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Cells enter a unique intermediate 4N stage, not 4N-G1, after aborted mitosis.
Mantel, Charlie,Guo, Ying,Lee, Man Ryul,Han, Myung Kwan,Rhorabough, Sara,Kim, Kye Seong,Broxmeyer, Hal E Landes Bioscience 2008 Cell Cycle Vol.7 No.4
<P>It is widely accepted that mammalian cells enter the next G(1)-phase (G(1)) with 4N DNA after slippage from prolonged drug-induced mitotic block caused by activation of the transient spindle checkpoint. Understanding cell fate after mitotic slippage (MS) has significant clinical importance. The conclusion the MS cells enter 4N-G(1) is based on morphology and mitotic cyclin destruction. Definitive biochemical evidence for G(1) is scarce or unconvincing, in part because of methods of protein extraction required for immunoblot analysis that cannot take into account the cell cycle heterogeneity of cell cultures. We used single-cell-intracellular-flow-cytometric analysis to further define important factors determining cell fate after MS. Results from human and mouse embryonic stem cells (ESC) that reenter polyploid cell cycles are compared to human somatic cells that die after MS. We conclude that phosphorylation status of pRb, p53, CDK1, and especially cyclin B1 levels are important for cell fate decision in MS cells, which occur in a unique, intervening, non-G(1), tetraploid subphase.</P>
Enhancing Hematopoietic Stem Cell Transplantation Efficacy by Mitigating Oxygen Shock
Mantel, Charlie R.,O'Leary, Heather A.,Chitteti, Brahmananda R.,Huang, X.,Cooper, S.,Hangoc, G.,Brustovetsky, N.,Srour, Edward F.,Lee, M.,Messina-Graham, S.,Haas, David M.,Falah, N.,Kapur, R.,Pelus, L Cell Press ; MIT Press 2015 Cell Vol.161 No.7
Hematopoietic stem cells (HSCs) reside in hypoxic niches within bone marrow and cord blood. Yet, essentially all HSC studies have been performed with cells isolated and processed in non-physiologic ambient air. By collecting and manipulating bone marrow and cord blood in native conditions of hypoxia, we demonstrate that brief exposure to ambient oxygen decreases recovery of long-term repopulating HSCs and increases progenitor cells, a phenomenon we term extraphysiologic oxygen shock/stress (EPHOSS). Thus, true numbers of HSCs in the bone marrow and cord blood are routinely underestimated. We linked ROS production and induction of the mitochondrial permeability transition pore (MPTP) via cyclophilin D and p53 as mechanisms of EPHOSS. The MPTP inhibitor cyclosporin A protects mouse bone marrow and human cord blood HSCs from EPHOSS during collection in air, resulting in increased recovery of transplantable HSCs. Mitigating EPHOSS during cell collection and processing by pharmacological means may be clinically advantageous for transplantation.
Mantel, Charlie,Guo, Ying,Lee, Man Ryul,Kim, Min-Kyoung,Han, Myung-Kwan,Shibayama, Hirohiko,Fukuda, Seiji,Yoder, Mervin C.,Pelus, Louis M.,Kim, Kye-Seong,Broxmeyer, Hal E. American Society of Hematology 2007 Blood Vol.109 No.10
<B>Abstract</B><P>Karyotypic abnormalities in cultured embryonic stem cells (ESCs), especially near-diploid aneuploidy, are potential obstacles to ESC use in regenerative medicine. Events causing chromosomal abnormalities in ESCs may be related to events in tumor cells causing chromosomal instability (CIN) in human disease. However, the underlying mechanisms are unknown. Using multiparametric permeabilized-cell flow cytometric analysis, we found that the mitotic-spindle checkpoint, which helps maintain chromosomal integrity during all cell divisions, functions in human and mouse ESCs, but does not initiate apoptosis as it does in somatic cells. This allows an unusual tolerance to polyploidy resulting from failed mitosis, which is common in rapidly proliferating cell populations and which is reduced to near-diploid aneuploidy, which is also common in human neoplastic disease. Checkpoint activation in ESC-derived early-differentiated cells results in robust apoptosis without polyploidy/aneuploidy similar to that in somatic cells. Thus, the spindle checkpoint is “uncoupled” from apoptosis in ESCs and is a likely source of karyotypic abnormalities. This natural behavior of ESCs to tolerate/survive varying degrees of ploidy change could complicate genome-reprogramming studies and stem-cell plasticity studies, but could also reveal clues about the mechanisms of CIN in human tumors.</P>
Reliability and Validity of the Embouchure Dystonia Severity Rating Scale
Tobias Mantel,André Lee,Shinichi Furuya,Masanori Morise,Eckart Altenmüller,Bernhard Haslinger 대한파킨슨병및이상운동질환학회 2023 Journal Of Movement Disorders Vol.16 No.2
Embouchure dystonia (ED) is a task-specific movement disorder that leads to loss of fine motor control of the embouchure and tongue muscles in wind musicians. In contrast to musicians’ hand dystonia, no validated severity rating for ED exists, posing a major obstacle for structured assessment in scientific and clinical settings. The aim of this study is to validate an ED severity rating scale (EDSRS) allowing for a standardized estimation of symptom severity in ED.
Use of supercritical methanol/carbon dioxide mixtures for biodiesel production
María Belén García-Jarana,Jezabel Sánchez-Oneto,Juan Ramón Portela,Lourdes Casas,Casimiro Mantell,Enrique Martínez de la Ossa 한국화학공학회 2016 Korean Journal of Chemical Engineering Vol.33 No.8
The use of supercritical conditions for the production of biodiesel from both vegetables oils and waste-oils may be of great industrial interest because it can be carried out without those catalysts necessary in the conventional transesterification process, therefore avoiding a complex separation between the product and the catalyst. However, the use of supercritical alcohol requires higher operating temperatures and pressures. In this work, CO2 was added to the reaction mixture in order to reduce the operating conditions (temperature, pressure and molar ratio of alcohol to vegetable oil). The novelty of using CO2 may have two advantages: a possible combination of supercritical CO2 extraction of the oil and its subsequent transesterification reaction without CO2 depressurization, and a reduction of the supercritical temperature and pressure of the mixture. The effects of temperature (280-350 oC), pressure (140-280 bar), methanol- to-oil molar ratio (20-30), CO2-to-methanol molar ratio (0.05-0.2) and residence time (0-45minutes) on the yield of methyl esters (biodiesel) were studied in a batch reactor, obtaining in all cases a relatively low increase in the yield when CO2 was present in the medium. The yields of biodiesel were tested with three vegetable oils used as model compounds (palm, sunflower and borage), obtaining similar results.
Antonio Montes,Chandrasekar Chinnarasu,Clara Pereyra,Lourdes Casas,María Teresa Fernández-Ponce,Casimiro Mantell,Sangma Pattabhi,Enrique Martínez de la Ossa 한국화학공학회 2016 Korean Journal of Chemical Engineering Vol.33 No.2
Various extracts from olive leaves have been precipitated by a supercritical antisolvent (SAS) process to evaluate the possibility of producing polyphenol fine particles with controlled size and size distribution. Olive leaves were initially extracted with subcritical fluids using mixtures of CO2+ethanol at 10% and 50%, by pressurized liquid extraction (PLE) with water, ethanol and a hydroalcoholic mixture (50 : 50) (v/v), and also by conventional ethanol extraction (CE). PLE gave the extract with the highest yield and the best antioxidant activity. SAS precipitation was unsuccessful for the extracts obtained with pressurized water and with the hydroalcoholic mixture (50 : 50) (v/v). The SAS precipitates with the smallest particle sizes were produced from extracts obtained with subcritical fluids. The SAS precipitates obtained after the conventional ethanol extraction of olive leaves showed the best antioxidant activity.