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The Journal of Pathology Jun 2024Loss of the cell-cell adhesion protein E-cadherin underlies the development of diffuse-type gastric cancer (DGC), which is characterized by the gradual accumulation of...
Loss of the cell-cell adhesion protein E-cadherin underlies the development of diffuse-type gastric cancer (DGC), which is characterized by the gradual accumulation of tumor cells originating from the gastric epithelium in the surrounding stroma. How E-cadherin deficiency drives DGC formation remains elusive. Therefore, we investigated the consequences of E-cadherin loss on gastric epithelial organization utilizing a human gastric organoid model and histological analyses of early-stage DGC lesions. E-cadherin depletion from gastric organoids recapitulates DGC initiation, with progressive loss of a single-layered architecture and detachment of individual cells. We found that E-cadherin deficiency in gastric epithelia does not lead to a general loss of epithelial cohesion but disrupts the spindle orientation machinery. This leads to a loss of planar cell division orientation and, consequently, daughter cells are positioned outside of the gastric epithelial layer. Although basally delaminated cells fail to detach and instead reintegrate into the epithelium, apically mispositioned daughter cells can trigger the gradual loss of the single-layered epithelial architecture. This impaired architecture hampers reintegration of mispositioned daughter cells and enables basally delaminated cells to disseminate into the surrounding matrix. Taken together, our findings describe how E-cadherin deficiency disrupts gastric epithelial architecture through displacement of dividing cells and provide new insights in the onset of DGC. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Organoids; Madin Darby Canine Kidney Cells; Animals; Dogs; Stomach; Stomach Neoplasms; Epithelium; Cell Division; Cell Proliferation
PubMed: 38572612
DOI: 10.1002/path.6277 -
Canadian Journal of Ophthalmology.... Oct 2023
Topics: Humans; Retinal Detachment; Retinal Hemorrhage; Cysts
PubMed: 36828137
DOI: 10.1016/j.jcjo.2023.01.021 -
Retinal Cases & Brief Reports Nov 2023To describe a case of chronic pediatric retinal detachment with multiple macrocysts, its surgical management, and a review of the literature. (Review)
Review
PURPOSE
To describe a case of chronic pediatric retinal detachment with multiple macrocysts, its surgical management, and a review of the literature.
METHODS
Case report with fundus photography and optical coherence tomography.
RESULTS
We describe a case of an asymptomatic, 11-year-old boy with a chronic rhegmatogenous retinal detachment with multiple peripheral macrocysts. The patient had counting fingers visual acuity on presentation. The detachment was successfully surgically repaired with scleral buckling, subretinal fluid drainage, cryotherapy, and a SF6 tamponade. At the 12-month follow-up, the retina remained attached with improvement of visual acuity to 20/100 with resolution of the cysts. Optical coherence tomography revealed loss of macular ellipsoid zone. Genetic testing revealed a heterozygous dominant COL11A1 mutation.
CONCLUSION
To the authors' knowledge, this is the first reported case of chronic retinal detachment presenting with multiple peripheral macrocysts in a pediatric patient with Stickler syndrome. More research is needed into the cause and significance of retinal macrocysts, particularly in the pediatric population.
Topics: Male; Humans; Child; Retinal Detachment; Scleral Buckling; Retina; Visual Acuity; Cryotherapy; Vitrectomy; Tomography, Optical Coherence
PubMed: 35972836
DOI: 10.1097/ICB.0000000000001288 -
Frontiers in Microbiology 2023Plant breeding is used to develop crops with host resistance to aphids, however, virulent biotypes often develop that overcome host resistance genes. We tested whether...
Plant breeding is used to develop crops with host resistance to aphids, however, virulent biotypes often develop that overcome host resistance genes. We tested whether the symbionts, () and (), affect virulence and fecundity in soybean aphid biotypes Bt1 and Bt3 cultured on whole plants and detached leaves of three resistant, , and and one susceptible, , soybean genotypes. Whole plants and individual aphid experiments of with and without and did not show differences in overall fecundity. Differences were observed in peak fecundity, first day of deposition, and day of maximum nymph deposition of individual aphids on detached leaves. Bt3 had higher fecundity than Bt1 on detached leaves of all plant genotypes regardless of bacterial profile. Symbionts did not affect peak fecundity of Bt1 but increased it in Bt3 (++) and all Bt3 strains began to deposit nymphs earlier than the Bt1 (+-). in Bt1 delayed the first day of nymph deposition in comparison to aposymbiotic Bt1 except when reared on . For the Bt1 and Bt3 strains, symbionts did not result in a significant difference in the day they deposited the maximum number of nymphs nor was there a difference in survival or variability in number of nymphs deposited. Variability of number of aphids deposited was higher in aphids feeding on resistant plant genotypes. The impact of on soybean aphid patterns of fecundity was dependent on the aphid biotype and plant genotype. alone had no detectable impact but may have contributed to the increased fecundity of Bt3 (++). An individual based model, using data from the detached leaves experiment and with intraspecific competition removed, found patterns similar to those observed in the greenhouse and growth chamber experiments including a significant interaction between soybean genotype and aphid strain. Combining individual data with the individual based model of population growth isolated the impact of fecundity and host resistance from intraspecific competition and host health. Changes to patterns of fecundity, influenced by the composition and concentration of symbionts may contribute to competitive interactions among aphid genotypes and influence selection on virulent aphid populations.
PubMed: 37720159
DOI: 10.3389/fmicb.2023.1209595 -
The Journal of Biological Chemistry Dec 2023Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and glycosphingolipids and serve as major platforms for signal transduction. Cell...
Lipid rafts are highly ordered membrane domains that are enriched in cholesterol and glycosphingolipids and serve as major platforms for signal transduction. Cell detachment from the extracellular matrix (ECM) triggers lipid raft disruption and anoikis, which is a barrier for cancer cells to metastasize. Compared to single circulating tumor cells (CTCs), our recent studies have demonstrated that CD44-mediatd cell aggregation enhances the stemness, survival and metastatic ability of aggregated cells. Here, we investigated whether and how lipid rafts are involved in CD44-mediated cell aggregation. We found that cell detachment, which mimics the condition when tumor cells detach from the ECM to metastasize, induced lipid raft disruption in single cells, but lipid raft integrity was maintained in aggregated cells. We further found that lipid raft integrity in aggregated cells was required for Rac1 activation to prevent anoikis. In addition, CD44 and γ-secretase coexisted at lipid rafts in aggregated cells, which promoted CD44 cleavage and generated CD44 intracellular domain (CD44 ICD) to enhance stemness of aggregated cells. Consequently, lipid raft disruption inhibited Rac1 activation, CD44 ICD generation, and metastasis. Our findings reveal two new pathways regulated by CD44-mediated cell aggregation via maintaining lipid raft integrity. These findings also suggest that targeting cell aggregation-mediated pathways could be a novel therapeutic strategy to prevent CTC cluster-initiated metastasis.
Topics: Cell Aggregation; Extracellular Matrix; Membrane Microdomains; Monomeric GTP-Binding Proteins; Signal Transduction; MDA-MB-231 Cells; Humans; Animals; Mice; Cell Line, Tumor; Mice, Inbred BALB C; Hyaluronan Receptors; rac1 GTP-Binding Protein; Anoikis; Enzyme Activation; Neoplasm Metastasis
PubMed: 37866630
DOI: 10.1016/j.jbc.2023.105377 -
Journal of Experimental Botany Oct 2023Fruit quality traits are determined to a large extent by their metabolome. The metabolite content of climacteric fruit changes drastically during ripening and... (Review)
Review
Fruit quality traits are determined to a large extent by their metabolome. The metabolite content of climacteric fruit changes drastically during ripening and post-harvest storage, and has been investigated extensively. However, the spatial distribution of metabolites and how it changes in time has received much less attention as fruit are usually considered as homogenous plant organs. Yet, spatio-temporal changes of starch, which is hydrolyzed during ripening, has been used for a long time as a ripening index. As vascular transport of water, and hence convective transport of metabolites, slows down in mature fruit and even stalls after detachment, spatio-temporal changes in their concentration are probably affected by diffusive transport of gaseous molecules that act as substrate (O2), inhibitor (CO2), or regulator (ethylene and NO) of the metabolic pathways that are active during climacteric ripening. In this review, we discuss such spatio-temporal changes of the metabolome and how they are affected by transport of metabolic gases and gaseous hormones. As there are currently no techniques available to measure the metabolite distribution repeatedly by non-destructive means, we introduce reaction-diffusion models as an in silico tool to compute it. We show how the different components of such a model can be integrated and used to better understand the role of spatio-temporal changes of the metabolome in ripening and post-harvest storage of climacteric fruit that is detached from the plant, and discuss future research needs.
Topics: Fruit; Ethylenes; Metabolome; Climacteric; Gases
PubMed: 37317945
DOI: 10.1093/jxb/erad230 -
Food Research International (Ottawa,... Nov 2023Double-layered flat bread features an impressive oven rise and delamination during baking, leading to the formation of an internal pocket capable of holding various...
Double-layered flat bread features an impressive oven rise and delamination during baking, leading to the formation of an internal pocket capable of holding various solid foods - a key quality criterion for consumers. These breads are unique in their baking method, which requires specialized ovens and high temperatures between 350 and 550 °C. Use of high baking temperatures to achieve the double layering development (called delamination) during baking has raised concerns over excessive energy consumption. In this study, whether or not the application of fermentation (affecting the accumulation of dissolved CO) and baking temperature (which affects gas generation) were varied and the impacts on delamination were evaluated. To complement this evaluation, dough water content and temperature were monitored during baking. In a novel manner, this study characterized water distribution in flat bread, explaining the surprising decrease of water loss with increasing baking temperature. Our study has clearly shown water vapor to be the prime cause of delamination. The role of water pressure in dough inflation and in causing the edges to detach from the deck and the heterogeneity of flat bread water content were highlighted and a concept map proposed.
Topics: Cooking; Bread; Temperature
PubMed: 37803653
DOI: 10.1016/j.foodres.2023.113350 -
Polymers Oct 2023Supramolecular responsive microcarriers based on chitosan microspheres were prepared and applied for nonenzymatic cell detachment. Briefly, chitosan microspheres (CSMs)...
Supramolecular responsive microcarriers based on chitosan microspheres were prepared and applied for nonenzymatic cell detachment. Briefly, chitosan microspheres (CSMs) were first prepared by an emulsion crosslinking approach, the surface of which was then modified with β-cyclodextrin (β-CD) by chemical grafting. Subsequently, gelatin was attached onto the surface of the CSMs via the host-guest interaction between β-CD groups and aromatic residues in gelatin. The resultant microspheres were denoted CSM-g-CD-Gel. Due to their superior biocompatibility and gelatin niches, CSM-g-CD-Gel microspheres can be used as effective microcarriers for cell attachment and expansion. L-02, a human fetal hepatocyte line, was used to evaluate cell attachment and expansion with these microcarriers. After incubation for 48 h, the cells attached and expanded to cover the entire surface of microcarriers. Moreover, with the addition of adamantane (AD), cells can be detached from the microcarriers together with gelatin because of the competitive binding between β-CD and AD. Overall, these supramolecular responsive microcarriers could effectively support cell expansion and achieve nonenzymatic cell detachment and may be potentially reusable with a new cycle of gelatin attachment and detachment.
PubMed: 37836073
DOI: 10.3390/polym15194024 -
International Journal of Environmental... Jul 2023Owing to the COVID-19 pandemic, organizations worldwide have implemented remote working arrangements that have blurred the work-family boundaries and brought to the...
Owing to the COVID-19 pandemic, organizations worldwide have implemented remote working arrangements that have blurred the work-family boundaries and brought to the forefront employees' sense of disconnectedness from their workplace (i.e., organizational disconnectedness) as a concern for multiple organizational outcomes. Cynicism, a job burnout subdimension, refers to a negative and excessively detached response to relational overload at work. While both workplace disconnectedness and cynicism involve a toxic sense of detachment, they refer to different psychological mechanisms. The present study aims to examine how employee workplace disconnectedness differs from their cynicism, and how both constructs differentially exert their detrimental effects on employee performance, work-family interface, and wellbeing. Using anonymous survey data collected online in 2021 and 2022 from a sample of in-person and flexible workers nested within organizations, conceptual distinctiveness between workplace disconnectedness and cynicism was supported. Measurement invariance across the two groups was supported, and subsequent structural invariance analyses suggested a similar pattern of results for flexible and in-person workers. Specifically, compared to disconnectedness, cynicism exerted higher negative effects on mental health and higher positive effects on cognitive failures and family-to-work conflict. Conversely, compared to cynicism, disconnectedness exerted higher negative effects on performance and work-to-family conflict. That is, feeling indifferent toward others particularly affects mental health and errors, while feeling excluded especially hampers productivity and family life. Theoretical and practical (e.g., inclusive leadership, support groups) implications of these results are discussed in light of the globally rising rates of hybrid work arrangements and related costs for employee wellbeing and productivity.
Topics: Humans; Pandemics; COVID-19; Workplace; Leadership; Emotions
PubMed: 37444165
DOI: 10.3390/ijerph20136318 -
Cutis Mar 2024Carpet beetle larvae of the family Dermestidae have been documented to cause both acute and delayed hypersensitivity reactions in susceptible individuals. These larvae...
Carpet beetle larvae of the family Dermestidae have been documented to cause both acute and delayed hypersensitivity reactions in susceptible individuals. These larvae have specialized horizontal rows of spear-shaped hairs called hastisetae, which detach easily into the surrounding environment and are small enough to travel by air. Exposure to hastisetae has been tied to adverse effects ranging from dermatitis to rhinoconjunctivitis and acute asthma, with treatment being mostly empiric and symptom based. Due to the pervasiveness of carpet beetles in homes, improved awareness of dermestid-induced manifestations is valuable for clinicians.
Topics: Animals; Coleoptera; Humans; Larva
PubMed: 38648592
DOI: 10.12788/cutis.0979