DNA Breaks Clustering Into Radiation-Induced Foci Predicts Cell Death for A Broad Range of Radiation Quality
Explore the source record for details and available documents.
Floriane Poignant↗
SEARCH · Search NASA
Results for “Cell Death”
Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Detecting thermal discrepancies in vessel walls
An infrared, heat-sensing catheter particularly useful for identifying potentially fatal arterial plaques in patients with disease of the coronary or other arteries and its use are detailed. In one embodiment, an infrared fiberoptic system (with or without ultrasound) is employed at the tip of the catheter to locate inflamed, heat-producing, atherosclerotic plaque, which is at greater risk for rupture, fissure, or ulceration, and consequent thrombosis and occlusion of the artery. In another embodiment, a catheter with an infrared detector (with or without ultrasound) employed at its tip will likewise locate inflamed heat-producing atherosclerotic plaque. The devices and methods of the invention may be used to detect abscesses, infection, and cancerous regions by the heat such regions differentially display over the ambient temperature of immediately adjacent tissues. The methods and devices of the invention may also be used to detect regions of cooler than ambient tissue in a vessel or organ which indicate cell death, thrombosis, cell death, hemorrhage, calcium or cholesterol accumulations, or foreign materials.
Casscells, S. Ward↗
Report of prochloron research, IPE-7 (Palau, February 1982)
Various aspects of Prochloron research are discussed. At suitable low-tide periods about 5-6 new sites were surveyed as possible convenient sources of symbiotic didemnids. The Kanori Channel site peviously surveyed during IPE-VI remains by far the best, in terms of species, quantities and accessibility. Prochloron from the six major species of symbiotic didemnids was compared serum, cell size and vacuolation, etc. Tadpoles from Lissoclinum patella colonies were observed emerging from cloacal apertures; about 400 were collected. All but 4 carried a girdle of symbiotic Prochloron cells (about 40,000 per larva). Observations were made on cell viability indicated that a marked increase in protoplasm viscosity of the cell contents was associated with cell death. Living cells, in 5 microlitres of buffered sea water under a coverslip, when pressed with a 2 kg weight for 10 seconds, attempts made to culture Prochloron in sea-water media.
Lewin, R. A.↗
Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells
BACKGROUND: Data currently available on HIV-1-induced cytopathology is unclear regarding the mechanism of cell killing. OBJECTIVE: To clarify the extent to which apoptosis or necrosis is involved in HIV-1-induced cell death in view of conflicting existing data. METHODS: T lymphoblastoid cells or peripheral blood mononuclear cells were infected by various strains of HIV-1 and the numbers of apoptotic or necrotic cells were quantified at various times after infection using video-image analysis techniques; the results were compared with the amount of fragmented DNA using a quantitative method. Measurement of mitochondrial transmembrane potential (deltapsi(m)) and intracellular calcium concentrations [Ca2+]i was performed with fluorescent probes and fluorescence concentration analysis (FCA). RESULTS: Although lymphoblastoid and monocytoid cells acutely infected by HIV-1 had increased levels of fragmented DNA, a marker of apoptotic cell death, few (<12%) had condensed chromatin and fragmented nuclei, the morphological features of apoptosis. The predominant alterations in acutely infected cells were distended endoplasmic reticulum and abnormal mitochondria; these ultrastructural changes are consistent with necrosis, although some infected cells simultaneously displayed features of both necrosis and apoptosis. Viability of cells persistently infected by HIV-1 was only minimally reduced from that of uninfected cells. This reduction was accounted for by an increased propensity of the persistently infected cells to die by apoptosis. Alterations in [Ca2+]i and deltapsi(m) occurred in both acutely and persistently infected cells. CONCLUSION: Both necrosis and apoptosis contribute to HIV-1-induced killing of CD4 cells.
Non-NASA Center↗
Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice
The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'.
Non-NASA Center↗
Growth and differentiation of mammalian embryonic tissues exposed to hypergravity in vivo and in vitro
In about 10 years or so, men and women from Earth will be long-term inhabitants of a space station aboard which plants and animals will be growing and developing in gravities other than that of Earth. The effect of gravitational changes on development was examined. It is indicated that differentiation is speeded up under excess G and slowed in low or null G. The effects of exposure to excess gravity on fusion of the embryonic mouse secondary palate were studied. During fusion, the palatal shelves first adhere by means of glycoproteins appearing along the medial epithelial edge (MEE). The contacting epithelia then reorganize and undergo programmed cell death, allowing the underlying mesenchymes to come in contact. The process of cell death occurs in vitro at about the same rate that it occurs in vivo.
Duke, P. J.↗
Cytotoxic Effects of Re-Activated Lunar Dust Stimulant on Human Lung Cells
Lunar dust has been of significant concern due to various problems observed on the Apollo missions. Reports from astronauts have shown that the dust may have caused eye and nasal irritation as well as possible hay fever like symptoms. As NASA hopes to go to the Moon within the next few years, we hope to understand the possible toxic effects the dust might have. In these studies, we are looking at the effect of "re-activated" lunar dust stimulant on human bronchial cells. A simple grinding analog as a method of simulating micrometeorite crushing on the moon is used to "activate" the dust stimulant, i.e. capable of producing hydroxyl radicals. These radicals could then interact with human cells and may lead to a loss in membrane integrity and cell death. (Castranova, 1994) Cells are exposed to the dust for 6 and 24 hour intervals to assess cytotoxicity. Cytotoxicity is measured by looking at the production of inflammatory cytokines. Cells are exposed to ground and unground stimulant and compared to cytokine production from cells exposed to quartz which have a known toxicity. Here we look at the cytotoxicity of the lunar dust stimulant relative to quartz by measuring the production of inflammatory cytokines.
Upadhyaya, Krishna↗
Predicting Cancer Risk from Ionizing Radiation
The ability to predict cancer risk associated with exposure to low doses of high-LET ionizing radiation (IR) remains a challenge. Epidemiological methods lack the sensitivity and power to provide detailed risk estimates for cancer and ignore individual variance in IR sensitivity. We have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. Our hypothesis was tested in 15 different mouse strains as well as in primary human immune cells. We first approached individual ionizing radiation sensitivity in a mouse model by culturing primary skin fibroblasts extracted from 76 mice of 15 different genetic backgrounds and exposing them to HZE particles and X-rays. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Our results is in agreement with a DNA repair model we previously postulated, where nearby DNA double strand breaks (DSB) in the nucleus are brought together for more efficient repair, leading to RIF clustering. Such mechanism was evidenced by a specific dose and LET dependence of RIF numbers. Briefly, RIF quantification after low-LET X-ray exposure showed an asymptotic saturation for doses between 1 Gy and 4 Gy 4 hours post-irradiation across all 15 strains. The clustering of DSB across all strains also led to more RIF/Gy for lower LET (X-ray and 350 MeV/n Ar) than for higher LET (600 MeV/n Fe) 4 hours post-exposure. Considering the fact that the number of DSB/Gy should be independent of LET, our data suggest there are more DSB in individual RIF as the LET increases. RIF numbers for 24 and 48 hours post-exposure led to the inverse trend, with more remaining RIF/Gy for higher LET (by 600 MeV/n Fe). This result suggests cells have more difficulty resolving RIF from higher LET as they the number DSB/RIF increases. Note that for most conditions, the variance of RIF/Gy was small within individual animals of the same strain and large between strains, suggesting a strong genetics component. Furthermore, we present our preliminary data from an ongoing study on human genetic associations with IR sensitivity. To address the human variability in responses to HZE particle irradiation in a maximally comprehensive manner, we are in the process of collecting and isolating primary blood mononuclear cells from 768 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. We will next complete the quantification of HZE particle-induced DNA and cellular damage in the remaining subjects and compare it to their responses to low-LET irradiation. Finally, we will perform GWAS analysis to identify human genomic associations with IR sensitivity and potential targets for biomarker development.
High-LET radiation↗
DNA Damage Response to Low and High-LET in a Large Cohort of Mice and Humans and Latest Advancement in NASA Space Omics
This presentation will first focus on a thorough evaluation of the DNA damage response to both low and high-LET in a cohort of 76 mice primary skin fibroblast derived from 15 different strains or in human blood mononuclear cells derived from 550 healthy donors. In both the human and mice work, we have hypothesized that DNA repair capacity can be used as a marker to evaluate and differentiate individual radiation sensitivity. More specifically, this work is based on the concept that the combined time-dose dependence of radiation-induced foci (RIF) of p53-binding protein 1 (53BP1) following low-LET exposure contains sufficient information to infer sensitivity to any other LET. This work is one of the most extensive studies on the kinetics and possible genetic underpinnings of radiation-induced DNA damage and repair. Results on humans are still preliminary as we are still in the process of collecting and isolating primary blood mononuclear cells from 500 to 800 healthy subjects of European descent, 18-75 years of age, 50/50 male/female distribution. We have analyzed 53BP1+ RIF formation as well as oxidative stress and cell death in primary cells from 192 subjects in response to the same HZE particles as used in mice: 600 MeV/n Fe, 350 MeV/n Ar and 350 MeV/n Si, 1.1 and 3 particles/100m2, 4 and 24 hours after irradiation. The second part of the talk will focus on describing GeneLab: The NASA Systems Biology Platform for Space Omics Repository, Analysis and Visualization. NASA GeneLab is an open-access repository for omics datasets generated by biological experiments conducted in space or experiments relevant to spaceflight (e.g. simulated cosmic radiation, simulated microgravity, bed rest studies). Started as a repository designed to archive precious omics from space experiments, GeneLab has expanded its scope to maximize the intelligibility of the raw data (e.g. RNAseq, microarray, WGBS, metagenome), particularly for users with limited bioinformatics knowledge. As such GeneLab is now providing processed data derived from the raw data covering a large spectrum of omics (genome, epigenome, transcriptome, epitranscriptome, proteome, metabolome), to help users explore important questions: Which genes or proteins are expressed differently in space for various living organisms? What are the consequences arising from these changes? What specifics DNA mutations or epigenetic changes happen in space? What species or genetic features lead to better adaption to such a unique environment? In this presentation, we will report on the current and future objectives for GeneLab, and review recent published studies relating molecular changes observed in various animal models and tissue with microgravity, radiation, circadian rhythm, hydration and carbon dioxide conditions.
DNA repair kinetics↗
Coupling Kinesin Spindle Protein and Aurora B Inhibition with Apoptosis Induction Enhances Oral Cancer Cell Killing
Many proteins regulating mitosis have emerged as targets for cancer therapy, including the kinesin spindle protein (KSP) and Aurora kinase B (AurB). KSP is crucial for proper spindle pole separation during mitosis, while AurB plays roles in chromosome segregation and cytokinesis. Agents targeting KSP and AurB selectively affect dividing cells and have shown significant activity in vitro. However, these drugs, despite advancing to clinical trials, often yield unsatisfactory outcomes as monotherapy, likely due to variable responses driven by cyclin B degradation and apoptosis signal accumulation networks. Accumulated data suggest that combining emerging antimitotics with various cytostatic drugs can enhance tumor-killing effects compared to monotherapy. Here, we investigated the impact of inhibiting anti-apoptotic signals with the BH3-mimetic Navitoclax in oral cancer cells treated with the selective KSP inhibitor, Ispinesib, or AurB inhibitor, Barasertib, aiming to potentiate cell death. The combination of BH3-mimetics with both KSP and AurB inhibitors synergistically induced substantial cell death, primarily through apoptosis. A mechanistic analysis underlying this synergistic activity, undertaken by live-cell imaging, is presented. Our data underscore the importance of combining BH3-mimetics with antimitotics in clinical trials to maximize their effectiveness.
Silva, João P. N. (ORCID:0000000344554286)↗
Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo
The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.
NASA Discipline Neuroscience↗
Crosstalk between p38, Hsp25 and Akt in spinal motor neurons after sciatic nerve injury
The p38 stress-activated protein kinase pathway is involved in regulation of phosphorylation of Hsp25, which in turn regulates actin filament dynamic in non-neuronal cells. We report that p38, Hsp25 and Akt signaling pathways were specifically activated in spinal motor neurons after sciatic nerve axotomy. The activation of the p38 kinase was required for induction of Hsp25 expression. Furthermore, Hsp25 formed a complex with Akt, a member of PI-3 kinase pathway that prevents neuronal cell death. Together, our observations implicate Hsp25 as a central player in a complex system of signaling that may both promote regeneration of nerve fibers and prevent neuronal cell death in the injured spinal cord.
NASA Discipline Developmental Biology↗
Space Radiation Induces Long Term Impact on the Cardiovascular System by the Activation of FYN Through Reactive Oxygen Species
Space radiation can damage the cardiovascular system and thus is an important health risk factor for astronauts during long-term space missions. We utilized publicly available transcriptomic data through NASA's GeneLab platform (genelab.nasa.gov) to determine cardiovascular system response to space radiation. GeneLab is an open repository that houses all NASA related omics experiments including on the International Space Station (ISS) and related radiation ground studies. We analyzed 3 datasets from GeneLab: GLDS-117 and GLDS-109, which are ground studies of cardiomyocytes followed-up for 28 days after exposure to 90cGy of proton at 1GeV and 15cGy of 56Fe at 1GeV; and GLDS-52, human endothelial cells (HUVECs) that were cultured for 10 days on the ISS. The ground studies were designed to characterize the long-term impact following space irradiation on cardiomyocytes for 5 different time points up to 28 days after irradiation. Our analysis was guided by the hypothesis that there are common persistent molecules affecting the cardiovascular system due to radiation effects during spaceflight. Endothelial cells are known to directly regulate the development and activity of cardiomyocytes, and thus their response to spaceflight should be highly correlated with cardiomyocytes. To investigate our hypothesis, we identified the molecular pathways that were modified for all time points compared across both radiation on the ground and the pathways found in HUVECs flown in the ISS. We found the following key results related to the cardiovascular systems: 1) space radiation downregulate ROS functions; and 2) the key/driving genes: FYN, LCK, AKT1 are upregulated and LYN and FOS are downregulated with FYN being the central driver/hub for the cardiovascular response to space radiation. It is worth noting the activation of FYN is a key event which prevents cardiac cell death and ROS production. From our study we thus hypothesize that a feedback loop occurs from the oxidative stress caused by space radiation that upregulates FYN which in turn reduces ROS levels and thus ROS pathways, preventing cardiomyocyte and endothelial cell death and thus protecting the cardiovascular systems. We believe that this is a novel mechanism for space radiation induced cardiovascular risk directly linking radiation ground studies to spaceflight
Beheshti, Afshin↗
A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling
Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signalling that share mechanistic features with human antiviral systems1. In these pathways, including cyclic oligonucleotide-based antiphage signalling systems (CBASSs) and type III CRISPR systems in bacteria and cyclic GMP–AMP synthase–stimulator of interferon genes (cGAS–STING) in humans, oligonucleotide synthesis occurs upon detection of virus or foreign genetic material in the cell, triggering the antiviral response2, 3–4. Here, in an unexpected inversion of this process, we show that the CRISPR-related enzyme mCpol synthesizes cyclic oligonucleotides constitutively as part of an active mechanism that represses a toxic effector. Cell-based experiments demonstrated that the absence or loss of mCpol-produced cyclic oligonucleotides triggers cell death, preventing the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides. Structural and mechanistic investigation revealed mCpol to be a di-adenylate cyclase whose product, c-di-AMP, prevents toxic oligomerization of the effector protein 2TMβ. Analysis of cells by fluorescence microscopy showed that lack of mCpol allows 2TMβ-mediated cell death due to inner membrane collapse. These findings unveil a powerful defence strategy against virus-mediated immune suppression, expanding our understanding of the role of oligonucleotides in immunity.
Doherty, Erin E↗
DF-1, A Nontoxic Carbon Fullerene Based Antioxidant, is Effective as a Biomedical Countermeasure Against Radiation
A long-term goal of radiation research is the mitigation of inherent risks of radiation exposure. Thus the study and development of safe agents, whether biomedical or dietary, that act as effective radioprotectors is an important step in accomplishing this long-term goal. Some of the most effective agents to date have been aminothiols and their derivatives. Unfortunately, most of these agents have side effects such as nausea, vomiting, hypotension, weakness, and fatigability. For example, nausea and emesis occur in most patients treated with WR-2721 (Amifostine), requiring the use of effective antiemetics, with hypotension being the dose-limiting side effect in patients treated. Clearly, the need for a radioprotector that is both effective and safe still exists. Development of biocompatible nano-materials for radioprotection is a promising emerging technology that could be exploited to address the need to minimize biological effects when exposure is unavoidable. Testing free radical scavenging nanoparticles for potential use in radioprotection is exciting and highly relevant. Initial investigations presented here demonstrate the ability of a particular functionalized carbon fullerene nanoparticle, (DF-1), to act as an effective radioprotector. DF-1 was first identified as the most promising candidate in a screen of several functionalized carbon fullerenes based on lack of toxicity and antioxidant therapeutic potential against oxidative injuries (i.e. organ reperfusion and ionizing radiation). Subsequently, DF-1 has been shown to reduce chromosome aberration yield and cell death, as well as overall ROS levels in human lymphocytes and fibroblasts after exposure to gamma radiation and energetic protons while demonstrating no associated toxicity. The dose-reducing factor of DF-1 at LD50 is nearly 2.0 for gamma radiation. In addition, DF-1 treatment also significantly prevented cell cycle arrest after exposure. Finally, DF-1 markedly attenuated COX2 upregulation in cell culture after irradiation thus preventing an inflammatory response to irradiation. Taken together, these results suggest that DF-1 provides potent protection against several deleterious cellular consequences of irradiation in mammalian systems including oxidative stress, DNA damage, inflammation and cell death.
Theriot, Corey A.↗
Structural determinants for pH-dependent activation of a plant metacaspase
Arabidopsis thaliana metacaspase 9 (AtMC9) plays roles in clearing dead cells, forming xylem vessels, and regulating immunity and programmed cell death in plants. The protease's activation is controlled by pH levels, but the exact structural mechanism behind this has not been elucidated. In this work, high-resolution crystal structures for AtMC9 at active (pH 5.5 and pH 4.2) and inactive (pH 7.5) conditions are reported. The three structures are similar except for local conformations where their hydrogen bonding interactions with solvents are mediated through the protonation of specific titratable amino acid residues' side chains. By combining structural analysis, molecular dynamics simulations under constant pHs, and biochemical assays coupled with site-directed mutagenesis, we show that the regulation of AtMC9 activation involves multiple titratable glutamate and histidine residues across the three domains of p20, linker, and p10. Specifically, deprotonated Glu112, His193, and His208 can suppress AtMC9 proteolytic activity, while protonation of Glu255 and His307 at acidic pH may promote it. This study provides valuable insights into the pH-dependent activation of AtMC9 and could potentially lead to improving crops with enhanced immunity and controlled cell death, ultimately increasing agricultural productivity.
59 BASIC BIOLOGICAL SCIENCES↗
Transcript profiling of plastid ferrochelatase two mutants reveals that chloroplast singlet oxygen signals lead to global changes in RNA profiles and are mediated by Plant U-Box 4
Abstract Background In response to environmental stresses, chloroplasts generate reactive oxygen species, including singlet oxygen ( 1 O 2 ), an excited state of oxygen that regulates chloroplast-to-nucleus (retrograde) signaling, chloroplast turnover, and programmed cell death (PCD). Yet, the central signaling mechanisms and downstream responses remain poorly understood. TheArabidopsis thaliana plastid ferrochelatase two(fc2) mutant conditionally accumulates 1 O 2 , and Plant U-Box 4 (PUB4), a cytoplasmic E3 ubiquitin ligase, is involved in propagating 1 O 2 signals for chloroplast turnover and cellular degradation. Thus, thefc2andfc2 pub4mutants are useful genetic tools to elucidate these signaling pathways. Previous studies have focused on the role of 1 O 2 in promoting cellular degradation infc2mutants, but its impact on retrograde signaling from mature chloroplasts (the major site of 1 O 2 production) is poorly understood. Results To gain mechanistic insights into 1 O 2 signaling pathways, we compared transcriptomes of adult wt,fc2, andfc2 pub4plants. The accumulation of 1 O 2 infc2plants broadly repressed genes involved in chloroplast function and photosynthesis, while inducing genes and transcription factors involved in abiotic and biotic stress, the biosynthesis of jasmonic acid (JA) and salicylic acid (SA), microautophagy, and senescence. Elevated JA and SA levels were observed in 1 O 2 -stressedfc2plants.pub4reversed most of this 1 O 2 -induced gene expression and reduced the JA content infc2plants. Thepub4mutation also blocked JA-induced senescence pathways in the dark. However, fc2 pub4 plantsmaintained constitutively elevated levels of SA even in the absence of bulk 1 O 2 accumulation. Conclusions Together, this work demonstrates that infc2plants, 1 O 2 leads to a robust retrograde signal that may protect cells by downregulating photosynthesis and ROS production while simultaneously mounting a stress response involving SA and JA. The induction of microautophagy and senescence pathways indicate that 1 O 2 -induced cellular degradation is a genetic response to this stress, and the bulk of this transcriptional response is modulated by the PUB4 protein. However, the effect ofpub4on hormone synthesis and signaling is complex and indicates that an intricate interplay of SA and JA are involved in promoting stress responses and programmed cell death during photo-oxidative damage.
Plant Sciences↗
Size distribution of retrovirally marked lineages matches prediction from population measurements of cell cycle behavior
Mechanisms that regulate neuron production in the developing mouse neocortex were examined by using a retroviral lineage marking method to determine the sizes of the lineages remaining in the proliferating population of the ventricular zone during the period of neuron production. The distribution of clade sizes obtained experimentally in four different injection-survival paradigms (E11-E13, E11-E14, E11-E15, and E12-E15) from a total of over 500 labeled lineages was compared with that obtained from three models in which the average behavior of the proliferating population [i.e., the proportion of cells remaining in the proliferative population (P) vs. that exiting the proliferative population (Q)] was quantitatively related to lineage size distribution. In model 1, different proportions of asymmetric, symmetric terminal, and symmetric nonterminal cell divisions coexisted during the entire developmental period. In model 2, the developmental period was divided into two epochs: During the first, asymmetric and symmetric nonterminal cell divisions occurred, but, during the second, asymmetric and symmetric terminal cell divisions occurred. In model 3, the shifts in P and Q are accounted for by changes in the proportions of the two types of symmetric cell divisions without the inclusion of any asymmetric cell divisions. The results obtained from the retroviral experiments were well accounted for by model 1 but not by model 2 or 3. These findings demonstrate that: 1) asymmetric and both types of symmetric cell divisions coexist during the entire period of neurogenesis in the mouse, 2) neuron production is regulated in the proliferative population by the independent decisions of the two daughter cells to reenter S phase, and 3) neurons are produced by both asymmetric and symmetric terminal cell divisions. In addition, the findings mean that cell death and/or tangential movements of cells in the proliferative population occur at only a low rate and that there are no proliferating lineages "reserved" to make particular laminae or cell types. Copyright 2002 Wiley-Liss, Inc.
NASA Discipline Developmental Biology↗