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Understanding the mechanisms of the cellular aging processes is crucial for attempting to extend organismal lifespan and for studying age-related degenerative diseases. Yeast cells divide through budding, providing a classical biological model for studying cellular aging. With their powerful genetics, relatively short cell cycle, and well-established signaling pathways also found in animals, yeast cells offer valuable insights into the aging process. Recent experiments suggested the existence of two aging modes in yeast characterized by nucleolar and mitochondrial declines, respectively. By analyzing experimental data, this study shows that cells evolving into those two aging modes behave differently when they are young. While buds grow linearly in both modes, cells that consistently generate spherical buds throughout their lifespan demonstrate greater efficacy in controlling bud size and growth rate at young ages. A three-dimensional multiscale chemical-mechanical model was developed and used to suggest and test hypothesized impacts of aging on bud morphogenesis. Experimentally calibrated model simulations showed that during the early stage of budding, tubular bud shape in one aging mode could be generated by locally inserting new materials at the bud tip, a process guided by the polarized Cdc42 signal. Furthermore, the aspect ratio of the tubular bud could be stabilized during the late stage as observed in experiments in this work. The model simulation results suggest that the localization of new cell surface material insertion, regulated by chemical signal polarization, could be weakened due to cellular aging in yeast and other cell types, leading to the change and stabilization of the bud aspect ratio.

How a developing organ robustly coordinates the cellular mechanics and growth to reach a final size and shape remains poorly understood. Through iterations between experiments and model simulations that include a mechanistic description of interkinetic nuclear migration, we show that the local curvature, height, and nuclear positioning of cells in the Drosophila wing imaginal disc are defined by the concurrent patterning of actomyosin contractility, cell-ECM adhesion, ECM stiffness, and interfacial membrane tension. We show that increasing cell proliferation via different growth-promoting pathways results in two distinct phenotypes. Triggering proliferation through insulin signaling increases basal curvature, but an increase in growth through Dpp signaling and Myc causes tissue flattening. These distinct phenotypic outcomes arise from differences in how each growth pathway regulates the cellular cytoskeleton, including contractility and cell-ECM adhesion. The coupled regulation of proliferation and cytoskeletal regulators is a general strategy to meet the multiple context-dependent criteria defining tissue morphogenesis.

Thrombospondin-4 (TSP-4) belongs to the extracellular matrix glycoprotein family of thrombospondins (TSPs). The multidomain, pentameric structure of TSP-4 allows its interactions with numerous extracellular matrix components, proteins and signaling molecules that enable its modulation to various physiological and pathological processes. Characterization of TSP-4 expression under development and pathogenesis of disorders has yielded important insights into mechanisms underlying the unique role of TSP-4 in mediating various processes including cell-cell, cell-extracellular matrix interactions, cell migration, proliferation, tissue remodeling, angiogenesis, and synaptogenesis. Maladaptation of these processes in response to pathological insults and stress can accelerate the development of disorders including skeletal dysplasia, osteoporosis, degenerative joint disease, cardiovascular diseases, tumor progression/metastasis and neurological disorders. Overall, the diverse functions of TSP-4 suggest that it may be a potential marker or therapeutic target for prognosis, diagnosis, and treatment of various pathological conditions upon further investigations. This review article highlights recent findings on the role of TSP-4 in both physiological and pathological conditions with a focus on what sets it apart from other TSPs.

The development of ectodermal organs begins with the formation of a stratified epithelial placode that progressively invaginates into the underlying mesenchyme as the organ takes its shape. Signaling by secreted molecules is critical for epithelial morphogenesis, but how that information leads to cell rearrangement and tissue shape changes remains an open question. Using the mouse dentition as a model, we first establish that non-muscle myosin II is essential for dental epithelial invagination and show that it functions by promoting cell-cell adhesion and persistent convergent cell movements in the suprabasal layer. Shh signaling controls these processes by inducing myosin II activation via AKT. Pharmacological induction of AKT and myosin II can also rescue defects caused by the inhibition of Shh. Together, our results support a model in which the Shh signal is transmitted through myosin II to power effective cellular rearrangement for proper dental epithelial invagination.

The Hedgehog (Hh) pathway plays a crucial role in embryonic development, acting both as a morphogenic signal that organizes tissue formation and a potent mitogenic signal driving cell proliferation. Dysregulated Hh signaling leads to various developmental defects in the brain. This article aims to review the roles of Hh signaling in the development of the neocortex in the mammalian brain, focusing on its regulation of neural progenitor proliferation and neuronal production. The review will summarize studies on genetic mouse models that have targeted different components of the Hh pathway, such as the ligand Shh, the receptor Ptch1, the GPCR-like transducer Smo, the intracellular transducer Sufu, and the three Gli transcription factors. As key insights into the Hh signaling transduction mechanism were obtained from mouse models displaying neural tube defects, this review will also cover some studies on Hh signaling in neural tube development. The results from these genetic mouse models suggest an intriguing hypothesis that elevated Hh signaling may play a role in the gyrification of the brain in certain species. Additionally, the distinctive production of GABAergic interneurons in the dorsal cortex in the human brain may also be linked to the extension of Hh signaling from the ventral to the dorsal brain region. Overall, these results suggest key roles of Hh signaling as both a morphogenic and mitogenic signal during the forebrain development and imply the potential involvement of Hh signaling in the evolutionary expansion of the neocortex.

Large-scale cell flow characterizes gastrulation in animal development. In amniote gastrulation, particularly in avian gastrula, a bilateral vortex-like counter-rotating cell flow, called 'polonaise movements', appears along the midline. Here, through experimental manipulations, we addressed relationships between the polonaise movements and morphogenesis of the primitive streak, the earliest midline structure in amniotes. Suppression of the Wnt/planar cell polarity (PCP) signaling pathway maintains the polonaise movements along a deformed primitive streak. Mitotic arrest leads to diminished extension and development of the primitive streak and maintains the early phase of the polonaise movements. Ectopically induced Vg1, an axis-inducing morphogen, generates the polonaise movements, aligned to the induced midline, but disturbs the stereotypical cell flow pattern at the authentic midline. Despite the altered cell flow, induction and extension of the primitive streak are preserved along both authentic and induced midlines. Finally, we show that ectopic axis-inducing morphogen, Vg1, is capable of initiating the polonaise movements without concomitant PS extension under mitotic arrest conditions. These results are consistent with a model wherein primitive streak morphogenesis is required for the maintenance of the polonaise movements, but the polonaise movements are not necessarily responsible for primitive streak morphogenesis. Our data describe a previously undefined relationship between the large-scale cell flow and midline morphogenesis in gastrulation.

Angiogenesis is a morphogenic process resulting in the formation of new blood vessels from pre-existing ones, usually in hypoxic micro-environments. The initial steps of angiogenesis depend on robust differentiation of oligopotent endothelial cells into the Tip and Stalk phenotypic cell fates, controlled by NOTCH-dependent cell-cell communication. The dynamics of spatial patterning of this cell fate specification are only partially understood. Here, by combining a controlled experimental angiogenesis model with mathematical and computational analyses, we find that the regular spatial Tip-Stalk cell patterning can undergo an order-disorder transition at a relatively high input level of a pro-angiogenic factor VEGF. The resulting differentiation is robust but temporally unstable for most cells, with only a subset of presumptive Tip cells leading sprout extensions. We further find that sprouts form in a manner maximizing their mutual distance, consistent with a Turing-like model that may depend on local enrichment and depletion of fibronectin. Together, our data suggest that NOTCH signaling mediates a robust way of cell differentiation enabling but not instructing subsequent steps in angiogenic morphogenesis, which may require additional cues and self-organization mechanisms. This analysis can assist in further understanding of cell plasticity underlying angiogenesis and other complex morphogenic processes.

Formation of fluid-filled lumina by epithelial tissues is essential for organ development. How cells control the hydraulic and cortical forces to control lumen morphology is not well understood. Here, we quantified the mechanical role of tight junctions in lumen formation using MDCK-II cysts. We found that the paracellular ion barrier formed by claudin receptors is not required for the hydraulic inflation of a lumen. However, the depletion of the zonula occludens scaffold resulted in lumen collapse and folding of apical membranes. Combining quantitative measurements of hydrostatic lumen pressure and junctional tension with modeling enabled us to explain lumen morphologies from the pressure-tension force balance. Tight junctions promote lumen inflation by decreasing cortical tension via the inhibition of myosin. In addition, our results suggest that excess apical area contributes to lumen opening. Overall, we provide a mechanical understanding of how epithelial cells use tight junctions to modulate tissue and lumen shape. [Display omitted] • Depletion of ZO scaffold causes lumen collapse and apical membrane folding • The claudin permeability barrier is not necessary for hydraulic lumen inflation • Tight junctions promote lumen inflation by decreasing cortical tension • Lumen shape controlled by pressure-tension force balance and apical area constraints Mukenhirn et al. show that epithelial cells use tight junctions to control lumen shape, and the depletion of the tight junction scaffold leads to lumen collapse and increased cortical tension. Claudin-depleted MDCK-II cysts maintain lumen pressure and shape despite high ion permeability. [ABSTRACT FROM AUTHOR]

Hox transcription factors play crucial roles in organizing developmental patterning across metazoa, but how these factors trigger regional morphogenesis has largely remained a mystery. In the developing gut, Hox genes help demarcate identities of intestinal subregions early in embryogenesis, which ultimately leads to their specialization in both form and function. Although the midgut forms villi, the hindgut develops sulci that resolve into heterogeneous outgrowths. Combining mechanical measurements of the embryonic chick intestine and mathematical modeling, we demonstrate that the posterior Hox gene HOXD13 regulates biophysical phenomena that shape the hindgut lumen. We further show that HOXD13 acts through the transforming growth factor β (TGF-β) pathway to thicken, stiffen, and promote isotropic growth of the subepithelial mesenchyme—together, these features lead to hindgut-specific surface buckling. TGF-β, in turn, promotes collagen deposition to affect mesenchymal geometry and growth. We thus identify a cascade of events downstream of positional identity that direct posterior intestinal morphogenesis. [Display omitted] • Mechanical properties define epithelial buckling in the developing chick intestine • HOXD13 promotes hindgut mechanics through increased mesenchymal TGF-β signaling • Hindgut and ectopic midgut HOXD13- expressing smooth muscle upregulates INHBA • Mesenchymal TGF-β activation tunes mechanics via extracellular matrix remodeling Gill et al. mechanistically link HOXD13 expression to morphogenesis of the chick hindgut epithelium. HOXD13 activity within smooth muscle induces INHBA expression, which causes adjacent mesenchymal cells to remodel extracellular matrix (ECM) in response to TGF-β upregulation, thus promoting the biomechanical parameters that define the hindgut morphological trajectory. [ABSTRACT FROM AUTHOR]

Melatonin was discovered in plants in 1995, and so-called phytomelatonin. Its characteristic qualities as an antioxidant molecule and with amphiphilic nature make it an excellent candidate to use in plant biotechnological techniques. In plant physiology, melatonin has demonstrated with multiple studies great possibilities of application in crop improvement in aspects such as germination, rooting, plant growth, leaf-senescence, floration, fruit-set, parthenocarpy, fruit ripening and cut flower conservation, among others. In this work, we reviewed many studies on the possible role of melatonin to improve the different plant tissue culture goals, among them: the role of melatonin in callus culture induction and its effects in plant biomass production; the possible action of melatonin as an inductor or elicitor of different secondary metabolite generation in in vitro cultures; the interesting possibilities of melatonin as a protective agent (safener) against abiotic stressors present in in vitro cultures; the potential of melatonin in regulating plant organogenesis, modulating shooting/rooting responses; at last, the studies on the relevant role of melatonin in plant material cryopreservation and the improvement of cell transformation using A. tumefaciens have been discussed. [ABSTRACT FROM AUTHOR]

Background: Pineoblastoma (PB) represents a great challenge for clinical management due to lack of a specific therapeutic regimen. This study aims to identify relevant prognostic factors and potential treatment targets by mining public databases. Methods: The clinical characteristics and survival data of PB patients were obtained from the SEER database between 2000 and 2019 for Cox regression analysis and nomogram construction. The PB's DNA methylation data was acquired from two GEO datasets, GSE133801 and GSE215240, for bioinformatics analysis. Results: Of 383 PB patients, Cox univariate analysis unveiled that male gender (p = 0.017), age younger than 3 years at diagnosis (p < 0.001) and absence of radiotherapy (p < 0.001) correlated with poorer overall survival (OS), the subsequent multivariate analysis confirmed sex (p = 0.036), age (p < 0.001) and radiotherapy (p = 0.005) as independent prognostic factors for OS. A nomogram showed robust predictive accuracy as evidenced by AUC values (1-year OS: 0.774, 3-year OS: 0.692, 5-year OS: 0.643). DNA methylation analysis observed tumor hypomethylation, notably in promoter regions. Later, the GO enrichment analysis of aberrantly methylated genes indicated associations with embryonic organ development, cellular membrane composition and DNA-binding transcription, while KEGG analysis revealed enrichment in tumor-associated MAPK, calcium and RAS signaling pathways. Conclusions: The prognosis of PB is closely associated with sex, age and receipt of radiotherapy, potentially linked to aberrations in the RAS and MAPK signaling pathways. The individual case suggests that dasatinib and trametinib are potential targeted therapies for improving PB prognosis. [ABSTRACT FROM AUTHOR]

Currently available guidelines on the daily formula milk requirements of infants are based on the needs of infants with their growth pattern following the 50th percentile of the weight-for-age growth curve. Hence, current recommendations may not thoroughly detail the needs of infants across the broad spectrum of body weight percentiles. This study aimed to provide stratified recommendations for daily formula milk intake of fully formula-fed infants, across different weight-for-age categories from 0 to 4 months. At first, theoretical age- and gender-specific weight ranges were constructed for infants across five pre-defined weight-for-length percentile categories of the WHO growth standard. Thereafter, total daily energy requirements for each category were calculated and converted to daily formula milk needs. Subsequently, these stratified age- and weight-formula milk recommendations were compared to actual daily and relative formula milk of infants in these categories, retrieved from pooled individual infant formula milk intake data derived from 13 clinical intervention trials. A fitted regression model was used to evaluate differences in volume intakes across body weight categories as well as between theoretically derived and actual intake values. Median daily formula milk volume intake (ml/day) of infants differed significantly across the increasing weight-for-age categories at each time point, with significant differences between small and large infants. Interestingly, the relative daily formula milk volume intake (ml/kg/day) was higher for smaller infants compared to larger infants. The mean daily and relative formula milk intakes demonstrated the same pattern based on theoretical calculations as well as for the actual formula milk intake values retrieved from 13 pooled clinical intervention trials. Conclusions: Based on theoretical calculations and actual formula intake data, we conclude that larger infants require a significantly higher daily formula milk intake than smaller infants, and we postulate that infants could benefit from more tailored formula milk intake recommendations. What is Known: • Adequate energy intake during the infancy period is crucial to support optimal growth and organ development, with the potential for long-lasting health effects. • Current available guidelines on the daily formula milk requirements of infants are based on the needs of infants with their growth pattern following the 50th percentile of the weight-for-age growth curve. What is New: • Based on using both theoretical calculations and actual formula intake data, larger infants require a significantly higher daily formula milk intake than smaller infants. • Exclusive formula-fed infants could benefit from more tailored formula milk intake recommendations, in early infancy. [ABSTRACT FROM AUTHOR]

An intense black pigmented halotolerant yeast GUBPC1, was obtained from the solar salterns of Nerul, Goa-India. The isolate could tolerate 0 to 20 % NaCl. FE-SEM analysis revealed its polymorphic nature, exhibiting oval cells at higher salt concentrations and filamentous spindle like shapes at lower concentrations. Initially, the cells appear oval, yeast like in shape but gradually after 15 days of incubation, it becomes elongated and undergoes budding, exhibiting various budding patterns, from single polar bud to bipolar buds with annellidic ring, to lateral buds and eventually forming filamentous hyphae. The intracellular black pigment was identified as melanin based on ultraviolet–visible spectroscopy analysis. The molecular identification of the culture showed closest similarity with Hortaea werneckii. Plant polymer-degrading enzymatic activities such as cellulase, laccase, chitinase, xylanase, pectinase, amylase and protease were exhibited by the isolate GUBPC1. To further understand and explore its biotechnological potential, we performed whole-genome sequencing and analysis. The obtained genome size was 26.93 Mb with 686 contigs and a GC content of 53.24 %. We identified 9383 protein-coding genes, and their functional annotation revealed the presence of 435 CAZyme genes and 16 functional genes involved in secondary metabolite synthesis, thus providing a basis for its potential value in various biotechnological applications. [ABSTRACT FROM AUTHOR]

The ectoderm is the outermost of the three germ layers of the early embryo that arise during gastrulation. Once the germ layers are established, the complex interplay of cellular proliferation, differentiation, and migration results in organogenesis. The ectoderm is the progenitor of both the surface ectoderm and the neural ectoderm. Notably, the surface ectoderm develops into the epidermis and its associated appendages, nails, external exocrine glands, olfactory epithelium, and the anterior pituitary. Specification, development, and homeostasis of these organs demand a tightly orchestrated gene expression program that is often dictated by epigenetic regulation. In this review, we discuss the recent discoveries that have highlighted the importance of chromatin regulatory mechanisms mediated by transcription factors, histone and DNA modifications that aid in the development of surface ectodermal organs and maintain their homeostasis post-development. [Display omitted] • Chromatin regulatory mechanisms are inherently important for surface ectoderm organ development and homeostasis. • These mechanisms are mediated by transcription factors, histone, and DNA modifiers. • Recent studies have highlighted how signaling effectors, TFs, and chromatin modifiers converge to regulate key processes essential for tissue identity. [ABSTRACT FROM AUTHOR]

Fetal and neonatal development is a critical period for the establishment of the future metabolic health and disease risk of an individual. Both maternal undernutrition and overnutrition can result in abnormal fetal organ development resulting in inappropriate birth size, child and adult obesity, and increased risk of Type 2 diabetes and cardiovascular diseases. Inappropriate adaptive changes to the maternal pancreas, placental function, and the development of the fetal pancreas in response to nutritional stress during pregnancy are major contributors to a risk trajectory in the offspring. This interconnected maternal-placental-fetal metabolic axis is driven by endocrine signals in response to the availability of nutritional metabolites and can result in cellular stress and premature aging in fetal tissues and the inappropriate expression of key genes involved in metabolic control as a result of long-lasting epigenetic changes. Such changes result is insufficient pancreatic beta-cellmass and function, reduced insulin sensitivity in target tissues such as liver and white adipose and altered development of hypothalamic satiety centres and in basal glucocorticoid levels. Whilst interventions in the obese mother such as dieting and increased exercise, or treatment with insulin or metformin in mothers who develop gestational diabetes, can improve metabolic control and reduce the risk of a large-for-gestational age infant, their effectiveness in changing the adverse metabolic trajectory in the child is as yet unclear. [ABSTRACT FROM AUTHOR]

Plants have evolved a remarkable ability to sense and respond to changes in photoperiod, allowing adjustments to their growth and development based on seasonal and environmental cues. The floral transition is a pivotal stage in plant growth and development, signifying a shift from vegetative to reproductive growth. CONSTANS (CO), a central photoperiodic response factor conserved in various plants, mediates day‐length signals to control the floral transition, although its mechanisms of action vary among plants with different day‐length requirements. In addition, recent studies have uncovered roles for CO in organ development and stress responses. These pleiotropic roles in model plants and crops make CO a potentially fruitful target for molecular breeding aimed at modifying crop agronomic traits. This review systematically traces research on CO, from its discovery and functional studies to the exploration of its regulatory mechanisms and newly discovered functions, providing important insight into the roles of CO and laying a foundation for future research. [ABSTRACT FROM AUTHOR]

Chondrocyte columns, which are a hallmark of growth plate architecture, play a central role in bone elongation. Columns are formed by clonal expansion following rotation of the division plane, resulting in a stack of cells oriented parallel to the growth direction. In this work, we analyzed hundreds of Confetti multicolor clones in growth plates of mouse embryos using a pipeline comprising 3D imaging and algorithms for morphometric analysis. Surprisingly, analysis of the elevation angles between neighboring pairs of cells revealed that most cells did not display the typical stacking pattern associated with column formation, implying incomplete rotation of the division plane. Morphological analysis revealed that although embryonic clones were elongated, they formed clusters oriented perpendicular to the growth direction. Analysis of growth plates of postnatal mice revealed both complex columns, composed of ordered and disordered cell stacks, and small, disorganized clusters located in the outer edges. Finally, correlation between the temporal dynamics of the ratios between clusters and columns and between bone elongation and expansion suggests that clusters may promote expansion, whereas columns support elongation. Overall, our findings support the idea that modulations of division plane rotation of proliferating chondrocytes determines the formation of either clusters or columns, a multifunctional design that regulates morphogenesis throughout pre-and postnatal bone growth. Broadly, this work provides a new understanding of the cellular mechanisms underlying growth plate activity and bone elongation during development. [ABSTRACT FROM AUTHOR]

Tissue interfaces are essential for development and their disruption often leads to diseases such as tumor invasion. Here, we combine experiments, theoretical modeling, and numerical simulations to quantify the morphodynamics of interface in a biphasic system composed of Madin Darby canine kidney (MDCK) and mouse myoblast (C2C12) cells. We show that cellular activity regulates the interface morphodynamics and drives wave propagation along the interface. Based on the dispersion relationship, we identify that the wave dynamics results from the activity-mediated instability of the interface and coherent flow. It is found that the topological defects accumulate around and destabilize the interface and +1/2 topological defects are more likely to aggregate in MDCK cell clusters. A biphasic active nematic theory is employed to reproduce our experimental observations and decipher the underlying mechanisms. These findings provide physical insights into the interfacial evolution that could be implicated in tissue morphogenesis and tumor invasion. Interfaces are ubiquitous in living systems and play pivotal roles in physiological and pathological processes. The authors combine experiments and numerical simulations to investigate morphodynamics of the interface between dissimilar cell aggregations. [ABSTRACT FROM AUTHOR]

Recent advancements in 3D tissue engineering and organ‐on‐a‐chip systems have revolutionized biomedical research by providing sophisticated platforms that mimic complex physiological environments. This review explores various techniques in 3D printing, including bioprinting materials, laser‐induced forward transfer, ink‐jet systems, and microextrusion methods, highlighting their roles in fabricating intricate tissue constructs. Physical and biochemical characterization methods for assessing these engineered tissues on microchips are discussed in detail, emphasizing their importance in accurately replicating physiological conditions. The review further delves into the development of multiple organ and single organ‐on‐a‐chip systems. It covers two‐organ, three‐organ, and four‐organ platforms, as well as individual systems such as pancreas‐on‐a‐chip, kidney‐on‐a‐chip, liver‐on‐a‐chip, lung‐on‐a‐chip, blood–brain barrier‐on‐a‐chip, heart‐on‐a‐chip, breast cancer‐on‐a‐chip, gut‐on‐a‐chip, and blood vessels‐on‐a‐chip. Each section addresses the unique challenges and advancements associated with these models, providing insights into their potential applications in drug testing, disease modelling, and personalized medicine. In conclusion, the article discusses current challenges and offers perspectives on future directions in 3D tissue engineering and organ‐on‐a‐chip technology, highlighting the transformative impact of these systems on biomedical research and healthcare. [ABSTRACT FROM AUTHOR]

As the most advanced non‐viral delivery system, lipid nanoparticles (LNPs) were approved by the FDA, propelling the advancements of gene therapy. However, their clinical applications are hampered by the potential immunogenicity of the lipid components that trigger immune‐related adverse events, like inflammation and allergy. Herein, we formulate various dLNPs with diminished immunogenicity by incorporating dexamethasone (Dex) into liver‐, spleen‐, and lung‐targeting LNPs formulations that exhibit excellent abilities to target specific organs and deliver various types of RNA, such as mRNA and siRNA. In vivo investigations demonstrate unparalleled advantages in safety as compared to conventional LNPs, showing promising potential in the development of RNA therapeutics. Intriguingly, the encapsulation of runt‐related transcription factor‐1 siRNA (siRUNX1) into lung‐targeting dLNPs (dLNPs@siRUNX1) demonstrates remarkable advantages in the treatment of pulmonary fibrosis through the synergy of gene therapy and drug therapy. This research establishes secure and universal platforms for the precise delivery of nucleic acid therapeutics, showcasing promising clinical applications in gene therapy. [ABSTRACT FROM AUTHOR]

Fungal pathogens must exhibit strong nutritional plasticity, effectively sensing and utilizing diverse nutrients to support virulence. How the signals generated by nutritional sensing are efficiently translated to the morphogenetic machinery for optimal growth and support of virulence remains incompletely understood. Here, we show that the conserved morphogenesis-related kinase, CotA, imparts isoform-specific control over Aspergillus fumigatus invasive growth in host-mimicking environments and during infection. CotA-mediated invasive growth is responsive to exogenous carbon source quality, with only preferred carbon sources supporting hyphal morphogenesis in a mutant lacking one of two identified protein isoforms. Strikingly, we find that the CotA protein does not regulate, nor is cotA gene expression regulated by, the carbon catabolite repression system. Instead, we show that CotA partially mediates invasive growth in specific carbon sources and virulence through the conserved downstream effector and translational repressor, SsdA. Therefore, A. fumigatus CotA accomplishes its conserved morphogenetic functions to drive pathogenic growth by translating host-relevant carbon source quality signals into morphogenetic outputs for efficient tissue invasive growth. Here, Martin-Vicente et al. show that the Aspergillus fumigatus protein kinase, CotA, controls invasive growth in an isoform dependent manner in response to carbon source diversity, partially mediated by the downstream effector, SsdA. [ABSTRACT FROM AUTHOR]

The development of fetal organs can be impacted by systemic changes in maternal circulation, with the placenta playing a pivotal role in maintaining pregnancy homeostasis and nutrient exchange. In clinical obstetrics, oxytocin (OXT) is commonly used to induce labor. To explore the potential role of OXT in the placental homeostasis of OXT, we compared OXT levels in neonatal cord blood among neonates (23–42 weeks gestation) whose mothers either received prenatal OXT or experienced spontaneous labor. Our previous research revealed that the oxytocin receptor (OXTR), essential in forming the blood–retina barrier, is expressed in the retinal pigment epithelium (RPE). We hypothesized that perinatal OXT administration might influence the development of the neural retina and its vasculature, offering therapeutic potential for retinal diseases such as retinopathy of prematurity (ROP). Plasma OXT levels were measured using a commercial OXT ELISA kit. Human fetal RPE (hfRPE) cells treated with OXT (10 µM) were assessed for gene expression via RNA sequencing, revealing 14 downregulated and 32 upregulated genes. To validate these differentially expressed genes (DEGs), hfRPE cells were exposed to OXT (0.01, 0.1, 1, or 10 µM) for 12 h, followed by RNA analysis via real-time PCR. Functional, enrichment, and network analyses (Gene Ontology term, FunRich, Cytoscape) were performed to predict the affected pathways. This translational study suggests that OXT likely crosses the placenta, altering fetal OXT concentrations. RNA sequencing identified 46 DEGs involved in vital metabolic and signaling pathways and critical cellular components. Our results indicate that the perinatal administration of OXT may affect neural retina and retinal vessel development, making OXT a potential therapeutic option for developmental eye diseases, including ROP. [ABSTRACT FROM AUTHOR]

PKD2 was first identified as the pathogenic protein for autosomal dominant polycystic kidney disease (ADPKD) and is widely recognized as an ion channel. Subsequent studies have shown that PKD2 is widely expressed in various animal tissues and plays a crucial role in tissue and organ development. Additionally, PKD2 is conserved from single-celled organisms to vertebrates. Here, we provide an overview of recent advances in the function of PKD2 in key model animals, focusing on the establishment of left–right organ asymmetry, renal homeostasis, cardiovascular development, and signal transduction in reproduction and mating. We specifically focus on the roles of PKD2 in development and highlight future prospects for PKD2 research. [ABSTRACT FROM AUTHOR]

Mastitis is a common disease worldwide that affects the development of the dairy industry due to its high incidence and complex etiology. Precise regulation of cell death and survival plays a critical role in maintaining internal homeostasis, organ development, and immune function in organisms, and regulatory abnormalities are a common mechanism of various pathological changes. Recent research has shown that regulated cell death (RCD) plays a crucial role in mastitis. The development of drugs to treat cell death and survival abnormalities that can be widely used in mastitis treatment has important clinical significance. This paper will review the molecular mechanisms of apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis and their regulatory roles in mastitis to provide a new perspective for the targeted treatment of mastitis. [ABSTRACT FROM AUTHOR]

SUMMARY: De novo shoot apical meristem (SAM) organogenesis during regeneration in tissue culture has been investigated for several decades, but the precise mechanisms governing early‐stage cell fate specification remain elusive. In contrast to SAM establishment during embryogenesis, in vitro SAM formation occurs without positional cues and is characterized by autonomous initiation of cellular patterning. Here, we report on the initial stages of SAM organogenesis and on the molecular mechanisms that orchestrate gene patterning to establish SAM homeostasis. We found that SAM organogenesis in tobacco calli starts with protuberance formation followed by the formation of an intact L1 layer covering the nascent protuberance. We also exposed a complex interdependent relationship between L1 and WUS expression and revealed that any disruption in this interplay compromises shoot formation. Silencing WUS in nascent protuberances prevented L1 formation and caused the disorganization of the outer cell layers exhibiting both anticlinal and periclinal divisions, suggesting WUS plays a critical role in the proper establishment and organization of L1 during SAM organogenesis. We further discovered that silencing TONNEAU1 prevents the exclusive occurrence of anticlinal divisions in the outermost layer of the protuberances and suppresses the acquisition of L1 cellular identity and L1 formation, ultimately impeding SAM formation and regeneration. This study provides a novel molecular framework for the characterization of a WUS/L1 interplay that mediates SAM formation during regeneration. Significance Statement: This study highlights the importance of establishing an intact L1 cell layer to promote de novo shoot apical meristem (SAM) organogenesis in vitro. It identifies a complex interdependence between WUS and ML1 expression in directing anticlinal divisions for L1 formation, which in turn initiates gene expression patterning in the SAM and its formation. Disrupting this WUS/L1 interplay impairs SAM regeneration, underscoring its central role. [ABSTRACT FROM AUTHOR]

SUMMARY: Petal size is determined by cell division and cell expansion. Jasmonic acid (JA) has been reported to be associated with floral development, but its regulatory mechanism affecting petal size remains unclear. Here, we reveal the vital role of JA in regulating petal size and the duration of the cell division phase via the key JA signaling component RhMYC2. We show that RhMYC2 expression is induced by exogenous treatment with methyl jasmonate and decreases from stage 0 to stage 2 of flower organ development, corresponding to the cell division phase. Furthermore, silencing RhMYC2 shortened the duration of the cell division phase, ultimately accelerating flowering opening and resulting in smaller petals. In addition, we determined that RhMYC2 controls cytokinin homeostasis in rose petals by directly activating the expression of the cytokinin biosynthetic gene LONELY GUY3 (RhLOG3) and repressing that of the cytokinin catabolism gene CYTOKININ OXIDASE/DEHYDROGENASE6 (RhCKX6). Silencing RhLOG3 shortened the duration of the cell division period and produced smaller petals, similar to RhMYC2 silencing. Our results underscore the synergistic effects of JA and cytokinin in regulating floral development, especially for petal size in roses. [ABSTRACT FROM AUTHOR]

Background: Cryptolaemus montrouzieri (Coccinellidae) is widely utilized as biological control agents in modern agriculture. A comprehensive understanding of its food preference can help guide mass rearing and safety management during field application of pest control. Although some studies have paid attentions to the impacts of prey shift on C. montrouzieri, little is known regarding the role of post-transcriptional regulations in its acclimation to unnatural preys. Results: We performed a genome-wide investigation on alternative splicing dynamics in C. montrouzieri in response to the predation transition from natural prey to unnatural ones. When feeding on undesired diets, 402–764 genes were differentially alternative spliced in C. montrouzieri. It is noteworthy that the majority of these genes (> 87%) were not differentially expressed, and these differentially spliced genes regulated distinct biological processes from differentially expressed genes, such as organ development and morphogenesis, locomotory behavior, and homeostasis processes. These suggested the functionally nonredendant role of alternative splicing in modulating physiological and metabolic responses of C. montrouzieri to the shift to undesired preys. In addition, the individuals feeding on aphids were subject to a lower level of changes in splicing than other alternative diets, which might be because of the similar chemical and microbial compositions. Our study further suggested a putative coupling of alternative splicing and nonsense-mediated decay (AS-NMD), which may play an important role in fine-tuning the protein repertoire of C. montrouzieri, and promoting its acclimation to predation changes. Conclusion: These findings highlight the key role of alternative splicing in modulating the acclimation of ladybirds to prey shift and provide new genetic clues for the future application of ladybirds in biocontrol. [ABSTRACT FROM AUTHOR]

A tight regulation of morphogen production is key for morphogen gradient formation and thereby for reproducible and organised organ development. Although many genetic interactions involved in the establishment of morphogen production domains are known, the biophysical mechanisms of morphogen source formation are poorly understood. Here we addressed this by focusing on the morphogen Sonic hedgehog (Shh) in the vertebrate neural tube. Shh is produced by the adjacently located notochord and by the floor plate of the neural tube. Using a data-constrained computational screen, we identified different possible mechanisms by which floor plate formation can occur, only one of which is consistent with experimental data. In this mechanism, the floor plate is established rapidly in response to Shh from the notochord and the dynamics of regulatory interactions within the neural tube. In this process, uniform activators and Shh-dependent repressors are key for establishing the floor plate size. Subsequently, the floor plate becomes insensitive to Shh and increases in size due to tissue growth, leading to scaling of the floor plate with neural tube size. In turn, this results in scaling of the Shh amplitude with tissue growth. Thus, this mechanism ensures a separation of time scales in floor plate formation, so that the floor plate domain becomes growth-dependent after an initial rapid establishment phase. Our study raises the possibility that the time scale separation between specification and growth might be a common strategy for scaling the morphogen gradient amplitude in growing organs. The model that we developed provides a new opportunity for quantitative studies of morphogen source formation in growing tissues. Author summary: As organs grow during development, molecules called morphogens instruct cells to adopt specific fates at the right place and time. Morphogens are produced in specialized source regions and spread through organs, forming gradients of concentration. How morphogen source regions form in growing organs and contribute to the establishment of morphogen gradients is poorly understood. In this study, we combine theory and experiments to investigate the formation of a key morphogen source in the developing mouse spinal cord called floor plate. Uncommitted spinal cord cells adopt floor plate identity in response to the morphogen Sonic hedgehog (Shh), which is produced by the adjacent notochord and by the floor plate cells themselves. Over time, the floor plate expands, producing more Shh. We found that in theory, the floor plate could expand by distinct mechanisms. In one scenario, Shh produced by the floor plate itself is used to convert more cells into floor plate. Alternatively, once a few cells are initially specified, the floor plate expands passively by tissue growth. Our experimental and theoretical analysis indicate that the latter scenario is the one that is relevant to the biological system. Similar temporal decoupling of specification and growth might occur in other growing organs. [ABSTRACT FROM AUTHOR]

The terminal cells of the Drosophila larval tracheal system are perhaps the simplest delivery networks, providing an analogue for mammalian vascular growth and function in a system with many fewer components. These cells are a prime example of single-cell morphogenesis, branching significantly over time to adapt to the needs of the growing tissue they supply. While the genetic mechanisms governing local branching decisions have been studied extensively, an understanding of the emergence of a global network architecture is still lacking. Mapping out the full network architecture of populations of terminal cells at different developmental times of Drosophila larvae, we find that cell growth follows scaling laws relating the total edge length, supply area, and branch density. Using time-lapse imaging of individual terminal cells, we identify that the cells grow in three ways: by extending branches, by the side budding of new branches, and by internally growing existing branches. A generative model based on these modes of growth recapitulates statistical properties of the terminal cell network data. These results suggest that the scaling laws arise from the coupled contributions of branching and internal growth. This study establishes the terminal cell as a uniquely tractable model system for further studies of transportation and distribution networks. [ABSTRACT FROM AUTHOR]

Perionyx excavatus, an indigenous earthworm possesses exceptional regeneration capacity. Their anterior regeneration features wound closure, regeneration induction and morphogenesis of damaged organs. This study involved a complete analysis of their transcriptomic dataset, with an emphasis on identifying the genes expressed during regeneration and predicting their implications in the process of regeneration and morphogenesis. Control (first ten segments) and test (5th day blastema) RNA samples of biological replicates were isolated and sequenced on NovaSeq. 6000 using PE150 read length. An average of 98.64% of high-quality data was retained with assembly showing better continuity with the average transcript length with 823 bp and N50 value of 1,858 bp. This is the first report on the comparative transcriptome of P. excavatus during anterior regeneration and this study will shed light on the complexity of annelid regeneration. [ABSTRACT FROM AUTHOR]

The cortical cytoskeleton of subpellicular microtubules (SPMTs) supports the Plasmodium ookinete morphogenesis during mosquito transmission of malaria. SPMTs are hypothesized to function as the cytoskeletal tracks in motor-driven cargo transport for apical organelle and structure assembly in ookinetes. However, the SPMT-based transport motor has not been identified in the Plasmodium. The cytoplasmic dynein is the motor moving towards the minus end of microtubules (MTs) and likely be responsible for cargo transport to the apical part in ookinetes. Here we screen 7 putative dynein heavy chain (DHC) proteins in the P. yoelii and identify DHC3 showing peripheral localization in ookinetes. DHC3 is localized at SPMTs throughout ookinete morphogenesis. We also identify five other dynein subunits localizing at SPMTs. DHC3 disruption impairs ookinete development, shape, and gliding, leading to failure in mosquito infection of Plasmodium. The DHC3-deficient ookinetes display defective formation or localization of apical organelles and structures. Rab11A and Rab11B interact with DHC3 at SPMTs in a DHC3-dependent manner, likely functioning as the receptors for the cargoes driven by SPMT-dynein. Disturbing Rab11A or Rab11B phenocopies DHC3 deficiency in ookinete morphogenesis. Our study reveals an SPMT-based dynein motor driving the transport of Rab11A- and Rab11B-labeled cargoes in the ookinete morphogenesis of Plasmodium. Liu et al. identify a subpellicular microtubule-based dynein motor in ookinetes of Plasmodium. This motor transports the cargos for apical organelle and structure assembly in ookinetes. Dynein-deficient parasites fail ookinete morphogenesis and mosquito transmission of Plasmodium. [ABSTRACT FROM AUTHOR]

Talaromyces marneffei is a thermally dimorphic fungus that can cause life-threatening systemic mycoses, particularly in immunocompromised individuals. Fungal homeobox transcription factors control various developmental processes, including the regulation of sexual reproduction, morphology, metabolism, and virulence. However, the function of homeobox proteins in T. marneffei has not been fully explored. Here, we searched the T. marneffei genome for the total homeobox transcription factors and predicted their biological relevance by performing gene expression analysis in different cell types, including conidia, mycelia, yeasts, and during phase transition. RfeB is selected for further computational analysis since (i) its transcripts were differentially expressed in different phases of T. marneffei, and (ii) this protein contains the highly conserved protein-protein interaction region (IR), which could be important for pathobiology and have therapeutic application. To assess the structure-function of the IR region, in silico alanine substitutions were performed at three-conserved IR residues (Asp276, Glu279, and Gln282) of RfeB, generating a triple RfeB mutated protein. Using 3D modeling and molecular dynamics simulations, we compared the protein complex formation of wild-type and mutated RfeB proteins with the putative partner candidate TmSwi5. Our results demonstrated that the mutated RfeB protein exhibited increased free binding energy, elevated protein compactness, and a reduced number of atomic contacts, suggesting disrupted protein stability and interaction. Notably, our model revealed that the IR residues primarily stabilized the RfeB binding sites located in the central region (CR). This computational approach for protein mutagenesis could provide a foundation for future experimental studies on the functional characterization of RfeB and other homeodomain-containing proteins in T. marneffei. [ABSTRACT FROM AUTHOR]

Organogenesis, the phase of embryonic development that starts at the end of gastrulation and continues until birth is the critical process for understanding cellular differentiation and maturation during organ development. The rapid development of single‐cell transcriptomics technology has led to many novel discoveries in understanding organogenesis while also accumulating a large quantity of data. To fill this gap, OrganogenesisDB (http://organogenesisdb.com/), which is a comprehensive database dedicated to exploring cell‐type identification and gene expression dynamics during organogenesis, is developed. OrganogenesisDB contains single‐cell RNA sequencing data for more than 1.4 million cells from 49 published datasets spanning various developmental stages. Additionally, 3324 cell markers are manually curated for 1120 cell types across 9 human organs and 4 mouse organs. OrganogenesisDB leverages various analysis tools to assist users in annotating and understanding cell types at different developmental stages and helps in mining and presenting genes that exhibit specific patterns and play key regulatory roles during cell maturation and differentiation. This work provides a critical resource and useful tool for deciphering cell lineage determination and uncovering the mechanisms underlying organogenesis. [ABSTRACT FROM AUTHOR]

Themorphology of cells in vivo can arise from a variety of mechanisms. In the Caenorhabditis elegans hermaphrodite gonad, the distal tip cell (DTC) elaborates into a complex plexus over a relatively short developmental time period, but the mechanisms underlying this change in cell morphology are not well defined. We correlated the time of DTC elaboration with the L4-to-adult molt, but ruled out a relevant heterochronic pathway as a cue for DTCelaboration. Instead, we found that the timing of gonad elongation and aspects of underlying germline flux influence DTC elaboration. We propose a 'hitch and tow' aspect of organ-level dynamics that contributes to cellular morphogenesis, whereby germline flux drags the flexible DTC cell cortex away from its stationary cell body. More broadly, we speculate that this mechanism may contribute to cell shape changes in other contexts with implications for development and disease. [ABSTRACT FROM AUTHOR]

Organ sizes and shapes are highly reproducible, or robust, within a species and individuals. Arabidopsis thaliana sepals, which are the leaf-like organs that enclose flower buds, have consistent size and shape, indicating robust development. Cell growth is locally heterogeneous due to intrinsic and extrinsic noise. To achieve robust organ shape, fluctuations in cell growth must average to an even growth rate, which requires that fluctuations are uncorrelated or anticorrelated in time and space. Here, we live image and quantify the development of sepals with an increased or decreased number of cell divisions (lgo mutant and LGO overexpression, respectively), a mutant with altered cell growth variability (ftsh4), and double mutants combining these. Changes in the number of cell divisions do not change the overall growth pattern. By contrast, in ftsh4 mutants, cell growth accumulates in patches of over- and undergrowth owing to correlations that impair averaging, resulting in increased organ shape variability. Thus, we demonstrate in vivo that the number of cell divisions does not affect averaging of cell growth, preserving robust organ morphogenesis, whereas correlated growth fluctuations impair averaging. [ABSTRACT FROM AUTHOR]

Pharyngeal endoderm cells undergo convergence and extension (C&E), which is essential for endoderm pouch formation and craniofacial development. Our previous work implicates Gα13/RhoAmediated signaling in regulating this process, but the underlying mechanisms remain unclear. Here, we have used endoderm-specific transgenic and Gα13mutant zebrafish to demonstrate that Gα13 plays a crucial role in pharyngeal endodermC&E by regulating RhoA activation and E-cadherin expression. We showed that during C&E, endodermal cells gradually establish stable cell-cell contacts, acquire apical-basal polarity and undergo actomyosin-driven apical constriction, which are processes that require Gα13. Additionally, we found that Gα13-deficient embryos exhibit reduced E-cadherin expression, partially contributing to endoderm C&E defects. Notably, interfering with RhoA function disrupts spatial actomyosin activation without affecting E-cadherin expression. Collectively, our findings identify crucial cellular processes for pharyngeal endoderm C&E and reveal that Gα13 controls this through two independent pathways - modulating RhoA activation and regulating E-cadherin expression - thus unveiling intricate mechanisms governing pharyngeal endoderm morphogenesis. [ABSTRACT FROM AUTHOR]

Carotenoid cleavage oxygenases (CCOs) cleave carotenoid molecules to produce bioactive products that influence the synthesis of hormones such as abscisic acid (ABA) and strigolactones (SL), which regulate plant growth, development, and stress adaptation. Here, to explore the molecular characteristics of all members of the OsCCO family in rice, fourteen OsCCO family genes were identified in the genome-wide study. The results revealed that the OsCCO family included one OsNCED and four OsCCD subfamilies. The OsCCO family was phylogenetically close to members of the maize ZmCCO family and the Sorghum SbCCO family. A collinearity relationship was observed between OsNCED3 and OsNCED5 in rice, as well as OsCCD7 and OsNCED5 between rice and Arabidopsis, Sorghum, and maize. OsCCD4a and OsCCD7 were the key members in the protein interaction network of the OsCCO family, which was involved in the catabolic processes of carotenoids and terpenoid compounds. miRNAs targeting OsCCO family members were mostly involved in the abiotic stress response, and RNA-seq data further confirmed the molecular properties of OsCCO family genes in response to abiotic stress and hormone induction. qRT-PCR analysis showed the differential expression patterns of OsCCO members across various rice organs. Notably, OsCCD1 showed relatively high expression levels in all organs except for ripening seeds and endosperm. OsNCED2a, OsNCED3, OsCCD1, OsCCD4a, OsCCD7, OsCCD8a, and OsCCD8e were potentially involved in plant growth and differentiation. Meanwhile, OsNCED2a, OsNCED2b, OsNCED5, OsCCD8b, and OsCCD8d were associated with reproductive organ development, flowering, and seed formation. OsNCED3, OsCCD4b, OsCCD4c, OsCCD8b, and OsCCD8c were related to assimilate transport and seed maturation. These findings provide a theoretical basis for further functional analysis of the OsCCO family. [ABSTRACT FROM AUTHOR]

The initially homogeneous epithelium of the early Drosophila embryo differentiates into regional subpopulations with different behaviours and physical properties that are needed for morphogenesis. The factors at top of the genetic hierarchy that control these behaviours are known, but many of their targets are not. To understand how proteins work together to mediate differential cellular activities, we studied in an unbiased manner the proteomes and phosphoproteomes of the three main cell populations along the dorso- ventral axis during gastrulation using mutant embryos that represent the different populations. We detected 6111 protein groups and 6259 phosphosites of which 3398 and 3433 were differentially regulated, respectively. The changes in phosphosite abundance did not correlate with changes in host protein abundance, showing phosphorylation to be a regulatory step during gastrulation. Hierarchical clustering of protein groups and phosphosites identified clusters that contain known fate determinants such as Doc1, Sog, Snail, and Twist. The recovery of the appropriate known marker proteins in each of the different mutants we used validated the approach, but also revealed that two mutations that both interfere with the dorsal fate pathway, Toll10B and serpin27aex do this in very different manners. Diffused network analyses within each cluster point to microtubule components as one of the main groups of regulated proteins. Functional studies on the role of microtubules provide the proof of principle that microtubules have different functions in different domains along the DV axis of the embryo. [ABSTRACT FROM AUTHOR]

Elucidating the molecular dependencies behind the cancer-type specificity of driver mutations may reveal new therapeutic opportunities. We hypothesized that developmental programs would impact the transduction of oncogenic signaling activated by a driver mutation and shape its cancer-type specificity. Therefore, we designed a computational analysis framework by combining single-cell gene expression profiles during fetal organ development, latent factor discovery, and information theory-based differential network analysis to systematically identify transcription factors that selectively respond to driver mutations under the influence of organ-specific developmental programs. After applying this approach to VHL mutations, which are highly specific to clear cell renal cell carcinoma (ccRCC), we revealed important regulators downstream of VHL mutations in ccRCC and used their activities to cluster patients with ccRCC into three subtypes. This classification revealed a more significant difference in prognosis than the previous mRNA profile-based method and was validated in an independent cohort. Moreover, we found that EP300, a key epigenetic factor maintaining the regulatory network of the subtype with the worst prognosis, can be targeted by a small inhibitor, suggesting a potential treatment option for a subset of patients with ccRCC. This work demonstrated an intimate relationship between organ development and oncogenesis from the perspective of systems biology, and the method can be generalized to study the influence of other biological processes on cancer driver mutations. [ABSTRACT FROM AUTHOR]

Based on recent single-cell transcriptomics and lineage tracing, sst1.1 + cell transdifferentiation and krt4 + cell differentiation have recently been recognized as the major sources of regeneration of insulin-producing cells in zebrafish. Large-scale in vivo small molecule screening has been successfully applied in zebrafish for the unbiased identification of chemicals promoting β-cell regeneration and glucose control. Multiple compounds have been validated to also promote β-cell proliferation, differentiation, or function in mammalian systems. Live imaging in zebrafish enables visualization of complex biological processes at the single-cell resolution in vivo (e.g., calcium flux in β-cells) as well as innervation and immune cell behaviors in the islet. Role of genes identified in human genetic data [e.g. genome-wide association studies (GWAS) and single-cell sequencing data] can be efficiently elucidated in zebrafish. The zebrafish has become an outstanding model for studying organ development and tissue regeneration, which is prominently leveraged for studies of pancreatic development, insulin-producing β-cells, and diabetes. Although studied for more than two decades, many aspects remain elusive and it has only recently been possible to investigate these due to technical advances in transcriptomics, chemical-genetics, genome editing, drug screening, and in vivo imaging. Here, we review recent findings on zebrafish pancreas development, β-cell regeneration, and how zebrafish can be used to provide novel insights into gene functions, disease mechanisms, and therapeutic targets in diabetes, inspiring further use of zebrafish for the development of novel therapies for diabetes. [ABSTRACT FROM AUTHOR]

Purpose: In patients with acute necrotizing pancreatitis (ANP), the site, size, and the number of acute necrotic collections (ANC) may determine the outcome of patients. The current study aimed to correlate the nature of ANC with the adverse outcomes in ANP patients. Methods: This was a single-center, prospective study (August 2019-August 2022) recruiting patients with ANP, correlating the site, size, and number of ANC with the length of hospital stay, intensive care unit (ICU) stays, development of organ failure and infection, need for intervention, and mortality. Results: A total of 114 patients (mean age: 37.3 ± 13.4 years, 85.1% males) with ANP were included in the study. The number and maximum diameter of collections significantly correlated with the length of the hospital and ICU stay and the need for intervention. Taking a cut-off size of 8 cm, the sensitivity and specificity for predicting the need for intervention were 82.7% and 74.2%, respectively. ANCs located in the perinephric, paracolic, subhepatic, and epigastric regions had a significant correlation with two or more adverse outcomes. Additional points were added to the modified CT severity index (mCTSI) based on the present study's findings. The new score had significantly higher AUROC than mCTSI for predicting infection, need for intervention, ICU stay > 1 week, and mortality. Conclusion: The site, size, and number of EPNs have a significant correlation with adverse clinical outcomes in patients with ANP. The inclusion of these parameters, along with present scoring systems, will help further improve the prognostication of patients. [ABSTRACT FROM AUTHOR]

Recent years have seen a surge of interest in the potential use of 3D bioprinting technologies for the development of tissues and organs with the aim of restoring, maintaining, or improving tissue function. Bioprinting studies frequently claim to be close to clinical translation, yet only report research at very early stages of the translational pipeline. Technology readiness levels (TRLs) are a systematic metric used to objectively assess the maturity of a technology, allowing researchers and stakeholders to understand how far a particular project has progressed from the conceptual stage towards clinical application. Bioprinting is an annex of additive manufacturing, as defined by the American Society for Testing and Materials (ASTM) and International Organization for Standardization (ISO) standards, characterized by the automated deposition of living cells and biomaterials. The tissue engineering and regenerative medicine (TE&RM) community has eagerly adopted bioprinting, while review articles regularly herald its imminent translation to the clinic as functional tissues and organs. Here we argue that such proclamations are premature and counterproductive; they place emphasis on technological progress while typically ignoring the critical stage-gates that must be passed through to bring a technology to market. We suggest the technology readiness level (TRL) scale as a valuable metric for gauging the relative maturity of a bioprinting technology in relation to how it has passed a series of key milestones. We suggest guidelines for a bioprinting-oriented scale and use this to discuss the state-of-the-art of bioprinting in regenerative medicine (BRM) today. Finally, we make corresponding recommendations for improvements to BRM research that would support its progression to clinical translation. [ABSTRACT FROM AUTHOR]

The success with which minority teachers cope with socio-cultural integration indicates their transformative agency. However, teachers' ideational projects, which are converted into a set of established practices, are tightly connected with their ideologies. In this case what they transform is not a matter of integration for them but is irrevocably intertwined with protecting their own culture. Applying a symbolic interactionist methodological lens and Archer's 'social morphogenesis' explanatory framework, in this qualitative research I aim to examine the unique educational context of Estonia. Schools with Russian as the language of instruction co-exist with schools where instruction is in the national language. The paper explores the mechanisms that stand behind the social agency of minority teachers and why their practices are considered 'morphostatic' for the whole education system. The paper concludes that these teachers' agency is culturally mediated and their strategies are reflexive and morphogenetic in nature, even though they don't lead to integration. [ABSTRACT FROM AUTHOR]

Background: The ductus arteriosus (DA) is critical in maintaining postnatal circulation in neonates with obstructed systemic circulation (OSC) and pulmonary circulation (OPC). We hypothesized that the size of the DA and aortic isthmus (AoI) undergoes adaptive growth in utero to counteract the hemodynamic challenges in these congenital heart diseases (CHD). Methods: Postnatal echocardiograms of neonates diagnosed prenatally with ductal-dependent CHD who were started on prostaglandins within 24 h of birth were reviewed. We assessed the cross-sectional area of the aortic valve opening, pulmonary valve opening, AoI, and DA by calculating (diameter)2/body surface area. Neonates were classified into OSC or OPC then subgrouped depending upon the patency of semilunar valves: OSC with and without aortic atresia (OSC-AA and OSC-nAA, respectively) and OPC with and without pulmonary atresia (OPC-PA and OPC-nPA, respectively). Results: Ninety-four cases were studied. The DA in OSC was significantly larger than OPC, and the DA in OSC-AA was significantly larger than OSC-nAA. The size of the AoI was significantly larger in OPC than OSC and larger in OSC-AA than OSC-nAA. Within the OSC-nAA group, there was no significant difference in the size of the DA, AoI, or pulmonary valve opening between those with retrograde flow (RF) at the AoI and without (nRF) except the aortic valve opening was significantly larger in nRF. All groups had comparable cross-sectional areas of systemic output. Conclusions: Our findings suggest that DA and AoI show compensatory growth to maintain critical blood flow to vital organs against primary anatomical abnormalities in ductus-dependent CHD. (249 words) [ABSTRACT FROM AUTHOR]

The content of endogenous hormones (auxin IAA, cytokinines, ABA) in explants of various types (segments of the leaf, bud, and stem), primary calluses induced from them, and morphogenic and nonmorphogenic calluses at the initial stages of in vitro culture by the immunoassay method was studied for the first time for Lavandula angustifolia Mill. The maximum value of the hormone levels in explants such as segments of a bud was shown. An increase in the content of hormones in primary calluses was revealed in comparison with similar characteristics in all types of explants. The higher level of the active form of cytokinin (trans-zeatin) and ABA, as well as the lower level of the inactive form of cytokinin (zeatin-nucleotide) and auxin IAA, were identified in the morphogenic callus compared with the nonmorphogenic one. It is suggested that the content of endogenous hormones in explants and calluses of L. angustifolia is due to their histological status. A conclusion is made about the unified histophysiological mechanisms of callusogenesis and morphogenesis in vitro in the studied plant. [ABSTRACT FROM AUTHOR]

The second heart field (SHF) plays a pivotal role in heart development, particularly in outflow tract (OFT) morphogenesis and septation, as well as in the expansion of the right ventricle (RV). Two mouse Cre lines, the Mef2c - AHF - Cre (Mef2c - Cre) and Isl1 - Cre , have been widely used to study the SHF development. However, Cre activity is triggered not only in the SHF but also in the RV in the Mef2c - Cre mice, and in the Isl1 - Cre mice, Cre activation is not SHF-specific. Therefore, a more suitable SHF-Cre line is desirable for better understanding SHF development. Here, we generated and characterized the Prdm1 -Cre knock-in mice. In comparison with Mef2c - Cre mice, the Cre activity is similar in the pharyngeal and splanchnic mesoderm, and in the OFT of the Prdm1 - Cre mice. Nonetheless, it was noticed that Cre expression is largely reduced in the RV of Prdm1 - Cre mice compared to the Mef2c - Cre mice. Furthermore, we deleted Hand2 , Nkx2-5 , Pdk1 and Tbx20 using both Mef2c - Cre and Prdm1 - Cre mice to study OFT morphogenesis and septation, making a comparison between these two Cre lines. New insights were obtained in understanding SHF development including differentiation into cardiomyocytes in the OFT using Prdm1 - Cre mice. In conclusion, we found that Prdm1 - Cre mouse line is a more appropriate tool to monitor SHF development, while the Mef2c-Cre mice are excellent in studying the role and function of the SHF in OFT morphogenesis and septation. [Display omitted] • Lineage tracing using Prdm1 - Cre mice reveals Cre expression in the second heart field progenitors and derivatives. • Comparison of Prdm1 - Cre and Mef2c - Cre mediated gene deletion distinguishes difference in second heart field development. • Prdm1 - Cre is suitable for studying second heart development. • Mef2c - Cre is an excellent tool to investigate cardiac outflow tract morphogenesis and septation. [ABSTRACT FROM AUTHOR]

To bring about sexual dimorphism in form, information from the sex determination pathway must trigger sex-specific modifications in developmental programs. DM-domain encoding genes have been found to be involved in sex determination in a multitude of animals, often at the level of male somatic gonad formation. Here we report our findings that the DM-domain transcription factors MAB-3 and DMD-3 function together in multiple steps during the late stages of C. elegans male somatic gonad development. Both mab-3 and dmd-3 are expressed in the linker cell and hindgut of L4 males and dmd-3 is also expressed in presumptive vas deferens cells. Furthermore, dmd-3 , but not mab-3 , expression in the linker cell is downstream of nhr-67, a nuclear hormone receptor that was previously shown to control late stages of linker cell migration. In mab-3 ; dmd-3 double mutant males, the last stage of linker cell migration is partially defective, resulting in aberrant linker cell shapes and often a failure of the linker cell to complete its migration to the hindgut. When mab-3; dmd-3 double mutant linker cells do complete their migration, they fail to be engulfed by the hindgut, indicating that dmd-3 and mab-3 activity are essential for this process. Furthermore, linker cell death and clearance are delayed in mab-3; dmd-3 double mutants, resulting in the linker cell persisting into adulthood. Finally, DMD-3 and MAB-3 function to activate expression of the bZIP transcription factor encoding gene zip-5 and downregulate the expression of the zinc metalloprotease ZMP-1 in the linker cell. Taken together, these results demonstrate a requirement for DM-domain transcription factors in controlling C. elegans male gonad formation, supporting the notion that the earliest DM-domain genes were involved in male somatic gonad development in the last common ancestor of the bilaterians. [Display omitted] • Two C. elegans DM domain transcription factor encoding genes, mab-3 and dmd-3 , are expressed in multiple tissues involved in male somatic gonad development. • m ab-3; dmd-3 double mutants display defects in linker cell migration, resulting in aberrant linker cell morphology and premature arrest in many double mutant males. • m ab-3; dmd-3 double mutants also display defects in linker cell engulfment by the hindgut and subsequent linker cell death and clearance. • MAB-3 and DMD-3 partially inhibit expression of the zinc matrix metalloproteinase encoding gene zmp-1 and activate expression of a basic leucine zipper containing transcription factor encoding gene zip-5 in the linker cell. • These results support the hypothesis that ancestral DM-domain genes were involved in male somatic gonad development. [ABSTRACT FROM AUTHOR]

[Objective] This study explored the cytological characteristics of different developmental stages of Prunus sibirica microspores and revealed the relationships between microspore periods and floral organ morphology to provide basis for reproductive biology research and germplasm innovation of Prunus sibirica. [Method] The flower buds of male sterile and fertile lines of Prunus sibirica were selected as the research subjects. The paraffin section technique and modified carmine acetate staining technique were used to observe morphology of microspores at various development stages. Phenotypic observation and analysis of flower organ morphology were also conducted during corresponding periods. [Result] The microspore development periods of Prunus sibirica included tetrad stage, microspore period and mature stage. The microspore period included uninucleate stage (early-uninucleate stage, mid-uninucleate stage, late-uninucleate stage) and binucleate stage (early-binucleate stage, middle-binucleate stage, late-binucleate stage) with distinct cytological features in each stage. In the early-binucleate stage, the microspores of the male sterile line were abnormal due to the failure to complete mitosis, but there was no abnormality in the development of floral organs. The bud transverse diameter, bud longitudinal diameter, anther transverse diameter and anther longitudinal diameter gradually increased with the advance of microspore development stage in Prunus sibirica. There were corresponding relationships between microspore periods and morphological characteristics of floral organs. The bud transverse diameter, anther transverse diameter and anther longitudinal diameter were utilized to differentiate microspores between various microspore stages ranging from early-binucleate stage to late-binucleate stage. The color of calyx was employed to differentiate microspores between mid-uninucleate stage and late-uninucleate stage. Additionally, microspore diameter distinguished different stages of microspores from early-uninucleate stage to early-binucleate stage. At the early-binucleate stage, bud transverse diameters of male sterile line and male fertile line in Prunus sibirica were 3.36 and 3.34 mm, respectively. The anther longitudinal diameters of male sterile line and male fertile line were 0.95 and 0.96 mm, respectively. The anther transverse diameters of male sterile line and male fertile line were both 0.73 mm. The microspore diameter of male sterile line and male fertile line were both 28.90 μm. [Conclusion] The microspore period of Prunus sibirica was correlated with bud transverse diameter, anther transverse diameter, anther longitudinal diameter, and calyx color, which could be used as an important basis for dividing microspore stages. [ABSTRACT FROM AUTHOR]

Ciliated microeukaryotes are insufficiently investigated despite their ubiquity and ecological significance. The morphology and morphogenesis of a new Stichotrichida species, Pseudosincirra binaria sp. nov., and the known Perisincirra paucicirrata Foissner et al., 2002, are here studied using live observations and protargol staining methods. The new species is characterized by having one buccal, one parabuccal and three frontal cirri, one frontoventral row extending to the posterior half of the cell, three left and two right marginal rows and three dorsal kineties with the left kinety conspicuously bipartite, along with one caudal cirrus at the rear end of each kinety. During morphogenesis, there exist five frontal-ventral cirral anlagen with anlagen IV and V forming a frontoventral row in the proter, and four cirral anlagen with only anlage IV generating a frontoventral row in the opisthe. The anlagen for marginal rows and dorsal kineties develop intrakinetally. The new population of Perisincirra paucicirrata corresponds well with other isolates regarding morphology and cell development. Phylogenetic analyses based on small subunit ribosomal gene sequence data revealed that both Perisincirra and Pseudosincirra are deeply clustered in the clade consisting of species from the genera Deviata and Heterodeviata, supporting the placement of both genera into the family Deviatidae Foissner, 2016. [ABSTRACT FROM AUTHOR]

The regulation of vital plant activities by hormones is governed by a family of macromolecular peptides referred to as GH3 genes. This work analyzed the expression patterns of GH3 family genes in pear tissues using transcriptome data and bioinformatics analysis. In the Bai Li pear genome, a total of 18 PbGH3 genes were identified. Comparative evolutionary studies have shown a strong association between PbGH3 and AtGH3 class I and class II proteins. The role of PbGH3 genes in growth activities and hormone regulation was revealed using gene ontology (GO) and promoter region analysis. In addition, although certain PbGH3 genes exhibited tissue-specific expression in sepals, the majority had a ubiquitous expression across all tissues. Bioinformatics and expression studies suggest that the GH3 gene family in pears may have a role in controlling the abscission of the fruit's sepals. This work sheds light on the pear fruit sepal shedding process and may inspire further research. [ABSTRACT FROM AUTHOR]