•Growing embryos are mathematically modeled as isotropically expanding fields.•Morphogenesis of tissues on the fields is mathematically and analytically studied.•Cell clusters are passively elongated ...on the isotropically expanding field.•Elongation of cell clusters is primarily caused by their intrinsic features.•Interactions between cell clusters and growing embryos enhance asymmetries.
Cell movement is crucial for morphogenesis in multicellular organisms. Growing embryos or tissues often expand isotropically, i.e., uniformly, in all dimensions. On the surfaces of these expanding environments, which we call “fields,” cells are subjected to frictional forces and move passively in response. However, the potential roles of isotropically expanding fields in morphogenetic events have not been investigated well. Our previous mathematical simulations showed that a tissue was elongated on an isotropically expanding field (Imuta et al., 2014). However, the underlying mechanism remains unclarified, and how cells behave during tissue elongation was not investigated. In this study, we mathematically analyzed the effect of isotropically expanding fields using a vertex model, a standard type of multi-cellular model. We found that cells located on fields were elongated along a similar direction each other and exhibited a columnar configuration with nearly single-cell width. Simultaneously, it was confirmed that the cell clusters were also elongated, even though field expansion was absolutely isotropic. We then investigated the mechanism underlying these counterintuitive phenomena. In particular, we asked whether the dynamics of elongation was predominantly determined by the properties of the field, the cell cluster, or both. Theoretical analyses involving simplification of the model revealed that cell clusters have an intrinsic ability to asymmetrically deform, leading to their elongation. Importantly, this ability is effective only under the non-equilibrium conditions provided by field expansion. This may explain the elongation of the notochord, located on the surface of the growing mouse embryo. We established the mechanism underlying tissue elongation induced by isotropically expanding external environments, and its involvement in collective cell alignment with cell elongation, providing key insight into morphogenesis involving multiple adjacent tissues.
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Mechanical forces are critical for the emergence of diverse three-dimensional morphologies of multicellular systems. However, it remains unclear what kind of mechanical parameters at cellular level ...substantially contribute to tissue morphologies. This is largely due to technical limitations of live measurements of cellular forces. Here we developed a framework for inferring and modeling mechanical forces of cell-cell interactions. First, by analogy to coarse-grained models in molecular and colloidal sciences, we approximated cells as particles, where mean forces (i.e. effective forces) of pairwise cell-cell interactions are considered. Then, the forces were statistically inferred by fitting the mathematical model to cell tracking data. This method was validated by using synthetic cell tracking data resembling various in vivo situations. Application of our method to the cells in the early embryos of mice and the nematode Caenorhabditis elegans revealed that cell-cell interaction forces can be written as a pairwise potential energy in a manner dependent on cell-cell distances. Importantly, the profiles of the pairwise potentials were quantitatively different among species and embryonic stages, and the quantitative differences correctly described the differences of their morphological features such as spherical vs. distorted cell aggregates, and tightly vs. non-tightly assembled aggregates. We conclude that the effective pairwise potential of cell-cell interactions is a live measurable parameter whose quantitative differences can be a parameter describing three-dimensional tissue morphologies.
Tubular organs and tissues often show various morphological fold patterns in their luminal epithelia. Computational studies have revealed that these patterns could be explained by mechanical ...deformation of the epithelia. However, experimental validations of this are sparse, and the mechanisms linking genetic and cellular functions to fold mechanics are poorly understood. In the oviduct of the female reproductive tract, the epithelium forms multiple well-aligned straight folds. Disruption of Celsr1, a planar cell polarity-related gene, causes ectopically-branched folds in mice. Here we discuss the pattern formation of the folds with respect to the growth and mechanics of the epithelium, and the cellular and genetic functions, and compare these with other tubular organs such as the gut.
Purpose
This study aims to clarify the influence of the COVID-19 pandemic on cancer surgery in Gunma Prefecture.
Methods
A total of 9839 cases (1406 gastric cancer, 3569 colorectal cancer, 1614 lung ...cancer, and 3250 breast cancer) from 17 hospitals in Gunma Prefecture were investigated. We compared the number of surgical cases, proportion of cases found by screening, and cStage at the time of the first visit by month in 2020 and 2021 with those in 2019.
Results
The rate of decline in cancer surgery was 8.9% in 2020 compared with 2019 (
p
= 0.0052). Compared with the same month of 2019, in some months of 2020 and 2021, significant decreases were observed in the number of surgeries for gastric and colorectal cancer, the percentage of surgical cases detected by screening in all four cancers, and the proportion of cancers with a relatively early cStage in gastric and breast cancer.
Conclusions
The number of surgical cases of the four cancer types detected by cancer screening decreased in Gunma Prefecture owing to the influence of the COVID-19 pandemic. Furthermore, for some cancer types, the number of operations performed in patients with early-stage cancer is also decreased.
Three‐dimensional (3D) registration (i.e., alignment) between two microscopic images is very helpful to study tissues that do not adhere to substrates, such as mouse embryos and organoids, which are ...often 3D rotated during imaging. However, there is no 3D registration tool easily accessible for experimental biologists. Here we developed an ImageJ‐based tool which allows for 3D registration accompanied with both quantitative evaluation of the accuracy and reconstruction of 3D rotated images. In this tool, several landmarks are manually provided in two images to be aligned, and 3D rotation is computed so that the distances between the paired landmarks from the two images are minimized. By simultaneously providing multiple points (e.g., all nuclei in the regions of interest) other than the landmarks in the two images, the correspondence of each point between the two images, i.e., to which nucleus in one image a certain nucleus in another image corresponds, is quantitatively explored. Furthermore, 3D rotation is applied to one of the two images, resulting in reconstruction of 3D rotated images. We demonstrated that this tool successfully achieved 3D registration and reconstruction of images in mouse pre‐ and post‐implantation embryos, where one image was obtained during live imaging and another image was obtained from fixed embryos after live imaging. This approach provides a versatile tool applicable for various tissues and species.
We propose a user‐friendly image processing method by which we can three‐dimensionally align two images with multiple z‐slices. This method enables us to easily compare two tissues or embryos labeled by different markers under three‐dimensional situations.
Optimal timing for intubating patients with coronavirus disease 2019 (COVID-19) has been debated throughout the pandemic. Early use of high-flow nasal cannula (HFNC) can help reduce the need for ...intubation, but delay can result in poorer outcomes. This study examines trends in laboratory parameters and serum severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA levels of patients with COVID-19 in relation to HFNC failure. Patients requiring HFNC within three days of hospitalization between July 1 and September 30, 2021 were enrolled. The primary outcome was HFNC failure (early failure less than or equal toDay 3; late failure greater than or equal toDay 4), defined as transfer to intensive care just before/after intubation or in-hospital death. We examined changes in laboratory markers and SARS-CoV2-RNAemia on Days 1, 4, and 7, together with demographic data, oxygenation status, and therapeutic agents. We conducted a univariate logistic regression with the explanatory variables defined as 10% change rate in each laboratory marker from Day 1 to 4. We utilized the log-rank test to assess the differences in HFNC failure rates, stratified based on the presence of SARS-CoV2 RNAemia. Among 122 patients, 17 (13.9%) experienced HFNC failure (early: n = 6, late: n = 11). Seventy-five patients (61.5%) showed an initial SpO.sub.2 /FiO.sub.2 ratio less than or equal to243, equivalent to PaO.sub.2 /FiO.sub.2 ratio less than or equal to200, and the initial SpO.sub.2 /FiO.sub.2 ratio was significantly lower in the failure group (184 vs. 218, p = 0.018). Among the laboratory markers, a 10% increase from Day 1 to 4 of lactate dehydrogenase (LDH) and interleukin (IL)-6 was associated with late failure (Odds ratio OR: 1.42, 95% confidence interval CI: 1.09-1.89 and OR: 1.04, 95%CI: 1.00-1.19, respectively). Furthermore, in patients with persistent RNAemia on Day 4 or 7, the risk of late HFNC failure was significantly higher (Log-rank test, p<0.01). In conclusion, upward trends in LDH and IL-6 levels and the persistent RNAemia even after treatment were associated with HFNC failure.
Life expectancy acts as a population measure of the performance of healthcare systems. Regional disparities on life expectancy in Indonesia has been persisted and become a public health policy ...challenge. A systematic clustering of provinces can be a valuable alternative for organizing cooperation that aimed to increase life expectancy and reduce disparities. This study aimed to identify determinants of life expectancy and designate clusters of Indonesian provinces with similar characteristics. This approach can be useful in generating alternative cooperation strategies to improve life expectancy.
We carefully selected variables that have been shown to impact life expectancy and gathered 2015 data from Indonesia's Ministry of Health. All 34 Indonesian provinces were included as analysis units. We performed structural equation modeling (SEM) to select domains that needed to work on from theoretical models. Based on SEM results, we performed cluster analysis to arrange cooperation groups.
Life expectancy showed correlations with mean years of schooling, expenditure per capita, health workforce, healthcare facilities, and environment. Expenditure per capita also was the strongest of all constructs. Based on SEM results, we performed cluster analysis to arrange cooperation groups of total 34 provinces and generated five clusters of provinces.
Enhancing the economy is the most effective approach for improving life expectancy and other constructs. These clusters can build cooperation that is new, within, and across clusters. These results may be useful in formulating cooperation strategies aimed at increasing life expectancy.
In Bandung, Indonesia, urban expansion, rapid economic growth, and population increase present enormous challenges to the maintenance of a high quality of life (QOL) for its citizens. Moreover, ...income distribution in the city has become more unequal, thereby threatening social cohesion. Such situations led us to investigate the states and correlation of social cohesion and QOL in Bandung. In 2018, we conducted a questionnaire survey of social cohesion and QOL using 13 and 18 question items, respectively. We employed the Rasch model analysis to analyze the logit measures of 752 responses. The results revealed that the population of Bandung has high social cohesion and decent QOL. Our findings suggest that in Bandung QOL is significantly correlated with social cohesion, therefore strategies that seek to enhance social cohesion may be beneficial to improve the QOL.
Organs and tissues in multi-cellular organisms exhibit various morphologies. Tubular organs have multi-scale morphological features which are closely related to their functions. Here we discuss ...morphogenesis and the mechanical functions of the vertebrate oviduct in the female reproductive tract, also known as the fallopian tube. The oviduct functions to convey eggs from the ovary to the uterus. In the luminal side of the oviduct, the epithelium forms multiple folds (or ridges) well-aligned along the longitudinal direction of the tube. In the epithelial cells, cilia are formed orienting toward the downstream of the oviduct. The cilia and the folds are supposed to be involved in egg transportation. Planar cell polarity (PCP) is developed in the epithelium, and the disruption of the Celsr1 gene, a PCP related-gene, causes randomization of both cilia and fold orientations, discontinuity of the tube, inefficient egg transportation, and infertility. In this review article, we briefly introduce various biophysical and biomechanical issues in the oviduct, including physical mechanisms of formation of PCP and organized cilia orientation, epithelial cell shape regulation, fold pattern formation generated by mechanical buckling, tubulogenesis, and egg transportation regulated by fluid flow. We also mention about possible roles of the oviducts in egg shape formation and embryogenesis, sinuous patterns of tubes, and fold and tube patterns observed in other tubular organs such as the gut, airways, etc.
The aim of this study was to examine the effects of perinatal exposure to gadolinium (Gd)-based contrast agents (GBCAs) on the behavior of adulthood offspring.
Pregnant Balb/C mice (n = 5 per group) ...were intravenously injected with gadoterate meglumine (Magnescope, macrocyclic GBCA), gadodiamide (Omniscan, linear GBCA), or vehicle from pregnancy day 15 to 19, corresponding to embryonic day 15 to 19 of the fetus, at 2 mmol/kg body weight per day. Brain samples from dams and pups were collected on postpartum day 28. The total Gd concentration was quantified by inductively coupled plasma-mass spectrometry (dams, n = 3; gadoterate meglumine-treated pups group, n = 9; and gadodiamide-treated pups group, n = 10). Behavioral testing of offspring was started on postpartum day 70 (control group, n = 22; gadoterate meglumine-treated group, n = 23; and gadodiamide-treated group, n = 20).
Higher levels of Gd retention were observed in dams and pups in the gadodiamide-treated group. Perinatal exposure to GBCAs caused anxiety-like behavior, disrupted motor coordination, impaired memory function, stimulated tactile sensitivity, and decreased muscle strength, particularly in the gadodiamide-treated group.
In the present study, we showed that Gd was transferred to pups and was retained in their brain during postnatal development. Gadolinium retention may lead to impaired brain development. These findings indicate that the use of GBCAs in pregnant women should be avoided because it may have adverse effects on the fetus, particularly on brain development.
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