MORPHOMETRIC ANALYSIS OF YEAST CELLS: III. SIZE DISTRIBUTION OF 2-DEOXYGLUCOSE-INDUCED LYSING SCHIZOSACCAROMYCES POMBE CELLS AND THEIR SITES OF LYSIS

1974 ◽  
Vol 16 (3) ◽  
pp. 593-598 ◽  
Author(s):  
Byron F. Johnson ◽  
Calvin Lu ◽  
Sidney Brandwein

To cultures of Schizosaccharomyces pombe, 2-deoxyglucose (2DG) was added, either as 7 μg/ml during inoculation of the cultures (low dosage), or as 250 μg/ml during the log phase (high dosage). Samples were removed from the cultures, and lysing and non-lysing cells were measured and tabulated. Addition of the high dosage was followed immediately by lysis, with over 85% of the lysing cells found in cytolysis at their primary growing ends Lysis ensued only at the beginning of the stationary phase in the low dosage experiments; 64% of the affected cells lysed at their cell plates. Cells lysing at their primary ends (high dose experiments) were shorter than the controls; cells lysing at their cell plates (low dose experiments) were longer than the controls. The cell division process of the last cell cycle completed in the culture is unusual in its susceptibility to the low initial dose of 2DG, suggesting that cell division metabolism is fundamentally different from wall extension metabolism in the fission yeast.

1981 ◽  
Vol 26 (6) ◽  
pp. 395-401 ◽  
Author(s):  
D. Garfinkel Barry ◽  
D. Webster Christopher ◽  
Leon Sloman

Six children with the diagnosis of Attention Deficit Disorder were treated as day hospital patients, using different stimulant medication. They were studied in a double-blind crossover experiment in which they received caffeine in low dose or in a high dose. Methylphenidate was added to both dosages, as well as administered alone. Results indicated that caffeine in low dosage when added to methylphenidate was superior to all other treatment conditions. Caffeine in low dosage could not be differentiated from 10 mg of methylphenidate. High dosage caffeine was not different from placebo or no-drug conditions. This study offers evidence to support a curvilinear pattern of dose-response for caffeine, in attenuating the behavioural manifestations of this syndrome.


2020 ◽  
Vol 31 (10) ◽  
pp. 1069-1084 ◽  
Author(s):  
Heidi M. Blank ◽  
Ophelia Papoulas ◽  
Nairita Maitra ◽  
Riddhiman Garge ◽  
Brian K. Kennedy ◽  
...  

In several systems, including budding yeast, cell cycle-dependent changes in the transcriptome are well studied. In contrast, few studies queried the proteome during cell division. There is also little information about dynamic changes in metabolites and lipids in the cell cycle. Here, the authors present such information for dividing yeast cells.


1998 ◽  
Vol 42 (7) ◽  
pp. 1722-1725 ◽  
Author(s):  
Mohammad Ashraf Hossain ◽  
Shigefumi Maesaki ◽  
Hiroshi Kakeya ◽  
Tetsuhiro Noda ◽  
Katsunori Yanagihara ◽  
...  

ABSTRACT In vitro and in vivo efficacies of NS-718, a lipid nanosphere-encapsulated amphotericin B (AMPH-B), have been studied. Of the tested AMPH-B formulations, NS-718 had the lowest MIC forCryptococcus neoformans. In a murine model, low-dose therapy (0.8 mg/kg of body weight) with NS-718 showed higher efficacy than that with AmBisome. High-dose therapy (2.0 mg/kg) with NS-718 was much more effective than those with Fungizone and AmBisome. In mice treated with a high dose of NS-718, only a few yeast cells had grown in lung by 7 days after inoculation. A pharmacokinetic study showed higher concentrations of AMPH-B in lung following administration of NS-718 than after administration of AmBisome. Our results indicated that NS-718, a new AMPH-B formulation, is a promising antifungal agent for treatment of pulmonary cryptococcosis and could be the most effective antifungal agent against C. neoformans infections.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 5542-5542
Author(s):  
S. J. Wong ◽  
Z. Agha ◽  
S. Milligan

5542 Background: The superiority of concurrent high dose cisplatin and radiation (RT) compared to RT alone for pts with locally advanced squamous cell cancer of the head and neck (SCCHN) has been demonstrated in large prospective phase III clinical trials. However, little is known regarding general prescribing patterns for chemotherapy (CT) utilization in combined modality treatment (CMT) for SCCHN. We conducted the present study to gain insight as to whether results from pivotal phase III trials affect utilization of concurrent CT in academic and community centers. Methods: We analyzed individual data from 326 SCCHN pts treated with concurrent CT and RT between 03/2003 and 12/2004 from 53 centers (43 community-based, 7 academic, and 3 VA or military) using electronically captured data from IntelliDose, a chemotherapy order software program. Results: Of 326 total pts, 123 pts (38%) received single agent cisplatin. From this group, 71 (58%) received low dose cisplatin (<74 mg/m2, mean initial dose 67 mg), while 52 patients (42%) received high dose cisplatin (≥ 74 mg/m2, mean initial dose 189 mg). 72 pts (22%) received carboplatin/paclitaxel, 60 pts (18%) received cisplatin /5FU, 18 pts (5.5%) received single agent carboplatin, while 6 pts (1.8%) received cetuximab either alone or in combination with cisplatin. Other infrequently used regimens (each < 5%) cumulatively accounted for 14% of pts treated. Comparison of chemotherapy utilization between academic and community-based practice centers showed no statistical difference with respect to use of high dose cisplatin versus low dose cisplatin, or single agent cisplatin versus non-cisplatin regimens. Conclusions: Despite evidence from phase III studies that concurrent high dose cisplatin is the standard of care for CMT of locally advanced SCCHN, utilization of other regimens, such as weekly low dose cisplatin, are commonly utilized. [Table: see text]


2005 ◽  
Vol 289 (1) ◽  
pp. F175-F185 ◽  
Author(s):  
Midhun C. Korrapati ◽  
Edward A. Lock ◽  
Harihara M. Mehendale

Sustained activation of ERK 1/2 by a low dose (15 mg/kg ip) of S-1,2-dichlorovinyl-l-cysteine (DCVC) 72 h before administration of a lethal dose of DCVC (75 mg/kg ip) enhances renal cell division and protects mice against acute renal failure (ARF) and death (autoprotection). The objective of this study was to determine correlation among extent of S-phase DNA synthesis, activation of transcription factors, expression of G1/S cyclins, cyclin-dependent kinases (CDKs), and CDK inhibitors downstream of ERK 1/2 following DCVC-induced ARF in autoprotection. Administration of the lethal dose alone caused a general downregulation or an unsustainable increase, in transcriptional and posttranscriptional events thereby preventing G1-S transition of renal cell cycle. Phosphorylation of IκBα was inhibited resulting in limited nuclear translocation of NF-κB. However, cyclin D1 expression was high probably due to transcriptional cooperation of AP-1. Cyclin D1/cyclin-dependent kinase 4 (cdk4)-cdk6 system-mediated phosphorylation of retinoblastoma protein was downregulated due to overexpression of p16 at 24 h after exposure to the lethal dose alone. Inhibition of S-phase stimulation was confirmed by proliferating cell nuclear antigen assay (PCNA). This inhibitory response was prevented if the lethal dose was administered 72 h after the low priming dose of DCVC due to promitogenic effect of the low dose. NF-κB-DNA binding is not limited if mice were pretreated with the priming dose. Cyclin D1/cdk4-cdk6 expression stimulated by the priming dose of DCVC was unaltered even after the lethal dose in the autoprotected group, explaining higher phosphorylated-pRB and S-phase stimulation found in this group. These results were corroborated with PCNA immunohistochemistry. These findings suggest that the priming dose relieves the block on compensatory tissue repair by upregulation of promitogenic mechanisms, normally blocked by the high dose when administered without the prior priming dose.


1999 ◽  
Vol 181 (18) ◽  
pp. 5669-5675 ◽  
Author(s):  
Karin Hjort ◽  
Rolf Bernander

ABSTRACT Stationary-phase cultures of different hyperthermophilic species of the archaeal genus Sulfolobus were diluted into fresh growth medium and analyzed by flow cytometry and phase-fluorescence microscopy. After dilution, cellular growth started rapidly but no nucleoid partition, cell division, or chromosome replication took place until the cells had been increasing in size for several hours. Initiation of chromosome replication required that the cells first go through partition and cell division, revealing a strong interdependence between these key cell cycle events. The time points at which nucleoid partition, division, and replication occurred after the dilution were used to estimate the relative lengths of the cell cycle periods. When exponentially growing cultures were diluted into fresh growth medium, there was an unexpected transient inhibition of growth and cell division, showing that the cultures did not maintain balanced growth. Furthermore, when cultures growing at 79°C were shifted to room temperature or to ice-water baths, the cells were found to “freeze” in mid-growth. After a shift back to 79°C, growth, replication, and division rapidly resumed and the mode and kinetics of the resumption differed depending upon the nature and length of the shifts. Dilution of stationary-phase cultures provides a simple protocol for the generation of partially synchronized populations that may be used to study cell cycle-specific events.


1998 ◽  
Vol 84 (4) ◽  
pp. 1131-1137 ◽  
Author(s):  
N. Loos ◽  
P. Haouzi ◽  
F. Marchal

Intravenous injection of dopamine (DA) has consistently been shown to depress minute ventilation (V˙e). Whereas at low dosage (≤10 μg/kg) this effect may be accounted for by inhibition of the carotid sinus nerve chemosensory discharge (CSNCD), other mechanisms appear to be involved with large dosage (≥50 μg/kg). The purpose of this study was to elucidate the mechanisms of DA-inducedV˙e depression. The effects of intravenous injection of DA doses ranging from 1 to 200 μg/kg were studied in 18 anesthetized cats. DA was injected during air and O2 breathing, after α-adrenergic blockade by phenoxybenzamine and after baro- and chemodenervation.V˙e and CSNCD were also simultaneously recorded on four occasions. In contrast to that with use of low-dose DA, V˙e depression induced by high-dose DA was dissociated from CSNCD, persisted during 100% O2 breathing, and was significantly correlated with the rise in arterial blood pressure. Although blunted, V˙e depression was still present after complete chemo- and barodenervation but was suppressed by blocking of the concomitant vasoconstriction with phenoxybenzamine. It is concluded that reflexes of circulatory origin contribute to the V˙e depression induced by large-dose DA, in addition to its effects on arterial chemoreceptors. The contribution of baroreceptor stimulation and peripheral vasoconstriction is discussed.


2013 ◽  
Vol 3 (1) ◽  
pp. 75-90 ◽  
Author(s):  
Martin Bonke ◽  
Mikko Turunen ◽  
Maria Sokolova ◽  
Anna Vähärautio ◽  
Teemu Kivioja ◽  
...  

Abstract In this work, we map the transcriptional targets of 107 previously identified Drosophila genes whose loss caused the strongest cell-cycle phenotypes in a genome-wide RNA interference screen and mine the resulting data computationally. Besides confirming existing knowledge, the analysis revealed several regulatory systems, among which were two highly-specific and interconnected feedback circuits, one between the ribosome and the proteasome that controls overall protein homeostasis, and the other between the ribosome and Myc/Max that regulates the protein synthesis capacity of cells. We also identified a set of genes that alter the timing of mitosis without affecting gene expression, indicating that the cyclic transcriptional program that produces the components required for cell division can be partially uncoupled from the cell division process itself. These genes all have a function in a pathway that regulates the phosphorylation state of Cdk1. We provide evidence showing that this pathway is involved in regulation of cell size, indicating that a Cdk1-regulated cell size checkpoint exists in metazoans.


Genetics ◽  
1998 ◽  
Vol 149 (3) ◽  
pp. 1265-1275 ◽  
Author(s):  
Mohan K Balasubramanian ◽  
Dannel McCollum ◽  
Louise Chang ◽  
Kelvin C Y Wong ◽  
Naweed I Naqvi ◽  
...  

Abstract Schizosaccharomyces pombe is an excellent organism in which to study cytokinesis as it divides by medial fission using an F-actin contractile ring. To enhance our understanding of the cell division process, a large genetic screen was carried out in which 17 genetic loci essential for cytokinesis were identified, 5 of which are novel. Mutants identifying three genes, rng3+, rng4+, and rng5+, were defective in organizing an actin contractile ring. Four mutants defective in septum deposition, septum initiation defective (sid)1, sid2, sid3, and sid4, were also identified and characterized. Genetic analyses revealed that the sid mutants display strong negative interactions with the previously described septation mutants cdc7-24, cdc11-123, and cdc14-118. The rng5+, sid2+, and sid3+ genes were cloned and shown to encode Myo2p (a myosin heavy chain), a protein kinase related to budding yeast Dbf2p, and Spg1p, a GTP binding protein that is a member of the ras superfamily of GTPases, respectively. The ability of Spg1p to promote septum formation from any point in the cell cycle depends on the activity of Sid4p. In addition, we have characterized a phenotype that has not been described previously in cytokinesis mutants, namely the failure to reorganize actin patches to the medial region of the cell in preparation for septum formation.


2021 ◽  
Author(s):  
Alexandra Colin ◽  
Gabriele Micali ◽  
Louis Faure ◽  
Marco Cosentino Lagomarsino ◽  
Sven van Teeffelen

AbstractCells must control the cell cycle to ensure that key processes are brought to completion. In Escherichia coli, it is controversial whether cell division is tied to chromosome replication or to a replication-independent inter-division process. A recent model suggests instead that both processes may limit cell division with comparable odds in single cells. Here, we tested this possibility experimentally by monitoring single-cell division and replication over multiple generations at slow growth. We then perturbed cell width, causing an increase of the time between replication termination and division. As a consequence, replication became decreasingly limiting 21 for cell division, while correlations between birth and division and between subsequent replication-initiation events were maintained. Our experiments support the hypothesis that both chromosome replication and a replication-independent inter-division process can limit cell division: the two processes have balanced contributions in non-perturbed cells, while our width perturbations increase the odds of the replication-independent process being limiting.


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