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Biophysical Journal Oct 2023In the epithelium, cell density and cell proliferation are closely connected to each other through contact inhibition of proliferation (CIP). Depending on cell density,...
In the epithelium, cell density and cell proliferation are closely connected to each other through contact inhibition of proliferation (CIP). Depending on cell density, CIP proceeds through three distinct stages: the free-growing stage at low density, the pre-epithelial transition stage at medium density, and the post-epithelial transition stage at high density. Previous studies have elucidated how cell morphology, motion, and mechanics vary in these stages. However, it remains unknown whether cellular metabolism also has a density-dependent behavior. By measuring the mitochondrial membrane potential at different cell densities, here we reveal a heterogeneous landscape of metabolism in the epithelium, which appears qualitatively distinct in three stages of CIP and did not follow the trend of other CIP-associated parameters, which increases or decreases monotonically with increasing cell density. Importantly, epithelial cells established a collective metabolic heterogeneity exclusively in the pre-epithelial transition stage, where the multicellular clusters of high- and low-potential cells emerged. However, in the post-epithelial transition stage, the metabolic potential field became relatively homogeneous. Next, to study the underlying dynamics, we constructed a system biology model, which predicted the role of cell proliferation in metabolic potential toward establishing collective heterogeneity. Further experiments indeed revealed that the metabolic pattern spatially correlated with the proliferation capacity of cells, as measured by the nuclear localization of a pro-proliferation protein, YAP. Finally, experiments perturbing the actomyosin contractility revealed that, while metabolic heterogeneity was maintained in the absence of actomyosin contractility, its ab initio emergence depended on the latter. Taken together, our results revealed a density-dependent collective heterogeneity in the metabolic field of a pre-epithelial transition-stage epithelial monolayer, which may have significant implications for epithelial form and function.
Topics: Contact Inhibition; Actomyosin; Epithelial Cells; Epithelium; Cell Proliferation
PubMed: 37598292
DOI: 10.1016/j.bpj.2023.08.014 -
Proceedings. Biological Sciences Nov 2023Following severe environmental change that reduces mean population fitness below replacement, populations must adapt to avoid eventual extinction, a process called...
Following severe environmental change that reduces mean population fitness below replacement, populations must adapt to avoid eventual extinction, a process called evolutionary rescue. Models of evolutionary rescue demonstrate that initial size, genetic variation and degree of maladaptation influence population fates. However, many models feature populations that grow without negative density dependence or with constant genetic diversity despite precipitous population decline, assumptions likely to be violated in conservation settings. We examined the simultaneous influences of density-dependent growth and erosion of genetic diversity on populations adapting to novel environmental change using stochastic, individual-based simulations. Density dependence decreased the probability of rescue and increased the probability of extinction, especially in large and initially well-adapted populations that previously have been predicted to be at low risk. Increased extinction occurred shortly following environmental change, as populations under density dependence experienced more rapid decline and reached smaller sizes. Populations that experienced evolutionary rescue lost genetic diversity through drift and adaptation, particularly under density dependence. Populations that declined to extinction entered an extinction vortex, where small size increased drift, loss of genetic diversity and the fixation of maladaptive alleles, hindered adaptation and kept populations at small densities where they were vulnerable to extinction via demographic stochasticity.
Topics: Animals; Biological Evolution; Population Dynamics; Population Density; Probability; Extinction, Biological
PubMed: 37989246
DOI: 10.1098/rspb.2023.1228 -
Frontiers in Plant Science 2023Leaf phenology (evergreen vs. deciduous) and morphology (simple vs. compound) are known to be related to water use strategies in tree species and critical adaptation to...
Leaf phenology (evergreen vs. deciduous) and morphology (simple vs. compound) are known to be related to water use strategies in tree species and critical adaptation to certain climatic conditions. However, the effect of these two traits and their interactions on the coordination between minor vein density (MVD) and stomatal density (SD) remains unclear. In this study, we examined the leaves of 108 tree species from plots in a primary subtropical forest in southern China, including tree species with different leaf morphologies and phenologies. We assessed nine leaf water-related functional traits for all species, including MVD, SD, leaf area (LA), minor vein thickness (MVT), and stomatal length (SL). The results showed no significant differences in mean LA and SD between either functional group (simple vs. compound and evergreen vs. deciduous). However, deciduous trees displayed a significantly higher mean MVD compared to evergreen trees. Similarly, compound-leaved trees have a higher (marginally significant) MVD than simple-leaved trees. Furthermore, we found that leaf morphology and phenology have significantly interactive effects on SL, and the compound-leafed deciduous trees exhibited the largest average SL among the four groups. There were significant correlations between the MVD and SD in all different tree groups; however, the slopes and interceptions differed within both morphology and phenology. Our results indicate that MVD, rather than SD, may be the more flexible structure for supporting the coordination between leaf water supply and demand in different leaf morphologies and phenologies. The results of the present study provide mechanistic understandings of the functional advantages of different leaf types, which may involve species fitness in community assembly and divergent responses to climate changes.
PubMed: 37564389
DOI: 10.3389/fpls.2023.1051692 -
APL Bioengineering Sep 2023Accurately modeling oxygen transport and consumption is crucial to predict metabolic dynamics in cell cultures and optimize the design of tissue and organ models. We...
Accurately modeling oxygen transport and consumption is crucial to predict metabolic dynamics in cell cultures and optimize the design of tissue and organ models. We present a methodology to characterize the Michaelis-Menten oxygen consumption parameters , integrating novel experimental techniques and computational tools. The parameters were derived for hepatic cell cultures with different dimensionality (i.e., 2D and 3D) and with different surface and volumetric densities. To quantify cell packing regardless of the dimensionality of cultures, we devised an image-based metric, referred to as the proximity index. The Michaelis-Menten parameters were related to the proximity index through an uptake coefficient, analogous to a diffusion constant, enabling the quantitative analysis of oxygen dynamics across dimensions. Our results show that Michaelis-Menten parameters are not constant for a given cell type but change with dimensionality and cell density. The maximum consumption rate per cell decreases significantly with cell surface and volumetric density, while the Michaelis-Menten constant tends to increase. In addition, the dependency of the uptake coefficient on the proximity index suggests that the oxygen consumption rate of hepatic cells is superadaptive, as they modulate their oxygen utilization according to its local availability and to the proximity of other cells. We describe, for the first time, how cells consume oxygen as a function of cell proximity, through a quantitative index, which combines cell density and dimensionality. This study enhances our understanding of how cell-cell interaction affects oxygen dynamics and enables better prediction of aerobic metabolism in tissue models, improving their translational value.
PubMed: 37664826
DOI: 10.1063/5.0160422 -
Journal of Clinical Medicine Sep 2023We aimed to analyze retinal microvascular parameters, measured by optical coherence tomography angiography in patients with internal carotid artery stenosis compared to...
We aimed to analyze retinal microvascular parameters, measured by optical coherence tomography angiography in patients with internal carotid artery stenosis compared to healthy individuals. A total of 41 eyes from 30 patients who had varying degrees of carotid stenosis, and 42 eyes from 42 healthy controls, were enrolled in this study. Depending on the degree of stenosis evaluated by Doppler ultrasonographic imaging, the patient group was further subclassified into mild, moderate, and severe carotid artery stenosis. Superficial and deep capillary plexus vessel densities, radial peripapillary capillary vessel density, foveal avascular zone, and flow densities in the choriocapillaris and outer retina were evaluated by optical coherence tomography angiography. The superficial and deep capillary plexus vessel densities were significantly reduced among the groups, only sparing the foveal region. The mean superficial plexus vessel density was 45.67 ± 4.65 and 50.09 ± 4.05 for the patient and control group, respectively ( = 0.000). The mean deep capillary plexus density was 46.33% ± 7.31% and 53.27% ± 6.31% for the patient and control group, respectively ( = 0.000). The mean superficial and deep capillary vessel densities in the foveal region did not show any statistical difference between the patient and control groups ( = 0.333 for the superficial and = 0.195 for the deep plexus vessel density). Radial peripapillary capillary vessel density was decreased in the patient group ( = 0.004). The foveal avascular zone area was wider in the patient group but this difference did not show a significant difference ( = 0.385). Retinal microvascular changes are a prominent outcome of internal carotid disease, and even mild stenosis can lead to alterations in the retinal microvascular bed which could be detected by OCTA. By early detection of microvascular changes in the retina in this patient group, we might speculate the overall vascular condition.
PubMed: 37762953
DOI: 10.3390/jcm12186014 -
Communications Chemistry Feb 2024Amorphous ices are usually classified as belonging to low-density or high-density amorphous ice (LDA and HDA) with densities ρ ≈ 0.94 g/cm and...
Amorphous ices are usually classified as belonging to low-density or high-density amorphous ice (LDA and HDA) with densities ρ ≈ 0.94 g/cm and ρ ≈ 1.15-1.17 g/cm. However, a recent experiment crushing hexagonal ice (ball-milling) produced a medium-density amorphous ice (MDA, ρ ≈ 1.06 g/cm) adding complexity to our understanding of amorphous ice and the phase diagram of supercooled water. Motivated by the discovery of MDA, we perform computer simulations where amorphous ices are produced by isobaric cooling and isothermal compression/decompression. Our results show that, depending on the pressure employed, isobaric cooling can generate a continuum of amorphous ices with densities that expand in between those of LDA and HDA (briefly, intermediate amorphous ices, IA). In particular, the IA generated at P ≈ 125 MPa has a remarkably similar density and average structure as MDA, implying that MDA is not unique. Using the potential energy landscape formalism, we provide an intuitive qualitative understanding of the nature of LDA, HDA, and the IA generated at different pressures. In this view, LDA and HDA occupy specific and well-separated regions of the PEL; the IA prepared at P = 125 MPa is located in the intermediate region of the PEL that separates LDA and HDA.
PubMed: 38378859
DOI: 10.1038/s42004-024-01117-2 -
Poultry Science Jul 2023This experiment was conducted to study the effect of housing systems and housing densities on the performance and digestive tract growth of broiler chicks during the...
This experiment was conducted to study the effect of housing systems and housing densities on the performance and digestive tract growth of broiler chicks during the first 2 wk of age. A total of 3,600 Cobb500 day-old chicks were stocked at 4 densities (30, 60, 90, and 120 chicks/m), and reared under 2 housing systems (conventional housing system and newly developed housing system), yielding a 2 × 4 factorial arrangement. The studied traits were performance, viability, and gastrointestinal tract development. The results indicated that housing systems and housing densities significantly (P < 0.001) affected the performance and GIT development of chicks. There were no significant interactions between housing system and housing density for body weight, body weight gain, feed intake, and feed conversion. The results also showed that the effects of housing density were age-dependent. That is, the higher the density, the lower the performance and digestive tract growth with advancing age. In conclusion, birds in the conventional system outperformed birds in the newly developed housing system, and further work is needed to improve the new housing system. To achieve the highest performance, digestive tract growth, and digesta content, a density of 30 chicks/m is recommended for chicks up to 14-days old.
Topics: Animals; Animal Feed; Body Weight; Chickens; Diet; Eating; Gastrointestinal Tract; Housing, Animal
PubMed: 37245440
DOI: 10.1016/j.psj.2023.102752 -
Acta Crystallographica Section B,... Oct 2023Five different electron density datasets obtained from conventional and synchrotron single crystal X-ray diffraction experiments are compared. The general aim of the...
Five different electron density datasets obtained from conventional and synchrotron single crystal X-ray diffraction experiments are compared. The general aim of the study is to investigate the quality of data for electron density analysis from current state-of-the-art conventional sources, and to see how the data perform in comparison with high-quality synchrotron data. A molecular crystal of melamine was selected as the test compound due to its ability to form excellent single crystals, the light atom content, and an advantageous suitability factor of 3.6 for electron density modeling. These features make melamine an optimal system for conventional X-ray diffractometers since the inherent advantages of synchrotron sources such as short wavelength and high intensity are less critical in this case. Data were obtained at 100 K from new in-house diffractometers Rigaku Synergy-S (Mo and Ag source, HyPix100 detector) and Stoe Stadivari (Mo source, EIGER2 1M CdTe detector), and an older Oxford Diffraction Supernova (Mo source, Atlas CCD detector). The synchrotron data were obtained at 25 K from BL02B1 beamline at SPring-8 in Japan (λ = 0.2480 Å, Pilatus3 X 1M CdTe detector). The five datasets were compared on general quality parameters such as resolution, ⟨I/σ⟩, redundancy and R factors, as well as the more model specific fractal dimension plot and residual density maps. Comparison of the extracted electron densities reveals that all datasets can provide reliable multipole models, which overall convey similar chemical information. However, the new laboratory X-ray diffractometers with advanced pixel detector technology clearly measure data with significantly less noise and much higher reliability giving densities of higher quality, compared to the older instrument. The synchrotron data have higher resolution and lower measurement temperature, and they allow for finer details to be modeled (e.g. hydrogen κ parameters).
PubMed: 37669152
DOI: 10.1107/S2052520623006625 -
Frontiers in Bioengineering and... 2023Modern orthopaedic implants use lattice structures that act as 3D scaffolds to enhance bone growth into and around implants. Stochastic scaffolds are of particular...
Modern orthopaedic implants use lattice structures that act as 3D scaffolds to enhance bone growth into and around implants. Stochastic scaffolds are of particular interest as they mimic the architecture of trabecular bone and can combine isotropic properties and adjustable structure. The existing research mainly concentrates on controlling the mechanical and biological performance of periodic lattices by adjusting pore size and shape. Still, less is known on how we can control the performance of stochastic lattices through their design parameters: nodal connectivity, strut density and strut thickness. To elucidate this, four lattice structures were evaluated with varied strut densities and connectivity, hence different local geometry and mechanical properties: low apparent modulus, high apparent modulus, and two with near-identical modulus. Pre-osteoblast murine cells were seeded on scaffolds and cultured for 28 days. Cell adhesion, proliferation and differentiation were evaluated. Additionally, the expression levels of key osteogenic biomarkers were used to assess the effect of each design parameter on the quality of newly formed tissue. The main finding was that increasing connectivity increased the rate of osteoblast maturation, tissue formation and mineralisation. In detail, doubling the connectivity, over fixed strut density, increased collagen type-I by 140%, increased osteopontin by 130% and osteocalcin by 110%. This was attributed to the increased number of acute angles formed by the numerous connected struts, which facilitated the organization of cells and accelerated the cell cycle. Overall, increasing connectivity and adjusting strut density is a novel technique to design stochastic structures which combine a broad range of biomimetic properties and rapid ossification.
PubMed: 38107615
DOI: 10.3389/fbioe.2023.1305936 -
Scientific Data Sep 2023An in-depth insight into the chemistry and nature of the individual chemical bonds is essential for understanding materials. Bonding analysis is thus expected to provide...
An in-depth insight into the chemistry and nature of the individual chemical bonds is essential for understanding materials. Bonding analysis is thus expected to provide important features for large-scale data analysis and machine learning of material properties. Such chemical bonding information can be computed using the LOBSTER software package, which post-processes modern density functional theory data by projecting the plane wave-based wave functions onto an atomic orbital basis. With the help of a fully automatic workflow, the VASP and LOBSTER software packages are used to generate the data. We then perform bonding analyses on 1520 compounds (insulators and semiconductors) and provide the results as a database. The projected densities of states and bonding indicators are benchmarked on standard density-functional theory computations and available heuristics, respectively. Lastly, we illustrate the predictive power of bonding descriptors by constructing a machine learning model for phononic properties, which shows an increase in prediction accuracies by 27% (mean absolute errors) compared to a benchmark model differing only by not relying on any quantum-chemical bonding features.
PubMed: 37696882
DOI: 10.1038/s41597-023-02477-5