Branch Points Research Articles

Bacteria as ecosystem engineers: Unraveling clues through a novel functional response and tritrophic model

Bacteria play a crucial role in regulating the nutrient cycle of ecosystems, making their abundance essential for the sustainability of these environments. Maintaining a thriving bacterial population is achieved through complex nutrient–bacteria–protozoa interactive dynamics, which can be likened to a tritrophic food chain model. The interaction between bacteria and protozoa is governed by a critical factor known as the bacteria–protozoa functional response, which serves as the foundation for developing this tritrophic model. However, existing functional responses have shown limitations in accurately describing the intricacies of the bacteria–protozoa interaction. One significant drawback is the neglect of bacterial behavioral traits. To address this issue, we consider the concept of cooperation as a group defense mechanism employed by bacteria facilitated through a quorum-sensing communication process. By incorporating the cooperation trait into the functional response, our model offers a more comprehensive understanding of the complex tritrophic food chain dynamics. We evaluate the stability of different equilibrium points, along with Hopf-bifurcation around the coexistence equilibrium point. We find that a balance between strong group defense and moderate cooperation is essential for bacteria sustainability and overall system stability. Our results also elaborately address the effects of the increasing group defense through the bistable equilibrium followed by a branch point and saddle–node bifurcation. Through comprehensive analyses and simulations, we examine the paradox of enrichment in nutrition flow at the community level and explore how nutrient washout controls system stability. This innovation not only enhances our comprehension of ecosystem sustainability but also opens up new avenues for studying the intricate relationships that govern the overall balance of nature.

Numerical investigation of unruptured middle cerebral artery bifurcation aneurysms: influence of aspect ratio

An aneurysm is a disease condition, which is due to the pathological weakening of an arterial wall. These aneurysms are often found in various branch points and bifurcations of an artery in the cerebral circulation. Most aneurysms come to medical attention, either due to brain hemorrhages caused by rupture or found unruptured. To consider surgically invasive treatment modalities, clinicians need scientific methods such as, hemodynamic analysis to assess rupture risk. The arterial wall loses its structural integrity when wall shear stress (WSS) and other hemodynamic parameters exceed a certain threshold. In the present study, numerical simulations are carried out for unruptured middle cerebral artery (MCA) aneurysms. Three distinct representative sizes are chosen from a larger patient pool of 26 MCA aneurysms. Logically, these aneurysms represent three growth stages of any patient with similar anatomical structure. Simulations are performed to compare the three growth phases (with different aspect ratios) of an aneurysm and correlate their hemodynamic parameters. Simulations with patient specific boundary conditions reveal that, aneurysms with a higher aspect ratio (AR) correspond to an attendant decrease in both time-averaged wall shear stress (TAWSS) and spatial wall shear stress gradients (WSSG). Smaller MCAs were observed to have higher positive wall shear stress divergence (WSSD), exemplifying the tensile nature of arterial wall stretching. Present study identifies positive wall shear stress divergence (PWSSD) to be a potential biomarker for evaluating the growth of an aneurysm.

Comparative Tensile Properties and Collagen Patterns in Domestic Cat (Felis catus) and Dog (Canis lupus familiaris) Ovarian Cortical Tissues.

The importance of the ovarian extracellular environment and tissue rigidity on follicle survival and development has gained attention in recent years. Our laboratory has anecdotally observed differences in the rigidity of domestic cat and dog ovarian cortical tissues, which have been postulated to underlie the differences in in vitro culture responses between the species, wherein cat ovarian tissues display higher survival in extended incubation. Here, the tensile strengths of cat and dog ovarian cortical tissues were compared via micropipette aspiration. The underlying collagen patterns, including fiber length, thickness, alignment, curvature, branch points and end points, and overall tissue lacunary and high-density matrix (HDM) were quantified via picrosirius red staining and TWOMBLI analysis. Finally, we explored the potential of MMP (-1 and -9) and TIMP1 supplementation in modulating tissue rigidity, collagen structure, and follicle activation in vitro. No differences in stiffness were observed between cat or dog cortical tissues, or pre- versus post-pubertal status. Cat ovarian collagen was characterized by an increased number of branch points, thinner fibers, and lower HDM compared with dog ovarian collagen, and cat tissues exposed to MMP9 in vitro displayed a reduced Young's modulus. Yet, MMP exposure had a minor impact on follicle development in vitro in either species. This study contributes to our growing understanding of the interactions among the physical properties of the ovarian microenvironment, collagen patterns, and follicle development in vitro.

Early Molecular Steps in Human Bone Marrow Stem Cell Differentiation Trajectories

Understanding the molecular signatures of human hematopoietic stem/progenitor cells (HSCPs) and gene network changes leading to differentiation induction are of utmost importance to achieve therapeutic hematopoietic stem cell (HSC) expansion. The identification of surface markers has improved the prospective isolation of human bone marrow HSCs over the last decades, but the isolated population still remains very heterogeneous. Single cell sequencing approaches have the potential to unbiased assort stem cells along their differentiation stages and trajectories, and to decipher molecular markers in differentiation hierarchies. However, whole transcriptome single cell sequencing often suffers from inadequate detection of low-expressed genes with increased drop-outs. To address this limitation and to provide sensitive mRNA quantification in human HSPCs, we developed a selected targeted gene panel (600 genes) in combination with 50 protein markers to cover most relevant genes/proteins of early HSPC differentiation and cell cycle status. We employed single cell CITE-Seq (cellular indexing of transcriptomes and epitopes by sequencing) based multi-omic profiling to >60.000 high-quality FACS-enriched human bone marrow HSPCs (CD34 + and CD34 +CD38 - cells) from 15 healthy donors representing young, mid and old age groups. Here, we demonstrate the most comprehensive molecular map of early human HSC differentiation and provide evidence of early branching points into lineage trajectories across different age groups using Slingshot pseudotime analysis. Our data demonstrate that the HSC branched into two main lineages, with the first branching point giving rise to megakaryocytic and erythroid progenitors (MKP/ERP), followed by lymphoid and myeloid progenitors (LMP/MDP). As expected, the most immature HSCs were defined by high expression of CD34, CD90, CRHBP, HOPX, HLF, MLLT3. However, we observed a number of hitherto undescribed HSC markers. The MKP/ERP lineage was defined by GATA1, TFRC, CD36, MPL and VWF expression. Furthermore, we found CD274, the Programmed Cell Death receptor ligand 1, to be selectively expressed in the MKP cluster. Re-clustering and trajectory analysis of the most immature CD34 +CD38 -/low cells confirmed early lineage commitment, suggesting that an MKP/ERP development does not include myeloid or lymphoid progenitors. A similar pattern was observed for all age groups. Interestingly, we observed increased expression of novel marker genes ( HLA-E, DLK1, ADGRG6, ADGRG1, MMRN1) and proteins (CD137 and CD273) in the most immature HSCs. Besides a gradual upregulation of CD38 along differentiation, differentiated cells showed lower CD45 levels. Furthermore, MKP/ERP committed cells showed a downregulation of SPINK2. TradeSeq analysis defined the continuous single cell expression changes in genes and markers upon early differentiation and lineage commitment, allowing the detection of decision-making gene networks. Our data adds further evidence to the revised model of hematopoiesis that challenges the dogma of a common myeloid progenitor giving rise to erythroid, megakaryocytic and myeloid cells. Furthermore, we see a structured hierarchical organization with a sequential loss of lineage potential and not an early commitment of uni-lineage restricted precursors. We report on the upregulation of ADGRG6, ADGRG1, DLK1, HLA-E, MMRN1 CD137 and CD273 in the most immature HSCs. Molecular and functional characterization of CD273 hi and low HSCs are presented in an adjacent report by our group at this meeting (Schmachtel et al.). In conclusion, we provide a valuable resource for the continuous regulation of genes and surface proteins along early differentiation of very immature human HSCs.

Chemical characterization, antioxidant and immunomodulatory activities of acetylated polysaccharides from Cyperus esculentus.

This research was designed to characterize the structure of Cyperus esculentus polysaccharide (CEP) and its acetylated one (ACEP), and then investigated the effects of acetylation on the changes in physicochemical properties, thermal stability, antioxidant and immunomodulatory activities. Results showed that CEP and ACEP were heteropolysaccharides consisting of glucose, mannose, arabinose and xylose. The main chain of CEP included α-1,4-Glcp residues with the branching points at the O-6 position of the α-1,6-Manp residues. Acetyl groups were substituted at the O-2 and O-6 positions of some glucose residues. Meanwhile, the acetylation remarkably improved the polysaccharides thermal stability, and the ACEP exhibited a greater antioxidant activity. Furthermore, CEP and ACEP were proved to protect RAW 264.7 cells against LPS-induced inflammation by improving cellular morphology and decreasing reactive oxygen species secretion. This study may highlight a new approach for developing a high value-added ingredient from C. esculentus for functional food industry.

Modeling the Motion of an Elongated Contour under Free Surface of a Heavy Fluid under Large Froude Numbers

The flow around an elongated smooth contour under the free surface of a fluid is considered. The fluid is perfect, incompressible, and heavy. The critical flow branching and flow shedding points are located on the contour. The depth of the contour immersion and its length are given. It is assumed that the velocity magnitude on the free surface is close to its value in the undisturbed flow. A nonlinear approximation of the Bernoulli integral on the free surface associated with logarithm is used. Two auxiliary planes in which the flow domain is a half-plane with an excluded circle and an annular region are used. The complex potential is determined in the first parametric plane using a conformal mapping onto the annular region. A system of equations is derived for finding the defining parameters. This system is solved using the minimization of a functional and an iteration method over two sets of parameters. An algorithm and computer program for solving this system are developed. The hydrodynamic characteristics of a specific hydrofoil are computed. Results for the coefficients of wave drag, lift force, moment, and position of the contour center are analyzed depending on the Froude number and circulation of different signs. Examples of computations of nonlinear waves formed on the free surface at significant Froude numbers are given.

Identification of Tropane Alkaloid Chemotypes and Genotypes in Hyoscyamus niger L.

Tropane alkaloids (TA) are compounds widespread in the Solanaceae family. The genera Atropa, Brugmansia, Hyoscyamus, and Scopolia, produce the pharmaceuticals hyoscyamine (Hy) and scopolamine (Sc), which are valued for their antimuscarinic and anticholinergic actions. The enzyme hyoscyamine 6β-hydroxylase (H6H) [electrical conductivity (EC) 1.14.11.11] catalyzes both the hydroxylation of hyoscyamine to 6β-hydroxyhyoscyamine and the epoxidation of the latter, leading to scopolamine (Hashimoto et al. 1993). During the examination of three genes in the TA biosynthetic pathway, the first committed step, the path branch point, and the final step in 13 accessions of Hyoscyamus niger from North America and Europe, genetic variations were found to be absent except in the h6h gene locus (GenBank: D26583.1). Quantification of TA showed average concentrations of 26 to 520 μg/g of dry leaf tissue among the accessions. From a monohybrid cross of the expected (Pennsylvania accession Ames 3103, aa) and novel (Netherlands accession PI 641691, bb) genotypes, the F2 population (n = 104) leaf and root tissues were extracted, analyzed for Hy and Sc contents, and compared with the h6h genotypes (aa, ab, bb). The polymorphism showed Mendelian inheritance. The presence of the polymorphic gene bb showed a marginally significantly greater concentration of hyoscyamine in the leaf tissue (P = 0.0675) and significantly greater concentration in root tissue (P = 0.0436), along with increased concentration of scopolamine in the root tissue (P = 0.0494) compared with the aa genotype. The increase in overall TA in the root tissue of the genotype bb was accompanied by a reduction in scopolamine in the foliar tissue. The 694-bp b amplicon has been sequenced for comparison with the expected 550-bp a amplicon and can be a useful enzymatic variant for TA metabolic engineering.

Cholesterol mediated ferroptosis suppression reveals essential roles of Coenzyme Q and squalene

AbstractRecent findings have shown that fatty acid metabolism is profoundly involved in ferroptosis. However, the role of cholesterol in this process remains incompletely understood. In this work, we show that modulating cholesterol levels changes vulnerability of cells to ferroptosis. Cholesterol alters metabolic flux of the mevalonate pathway by promoting Squalene Epoxidase (SQLE) degradation, a rate limiting step in cholesterol biosynthesis, thereby increasing both CoQ10 and squalene levels. Importantly, whereas inactivation of Farnesyl-Diphosphate Farnesyltransferase 1 (FDFT1), the branch point of cholesterol biosynthesis pathway, exhibits minimal effect on ferroptosis, simultaneous inhibition of both CoQ10 and squalene biosynthesis completely abrogates the effect of cholesterol. Mouse models of ischemia-reperfusion and doxorubicin induced hepatoxicity confirm the protective role of cholesterol in ferroptosis. Our study elucidates a potential role of ferroptosis in diseases related to dysregulation of cholesterol metabolism and suggests a possible therapeutic target that involves ferroptotic cell death.

The size and shape of snowflake-shaped polymers in dilute solution: Analytical and numerical approaches

We investigate the conformational properties of a hyper-branched polymer structure with a dendrimer-like topology, known as a snowflake polymer. This polymer is characterized by two parameters: fs, which represents the functionality of the central star-like core, and f, which represents the functionality of the side branching points. To analyze the conformational properties, we have employed various approaches, including analytical methods based on direct polymer renormalization and the Wei's approach as well as numerical molecular dynamics simulations. These methods have allowed us to estimate a size and shape characteristics of the snowflake polymer as functions of f and fs. Our results consistently illustrate that as the number of branching points increases, the typical polymer conformation becomes more effectively compact compared to a linear polymer. Overall, our study provides valuable insights into the conformational behavior of the snowflake polymer and highlights the impact of branching parameters on its overall compactness.

XAI SHAP 기반 토지 피복 구성에 따른 지표면 온도의 영향 분석

Recently, with the development of artificial intelligence architecture and the rapid improvement of hardware performance, various artificial intelligence models are attracting attention and their usefulness are increasing. However, unlike the rate of development of performance, the development of model's explanatory ability is slow to progress. The increasingly complex decision branching points of AI models are increasing exponentially, which hinders researchers' ease of model interpretation. Explainable Artificial Intelligence, XAI has emerged to solve the above complexity, and helps to improve interpretability and reliability by decomposing the black box of the model to a level that researchers can understand. This study estimates the surface temperature of a specific spatial unit using land cover data of a cell unit in Korea, Seoul. The limitations of the existing statistical model for high-dimensional data were examined, and the estimation results were compared using a machine learning model. Models used include Lasso regression(Least absolute linkage and selection operator), random forest regression, and XGBoost (eXtreme Gradient Boosting) regression. Finally, based on the fitted result of the XGBoost regression model, XAI SHAP was carried out.

Anatomical location of motor branch points in the flexor digitorum superficialis for the injection site of botulinum toxin.

To locate the intramuscular nerve branches of the flexor digitorum superficialis (FDS) and determine the accurate site for botulinum toxin injection. This study anatomically dissected 24 arms of 12 fresh adult cadavers to find intramuscular nerve endings in the FDS. The motor branch points (MBPs), proximal limit points (PLPs), and distal limit points (DLPs) of the terminal intramuscular nerve endings were identified. These three parameters were expressed in longitudinal and transverse coordinates in relation to the FDS driving as a reference line. The mean length of the reference line was 234.6 ± 11.2mm. In the longitudinal coordinate, the MBPs, PLPs, and DLPs were located at 41.6% (standard deviation (SD) 2.6%), 35.1% (SD 4.1%), and 53.4% (SD 4.6%) of the reference line in the first main branch and 72.4% (SD 4.5%), 67.5% (SD 1.5%), and 82.0% (SD 5.7%) in the second main branch, respectively. The mean value of the transverse coordinate was not greatly deviated from the reference line. The MBPs of the first and second main branches are located approximately 41.6% and 72.4% of the reference line, which considers the FDS direction, respectively. This finding helps determine the optimal injection site for botulinum toxin in the FDS.

Evaluating E. coli genome-scale metabolic model accuracy with high-throughput mutant fitness data.

The Escherichia coli genome-scale metabolic model (GEM) is an exemplar systems biology model for the simulation of cellular metabolism. Experimental validation of model predictions is essential to pinpoint uncertainty and ensure continued development of accurate models. Here, we quantified the accuracy of four subsequent E. coli GEMs using published mutant fitness data across thousands of genes and 25 different carbon sources. This evaluation demonstrated the utility of the area under a precision-recall curve relative to alternative accuracy metrics. An analysis of errors in the latest (iML1515) model identified several vitamins/cofactors that are likely available to mutants despite being absent from the experimental growth medium and highlighted isoenzyme gene-protein-reaction mapping as a key source of inaccurate predictions. A machine learning approach further identified metabolic fluxes through hydrogen ion exchange and specific central metabolism branch points as important determinants of model accuracy. This work outlines improved practices for the assessment of GEM accuracy with high-throughput mutant fitness data and highlights promising areas for future model refinement in E. coli and beyond.

Impact on splicing in Saccharomyces cerevisiae of random 50-base sequences inserted into an intron.

Intron splicing is a key regulatory step in gene expression in eukaryotes. Three sequence elements required for splicing-5' and 3' splice sites and a branchpoint-are especially well-characterized in Saccharomyces cerevisiae, but our understanding of additional intron features that impact splicing in this organism is incomplete, due largely to its small number of introns. To overcome this limitation, we constructed a library in S. cerevisiae of random 50-nt (N50) elements individually inserted into the intron of a reporter gene and quantified canonical splicing and the use of cryptic splice sites by sequencing analysis. More than 70% of approximately 140,000 N50 elements reduced splicing by at least 20%. N50 features, including higher GC content, presence of GU repeats, and stronger predicted secondary structure of its pre-mRNA, correlated with reduced splicing efficiency. A likely basis for the reduced splicing of such a large proportion of variants is the formation of RNA structures that pair N50 bases-such as the GU repeats-with other bases specifically within the reporter pre-mRNA analyzed. However, multiple models were unable to explain more than a small fraction of the variance in splicing efficiency across the library, suggesting that complex nonlinear interactions in RNA structures are not accurately captured by RNA structure prediction methods. Our results imply that the specific context of a pre-mRNA may determine the bases allowable in an intron to prevent secondary structures that reduce splicing. This large data set can serve as a resource for further exploration of splicing mechanisms.

Instability of a viscoelastic film with insoluble surfactants on an oscillating plane

The linear instability of viscoelastic film with insoluble surfactants on an oscillating plane for disturbances with arbitrary wavenumbers is investigated. The combined effects of viscoelastic and insoluble surfactants on the instability are described using Floquet theory. For long-wavelength instability, the solution in the limit of long wave perturbations is obtained by the asymptotic expansion method. The results show that the presence of viscoelastic film shifts the stability boundaries to the low-frequency region in the absence of gravity when the imposed frequency is less than 6. The U-shaped neutral curves with separation bandwidth appear in the presence of gravity. The finite-wavelength instability is solved numerically based on the Chebyshev spectral collocation method. Different from the previous results, a new branch point with special structure of a neutral curve is detected for clean-surface film. Results show that the presence of the surfactants will decrease the unstable frequency bandwidth and increase the critical Reynolds number. Both the travelling-wave mode and standing-wave mode are found due to the existence of surface surfactants. For high-frequency oscillation, the viscoelastic parameter may significantly destabilize the flow and the instability is determined by the finite-wavelength mode over a relatively large frequency range.

Development of a model for granule-bound starch synthase I activity using free-energy calculations

Starch is a branched polymer of glucose with two components, both of which have (1 → 4)-α linear links and (1 → 6)-α branch points: amylopectin, of high molecular weight with many short branches, and amylose, of lower molecular weight and only a few long-chain branches. Granule-bound starch synthase I (GBSSI) is one of the main enzymes controlling amylose synthesis and chain-length distribution. As production of different GBSSI mutants is time-consuming and laborious, molecular dynamics (MD) simulations are used here to predict the binding of different GBSSI mutants to a representative amylose fragment. The simulations were atomistic, with explicit solvent and docking, a method successfully used to understand the binding of wild-type GBSSI to amylose fragments. The binding of GBSSI to G5 (a pentasaccharide amylose fragment) is combined with free-energy calculations employing a thermodynamic integration method to predict the effects of mutations on enzyme activity. Ten GBSSI mutants with different enzyme activities were analyzed to find the structural and energy changes among different single amino-acid mutants and their possible relationship to starch characteristics. Comparing the structural changes and the relative binding free energy of G5 to the wild type GBSSI and GBSSI mutants, it was found that mutants with negative binding energy (lower than −2.0 kcal/mol) are more likely to have higher enzyme activity and amylose content compared to the wild type. This theoretical paper used simulations and robust free energy calculations to interpret in planta data with potential predictions as to what mutants might be generated to give desired properties. This study can be used to help develop grains with improved functional properties.

Solution Self‐Assembly of Branched Macromolecules Obtained via Iterative OPE Synthesis and the Passerini Three‐Component Reaction

AbstractIn the last decade, isocyanide‐based multicomponent reactions, like the Passerini three‐component reaction (P‐3CR), have gained significant interest in the synthesis of sequence‐defined macromolecules due to their high efficiency and straightforward one‐pot procedures. The P‐3CR results in unique product structures that are particularly interesting for the synthesis of uniform, branched macromolecules, as they enable the direct introduction of a new branching point into the molecule. In this work, the synthesis of uniform first‐generation dendrons is performed via the P‐3CR using a divergent approach, utilizing three uniform and poorly soluble oligo(phenylene ethynylene)s (OPEs) of varying lengths as a focal moiety. Self‐assembly of the dendrons in cyclohexane solution is confirmed by fluorescence spectroscopy and diffusion‐ordered NMR (DOSY NMR) spectroscopy, highlighting the utility of DOSY NMR spectroscopy for the investigation of solution self‐assembly. Diffusion coefficients for the dendrons and their aggregates are determined and compared for different lengths of the OPE focal moiety. The successful synthesis of the dendrons in good yields and the selective branching introduced on the OPEs by the P‐3CR emphasize the high efficiency and synthetic advantages of multicomponent reactions for the preparation of uniform, branched macromolecules.

Exploring morphological variations and clinical significance of interconnections between flexor hallucis longus and flexor digitorum longus tendons

BackgroundThe tendons of the flexor hallucis longus (FHL) and flexor digitorum longus (FDL) are commonly utilized in reconstructive foot surgery to address deformities. These tendons intersect on the plantar surface and exhibit varying interconnections that can significantly impact graft length and complicate the tendon harvesting process. The objective of this study was to comprehensively categorize these interconnections using a modified classification system and precisely determine their positional relationships with surgically significant bony landmarks. MethodsSixty embalmed feet of 30 cadavers were studied to analyze the interconnections between FHL and FDL in the planta pedis, classify them in a modified classification system and measure distances to surgically relevant anatomic landmark. ResultsThe study revealed three primary types of interconnections. Type I, representing a proximal-to-distal connection from the FHL to the FDL, was observed in 85% of the feet. Type II, signifying a proximal-to-distal connection from the FDL to the FHL, was found in 11.66% of the feet. Type III, characterized by a crossed connection, was identified in 3.33% of the feet. The average point of branching for the FHL and FDL tendons was situated 4.5 cm and 3.5 cm distal to the navicular tuberosity, respectively. ConclusionThe presence of atypical proximal-to-distal interconnections from the FHL to the FDL may play a role in preserving residual function in the lesser toes following FDL transfer procedures. Awareness of anatomical variations in the location of these interconnections is crucial for preserving them during surgical interventions, ultimately mitigating the risk of functional impairment in the lateral toes post-tendon grafting.

A down‐up chain with persistent labels on multifurcating trees

AbstractIn this article, we propose to study a general notion of a down‐up Markov chain for multifurcating trees with labeled leaves. We study in detail down‐up chains associated with the ‐model of Chen et al. (Electron. J. Probab. 14 (2009), 400–430.), generalizing and further developing previous work by Forman et al. (arXiv:1802.00862, 2018; arXiv:1804.01205, 2018; arXiv:1809.07756, 2018; Random Struct. Algoritm. 54 (2020), 745–769; Electron. J. Probab. 25 (2020), 1–46.) in the binary special cases. The technique we deploy utilizes the construction of a growth process and a down‐up Markov chain on trees with planar structure. Our construction ensures that natural projections of the down‐up chain are Markov chains in their own right. We establish label dynamics that at the same time preserve the labeled alpha‐gamma distribution and keep the branch points between the smallest labels for order time steps for all . We conjecture the existence of diffusive scaling limits generalizing the “Aldous diffusion” by Forman et al. (arXiv:1802.00862, 2018; arXiv:1804.01205, 2018; arXiv:1809.07756, 2018.) as a continuum‐tree‐valued process and the “algebraic ‐Ford tree evolution” by Löhr et al. (Ann. Probab. 48 (2020), 2565–2590.) and by Nussbaumer and Winter (arXiv:2006.09316, 2020.) as a process in a space of algebraic trees.

Mesothelial Cells Exhibit Characteristics of Perivascular Cells in an In Vitro Angiogenesis Assay.

Mesothelial cells have been shown to have remarkable plasticity towards mesenchymal cell types during development and in disease situations. Here, we have characterized the potential of mesothelial cells to undergo changes toward perivascular cells using an in vitro angiogenesis assay. We demonstrate that GFP-labeled mesothelial cells (GFP-MCs) aligned closely and specifically with endothelial networks formed when human dermal microvascular endothelial cells (HDMECs) were cultured in the presence of VEGF-A165 on normal human dermal fibroblasts (NHDFs) for a 7-day period. The co-culture with GFP-MCs had a positive effect on branch point formation indicating that the cells supported endothelial tube formation. We interrogated the molecular response of the GFP-MCs to the angiogenic co-culture by qRT-PCR and found that the pericyte marker Ng2 was upregulated when the cells were co-cultured with HDMECs on NHDFs, indicating a change towards a perivascular phenotype. When GFP-MCs were cultured on the NHDF feeder layer, they upregulated the epithelial-mesenchymal transition marker Zeb1 and lost their circularity while increasing their size, indicating a change to a more migratory cell type. We analyzed the pericyte-like behavior of the GFP-MCs in a 3D cardiac microtissue (spheroid) with cardiomyocytes, cardiac fibroblasts and cardiac endothelial cells where the mesothelial cells showed alignment with the endothelial cells. These results indicate that mesothelial cells have the potential to adopt a perivascular phenotype and associate with endothelial cells to potentially support angiogenesis.

New energy effect in non-cylindrical domains with a thermally insulated moving boundary

Objectives. To develop mathematical model representations of the energy effect in non-cylindrical domains having a thermally insulated moving boundary; to introduce a new boundary condition for thermal insulation of a moving boundary both for locally equilibrium heat transfer processes in the framework of classical Fourier phenomenology, as well as for more complex locally non-equilibrium processes in the framework of Maxwell–Cattaneo–Lykov–Vernott phenomenology, taking into account the finite rate of heat propagation into analytical thermophysics and applied thermomechanics; to consider an applied problem of analytical thermophysics according to the theory of thermal shock for a domain with a moving thermally insulated boundary free from external and internal influences; to obtain an exact analytical solution of the formulated mathematical models for hyperbolic type equations; to investigate the solutions obtained using a computational experiment at various values of the parameters included in it; to describe the wave nature of the kinetics of the processes under consideration.Methods. Methods and theorems of operational calculus, Riemann–Mellin contour integrals are used in calculating the originals of complex images with two branch points. A new mathematical apparatus for the equivalence of functional constructions for the originals of the obtained operational solutions, which considers the computational difficulties in finding analytical solutions to boundary value problems for equations of hyperbolic type in the domain with a moving boundary, is developed.Results. Developed mathematical models of locally nonequilibrium heat transfer and the theory of thermal shock for equations of hyperbolic type in a domain with a moving thermally insulated boundary are presented. It is shown that, despite the absence of external and internal sources of heat, the presence of a thermally insulated moving boundary leads to the appearance of a temperature gradient in the domain and, consequently, to the appearance of a temperature field and corresponding thermoelastic stresses in the domain, which have a wave character. A stochastic analysis of this energy effect forms the basis for a proposed transition of the kinetic energy of a moving thermally insulated boundary into the thermal energy of the domain. The presented model representations of the indicated effect confirmed the stated assumption.Conclusions. Mathematical models for locally nonequilibrium heat transfer processes and the theory of thermal stresses are developed and investigated on the basis of constitutive relations of the theory of thermal shock for equations of hyperbolic type in a domain with a thermally isolated moving boundary. A numerical experiment is presented to demonstrate the possibility of transiting from one form of analytical solution of a thermophysical problem to another equivalent form of a new type. The described energy effect manifests itself both for parabolic type equations based on the classical Fourier phenomenology, as well as for hyperbolic type equations based on the generalized Maxwell–Cattaneo–Lykov–Vernott phenomenology.