Mean diameter of nucleolar bodies in cultured human leukemic myeloblasts is mainly related to the S and G2 phase of the cell cycle

Mean diameter of nucleolar bodies (nucleoli without the perinucleolar chromatin) per cell was studied in human leukemic myeloblasts represented by K 562 and Kasumi 1 cell lines which originated from chronic and acute myeloid leukaemia. The measurement of mean diameter of nucleolar bodies in specimens stained for RNA was very simple. Such approach eliminated the variability of the perinucleolar chromatin discontinuous shell which might influence the measured nucleolar size as suggested by earlier studies. Ageing of K 562 myeloblasts produced a significant decrease of cells in S+G2 phase of the cell cycle accompanied by a significant reduction of mean diameter of nucleolar bodies (MDNoBs) per cell. In contrast, treatment of Kasumi 1 myeloblasts with histone deacetylase inhibitor - Trichostatin A - produced a large incidence of resistant cells in S+G2 phase which were characterised by a large increase of MDNoBs. Thus, MDNoBs in leukemic myeloblasts might be a helpful tool to estimate the incidence of cells in the S+G2 phase at the single cell level in smear preparations when the number of cells is very small

USING REMOTELY SENSED DATA FOR DOCUMENTATION OF ARCHAEOLOGICAL SITES IN NORTHEASTERN MESOPOTAMIA

This paper introduces two archaeological sites documented during the MULINEM (The Medieval Urban Landscape in Northeastern Mesopotamia) project. This project investigates the Late Sasanian and Islamic urban network in the land of Erbil, a historic province of Hidyab (Adiabene) that is located in northern Iraq. The investigated sites are the two deserted cities of Makhmúr al-Quadíma and Al-Hadítha. It is assumed that these two sites used to form large cities with high business and cultural importance in the medieval period. The archaeological locations are endangered by various threats.The Al-Hadítha site seems to be under the control of the „Islamic state“ at the moment and Makhmúr al-Quadíma is located just next to the town of new Makhmúr that expands rapidly and without complex urban plans. Documentation of the archaeological sites has been done by using remotely sensed methods together with in-situ measurements (where available). FORMOSAT-2 data that has been gained through a research announcement: Free FORMOSAT-2 satellite imagery and when combined with other sources (recent and historical data) it provides a powerful documentation tool. In-situ RPAS measurements and a DTM creation furnish a new source of highly valuable information. Influence of the political and security situation in Al-Hadítha will be analysed

Original Article Experimental Therapy with 9-[2-(Phosphonomethoxy)ethyl]- 2,6-diaminopurine (PMEDAP): Origin of Resistance (MRP4 / MRP5 / PMEDAP resistance)

Abbreviations: DTX -docetaxel, MRP (1-5) -multiple drug resistance protein, PMEA -9-[2-(phosphonomethoxy)ethyl]adenine, PMEDAP -9-[2-(phosphonomethoxy)ethyl]-2,6-diaminopurine, RQ-RT-PCR -real-time quantitative reverse transcriptasepolymerase chain reaction, SD/Cub -Sprague-Dawley inbred rats/Charles University Biology. Abstract. The role of MRP4 and MRP5 transporters in the acyclic nucleoside phosphonate PMEDAP efflux was studied in vitro (CCRF-CEM cells) and in vivo (spontaneous transplantable T-cell lymphoma of SD/Cub inbred rats). The increased resistance against the cytostatic agent PMEDAP during longterm treatment was found to be associated with overexpression of MRP4 and MRP5 genes. The course of both gene activation differs significantly. While the MRP5 function is important in the onset of PMEDAP resistance, the intensity of the relative MRP4 gene expression increases rather continuously. Our data indicate cooperative acting of both MRP4 and MRP5 genes during the PMEDAP resistance development

Re-emerging Aspartic Protease Targets: Examining Cryptococcus neoformans Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery

[Image: see text] Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted Cryptococcus neoformans protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors

Re-emerging Aspartic Protease Targets: Examining Cryptococcus neoformans Major Aspartyl Peptidase 1 as a Target for Antifungal Drug Discovery.

Cryptococcosis is an invasive infection that accounts for 15% of AIDS-related fatalities. Still, treating cryptococcosis remains a significant challenge due to the poor availability of effective antifungal therapies and emergence of drug resistance. Interestingly, protease inhibitor components of antiretroviral therapy regimens have shown some clinical benefits in these opportunistic infections. We investigated Major aspartyl peptidase 1 (May1), a secreted Cryptococcus neoformans protease, as a possible target for the development of drugs that act against both fungal and retroviral aspartyl proteases. Here, we describe the biochemical characterization of May1, present its high-resolution X-ray structure, and provide its substrate specificity analysis. Through combinatorial screening of 11,520 compounds, we identified a potent inhibitor of May1 and HIV protease. This dual-specificity inhibitor exhibits antifungal activity in yeast culture, low cytotoxicity, and low off-target activity against host proteases and could thus serve as a lead compound for further development of May1 and HIV protease inhibitors