Cell Cycle Parameters of the Different Cell Types in the Rodent Brain During Pre- and Postnatal Ontogeny

1980 ◽  
pp. 17-35
Author(s):  
Hubert Korr
Keyword(s):  
Cell Cycle ◽  
Cell Types ◽  
Postnatal Ontogeny ◽  
Rodent Brain ◽  
Different Cell Types

scholarly journals CA Mutation N57A Has Distinct Strain-Specific HIV-1 Capsid Uncoating and Infectivity Phenotypes

2019 ◽  
Vol 93 (9) ◽  
Author(s):  
Douglas K. Fischer ◽  
Akatsuki Saito ◽  
Christopher Kline ◽  
Romy Cohen ◽  
Simon C. Watkins ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Amino Acid ◽  
Cell Types ◽  
Careful Consideration ◽  
Immunodeficiency Virus ◽  
Cell Cycle Dependence ◽  
Cycle Dependent ◽  
Multiple Strains ◽  
Different Cell Types ◽  
Hiv 1

ABSTRACTThe ability of human immunodeficiency virus type 1 (HIV-1) to transduce nondividing cells is key to infecting terminally differentiated macrophages, which can serve as a long-term reservoir of HIV-1 infection. The mutation N57A in the viral CA protein renders HIV-1 cell cycle dependent, allowing examination of HIV-1 infection of nondividing cells. Here, we show that the N57A mutation confers a postentry infectivity defect that significantly differs in magnitude between the common lab-adapted molecular clones HIV-1NL4-3(>10-fold) and HIV-1LAI(2- to 5-fold) in multiple human cell lines and primary CD4+T cells. Capsid permeabilization and reverse transcription are altered when N57A is incorporated into HIV-1NL4-3but not HIV-1LAI. The N57A infectivity defect is significantly exacerbated in both virus strains in the presence of cyclosporine (CsA), indicating that N57A infectivity is dependent upon CA interacting with host factor cyclophilin A (CypA). Adaptation of N57A HIV-1LAIselected for a second CA mutation, G94D, which rescued the N57A infectivity defect in HIV-1LAIbut not HIV-1NL4-3. The rescue of N57A by G94D in HIV-1LAIis abrogated by CsA treatment in some cell types, demonstrating that this rescue is CypA dependent. An examination of over 40,000 HIV-1 CA sequences revealed that the four amino acids that differ between HIV-1NL4-3and HIV-1LAICA are polymorphic, and the residues at these positions in the two strains are widely prevalent in clinical isolates. Overall, a few polymorphic amino acid differences between two closely related HIV-1 molecular clones affect the phenotype of capsid mutants in different cell types.IMPORTANCEThe specific mechanisms by which HIV-1 infects nondividing cells are unclear. A mutation in the HIV-1 capsid protein abolishes the ability of the virus to infect nondividing cells, serving as a tool to examine cell cycle dependence of HIV-1 infection. We have shown that two widely used HIV-1 molecular clones exhibit significantly different N57A infectivity phenotypes due to fewer than a handful of CA amino acid differences and that these clones are both represented in HIV-infected individuals. As such minor differences in closely related HIV-1 strains may impart significant infectivity differences, careful consideration should be given to drawing conclusions from one particular HIV-1 clone. This study highlights the potential for significant variation in results with the use of multiple strains and possible unanticipated effects of natural polymorphisms.

scholarly journals Antiproliferative Effect of Dihydroxyacetone on Trypanosoma brucei Bloodstream Forms: Cell Cycle Progression, Subcellular Alterations, and Cell Death

2007 ◽  
Vol 51 (11) ◽  
pp. 3960-3968 ◽  
Author(s):  
Néstor L. Uzcátegui ◽  
Didac Carmona-Gutiérrez ◽  
Viola Denninger ◽  
Caroline Schoenfeld ◽  
Florian Lang ◽  
...  
Keyword(s):  
Energy Source ◽  
Cell Cycle ◽  
Trypanosoma Brucei ◽  
Rational Design ◽  
Cell Cycle Progression ◽  
Cell Types ◽  
Cycle Arrest ◽  
Starting Point ◽  
M Phase ◽  
Different Cell Types

ABSTRACT We evaluated the effects of dihydroxyacetone (DHA) on Trypanosoma brucei bloodstream forms. DHA is considered an energy source for many different cell types. T. brucei takes up DHA readily due to the presence of aquaglyceroporins. However, the parasite is unable to use it as a carbon source because of the absence of DHA kinase (DHAK). We could not find a homolog of the relevant gene in the genomic database of T. brucei and have been unable to detect DHAK activity in cell lysates of the parasite, and the parasite died quickly if DHA was the sole energy source in the medium. In addition, during trypanosome cultivation, DHA induced growth inhibition with a 50% inhibitory concentration of about 1 mM, a concentration that is completely innocuous to mammals. DHA caused cell cycle arrest in the G2/M phase of up to 70% at a concentration of 2 mM. Also, DHA-treated parasites showed profound ultrastructural alterations, including an increase of vesicular structures within the cytosol and the presence of multivesicular bodies, myelin-like structures, and autophagy-like vacuoles, as well as a marked disorder of the characteristic mitochondrion structure. Based on the toxicity of DHA for trypanosomes compared with mammals, we consider DHA a starting point for a rational design of new trypanocidal drugs.

scholarly journals Cell Cycle Control of a Holdfast Attachment Gene inCaulobacter crescentus

1999 ◽  
Vol 181 (4) ◽  
pp. 1118-1125 ◽  
Author(s):  
Raji S. Janakiraman ◽  
Yves V. Brun
Keyword(s):  
Cell Cycle ◽  
Polar Region ◽  
Caulobacter Crescentus ◽  
Cell Cycle Control ◽  
Indirect Evidence ◽  
Cell Types ◽  
Transmission Electron ◽  
Different Cell Types ◽  
Prosthecate Bacterium ◽  
Maximal Expression

ABSTRACT Attachment to surfaces by the prosthecate bacteriumCaulobacter crescentus is mediated by an adhesive organelle, the holdfast, found at the tip of the stalk. Indirect evidence suggested that the holdfast first appears at the swarmer pole of the predivisional cell. We used fluorescently labeled lectin and transmission electron microscopy to detect the holdfast in different cell types. While the holdfast was readily detectable in stalked cells and at the stalked poles of predivisional cells, we were unable to detect the holdfast in swarmer cells or at the flagellated poles of predivisional cells. This suggests that exposure of the holdfast to the outside of the cell occurs during the differentiation of swarmer to stalked cells. To investigate the timing of holdfast synthesis and exposure to the outside of the cell, we have examined the regulation of a holdfast attachment gene, hfaA. The hfaA gene is part of a cluster of four genes (hfaABDC), identified in strain CB2A and involved in attachment of the holdfast to the polar region of the cell. We have identified the hfaA gene in the synchronizable C. crescentus strain CB15. The sequence of the CB2A hfaA promoter suggested that it was regulated by ς54. We show that the transcription of hfaAfrom either strain is not dependent on ς54. Using ahfaA-lacZ fusion, we show that the transcription ofhfaA is temporally regulated during the cell cycle, with maximal expression in late-predivisional cells. This increase in expression is largely due to the preferential transcription ofhfaA in the swarmer pole of the predivisional cell.

scholarly journals Early Induction of Apoptosis in Hematopoietic Cell Lines After Exposure to Flavopiridol

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 458-465 ◽  
Author(s):  
Bernard W. Parker ◽  
Gurmeet Kaur ◽  
Wilberto Nieves-Neira ◽  
Mohammed Taimi ◽  
Glenda Kohlhagen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Prostate Carcinoma ◽  
Cell Types ◽  
Carcinoma Cells ◽  
Cycle Arrest ◽  
Induced Apoptosis ◽  
Different Cell Types ◽  
Hematopoietic Cell Lines

Abstract Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4:120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bax protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority.

scholarly journals Control of tissue development by cell cycle dependent transcriptional filtering

2020 ◽  
Author(s):  
Maria Abou Chakra ◽  
Ruth Isserlin ◽  
Thinh Tran ◽  
Gary D. Bader
Keyword(s):  
Cell Cycle ◽  
Cell Fate ◽  
Control Cell ◽  
Cell Types ◽  
Cycle Duration ◽  
Cell Diversity ◽  
Cycle Dependent ◽  
Cell Cycle Dynamics ◽  
Different Cell Types ◽  
Long Genes

AbstractCell cycle duration changes dramatically during development, starting out fast to generate cells quickly and slowing down over time as the organism matures. The cell cycle can also act as a transcriptional filter to control the expression of long genes which are partially transcribed in short cycles. Using mathematical simulations of cell proliferation, we identify an emergent property, that this filter can act as a tuning knob to control cell fate, cell diversity and the number and proportion of different cell types in a tissue. Our predictions are supported by comparison to single-cell RNA-seq data captured over embryonic development. Evolutionary genome analysis shows that fast developing organisms have a narrow genomic distribution of gene lengths while slower developers have an expanded number of long genes. Our results support the idea that cell cycle dynamics may be important across multicellular animals for controlling gene expression and cell fate.

scholarly journals CcnA, a novel non-coding RNA regulating the bacterial cell cycle

2019 ◽  
Author(s):  
Wanassa Beroual ◽  
David Lalaouna ◽  
Nadia Ben Zaina ◽  
Odile Valette ◽  
Karine Prévost ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Sinorhizobium Meliloti ◽  
Caulobacter Crescentus ◽  
Direct Interaction ◽  
Cell Types ◽  
Bacterial Cells ◽  
Non Coding Rna ◽  
Sequential Activation ◽  
Bacterial Cell Cycle ◽  
Different Cell Types

SummaryBacterial cells are powerful models for understanding how cells divide and accomplish global regulatory programs. In Caulobacter crescentus a cascade of essential master regulators regulate the correct and sequential activation of DNA replication, cell division and development of different cell types. Among them CtrA plays a crucial role coordinating all those functions. Despite decades of investigation, no control by non-coding RNAs (ncRNAs) has been linked to Caulobacter cell cycle. Here, for the first time we describe the role of a novel essential factor named CcnA, a ncRNA located at the origin of replication, activated by CtrA and responsible for the rapid and strong accumulation of CtrA itself. In addition CcnA is also responsible for the inhibition of GcrA translation by direct interaction with its UTR region. By a combination of probing experiments and mutagenesis, we propose a new mechanism by liberation (CtrA) or sequestration (GcrA) of the Ribosome Binding Site (RBS). CcnA role is conserved in other alphaproteobacterial species, such as Sinorhizobium meliloti, representing indeed a conserved and fundamental process regulating cell cycle in Rhizobiales and Caulobacterales.

scholarly journals Early Induction of Apoptosis in Hematopoietic Cell Lines After Exposure to Flavopiridol

Blood ◽  
1998 ◽  
Vol 91 (2) ◽  
pp. 458-465 ◽  
Author(s):  
Bernard W. Parker ◽  
Gurmeet Kaur ◽  
Wilberto Nieves-Neira ◽  
Mohammed Taimi ◽  
Glenda Kohlhagen ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Prostate Carcinoma ◽  
Cell Types ◽  
Carcinoma Cells ◽  
Cycle Arrest ◽  
Induced Apoptosis ◽  
Different Cell Types ◽  
Hematopoietic Cell Lines

Flavopiridol (NSC 649890; Behringwerke L86-8275, Marburg, Germany), is a potent inhibitor of cyclin dependent kinases (CDKs) 1, 2, and 4. It has potent antiproliferative effects in vitro and is active in tumor models in vivo. While surveying the effect of flavopiridol on cell cycle progression in different cell types, we discovered that hematopoietic cell lines, including SUDHL4, SUDHL6 (B-cell lines), Jurkat, and MOLT4 (T-cell lines), and HL60 (myeloid), displayed notable sensitivity to flavopiridol-induced apoptosis. For example, after 100 nmol/L for 12 hours, SUDHL4 cells displayed a similar degree of DNA fragmentation to that shown by the apoptosis-resistant PC3 prostate carcinoma cells only after 3,000 nmol/L for 48 hours. After exposure to 1,000 nmol/L flavopiridol for 12 hours, typical apoptotic morphology was observed in SUDHL4 cells, but not in PC3 prostate carcinoma cells despite comparable potency (SUDHL4:120 nmol/L; PC3: 203 nmol/L) in causing growth inhibition by 50% (IC50). Flavopiridol did not induce topoisomerase I or II cleavable complex activity. A relation of p53, bcl2, or bax protein levels to apoptosis in SUDHL4 was not appreciated. While flavopiridol caused cell cycle arrest with decline in CDK1 activity in PC3 cells, apoptosis of SUDHL4 cells occurred without evidence of cell cycle arrest. These results suggest that antiproliferative activity of flavopiridol (manifest by cell cycle arrest) may be separated in different cell types from a capacity to induce apoptosis. Cells from hematopoietic neoplasms appear in this limited sample to be very susceptible to flavopiridol-induced apoptosis and therefore clinical trials in hematopoietic neoplasms should be of high priority.

scholarly journals p107 is active in the nucleolus in non-dividing human granulosa lutein cells

2000 ◽  
Vol 25 (3) ◽  
pp. 275-286 ◽  
Author(s):  
C Green ◽  
R Chatterjee ◽  
HH McGarrigle ◽  
F Ahmed ◽  
NS Thomas
Keyword(s):  
Cell Cycle ◽  
Cell Types ◽  
Quiescent State ◽  
Cdk Inhibitor ◽  
Proliferating Cells ◽  
Dividing Cells ◽  
E2f Transcription Factors ◽  
Almost All ◽  
Different Cell Types ◽  
P27 Kip1

Cells are maintained in a quiescent state by members of the retinoblastoma protein family, pRb and p130. Both are phosphoproteins and hypophosphorylated forms of pRb and p130 bind and repress the activity of E2F transcription factors, thereby preventing entry into the cell cycle. Mitogenic stimulation causes activation of cyclin dependent kinases (cdk) that phosphorylate both pRb and p130, thereby releasing E2F factors which stimulate the transcription of a number of genes that are required for DNA synthesis and for regulating the cell cycle. In non-dividing cells, cdks are maintained in an inactive state by cdk inhibitor proteins such as p27(Kip1). The aim of our study was to determine how E2F complexes are regulated during the differentiation of human primary granulosa lutein cells (GLC) of the corpus luteum (CL). The CL is formed in the ovary after ovulation at the terminal stage of folliculogenesis after completion of maturation and differentiation of Graafian follicles. As shown by flow cytometry GLC are not dividing, being predominantly in the G(0)/G(1) phase of the cell cycle and, consistent with this, they contain the cdk inhibitor protein, p27(Kip1), but not E2F-1 which is normally expressed only in proliferating cells. The GLC do express E2F-4, hypophosphorylated pRb, p130 forms 1 and 2 and, surprisingly, hypophosphorylated p107. p107 is normally present only in dividing cells where it regulates E2F activity during the cell cycle. These forms of pRb, p130 as well as p107, together with E2F-4 are all active in that they can bind an E2F DNA-binding site in a pull-down assay. Immunocytochemistry shows that these proteins are expressed in almost all GLC but have different sub-cellular distribution: p107 is concentrated in nucleoli, while p130 and E2F-4 show relatively even nuclear and cytoplasmic distributions. Both pRb and p130 have been implicated previously in repressing E2F activity in many different cell types during cell cycle arrest in G(0)/G(1). We conclude that p107 is active in human primary GLC but its nucleolar localisation would suggest that it represses ribosomal RNA synthesis rather than E2F activity.

scholarly journals Histone modification dynamics as revealed by multicolor immunofluorescence-based single-cell analysis

2020 ◽  
Vol 133 (14) ◽  
pp. jcs243444 ◽  
Author(s):  
Yoko Hayashi-Takanaka ◽  
Yuto Kina ◽  
Fumiaki Nakamura ◽  
Leontine E. Becking ◽  
Yoichi Nakao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Histone Modifications ◽  
Histone Deacetylases ◽  
Single Cell Analysis ◽  
Single Cells ◽  
Cell Types ◽  
Transient Overexpression ◽  
Overexpression System ◽  
Different Cell Types ◽  
External Stimuli

ABSTRACTPost-translational modifications on histones can be stable epigenetic marks or transient signals that can occur in response to internal and external stimuli. Levels of histone modifications fluctuate during the cell cycle and vary among different cell types. Here, we describe a simple system to monitor the levels of multiple histone modifications in single cells by multicolor immunofluorescence using directly labeled modification-specific antibodies. We analyzed histone H3 and H4 modifications during the cell cycle. Levels of active marks, such as acetylation and H3K4 methylation, were increased during the S phase, in association with chromatin duplication. By contrast, levels of some repressive modifications gradually increased during G2 and the next G1 phases. We applied this method to validate the target modifications of various histone demethylases in cells using a transient overexpression system. In extracts of marine organisms, we also screened chemical compounds that affect histone modifications and identified psammaplin A, which was previously reported to inhibit histone deacetylases. Thus, the method presented here is a powerful and convenient tool for analyzing the changes in histone modifications.

scholarly journals ON THE RECOVERY OF TRANSCRIPTION AFTER INHIBITION BY ACTINOMYCIN D

1972 ◽  
Vol 55 (2) ◽  
pp. 299-309 ◽  
Author(s):  
Stanley G. Sawicki ◽  
Gabriel C. Godman
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Rna Synthesis ◽  
Actinomycin D ◽  
Cell Types ◽  
Vero Cells ◽  
Sufficient Condition ◽  
Long Period ◽  
Different Cell Types ◽  
Early Restoration

After pulse exposure to concentrations of actinomycin D (AMD) sufficient to abolish transcription, Vero cells recover RNA synthesis much more rapidly than most other cell types. This is only in part attributable to the remarkable capacity of Vero very promptly to excrete bound AMD, elimination of which, although necessary, is not a sufficient condition for resurgence of RNA synthesis. After elimination of higher concentrations of AMD from Vero, although over-all RNA synthesis resumes a normal rate within 24 hr, protein synthesis lags, and a long period of division-delay ensues. Division-delay lasting 2–3 days results from exposure of Vero to doses of AMD greater than those that suppress RNA synthesis by greater than 90% (e.g. 1 µg/ml for 2 hr) but not by lower doses, which permit almost immediate reentry into the cell cycle. In contrast, although L cells recover over-all RNA synthesis very slowly after pulse treatment with AMD, resumption of protein synthesis or cell division is not comparably delayed thereafter. These and other data suggest that the early restoration of RNA synthesis in Vero after relief of inhibition by AMD is qualitatively imperfect. The results reported herein are explainable by the hypothesis that the synthesis of those species of RNA which are involved, directly or indirectly, in reactivating the transcription of genes controlling progression in the cell cycle is relatively resistant to suppression by AMD. Decay of such RNA templates and their products, which differs in different cell types during inhibition by AMD, determines the duration of division-delay.

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