Proliferating activity in a bryozoan lophophore

Bryozoans are small benthic colonial animals; their colonies consist of zooids which are composed of a cystid and polypide. According to morphological and molecular data, three classes of bryozoans are recognized: Phylactolaemata, Gymnolaemata and Stenolaemata. Bryozoans are active suspension feeders and their feeding apparatus, the lophophore, is fringed with a single row of ciliated tentacles. In gymnolaemates, the lophophore is bell-shaped and its tentacles may be equal in length (equitentacled lophophores) or some tentacles may be longer than others (obliquely truncated lophophores). In encrusting colonies, polypides with obliquely truncated lophophores usually border specific sites of excurrent water outlets (colony periphery and chimneys) where depleted water has to be removed. It is known that during colony astogeny, colony-wide water currents rearrange: new chimneys are formed and/or location of the chimneys within a given colony changes with time. Such rearrangement requires remodeling of the lophophore shape and lengthening of some tentacles in polypides surrounding water outlets. However, proliferating activity has not been described for bryozoans. Here, we compared the distribution of S-phase and mitotic cells in young and adult polypides in three species of Gymnolaemata. We tested the hypothesis that tentacle growth/elongation is intercalary and cell proliferation takes place somewhere at the lophophore base because such pattern does not interfere with the feeding process. We also present a detailed description of ultrastructure of two parts of the lophophore base: the oral region and ciliated pits, and uncover the possible function of the latter. The presence of stem cells within the ciliated pits and the oral region of polypides provide evidence that both sites participate in tentacle elongation. This confirms the suggested hypothesis about intercalary tentacle growth which provides a potential to alter a lophophore shape in adult polypides according to rearrangement of colony wide water currents during colony astogeny. For the first time deuterosome-like structures were revealed during kinetosome biogenesis in the prospective multiciliated epithelial cells in invertebrates. Tentacle regeneration experiments in Electra pilosa demonstrated that among all epidermal cell types, only non-ciliated cells at the abfrontal tentacle surface are responsible for wound healing. Ciliated cells on the frontal and lateral tentacle surfaces are specialized and unable to proliferate, not even under wound healing. Tentacle regeneration in E. pilosa is very slow and similar to the morphallaxis type. We suggest that damaged tentacles recover their length by a mechanism similar to normal growth, powered by proliferation of cells both within ciliated pits and the oral region.

Prognostic significance of tartrate-resistant acid phosphatase expression in breast cancer.

e12594 Background: Tartrate-resistant acid phosphatase (TRAP) is a metalloproteinase-like protein that is expressed in several primary and metastatic tumors, and its expression is positively correlated with the oncogenic process. Tartrate-resistant acid phosphatase is also a novel product of activated macrophage. We have previously demonstrated the clinical significance of TRAP expression in tumor-infiltrating macrophages and serum TRAP in patients with metastatic breast cancer (BC). Therefore, TRAP protein can potentially be a predictive and prognostic marker to evaluate disease progression and therapeutic response in breast cancer patients with bone metastasis. We aim to investigate the role of TRAP expression in breast cancer metastasis and survival. Methods: RNA-seq expression data were obtained from The Cancer Genome Atlas (TCGA) database. Estrogen receptor (ER)-positive, human epidermal growth factor receptor-2 (HER2)-negative, and TNBC subtypes were included in the analyses. The TRAP-overexpressed and -silenced breast cancer cells (MCF7, 4T1, MDA-MB-231) were used for validation. Survival data was also retrieved from the TCGA database to verify the prognostic biomarker. Results: Through TCGA database analysis, we found that TRAP expression correlated to the Ki-67 expression indicating the cancer cell proliferating activity. Additionally, TRAP expression positively correlated with mesenchymal markers (SNAIL, CDH1, MMP9, Fibronectin), and negatively correlated with epithelial markers (SMAD2, SOX10), implying that the TRAP expression is related to the breast cancer Epithelial-Mesenchymal-Transition process. This phenomenon was validated in TRAP-altered cell and confirmed inferior survival with TRAP-expressed breast cancer patients in TCGA database. Conclusions: Combining clinical TCGA data and cell-based analyses showed that TRAP expression was significantly associated with breast cancer proliferating activity, metastatic potential, and inferior survival. TRAP serves as a breast cancer prognostic biomarker and can be considered as a therapeutic target. Further investigation is warranted.

Inhibition of Hippocampal Regeneration by Adjuvant Dexamethasone in Experimental Infant Rat Pneumococcal Meningitis

Pneumococcal meningitis (PM) causes neurological sequelae in up to half of surviving patients. Neuronal damage associated with poor outcome is largely mediated by the inflammatory host response. Dexamethasone (DXM) is used as an adjuvant therapy in adult PM, but its efficacy in the treatment of pneumococcal meningitis in children is controversially discussed. While DXM has previously been shown to enhance hippocampal apoptosis in experimental PM, its impact on hippocampal cell proliferation is not known. This study investigated the impact of DXM on hippocampal proliferation in infant rat PM. Eleven-day-old nursing Wistar rats (n= 90) were intracisternally infected withStreptococcus pneumoniaeto induce experimental meningitis. Treatment with DXM or vehicle was started 18 h after infection, concomitantly with antibiotics (ceftriaxone 100 mg/kg of body weight twice a day [b.i.d.]). Clinical parameters were monitored, and the amount of cells with proliferating activity was assessed usingin vivoincorporation of bromodeoxyuridine (BrdU) and anin vitroneurosphere culture system at 3 and 4 d postinfection. DXM significantly worsened weight loss and survival. Density of BrdU-positive cells, as an index of cells with proliferating activity, was significantly lower in DXM-treated animals compared to vehicle controls (P< 0.0001). In parallel, DXM reduced neurosphere formation as an index for stem/progenitor cell density compared to vehicle treatment (P= 0.01). Our findings provide clear evidence that DXM exerts an antiproliferative effect on the hippocampus in infant rat PM. We conclude that an impairment of regenerative hippocampal capacity should be taken into account when considering adjuvant DXM in the therapeutic regimen for PM in children.