Macrocyst Formation Research Articles

Characteristics of the magnetic resonance imaging findings of cervical gastric-type adenocarcinoma

This study identified the distinct magnetic resonance imaging findings of cervical gastric-type adenocarcinoma (GAS) that can help differentiate it from squamous cell carcinoma (SCC) and usual-type endocervical adenocarcinoma (UEA) and reveal the radiologic-pathologic correlation. All consecutive patients with cervical GAS treated at our hospital from November 2009 to August 2021 were included. The SCC and UEA cases were considered controls. Tumor location, tumor shape, presence and size of cysts, presence of uterine fluid, and apparent diffusion coefficient (ADC) were evaluated. Overall, 18 GAS, 55 SCC, and 23 UEA cases were evaluated. The tumor was located in the entire cervix in 13/18 GAS cases, whereas it was predominantly located in the lower cervix in 38/55 SCC cases and 14/23 UEA cases. Most GAS cases exhibited a diffuse infiltration growth pattern (17/18), whereas most SCC and UEA cases exhibited a mass-forming pattern (39/55 and 20/23, respectively). Moreover, the percentages of cases presenting microcysts or macrocysts and undergoing uterine fluid collection were significantly higher in the GAS group (14/18 and 13/18) than in the SCC and UEA groups. ADC was significantly higher in the GAS group than in the SCC group (1.092×10-3 vs. 0.819×10-3 mm2/s). This study revealed that GAS is characterized by tumor presence in the entire cervix, infiltrative growth pattern, intrauterine fluid collection, and frequent microcyst or macrocyst formation. Moreover, ADC was significantly higher in the GAS group than in the SCC group.

Case Series: Transient Corneal Subepithelial Macrocysts with Scleral Contact Lens Wear

Scleral lens wear is indicated in cases of corneal irregularity and ocular surface disease to improve vision and ocular surface condition. The purpose of this case series is to discuss transitory corneal subepithelial macrocysts associated with scleral lens wear in various conditions such as dry eye, post-radial keratotomy, and post-superficial keratectomy. Such diseased or damaged corneas have weakened epithelial attachments which can lead to macrocyst formation. Three cases documented with spectral-domain anterior segment optical coherence tomography highlight the clinical presentation of corneal subepithelial macrocysts. CE Notification: This article is available as a COPE accredited CE course. You may take this course for 1-hour credit. Read the article and take the qualifying test to earn your credit. Please check COPE course expiry date prior to enrollment. The COPE course test must be taken before the course expiry date.

Challenging Disease Ontology by Instances of Atypical PKHD1 and PKD1 Genetics.

BackgroundAutosomal polycystic kidney disease is distinguished into dominant (ADPKD) and recessive (ARPKD) inheritance usually caused by either monoallelic (PKD1/PKD2) or biallelic (PKHD1) germline variation. Clinical presentations are genotype-dependent ranging from fetal demise to mild chronic kidney disease (CKD) in adults. Additionally, exemptions from dominant and recessive inheritance have been reported in both disorders resulting in respective phenocopies. Here, we comparatively report three young adults with microcystic-hyperechogenic kidney morphology based on unexpected genetic alterations beyond typical inheritance.MethodsNext-generation sequencing (NGS)-based gene panel analysis and multiplex ligation-dependent probe amplification (MLPA) of PKD-associated genes, familial segregation analysis, and reverse phenotyping.ResultsThree unrelated individuals presented in late adolescence for differential diagnosis of incidental microcystic-hyperechogenic kidneys with preserved kidney and liver function. Upon genetic analysis, we identified a homozygous hypomorphic PKHD1 missense variant causing pseudodominant inheritance in a family, a large monoallelic PKDH1-deletion with atypical transmission, and biallelic PKD1 missense hypomorphs with recessive inheritance.ConclusionBy this report, we illustrate clinical presentations associated with atypical PKD-gene alterations beyond traditional modes of inheritance. Large monoallelic PKHD1-alterations as well as biallelic hypomorphs of both PKD1 and PKHD1 may lead to mild CKD in the absence of prominent macrocyst formation and functional liver impairment. The long-term renal prognosis throughout life, however, remains undetermined. Increased detection of atypical inheritance challenges our current thinking of disease ontology not only in PKD but also in Mendelian disorders in general.

Sex and macrocyst formation in Dictyostelium.

Sex in Dictyostelia involves a remarkable form of cannibalism in which zygotes attract large numbers of surrounding amoebae and then ingest them. Before they are consumed, the attracted amoebae help the zygote by synthesising an outer wall around the aggregate that traps them inside and helps to protect the mature developed zygotic structure, the macrocyst. Competition between cells vying to contribute genetically to zygotes and through to the next generation seems likely to have promoted the evolution of several unusual features of dictyostelid sex: individual species often have more than two mating types, increasing haploid cells' chances of matching with a compatible partner, and fusion of many gametes to form transient syncytia allows cytoplasmic mixing and lateral transmission of mitochondrial genomes. This review will summarise recent advances in our understanding of mating-type determination, gamete fusion, and inheritance in Dictyostelium, and highlight the key gaps in our understanding of this fascinating set of phenomena.

Cyclic dominance emerges from the evolution of two inter-linked cooperative behaviours in the social amoeba.

Evolution of cooperation has been one of the most important problems in sociobiology, and many researchers have revealed mechanisms that can facilitate the evolution of cooperation. However, most studies deal only with one cooperative behaviour, even though some organisms perform two or more cooperative behaviours. The social amoeba Dictyostelium discoideum performs two cooperative behaviours in starvation: fruiting body formation and macrocyst formation. Here, we constructed a model that couples these two behaviours, and we found that the two behaviours are maintained because of the emergence of cyclic dominance, although cooperation cannot evolve if only either of the two behaviours is performed. The common chemoattractant cyclic adenosine 3',5'-monophosphate (cAMP) is used in both fruiting body formation and macrocyst formation, providing a biological context for this coupling. Cyclic dominance emerges regardless of the existence of mating types or spatial structure in the model. In addition, cooperation can re-emerge in the population even after it goes extinct. These results indicate that the two cooperative behaviours of the social amoeba are maintained because of the common chemical signal that underlies both fruiting body formation and macrocyst formation. We demonstrate the importance of coupling multiple games when the underlying behaviours are associated with one another.

Cooperation induces other cooperation: Fruiting bodies promote the evolution of macrocysts in Dictyostelium discoideum

Biological studies of the evolution of cooperation are challenging because this process is vulnerable to cheating. Many mechanisms, including kin discrimination, spatial structure, or by-products of self-interested behaviors, can explain this evolution. Here we propose that the evolution of cooperation can be induced by other cooperation. To test this idea, we used a model organism Dictyostelium discoideum because it exhibits two cooperative dormant phases, the fruiting body and the macrocyst. In both phases, the same chemoattractant, cyclic AMP (cAMP), is used to collect cells. This common feature led us to hypothesize that the evolution of macrocyst formation would be induced by coexistence with fruiting bodies. Before forming a mathematical model, we confirmed that macrocysts coexisted with fruiting bodies, at least under laboratory conditions. Next, we analyzed our evolutionary game theory-based model to investigate whether coexistence with fruiting bodies would stabilize macrocyst formation. The model suggests that macrocyst formation represents an evolutionarily stable strategy and a global invader strategy under this coexistence, but is unstable if the model ignores the fruiting body formation. This result indicates that the evolution of macrocyst formation and maintenance is attributable to coexistence with fruiting bodies. Therefore, macrocyst evolution can be considered as an example of evolution of cooperation induced by other cooperation.

Induction of macrocyst wall formation by ZYG1 in Dictyostelium discoideum

Abstract Background: Macrocyst is known as the sexual developmental form in cellular slime molds. ZYG1 is known to be involved in zygote formation by cell fusion during macrocyst formation in

A surface glycoprotein indispensable for gamete fusion in the social amoeba Dictyostelium discoideum.

Sexual reproduction is essential for the maintenance of species in a wide variety of multicellular organisms, and even unicellular organisms that normally proliferate asexually possess a sexual cycle because of its contribution to increased genetic diversity. Information concerning the molecules involved in fertilization is accumulating for many species of the metazoan, plant, and fungal lineages, and the evolutionary consideration of sexual reproduction systems is now an interesting issue. Macrocyst formation in the social amoeba Dictyostelium discoideum is a sexual process in which cells become sexually mature under dark and submerged conditions and fuse with complementary mating-type cells. In the present study, we isolated D. discoideum insertional mutants defective in sexual cell fusion and identified the relevant gene, macA, which encodes a highly glycosylated, 2,041-amino-acid membrane protein (MacA). Although its overall similarity is restricted to proteins of unknown function within dictyostelids, it contains LamGL and discoidin domains, which are implicated in cell adhesion. The growth and development of macA-null mutants were indistinguishable from those of the parental strain. The overexpression of macA using the V18 promoter in a macA-null mutant completely restored its sexual defects. Although the macA gene encoded exactly the same protein in a complementary mating-type strain, it was expressed at a much lower level. These results suggest that MacA is indispensable for gamete interactions in D. discoideum, probably via cell adhesion. There is a possibility that it is controlled in a mating-type-dependent manner.

Ethylene as a potent inducer of sexual development

A novel and critical function of ethylene, a potent plant hormone, has been well documented in Dictyostelium, because it leads cells to the sexual development (macrocyst formation) by inducing zygote formation. Zygote formation (sexual cell fusion) and the subsequent nuclear fusion are the characteristic events occurring during macrocyst formation. A novel gene, zyg1 was found to be predominantly expressed during the sexual development, and its enforced expression actually induces zygote formation. As expected, the zygote inducer, ethylene enhances the expression of zyg1. Thus the function of ethylene has been verified at all of individual (macrocyst formation), cellular (zygote formation), and molecular levels (zyg1 expression). Based on our recent studies concerning the behavior and function of the zyg1 product (ZYG1 protein), the signal transduction pathways involved in zygote formation are proposed in this review.

Phylogeography and sexual macrocyst formation in the social amoeba Dictyostelium giganteum

BackgroundMicroorganisms are ubiquitous, yet we are only beginning to understand their diversity and population structure. Social amoebae (Dictyostelia) are a diverse group of unicellular eukaryotic microbes that display a unique social behaviour upon starvation in which cells congregate and then some die to help others survive and disperse. The genetic relationships among co-occurring cells have a major influence on the evolution of social traits and recent population genetic analysis found extensive genetic variation and possible cryptic speciation in one dictyostelid species (Dictyostelium purpureum). To further characterize the interplay among genetic variation, species boundaries, social behaviour, and reproductive isolation in the Dictyostelia, we conducted phylogenetic analyses and mating experiments with the geographically widespread social amoeba Dictyostelium giganteum.ResultsWe sequenced approximately 4,000 basepairs of the nuclear ribosomal DNA from 24 isolates collected from Texas, Michigan, Massachusetts, Virginia, and Wisconsin and identified 16 unique haplotypes. Analyses of the sequence data revealed very little genetic differentiation among isolates and no clear evidence of phylogenetic structure, although there was evidence for some genetic differentiation between the Massachusetts and Texas populations. These results suggest that sexual mating (macrocyst formation) is not likely to correlate with either genetic or geographical distance. To test this prediction, we performed 108 mating experiments and found no association between mating probability and genetic or geographical distance.ConclusionsD. giganteum isolates from across North America display little genetic variation, phylogeographic structure, and genetic differentiation among populations relative to the cryptic species observed within D. purpureum. Furthermore, variation that does exist does not predict the probability of mating among clones. These results have important implications for our understanding of speciation and social evolution in microbes.

A novel function of ethylene.

The cellular slime mold, Dictyostelium mucoroides-7 (Dm7) exhibits clear dimorphism; macrocyst formation as a sexual process and sorocap formation as an asexual process. These two life cycles are regulated by two regulators, ethylene and cyclic AMP (cAMP). This is the first report demonstrating a novel function of ethylene at the cellular level. That is, ethylene induces a zygote formed by cell fusion and subsequent nuclear fusion. Recently, the function of ethylene at the molecular level has been clarified as it induces zygote formation through an enhanced expression of a novel gene, zyg1. The signaling pathway for induction or inhibition of zygote formation is now trying to be clarified focusing on the ZYG1 protein.

Genes involved in Dictyostelium discoideum sexual reproduction

Macrocyst formation in the cellular slime moulds is a sexual process induced under dark and humid conditions. Normal development life cycle in these organisms involves proliferation by cell division and, upon starvation, formation of multicellular aggregates and fruiting bodies, consisting of spores and stalk cells. Macrocyst formation, cell division by binary fission and spore formation are thus three alternative modes of reproduction, for which it is of interest to understand how a choice is made. The genetic basis of asexual development and fruiting body formation is well known, by contrast information on the genetic control of sexual reproduction during macrocyst formation is scarce. In Dictyostelium discoideum, the most widely used species, several cell-surface proteins relevant to sexual cell fusion have been identified using cell fusion-blocking antibodies, but isolation of the relevant genes has been unsuccessful. Analysis of sexually deficient mutants, some of which are normal for asexual development, has shown that sexual reproduction is regulated by both specific genes and genes that are also involved in asexual development. Reverse genetic analysis of 24 genes highly enriched in a gamete-specific subtraction library has revealed four genes involved in the regulation of sexual cell interactions. One of them was found to be a novel regulator of the cAMP signalling pathway specific to sexual development. Studies on the molecular genetic control of the sexual cycle will be reviewed and their contribution to our understanding of the organization and function of the D. discoideum genome as a whole discussed.

Laser Treatment of Coats' Disease

A 9-year-old boy presented with an exudative retinal detachment, vascular telangiectasias, subretinal lipid, and retinal macrocyst formation. He underwent three sessions of large-spot diode laser for the treatment of Coats' disease. Serial examinations and fundus photography documented an excellent involutional response with an improvement in visual acuity.

Reverse genetic analyses of gamete-enriched genes revealed a novel regulator of the cAMP signaling pathway in Dictyostelium discoideum

Sexual development in Dictyostelium discoideum is initiated by the fusion of opposite mating type cells to form zygote giant cells, which subsequently gather and phagocytose surrounding cells for nutrition to form macrocysts. Here we performed the targeting of 24 highly gamete-enriched genes we previously isolated, and successfully generated knockout mutants for 16 genes and RNAi mutants for 20 genes including 6 genes without disruptants. In the knockout mutants of two genes, cell aggregation toward the giant cells was much less extensive and many cells remained around poorly formed macrocysts. We named these genes tmcB and tmcC. Although macrocyst formation of wild type cells was suppressed by the addition of exogenous cAMP, that of knockout mutants of tmcB was much less sensitive. The mRNA level of phosphodiesterase ( pde) was higher and that of its inhibitor ( pdi) was lower in the latter cells compared to the parental strains during sexual development. Thus, tmcB appeared to be a novel regulator of the cAMP signaling pathway specific to sexual development. Knockout mutants of tmcC were indistinguishable from the wild type cells with respect to the cAMP response, suggesting that this gene is relevant to other processes.

Involvement of actin dephosphorylation in germination of Physarum sclerotium.

The plasmodium of Physarum polycephalum grows without cytokinesis and shows an active cytoplasmic streaming under wet and nutritious conditions. It can undergo reversible differentiation into several types of dormancy to survive in adverse environments. Temperature change or osmotic stress leads to cytoplasmic division of the plasmodium into cells containing one or more nuclei: these form a macrocyst, the spherule. Desiccation also induces cell division of the plasmodium followed by formation of a sclerotium, a dormant body resistant to dry stress. More than half of the actin in a sclerotium is phosphorylated at a single site, threonine 203, resulting in loss of its ability to polymerize into actin filaments. In the present study, actin phosphorylation was found in the sclerotium but not in either the plasmodium or in the spherule. This result suggests that phosphorylation of sclerotium actin may be related to the mechanism associated with desiccation resistance rather than morphological changes through cell compartmentalization in the macrocyst formation. Moreover. dephosphorylation of the phosphorylated form of sclerotium actin began within 5 min after addition of water. Dephosphorylation was not affected by sucrose and sorbitol sugars, but was inhibited by ammonium bicarbonate, ammonium phosphate, sodium phosphate, NaCl, and KCl in a dose-dependent manner. On the other hand, in germination of the sclerotium there was measurable sensitivity to both carbohydrates and salts. Actin dephosphorylation seems to be one of the important processes in the early phase of sclerotium germination.

Involvement of a novel gene, zyg1, in zygote formation of Dictyostelium mucoroides.

A gene, zyg1, was isolated by differential screening from Dictyostelium mucoroides-7 (Dm7) cells, as one preferentially expressed during their sexual development. The zyg1 gene encodes for a novel protein (ZYG1; deduced Mr 29.4 x 10(3)) consisting of 268 amino acids. Although the ZYG1 protein has predicted PKC phosphorylation sites, it has neither transmembrane domains nor specified signal sequences. The expression of zyg1 was initiated after 2 h of starvation and reached its maximum level at 8 h under submerged conditions. The expression pattern is quite similar to the temporal change of zygote formation during sexual development (macrocyst formation) with 1 h of precedence. The zyg1 mRNA in Dm7 cells developing on agar was retained until zygotes were formed. Zyg1-overexpressing cells derived from Dm7 cells eventually formed many loose mounds, in which giant cells were surrounded by normal-sized cells, in addition to mature macrocysts even under the conditions favouring for asexual sorocarp formation. Giant cells were found by DAPI-staining to be multinucleate, possibly because of the precocious overexpression of zyg1 mRNA. Western blottings using a specific antibody raised against the oligopeptide near the C-terminal region of ZYG1 also showed that ZYG1 was actually over-produced in the zyg1-overexpressing cells. From these results, it is evident that the zyg1 gene has an essential role in zygote formation by inducing sexual cell fusion.

Macrocyst formation in three dictyostelid species, Dictyostelium monochasioides, Polysphondylium candidum, and P. pseudo-candidum

Macrocyst formation in the sexual cycle was found in three dictyostelid species:Dictyostelium monochasioides, Polysphondylium candidum, andP. pseudo-candidum. Mating tests suggested thatD. monochasioides andP. pseudocandidum were heterothallic andP. candidum was homothallic. The primary walls of macrocysts had partially or fully degenerated, while the inner walls, believed to be tertiary walls, showed an undulate structure.

A mutation in the cAMP signaling pathway affects sexual development of Dictyostelium discoideum.

Amoebae of cellular slime molds have two developmental modes, asexual fruiting body formation and sexual macrocyst formation. How developmental choice is made is an interesting subject of wide importance. Light exposure and dry conditions are favorable for asexual development, while conditions of darkness and high humidity are so for sexual development. In Dictyostelium discoideum, the latter conditions enhance zygote formation, which determines the fate of surrounding cells for sexual development. Here, a mutant (TMC1) defective in the post-fusion aggregation of cells during sexual development is described. This mutant is also aggregationless in asexual development, and the level of cyclic adenosine monophosphate (cAMP) receptor is reduced. Correspondingly, a series of existing mutants with defects in cAMP signaling pathways showed the same sexual phenotype as TMC1. These results suggest that molecular mechanisms of development are shared by the two alternative developmental modes.

Promotion of Zygote Formation by Protein Kinase Inhibitors during the Sexual Development of Dictyostelium mucoroides: (macrocyst/PKA/calmodulin/cAMP/cellular slime mold).

To analyze the possible involvement of protein kinases in the sexual development (macrocyst formation) of the cellular slime mold Dictyostelium mucoroides-7 (Dm7), the effects of several protein kinase inhibitors were examined. K252a, a potent inhibitor of protein kinase activities, promoted the sexual cell fusion, through enhancement of gamete formation. In contrast, staurosporine (structurally and functionally similar to K252a) inhibited markedly the progress of development including cell aggregation, thus resulting in the failure of cells to form mature macrocysts. The effective period of K252a was 5-7 hr after starvation, during which Dm7 cells could acquire fusion competence, and the inhibitory effect of cAMP on zygote formation was nullified by the co-application of K252a. Although KT5720 (a specific inhibitor of cAMP-dependent protein kinase) and W7 (a calmodulin inhibitor) had no effects on zygote formation when applied separately, their combined application enhanced zygote formation like K252a did. Neither calphostin C (a specific inhibitor of Ca2+ -dependent protein kinase) nor herbimycin A (a specific inhibitor of tyrosine kinase) exerted a stimulative influence upon macrocyst formation. These results strongly suggest that the two signal transduction pathways mediated by cAMP-dependent protein kinase (PKA) and calmodulin are closely related to zygote formation, their blockage being favorable to zygote formation.

The ethylene action in the development of cellular slime molds: an analogy to higher plants

The cellular slime moldDictyostelium mucoroides-7 (Dm 7) and its mutant (MF 1) exhibit sexual or asexual development depending upon culture conditions. During the sexual cycle macrocyst formation occurs, whereas sorocarps containing spores and stalk cells are asexually formed. As previously reported, the macrocyst formation is marked by the emergence of true zygotes, and is induced by a potent plant hormone, ethylene. The concentration of ethylene required for macrocyst induction was determined to establish the similarity of ethylene action between this organism and higher plants. Macrocysts are induced by low (1 μl/l) exogenous concentrations of ethylene. Higher concentrations (10–1,000 ul/l) also gave essentially the same inductive activity. Ethionine, an analogue of methionine, was found to inhibit zygote formation during sexual development through its interference with ethylene production by Dm 7 and MF 1 cells. In fact, the inhibitory effect of ethionine was mostly nullified by the application of ethylene, S-adenosyl-L-methionine, or 1-aminocyclopropane-1-carboxylic acid. Taken together these results suggest that both the effective concentration of ethylene and the pathway of ethylene biosynthesis inD. mucoroides may be similar to those in higher plants. Ethylene was also found to be produced in various species and strains of cellular slime molds, even during the asexual process. The possible functions of ethylene in the asexual development are discussed in relation to cell aggregation and differentiation.