Cup Cell Research Articles

Abstract 6957: Extrachromosomal FGFR2 is delivered in extracellular vesicles in two models of cancer of unknown primary

Abstract The extracellular vesicle (EV) route is essential for cell-to-cell communication. Cancer cells release EVs in the extracellular space, where they can interact with recipient cells inducing regulation of gene expression, activation of specific signaling pathways and tumor microenvironment remodeling. We investigated the EVs released by two cell lines of cancer of unknown primary site (CUP) that we established from patient’s tumor cells, namely CUP#55 and CUP#96, as described in https://www.medrxiv.org/content/10.1101/2023.03.12.23287041v1). CUP comprises 3-5% of new cancer cases and presents with metastases of unknown or uncertain origin and no apparent primary tumor. Our CUP cell lines are both characterized by FGFR2 gene amplification. It has been recognized that tumors use circular extrachromosomal DNA (ecDNA) as a way to increase oncogenic amplification. We hypothesized that FGFR2 amplification in CUP cell lines could be associated with ecDNA generation and that this ecDNA could be loaded as cargo inside EVs. FGFR2 copy number was quantified using a probe-based droplet digital PCR assay then we identified the different nature of FGFR2 amplification in the two models using FGFR2 FISH assay: CUP#55 presented a chromosomal homogeneously staining region while CUP#96 displayed double minute chromosomes. FGFR2 DNA was detectable in the cytoplasm fraction, therefore we isolated extracellular vesicles from culture medium using an ultracentrifugation-based protocol and confirmed the presence of the entire length of FGFR2 gene inside small and large vesicles. Since ecDNA contributes to cancer genome remodeling also forming chimeric circles, we confirmed the circular nature of a fraction of FGFR2 ecDNA using the Plasmid-Safe ATP-dependent DNAse test. Finally, we tested the oncogene delivery capability of CUP EVs by administering CUP#96 and CUP#55 small and large vesicles to recipient cell lines. We observed an increase of FGFR2 DNA at 24 hours upon EV treatments, and its functional transcription in FGFR2 mRNA after 48 hours. In conclusion, we identified a model of oncogene amplification and delivery in two cell lines of cancer of unknown primary, which could explain the high metastatic potential of this cancer type. (The research leading to these results has received funding from AIRC under IG 2021 - ID. 25789 project - P.I. Ferracin Manuela) Citation Format: Irene Salamon, Gianluca Storci, Beatrice Fontana, Salvatore Serravalle, Giulia Gallerani, Roberta Roncarati, Spartaco Santi, Massimiliano Bonafè, Manuela Ferracin. Extrachromosomal FGFR2 is delivered in extracellular vesicles in two models of cancer of unknown primary [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6957.

Telmisartan loading thermosensitive hydrogel repairs gut epithelial barrier for alleviating inflammatory bowel disease

Inflammatory bowel disease (IBD) remains a global health concern with a complex and incompletely understood pathogenesis. In the course of IBD development, damage to intestinal epithelial cells and a reduction in the expression of tight junction (TJ) proteins compromise the integrity of the intestinal barrier, exacerbating inflammation. Notably, the renin-angiotensin system and angiotensin II receptor type 1 (AT1R) play a crucial role in regulating the pathological progression including vascular permeability, and immune microenvironment. Thus, Telmisartan (Tel), an AT1R inhibitor, loading thermosensitive hydrogel was constructed to investigate the potential of alleviating inflammatory bowel disease through rectal administration. The constructed hydrogel exhibits an advantageous property of rapid transformation from a solution to a gel state at 37°C, facilitating prolonged drug retention within the gut while mitigating irritation associated with rectal administration. Results indicate that Tel also exhibits a beneficial effect in ameliorating colon shortening, colon wall thickening, cup cell lacking, crypt disappearance, and inflammatory cell infiltration into the mucosa in colitis mice. Moreover, it significantly upregulates the expression of TJ proteins in colonic tissues thereby repairing the intestinal barrier damage and alleviating the ulcerative colitis (UC) disease process. In conclusion, Tel-loaded hydrogel demonstrates substantial promise as a potential treatment modality for IBD.

Evaluation of body weight and morphometric characteristics of the young queen of Apis cerana javana at different queen cup cell sizes

Abstract. Masyithoh D, Kentjonowaty I, Salleh SM, Ustadi, Agussalim, Nastain FS. 2023. Evaluation of body weight and morphometric characteristics of the young queen of Apis cerana javana at different queen cup cell sizes. Biodiversitas 24: 5626-5633. This study investigates body weight and morphometric characteristics of Apis cerana javana queen rearing based on differences in the queen cup sizes. The queen cell sizes were divided into three categories; the first group was a small category (T1) with a height of 0.75 cm, top diameter of 0.65 cm, and bottom diameter of 0.44 cm. The second treatment was medium category (T2) with a height of 0.85 cm, a top diameter of 0.71 cm, and a bottom diameter of 0.54 cm. The third treatment was a large category (T3) with a height of 1.00 cm, a top diameter of 0.71 cm, and a bottom diameter of 0.62 cm. The morphometrics investigated consisted of hatch weight, pupae length, body length, head, abdomen, wing, and hind leg morphometrics. The results showed that the differences in the queen cup size had no effect (P>0.05) on the hatch weight, body length, width, and length of the head, thorax, fore and hind wing (length and width), and abdomen (length and height). The different queen cell sizes did not affect the wing morphometrics (P>0.05). In addition, the leg morphometrics consisting of femur, tibia, tarsus, and metatarsus were also not affected (P>0.05) by the different queen cup sizes. These results revealed that the different queen cup sizes did not negatively impact the morphometric characteristics of A. cerana javana queen’s.

Efficacy of autologous dermal sheath cup cell transplantation in male and female pattern hair loss: A Single-Arm, Multi-Center, phase III equivalent clinical study.

A previous, proof-of-concept clinical study suggested that dermal sheath cup cell injections into the affected areas of male/female pattern hair loss (PHL) may have some amelioratory effects, the clinical efficacy of which needs further examination. A phase III equivalent clinical study was conducted to further probe the therapeutic potential of this novel approach and verify its safety and efficacy in improving the appearance of PHL. Thirty-six participants with PHL were injected with dermal sheath cup cell harvested from non-affected occipital hair follicles twice in quarterly intervals. Global photographic assessment and phototrichogram were performed in a blinded manner. Patient-reported outcomes were assessed for 12 months. On global photographic assessment, 30% of the participants showed improvement. The analysis of phototricogram data detected the increases in the cumulative hair diameter, hair cross-sectional area, and mean hair diameter of 107.6 ± 152.6 μm/cm2 , 13069.1 ± 10960.7 μm2 /cm2 , and 0.9 ± 0.9 μm (ratios vs. baseline: +1.4%, +3.4%, and +2.2%), respectively. The female and high terminal hair ratio groups achieved better improvement. Of the total participants, 62.9% noted some degree of improvement. No serious adverse events were detected. This novel approach exhibited visible effects while ensuring safety and patient satisfaction. Therefore, it holds promise as a possible therapeutic option for treating PHL, especially in women.

In vitro caecum fermentation and in vivo (Gallus gallus) of calcium delivery systems fabricated by desalted duck egg white peptides and chitosan oligosaccharide on gut health

AbstractAs calcium supplements, two novel calcium delivery systems were prepared with desalted duck egg white peptides (DPs) and chitosan oligosaccharide (COS) by Amadori‐linkage and transglutaminase (TGase)‐induced reaction, with high calcium‐binding ability of promoting calcium absorption in vivo and in vitro. However, there are relatively few studies on the gut health of calcium delivery systems. In this experiment, in vitro caecum fermentation experiment and Gallus gallus intra amniotic feeding model were used to assess the gut health of calcium delivery systems and phytic acid. Results showed that two calcium delivery systems improved the microbial community structure by inhibiting the proliferation of Escherichia coli, and promoting the proliferation of Bifidobacterium and Lactobacillus. The addition of calcium delivery systems significantly increased short chain fatty acids (SCFAs) and improved the boundary membrane function of brush nutrients by significantly increasing villi structure, surface area, cup cell expansion and production of associated genes (P < 0.05). Moreover, calcium delivery systems present significant reverse of the inhibitory effect of phytic acid on gut health through in vitro and in vivo experiments. This study suggested that DPs‐COS‐Ca systems were superior to the commercially available calcium supplement CaCO3 and had excellent calcium absorption and gut health regulating effects.

Queen cells acceptance rate and royal jelly production in worker honey bees of two Apis mellifera races.

Royal jelly (RJ) is an acidic yellowish-white secretion of worker honey bee glands, used as food material of worker bee larvae for the first three days and queen bee larvae for the entire life. It is commercially used in cosmetics and medicinal industry in various parts of the world. This study determined the queen cell acceptance rate and RJ production difference among Italian and Carniolan bee races. Furthermore, the effect of plastic cup cell priming media, diets and seasons were tested on the larval cell acceptance rate and RJ yield of both races. The results indicated that average queen cell acceptance rate was significantly (p<0.001) higher in Italian race (75.53 ± 1.41%) than Carniolan race (58.20 ± 1.30%). Similarly, mean RJ yield per colony significantly (p<0.001) differed between both bee races, which were 13.10 ± 0.42 g and 9.66 ± 0.43 g, in Italian and Carniolan races, respectively. Moreover, priming media, diets and seasons significantly (p<0.001) affected queen cell acceptance rate and RJ production of both bee races. This study would help breeders to select the bees with higher-level of queen cell acceptance rate and RJ production in the future.

Es-ATG7 is required for spermatogenesis of Eriocheir sinensis and modulates p53-dependent apoptosis in germ cells

Spermatogenesis is a complicated and highly regulated male gamete differentiation process that begins with the proliferation and differentiation of spermatogonia to the release of the mature spermatozoa. The autophagy-related gene <i>atg7</i> has been reported as closely related to spermatogenesis and communication of Sertoli cell-germ cells in mice, including acrosome biogenesis, sperm flagellum development, and ectoplasmic specialization assembly. However, the function of es-ATG7 and its molecular regulatory mechanism during spermatogenesis in Crustacea remain largely unknown. Here, we cloned and identified <i>es-atg7</i> from the testes of the Chinese mitten crabs <i>Eriocheir sinensis</i> and found that the expression of <i>es-atg7</i> was relatively high in testes through semi-quantitative RT-PCR. The dynamic localization of es-ATG7 detected by immunofluorescence may convey information about its role in the spermatogenesis of <i>E. sinensis</i>. Furthermore, a knockdown of <i>es-atg7</i> revealed that the malformed sperm with irregular sperm shape or loose nuclear cup and germ cell apoptosis were increased significantly. Accompanying this, we found an up-regulated expression of es-p53 during spermatogenesis in <i>es-atg7</i> knockdown groups. Altogether, our results indicate that es-ATG7 plays an essential role during spermatogenesis of <i>E. sinensis</i>, and we demonstrated that es-ATG7 acts as an antagonist for p53-dependent apoptosis induction in this process.

Effect of Different Seasons on the Royal Jelly Production Under Nasr City Conditions – Cairo - Egypt

The study was executed at apiary of Plant protection Dept. Fac. of Agric. Al-Azhar Univ., Cairo, Egypt, during two successive years 2019 and 2020 to determine the effectiveness of different seasons on the acceptance rates of the larvae and royal jelly production. In the first year, the highest acceptance means for Italian hybrid 72.1 and 65.43% for Carniolan hybrid were recorded at mid-spring on the other hand, the lowest acceptance percentages means were 50.86 and 55.8 % recorded at early summer for Carniolan and Italian hybrids respectively. Also, results demonstrated that mid spring gave the best mean weight of royal jelly per queen cell cup 238.35 mg. for Italian hybrid and 236.31 mg. for the Carniolan hybrid. The lowest quantity means were recorded in early summer 187.24 mg./cup for Carniolan hybrid and 198.74 mg./cup for Italian hybrid. In the second year, the highest acceptance means were 66.42 and 62.96% at mid spring for Italian and Carniolan hybrids respectively. Whereas the lowest acceptance percentage means were 44.44 and 48.4 % at early summer for Carniolan and Italian hybrids. Also, results cleared that mid-spring gave the best mean weight of royal jelly per queen cell cup, 229.71 mg. for Italian hybrid and 227.5 mg. for Carniolan hybrid. The lowest quantity means were recorded at early summer 186.72 mg./cup for Carniolan hybrid and 189.06 mg./cup for Italian hybrid. As for the effect of the bar level, the middle bar level gave the best results for royal jelly quantity and cup acceptance while the upper level gave the least royal jelly quantity and acceptance percentages in different seasons. There was a significant difference in acceptance percent and the royal jelly production per cup cell between mid-spring and early summer. Mid-spring gave the best results while the early summer gave the least results.

Comments on the eyes of tardigrades

A survey is given on the scarce information on the visual organs (eyes or ocelli) of Tardigrada. Many Eutardigrada and some Arthrotardigrada, namely the Echiniscidae, possess inverse pigment-cup ocelli, which are located in the outer lobe of the brain, and probably are of cerebral origin. Occurrence of such organs in tardigrades, suggested as being eyeless, has never been checked. Depending on the species, response to light (photokinesis) is negative, positive or indifferent, and may change during the ontogeny. The tardigrade eyes of the two eutardigrades examined up to now comprise a single pigment cup cell, one or two microvillous (rhabdomeric) sensory cells and ciliary sensory cell(s). In the eyes of the eutardigrade Milnesium tardigradum the cilia are differentiated in an outer branching segment and an inner (dendritic) segment. Because of the scarcity of information on the tardigrade eyes, their homology with the visual organs of other bilaterians is currently difficult to establish and further comparative studies are needed. Thus, the significance of these eyes for the evolution of arthropod visual systems is unclear yet.

The ultrastructure of the eyes of Paravortex karlingi (Plathelminthes, Rhabdocoela)

Both eyes of Paravortex karlingi belong to the rhabdomeric type. Each eye consists of a single pigment cup cell and three sensory cells. Modified mitochondria lie in three protrusions of the cup cell, and several of these mitochondria form giant mitochondrial derivates. The centres of the derivates include electron-dense substances. These modified structures may have lenticular functions. Furthermore, it is shown that giant mitochondrial derivates develop by fusion of smaller ones. Embryos have many small mitochondria in the developing eyes whereas the adult possesses less numerous, but giant forms. This circumstance leads to the assumption that all such lenticular structures within the rhabdocoels result from identical processes.

'Cup cell disease' in the colonial tunicate Botryllus schlosseri.

A new progressive, fatal disease called 'cup cell disease' was characterized in ex situ cultures of Botryllus schlosseri, a colonial tunicate. The disease originated as a few dark spots growing within zooids. The infected colonies then started to deteriorate, morphologically diagnosed by ampullar retraction, lethargic blood circulation and by a swollen and soft tunic matrix. In later stages of the disease, developed buds were also affected. Many large black dots were scattered within the tunic matrix, and zooids were transformed to opaque, dilated, sac-like structures, signaling impending death. Colonies were infected periodically, even without direct tissue contact. The time course from first appearance to colony death ranged between 30 and 45 d. Histological studies, in vitro culturing of blood cells and blood smears revealed the existence of numerous cup-like cells (up to 4.8 microm diameter on average) with a yellowish cell wall and transparent cytoplasm that was not stained by various dyes (except azocarmine-G). Cells were refractive under bright-field illumination and revealed a flattened wall with flanges, characteristic of species of the phylum Haplosporidia. Cup cells aggregated in blood vessels and in internal parts of zooids and buds and were phagocytosed by blood cells. In a single case, plasmodia-like structures were found only in the tunic matrix of an infected colony. This is the first record in botryllid ascidians of an infectious lethal disease associated with haplosporidian protists.

Ultrastructure of pigmented and unpigmented photoreceptors in cercariae of Trichobilharzia ocellata (Plathelminthes, Trematoda, Schistosomatidae): evidence for the evolution of parasitism in Neodermata.

The lens-covered pigment cup ocelli in free-swimming cercariae of Trichobilharzia ocellata were re-examined and the differentiation of the lenticular elements was studied in cercariae still enclosed in sporocysts. Each eye consists of a single rhabdomeric sensory cell, a single cup cell harboring pigment granules and the lens. This lens is developed step by step by the fusion of numerous dark platelets not enclosed by a bordering membrane. The material is presumably proteinaceous. There is no evidence that the lenses are of mitochondrial origin. Besides the pigment cup ocelli, a special type of unpigmented rhabdomeric photoreceptor was discovered. Three unicellular photoreceptors arranged in a three-dimensional configuration exist. These light-sensing organs show a principle of construction similar to that of phaosomous photoreceptors. We hypothesize that both types of photoreceptors are relevant for distinct reactions in the host-finding behaviour of the cercariae. The special type of lensing in the pigmented eyes seems to be restricted to Trichobilharzia species, whereas the phaosomous-like receptors may be more widespread in members of the Schistosomatidae. The obvious absence of any mitochondrial lensing in T. ocellata, and probably all other species of the Digenea, may be correlated with the evolution of endoparasitism in the Trematoda.

Ultrastructural and immunocytochemical observations of the nervous systems of three macrodasyidan gastrotrichs

AbstractThe nervous systems of three macrodasyidan gastrotrichs, Dactylopodola baltica, Macrodasys caudatus and Dolichodasys elongatus, were investigated using immunocytochemistry and electron microscopy. Labelling of neural structures against serotonin revealed the presence of two pairs of cerebral cells, a dorsal cerebral connective, and paired ventral nerve cords in D. baltica. In M. caudatus and D. elongatus serotonin immunoreactivity was present in a single pair of dorsal cerebral cells and the ventral nerve cords; the dorsal connective of D. elongatus was also immunoreactive to serotonin and acetylated α‐tubulin. The presence of paired, serotonin‐like immunoreactive cells in D. baltica and other species may represent the plesiomorphic condition in Macrodasyida. The fine structure of the photoreceptors in D. baltica was also investigated to explore the potential ground pattern for eyes in the Macrodasyida. The pigmented photoreceptors of D. baltica contain a unicellular pigment cup, sheath cell and sensory receptor. The pigment cup contains numerous osmiophilic granules that presumably function to shield the eyes from downwelling light in the red part of the spectrum. Projecting into the pigment cup and sheath cell are numerous microvilli from a bipolar sensory cell. A single sensory cell may represent the plesiomorphic condition in Macrodasyida, with multiplication of sensory cells representative of more derived taxa.

Immortalization of equine trophoblast cell lines of chorionic girdle cell lineage by simian virus-40 large T antigen.

Immortalized cell lines have many potential experimental applications including the analysis of molecular mechanisms underlying cell-specific gene expression. We have utilized a recombinant retrovirus encoding the simian virus-40 (SV-40) large T antigen to construct several immortalized cell lines of equine chorionic girdle cell lineage - the progenitor cells that differentiate into the equine chorionic gonadotropin (eCG) producing endometrial cups. Morphologically, the immortalized cell lines appear similar to normal chorionic girdle cells. Derivation of the immortalized cell lines from a chorionic girdle cell lineage was verified by immunological detection of cell-surface antigens specific to equine invasive trophoblasts. The cell lines differed, however, from mature chorionic girdle cells or endometrial cup cells in that they did not produce eCG and did express MHC class I molecules. Thus, these cell lines appear to have been arrested at a stage of development prior to final differentiation into endometrial cup cells. It was also determined that some of these cell lines as well as endometrial cups express the estrogen receptor-related receptor beta gene, but not the glial cell missing gene (GCMa) both of which are expressed in the murine and human placenta. Among these cell lines, three (eCG 50.5, 100.6 and 500.1) express eCG alpha mRNA. Since regulation of eCG alpha subunit gene is largely unknown, we investigated the signal transduction pathways regulating the eCG alpha subunit gene. Both activators of protein kinase A (PKA) and protein kinase C (PKC) induced the expression of eCG alpha subunit expression 3.2 (P<0.05)- and 1.9 (P<0.05)-fold respectively, in the eCG 500.1 cell line. However, activation of these pathways failed to induce eCG beta subunit expression. In conclusion, lines of equine trophoblast cells have been immortalized that display markers characteristic of those with the equine chorionic girdle and endometrial cup cell lineage. A subset of these cells expresses the eCG alpha subunit gene which is responsive to activators of the PKA and PKC signal transduction pathways.

A Structural and Immunological Study of Chorionic Gonadotrophin Production by Equine Trophoblast Girdle and Cup Cells

Equine chorionic gonadotropin (eCG) production by the fetally derived endometrial cups appears to be necessary for the establishment and maintenance of normal equine pregnancy.Starting at about the 27th day of pregnancy, an equatorial band of trophectodermal cells on the surface of the spherical conceptus forms the chorionic girdle. This girdle consists initially of flat trophectodermal epithelium which corrugates into folds as the cells proliferate. The folds are then pressed against the uterine epithelium by expansion of the conceptus. The cells on the apices of the folds become binucleate before they start to invade the endometrium at days 35–37. Ultrastructural immunogold labelling shows that they begin to synthesize eCG as early as day 32, before they migrate into and through the maternal epithelium. Clusters of the girdle binucleate cells penetrate deep into the endometrium. The mature cup cell has a cytoplasm full of mitochondria, rough endoplasmic reticulum cisternae, a large Golgi apparatus and a strong immunoreactivity for the glucose transporter 1 isoform on its plasmalemma. Immunocytochemistry also demonstrates that eCG is localized in the Golgi cisternae, and in small dense granules similar to those found in the migrating girdle cell and present both in the Golgi region and at the peripheral plasmalemma. Release of eCG would therefore seem to be by the usual exocytotic mechanism as found for other protein hormones. The small size and absence of any significant accumulation of eCG-containing granules are in marked contrast to the numerous large luteinizing hormone (eLH) containing granules in the equine pituitary gonadotroph, although both hormones, eLH and eCG, show complete identity at the amino acid sequence level. These morphological indicators suggest that the cup cell secretes eCG constitutively (that is, continuously), with no requirement for secretagogues, whereas in the pituitary cell the regulated pathway is utilized capable of massive secretion under appropriate stimulation.

Photoreceptors in species of the Macrostomida (Plathelminthes): ultrastructural findings and phylogenetic implications

The submicroscopic anatomy of intracerebral and pericerebral photoreceptors in six species of the Macrostomida is described. Cylindromacrostomum notan-dum, Paramyozonaria simplex and Macrostomum hystricinum marinum possess two rhabdomeric intracerebral photoreceptors each consisting of two pigmented cup cells and three (C. notandum and P. simplex) or two sensory cells (M. hystricinum marinum). In C. notandum and P. simplex two of the sensory cells are equal in size, while the third one is much smaller. This organisation is hypothesised as an autapomorphy of the Dolichomacrostomidae. Photoreceptors with two mantle cells are also known for Microstomum spiculifer. Since only one cup cell exists in representatives of nearly all other high-ranked taxa of the Rhabditophora, it is concluded that the characteristic ”two cup cells in rhabdomeric photoreceptors” has evolved in the stem lineage of the taxon Macrostomida or Macrostomorpha, respectively. In Myozona purpurea and Psammomacrostomum turbanelloides rhabdomeric intracerebral photoreceptors of a special type were encountered. These light-sensing organs consist of numerous cells forming an ellipsoid. The surface membranes of these cells are elongated to form filiform extensions which are tightly intertwined with each other. Pericerebral ciliary aggregations consisting of cells with an internal cavity into which axonemata of modified cilia project were observed in all species mentioned above and in Bradynectes sterreri as well. Such putative light-perceiving organs are widespread within taxa of the Plathelminthes Rhabditophora and have been hypothesised either as homologous characteristics or as analogous ones. With increasing examples being described it becomes likely that pericerebral ciliary aggregations are an apomorphic ground pattern characteristic of the Rhabditophora.

Evidence for the mitochondrial origin of the eye lenses in embryos of Entobdella soleae (Plathelminthes, Monogenea).

The lens associated with each of the four pigmented eyes of the oncomiracidium of Entobdella soleae (Plathelminthes, Monogenea, Capsalidae) develops in a special region of the pigment cup cell of the eye. It is confirmed that the inner of the two membranes enclosing each lens bears short, inwardly projecting, membranous profiles identical to mitochondrial cristae. Studies of embryos incubated for 19 days at 12 degrees C (hatching begins at 28 days at this temperature) revealed that the matrix of the developing lens of each anterior eye contains many mitochondrial membrane compartments, some having the configuration of separate, small mitochondria. The implication is that the lens is derived from many fused mitochondria, rather than from a single large one. The anterior eyes of 19-day-old embryos are less well developed than the posterior eyes. Pigment granules in the anterior eyes appear to be at the premelanosome stage and contain dispersed dense particles lacking an obvious orderly arrangement. The posterior eyes mostly contain mature melanosomes. Membranous compartments in the matrix of the posterior eye lenses are rare. Apart from longer peripheral cristae, lenses of 22-day-old embryos are identical with those of oncomiracidia. The evolution of mitochondrial lenses in Plathelminthes is considered.

First evidence of unpigmented rhabdomeric photoreceptors in a Microstomum species (Plathelminthes, Macrostomorpha, Microstomidae) and ultrastructure of photoreceptor-like ciliary aggregations

Microstomum spiculifer possesses a pair of intracerebral photoreceptors each consisting of a single rhabdomeric sensory cell and two cup or mantle cells. The mantle cells are devoid of pigment. In addition, four so-called ciliary aggregations, presumed to have a light-sensing function, are present. Each ciliary aggregation represents a specialized cell with an internal cavity filled with axonemes of modified cilia. Rhabdomeric photoreceptors consisting of one to three sensory cells and a single pigmented or unpigmented mantle cell are widespread within taxa of the Plathelminthes Rhabditophora. On the contrary, the existence of two mantle cells forming the eye cup is only known for M. spiculifer and a few other species of the Macrostomida. Therefore, at least two hypotheses are possible: (1) two cup cells are a basic characteristic of the Rhabditophora and a reduction from two to one cup cell has occurred secondarily or (2) the stem species of the Rhabditophora possessed rhabdomeric eyes with one cup cell, and two mantle cells have evolved within the Macrostomorpha. The existence of ciliary aggregates has been documented for several taxa of the Plathelminthes Rhabditophora. From their distribution it can not be concluded whether these differentiations are either a basic feature of the Rhabditophora or have evolved several times convergently.

Toxic epidermal necrolysis following morbilli-parotitis-rubella vaccination

We present the first reported case of toxic epidermal necrolysis (TEN) caused by morbilli-parotitis-rubella (MPR) vaccine. A 13-year-old girl developed TEN 7 days after she received live, attenuated, triple MPR vaccine. The history of drug intake and any illness was negative. At admission the patient was acutely ill with high fever. The whole body was erythematous. The epidermis was wrinkled and the Nikolsky sign was positive. Numerous erosions were present on the lips and genital region. On the seventh day of illness, the eruption involved 80% of the skin. Systemic corticosteroid therapy was not employed. The skin and mucosal defects completely epithelized by the end of the third week of illness. Mild keratoconjunctivitis sicca remained because of permanent cup cell damage.

Toxic epidermal necrolysis following morbilli‐parotitis‐rubella vaccination

We present the first reported case of toxic epidermal necrolysis (TEN) caused by morbilli-parotitis-rubella (MPR) vaccine. A 13-year-old girl developed TEN 7 days after she received live, attenuated, triple MPR vaccine. The history of drug intake and any illness was negative. At admission the patient was acutely ill with high fever. The whole body was erythematous. The epidermis was wrinkled and the Nikolsky sign was positive. Numerous erosions were present on the lips and genital region. On the seventh day of illness, the eruption involved 80% of the skin. Systemic corticosteroid therapy was not employed. The skin and mucosal defects completely epithelized by the end of the third week of illness. Mild keratoconjunctivitis sicca remained because of permanent cup cell damage.