Cell Delamination Research Articles

Non-apical mitoses contribute to cell delamination during mouse gastrulation

During the epithelial-mesenchymal transition driving mouse embryo gastrulation, cells divide more frequently at the primitive streak, and half of those divisions happen away from the apical pole. These observations suggest that non-apical mitoses might play a role in cell delamination. We aim to uncover and challenge the molecular determinants of mitosis position in different regions of the epiblast through computational modeling and pharmacological treatments of embryos and stem cell-based epiblast spheroids. Blocking basement membrane degradation at the streak has no impact on the asymmetry in mitosis frequency and position. By contrast, disturbance of the actomyosin cytoskeleton or cell cycle dynamics elicits ectopic non-apical mitosis and shows that the streak region is characterized by local relaxation of the actomyosin cytoskeleton and less stringent regulation of cell division. These factors are essential for normal dynamics at the streak and favor cell delamination from the epiblast.

Experimental and numerical investigation of damage in multilayer sandwich panels with square and trapezoidal corrugated cores under quasi-static three-point bending

Multilayer composite sandwich panels with corrugated cores have the potential for structural applications requiring high stiffness and strength-to-weight ratios. This study aims to experimentally and numerically investigate the bending response of sandwich panels with novel square and trapezoidal corrugated core configurations fabricated from E-glass fiber-reinforced epoxy composites, both with and without polyurethane foam filling. Quasi-static three-point bending tests were conducted to evaluate and compare the flexural stiffness and maximum load capacity of the panel designs. The cores were manufactured using vacuum-assisted resin transfer molding. Key results showed that changing the core geometry from square to trapezoidal improved the bending stiffness by up to 26 %. Incorporating polyurethane foam further increased the bending stiffness by up to 41 % and maximum load by up to 47 % compared to solid cores. Failure initiation and progression were governed by matrix cracking in the face sheets and cores, followed by core cell wall buckling and delamination. Finite element modeling using ABAQUS captured the progressive damage behavior, exhibiting good agreement with experimental force-displacement responses. Failure modes included matrix cracks, fiber fractures, core buckling and delamination. This study provides valuable insights into the mechanical performance of innovative corrugated core sandwich panel designs under quasi-static bending loads. The validated FE approach also enables virtual testing and optimization of composite sandwich structures.

Basal delamination during mouse gastrulation primes pluripotent cells for differentiation

The blueprint of the mammalian body plan is laid out during gastrulation, when a trilaminar embryo is formed. This process entails a burst of proliferation, the ingression of embryonic epiblast cells at the primitive streak, and their priming toward primitive streak fates. How these different events are coordinated remains unknown. Here, we developed and characterized a 3D culture of self-renewing mouse embryonic cells that captures the main transcriptional and architectural features of the early gastrulating mouse epiblast. Using this system in combination with microfabrication and invivo experiments, we found that proliferation-induced crowding triggers delamination of cells that express high levels of the apical polarity protein aPKC. Upon delamination, cells become more sensitive to Wnt signaling and upregulate the expression of primitive streak markers such as Brachyury. This mechanistic coupling between ingression and differentiation ensures that the right cell types become specified at the right place during embryonic development.

Collective cell migration relies on PPP1R15-mediated regulation of the endoplasmic reticulum stress response

Collective cell migration is integral to many developmental and disease processes. Previously, we discovered that protein phosphatase 1 (Pp1) promotes border cell collective migration in the Drosophila ovary. We now report that the Pp1 phosphatase regulatory subunit dPPP1R15 is a critical regulator of border cell migration. dPPP1R15 is an ortholog of mammalian PPP1R15 proteins that attenuate the endoplasmic reticulum (ER) stress response. We show that, in collectively migrating border cells, dPPP1R15 phosphatase restrains an active physiological protein kinase R-like ER kinase- (PERK)-eIF2α-activating transcription factor 4 (ATF4) stress pathway. RNAi knockdown of dPPP1R15 blocks border cell delamination from the epithelium and subsequent migration, increases eIF2α phosphorylation, reduces translation, and drives expression of the stress response transcription factor ATF4. We observe similar defects upon overexpression of ATF4 or the eIF2α kinase PERK. Furthermore, we show that normal border cells express markers of the PERK-dependent ER stress response and require PERK and ATF4 for efficient migration. In many other cell types, unresolved ER stress induces initiation of apoptosis. In contrast, border cells with chronic RNAi knockdown of dPPP1R15 survive. Together, our results demonstrate that the PERK-eIF2α-ATF4 pathway, regulated by dPPP1R15 activity, counteracts the physiological ER stress that occurs during collective border cell migration. We propose that invivo collective cell migration is intrinsically "stressful," requiring tight homeostatic control of the ER stress response for collective cell cohesion, dynamics, and movement.

Online monitoring of epithelial barrier kinetics and cell detachment during cisplatin-induced toxicity of renal proximal tubule cells.

Real-time and non-invasive assessment of tissue health is crucial for maximizing the potential of microphysiological systems (MPS) for drug-induced nephrotoxicity screening. Although impedance has been widely considered as a measure of the barrier function, it has not been incorporated to detect cell detachment in MPS with top and bottom microfluidic channels separated by a porous membrane. During cell delamination from the porous membrane, the resistance between both channels decreases, while capacitance increases, allowing the detection of such detachment. Previously reported concepts have solely attributed the decrease in the resistance to the distortion of the barrier function, ignoring the resistance and capacitance changes due to cell detachment. Here, we report a two-channel MPS with integrated indium tin oxide (ITO) electrodes capable of measuring impedance in real time. The trans-epithelial electrical resistance (TEER) and tissue reactance (capacitance) were extracted from the impedance profiles. We attributed the anomalous initial increase observed in TEER, upon cisplatin administration, to the distortion of tight junctions. Cell detachment was captured by sudden jumps in capacitance. TEER profiles illuminated the effects of cisplatin and cimetidine treatments in a dose-dependent and polarity-dependent manner. The correspondence between TEER and barrier function was validated for a continuous tissue using the capacitance profiles. These results demonstrate that capacitance can be used as a real-time and non-invasive indicator of confluence and will support the accuracy of the drug-induced cytotoxicity assessed by TEER profiles in the two-channel MPS for the barrier function of a cell monolayer.

Conductive filament distribution in nano-scale electrochemical metallization cells.

We report a combined experimental and theoretical study of the spatial distributions and sizes of conductive filaments in nano-scale electrochemical metallization (ECM) cells. Each cell comprises a silver nanocube as active electrode, a titanium dioxide (TiO2) or aluminum oxide (Al2O3) layer as dielectric, and a highly-doped silicon substrate as passive counter electrode. Following electroforming of the ECM cell and subsequent mechanical delamination of the silver nanocubes, current maps at previous particle locations reveal an intriguing metal distribution in the TiO2, with preferential accumulation close to the original locations of the nanocube edges. We assign this behavior to electric field enhancements close to the cube edge positions. In contrast, filaments in Al2O3 layers show a comparatively homogenous distribution, which may be assigned to its lower dielectric permittivity. By increasing the oxide thickness, the total area of conductive spots in the current maps increases monotonically for both materials. Kinetic Monte-Carlo simulations of ion migration dynamics in TiO2 confirm the experimental observations, describing both the preferred locations and oxide thickness-dependent metal loadings associated with filament formation. Overall, our findings are highly valuable for the design of future electrochemical metallization cells, especially in the sub-100 nm regime, where optimal filament control is of major importance for achieving lowest device-to-device variability.

Integrins Can Act as Suppressors of Ras-Mediated Oncogenesis in the Drosophila Wing Disc Epithelium.

Cancer is the second leading cause of death worldwide. Key to cancer initiation and progression is the crosstalk between cancer cells and their microenvironment. The extracellular matrix (ECM) is a major component of the tumour microenvironment and integrins, main cell-ECM adhesion receptors, are involved in every step of cancer progression. However, accumulating evidence has shown that integrins can act as tumour promoters but also as tumour suppressor factors, revealing that the biological roles of integrins in cancer are complex. This incites a better understating of integrin function in cancer progression. To achieve this goal, simple model organisms, such as Drosophila, offer great potential to unravel underlying conceptual principles. Here, we find that in the Drosophila wing disc epithelium the βPS integrins act as suppressors of tumours induced by a gain of function of the oncogenic form of Ras, RasV12. We show that βPS integrin depletion enhances the growth, delamination and invasive behaviour of RasV12 tumour cells, as well as their ability to affect the tumour microenvironment. These results strongly suggest that integrin function as tumour suppressors might be evolutionarily conserved. Drosophila can be used to understand the complex tumour modulating activities conferred by integrins, thus facilitating drug development.

IAC-22-C3.3.8 Six years of spaceflight results from the AlSat-1N Thin-Film Solar Cell (TFSC) experiment

The increasing power demands of spacecraft payloads and the realistic prospect of space based solar power (SBSP) stations as a means of providing zero carbon electricity in the 2030s, means that there is an emerging requirement for large area, yet lightweight, solar photovoltaic (PV) arrays that will provide far greater power (kWpeak) than is currently available. To be practical, such arrays will need to use solar cells which have a much higher specific power (i.e., power per unit mass) and a much lower cost per watt than current space-rated solar PV technologies. To this end, the Centre for Solar Energy Research (CSER) at Swansea University have been working on a new solar cell technology, based on thin-film cadmium telluride (CdTe), deposited directly onto ultra-thin space qualified cover glass material. This offers a potentially high specific power and when adopting the conventional CdTe manufacturing process, a low-cost technology. The ultra-thin glass can produce a solar cell which is sufficiently flexible to allow “roll-out” deployment strategies. Four prototype cells were flown as part of the Thin-Film Solar Cell (TFSC) experimental payload, developed by CSER and the Surrey Space Centre (SSC), on the joint Algerian Space Agency (ASAL) – UK Space Agency AlSAT-1N Technology Demonstration CubeSat, launched into a 661 km × 700 km, 98.20° Sun Synchronous orbit, on September 26, 2016. The experiment has provided the first in-orbit current/voltage (I/V) measurements of this novel technology, and more than five years of flight results have now yielded new insights into its longer-term performance and inherent radiation hardness, which makes them particularly attractive for maintaining high end-of-life (EOL) performance for long duration space missions. The results help to strengthen the argument for further development of this technology for space application. The data, collected over ∼30,000 orbits, show no signs of cell delamination (a potential risk for such technologies), no deterioration in short circuit current or in series resistance. However, all four cell's fill factors were observed to decrease over the duration of the mission, caused primarily by a decrease in their shunt resistance. This has been attributed to the diffusion of gold atoms from the back electrical contacts. We conclude therefore that further development of this technology should utilize more stable back contacting methodologies more commonly employed for terrestrial CdTe modules. However, this flight has proven the basic soundness of the technology for use in space.

High and durable performance of an external-manifold designed reversible solid oxide cell stack

A 5-cell reversible solid oxide cell stack in external-manifold design is fabricated with planar cells with an active area of 169 cm2, Ni–Y2O3 stabilized ZrO2 (Ni-YSZ) support, Ni-YSZ functional anode (fuel electrode), YSZ electrolyte, and YSZ-composite cathode (air electrode). It is operated at various temperatures in different atmospheres. In fuel cell mode at 750 °C with H2 fuel and air oxidant, the stack generates 407 W (481.7 mW cm−2, 81.4 W per cell) at 0.68 A cm−2. In electrolysis mode, with H2-55% H2O at 750 °C, the current density at the thermo-neutral voltage (6.45 V) is −0.340 A cm−2, and concentration polarization starts at around −0.3 A cm−2. They are −0.592 A cm−2 and above −0.50 A cm−2, respectively, under 80% H2O and 800 °C. H2 production rate increases from 88 NL h−1 to 209 NL h−1, accordingly. Using H2-80% H2O for fuel electrode at 800 °C, the stack performs at around 7.0 V and −0.5 A cm−2 for up to 900 h without gas leaking and cell delamination and with more severe metal oxidation at the spots where the SUS430 interconnect contacts with Ni foam current collector on the fuel electrode side.

Apoptotic extracellular vesicle formation via local phosphatidylserine exposure drives efficient cell extrusion.

Cell extrusion is a universal mode of cell removal from tissues, and it plays an important role in regulating cell numbers and eliminating unwanted cells. However, the underlying mechanisms of cell delamination from the cell layer are unclear. Here, we report a conserved execution mechanism of apoptotic cell extrusion. We found extracellular vesicle (EV) formation in extruding mammalian and Drosophila cells at a site opposite to the extrusion direction. Lipid-scramblase-mediated local exposure of phosphatidylserine is responsible for EV formation and is crucial for executing cell extrusion. Inhibition of this process disrupts prompt cell delamination and tissue homeostasis. Although the EV has hallmarks of an apoptotic body, its formation is governed by the mechanism of microvesicle formation. Experimental and mathematical modeling analysis illustrated that EV formation promotes neighboring cells' invasion. This study showed that membrane dynamics play a crucial role in cell exit by connecting the actions of the extruding cell and neighboring cells.

291-LB: Possible Alpha-Cell Regeneration from Mucin-Producing Ducts in Zinc-Binding Site-Mutated CRY1-Expressing Diabetic Mice

C414A-CRY1 transgenic mice (TG) show the symptoms of diabetes due to cellular senescence-like phenotypes in their β-cells as we have reported at ADA Scientific Sessions in 2015. Due to the cellular phenotypes, structural remodeling in islets of TG progresses with age (S. Okano et al., ADA 2016-2022): the increase of the population ratios of α-cell to β-cell and of δ-cell to β-cell as well as the occurrence of fibrillation, angiogenesis and also the generation of mucin-producing intra-islet ductal cells (IIDCs) were observed. Contrary to normal ductal cells, IIDCs only weakly react with DBA lectin, indicating unique characters different from normal ductal cells (ADA 2019). Also, we have shown the results suggesting that δ-cells may play some role as the source for β-cells to supply new β-cells in TG (ADA 2022). To examine the possible roles of IIDCs to maintain of the amount of pancreatic endocrine cells under hyperglycemia for prolonged period in TG, in this study, we conducted detailed immune-staining experiments which focused on fully developed IIDCs, not small ones that still not fully developed. We distinguished IIDCs from normal ducts, PanINs as well as PDGs as the measure of the reactivity to DBA-lectin. Chromogranin A-positive cells were observed in IIDCs, but not in normal ducts, PanINs and PDGs. Then we examined IIDCs with anti-hormone antibodies. In the region of developed IIDCs, cytokeratin 17/19 and glucagon double-positive cells were predominantly observed. Only small portion of somatostatin-positive cells were clearly located adjacent to IIDCs. Cluster of β-cells were located apart from IIDCs. In addition, scrutinized observations suggested the delamination of glucagon-positive cells from the ductal epithelium of the IIDCs. Taken together, these results strongly suggest the possible neogenesis of endocrine cells in IIDCs, that is, IIDCs and their lining cells play roles as the source for endocrine cells, particularly for α, and also for δ cells. Disclosure S. Okano: None. A. Yasui: None. S. Kanno: None. Y. Sasaki: None. K. Satoh: None. M. Igarashi: None. O. Nakajima: None. Funding Grants-in-Aid for Scientific Research (19K07498); Tohoku University Institute of Development, Aging and Cancer

Understanding Chemo-Mechanical Stability of Protonic Ceramic Cells Through Electronic Conduction in the BaCe0.7Zr0.1Y0.1Yb0.1O3-δ Electrolyte

BaCe0.7Zr0.1Y0.1Yb0.1O3-δ (BCZYYb) is a promising ceramic electrolyte for reversible protonic ceramic cells. It is reported that BCZYYb-based cells show excellent long-term durability, particularly in the electrolysis mode, in contrast to the cells based on the conventional electrolyte yttria-stabilized zirconia. In this study, we investigate the chemo-mechanical stability behavior (a low tendency of delamination) of the BCZYYb-based protonic ceramic cells in terms of local electronic conduction in the electrolyte. The local electronic conductivity of the BCZYYb electrolyte is determined using Pt-probe-embedded cells near each electrode interface. The BCZYYb electrolyte exhibits sufficient p-type conductivity (∼10−3 S cm−1) near the oxygen electrode (corresponding 5.27–21 × 10−2 atm) and n-type conductivity (∼10−4 S cm−1) near the hydrogen electrode (corresponding 0.99–1.30 × 10−24 atm) at 600 °C. A standard cell is prepared and tested over long-term in the fuel cell (at positive and negative voltages) and electrolysis modes. The cell exhibits stable performance without delamination or cracks in both operating modes, owing to local electronic conduction.

Early stages of decay in Eucalyptus grandis trees inoculated with brown-rot fungi

In natural ecosystems, brown-rot fungi are major biodegrading agents of standing trees and dead wood. Decay caused by basidiomycetes results in structural instability and therefore negatively affects the quality and quantity of the produced wood. Fungal attack can also trigger defense mechanisms within the tree aimed at delaying or halting the progress of infection. As these defense mechanisms can decrease the value of the wood, their identification and study are of foremost importance. In this work, healthy trees of Eucalyptus grandis W.Hill — a widely commercialized species in Uruguay — were inoculated with Laetiporus sulphureus and Gloeophyllum trabeum. The decay process was characterized in terms of chemical and anatomical changes, and the defense mechanisms elicited by the tree were identified. Three months after inoculation, no symptoms of infection could be detected with the naked eye; however, microscopic analysis revealed anatomical and chemical changes (weakening, delamination, and rupture of vascular and parenchymal cells) and decreased holocellulose and lignin contents. Compartmentalization and the production of kino were used by the tree as defense mechanisms.

CAM-Delam Assay to Score Metastatic Properties by Quantifying Delamination and Invasion Capacity of Cancer Cells.

The major cause of cancer-related deaths is metastasis formation (i.e., when cancer cells spread from the primary tumor to distant organs and form secondary tumors). Delamination, defined as the degradation of the basal lamina and basement membrane, is the initial process that facilitates the transmigration and spread of cancer cells to other tissues and organs. Scoring the delamination capacity of cancer cells would indicate the metastatic potential of these cells. We have developed a standardized method, the ex ovo CAM-Delam assay, to visualize and quantify the ability of cancer cells to delaminate and invade, thereby being able to assess metastatic aggressiveness. Briefly, the CAM-Delam method includes seeding cancer cells in silicone rings on the chick chorioallantoic membrane (CAM) at embryonic day 10, followed by incubation from hours to a few days. The CAM-Delam assay includes the use of an internal humidified chamber during chick embryo incubation. This novel approach increased embryo survival from 10%-50% to 80%-90%, which resolved previous technical problems with low embryo survival rates in different CAM assays. Next, the CAM samples with associated cancer cell clusters were isolated, fixed, and frozen. Finally, cryostat-sectioned samples were visualized and analyzed for basement membrane damage and cancer cell invasion using immunohistochemistry. By evaluating various known metastatic and non-metastatic cancer cell lines designed to express green fluorescent protein (GFP), the CAM-Delam quantitative results showed that the delamination capacity patterns reflect metastatic aggressiveness and can be scored into four categories. Future use of this assay, apart from quantifying delamination capacity as an indication of metastatic aggressiveness, is to unravel the molecular mechanisms that control delamination, invasion, the formation of micrometastases, and changes in the tumor microenvironment.

CAM-Delam Assay to Score Metastatic Properties by Quantifying Delamination and Invasion Capacity of Cancer Cells

The major cause of cancer-related deaths is metastasis formation (i.e., when cancer cells spread from the primary tumor to distant organs and form secondary tumors). Delamination, defined as the degradation of the basal lamina and basement membrane, is the initial process that facilitates the transmigration and spread of cancer cells to other tissues and organs. Scoring the delamination capacity of cancer cells would indicate the metastatic potential of these cells. We have developed a standardized method, the ex ovo CAM-Delam assay, to visualize and quantify the ability of cancer cells to delaminate and invade, thereby being able to assess metastatic aggressiveness. Briefly, the CAM-Delam method includes seeding cancer cells in silicone rings on the chick chorioallantoic membrane (CAM) at embryonic day 10, followed by incubation from hours to a few days. The CAM-Delam assay includes the use of an internal humidified chamber during chick embryo incubation. This novel approach increased embryo survival from 10%-50% to 80%-90%, which resolved previous technical problems with low embryo survival rates in different CAM assays. Next, the CAM samples with associated cancer cell clusters were isolated, fixed, and frozen. Finally, cryostat-sectioned samples were visualized and analyzed for basement membrane damage and cancer cell invasion using immunohistochemistry. By evaluating various known metastatic and non-metastatic cancer cell lines designed to express green fluorescent protein (GFP), the CAM-Delam quantitative results showed that the delamination capacity patterns reflect metastatic aggressiveness and can be scored into four categories. Future use of this assay, apart from quantifying delamination capacity as an indication of metastatic aggressiveness, is to unravel the molecular mechanisms that control delamination, invasion, the formation of micrometastases, and changes in the tumor microenvironment.

Border cell polarity and collective migration require the spliceosome component Cactin.

Border cells are an in vivo model for collective cell migration. Here, we identify the gene cactin as essential for border cell cluster organization, delamination, and migration. In Cactin-depleted cells, the apical proteins aPKC and Crumbs (Crb) become abnormally concentrated, and overall cluster polarity is lost. Apically tethering excess aPKC is sufficient to cause delamination defects, and relocalizing apical aPKC partially rescues delamination. Cactin is conserved from yeast to humans and has been implicated in diverse processes. In border cells, Cactin's evolutionarily conserved spliceosome function is required. Whole transcriptome analysis revealed alterations in isoform expression in Cactin-depleted cells. Mutations in two affected genes, Sec23 and Sec24CD, which traffic Crb to the apical cell surface, partially rescue border cell cluster organization and migration. Overexpression of Rab5 or Rab11, which promote Crb and aPKC recycling, similarly rescues. Thus, a general splicing factor is specifically required for coordination of cluster polarity and migration, and migrating border cells are particularly sensitive to splicing and cell polarity disruptions.

The Desmosome-Keratin Scaffold Integrates ErbB Family and Mechanical Signaling to Polarize Epidermal Structure and Function.

While classic cadherin-actin connections in adherens junctions (AJs) have ancient origins, intermediate filament (IF) linkages with desmosomal cadherins arose in vertebrate organisms. In this mini-review, we discuss how overlaying the IF-desmosome network onto the existing cadherin-actin network provided new opportunities to coordinate tissue mechanics with the positioning and function of chemical signaling mediators in the ErbB family of receptor tyrosine kinases. We focus in particular on the complex multi-layered outer covering of the skin, the epidermis, which serves essential barrier and stress sensing/responding functions in terrestrial vertebrates. We will review emerging data showing that desmosome-IF connections, AJ-actin interactions, ErbB family members, and membrane tension are all polarized across the multiple layers of the regenerating epidermis. Importantly, their integration generates differentiation-specific roles in each layer of the epidermis that dictate the form and function of the tissue. In the basal layer, the onset of the differentiation-specific desmosomal cadherin desmoglein 1 (Dsg1) dials down EGFR signaling while working with classic cadherins to remodel cortical actin cytoskeleton and decrease membrane tension to promote cell delamination. In the upper layers, Dsg1 and E-cadherin cooperate to maintain high tension and tune EGFR and ErbB2 activity to create the essential tight junction barrier. Our final outlook discusses the emerging appreciation that the desmosome-IF scaffold not only creates the architecture required for skin’s physical barrier but also creates an immune barrier that keeps inflammation in check.

Mismatching and partial shading identification in photovoltaic arrays by an artificial neural network ensemble

Photovoltaic arrays may suffer from a number of temporary and permanent faults. Partial shading and soiling belong to the former group, while cell cracking and delamination fall within the latter one. In these cases, the shape of the current vs voltage curve around the maximum power point shows features that are different from those ones of an array operating in normal conditions. The shape change should allow triggering, in case of a temporary fault, control actions that might improve the electrical power production. Instead, if the fault is permanent, the identification of the modified shape should activate a procedure for a more in-depth analysis of the problem and a maintenance action. In this paper, the conditions leading to a change in the array behavior during its delivering of the maximum power are examined. The change of curvature of the current vs voltage curve around its maximum power point is suitably detected to trigger the fault mitigation action. The feature is caught through an ensemble of artificial neural networks, which analyzes the current vs voltage curve and classifies the module as healthy or faulty. It is demonstrated that few samples around the maximum power point are required, this meaning that the proposed approach is compatible with the operation of any perturbative maximum power point tracking algorithm and its application does not lead to any power production drop. In addition, the approach does not require neither temperature nor irradiance measurements as inputs. The neural networks are trained through synthetic data, so that their application is not limited to arrays including a specific photovoltaic module. The method is also validated through experimental data.

Low thermal-expansion and high proton uptake for protonic ceramic fuel cell cathode

Nowadays, the excessive thermal expansion behavior of Co-based electrode always leads to the cell degradation or delamination. Especially for BaCoO3-δ-type perovskite oxides, as the result of the large ionic radius of Ba2+ (1.61 Å), the phase structures of these materials are not stable. Herein, we developed a novel single-phase electrode Ba2Sc0.1Nb0.1Co1.5Fe0.3O6-δ (BSNCF) with a stable cubic perovskite structure and suitable thermal expansion coefficient (TEC, 11.9 × 10−6 K−1), which showed a great stability in symmetrical cell area specific resistances (ASRs) subjecting to the harsh thermal cycling procedure with 30 cycles between 300 °C and 600 °C (increased from 0.197 Ω cm2 to 0.222 Ω cm2,13% increase). The high-temperature hard X-ray absorption spectroscopy measurement directly monitored a small change of Co valence in BSNCF as the temperatures rising. Also, BSNCF exhibits well proton uptake for its appropriate oxygen-site basicity and excellent surface reaction activity. The single cell based on BSNCF achieved an outstanding peak power density of 977 mW cm−2 at 600 °C.

Regulation of Cell Delamination During Cortical Neurodevelopment and Implication for Brain Disorders.

Cortical development is dependent on key processes that can influence apical progenitor cell division and progeny. Pivotal among such critical cellular processes is the intricate mechanism of cell delamination. This indispensable cell detachment process mainly entails the loss of apical anchorage, and subsequent migration of the mitotic derivatives of the highly polarized apical cortical progenitors. Such apical progenitor derivatives are responsible for the majority of cortical neurogenesis. Many factors, including transcriptional and epigenetic/chromatin regulators, are known to tightly control cell attachment and delamination tendency in the cortical neurepithelium. Activity of these molecular regulators principally coordinate morphogenetic cues to engender remodeling or disassembly of tethering cellular components and external cell adhesion molecules leading to exit of differentiating cells in the ventricular zone. Improper cell delamination is known to frequently impair progenitor cell fate commitment and neuronal migration, which can cause aberrant cortical cell number and organization known to be detrimental to the structure and function of the cerebral cortex. Indeed, some neurodevelopmental abnormalities, including Heterotopia, Schizophrenia, Hydrocephalus, Microcephaly, and Chudley-McCullough syndrome have been associated with cell attachment dysregulation in the developing mammalian cortex. This review sheds light on the concept of cell delamination, mechanistic (transcriptional and epigenetic regulation) nuances involved, and its importance for corticogenesis. Various neurodevelopmental disorders with defective (too much or too little) cell delamination as a notable etiological underpinning are also discussed.