone, progesterone, testosterone and estrogens (vertebrate hormones) in invertebrate hydrobionts of different phylogenetic levels was revealed in the experiments. The features of the quantitative content of BASC in different organs/tissues of hydrobionts and their changes at different stages of development are shown. The level of BASC in organisms or their organs is largely due to their own steroidogenesis, but at the same time, organisms can accumulate exogenous steroid compounds. The adaptive role of ALS in some invertebrates in changing conditions of the aquatic environment has been found. The similarity of the concentration of steroid compounds in different groups of bionts leads to the idea of a certain “physiological constant” of this complex of compounds in all organisms.

Masting ontogeny: the largest masting benefits accrue to the largest trees.

Both plants and animals display considerable variation in their phe- notypic traits as they grow. This variation helps organisms to adapt to specific challenges at different stages of development. Masting, the variable and synchronized seed production across years by a population of plants, is a common reproductive strategy in perennial plants that can enhance reproductive efficiency through increasing pollination efficiency and decreasing seed predation. Masting represents a population-level phenomenon generated from individual plant behaviors. While the developmental trajectory of individual plants influences their masting be- havior, the translation of such changes into benefits derived from masting remains unexplored. We used 43 years of seed production monitoring in European beech (Fagus sylvatica) to address that gap. The largest improvements in reproductive efficiency from masting happen in the largest trees. Masting leads to a 48-fold reduction in seed predation in large, compared to 28-fold in small trees. Masting yields an 6-fold increase in pollination efficiency in large, compared to 2.5-fold in small trees. Paradoxically, although the largest trees show the biggest reproductive efficiency benefits from masting, large trees mast less strongly than small trees. That apparently suboptimal allocation of effort across years by large plants may be a consequence of anatomical constraints or bet-hedging. Ontogenetic shifts in individual mast- ing behavior and associated variable benefits have implications for the reproductive potential of plant populations as their age distribution changes, with applications in plant conservation and management.

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.

Characteristics of the hydrological regime of the periglacial moraine lakes in the Altai

In the last decade glaciers of Inner Asia have been shrinking with acceleration, and the number of glacial lakes has been growing significantly, including those with a high probability of outburst and high-water discharge. The hydrological regime of lakes in the Altai is understudied in comparison with lakes in other high mountain countries. The article is based on our extensive field material on hydrological and morphometric characteristics of moraine lakes collected in the Russian and Mongolian parts of the Altai Mountains and combined with the Earth remote sensing data. We have proposed detailed indicators (criteria) of transgressive, regressive and post-regressive stages of lake development. It allows allow to determine at a qualitative level at what stage a lake is at and to assess its further development. The characteristics of hydrological regime of Altai lakes at different stages of development are described for the first time. Based on the criteria proposed, the classification of glacial and moraine lakes in the Altai high mountains was carried out. It shows that at present most of the lakes are in the transgressive stage. Over the last 22 years, the number of lakes has increased significantly: on the territory of the North Chuya Ridge – from 28 to 60, on the South Chuya Ridge – from 39 to 73, on the Katun Ridge – from 57 to 89, on the territory of the Tavan-Bogdo-Ola massif – from 11 to 19, and on the territory of the Mongun-Taiga massif – from 8 to 11 lakes.

Distinct mechanisms for online and offline motor skill learning across human development.

The human central nervous system (CNS) undergoes tremendous changes from childhood to adulthood and this may affect how individuals at different stages of development learn new skills. Here, we studied motor skill learning in children, adolescents, and young adults to test the prediction that differences in the maturation of different learning mechanisms lead to distinct temporal patterns of motor learning during practice and overnight. We found that overall learning did not differ between children, adolescents, and young adults. However, we demonstrate that adult-like skill learning is characterized by rapid and large improvements in motor performance during practice (i.e., online) that are susceptible to forgetting and decay over time (i.e., offline). On the other hand, child-like learning exhibits slower and less pronounced improvements in performance during practice, but these improvements are robust against forgetting and lead to gains in performance overnight without further practice. The different temporal dynamics of motor skill learning suggest an engagement of distinct learning mechanisms in the human CNS during development. In conclusion, adult-like skill learning mechanisms favor online improvements in motor performance whereas child-like learning mechanisms favors offline behavioral gains. RESEARCH HIGHLIGHTS: Many essential motor skills, like walking, talking, and writing, are acquired during childhood, and it is colloquially thought that children learn better than adults. We investigated dynamics of motor skill learning in children, adolescents, and young adults. Adults displayed substantial improvements during practice that was susceptible to forgetting over time. Children displayed smaller improvements during practice that were resilient against forgetting. The distinct age-related characteristics of these processes of acquisition and consolidation suggest that skill learning relies on different mechanisms in the immature and mature central nervous system.

The Limping Child: A Guide for the Trainees.

Limping is a common presenting complaint in children. Despite this, it remains to be a diagnostic challenge for treating physicians due to an expanded list of etiologies. It arises from a spectrum of disorders, ranging from physiological variations of gait at different stages of development to systemic causes, such as inflammatory diseases or musculoskeletal infections. On rare occasions, non-musculoskeletal causes could result in limping. The diagnostic challenge increases in younger age children where a detailed physical examination that helps identify the exact source of pathology may not be possible. In older patients who have a well-developed gait cycle, the physical assessment might be easier. Clinical assessment in a child presenting with a limp includes gait analysis, which is essential to guide the appropriate request of diagnostic laboratory tests and imaging studies. In this paper, we provide a practical guide for a trainee in General Pediatric and Pediatric Rheumatology on an approach to a limping child, aiming to identify the common causes of limping and to describe normal and abnormal gait cycles. We also discuss other diagnostic considerations in the assessment of these children.

Application of ultrasonic imaging technology in beef cattle breeding management

ObjectiveThe aim of this study was to explore in depth the application of ultrasonic imaging technology in beef cattle reproduction management in order to improve the efficiency and management of beef cattle reproduction. MethodsIn this study, ultrasonographic diagnostic techniques were used to follow up the follicles and corpus luteum in the uterus and ovaries of dairy cows at different stages of development as well as at different periods of gestation of dairy cows, and to detect the effects of different fattening conditions of the cows and the number of litters on the sitting rate. ResultsThe diameter of mature follicles was generally around 16 mm, and the majority of them were 11–20 mm in diameter. Ultrasonography was used to detect early pregnancy in cows at 33–55 d. Ultrasound was used to identify the sex of the foetus most easily at 70–80 d. The results of this study showed that the sex of the foetus was most easily identified in cows at 70–80 d. The fat of the cow and the number of births also had a significant impact on pregnancy rates. ConclusionUltrasound imaging technology has an important application value in the management of beef cattle reproduction, and in pregnancy detection, it can achieve early and accurate diagnosis, improve the accuracy of detection, and differentiate between heifers in estrus and pregnant heifers. In addition, it can also be used for foetal sex identification at a specific period of time, providing a basis for breeding programmes.

Early development of smallscale weakfish Cynoscion microlepidotus (Cuvier, 1830) (Sciaenidae: Teleostei).

Larval and transforming stages of smallscale weakfish Cynoscion microlepidotus (Sciaenidae) are described and illustrated based on samples obtained in three different sites along the Brazilian coast: São Marcos Bay (Maranhão state), Camamu Bay (Bahia state), and the Cananéia-Iguape Estuarine System (São Paulo state). Identification of early stages of C. microlepidotus was based on meristic counts, such as number of myomeres (22), number of fin spines and rays (dorsal XI, 24, anal II, 9 and pectoral 19), morphological features (presence of supraoccipital crest in larvae from flexion to transformation stages, branched anal fin spines) and pigmentation pattern. Early stages of this species are likely to be confused with Carangidae and Scorpaenidae due to the presence of a supraoccipital crest, and with the Sciaenidae species Stellifer rastrifer, Macrodon atricauda, M. ancylodon, and Isopistus parvipinnis due to branched anal fin elements. However, a distinction can be made when analyzing the set of characters (morphology, morphometry, pigmentation) in relation to the different stages of development.

Role of industrial growth on economic development: A comparative analysis of developed and developing countries

Industrialization has played a pivotal role in shaping economic transformation, influencing growth patterns globally across different stages of development. This study investigates the role of industrialization on economic development by controlling labor force, capital formation, school enerollment, and institutional quality. The panel data of 62 developing and 96 developed countries are collected from World Bank from 1990 to 2023. The empirical results are estimated by using the Panel Quantile Regression (PQR), and its robustness is checked through the Method of Moverment-Quantile Regression (MM-QR) approach. The empirical results found the U-shaped relationship between industrialization and economic development in both samples. The labor force significantly increases economic development in developed countries while declines in developing countries. Gross capital formation and preprimary education also significantly enhance economic development. The institutional quality surges economic development in developed countries and declines in developing countries. The MM-QR approach also shows similar results, proving the PQR approach's robustness. This study recommends that all countries should focus on industrial diversification, improving infrastructure and energy access, strengthening institutions, building a skilled workforce, and ensuring environmental sustainability.

The impact of cell states on heterochromatin dynamics.

Establishing, maintaining, and removing histone post-translational modifications associated with heterochromatin is critical for shaping genomic structure and function as a cell navigates different stages of development, activity, and disease. Dynamic regulation of the repressive chromatin landscape has been documented in several key cell states - germline cells, activated immune cells, actively replicating, and quiescent cells - with notable variations in underlying mechanisms. Here, we discuss the role of cell states of these diverse contexts in directing and maintaining observed chromatin landscapes. These investigations reveal heterochromatin architectures that are highly responsive to the functional context of a cell's existence and, in turn, their contribution to the cell's stable identity.

Tau Immunotherapies for Alzheimer's Disease and Related Tauopathies: Status of Trials and Insights from Preclinical Studies.

The tau protein undergoes pathological changes in Alzheimer's disease and other tauopathies that eventually lead to functional impairments. Over the years, several therapeutic approaches have been examined to slow or halt the progression of tau pathology but have yet to lead to an approved disease-modifying treatment. Of the drugs in clinical trials that directly target tau, immunotherapies are the largest category and mostly consist of antibodies in different stages of development. There is a reasonable optimism that at least some of these compounds will have a clinically meaningful efficacy. This view is based on the significant although modest efficacy of some antibodies targeting amyloid-β in Alzheimer's disease and the fact that tau pathology correlates much better with the degree of dementia than amyloid-β lesions. In Alzheimer's disease, clearing pathological tau may therefore improve function later in the disease process than when removing amyloid-β. This review provides a brief update on the active and passive clinical tau immunization trials with insight from preclinical studies. Various epitopes are being targeted and some of the antibodies are said to target extracellular tau but because almost all of pathological tau is found intracellularly, the most efficacious antibodies should be able to enter the cell.

Do complement clauses with first- or third-person perspective support false-belief reasoning? A training study with English-speaking 3-year-olds.

To investigate whether acquisition of the perspective-marking grammar of complement-clause constructions supports progression in children's false-belief reasoning, we conducted a training study with 76 English-speaking 3-year-olds from the North-West of England (age range: 3;0-3;10 years, 50% female, 80% White). Children were randomly assigned to one of three maximally comparable training conditions, and in a 4-week eight-session program, all children participated in the same training activities with mental-state contrasts. Depending on condition, activities were mediated linguistically with either simple clauses, first-person complements, or third-person complements. The study addressed critical confounds in previous training studies by avoiding the use of complement clauses in false-belief tests and controlling individual differences in memory, executive functioning, general language, and pretest proficiency with complement clauses. The results yielded strong support for the hypothesis of a causal influence of complement-clause exposure on false-belief progression, as children trained with first-person complements advanced significantly more in false-belief reasoning from pretest to posttest than children trained with simple clauses. Examining the roles of first- and third-person complements, a direct comparison between progression in the two complement-clause conditions showed no significant difference, but only children trained with first-person complements progressed significantly more than children in the control condition trained with simple clauses. Follow-up analyses suggested that first- and third-person complements each support false-belief progression at different stages of development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A validated and standardized pseudotyped microneutralization assay as a safe and powerful tool to measure LASSA virus neutralising antibodies for vaccine development and comparison.

Over the past few decades, World Health Organization (WHO) has made massive efforts to promote the development of a vaccine against Lassa virus (LASV), one of the top ten priority pathogens for research and development under the WHO R&D Blueprint for Emerging Infections. To date, several vaccines are at different stages of development. In this scenario, a validated and standardised assay to measure LASV neutralising antibodies is urgently needed for vaccine development and comparison. The neutralisation assay remains the gold standard for determining antibody efficacy. Here we have proposed a safe and validated pseudotyped neutralisation assay for LASV, taking advantage of the development of the first WHO International Standard and Reference Panel for Anti-Lassa Fever (NIBSC code 21/332). The proposed results demonstrate that the pseudotyped luciferase neutralisation assay is a specific serological test for the measurement of LASV neutralising antibodies without cross-reacting with standard sera specific for heterologous viral infections. In addition, the assay is accurate, precise, and linear according to criteria and statistical analyses defined and accepted by international guidelines.