Mechanical Feedback Control for Multicellular Tissue Size Maintenance: A Minireview

All living tissues and organs have their respective sizes, critical to various biological functions, such as development, growth, and homeostasis. As tissues and organs generally converge to a certain size, intrinsic regulatory mechanisms may be involved in the maintenance of size regulation. In recent years, important findings regarding size regulation have been obtained from diverse disciplines at the molecular and cellular levels. Here, I briefly review the size regulation of biological tissues from the perspective of control systems. This minireview focuses on how feedback systems engage in tissue size maintenance through the mechanical interactions of constituent cell collectives through intracellular signaling. I introduce a general framework of a feedback control system for tissue size regulation, followed by two examples: maintenance of epithelial tissue volume and epithelial tube diameter. The examples deliver the idea of how cellular mechano-response works for maintaining tissue size.

The prevalence of incidental finding of gynecomastia on thoracic computed tomography in the pediatric age group

Objectives This study aimed to determine the prevalence rate of gynecomastia, determine mean glandular breast tissue sizes, and evaluate whether there is any difference in the prevalence rate of gynecomastia according to age using three different reference values of glandular breast tissue size (≥5, ≥10, ≥20 mm) in the pediatric age group. Methods Glandular breast tissue sizes were measured retrospectively from thoracic computed tomography (CT) images taken for other reasons in 961 boys aged 1–18 years. Results When each breast was evaluated separately (1,922 breasts), gynecomastia was observed in 1,001 (52.1%), 719 (37.4%), and 216 (11.2%) breasts with ≥5, ≥10, and ≥20 mm considered as reference values, respectively. A significant difference was found in terms of gynecomastia (p<0.001) and mean glandular breast tissue size (p<0.001) with respect to age. Conclusions New studies are currently needed to determine the glandular breast tissue size and the prevalence rate of gynecomastia in boys, and thoracic CT images can be used for this purpose.

Prechoroidal cleft thickness correlates with disease activity in neovascular age-related macular degeneration

Purpose The purpose of this study was to investigate the structural variations of the hyporeflective pocket of fluid (prechoroidal cleft) located between Bruch’s membrane and the hyperreflective material within the pigment epithelial detachment (PED) in patients with neovascular age-related macular degeneration (nAMD). Methods In this retrospective, observational case series study, patients diagnosed with nAMD and prechoroidal cleft associated with other activity signs of the macular neovascularization (MNV) were included. Structural optical coherence tomography (OCT) scans were evaluated to obtain anatomical measurements of prechoroidal cleft and PED at three different visits (T0, inactive MNV; T1, active MNV; T2, treated inactive MNV). The variations in size of the cleft and the PED were correlated with nAMD activity. Results Twenty-nine eyes from 27 patients were included. The subfoveal measurements showed a significant increase of prechoroidal cleft height and width from T0 to T1 (P < 0.05) and a subsequent decrease of the cleft height after treatment with anti-VEGF agents (P = 0.004). A similar significant trend was observed for the greatest prechoroidal cleft height and width, obtained assessing the whole OCT raster. In the multivariate analysis, the cleft height was significantly affected by both time (P = 0.001) and PED height (P < 0.0001). By contrast, the effect of fibrovascular tissue size within the PED was not significant. Visual acuity did not correlate with prechoroidal cleft size. Conclusion Prechoroidal cleft increased in association with MNV reactivation and decreased after treatment. Our results suggest that prechoroidal cleft could represent an accumulation of fluid actively exudating from the MNV and should be considered a sign of nAMD activity.

Relationship between physical activity times and intramuscular adipose tissue contents of the thigh muscle groups in younger and older men

The present study aimed to investigate the effect of daily physical activities evaluated by steps and time on muscle tissue size and intramuscular adipose tissue (IntraMAT) content in the thigh muscle groups for younger and older men. Twenty younger (23.8 ± 3.7 years) and 20 older (70.7 ± 5.6 years) men participated in this study. We measured the muscle tissue cross-sectional area (CSA) and the IntraMAT content in the quadriceps femoris (QF), hamstrings (HM), hip adductors (AD), and total of mid-thigh by magnetic resonance imaging. We measured physical activity time using a triaxial accelerometer and determined four levels of physical activity depending on the metabolic equivalent (METs), e.g., sedentary (≤ 1.5 METs), light-intensity (≤ 2.9 METs), moderate-intensity (3.0 to 5.9 METs) and vigorous-intensity (≥ 6.0 METs). The muscle tissue CSA of AD was a significantly correlated with the time of vigorous-intensity activity in the older group (rs = 0.446, P < 0.05), but not in the younger group. The IntraMAT content of the three muscle groups (QF, AD, and HM) and the total thigh were significantly correlated with the time of moderate-intensity activity (rs = − 0.625 to − 0.489, P < 0.05, for all comparisons) in the younger group, but not in the older group. Our results suggest that the relationship of muscle tissue size and IntraMAT content with physical activity times is affected by age.

The cAMP effector PKA mediates Moody GPCR signaling inDrosophilablood-brain barrier formation and maturation

The blood-brain barrier (BBB) ofDrosophilais comprised of a thin epithelial layer of subperineural glia (SPG), which ensheath the nerve cord and insulate it against the potassium-rich hemolymph by forming intercellular septate junctions (SJs). Previously, we identified a novel Gi/Go protein-coupled receptor (GPCR), Moody, as a key factor in BBB formation at the embryonic stage. However, the molecular and cellular mechanisms of Moody signaling in BBB formation and maturation remain unclear. Here, we identify cAMP-dependent protein kinase A (PKA) as a crucial antagonistic Moody effector that is required for the formation, as well as for the continued SPG growth and BBB maintenance in the larva and adult stage. We show that PKA is enriched at the basal side of the SPG cell and that this polarized Moody/PKA pathway finely tunes the enormous cell growth and BBB integrity, by precisely regulating the actomyosin contractility, vesicle trafficking, and the proper SJ organization in a highly coordinated spatiotemporal manner. These effects are mediated in part by PKA’s molecular targets MLCK and Rho1. Moreover, 3D reconstruction of SJ ultrastructure demonstrates that the continuity of individual SJ segments and not their total length is crucial for generating a proper paracellular seal. Based on these findings, we propose a model that polarized Moody/PKA signaling plays a central role in controlling the cell growth and maintaining BBB integrity during the continuous morphogenesis of the SPG secondary epithelium, which is critical for maintain tissue size and brain homeostasis during organogenesis.

Size matters: An analytical study on the role of tissue size in spatiotemporal distribution of morphogens unveils a transition between different Reaction-Diffusion regimes

The reaction-diffusion model constitutes one of the most influential mathematical models to study the distribution of morphogens spreading within tissues. Despite its widespread appearance, the role that the finitude of the tissue plays in the spatiotemporal morphogen distribution predicted by the model has not been unveiled so far. In this study, we investigated the spatiotemporal distribution of a morphogen predicted by a reaction-diffusion model in a 1D finite domain as a proxy to simulate a biological tissue. We analytically solved, for the first time to our knowledge, the model assuming morphogen produced de novo within a finite domain and compared it with the scenario considering an infinite domain, which was previously solved. We explored the only relevant parameter in the reduced model, the tissue length in units of a characteristic reaction-diffusion length, and fully characterized the model behavior in terms of: i) geometrical aspects of the spatial distributions and ii) kinetic features derived from the time elapsed to reach the steady state. We found a critical tissue size that we estimated as ∼3.3 characteristic reaction-diffusion lengths, above which the model assuming the infinite domain could suffice as a reasonable approximation. In contrast, for tissues smaller than the critical size, the error of assuming an infinite domain could rapidly accumulate, indicating that the model assuming finite domains is a better description. This new solution could replace the one used to estimate diffusion coefficients and degradation constants during the analysis of Fluorescence Recovery After Photobleaching (FRAP) experiments and it could also help to improve the performance of multiscale computational approaches, which involve a morphogen dynamics scale, typically modeled with a reaction diffusion scheme. These findings could drive new modeling strategies to understand tissue morphogenesis as well as cancer invasion, among many other relevant problems in biology and medicine.

The Ubiquitin Ligase SIAH2 Negatively Regulates Glucocorticoid Receptor Activity and Abundance

Glucocorticoids are clinically essential drugs used routinely to control inflammation. However, a host of metabolic side effects manifests upon usage beyond a few days. In the present study, we tested the hypothesis that seven-in-absentia mammalian homolog-2 (SIAH2), a ubiquitin ligase that regulates adipogenesis, is important for controlling adipocyte size, inflammation, and the ability of adipose tissue to expand in response to a glucocorticoid challenge. Using mice with global deletion of SIAH2 exposed or not to corticosterone, we found that adipocytes are larger in response to glucocorticoids in the absence of SIAH2. In addition, SIAH2 regulates glucocorticoid receptor (GR) transcriptional activity and total GR protein abundance. Moreover, these studies reveal that there is an increased expression of genes involved in fibrosis and inflammatory signaling pathways found in white adipose tissue in response to glucocorticoids in the absence of SIAH2. In summary, this is the first study to identify a role for SIAH2 to regulate transcriptional activity and abundance of the GR, which leads to alterations in adipose tissue size and gene expression during in vivo exposure to glucocorticoids.

Dimorphism in Dental Tissues: Sex differences in Archaeological Individuals for Multiple Tooth Types

ObjectivesDimorphism in the dentition has been observed in human populations worldwide. However, research has largely focused on traditional linear crown measurements. As imaging systems, such as micro-computed tomography (micro-CT), become increasingly more accessible, new dental measurements such as dental tissue size and proportions can be obtained. This research investigates the variation of dental tissues and proportions by sex in archaeological samples.Materials and MethodsUpper and lower first incisor to second premolar tooth rows were obtained from 30 individuals (n=300), from 3 archaeological samples. The teeth were micro-CT scanned and surface area and volumetric measurements were obtained from the surface meshes extracted. Dental wear was also recorded and differences between sexes determined.ResultsEnamel and crown measurements were found to be larger in females. Conversely, dentine and root measurements were larger in males.DiscussionThe findings support the potential use of dental tissues to estimate sex of individuals from archaeological samples, whilst also indicating that individuals aged using current dental ageing methods may be under- or over-aged due to sex differences in enamel thickness.