Multiple transcriptome analyses reveal mouse testis developmental dynamics.

The testes are the organs of gamete production and testosterone synthesis. Up to date, no model system is available for mammalian testicular development, and only few studies have characterized the mouse testis transcriptome from no more than three postnatal ages. To describe the transcriptome landscape of the developing mouse testis and identify the potential molecular mechanisms underlying testis maturation, we examined multiple RNA-seq data of mouse testes from 3-week-old (puberty) to 11-week-old (adult). Sperm cells appeared as expected in 5-week-old mouse testis, suggesting the proper sample collection. The principal components analysis revealed the genes from 3w to 4w clustered away from other timepoints, indicating they may be the important nodes for testicular development. The pairwise comparisons at two adjacent timepoints identified 7,612 differentially expressed genes (DEGs), resulting in 58 unique mRNA expression patterns. Enrichment analysis identified functions in tissue morphogenesis (3-4w), regulation of peptidase activity (4-5w), spermatogenesis (7-8w), and antigen processing (10-11w), suggesting distinct functions in different developmental periods. 50 hub genes and 10 gene cluster modules were identified in the testis maturation process by protein-protein interaction (PPI) network analysis, and the miRNA-lncRNA-mRNA, miRNA-circRNA-mRNA and miRNA-circRNA-lncRNA-mRNA competing endogenous RNA (ceRNA) networks were constructed. The results suggest that testis maturation is a complex developmental process modulated by various molecules, and that some potential RNA-RNA interactions may be involved in specific developmental stages. In summary, this study provides an update on the molecular basis of testis development, which may help to understand the molecular mechanisms of mouse testis development and provide guidance for mouse reproduction.

Mesenchymal stem cell-based therapies for treating well-studied neurological disorders: a systematic review.

Background: Millions of people across the globe are affected by conditions like Amyotrophic Lateral Sclerosis (ALS), Parkinson's Disease (PD), Multiple Sclerosis (MS), Spinal Cord Injury (SCI), and Traumatic Brain Injury (TBI), although most occurrences are common in the elderly population. This systematic review aims to highlight the safety of the procedures, their tolerability, and efficacy of the available therapies conducted over the years using mesenchymal stem cells (MSCs) in treating the neurological conditions mentioned above. Methods: PubMed was used to search for published data from clinical trials performed using mesenchymal stem cells. Studies that provided the necessary information that mentioned the efficacy and adverse effects of the treatment in patients were considered for this review. Results: In total, 43 manuscripts were selected after a strategic search, and these studies have been included in this systematic review. Most included studies reported the safety of the procedures used and the treatment's good tolerability, with mild adverse events such as fever, headache, mild pain at the injection site, or nausea being common. A few studies also reported death of some patients, attributed to the progression of the disease to severe stages before the treatment. Other severe events, such as respiratory or urinary infections reported in some studies, were not related to the treatment. Different parameters were used to evaluate the efficacy of the treatment based on the clinical condition of the patient. Conclusion: Mesenchymal stem cells transplantation has so far proven to be safe and tolerable in select studies and patient types. This systematic review includes the results from the 43 selected studies in terms of safety and tolerability of the procedures, and several adverse events and therapeutic benefits during the follow-up period after administration of MSCs.

H3 Acetylation-Induced Basal Progenitor Generation and Neocortex Expansion Depends on the Transcription Factor Pax6.

Enrichment of basal progenitors (BPs) in the developing neocortex is a central driver of cortical enlargement. The transcription factor Pax6 is known as an essential regulator in generation of BPs. H3 lysine 9 acetylation (H3K9ac) has emerged as a crucial epigenetic mechanism that activates the gene expression program required for BP pool amplification. In this current work, we applied immunohistochemistry, RNA sequencing, chromatin immunoprecipitation and sequencing, and the yeast two-hybrid assay to reveal that the BP-genic effect of H3 acetylation is dependent on Pax6 functionality in the developing mouse cortex. In the presence of Pax6, increased H3 acetylation caused BP pool expansion, leading to enhanced neurogenesis, which evoked expansion and quasi-convolution of the mouse neocortex. Interestingly, H3 acetylation activation exacerbates the BP depletion and corticogenesis reduction effect of Pax6 ablation in cortex-specific Pax6 mutants. Furthermore, we found that H3K9 acetyltransferase KAT2A/GCN5 interacts with Pax6 and potentiates Pax6-dependent transcriptional activity. This explains a genome-wide lack of H3K9ac, especially in the promoter regions of BP-genic genes, in the Pax6 mutant cortex. Together, these findings reveal a mechanistic coupling of H3 acetylation and Pax6 in orchestrating BP production and cortical expansion through the promotion of a BP gene expression program during cortical development.

The development of thoracic and abdominal muscle depends on SDF1 and CXCR4.

In vertebrates, the lateral body wall muscle formation is thought to be initiated by direct outgrowth of the dermomyotomes resulting in the elongation of the hypaxial myotomes. This contrasts with the formation of the muscles of the girdle, limbs and intrinsic tongue muscles, which originate from long-range migrating progenitors. Previous work shows that the migration of these progenitors requires CXCR4 which is specifically expressed in the migrating cells, but not in the dermomyotome. Here, we show that cells in the ventrolateral-lip (VLL) of the dermomyotome at the flank level express CXCR4 in a pattern consistent with that of Pax3 and MyoR. In ovo gain-of-function experiments using electroporation of SDF-1 constructs into the VLL resulted in increased expression of c-Met, Pax3 and MyoD. In contrast, a loss-of-function approach by implantation of CXCR4-inhibitor beads into the VLL of the flank region caused a reduction in the expression of these markers. These data show that CXCR4 is expressed in the VLL, and by experimentally manipulating the CXCR4/SDF-1 signaling, we demonstrate the importance of this axis in body wall muscle development.

Human skeletal muscle organoids model fetal myogenesis and sustain uncommitted PAX7 myogenic progenitors.

In vitro culture systems that structurally model human myogenesis and promote PAX7+ myogenic progenitor maturation have not been established. Here we report that human skeletal muscle organoids can be differentiated from induced pluripotent stem cell lines to contain paraxial mesoderm and neuromesodermal progenitors and develop into organized structures reassembling neural plate border and dermomyotome. Culture conditions instigate neural lineage arrest and promote fetal hypaxial myogenesis toward limb axial anatomical identity, with generation of sustainable uncommitted PAX7 myogenic progenitors and fibroadipogenic (PDGFRa+) progenitor populations equivalent to those from the second trimester of human gestation. Single-cell comparison to human fetal and adult myogenic progenitor /satellite cells reveals distinct molecular signatures for non-dividing myogenic progenitors in activated (CD44High/CD98+/MYOD1+) and dormant (PAX7High/FBN1High/SPRY1High) states. Our approach provides a robust 3D in vitro developmental system for investigating muscle tissue morphogenesis and homeostasis.

Humans contains around 650 skeletal muscles which allow the body to move around and maintain its posture. Skeletal muscles are made up of individual cells that bundle together into highly organized structures. If this group of muscles fail to develop correctly in the embryo and/or fetus, this can lead to muscular disorders that can make it painful and difficult to move. One way to better understand how skeletal muscles are formed, and how this process can go wrong, is to grow them in the laboratory. This can be achieved using induced pluripotent stem cells (iPSCs), human adult cells that have been 'reprogrammed' to behave like cells in the embryo that can develop in to almost any cell in the body. The iPSCs can then be converted into specific cell types in the laboratory, including the cells that make up skeletal muscle. Here, Mavrommatis et al. created a protocol for developing iPSCs into three-dimensional organoids which resemble how cells of the skeletal muscle look and arrange themselves in the fetus. To form the skeletal muscle organoid, Mavrommatis et al. treated iPSCs that were growing in a three-dimensional environment with various factors that are found early on in development. This caused the iPSCs to organize themselves in to embryonic and fetal structures that will eventually give rise to the parts of the body that contain skeletal muscle, such as the limbs. Within the organoid were cells that produced Pax7, a protein commonly found in myogenic progenitors that specifically mature into skeletal muscle cells in the fetus. Pax 7 is also present in 'satellite cells' that help to regrow damaged skeletal muscle in adults. Indeed, Mavrommatis et al. found that the myogenic progenitors produced by the organoid were able to regenerate muscle when transplanted in to adult mice. These findings suggest that this organoid protocol can generate cells that will give rise to skeletal muscle. In the future, these lab-grown progenitors could potentially be created from cells isolated from patients and used to repair muscle injuries. The organoid model could also provide new insights in to how skeletal muscles develop in the fetus, and how genetic mutations linked with muscular disorders disrupt this process.

CRISPR/Cas9 Genome Editing in LGMD2A/R1 Patient-Derived Induced Pluripotent Stem and Skeletal Muscle Progenitor Cells.

Large numbers of Calpain 3 (CAPN3) mutations cause recessive forms of limb-girdle muscular dystrophy (LGMD2A/LGMDR1) with selective atrophy of the proximal limb muscles. We have generated induced pluripotent stem cells (iPSC) from a patient with two mutations in exon 3 and exon 4 at the calpain 3 locus (W130C, 550delA). Two different strategies to rescue these mutations are devised: (i) on the level of LGMD2A-iPSC, we combined CRISPR/Cas9 genome targeting with a FACS and Tet transactivator-based biallelic selection strategy, which resulted in a new functional chimeric exon 3-4 without the two CAPN3 mutations. (ii) On the level of LGMD2A-iPSC-derived CD82+/Pax7+ myogenic progenitor cells, we demonstrate CRISPR/Cas9 mediated rescue of the highly prevalent exon 4 CAPN3 mutation. The first strategy specifically provides isogenic LGMD2A corrected iPSC for disease modelling, and the second strategy can be further elaborated for potential translational approaches.

Detection of Math6-Expressing Cell Types in Murine Placenta.

The transcription factor Math6, mouse atonal homolog 6, belongs to the family of highly conserved basic helix-loop-helix transcription factors. It plays an important role in embryonic development and shows a wide expression pattern in murine tissues. The placenta, as a life-sustaining transient organ for the fetus, also depends on the expression of Math6. The adverse effects of deleting Math6 in mice, leading to deficient placental development and pregnancy loss, have already been demonstrated by us. Until now, detailed investigations regarding the specific mechanisms underlying the improper placental development in these murine mutants have failed, as the Math6 expression could not be confined to a specific cell type due to the lack of a highly specific Math6 antibody. To circumvent this problem, we used transgenic mice, where Math6 is marked with a Flag sequence that functions as a specific epitope. Tissues from these transgenic mice were used to establish immunohistochemical staining and fluorescence-activated cell sorting (FACS). The establishment of these methods yielded initial findings pertaining to the identification of Math6-expressing cell types and their localization. Our results reveal that Math6 shows a wide expression pattern in both maternal and fetal components of the murine placenta. It shows expression in various cell types, but predominantly in trophoblast giant cells, endothelial cells and macrophages. The largest subpopulation that we detected in the group of Math6-positive cells were identified as DBA+ uterine natural killer cells. These findings reveal information and a chance for further investigation on the involvement of Math6 in placental development and the molecular pathomechanisms of spontaneous abortion.

Rethinking Learning Experience: How Generally Perceived Life Stress Influences Students' Course Perceptions in Different Learning Environments.

Previous research work has already demonstrated that both the form of teaching as well as different teaching methods directly influence students' learning experience along with their psychobiological responses at the endocrine and autonomic level. Aiming to gain deeper insights into the constitution of the learning experience, this study examined the influence of external factors such as generally perceived life stress and self-efficacy on the immediate learning experience in different learning environments. Therefore, a randomized experimental field study was conducted in which both psychological constructs and physiological data (heart rate variability) were collected from healthy first-year medical students (n = 101) during the COVID-19 pandemic. In an effort to determine the consistency of the effects across various teaching formats, the same content of a practical histology course was carried out in a face-to-face setting as well as in passive and active online teaching. While self-efficacy was a strong predictor for positive course perceptions in all learning conditions (Pearson's r = 0.41-0.58), generally perceived worries correlated with higher anxiety during passive online learning and face-to-face learning (Pearson's r = 0.21-0.44), a finding supported by the negative correlation between the level of perceived life demands and enjoyment during the learning unit (Pearson's r = -0.40--0.43). Here, we additionally report initial evidence pointing towards the role of reduced general life stress as a resilience factor for the expression of physiological stress parameters in an academic context (small-sized effect; Pearson's r = 0.18). The data gathered in this study illustrate the relevance of emerging emotional manifestations-either aversive; negative effect or positive; protective effect-for the immediate learning process and thus establish a connection between medical education and the importance of mental health and wellbeing-especially discussed against the background of current social and political challenges in increasingly complex societal structures.

Dynamically Changing Mental Stress Parameters of First-Year Medical Students over the Three-Year Course of the COVID-19 Pandemic: A Repeated Cross-Sectional Study.

Numerous research results have already pointed towards the negative influence of increased mental stress on educational processes and motivational criteria. It has also been shown that the global public health crisis induced by COVID-19 was related to anxiety symptoms and elevated levels of distress. To holistically elucidate the dynamics of the pandemic-related mental stress of first-year medical students, the associated parameters of three different cohorts were measured at the beginning of the pandemic-related restrictions on university life in Germany (20/21), at the peak of the COVID-19-related restrictions (21/22) and during the easing of the restrictions in the winter term 22/23. In a repeated cross-sectional study design, the constructs of worries, tension, demands and joy were collected from first-year medical students (n = 578) using the Perceived Stress Questionnaire. The results demonstrate significantly increased values of the constructs worries (p < 0.001), tension (p < 0.001) and demands (p < 0.001) at the peak of the pandemic related restrictions compared to the previous and following year as well as significantly decreasing values of general joy of life during the observed period of 3 years (all p-values < 0.001). A confirmatory factor analysis was performed to verify the questionnaire's factor structure regarding the addressed target group during the pandemic (CFI: 0.908, RMSEA: 0.071, SRMR: 0.052). These data, collected over a period of three years, provide information regarding dynamically manifesting mental stress during the COVID-19 pandemic, and refer to new areas of responsibility for the faculties to adequately counteract future crisis situations.

Systemic Prenatal Stress Exposure through Corticosterone Application Adversely Affects Avian Embryonic Skin Development.

Prenatal stress exposure is considered a risk factor for developmental deficits and postnatal behavioral disorders. While the effect of glucocorticoid-associated prenatal stress exposure has been comprehensively studied in many organ systems, there is a lack of in-depth embryological investigations regarding the effects of stress on the integumentary system. To approach this, we employed the avian embryo as a model organism and investigated the effects of systemic pathologically-elevated glucocorticoid exposure on the development of the integumentary system. After standardized corticosterone injections on embryonic day 6, we compared the stress-exposed embryos with a control cohort, using histological and immunohistochemical analyses as well as in situ hybridization. The overarching developmental deficits observed in the stress-exposed embryos were reflected through downregulation of both vimentin as well as fibronectin. In addition, a deficient composition in the different skin layers became apparent, which could be linked to a reduced expression of Dermo-1 along with significantly reduced proliferation rates. An impairment of skin appendage formation could be demonstrated by diminished expression of Sonic hedgehog. These results contribute to a more profound understanding of prenatal stress causing severe deficits in the integumentary system of developing organisms.

Chicken embryo as a model in second heart field development.

Previously, a single source of progenitor cells was thought to be responsible for the formation of the cardiac muscle. However, the second heart field has recently been identified as an additional source of myocardial progenitor cells. The chicken embryo, which develops in the egg, outside the mother can easily be manipulated in vivo and in vitro. Hence, it was an excellent model for establishing the concept of the second heart field. Here, our review will focus on the chicken model, specifically its role in understanding the second heart field. In addition to discussing historical aspects, we provide an overview of recent findings that have helped to define the chicken second heart field progenitor cells. A better understanding of the second heart field development will provide important insights into the congenital malformations affecting cardiac muscle formation and function.

Interactive teaching enhances students' physiological arousal during online learning.

The pure transfer of face-to-face teaching to a digital learning environment can be accompanied by a significant reduction in the physiological arousal of students, which in turn can be associated with passivity during the learning process, often linked to insufficient levels of concentration and engagement in the course work. Therefore, the aim of this study was to investigate whether students' psychobiological stress responses can be enhanced in the context of anatomical online learning and how increased physiological parameters correlate with characteristics of learning experiences in a digital learning environment. Healthy first-year medical students (n = 104) experienced a regular practical course in Microscopic Anatomy either in face-to-face learning, in passive online learning or in an interaction-enhanced version of online learning. Compared to passive online learning, students engaged in the interaction-enhanced version of online learning displayed a significantly reduced Heart Rate Variability (P 0.001, partial η2 = 0.381) along with a strong increase in salivary cortisol (P 0.001, partial η2 = 0.179) and salivary alpha-amylase activity (P 0.001, partial η2 = 0.195). These results demonstrated that the physiological arousal of students engaged in online learning can be enhanced via interactive teaching methods and pointed towards clear correlations between higher physiological responses and elementary criteria of learning experience such as engagement and attention.

Spatiotemporal expression pattern of the chicken glucocorticoid receptor during early embryonic development.

Glucocorticoids - commonly known as stress hormones - belong to the family of steroid hormones and regulate numerous life essential physiological processes. As lipophilic molecules, glucocorticoids are known to cross the placental barrier in mammals, which - applied for therapeutic reasons or arising from environmental influences - illustrates the role of prenatal stress during embryonic developmental processes. The hormones employ their functions by binding to the glucocorticoid receptor (GR) and thus are involved in regulating the transcription of thousands of genes. Therefore, the aim of this study was to investigate the spatiotemporal expression pattern of the GR during early embryonic vertebrate development, using the chicken embryo as a model organism. The results should contribute to enhance and expand the current understanding of glucocorticoid signaling. By performing in-situ hybridization on whole mount chicken embryos from stage HH10 to HH29 and analyzing vibratome sections of hybridized embryos, we described the spatiotemporal expression pattern of the GR during early embryogenesis. Moreover, we compared the expression pattern of the GR with other developmental markers such as Pax7, Desmin, MyoD and HNK-1 using double in-situ hybridization and immunohistochemistry. We were able to determine the first emergence of GR expression in stage HH13 of chicken development in the cranial area, especially in the muscle anlagen of the branchial arches and of non-somitic neck muscles. Furthermore, we monitored the extension of GR expression pattern throughout later stages and found transcripts of GR during somitogenesis, limb development, myogenesis, neurulation and neural differentiation and moreover during organogenesis of the gastrointestinal organs, the heart, the kidneys and the lungs. Toward later stages, GR expression transitioned from more distinct areas of expression to an increasingly ubiquitous expression pattern. Our results support the notion of an enormous relevance of glucocorticoid signaling during vertebrate embryonic development and contribute to a better understanding of the consequences of prenatal stress and the clinical administration of prenatal glucocorticoids.

Implementing a multi-colour genetic marker analysis technique for embryology education.

Embryology belongs to the basic sciences and is usually an integral part of the anatomy. The subject is traditionally taught by visual inspection of embryonic tissue slides stained with Haematoxylin and Eosin (H&E) to expose the dynamics of tissue histology as development proceeds. While combining in situ hybridization for gene expression analysis and immunostaining for protein expression analysis is an established technique for embryology research, the implementation of this tool in embryology teaching has not been described. The present study was conducted to assess the use of an online multi-colour gene expression analysis technique, alongside histological sections and diagrams, to improve students' understanding of embryology. The participants of this study were bachelor's students of Veterinary Medicine at the University of Khartoum. The method was also evaluated by distributing questionnaire items to Veterinary students via Google forms; subsequently, their responses were analysed qualitatively. The majority of students stated that the new technique was beneficial for their learning of embryology. The multi-colour images proved a more effective means for learning embryology than the traditional H&E image. Results from the students strengthen the belief in applying the multi-colour technique for better embryology course learning.

Local Glucocorticoid Administration Impairs Embryonic Wound Healing.

Understanding the complex processes of fetal wound healing and skin regeneration can help to improve fetal surgery. As part of the integumentary system, the skin protects the newborn organism against environmental factors and serves various functions. Glucocorticoids can enter the fetal circulatory system by either elevated maternal stress perception or through therapeutic administration and are known to affect adult skin composition and wound regeneration. In the present study, we aimed at investigating the effects of local glucocorticoid administration on the process of embryonic wound healing. We performed in-ovo bead implantation of dexamethasone beads into skin incisional wounds of avian embryos and observed the local effects of the glucocorticoid on the process of skin regeneration through histology, immunohistochemistry and in-situ hybridization, using vimentin, fibronectin, E-cadherin, Dermo-1 and phospho-Histone H3 as investigational markers. Local glucocorticoid administration decelerated the healing of the skin incisional wounds by impairing mesenchymal contraction and re-epithelialization resulting in morphological changes, such as increased epithelialization and disorganized matrix formation. The results contribute to a better understanding of scarless embryonic wound healing and how glucocorticoids might interfere with the underlying molecular processes, possibly indicating that glucocorticoid therapies in prenatal clinical practice should be carefully evaluated.

Zebrafish as an Orthotopic Tumor Model for Retinoblastoma Mimicking Routes of Human Metastasis.

BACKGROUND: Retinoblastoma (RB) is the most common eye cancer in children that has a high mortality rate when left untreated. Mouse models for retinoblastoma have been established but are time- and cost-intensive. The aim of this work was to evaluate an orthotopic transplantation model of retinoblastoma in zebrafish that also allows for tracking migratory routes and to explore advantages and disadvantages with respect to drug testing. METHODS: Three fluorescence-labeled retinoblastoma cell lines (RB355, WERI-RB-1, Y79) were injected into the left eye of two-day-old zebrafish, while the un-injected right eye served as control. The migratory trajectories of injected retinoblastoma cells were observed until 8 days post injection (dpi), both in lateral and dorsal view, and measuring fluorescence intensity of injected cells was done for RB355 cells. RESULTS: Time until the onset of migration and routes for all three retinoblastoma cell lines were comparable and resulted in migration into the brain and ventricles of the forebrain, midbrain and hindbrain. Involvement of the optic nerve was observed in 10% of injections with the RB355 cell line, 15% with Y79 cells and 5% with WERI-RB-1 cells. Fluorescence intensity of injected RB355 cells showed an initial increase until five dpi, but then decreased with high variability until the end of observation. CONCLUSION: The zebrafish eye is well suited for the analysis of migratory routes in retinoblastoma and closely mirrors patterns of retinoblastoma metastases in humans.

BAF (mSWI/SNF) complex regulates mediolateral cortical patterning in the developing forebrain.

Early forebrain patterning entails the correct regional designation of the neuroepithelium, and appropriate specification, generation, and distribution of neural cells during brain development. Specific signaling and transcription factors are known to tightly regulate patterning of the dorsal telencephalon to afford proper structural/functional cortical arealization and morphogenesis. Nevertheless, whether and how changes of the chromatin structure link to the transcriptional program(s) that control cortical patterning remains elusive. Here, we report that the BAF chromatin remodeling complex regulates the spatiotemporal patterning of the mouse dorsal telencephalon. To determine whether and how the BAF complex regulates cortical patterning, we conditionally deleted the BAF complex scaffolding subunits BAF155 and BAF170 in the mouse dorsal telencephalic neuroepithelium. Morphological and cellular changes in the BAF mutant forebrain were examined using immunohistochemistry and in situ hybridization. RNA sequencing, Co-immunoprecipitation, and mass spectrometry were used to investigate the molecular basis of BAF complex involvement in forebrain patterning. We found that conditional ablation of BAF complex in the dorsal telencephalon neuroepithelium caused expansion of the cortical hem and medial cortex beyond their developmental boundaries. Consequently, the hippocampal primordium is not specified, the mediolateral cortical patterning is compromised, and the cortical identity is disturbed in the absence of BAF complex. The BAF complex was found to interact with the cortical hem suppressor LHX2. The BAF complex suppresses cortical hem fate to permit proper forebrain patterning. We provide evidence that BAF complex modulates mediolateral cortical patterning possibly by interacting with the transcription factor LHX2 to drive the LHX2-dependent transcriptional program essential for dorsal telencephalon patterning. Our data suggest a putative mechanistic synergy between BAF chromatin remodeling complex and LHX2 in regulating forebrain patterning and ontogeny.

Atonal homolog 8/Math6 regulates differentiation and maintenance of skeletal muscle.

Atonal Homolog 8 (Atoh8) belongs to a large superfamily of transcriptional regulators called basic helix-loop-helix (bHLH) transcription factors. Atoh8 (murine homolog "Math6") has been shown to be involved in organogenesis during murine embryonic development. We have previously identified the expression of Atoh8 during skeletal myogenesis in chicken where we described its involvement in hypaxial myotome formation suggesting a regulatory role of Atoh8 in skeletal muscle development. Within the current study, we analyzed the effect of the loss of function of Atoh8 in murine primary myoblasts and during differentiation of pluripotent stem cells into myotubes, and the effect of its gain of function in C2C12 cells. Based on the observed results, we conclude that Atoh8 regulates myoblast proliferation via modulating myostatin signaling. Further, our data revealed a reduced muscle mass, strength and fiber size with significant changes to the muscle fiber type suggesting atrophy in skeletal muscle of Atoh8 mutants. We further report that Atoh8 knockout mice suffer from a condition similar to ambient hypoxia which may be the primary cause of the phenotype. Altogether, this study shows the significance of Atoh8 not only in myogenesis but also in the maintenance of skeletal muscle.

Decreased sympathetic cardiovascular influences and hormone-physiological changes in response to Covid-19-related adaptations under different learning environments.

To examine the implications of the transition from face-to-face to online learning from a psychobiological perspective, this study investigated potential differences in physiological stress parameters of students engaged in online or face-to-face learning and determined whether these can be identified as possible mediators between learning experience and achievement emotions. In a randomized experimental field study, medical students (n = 82) attended either regular face-to-face classes of the microscopic anatomy course or the same practical course online using Zoom videoconferencing platform. The present study investigated Heart Rate Variability (HRV) and salivary cortisol concentration as stress correlates, within the contexts of online and face-to-face learning and compared these parameters with a control group that was measured at rest. Additionally, participants completed a standardized questionnaire about their experienced emotions in relation to task achievement and subjective stress levels. A significant reduction in HRV was found in face-to-face learning, suggesting stronger stress responses in the face-to-face learning environment (η2  = 0.421, P < 0.001). Furthermore, participants engaged in face-to-face learning showed significantly higher cortisol concentrations (η2  = 0.115, P = 0.032). Additionally, increased sympathetic activation correlated with the discrete positive emotion of enjoyment exclusively within the face-to-face condition (r = 0.365, P = 0.043). These results indicate that the transfer of a face-to-face practical course in microscopic anatomy to an online learning environment is associated with decreased sympathetic and enhanced vagal cardiovascular influences, together with lower cortisol concentrations in healthy medical students.

New Insights into the Diversity of Branchiomeric Muscle Development: Genetic Programs and Differentiation.

Branchiomeric skeletal muscles are a subset of head muscles originating from skeletal muscle progenitor cells in the mesodermal core of pharyngeal arches. These muscles are involved in facial expression, mastication, and function of the larynx and pharynx. Branchiomeric muscles have been the focus of many studies over the years due to their distinct developmental programs and common origin with the heart muscle. A prerequisite for investigating these muscles' properties and therapeutic potential is understanding their genetic program and differentiation. In contrast to our understanding of how branchiomeric muscles are formed, less is known about their differentiation. This review focuses on the differentiation of branchiomeric muscles in mouse embryos. Furthermore, the relationship between branchiomeric muscle progenitor and neural crest cells in the pharyngeal arches of chicken embryos is also discussed. Additionally, we summarize recent studies into the genetic networks that distinguish between first arch-derived muscles and other pharyngeal arch muscles.