The dynamics of phytoplankton seasonal development and its horizontal distribution in Lake Sevan (Armenia).

High-altitude freshwater lakes are experiencing ever-increasing risk of harmful algal blooms (HABs) on the face of climate change and a growing demand on agricultural production. The biggest alpine lake of the Caucasus, Lake Sevan, has "blooming" recently almost every year. Thus, the study of phytoplankton community' development patterns in Lake Sevan is gaining urgency. The aim of the work has been the study of the seasonal dynamics of quantitative and qualitative characteristics of phytoplankton in Lake Sevan. Also, we have tried to determine the features of horizontal distribution of phytoplankton within different seasons with the focus on Cyanobacteria distribution to identify current spatial-temporal features of HABs in Lake Sevan. Seasonal ground data collected from the photic zone of 178 stations in 2016-2018 was analysed and spatially interpolated. The results of analysis of seasonal dynamics of phytoplankton groups abundance have revealed the increased role of Cyanobacteria in the algal "blooms". Particularly, HABs were led by the dominant species of the genus Dolichospermum/Anabaena that are potentially toxic. Univariate analysis of variance with the post hoc Tukey test has proved the significance of changes in the quantitative parameters of phytoplankton development within years with the peak in 2018. Some antagonistic relations between the groups of phytoplankton under the HAB events were also shown through factorial and correlation analysis. Spatial interpolations revealed very limited extents of HABs compared with "blooms" led by Bacillariophyta species. HABs were mainly occurring in the littoral zone in a close proximity to the estuaries of Lake Sevan major tributaries.

Optimization of a Neural Stem-Cell-Mediated Carboxylesterase/Irinotecan Gene Therapy for Metastatic Neuroblastoma.

Despite improved survival for children with newly diagnosed neuroblastoma (NB), recurrent disease is a significant problem, with treatment options limited by anti-tumor efficacy, patient drug tolerance, and cumulative toxicity. We previously demonstrated that neural stem cells (NSCs) expressing a modified rabbit carboxylesterase (rCE) can distribute to metastatic NB tumor foci in multiple organs in mice and convert the prodrug irinotecan (CPT-11) to the 1,000-fold more toxic topoisomerase-1 inhibitor SN-38, resulting in significant therapeutic efficacy. We sought to extend these studies by using a clinically relevant NSC line expressing a modified human CE (hCE1m6-NSCs) to establish proof of concept and identify an intravenous dose and treatment schedule that gave maximal efficacy. Human-derived NB cell lines were significantly more sensitive to treatment with hCE1m6-NSCs and irinotecan as compared with drug alone. This was supported by pharmacokinetic studies in subcutaneous NB mouse models demonstrating tumor-specific conversion of irinotecan to SN-38. Furthermore, NB-bearing mice that received repeat treatment with intravenous hCE1m6-NSCs and irinotecan showed significantly lower tumor burden (1.4-fold, p = 0.0093) and increased long-term survival compared with mice treated with drug alone. These studies support the continued development of NSC-mediated gene therapy for improved clinical outcome in NB patients.